NCBI Conserved Domain Search

Immunoglobulin (Ig) domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig) domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

Pssm-ID: 409398 Cd Length: 101 Bit Score: 222.75 E-value: 8.87e-68

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  328 KIPAMITSYPNTTLATQGQRKEMSCTAHGEKPIIVRWEKEDRIINP-EMARYLVSTKEVGEEVISTLQILPTVREDSGFF 406
Cdd:cd05735      1 KIPAMITSYPNTTLATKGQKKEMSCTAHGEKPIIVRWEKEDTIINPsEMSRYLVTTKEVGDEVISTLQILPTVREDSGFF 80

                           90       100
                   ....*....|....*....|.
gi 1958664483  407 SCHAINSYGEDRGIIQLTVQE 427
Cdd:cd05735     81 SCHAINSYGEDRGIIQLTVQE 101

Immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

Pssm-ID: 409397 [Multi-domain] Cd Length: 97 Bit Score: 208.12 E-value: 1.28e-62

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  232 PPKFVVQPRDQDGIYGKAVILNCSAEGYPVPTIVWKFSKGAGVPQFQPIA-LNGRIQVLSNGSLLIKHVVEEDSGYYLCK 310
Cdd:cd05734      1 PPRFVVQPNDQDGIYGKAVVLNCSADGYPPPTIVWKHSKGSGVPQFQHIVpLNGRIQLLSNGSLLIKHVLEEDSGYYLCK 80

                           90
                   ....*....|....*..
gi 1958664483  311 VSNDVGADVSKSMYLTV 327
Cdd:cd05734     81 VSNDVGADISKSMYLTV 97

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409550 [Multi-domain] Cd Length: 89 Bit Score: 137.70 E-value: 3.92e-38

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483   47 PASIRPMKNITAIAGRDTYIHCRVIGYPYYSIKWYKNANLLPFNHRQVAFeNNGTLKLSDVQKEVDEGEYTCNVLVQPQL 126
Cdd:cd20958      1 PPFIRPMGNLTAVAGQTLRLHCPVAGYPISSITWEKDGRRLPLNHRQRVF-PNGTLVIENVQRSSDEGEYTCTARNQQGQ 79

                           90
                   ....*....|
gi 1958664483  127 STSQSVHVTV 136
Cdd:cd20958     80 SASRSVFVKV 89

Seventh immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the seventh immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409546 [Multi-domain] Cd Length: 96 Bit Score: 110.87 E-value: 1.17e-28

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  232 PPKFVVQPRDQDGIYGKAVILNCSAEGYPVPTIVWKFSKGAGVPQFQPIALNGRIQVLSNGSLLIKHVVEEDSGYYLCKV 311
Cdd:cd20954      1 PPRWIVEPVDANVAAGQDVMLHCQADGFPTPTVTWKKATGSTPGEYKDLLYDPNVRILPNGTLVFGHVQKENEGHYLCEA 80

                           90
                   ....*....|....*.
gi 1958664483  312 SNDVGADVSKSMYLTV 327
Cdd:cd20954     81 KNGIGSGLSKVIFLKV 96

Sixth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the sixth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409551 Cd Length: 94 Bit Score: 91.40 E-value: 7.93e-22

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  139 PPFIQPFEFPR--FSIGQRVFIPCVVVSGDLPITITWQKDGRPIPASLGVTIDNID-FTSSLRISNLSLMHNGNYTCIAR 215
Cdd:cd20959      1 PPRIIPFAFGEgaAQVGMRAQLHCGVPGGDLPLNIRWTLDGQPISDDLGITVSRLGrRSSILSIDSLEASHAGNYTCHAR 80

                           90
                   ....*....|....
gi 1958664483  216 NEAAAVEHQSQLIV 229
Cdd:cd20959     81 NSAGSASYTAPLTV 94

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 81.00 E-value: 3.27e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  923 PDQPR-LTVSKTTSSSITLSWLPGDNGGSSIRGYILQYSEDNSEQWGSFPISP-SERSYRLENLKCGTWYKFTLTAQNGV 1000
Cdd:cd00063      1 PSPPTnLRVTDVTSTSVTLSWTPPEDDGGPITGYVVEYREKGSGDWKEVEVTPgSETSYTLTGLKPGTEYEFRVRAVNGG 80

                           90
                   ....*....|...
gi 1958664483 1001 GPGRISEIIEAKT 1013
Cdd:cd00063     81 GESPPSESVTVTT 93

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 77.46 E-value: 4.28e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  924 DQPR-LTVSKTTSSSITLSWLPGDNGGSSIRGYILQYSEDNSEQ-WGSFPISPSERSYRLENLKCGTWYKFTLTAQNGVG 1001
Cdd:pfam00041    1 SAPSnLTVTDVTSTSLTVSWTPPPDGNGPITGYEVEYRPKNSGEpWNEITVPGTTTSVTLTGLKPGTEYEVRVQAVNGGG 80


                   ....*
gi 1958664483 1002 PGRIS 1006
Cdd:pfam00041   81 EGPPS 85

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 84.67 E-value: 2.02e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  480 DVSPQLNSATIIDIHPSSTYSIRMYAKNRIGKSEPSNEITITADEAAPDgPPQEVHLEPTSSQSIRVTWKAPKkhlqNGI 559
Cdd:COG3401    186 TVTSTTLVDGGGDIEPGTTYYYRVAATDTGGESAPSNEVSVTTPTTPPS-APTGLTATADTPGSVTLSWDPVT----ESD 260

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  560 IRGYQIgYREYSTGGNFQfniiSIDTTGDSEvYTLDNLNKFTQYGLVVQACNRAGTGPSSQEIITTTLEDVPSYPPENVQ 639
Cdd:COG3401    261 ATGYRV-YRSNSGDGPFT----KVATVTTTS-YTDTGLTNGTTYYYRVTAVDAAGNESAPSNVVSVTTDLTPPAAPSGLT 334

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  640 AIATSPESISISWStlskEALNGILQGFRvIYWANLIDGELGEIkNVTTTQPSLELDGLEKYTNYSIQVLAFTRAGDG-- 717
Cdd:COG3401    335 ATAVGSSSITLSWT----ASSDADVTGYN-VYRSTSGGGTYTKI-AETVTTTSYTDTGLTPGTTYYYKVTAVDAAGNEsa 408

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  718 ----VRSEQIFTRTKEDVPGPPAGVKAAAASASMVFVSWLPPLKLNGIIRKYTVFC-SHPYPTVISEFEASPDSFSYrip 792
Cdd:COG3401    409 pseeVSATTASAASGESLTASVDAVPLTDVAGATAAASAASNPGVSAAVLADGGDTgNAVPFTTTSSTVTATTTDTT--- 485

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1958664483  793 nlsrnrqYSVWVVAVTSAGRGNSSEIITVEPLAKAPARILTFSGTVTTPWM 843
Cdd:COG3401    486 -------TANLSVTTGSLVGGSGASSVTNSVSVIGASAAAAVGGAPDGTPN 529

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409548 [Multi-domain] Cd Length: 96 Bit Score: 76.06 E-value: 2.23e-16

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1958664483    2 ITSEGNVVSYLNISSSQVRDGGVYRCTANNSAGVVLYQARINV 44
Cdd:cd20956     54 VTSDGDVVSYVNISSVRVEDGGEYTCTATNDVGSVSHSARINV 96

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 71.44 E-value: 4.73e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  232 PPKFVVQPRDQDGIYGKAVILNCSAEGYPVPTIVWKFSKGAGVPQFQPIalngRIQVLSNGSLLIKHVVEEDSGYYLCKV 311
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRS----RSLSGSNSTLTISNVTRSDAGTYTCVA 76


                   ..
gi 1958664483  312 SN 313
Cdd:pfam13927   77 SN 78

First immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409387 Cd Length: 97 Bit Score: 71.74 E-value: 6.36e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  235 FVVQPRDQDGIYGKAVILNCSAEGYPVPTIVWKFSkgaGVpqFQPIALNGRIQVLSNGSLLIKHVV-----EEDSGYYLC 309
Cdd:cd05722      4 FLSEPSDIVAMRGGPVVLNCSAESDPPPKIEWKKD---GV--LLNLVSDERRQQLPNGSLLITSVVhskhnKPDEGFYQC 78

                           90
                   ....*....|....*....
gi 1958664483  310 KVSN-DVGADVSKSMYLTV 327
Cdd:cd05722     79 VAQNeSLGSIVSRTARVTV 97

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 70.60 E-value: 1.69e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  428 PPDPPEIEIKDVKARTITLRWTMGFDGNSPITGYDIECKNKSDswDSAQRTKDVSPQLNSATIIDIHPSSTYSIRMYAKN 507
Cdd:cd00063      1 PSPPTNLRVTDVTSTSVTLSWTPPEDDGGPITGYVVEYREKGS--GDWKEVEVTPGSETSYTLTGLKPGTEYEFRVRAVN 78

                           90
                   ....*....|....
gi 1958664483  508 RIGKSEPSNEITIT 521
Cdd:cd00063     79 GGGESPPSESVTVT 92

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 70.12 E-value: 1.94e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  237 VQPRDQDGIYGKAVILNCSA-EGYPVPTIVWKfSKGagvpqfQPIAL-NGRIQVLSNGSLLIKHVVEEDSGYYLCKVSND 314
Cdd:cd05724      2 VEPSDTQVAVGEMAVLECSPpRGHPEPTVSWR-KDG------QPLNLdNERVRIVDDGNLLIAEARKSDEGTYKCVATNM 74

                           90
                   ....*....|...
gi 1958664483  315 VGADVSKSMYLTV 327
Cdd:cd05724     75 VGERESRAARLSV 87

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 69.21 E-value: 4.22e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  233 PKFVVQPRDQDGIYGKAVILNCSAEGYPVPTIVWkFSKGagvpqfQPIALNGRIQVLSNG---SLLIKHVVEEDSGYYLC 309
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSW-FKDG------QPLRSSDRFKVTYEGgtyTLTISNVQPDDSGKYTC 73

                           90
                   ....*....|....*...
gi 1958664483  310 KVSNDVGADvSKSMYLTV 327
Cdd:pfam07679   74 VATNSAGEA-EASAELTV 90

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 68.02 E-value: 8.14e-14

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483   923 PDQPR-LTVSKTTSSSITLSWLP--GDNGGSSIRGYILQYSEDNSEqWGSFPISPSERSYRLENLKCGTWYKFTLTAQNG 999
Cdd:smart00060    1 PSPPSnLRVTDVTSTSVTLSWEPppDDGITGYIVGYRVEYREEGSE-WKEVNVTPSSTSYTLTGLKPGTEYEFRVRAVNG 79


                    ....
gi 1958664483  1000 VGPG 1003
Cdd:smart00060   80 AGEG 83

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 68.21 E-value: 9.42e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  429 PDPPEIEIKDVKARTITLRWTMGFDGNSPITGYDIECKNKSDSWDSAQRTkdVSPQLNSATIIDIHPSSTYSIRMYAKNR 508
Cdd:pfam00041    1 SAPSNLTVTDVTSTSLTVSWTPPPDGNGPITGYEVEYRPKNSGEPWNEIT--VPGTTTSVTLTGLKPGTEYEVRVQAVNG 78


                   ....*..
gi 1958664483  509 IGKSEPS 515
Cdd:pfam00041   79 GGEGPPS 85

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 68.05 E-value: 1.05e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  139 PPFIQPfefPR---FSIGQRVFIPCVVvSGDLPITITWQKDGRPIPASLGVTIDNIDFTSSLRISNLSLMHNGNYTCIAR 215
Cdd:pfam07679    1 PKFTQK---PKdveVQEGESARFTCTV-TGTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAT 76

                           90
                   ....*....|....
gi 1958664483  216 NEAAAVEHQSQLIV 229
Cdd:pfam07679   77 NSAGEAEASAELTV 90

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 67.52 E-value: 1.78e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  529 GPPQEVHLEPTSSQSIRVTWKAPKKHlqNGIIRGYQIGYREYSTGGNFQFNIISIDTTGdsevYTLDNLNKFTQYGLVVQ 608
Cdd:cd00063      2 SPPTNLRVTDVTSTSVTLSWTPPEDD--GGPITGYVVEYREKGSGDWKEVEVTPGSETS----YTLTGLKPGTEYEFRVR 75

                           90
                   ....*....|....*...
gi 1958664483  609 ACNRAGTGPSSQEIITTT 626
Cdd:cd00063     76 AVNGGGESPPSESVTVTT 93

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 66.05 E-value: 4.28e-13

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958664483  830 RILTFSGTVTTPWMKDIVLPCKAVGDPSPAVKWMKDSNGTPSLVTIDGRRSiFSNGSFVIRTVKAEDSGYYSCVANN 906
Cdd:pfam13927    3 VITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLS-GSNSTLTISNVTRSDAGTYTCVASN 78

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 65.88 E-value: 5.54e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  239 PRDQDGIYGKAVILNCSAEGYPVPTIVWKFSKGAgvpqfQPIalnGRIQVLSNGSLLIKHVVEEDSGYYLCKVSNDVGAd 318
Cdd:cd05725      4 PQNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGE-----LPK---GRYEILDDHSLKIRKVTAGDMGSYTCVAENMVGK- 74


                   ....*....
gi 1958664483  319 VSKSMYLTV 327
Cdd:cd05725     75 IEASATLTV 83

Second immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. DSCAM is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409545 Cd Length: 95 Bit Score: 66.03 E-value: 6.73e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  232 PPKFVVQPRDQDGIYGKAVILN--CSAEGYPVPTIVW-KFSKGAgvPQFQPIALNGRIQVLSnGSLLIKHVVEEDSGYYL 308
Cdd:cd20953      1 APKIPGLSKSQPLTVSSASSIAllCPAQGYPAPSFRWyKFIEGT--TRKQAVVLNDRVKQVS-GTLIIKDAVVEDSGKYL 77

                           90
                   ....*....|....*....
gi 1958664483  309 CKVSNDVGADvSKSMYLTV 327
Cdd:cd20953     78 CVVNNSVGGE-SVETVLTV 95

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 65.04 E-value: 6.94e-13

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  156 VFIPCVVvSGDLPITITWQKDGRPIPASLGVTIDNIDFTSSLRISNLSLMHNGNYTCIARNEAAAVEHQS 225
Cdd:cd00096      1 VTLTCSA-SGNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASAS 69

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 65.21 E-value: 9.22e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  235 FVVQPRDQDGIYGKAVILNCSAEGYPVPTIVWkfSKGAgvpqFQPIALNGRIQVLSNGSLLIKHVVEEDSGYYLCKVSND 314
Cdd:cd20952      2 ILQGPQNQTVAVGGTVVLNCQATGEPVPTISW--LKDG----VPLLGKDERITTLENGSLQIKGAEKSDTGEYTCVALNL 75

                           90
                   ....*....|...
gi 1958664483  315 VGaDVSKSMYLTV 327
Cdd:cd20952     76 SG-EATWSAVLDV 87

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 65.61 E-value: 9.26e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  238 QPRDQDGIYGKAVILNCSAEGYPVPTIVWKFSKGagvpqfQPIALNGRIQVLSNGSLL-IKHVVEEDSGYYLCKVSNDVG 316
Cdd:cd20970      8 PSFTVTAREGENATFMCRAEGSPEPEISWTRNGN------LIIEFNTRYIVRENGTTLtIRNIRRSDMGIYLCIASNGVP 81

                           90
                   ....*....|.
gi 1958664483  317 ADVSKSMYLTV 327
Cdd:cd20970     82 GSVEKRITLQV 92

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 64.45 E-value: 1.78e-12

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483   151 SIGQRVFIPCVVvSGDLPITITWQKDG-RPIPASLGVTIDNIDFTSSLRISNLSLMHNGNYTCIARNEAAAVEHQSQLIV 229
Cdd:smart00410    7 KEGESVTLSCEA-SGSPPPEVTWYKQGgKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGTTLTV 85

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 63.89 E-value: 2.09e-12

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958664483  846 IVLPCKAVGDPSPAVKWMKDsNGTPSLVTIDGRRSIFSNGSFVIRTVKAEDSGYYSCVANNNWG 909
Cdd:cd00096      1 VTLTCSASGNPPPTITWYKN-GKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAG 63

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1) and similar proteins; The members here are composed of the fourth immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. Also included in this group is NCAM-2 (also known as OCAM/mamFas II and RNCAM) NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE). One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 409395 [Multi-domain] Cd Length: 96 Bit Score: 64.08 E-value: 3.05e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  231 VPPKfVVQPRDQDGIYGKAVILNCSAEGYPVPTIVWKFSkgAGVPQFQPIALNGRIQVLSN---GSLLIKHVVEEDSGYY 307
Cdd:cd05732      1 VQPK-ITYLENQTAVELEQITLTCEAEGDPIPEITWRRA--TRGISFEEGDLDGRIVVRGHarvSSLTLKDVQLTDAGRY 77

                           90       100
                   ....*....|....*....|
gi 1958664483  308 LCKVSNDVGADvSKSMYLTV 327
Cdd:cd05732     78 DCEASNRIGGD-QQSMYLEV 96

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 63.12 E-value: 3.62e-12

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958664483  250 VILNCSAEGYPVPTIVWKFSKGagvpQFQPIALNGRIQVLSNGSLLIKHVVEEDSGYYLCKVSNDVGADVSKS 322
Cdd:cd00096      1 VTLTCSASGNPPPTITWYKNGK----PLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASAS 69

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 63.68 E-value: 3.82e-12

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483   247 GKAVILNCSAEGYPVPTIVWKFSKGagvpqfQPIALNGRIQVLSNG---SLLIKHVVEEDSGYYLCKVSNDVGaDVSKSM 323
Cdd:smart00410    9 GESVTLSCEASGSPPPEVTWYKQGG------KLLAESGRFSVSRSGstsTLTISNVTPEDSGTYTCAATNSSG-SASSGT 81


                    ....
gi 1958664483   324 YLTV 327
Cdd:smart00410   82 TLTV 85

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 62.91 E-value: 5.58e-12

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958664483   845 DIVLPCKAVGDPSPAVKWMKDSngtPSLVTIDGRRSIFSNG---SFVIRTVKAEDSGYYSCVANNNWGSDEIILNLQV 919
Cdd:smart00410   11 SVTLSCEASGSPPPEVTWYKQG---GKLLAESGRFSVSRSGstsTLTISNVTPEDSGTYTCAATNSSGSASSGTTLTV 85

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 62.90 E-value: 7.01e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  634 PPENVQAIATSPESISISWSTLSKEalNGILQGFRVIYWaNLIDGELGEIKNVTTTQPSLELDGLEKYTNYSIQVLAFTR 713
Cdd:cd00063      3 PPTNLRVTDVTSTSVTLSWTPPEDD--GGPITGYVVEYR-EKGSGDWKEVEVTPGSETSYTLTGLKPGTEYEFRVRAVNG 79

                           90
                   ....*....|....
gi 1958664483  714 AGDGVRSEQIFTRT 727
Cdd:cd00063     80 GGESPPSESVTVTT 93

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409548 [Multi-domain] Cd Length: 96 Bit Score: 62.96 E-value: 8.30e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  153 GQRVFIPCVVVSGDLPiTITWQKDGRPIPASLG------VTIDNiDFTSSLRISNLSLMHNGNYTCIARNEAAAVEHQSQ 226
Cdd:cd20956     16 GPSVSLKCVASGNPLP-QITWTLDGFPIPESPRfrvgdyVTSDG-DVVSYVNISSVRVEDGGEYTCTATNDVGSVSHSAR 93


                   ...
gi 1958664483  227 LIV 229
Cdd:cd20956     94 INV 96

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 62.41 E-value: 8.97e-12

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958664483  845 DIVLPCKAVGDPSPAVKWMKdsNGTPslvtIDGR--RSIFSNGSFVIRTVKAEDSGYYSCVANNNWGSDEIILNLQV 919
Cdd:cd20978     18 DVTLPCQVTGVPQPKITWLH--NGKP----LQGPmeRATVEDGTLTIINVQPEDTGYYGCVATNEIGDIYTETLLHV 88

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409550 [Multi-domain] Cd Length: 89 Bit Score: 62.20 E-value: 1.04e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  247 GKAVILNCSAEGYPVPTIVWKfsKGAgvpqfQPIALNGRIQVLSNGSLLIKHVV-EEDSGYYLCKVSNDVGADVSKSMYL 325
Cdd:cd20958     15 GQTLRLHCPVAGYPISSITWE--KDG-----RRLPLNHRQRVFPNGTLVIENVQrSSDEGEYTCTARNQQGQSASRSVFV 87


                   ..
gi 1958664483  326 TV 327
Cdd:cd20958     88 KV 89

Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; Members here are composed the fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1, Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409391 [Multi-domain] Cd Length: 98 Bit Score: 61.90 E-value: 2.31e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  234 KFVVQPRDQDGIYGKAVILNCSAEGYPVPTIVWKfSKGAGVPQF--QPIALNGRIQVLSNGSLLIKHVVEEDSGYYLCKV 311
Cdd:cd05726      1 QFVVKPRDQVVALGRTVTFQCETKGNPQPAIFWQ-KEGSQNLLFpyQPPQPSSRFSVSPTGDLTITNVQRSDVGYYICQA 79

                           90
                   ....*....|....*..
gi 1958664483  312 SNDVGADVSKSmYLTVK 328
Cdd:cd05726     80 LNVAGSILAKA-QLEVT 95

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 61.36 E-value: 2.72e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  732 PGPPAGVKAAAASASMVFVSWLPPLKLNGIIRKYTVFCSHPYPTVISEFE-ASPDSFSYRIPNLSRNRQYSVWVVAVTSA 810
Cdd:cd00063      1 PSPPTNLRVTDVTSTSVTLSWTPPEDDGGPITGYVVEYREKGSGDWKEVEvTPGSETSYTLTGLKPGTEYEFRVRAVNGG 80

                           90
                   ....*....|.
gi 1958664483  811 GRGNSSEIITV 821
Cdd:cd00063     81 GESPPSESVTV 91

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 60.66 E-value: 2.87e-11

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958664483  153 GQRVFIPCVVVSGDLPiTITWQKDGRPIPASLGVTIDNIDFTSSLRISNLSLMHNGNYTCIARN 216
Cdd:pfam13927   16 GETVTLTCEATGSPPP-TITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 60.97 E-value: 3.03e-11

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958664483  845 DIVLPCKAVGDPSPAVKWMKDSNgtpSLVTIDGRRSIFSNGSFVIRTVKAEDSGYYSCVANNNWGS 910
Cdd:cd20952     16 TVVLNCQATGEPVPTISWLKDGV---PLLGKDERITTLENGSLQIKGAEKSDTGEYTCVALNLSGE 78

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 60.89 E-value: 3.18e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  634 PPENVQAIATSPESISISWSTLskEALNGILQGFRVIYWAnlIDGELGEI-KNVTTTQPSLELDGLEKYTNYSIQVLAFT 712
Cdd:pfam00041    2 APSNLTVTDVTSTSLTVSWTPP--PDGNGPITGYEVEYRP--KNSGEPWNeITVPGTTTSVTLTGLKPGTEYEVRVQAVN 77


                   ....*...
gi 1958664483  713 RAGDGVRS 720
Cdd:pfam00041   78 GGGEGPPS 85

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 60.71 E-value: 3.41e-11

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483   529 GPPQEVHLEPTSSQSIRVTWKAPKKHLQNGIIRGYQIGYREYSTggnfqfNIISIDTTGDSEVYTLDNLNKFTQYGLVVQ 608
Cdd:smart00060    2 SPPSNLRVTDVTSTSVTLSWEPPPDDGITGYIVGYRVEYREEGS------EWKEVNVTPSSTSYTLTGLKPGTEYEFRVR 75


                    ....*...
gi 1958664483   609 ACNRAGTG 616
Cdd:smart00060   76 AVNGAGEG 83

Immunoglobulin I-set domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1); The members here are composed of the immunoglobulin I-set (IgI) domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1). Human Lingo-1 is a central nervous system-specific transmembrane glycoprotein also known as LERN-1, which functions as a negative regulator of neuronal survival, axonal regeneration, and oligodendrocyte differentiation and myelination. Lingo-1 is a key component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors. The ligand-binding ectodomain of human Lingo-1 contains a bimodular, kinked structure composed of leucine-rich repeat (LRR) and immunoglobulin (Ig)-like modules. Diseases associated with Lingo-1 include mental retardation, autosomal recessive 64 and essential tremor. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the Lingo-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409561 Cd Length: 92 Bit Score: 60.87 E-value: 3.58e-11

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958664483  844 KDIVLPCKAVGDPSPAVKWMkdSNGT-PSLVTIDGRRSIFSNGSFVIRTVKAEDSGYYSCVANNNWGSDEIILNLQV 919
Cdd:cd20969     18 HTVQFVCRADGDPPPAILWL--SPRKhLVSAKSNGRLTVFPDGTLEVRYAQVQDNGTYLCIAANAGGNDSMPAHLHV 92

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 60.73 E-value: 4.11e-11

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958664483  844 KDIVLPCKAVGDPSPAVKWMKDsnGTPslVTIDGRRSIFSNG---SFVIRTVKAEDSGYYSCVANNNWGSDEIILNLQV 919
Cdd:pfam07679   16 ESARFTCTVTGTPDPEVSWFKD--GQP--LRSSDRFKVTYEGgtyTLTISNVQPDDSGKYTCVATNSAGEAEASAELTV 90

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 59.74 E-value: 7.22e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  529 GPPQEVHLEPTSSQSIRVTWKAPKKHlqNGIIRGYQIGYREYSTGGNFQfniiSIDTTGDSEVYTLDNLNKFTQYGLVVQ 608
Cdd:pfam00041    1 SAPSNLTVTDVTSTSLTVSWTPPPDG--NGPITGYEVEYRPKNSGEPWN----EITVPGTTTSVTLTGLKPGTEYEVRVQ 74

                           90
                   ....*....|.
gi 1958664483  609 ACNRAGTGPSS 619
Cdd:pfam00041   75 AVNGGGEGPPS 85

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 59.44 E-value: 9.92e-11

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483   337 PNTTLATQGQRKEMSCTAHGEKPIIVRWEKEDRIINPEMARYLVStkevGEEVISTLQILPTVREDSGFFSCHAINSYGE 416
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVS----RSGSTSTLTISNVTPEDSGTYTCAATNSSGS 76


                    ....*....
gi 1958664483   417 DRGIIQLTV 425
Cdd:smart00410   77 ASSGTTLTV 85

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 58.75 E-value: 2.03e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  232 PPKFVVQPRDQDGIYGKAVILNCSAEGYPVPTIVWkFSKGAGVpQFQPialngRIQVLSNG---SLLIKHVVEEDSGYYL 308
Cdd:cd20972      1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRW-FCEGKEL-QNSP-----DIQIHQEGdlhSLIIAEAFEEDTGRYS 73

                           90
                   ....*....|..
gi 1958664483  309 CKVSNDVGADVS 320
Cdd:cd20972     74 CLATNSVGSDTT 85

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409560 [Multi-domain] Cd Length: 88 Bit Score: 58.79 E-value: 2.20e-10

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958664483  847 VLPCKAVGDPSPAVKWMKDSngtpSLVTIDGRRSIFSNGSFVIRTVKAEDSGYYSCVANNNWGS 910
Cdd:cd20968     18 VLPCTTMGNPKPSVSWIKGD----DLIKENNRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLGI 77

Immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

Pssm-ID: 409397 [Multi-domain] Cd Length: 97 Bit Score: 58.66 E-value: 2.33e-10

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958664483  844 KDIVLPCKAVGDPSPAVKWmKDSNGT-----PSLVTIDGRRSIFSNGSFVIRTVKAEDSGYYSCVANNNWGSD 911
Cdd:cd05734     17 KAVVLNCSADGYPPPTIVW-KHSKGSgvpqfQHIVPLNGRIQLLSNGSLLIKHVLEEDSGYYLCKVSNDVGAD 88

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 57.79 E-value: 3.47e-10

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958664483  846 IVLPCKAVGDPSPAVKWMKDSNGTPslvtiDGRRSIFSNGSFVIRTVKAEDSGYYSCVANNNWGSDEIILNLQV 919
Cdd:cd05725     15 AEFQCEVGGDPVPTVRWRKEDGELP-----KGRYEILDDHSLKIRKVTAGDMGSYTCVAENMVGKIEASATLTV 83

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 57.62 E-value: 4.58e-10

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483   634 PPENVQAIATSPESISISWSTLSKEALNGILQGFRVIYWAnliDGELGEIKNVTTTQPSLELDGLEKYTNYSIQVLAFTR 713
Cdd:smart00060    3 PPSNLRVTDVTSTSVTLSWEPPPDDGITGYIVGYRVEYRE---EGSEWKEVNVTPSSTSYTLTGLKPGTEYEFRVRAVNG 79


                    ....
gi 1958664483   714 AGDG 717
Cdd:smart00060   80 AGEG 83

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 57.24 E-value: 5.46e-10

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483   428 PPDPPEIEIKDVKARTITLRWTMGFDGN--SPITGYDIECKNKSDSWdsaqRTKDVSPQLNSATIIDIHPSSTYSIRMYA 505
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTLSWEPPPDDGitGYIVGYRVEYREEGSEW----KEVNVTPSSTSYTLTGLKPGTEYEFRVRA 76


                    ....*..
gi 1958664483   506 KNRIGKS 512
Cdd:smart00060   77 VNGAGEG 83

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 57.02 E-value: 7.30e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  233 PKFVVQPRDQDGIY-GKAVILNCSAEGYPVPTIVWkFSKGagvpqfQPI-ALNGRIQVlSNGSLLIKHVVEEDSGYYLCK 310
Cdd:cd20978      1 PKFIQKPEKNVVVKgGQDVTLPCQVTGVPQPKITW-LHNG------KPLqGPMERATV-EDGTLTIINVQPEDTGYYGCV 72

                           90
                   ....*....|....*..
gi 1958664483  311 VSNDVGaDVSKSMYLTV 327
Cdd:cd20978     73 ATNEIG-DIYTETLLHV 88

Seventh immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the seventh immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409546 [Multi-domain] Cd Length: 96 Bit Score: 57.32 E-value: 7.80e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  820 TVEPLAKAPARiltfsgtvttpwMKDIVLPCKAVGDPSPAVKWMKDSNGTPSL---VTIDGRRSIFSNGSFVIRTVKAED 896
Cdd:cd20954      5 IVEPVDANVAA------------GQDVMLHCQADGFPTPTVTWKKATGSTPGEykdLLYDPNVRILPNGTLVFGHVQKEN 72

                           90
                   ....*....|....*
gi 1958664483  897 SGYYSCVANNNWGSD 911
Cdd:cd20954     73 EGHYLCEAKNGIGSG 87

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 57.08 E-value: 8.95e-10

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958664483  845 DIVLPCKAVGDPSPAVKWMKdsnGTpSLVTIDGRRSIFSNGSFVIRTVKAEDSGYYSCVANNNWGSDEIILNLQV 919
Cdd:cd04969     19 DVIIECKPKASPKPTISWSK---GT-ELLTNSSRICILPDGSLKIKNVTKSDEGKYTCFAVNFFGKANSTGSLSV 89

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 56.27 E-value: 1.34e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  733 GPPAGVKAAAASASMVFVSWLPPLKLNGIIRKYTVFCSHPY-PTVISEFEASPDSFSYRIPNLSRNRQYSVWVVAVTSAG 811
Cdd:pfam00041    1 SAPSNLTVTDVTSTSLTVSWTPPPDGNGPITGYEVEYRPKNsGEPWNEITVPGTTTSVTLTGLKPGTEYEVRVQAVNGGG 80


                   ....*
gi 1958664483  812 RGNSS 816
Cdd:pfam00041   81 EGPPS 85

Third immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the third immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143222 [Multi-domain] Cd Length: 74 Bit Score: 55.71 E-value: 1.55e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  247 GKAVILNCSAEGYPVPTIVWkfSKGAGvpqfqPIALNGRIQVLSNGSLLIKHVVEEDSGYYLCKVSNDVGAdVSKSMYLT 326
Cdd:cd05745      2 GQTVDFLCEAQGYPQPVIAW--TKGGS-----QLSVDRRHLVLSSGTLRISRVALHDQGQYECQAVNIVGS-QRTVAQLT 73


                   .
gi 1958664483  327 V 327
Cdd:cd05745     74 V 74

Immunoglobulin I-set domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1); The members here are composed of the immunoglobulin I-set (IgI) domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1). Human Lingo-1 is a central nervous system-specific transmembrane glycoprotein also known as LERN-1, which functions as a negative regulator of neuronal survival, axonal regeneration, and oligodendrocyte differentiation and myelination. Lingo-1 is a key component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors. The ligand-binding ectodomain of human Lingo-1 contains a bimodular, kinked structure composed of leucine-rich repeat (LRR) and immunoglobulin (Ig)-like modules. Diseases associated with Lingo-1 include mental retardation, autosomal recessive 64 and essential tremor. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the Lingo-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409561 Cd Length: 92 Bit Score: 56.24 E-value: 1.56e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  237 VQPRDQDGIY---GKAVILNCSAEGYPVPTIVWKFskgagvPQFQPIAL--NGRIQVLSNGSLLIKHVVEEDSGYYLCKV 311
Cdd:cd20969      4 IRDRKAQQVFvdeGHTVQFVCRADGDPPPAILWLS------PRKHLVSAksNGRLTVFPDGTLEVRYAQVQDNGTYLCIA 77


                   ....*..
gi 1958664483  312 SNDVGAD 318
Cdd:cd20969     78 ANAGGND 84

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 55.73 E-value: 2.12e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483   47 PASIRPMKNITAIAGRDTYIHCRVIGYPYYSIKWYKNANLLPFN--HRQVAFENNGTLKLSDVQKEvDEGEYTCNVLVqp 124
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSdrFKVTYEGGTYTLTISNVQPD-DSGKYTCVATN-- 77

                           90
                   ....*....|....
gi 1958664483  125 qLSTSQSVHVTVKV 138
Cdd:pfam07679   78 -SAGEAEASAELTV 90

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule 1(NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM) and heterophilic (NCAM-non-NCAM) interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 143277 [Multi-domain] Cd Length: 97 Bit Score: 55.76 E-value: 2.56e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  250 VILNCSAEGYPVPTIVWKFSKGAGVPQFQpiALNGRIQVLSN---GSLLIKHVVEEDSGYYLCKVSNDVGADvSKSMYLT 326
Cdd:cd05869     20 ITLTCEASGDPIPSITWRTSTRNISSEEK--TLDGHIVVRSHarvSSLTLKYIQYTDAGEYLCTASNTIGQD-SQSMYLE 96


                   .
gi 1958664483  327 V 327
Cdd:cd05869     97 V 97

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 55.23 E-value: 3.03e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  232 PPKFVVQPRDQDGIYGKAVILNCSAEGYPVPTIVWKFSKgagvpqfQPIALNGRIQVLSNGSLLIKHVVEEDSGYYLCKV 311
Cdd:cd20957      1 PLSATIDPPVQTVDFGRTAVFNCSVTGNPIHTVLWMKDG-------KPLGHSSRVQILSEDVLVIPSVKREDKGMYQCFV 73


                   ....
gi 1958664483  312 SNDV 315
Cdd:cd20957     74 RNDG 77

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 54.26 E-value: 4.49e-09

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958664483   66 IHCRVIGYPYYSIKWYKNANLLPFNHRQVAFE--NNGTLKLSDVQKEvDEGEYTCNVLVQPQLSTSQSV 132
Cdd:cd00096      3 LTCSASGNPPPTITWYKNGKPLPPSSRDSRRSelGNGTLTISNVTLE-DSGTYTCVASNSAGGSASASV 70

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 54.43 E-value: 6.54e-09

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483    54 KNITAIAGRDTYIHCRVIGYPYYSIKWYKNA-NLLPFNHRQVAFENNG--TLKLSDVQKEvDEGEYTCNVLVqPQLSTSQ 130
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGgKLLAESGRFSVSRSGStsTLTISNVTPE-DSGTYTCAATN-SSGSASS 79


                    ....*.
gi 1958664483   131 SVHVTV 136
Cdd:smart00410   80 GTTLTV 85

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409550 [Multi-domain] Cd Length: 89 Bit Score: 54.50 E-value: 6.93e-09

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958664483  844 KDIVLPCKAVGDPSPAVKWMKDSNGTPslvtIDGRRSIFSNGSFVIRTV-KAEDSGYYSCVANNNWG-SDEIILNLQV 919
Cdd:cd20958     16 QTLRLHCPVAGYPISSITWEKDGRRLP----LNHRQRVFPNGTLVIENVqRSSDEGEYTCTARNQQGqSASRSVFVKV 89

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143223 Cd Length: 69 Bit Score: 53.34 E-value: 8.46e-09

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958664483  846 IVLPCKAVGDPSPAVKWMKDSngtpSLVTIDGRRSIFSNGSFVIRTVKAEDSGYYSCVANNNWGSDEIILNL 917
Cdd:cd05746      1 VQIPCSAQGDPEPTITWNKDG----VQVTESGKFHISPEGYLAIRDVGVADQGRYECVARNTIGYASVSMVL 68

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 54.14 E-value: 8.62e-09

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958664483  850 CKAVGDPSPAVKWMKDSNGTPSlvtiDGRRSIfSNGSFVIRTVKAEDSGYYSCVANNNWGS 910
Cdd:cd05728     21 CKASGNPRPAYRWLKNGQPLAS----ENRIEV-EAGDLRITKLSLSDSGMYQCVAENKHGT 76

First immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409387 Cd Length: 97 Bit Score: 54.02 E-value: 1.29e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958664483  846 IVLPCKAVGDPSPAVKWMKDsnGTPSLVTIDGRRSIFSNGSFVIRTVK-----AEDSGYYSCVANN-NWGS 910
Cdd:cd05722     19 VVLNCSAESDPPPKIEWKKD--GVLLNLVSDERRQQLPNGSLLITSVVhskhnKPDEGFYQCVAQNeSLGS 87

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 2 (NCAM-2); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule NCAM-2 (also known as OCAM/mamFas II and RNCAM). NCAM-2 is organized similarly to NCAM, including five N-terminal Ig-like domains and two fibronectin type III domains. NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE), and may function like NCAM, as an adhesion molecule. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 143278 [Multi-domain] Cd Length: 98 Bit Score: 53.83 E-value: 1.45e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  236 VVQPRDQDGIYGKAVILNCSAEGYPVPTIVWK-------FSKGAGVPqfqpialNGRIQV---LSNGSLLIKHVVEEDSG 305
Cdd:cd05870      5 IIQLKNETTVENGAATLSCKAEGEPIPEITWKrasdghtFSEGDKSP-------DGRIEVkgqHGESSLHIKDVKLSDSG 77

                           90       100
                   ....*....|....*....|..
gi 1958664483  306 YYLCKVSNDVGADvSKSMYLTV 327
Cdd:cd05870     78 RYDCEAASRIGGH-QKSMYLDI 98

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 53.16 E-value: 1.83e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  139 PPFIQPFEFPR-FSIGQRVFIPCVVvSGDLPITITWQKDGRPIPASLGvtidNIDFT-SSLRISNLSLMHNGNYTCIARN 216
Cdd:cd20978      1 PKFIQKPEKNVvVKGGQDVTLPCQV-TGVPQPKITWLHNGKPLQGPME----RATVEdGTLTIINVQPEDTGYYGCVATN 75

                           90
                   ....*....|...
gi 1958664483  217 EAAAVEHQSQLIV 229
Cdd:cd20978     76 EIGDIYTETLLHV 88

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 53.28 E-value: 1.86e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  835 SGTVTTPWMKDIVLPCKAVGDPSPAVKWMKDSNgtpSLVTIDGRRSIFSNGS-FVIRTVKAEDSGYYSCVANNN-WGSDE 912
Cdd:cd20970      9 SFTVTAREGENATFMCRAEGSPEPEISWTRNGN---LIIEFNTRYIVRENGTtLTIRNIRRSDMGIYLCIASNGvPGSVE 85


                   ....*..
gi 1958664483  913 IILNLQV 919
Cdd:cd20970     86 KRITLQV 92

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 52.57 E-value: 2.36e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  333 ITSYPNTTLATQGQRKEMSCTAHGEKPIIVRWEKEDRIINPEMARYLVSTKEVgeeviSTLQILPTVREDSGFFSCHAIN 412
Cdd:pfam13927    4 ITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSGSN-----STLTISNVTRSDAGTYTCVASN 78

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 53.02 E-value: 2.38e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  232 PPKFVVQPRDQDGIYGKAVILNCSAEGYPVPTIVWkfskgagVPQFQPIALNG-RIQV-LSNGSLLIKHVVEEDSGYYLC 309
Cdd:cd20976      1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITW-------IRNAQPLQYAAdRSTCeAGVGELHIQDVLPEDHGTYTC 73

                           90
                   ....*....|....*...
gi 1958664483  310 KVSNDVGAdVSKSMYLTV 327
Cdd:cd20976     74 LAKNAAGQ-VSCSAWVTV 90

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 52.85 E-value: 2.80e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  247 GKAVILNCSAEGYPVPTIVWKFSKGAgvpqfqpIALNGRIQVLSNGSLLIKHVVEEDSGYYLCKVSNDVGAdVSKSMYLT 326
Cdd:cd04969     17 GGDVIIECKPKASPKPTISWSKGTEL-------LTNSSRICILPDGSLKIKNVTKSDEGKYTCFAVNFFGK-ANSTGSLS 88


                   .
gi 1958664483  327 V 327
Cdd:cd04969     89 V 89

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409560 [Multi-domain] Cd Length: 88 Bit Score: 52.24 E-value: 3.81e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  239 PRDQDGIYGKAVILNCSAEGYPVPTIVWkfSKGAGVpqfqpIALNGRIQVLSNGSLLIKHVVEEDSGYYLCKVSNDVGAD 318
Cdd:cd20968      6 PTNVTIIEGLKAVLPCTTMGNPKPSVSW--IKGDDL-----IKENNRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLGIA 78

                           90
                   ....*....|
gi 1958664483  319 VSKSMYLTVK 328
Cdd:cd20968     79 YSKPVTIEVE 88

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409560 [Multi-domain] Cd Length: 88 Bit Score: 51.86 E-value: 4.86e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483   51 RPMKNITAIAGRDTYIHCRVIGYPYYSIKWYKNANLLPFNHRqVAFENNGTLKLSDVQKEvDEGEYTCnvLVQPQLSTSQ 130
Cdd:cd20968      4 RPPTNVTIIEGLKAVLPCTTMGNPKPSVSWIKGDDLIKENNR-IAVLESGSLRIHNVQKE-DAGQYRC--VAKNSLGIAY 79


                   ....*...
gi 1958664483  131 SVHVTVKV 138
Cdd:cd20968     80 SKPVTIEV 87

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409548 [Multi-domain] Cd Length: 96 Bit Score: 52.18 E-value: 5.19e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958664483  247 GKAVILNCSAEGYPVPTIVWKFSKgagvpqfQPIALNGRIQ----VLSNGSLL----IKHVVEEDSGYYLCKVSNDVGA 317
Cdd:cd20956     16 GPSVSLKCVASGNPLPQITWTLDG-------FPIPESPRFRvgdyVTSDGDVVsyvnISSVRVEDGGEYTCTATNDVGS 87

First immunoglobulin (Ig) domain of contactin; member of the I-set of (Ig) superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409356 [Multi-domain] Cd Length: 96 Bit Score: 51.86 E-value: 6.18e-08

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958664483  844 KDIVLPCKAVGDPSPAVKWMKdsNGTPSLVTIDGRRSIFSnGSFVIRT-VKAEDSGYYSCVANNNWGS 910
Cdd:cd04967     20 KKVALNCRARANPVPSYRWLM--NGTEIDLESDYRYSLVD-GTLVISNpSKAKDAGHYQCLATNTVGS 84

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 51.63 E-value: 6.42e-08

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958664483  847 VLPCKA-VGDPSPAVKWMKDsnGTPsLVTIDGRRSIFSNGSFVIRTVKAEDSGYYSCVANNNWGSDE 912
Cdd:cd05724     16 VLECSPpRGHPEPTVSWRKD--GQP-LNLDNERVRIVDDGNLLIAEARKSDEGTYKCVATNMVGERE 79

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 51.24 E-value: 8.22e-08

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958664483   52 PMKNITAIAGRDTYIHCRVIGYPYYSIKWYKNANLLPFNHRQVAFEnNGTLKLSDVQKEvDEGEYTCN 119
Cdd:cd20978      7 PEKNVVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMERATVE-DGTLTIINVQPE-DTGYYGCV 72

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 50.64 E-value: 1.16e-07

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958664483   54 KNITAIAGRDTYIHCRVIGYPYYSIKWYKNANLLPFNHRQVAFE--NNGTLKLSDVQKEvDEGEYTCNV 120
Cdd:pfam13927    9 SSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLsgSNSTLTISNVTRS-DAGTYTCVA 76

Immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins; member of the I-set of IgSF domains; This group contains the immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins. The SALM (for synaptic adhesion-like molecules; also known as Lrfn for leucine-rich repeat and fibronectin type III domain containing) family of adhesion molecules consists of five known members: SALM1/Lrfn2, SALM2/Lrfn1, SALM3/Lrfn4, SALM4/Lrfn3, and SALM5/Lrfn5. SALMs share a similar domain structure, containing leucine-rich repeats (LRRs), an immunoglobulin (Ig) domain, and a fibronectin III (FNIII) domain, followed by a transmembrane domain and a C-terminal PDZ-binding motif. SALM5 is implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons. SALM5 interacts with the Ig domains of LAR (Leukocyte common Antigen-Related) family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPdelta, and PTPsigma). In addition, PTPdelta is implicated in ASDs, ADHD, bipolar disorder, and restless leg syndrome. Studies have shown that LAR-RPTPs are novel and splicing-dependent presynaptic ligands for SALM5, and that they mediate SALM5-dependent presynaptic differentiation. Furthermore, SALM5 maintains AMPA receptor (AMPAR)-mediated excitatory synaptic transmission through mechanisms involving the interaction of SALM5 with LAR-RPTPs. This group belongs to the I-set of immunoglobulin superfamily (IgSF) domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409421 [Multi-domain] Cd Length: 88 Bit Score: 50.94 E-value: 1.24e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958664483  848 LPCKAVGDPSPAVKWMKDSNgtpSLVTIDGRRSIFSNGSFVIRTVKAEDSGYYSCVANNNWGSDEIILNLQV 919
Cdd:cd05764     20 LRCKARGDPEPAIHWISPEG---KLISNSSRTLVYDNGTLDILITTVKDTGAFTCIASNPAGEATARVELHI 88

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 50.70 E-value: 1.30e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  235 FVVQPRDQDGIYGKAVILNCSAEGYPVPTIVWKFSKGAGVPQfqpiALNGRIQVLSNGSLL-IKHVVEEDSGYYLCKVSN 313
Cdd:cd05763      2 FTKTPHDITIRAGSTARLECAATGHPTPQIAWQKDGGTDFPA----ARERRMHVMPEDDVFfIVDVKIEDTGVYSCTAQN 77

                           90
                   ....*....|....
gi 1958664483  314 DVGAdVSKSMYLTV 327
Cdd:cd05763     78 SAGS-ISANATLTV 90

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 50.72 E-value: 1.30e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  345 GQRKEMSCTAHGEKPIIVRWEKEDRIINPEmARYLVSTkevgEEVISTLQILPTVREDSGFFSCHAINSYGEDRGIIQLT 424
Cdd:pfam07679   15 GESARFTCTVTGTPDPEVSWFKDGQPLRSS-DRFKVTY----EGGTYTLTISNVQPDDSGKYTCVATNSAGEAEASAELT 89


                   .
gi 1958664483  425 V 425
Cdd:pfam07679   90 V 90

Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409357 [Multi-domain] Cd Length: 88 Bit Score: 50.62 E-value: 1.68e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  232 PPKFVVQPRDQDGIYGKAVILNCSAEGYPVPTIVWKFSKGAGVPQfqpialngRIQVLSNGSLLIKHVVEEDSGYYLCKV 311
Cdd:cd04968      1 PSIKVRFPADTYALKGQTVTLECFALGNPVPQIKWRKVDGSPSSQ--------WEITTSEPVLEIPNVQFEDEGTYECEA 72


                   ....*..
gi 1958664483  312 SNDVGAD 318
Cdd:cd04968     73 ENSRGKD 79

Immunoglobulin-like domain of human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin I-set (IgI) domain of the Human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins. APEG-1 is a novel specific smooth muscle differentiation marker predicted to play a role in the growth and differentiation of arterial smooth muscle cells (SMCs). The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the human APEG-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409567 Cd Length: 91 Bit Score: 50.55 E-value: 1.80e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958664483  344 QGQRKEMSCTAHGEKPIIVRWEKEDRIINPEMARYlvstKEVGEEVISTLQILPTVREDSGFFSCHAINSYG 415
Cdd:cd20975     14 EGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRF----AEEAEGGLCRLRILAAERGDAGFYTCKAVNEYG 81

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 49.64 E-value: 2.12e-07

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958664483  349 EMSCTAHGEKPIIVRWEKEDRIINPEMarylvSTKEVGEEVISTLQILPTVREDSGFFSCHAINSYGE 416
Cdd:cd00096      2 TLTCSASGNPPPTITWYKNGKPLPPSS-----RDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGG 64

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 50.34 E-value: 2.34e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958664483  848 LPCKAVGDPSPAVKWMKdsNGTPSLVTIDGRRSIFSNGS-FVIRTVKAEDSGYYSCVANNNWGSDEIILNLQVQ 920
Cdd:cd05736     20 LRCHAEGIPLPRVQWLK--NGMDINPKLSKQLTLIANGSeLHISNVRYEDTGAYTCIAKNEGGVDEDISSLFVE 91

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 50.24 E-value: 2.62e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  233 PKFVVQPRDQDGIYGKAVILNCSAEGYPVPTIVWkFSKGAGVPQFQPIALNGRIqVLSNGSLLIKHVV-----EEDSGYY 307
Cdd:cd07693      1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQW-LKNGQPLETDKDDPRSHRI-VLPSGSLFFLRVVhgrkgRSDEGVY 78

                           90       100
                   ....*....|....*....|
gi 1958664483  308 LCKVSNDVGADVSKSMYLTV 327
Cdd:cd07693     79 VCVAHNSLGEAVSRNASLEV 98

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 49.93 E-value: 2.95e-07

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958664483  848 LPCKAVGDPSPAVKWMKDSnGTPSLVTIDGRRSIFSNGS-FVIRTVKAEDSGYYSCVANNNWGS 910
Cdd:cd05763     19 LECAATGHPTPQIAWQKDG-GTDFPAARERRMHVMPEDDvFFIVDVKIEDTGVYSCTAQNSAGS 81

First immunoglobulin (Ig) domain of contactin-5; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-5. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains, anchored to the membrane by glycosylphosphatidylinositol. The different contactins show different expression patterns in the central nervous system. In rats, a lack of contactin-5 (NB-2) results in an impairment of the neuronal activity in the auditory system. Contactin-5 is expressed specifically in the postnatal nervous system, peaking at about 3 weeks postnatal. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala; lower levels of expression have been detected in the corpus callosum, caudate nucleus, and spinal cord. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409435 Cd Length: 96 Bit Score: 49.56 E-value: 4.95e-07

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958664483  844 KDIVLPCKAVGDPSPAVKWMKdsNGTPSLVTIDGRRSIFsNGSFVIRTV-KAEDSGYYSCVANNNWGS 910
Cdd:cd05848     20 KKVILNCEARGNPVPTYRWLR--NGTEIDTESDYRYSLI-DGNLIISNPsEVKDSGRYQCLATNSIGS 84

Seventh immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the seventh immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409546 [Multi-domain] Cd Length: 96 Bit Score: 49.23 E-value: 5.10e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958664483   54 KNITAIAGRDTYIHCRVIGYPYYSIKWYKNANLLPFNHRQVAFEN------NGTLKLSDVQKEvDEGEYTC 118
Cdd:cd20954      9 VDANVAAGQDVMLHCQADGFPTPTVTWKKATGSTPGEYKDLLYDPnvrilpNGTLVFGHVQKE-NEGHYLC 78

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1) and similar proteins; The members here are composed of the fourth immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. Also included in this group is NCAM-2 (also known as OCAM/mamFas II and RNCAM) NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE). One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 409395 [Multi-domain] Cd Length: 96 Bit Score: 49.06 E-value: 5.84e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  832 LTFSGTVTTPWMKDIVLPCKAVGDPSPAVKWMKDSNG-TPSLVTIDGR---RSIFSNGSFVIRTVKAEDSGYYSCVANNN 907
Cdd:cd05732      5 ITYLENQTAVELEQITLTCEAEGDPIPEITWRRATRGiSFEEGDLDGRivvRGHARVSSLTLKDVQLTDAGRYDCEASNR 84

                           90
                   ....*....|..
gi 1958664483  908 WGSDEIILNLQV 919
Cdd:cd05732     85 IGGDQQSMYLEV 96

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 48.93 E-value: 5.85e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  330 PAMITSYPNTTLATQGQRKEMSCTAHGEKPIIVRWEKEDRIINPEMARYLVSTkevgeeviSTLQILPTVREDSGFFSCH 409
Cdd:cd20978      1 PKFIQKPEKNVVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMERATVED--------GTLTIINVQPEDTGYYGCV 72

                           90
                   ....*....|....*.
gi 1958664483  410 AINSYGEDRGIIQLTV 425
Cdd:cd20978     73 ATNEIGDIYTETLLHV 88

Eighth immunoglobulin (Ig)-like domain of human myosin light-chain kinase (MLCK) and similar protein; member of the I-set of IgSF domains; The members here are composed of the eighth immunoglobulin (Ig)-like domain of human myosin light-chain kinase (MLCK) and similar proteins. Myosin light-chain kinase (MLCK) is a key regulator of different forms of cell motility involving actin and myosin II. Agonist stimulation of smooth muscle cells increases cytosolic Ca2+ which binds calmodulin. This Ca2+-calmodulin complex in turn binds to and activates MLCK. Activated MLCK leads to the phosphorylation of the 20 kDa myosin regulatory light chain (RLC) of myosin II and the stimulation of actin-activated myosin MgATPase activity. MLCK is widely present in vertebrate tissues; it phosphorylates the 20 kDa RLC of both smooth and nonmuscle myosin II. Phosphorylation leads to the activation of the myosin motor domain and altered structural properties of myosin II. In smooth muscle MLCK it is involved in initiating contraction. In nonmuscle cells, MLCK may participate in cell division and cell motility; it has been suggested MLCK plays a role in cardiomyocyte differentiation and contraction through regulation of nonmuscle myosin II.

Pssm-ID: 409419 Cd Length: 99 Bit Score: 49.18 E-value: 6.51e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  139 PPFIQPF-EFPRFSIGQRVFIPCVVVsGDLPITITWQKDGRPIPASLGVTIDNIDFTSSLRISNLSLMHNGNYTCIARNE 217
Cdd:cd05762      1 PPQIIQFpEDMKVRAGESVELFCKVT-GTQPITCTWMKFRKQIQEGEGIKIENTENSSKLTITEGQQEHCGCYTLEVENK 79

                           90
                   ....*....|..
gi 1958664483  218 AAAVEHQSQLIV 229
Cdd:cd05762     80 LGSRQAQVNLTV 91

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 48.96 E-value: 7.10e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  844 KDIVLPCKAVGDPSPAVKWMKdsNGTP-SLVTIDGRRSIFSNG---SFVIRTVKAEDSGYYSCVANNNWG 909
Cdd:cd20951     16 SDAKLRVEVQGKPDPEVKWYK--NGVPiDPSSIPGKYKIESEYgvhVLHIRRVTVEDSAVYSAVAKNIHG 83

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 48.61 E-value: 8.14e-07

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958664483   52 PMKNITAIA-GRDTYIHCRVIGYPYYSIKWYKNANLLPFNHRqVAFENNGTLKLSDVQKEvDEGEYTC 118
Cdd:cd04969      7 PVKKKILAAkGGDVIIECKPKASPKPTISWSKGTELLTNSSR-ICILPDGSLKIKNVTKS-DEGKYTC 72

Third immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the third immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143222 [Multi-domain] Cd Length: 74 Bit Score: 48.01 E-value: 8.68e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958664483  848 LPCKAVGDPSPAVKWMKDSNGTPslvtIDGRRSIFSNGSFVIRTVKAEDSGYYSCVANNNWGSDEIILNLQV 919
Cdd:cd05745      7 FLCEAQGYPQPVIAWTKGGSQLS----VDRRHLVLSSGTLRISRVALHDQGQYECQAVNIVGSQRTVAQLTV 74

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 48.26 E-value: 9.31e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  233 PKFVVQPRDQDGIYGKAVILNCSAEGYPVPTIVWKFSKgagvpqfQPIALNGRIQVLSNG----SLLIKHVVEEDSGYYL 308
Cdd:cd05744      1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNG-------KPVRPDSAHKMLVREngrhSLIIEPVTKRDAGIYT 73


                   ....*...
gi 1958664483  309 CKVSNDVG 316
Cdd:cd05744     74 CIARNRAG 81

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM and human neurofascin.

Pssm-ID: 409394 [Multi-domain] Cd Length: 83 Bit Score: 47.79 E-value: 1.09e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483   52 PMKNITAIAGRDTYIHCRVIGYPYYSIKWYKNANLLPFNHRQvaFEN-NGTLKLSDVQKEvDEGEYTCnVLVQPQLSTSQ 130
Cdd:cd05731      1 SESSTMVLRGGVLLLECIAEGLPTPDIRWIKLGGELPKGRTK--FENfNKTLKIENVSEA-DSGEYQC-TASNTMGSARH 76


                   ....*..
gi 1958664483  131 SVHVTVK 137
Cdd:cd05731     77 TISVTVE 83

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.

Pssm-ID: 143207 [Multi-domain] Cd Length: 95 Bit Score: 48.39 E-value: 1.09e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958664483  846 IVLPCKAVGDPSPAVKWMKDsnGTPsLVTIDGRRSIFSNGS-FVIRTVKAEDSGYYSCVANNNWGSDEIILNLQV 919
Cdd:cd05730     21 VTLACDADGFPEPTMTWTKD--GEP-IESGEEKYSFNEDGSeMTILDVDKLDEAEYTCIAENKAGEQEAEIHLKV 92

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 47.77 E-value: 1.10e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958664483  140 PFIQPfEFPRFSIGQRVFIPCVVvSGDLPITITWQKDGRPIPASlgvtidnidftSSLRISNLSLMHNGNYTCIARN 216
Cdd:pfam13895    2 PVLTP-SPTVVTEGEPVTLTCSA-PGNPPPSYTWYKDGSAISSS-----------PNFFTLSVSAEDSGTYTCVARN 65

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 47.99 E-value: 1.18e-06

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483   732 PGPPAGVKAAAASASMVFVSWLPPLKLNGiiRKYTVFCSHPYPTVISEFE---ASPDSFSYRIPNLSRNRQYSVWVVAVT 808
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTLSWEPPPDDGI--TGYIVGYRVEYREEGSEWKevnVTPSSTSYTLTGLKPGTEYEFRVRAVN 78


                    ....*
gi 1958664483   809 SAGRG 813
Cdd:smart00060   79 GAGEG 83

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 48.03 E-value: 1.22e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  233 PKFVVQPRDQDGIYGKAVILNCSAEGYPVPTIVWkFSKGAGVPQFQPIALNgriqVLSNGS-LLIKHVVEEDSGYYLCKV 311
Cdd:cd05736      1 PVIRVYPEFQAKEPGVEASLRCHAEGIPLPRVQW-LKNGMDINPKLSKQLT----LIANGSeLHISNVRYEDTGAYTCIA 75


                   ....*..
gi 1958664483  312 SNDVGAD 318
Cdd:cd05736     76 KNEGGVD 82

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.

Pssm-ID: 395002 Cd Length: 86 Bit Score: 47.96 E-value: 1.25e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958664483  150 FSIGQRVFIPCVVVSGDLPITITWQKDG-RPIPASLGVTIDNIDFTSSLRISNLSLMHNGNYTCIARN 216
Cdd:pfam00047    8 VLEGDSATLTCSASTGSPGPDVTWSKEGgTLIESLKVKHDNGRTTQSSLLISNVTKEDAGTYTCVVNN 75

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 47.88 E-value: 1.25e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483   42 INVRGPAsirpmkNITAIAGRDTYIHCRVIGYPYYSIKWYKNANLLPFNHRQVAFENNGTLKLSDVQKEvDEGEYTCnvl 121
Cdd:cd20952      1 IILQGPQ------NQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDERITTLENGSLQIKGAEKS-DTGEYTC--- 70

                           90
                   ....*....|....*..
gi 1958664483  122 VQPQLSTSQSVHVTVKV 138
Cdd:cd20952     71 VALNLSGEATWSAVLDV 87

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.

Pssm-ID: 395002 Cd Length: 86 Bit Score: 47.57 E-value: 1.61e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958664483  247 GKAVILNCSA-EGYPVPTIVWKFSKGAGVPQFQPIALNGRIqvlSNGSLLIKHVVEEDSGYYLCKVSN 313
Cdd:pfam00047   11 GDSATLTCSAsTGSPGPDVTWSKEGGTLIESLKVKHDNGRT---TQSSLLISNVTKEDAGTYTCVVNN 75

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 47.57 E-value: 1.73e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  240 RDQDGIYGKAVILNCSAEGYPVPTIVWkfskgagVPQFQPIALNGRIQVLSNG----SLLIKHVVEEDSGYYLCKVSNDV 315
Cdd:cd20973      5 RDKEVVEGSAARFDCKVEGYPDPEVKW-------MKDDNPIVESRRFQIDQDEdglcSLIISDVCGDDSGKYTCKAVNSL 77


                   .
gi 1958664483  316 G 316
Cdd:cd20973     78 G 78

Second immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. DSCAM is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409545 Cd Length: 95 Bit Score: 47.54 E-value: 1.83e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  832 LTFSGTVTTPWMKDIVLPCKAVGDPSPAVKWMKDSNGT--PSLVTIDGRRSIFSnGSFVIRTVKAEDSGYYSCVANNNWG 909
Cdd:cd20953      7 LSKSQPLTVSSASSIALLCPAQGYPAPSFRWYKFIEGTtrKQAVVLNDRVKQVS-GTLIIKDAVVEDSGKYLCVVNNSVG 85


                   ....
gi 1958664483  910 SDEI 913
Cdd:cd20953     86 GESV 89

Immunoglobulin-like Ig0 domain of basigin-1 (BSG1) and similar proteins; The members here are composed of the immunoglobulin (Ig) domain of the collagenase stimulatory factor, basigin-1 (BSG1; also known as Cluster of Differentiation 147 (CD147) and Extracellular Matrix Metalloproteinase Inducer (EMMPRIN)) and similar proteins. CD147 is a transmembrane glycoprotein that belongs to the immunoglobulin superfamily. It is expressed in nearly all cells including platelets and fibroblasts and is involved in inflammatory diseases, and cancer progression. CD147 is highly expressed in several cancers and used as a prognostic marker. The two primary isoforms of CD147 that are related to cancer progression have been identified: CD147 Ig1-Ig2 (also called Basigin-2) that is ubiquitously expressed in most tissues and CD147 Ig0-Ig1-Ig2 (also called Basigin-1) that is retinal specific and implicated in retinoblastoma. Studies showed that CD147 Ig0 domain is a potent stimulator of interleukin-6 and suggest that the CD147 Ig0 dimer is the functional unit required for activity.

Pssm-ID: 409534 Cd Length: 116 Bit Score: 48.04 E-value: 2.23e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  235 FVVQPRDQDGIYGKAVILNCSAEGYPVPTIVWKFSKGAG---VPQFQPIALNGRIQV------LSNGSLLIKHVVEEDSG 305
Cdd:cd20940      3 FIKSPLSQQRLVGDSVELHCEAVGSPIPEIQWWFEGQEPneiCSQLWDGARLDRVHInatyhqHATSTISIDNLTEEDTG 82


                   ....*....
gi 1958664483  306 YYLCKVSND 314
Cdd:cd20940     83 TYECRASND 91

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.

Pssm-ID: 409408 [Multi-domain] Cd Length: 92 Bit Score: 47.51 E-value: 2.28e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  844 KDIVLPCKAVGD-PSPAVKWMKDSN----GTPSLVTIDGRRSifsNGSFVIRTVKAEDSGYYSCVANNNWGSDEIILNLQ 918
Cdd:cd05750     15 SKLVLKCEATSEnPSPRYRWFKDGKelnrKRPKNIKIRNKKK---NSELQINKAKLEDSGEYTCVVENILGKDTVTGNVT 91


                   .
gi 1958664483  919 V 919
Cdd:cd05750     92 V 92

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409393 [Multi-domain] Cd Length: 95 Bit Score: 47.21 E-value: 3.08e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958664483  846 IVLPCKAVGDPSPAVKWMKDSNGTPSLVTIDGRRSIFSNGSFVIRTVKAEDSGYYSCVANNNWGSDEIILNLQV 919
Cdd:cd05729     22 VRLECGAGGNPMPNITWLKDGKEFKKEHRIGGTKVEEKGWSLIIERAIPRDKGKYTCIVENEYGSINHTYDVDV 95

Eighth immunoglobulin (Ig)-like domain of human myosin light-chain kinase (MLCK) and similar protein; member of the I-set of IgSF domains; The members here are composed of the eighth immunoglobulin (Ig)-like domain of human myosin light-chain kinase (MLCK) and similar proteins. Myosin light-chain kinase (MLCK) is a key regulator of different forms of cell motility involving actin and myosin II. Agonist stimulation of smooth muscle cells increases cytosolic Ca2+ which binds calmodulin. This Ca2+-calmodulin complex in turn binds to and activates MLCK. Activated MLCK leads to the phosphorylation of the 20 kDa myosin regulatory light chain (RLC) of myosin II and the stimulation of actin-activated myosin MgATPase activity. MLCK is widely present in vertebrate tissues; it phosphorylates the 20 kDa RLC of both smooth and nonmuscle myosin II. Phosphorylation leads to the activation of the myosin motor domain and altered structural properties of myosin II. In smooth muscle MLCK it is involved in initiating contraction. In nonmuscle cells, MLCK may participate in cell division and cell motility; it has been suggested MLCK plays a role in cardiomyocyte differentiation and contraction through regulation of nonmuscle myosin II.

Pssm-ID: 409419 Cd Length: 99 Bit Score: 47.26 E-value: 3.19e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  330 PAMITSYPNTTLATQGQRKEMSCTAHGEKPIIVRWEKEDRIINPEMARYLVSTkevgeEVISTLQILPTVREDSGFFSCH 409
Cdd:cd05762      1 PPQIIQFPEDMKVRAGESVELFCKVTGTQPITCTWMKFRKQIQEGEGIKIENT-----ENSSKLTITEGQQEHCGCYTLE 75

                           90       100
                   ....*....|....*....|...
gi 1958664483  410 AINSYGEDRGIIQLTVQEPPDPP 432
Cdd:cd05762     76 VENKLGSRQAQVNLTVVDKPDPP 98

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 46.23 E-value: 3.39e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  247 GKAVILNCSAEGYPVPTIVWkfSKGAGVpqfqpialngriqVLSNGSLLIKHVVEEDSGYYLCKVSNDVGADVSKSMYLT 326
Cdd:pfam13895   14 GEPVTLTCSAPGNPPPSYTW--YKDGSA-------------ISSSPNFFTLSVSAEDSGTYTCVARNGRGGKVSNPVELT 78


                   .
gi 1958664483  327 V 327
Cdd:pfam13895   79 V 79

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 51.54 E-value: 3.45e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  508 RIGKSEPSNEITITADEAAPDGPPQEVHLEPTSSQSIRVTWKAPKKHLQNGIIRGYQIGYREYSTGGNFQFNIISIDTTG 587
Cdd:COG3401     12 GIAASAAANTAVNALSKAGGSGKTILVYLAVVLSVTTKESPGTLLVAAGLSSGGGLGTGGRAGTTSGVAAVAVAAAPPTA 91

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  588 DSEVY-TLDNLNKFTQYGLVVQACNRAGTGPSSQEIITTTLEDVPSYPPENVQAIATSPESISISWSTLSKEALNGILQG 666
Cdd:COG3401     92 TGLTTlTGSGSVGGATNTGLTSSDEVPSPAVGTATTATAVAGGAATAGTYALGAGLYGVDGANASGTTASSVAGAGVVVS 171

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  667 FRVIYWANLIDGELGeiknVTTTQPSLELDGLEKYTNYSIQVLAFTRAGDGVRSEQIFTRTKEDVPGPPAGVKAAAASAS 746
Cdd:COG3401    172 PDTSATAAVATTSLT----VTSTTLVDGGGDIEPGTTYYYRVAATDTGGESAPSNEVSVTTPTTPPSAPTGLTATADTPG 247

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  747 MVFVSWLPPLKLNgiIRKYTVF----CSHPYPTVisefeASPDSFSYRIPNLSRNRQYSVWVVAVTSAG-RGNSSEIITV 821
Cdd:COG3401    248 SVTLSWDPVTESD--ATGYRVYrsnsGDGPFTKV-----ATVTTTSYTDTGLTNGTTYYYRVTAVDAAGnESAPSNVVSV 320

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  822 EPLAKAPARILTFSGTVTTPwmKDIVLPCKAVGDPSPA---VKWMKDSNGTPSLVTidgrrSIFSNGSFVIRTVKAEDSG 898
Cdd:COG3401    321 TTDLTPPAAPSGLTATAVGS--SSITLSWTASSDADVTgynVYRSTSGGGTYTKIA-----ETVTTTSYTDTGLTPGTTY 393

                          410       420       430       440       450       460       470
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958664483  899 YYSCVANNNWG-----SDEI---ILNLQVQVPPDQPRLTVSKTTSSSITLSWLPGDNGGSSIRGYILQYSEDNS 964
Cdd:COG3401    394 YYKVTAVDAAGnesapSEEVsatTASAASGESLTASVDAVPLTDVAGATAAASAASNPGVSAAVLADGGDTGNA 467

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 51.54 E-value: 3.54e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  775 TVISEFEASPDSFSYRIPNLSRNRQYSVWVVAVTSAGRGNSSEIITVEPLAKAPARILTFSGTVTTPwmkdivlpckavg 854
Cdd:COG3401    180 VATTSLTVTSTTLVDGGGDIEPGTTYYYRVAATDTGGESAPSNEVSVTTPTTPPSAPTGLTATADTP------------- 246

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  855 dPSPAVKWmkDSNGTPSLVTIDGRRSIFSNGSFVIRTVKAE----DSG-------YYSCVANNNWG-----SDEIILNLQ 918
Cdd:COG3401    247 -GSVTLSW--DPVTESDATGYRVYRSNSGDGPFTKVATVTTtsytDTGltngttyYYRVTAVDAAGnesapSNVVSVTTD 323

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  919 VQvPPDQPR-LTVSKTTSSSITLSWlpGDNGGSSIRGYILQYSEDNSEQWGSFPISPSERSYRLENLKCGTWYKFTLTAQ 997
Cdd:COG3401    324 LT-PPAAPSgLTATAVGSSSITLSW--TASSDADVTGYNVYRSTSGGGTYTKIAETVTTTSYTDTGLTPGTTYYYKVTAV 400


                   ....
gi 1958664483  998 NGVG 1001
Cdd:COG3401    401 DAAG 404

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains, five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

Pssm-ID: 409460 [Multi-domain] Cd Length: 83 Bit Score: 46.44 E-value: 3.70e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  247 GKAVILNCSAEGYPVPTIVWKFSKGagvpqfqPIALNGRIQVLSNGSLLIKHVVEEDSGYYLCKVSNDVGAdVSKSMYLT 326
Cdd:cd05876     10 GQSLVLECIAEGLPTPTVKWLRPSG-------PLPPDRVKYQNHNKTLQLLNVGESDDGEYVCLAENSLGS-ARHAYYVT 81


                   ..
gi 1958664483  327 VK 328
Cdd:cd05876     82 VE 83

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409393 [Multi-domain] Cd Length: 95 Bit Score: 46.83 E-value: 3.82e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958664483  247 GKAVILNCSAEGYPVPTIVW-KFSKgagvpQFQPIALNGRIQVLSNG-SLLIKHVVEEDSGYYLCKVSNDVG 316
Cdd:cd05729     19 ANKVRLECGAGGNPMPNITWlKDGK-----EFKKEHRIGGTKVEEKGwSLIIERAIPRDKGKYTCIVENEYG 85

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 46.37 E-value: 4.05e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958664483  844 KDIVLPCKAVGDPSPAVKWMKDSNGTPSlvtiDGRRSIFSNGSFVIRTVKAEDSGYYSCVANNNWGSDEIILNLQV 919
Cdd:cd20957     17 RTAVFNCSVTGNPIHTVLWMKDGKPLGH----SSRVQILSEDVLVIPSVKREDKGMYQCFVRNDGDSAQATAELKL 88

Fifth immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3 protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3 protein (also known as Neph2). This protein has five Ig-like domains, one transmembrane domain, and a cytoplasmic tail. Included in this group is mammalian Kirrel (Neph1). These proteins contain multiple Ig domains, have properties of cell adhesion molecules, and are important in organ development. Neph1 and 2 may mediate axonal guidance and synapse formation in certain areas of the CNS. In the kidney they participate in the formation of the slit diaphragm.

Pssm-ID: 409479 Cd Length: 98 Bit Score: 46.87 E-value: 4.29e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  330 PAMITSYPnTTLATQGQRKEMSCTAHGEKP---IIVRWeKEDRIINPEMARYLVSTKEVGEEVISTLQILPTVRED-SGF 405
Cdd:cd05898      2 PPIISSEQ-VQYAVRGERGKVKCFIGSTPPpdrIAWAW-KENVLESGTLERYTVERTSTGSGVLSTLTINNIMEADfQTH 79

                           90
                   ....*....|....*...
gi 1958664483  406 FSCHAINSYGEDRGIIQL 423
Cdd:cd05898     80 YNCTAWNSFGSGTAIIQL 97

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 46.33 E-value: 4.62e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958664483   47 PASIRPMKNITAIAGRDTYIHCRVIGYPYYSIKWYKNANLLPFNHRQVAFENNG---TLKLSDVQKEvDEGEYTC 118
Cdd:cd05744      1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVRENgrhSLIIEPVTKR-DAGIYTC 74

First immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409387 Cd Length: 97 Bit Score: 46.70 E-value: 4.93e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  334 TSYPNTTLATQGQRKEMSCTAHGEKPIIVRWEKEDRIINPEMA--RYLVSTkevGEEVISTLQILPTVREDSGFFSCHAI 411
Cdd:cd05722      5 LSEPSDIVAMRGGPVVLNCSAESDPPPKIEWKKDGVLLNLVSDerRQQLPN---GSLLITSVVHSKHNKPDEGFYQCVAQ 81


                   ....*
gi 1958664483  412 N-SYG 415
Cdd:cd05722     82 NeSLG 86

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 46.04 E-value: 4.94e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958664483  853 VGDPSPAVKWMKDS--NGTPSLVTIDGRRSifsNGSFVIRTVKAEDSGYYSCVANNNWGSDEIILNLQV 919
Cdd:cd05748     17 KGRPTPTVTWSKDGqpLKETGRVQIETTAS---STSLVIKNAKRSDSGKYTLTLKNSAGEKSATINVKV 82

Third immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 143259 Cd Length: 88 Bit Score: 46.17 E-value: 5.08e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  232 PPKFVVQPRDQDGIYGKAVILNCSAEGYPVPTIVWKFSKGAgVPQFQPIALNGRIqvlsngsLLIKHVVEEDSGYYLCKV 311
Cdd:cd05851      1 PADINVKFKDTYALKGQNVTLECFALGNPVPVIRWRKILEP-MPATAEISMSGAV-------LKIFNIQPEDEGTYECEA 72


                   ....*..
gi 1958664483  312 SNDVGAD 318
Cdd:cd05851     73 ENIKGKD 79

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 45.67 E-value: 6.82e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  239 PRDQDGIYGKAVILNCSAEGYPVPTIVWkFSKGagvpqfQPIALNGRIQVlSNGSLLIKHVVEEDSGYYLCKVSNDVGAd 318
Cdd:cd05728      6 ISDTEADIGSSLRWECKASGNPRPAYRW-LKNG------QPLASENRIEV-EAGDLRITKLSLSDSGMYQCVAENKHGT- 76


                   ....*....
gi 1958664483  319 VSKSMYLTV 327
Cdd:cd05728     77 IYASAELAV 85

Second immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains.

Pssm-ID: 409400 [Multi-domain] Cd Length: 91 Bit Score: 45.77 E-value: 7.04e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  228 IVRVPPKFVVQPRDQdgiygKAVILnCSAEGYPVPTIVWkfskgagVPQFQPIAL---NGRIQVLSNGSLLIKHVVEEDS 304
Cdd:cd05738      1 IIDMGPQLKVVEKAR-----TATML-CAASGNPDPEISW-------FKDFLPVDTatsNGRIKQLRSGALQIENSEESDQ 67

                           90       100
                   ....*....|....*....|....
gi 1958664483  305 GYYLCKVSNDVGADVSKSMYLTVK 328
Cdd:cd05738     68 GKYECVATNSAGTRYSAPANLYVR 91

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM and human neurofascin.

Pssm-ID: 409394 [Multi-domain] Cd Length: 83 Bit Score: 45.48 E-value: 8.15e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958664483  247 GKAVILNCSAEGYPVPTIVWkFSKGAGVPqfqpialNGRIQVLS-NGSLLIKHVVEEDSGYYLCKVSNDVG 316
Cdd:cd05731     10 GGVLLLECIAEGLPTPDIRW-IKLGGELP-------KGRTKFENfNKTLKIENVSEADSGEYQCTASNTMG 72

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 45.27 E-value: 8.55e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958664483  155 RVFIPcvvVSGDLPITITWQKDGRPIPASLGVTIDNIDFTSSLRISNLSLMHNGNYTCIARNEAAavEHQSQLIVRV 231
Cdd:cd05748     11 RLDIP---IKGRPTPTVTWSKDGQPLKETGRVQIETTASSTSLVIKNAKRSDSGKYTLTLKNSAG--EKSATINVKV 82

Immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins; member of the I-set of IgSF domains; This group contains the immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins. The SALM (for synaptic adhesion-like molecules; also known as Lrfn for leucine-rich repeat and fibronectin type III domain containing) family of adhesion molecules consists of five known members: SALM1/Lrfn2, SALM2/Lrfn1, SALM3/Lrfn4, SALM4/Lrfn3, and SALM5/Lrfn5. SALMs share a similar domain structure, containing leucine-rich repeats (LRRs), an immunoglobulin (Ig) domain, and a fibronectin III (FNIII) domain, followed by a transmembrane domain and a C-terminal PDZ-binding motif. SALM5 is implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons. SALM5 interacts with the Ig domains of LAR (Leukocyte common Antigen-Related) family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPdelta, and PTPsigma). In addition, PTPdelta is implicated in ASDs, ADHD, bipolar disorder, and restless leg syndrome. Studies have shown that LAR-RPTPs are novel and splicing-dependent presynaptic ligands for SALM5, and that they mediate SALM5-dependent presynaptic differentiation. Furthermore, SALM5 maintains AMPA receptor (AMPAR)-mediated excitatory synaptic transmission through mechanisms involving the interaction of SALM5 with LAR-RPTPs. This group belongs to the I-set of immunoglobulin superfamily (IgSF) domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409421 [Multi-domain] Cd Length: 88 Bit Score: 45.54 E-value: 8.86e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  332 MITSYPNTTLATQGQRKEMSCTAHGEKPIIVRW-EKEDRIInPEMARYLVSTKevgeeviSTLQILPTVREDSGFFSCHA 410
Cdd:cd05764      2 LITRHTHELRVLEGQRATLRCKARGDPEPAIHWiSPEGKLI-SNSSRTLVYDN-------GTLDILITTVKDTGAFTCIA 73

                           90
                   ....*....|....*
gi 1958664483  411 INSYGEDRGIIQLTV 425
Cdd:cd05764     74 SNPAGEATARVELHI 88

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 45.46 E-value: 9.26e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958664483   50 IRPMKNITAIAGRDTYIHCRVIGYPYYSIKWYKNANLLPFNHRQVAFENngTLKLSDVQKEvDEGEYTC 118
Cdd:cd05725      1 VKRPQNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGELPKGRYEILDDH--SLKIRKVTAG-DMGSYTC 66

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1(FGFRL1); member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 is comprised of a signal peptide, three extracellular Ig-like modules, a transmembrane segment, and a short intracellular domain. FGFRL1 is expressed preferentially in skeletal tissues. Similar to FGF receptors, the expressed protein interacts specifically with heparin and with FGF2. FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409442 Cd Length: 92 Bit Score: 45.24 E-value: 1.15e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958664483  247 GKAVILNCSAEGYPVPTIVWKFSKGAGVPQfqPIALNGRIQVlsngSLLIKHVVEEDSGYYLCKVSNDVGA 317
Cdd:cd05856     19 GSSVRLKCVASGNPRPDITWLKDNKPLTPP--EIGENKKKKW----TLSLKNLKPEDSGKYTCHVSNRAGE 83

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.

Pssm-ID: 395002 Cd Length: 86 Bit Score: 44.88 E-value: 1.52e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  846 IVLPCKAV-GDPSPAVKWMK-DSNGTPSLVTIDGRRSIFSNgSFVIRTVKAEDSGYYSCVANNNWGSDEI 913
Cdd:pfam00047   14 ATLTCSAStGSPGPDVTWSKeGGTLIESLKVKHDNGRTTQS-SLLISNVTKEDAGTYTCVVNNPGGSATL 82

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 44.83 E-value: 1.62e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958664483  163 VSGDLPITITWQKDGRPIPASLGVTIDNIDftsSLRISNLSLMHNGNYTCIARNEAAAVEHQSQL 227
Cdd:cd20957     25 VTGNPIHTVLWMKDGKPLGHSSRVQILSED---VLVIPSVKREDKGMYQCFVRNDGDSAQATAEL 86

First immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409547 Cd Length: 99 Bit Score: 45.09 E-value: 1.88e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  826 KAPARILTFSGTVTTPwmkdivLPCKAVGDPSPAVKWMKdSNGTpSLVTIDGRRSIFSNGSFVIRTVKAED------SGY 899
Cdd:cd20955      6 KEPTNRIDFSNSTGAE------IECKASGNPMPEIIWIR-SDGT-AVGDVPGLRQISSDGKLVFPPFRAEDyrqevhAQV 77

                           90
                   ....*....|.
gi 1958664483  900 YSCVANNNWGS 910
Cdd:cd20955     78 YACLARNQFGS 88

Third immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the third immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143222 [Multi-domain] Cd Length: 74 Bit Score: 44.16 E-value: 2.00e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958664483   61 GRDTYIHCRVIGYPYYSIKWYKNANLLPFNHRQVAFeNNGTLKLSDVQKEvDEGEYTCNVlVQPQLSTSQSVHVTV 136
Cdd:cd05745      2 GQTVDFLCEAQGYPQPVIAWTKGGSQLSVDRRHLVL-SSGTLRISRVALH-DQGQYECQA-VNIVGSQRTVAQLTV 74

Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409357 [Multi-domain] Cd Length: 88 Bit Score: 44.46 E-value: 2.17e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  828 PARILTFSGTVTTPWMKDIVLPCKAVGDPSPAVKWMKdSNGTPSLVTIDGRrsifSNGSFVIRTVKAEDSGYYSCVANNN 907
Cdd:cd04968      1 PSIKVRFPADTYALKGQTVTLECFALGNPVPQIKWRK-VDGSPSSQWEITT----SEPVLEIPNVQFEDEGTYECEAENS 75


                   ....
gi 1958664483  908 WGSD 911
Cdd:cd04968     76 RGKD 79

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule 1(NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM) and heterophilic (NCAM-non-NCAM) interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 143277 [Multi-domain] Cd Length: 97 Bit Score: 44.59 E-value: 2.31e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958664483  846 IVLPCKAVGDPSPAVKWMKDS-NGTPSLVTIDGR---RSIFSNGSFVIRTVKAEDSGYYSCVANNNWGSDEIILNLQV 919
Cdd:cd05869     20 ITLTCEASGDPIPSITWRTSTrNISSEEKTLDGHivvRSHARVSSLTLKYIQYTDAGEYLCTASNTIGQDSQSMYLEV 97

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 44.13 E-value: 2.51e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958664483  151 SIGQRVFIPCVVvSGDLPITITWQKDGRPIPASLGVTIDNidftSSLRISNLSLMHNGNYTCIARNEAAAVEHQSQLIV 229
Cdd:cd05728     12 DIGSSLRWECKA-SGNPRPAYRWLKNGQPLASENRIEVEA----GDLRITKLSLSDSGMYQCVAENKHGTIYASAELAV 85

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; depending on isoform composition it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 143224 [Multi-domain] Cd Length: 92 Bit Score: 44.27 E-value: 3.08e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  828 PARILTFSGTVTTPWMKDIVLPCKAVGDPSPAVKWMKDSNgtpslVTIDGRRSIFSN----GSFVIRTVKAEDSGYYSCV 903
Cdd:cd05747      3 PATILTKPRSLTVSEGESARFSCDVDGEPAPTVTWMREGQ-----IIVSSQRHQITSteykSTFEISKVQMSDEGNYTVV 77


                   ....*....
gi 1958664483  904 ANNNWGSDE 912
Cdd:cd05747     78 VENSEGKQE 86

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 44.02 E-value: 3.19e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  139 PPFIQPFEFPRFSIGQRVFIPCVVvSGDLPITITWQKDGRPI-PASLGVTIDNIDFTSSLRISNLSLMHNGNYTCIARNE 217
Cdd:cd05744      1 PHFLQAPGDLEVQEGRLCRFDCKV-SGLPTPDLFWQLNGKPVrPDSAHKMLVRENGRHSLIIEPVTKRDAGIYTCIARNR 79

                           90
                   ....*....|..
gi 1958664483  218 AAAVEHQSQLIV 229
Cdd:cd05744     80 AGENSFNAELVV 91

First immunoglobulin (Ig) domain of contactin-5; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-5. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains, anchored to the membrane by glycosylphosphatidylinositol. The different contactins show different expression patterns in the central nervous system. In rats, a lack of contactin-5 (NB-2) results in an impairment of the neuronal activity in the auditory system. Contactin-5 is expressed specifically in the postnatal nervous system, peaking at about 3 weeks postnatal. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala; lower levels of expression have been detected in the corpus callosum, caudate nucleus, and spinal cord. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409435 Cd Length: 96 Bit Score: 44.16 E-value: 3.62e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  233 PKFVVQPrdQDGIYG-----KAVILNCSAEGYPVPTIVWkFSKGAGVpqfqPIALNGRIQvLSNGSLLIKHVVE-EDSGY 306
Cdd:cd05848      2 PVFVQEP--DDAIFPtdsdeKKVILNCEARGNPVPTYRW-LRNGTEI----DTESDYRYS-LIDGNLIISNPSEvKDSGR 73

                           90
                   ....*....|....*....
gi 1958664483  307 YLCKVSNDVGADVSKSMYL 325
Cdd:cd05848     74 YQCLATNSIGSILSREALL 92

C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein (also known as myomesin-2). Myomesin and M-protein are both structural proteins localized to the M-band, a transverse structure in the center of the sarcomere, and are candidates for M-band bridges. Both proteins are modular, consisting mainly of repetitive Ig-like and fibronectin type III (FnIII) domains. Myomesin is expressed in all types of vertebrate striated muscle; M-protein has a muscle-type specific expression pattern. Myomesin is present in both slow and fast fibers; M-protein is present only in fast fibers. It has been suggested that myomesin acts as a molecular spring with alternative splicing as a means of modifying its elasticity.

Pssm-ID: 319300 Cd Length: 92 Bit Score: 44.12 E-value: 3.62e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958664483  844 KDIVLPCKAVGDPSPAVKWMKDSNgtpSLVTIDGRRSIFSNGSFV---IRTVKAEDSGYYSCVANNNWGSDEIILNLQV 919
Cdd:cd05737     17 KTLNLTCNVWGDPPPEVSWLKNDQ---ALAFLDHCNLKVEAGRTVyftINGVSSEDSGKYGLVVKNKYGSETSDVTVSV 92

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.

Pssm-ID: 395002 Cd Length: 86 Bit Score: 43.72 E-value: 3.63e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958664483  339 TTLATQGQRKEMSCTA-HGEKPIIVRWEKEDRIINPEMaRYLVSTKEVGeevISTLQILPTVREDSGFFSC 408
Cdd:pfam00047    5 TVTVLEGDSATLTCSAsTGSPGPDVTWSKEGGTLIESL-KVKHDNGRTT---QSSLLISNVTKEDAGTYTC 71

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 43.78 E-value: 3.72e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958664483  844 KDIVLPCKAVGDPSPAVKWMKdsNGTPslVTIDGRRSIFS--NGSFVIRTVKAEDSGYYSCVANNNWG 909
Cdd:cd20976     17 QDFVAQCSARGKPVPRITWIR--NAQP--LQYAADRSTCEagVGELHIQDVLPEDHGTYTCLAKNAAG 80

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409548 [Multi-domain] Cd Length: 96 Bit Score: 44.09 E-value: 3.75e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  827 APARILTFSGTVTTPWMkDIVLPCKAVGDPSPAVKWMKDSNGTPSL--------VTIDGRRSifsngSFV-IRTVKAEDS 897
Cdd:cd20956      1 APVLLETFSEQTLQPGP-SVSLKCVASGNPLPQITWTLDGFPIPESprfrvgdyVTSDGDVV-----SYVnISSVRVEDG 74

                           90
                   ....*....|...
gi 1958664483  898 GYYSCVANNNWGS 910
Cdd:cd20956     75 GEYTCTATNDVGS 87

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 43.64 E-value: 4.00e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958664483  848 LPCKAVGDPSPAVKWMKDSNgtpsLVTIDGRRSIFSNG----SFVIRTVKAEDSGYYSCVANNNWGSDEIILNLQV 919
Cdd:cd05744     20 FDCKVSGLPTPDLFWQLNGK----PVRPDSAHKMLVREngrhSLIIEPVTKRDAGIYTCIARNRAGENSFNAELVV 91

Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409357 [Multi-domain] Cd Length: 88 Bit Score: 43.69 E-value: 4.06e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  330 PAMITSYPNTTLATQGQRKEMSCTAHGEKPIIVRWEKEDriiNPEMARYLVSTKEvgeeviSTLQILPTVREDSGFFSCH 409
Cdd:cd04968      1 PSIKVRFPADTYALKGQTVTLECFALGNPVPQIKWRKVD---GSPSSQWEITTSE------PVLEIPNVQFEDEGTYECE 71

                           90
                   ....*....|....*..
gi 1958664483  410 AINSYGEDRGIIQLTVQ 426
Cdd:cd04968     72 AENSRGKDTVQGRIIVQ 88

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains, five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

Pssm-ID: 409460 [Multi-domain] Cd Length: 83 Bit Score: 43.36 E-value: 4.36e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  339 TTLATQGQRKEMSCTAHGEKPIIVRWEKEDRIINPEMARYLVSTKevgeevisTLQILPTVREDSGFFSCHAINSYGEDR 418
Cdd:cd05876      4 SLVALRGQSLVLECIAEGLPTPTVKWLRPSGPLPPDRVKYQNHNK--------TLQLLNVGESDDGEYVCLAENSLGSAR 75


                   ....*...
gi 1958664483  419 GIIQLTVQ 426
Cdd:cd05876     76 HAYYVTVE 83

Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; Members here are composed the fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1, Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409391 [Multi-domain] Cd Length: 98 Bit Score: 43.79 E-value: 4.62e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  844 KDIVLPCKAVGDPSPAVKWMKDsnGTPSLV------TIDGRRSIFSNGSFVIRTVKAEDSGYYSCVANNNWGSdeIILNL 917
Cdd:cd05726     15 RTVTFQCETKGNPQPAIFWQKE--GSQNLLfpyqppQPSSRFSVSPTGDLTITNVQRSDVGYYICQALNVAGS--ILAKA 90


                   ....
gi 1958664483  918 QVQV 921
Cdd:cd05726     91 QLEV 94

Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues, and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409388 Cd Length: 84 Bit Score: 42.95 E-value: 5.68e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958664483  845 DIVLPCKAVGDPSPAVKWMKDSNGT-PSlvtiDGRRSIFSNGSFVIRTVKAeDSGYYSCVANNNWGS 910
Cdd:cd05723     14 DIVFECEVTGKPTPTVKWVKNGDVViPS----DYFKIVKEHNLQVLGLVKS-DEGFYQCIAENDVGN 75

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 43.33 E-value: 6.07e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958664483  848 LPCKAVGDPSPAVKWMKDSNGT--PSLVTIDGRRSifSNGSFVIRTVKAEDSGYYSCVANNNWG 909
Cdd:cd20973     17 FDCKVEGYPDPEVKWMKDDNPIveSRRFQIDQDED--GLCSLIISDVCGDDSGKYTCKAVNSLG 78

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 43.25 E-value: 6.39e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958664483 1029 SINTTRVRLNLIGWNDGGCPITSFTLEYRPFGTTVWTTAQRTSLSK-SYILYDLQEATWYELQMRVCNSAG 1098
Cdd:cd00063     11 DVTSTSVTLSWTPPEDDGGPITGYVVEYREKGSGDWKEVEVTPGSEtSYTLTGLKPGTEYEFRVRAVNGGG 81

Immunoglobulin (Ig) domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig) domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

Pssm-ID: 409398 Cd Length: 101 Bit Score: 43.63 E-value: 6.66e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  826 KAPARILTFSGTVTTPWMKDIVLPCKAVGDPSPAVKWMKDSNgtpslvTIDGRR------SIFSNGSFVIRTVKA----- 894
Cdd:cd05735      1 KIPAMITSYPNTTLATKGQKKEMSCTAHGEKPIIVRWEKEDT------IINPSEmsrylvTTKEVGDEVISTLQIlptvr 74

                           90       100
                   ....*....|....*....|....*.
gi 1958664483  895 EDSGYYSCVANNNWGSDEIILNLQVQ 920
Cdd:cd05735     75 EDSGFFSCHAINSYGEDRGIIQLTVQ 100

Immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM) and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains NrCAM [Ng(neuronglia)CAM-related cell adhesion molecule], which is primarily expressed in the nervous system, and human neurofascin. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lacks a C" strand.

Pssm-ID: 409396 [Multi-domain] Cd Length: 94 Bit Score: 43.16 E-value: 7.11e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  838 VTTPWMKDIVLPCKAVGDPSPAVKWMKDsnGTPSLVTIDGRRSIFSN-GSFVI--RTVKAED-SGYYSCVANNNWG---S 910
Cdd:cd05733     11 YIVDPRDNITIKCEAKGNPQPTFRWTKD--GKFFDPAKDPRVSMRRRsGTLVIdnHNGGPEDyQGEYQCYASNELGtaiS 88


                   ....*
gi 1958664483  911 DEIIL 915
Cdd:cd05733     89 NEIRL 93

Immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan, also known as HSPG2, and similar proteins. Perlecan consists of five domains: domain I has three putative heparan sulfate attachment sites, domain II has four LDL receptor-like repeats, and one Ig-like repeat, domain III resembles the short arm of laminin chains, domain IV has multiple Ig-like repeats (21 repeats in human perlecan), and domain V resembles the globular G domain of the laminin A chain and internal repeats of EGF. Perlecan may participate in a variety of biological functions including cell binding, LDL-metabolism, basement membrane assembly and selective permeability, calcium binding, and growth- and neurite-promoting activities.

Pssm-ID: 143220 Cd Length: 78 Bit Score: 42.48 E-value: 7.25e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958664483  247 GKAVILNCSAEGYPVPTIVWKFSKGagvpqfqPIALNGRIQVLSN---GSLLIKHVVEEDSGYYLCKVSNDVG 316
Cdd:cd05743      1 GETVEFTCVATGVPTPIINWRLNWG-------HVPDSARVSITSEggyGTLTIRDVKESDQGAYTCEAINTRG 66

Third immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 143259 Cd Length: 88 Bit Score: 43.09 E-value: 7.69e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958664483  844 KDIVLPCKAVGDPSPAVKWMKDSNGTPSLVTIDgrrsiFSNGSFVIRTVKAEDSGYYSCVANNNWGSDE 912
Cdd:cd05851     17 QNVTLECFALGNPVPVIRWRKILEPMPATAEIS-----MSGAVLKIFNIQPEDEGTYECEAENIKGKDK 80

Fifth immunoglobulin (Ig) domain of contactin-1; The members here are composed of the fifth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409438 Cd Length: 89 Bit Score: 43.06 E-value: 7.77e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958664483  846 IVLPCKAVGDPSPAVKWmkdSNGTPSLVTiDGRRSIFSNGSFVIRTVKAEDSGYYSCVANNNWG 909
Cdd:cd05852     20 VIIECKPKAAPKPKFSW---SKGTELLVN-NSRISIWDDGSLEILNITKLDEGSYTCFAENNRG 79

Immunoglobulin (Ig)-like domain of human neurofascin (NF); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of human neurofascin (NF). NF belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and a cytoplasmic domain. NF has many alternatively spliced isoforms having different temporal expression patterns during development. NF participates in axon subcellular targeting and synapse formation, however little is known of the functions of the different isoforms. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lacks a C" strand.

Pssm-ID: 409459 Cd Length: 95 Bit Score: 42.66 E-value: 9.99e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  235 FVVQPRDQdgiygkaVILNCSAEGYPVPTIVWKFSKgagvpQFQPIALNGRIQVLS-NGSLLI----KHVVEEDSGYYLC 309
Cdd:cd05875     11 YIVDPRDN-------ILIECEAKGNPVPTFHWTRNG-----KFFNVAKDPRVSMRRrSGTLVIdfrgGGRPEDYEGEYQC 78

                           90
                   ....*....|....*.
gi 1958664483  310 KVSNDVGADVSKSMYL 325
Cdd:cd05875     79 FARNKFGTALSNKIRL 94

Second immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains.

Pssm-ID: 409400 [Multi-domain] Cd Length: 91 Bit Score: 42.69 E-value: 1.02e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958664483  850 CKAVGDPSPAVKWMKDSngTP-SLVTIDGRRSIFSNGSFVIRTVKAEDSGYYSCVANNNWGS 910
Cdd:cd05738     21 CAASGNPDPEISWFKDF--LPvDTATSNGRIKQLRSGALQIENSEESDQGKYECVATNSAGT 80

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 42.52 E-value: 1.17e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958664483   60 AGRDTYIHCRVIGYPYYSIKWYKNANLLPFNHRqVAFENNGTLKLSDVQKEvDEGEYTCNV 120
Cdd:cd20957     15 FGRTAVFNCSVTGNPIHTVLWMKDGKPLGHSSR-VQILSEDVLVIPSVKRE-DKGMYQCFV 73

Fifth immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3 (also known as Neph2). This protein has five Ig-like domains, one transmembrane domain, and a cytoplasmic tail. Included in this group is mammalian Kirrel (also known as Neph1), Kirrel2 (also known as Neph3), and Drosophila RST (also known as irregular chiasm C-roughest) protein. These proteins contain multiple Ig domains, have properties of cell adhesion molecules, and are important in organ development.

Pssm-ID: 319310 Cd Length: 98 Bit Score: 42.52 E-value: 1.26e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  330 PAMITSyPNTTLATQGQRKEMSCTAHGEKP---IIVRWeKEDRIINPEMARYLVSTKEVGEEVISTLQILPTVRED-SGF 405
Cdd:cd05758      2 PPIITA-EATQPAILGEKARLECLVFSSPPpdrIVWSW-DEGFLESGSSGRFSVETFPTEPGVISVLHISGTQRSDfQTS 79

                           90
                   ....*....|....*...
gi 1958664483  406 FSCHAINSYGEDRGIIQL 423
Cdd:cd05758     80 FNCSAWNRFGEGTAIVSL 97

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 42.50 E-value: 1.32e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958664483   55 NITAIAGRDTYIHCRVIGYPYYSIKWYKNANLL-PFNHRQVAFENNGTLKLSDVQKEvDEGEYTC 118
Cdd:cd20970     11 TVTAREGENATFMCRAEGSPEPEISWTRNGNLIiEFNTRYIVRENGTTLTIRNIRRS-DMGIYLC 74

Third immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 143259 Cd Length: 88 Bit Score: 41.93 E-value: 1.47e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  139 PPFIQ-PFEFPRFSIGQRVFIPCVVVSGDLPItITWQKDGRPIPASLGVTIDNidftSSLRISNLSLMHNGNYTCIARNE 217
Cdd:cd05851      1 PADINvKFKDTYALKGQNVTLECFALGNPVPV-IRWRKILEPMPATAEISMSG----AVLKIFNIQPEDEGTYECEAENI 75

                           90
                   ....*....|...
gi 1958664483  218 AAAVEHQSQLIVR 230
Cdd:cd05851     76 KGKDKHQARVYVQ 88

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM and human neurofascin.

Pssm-ID: 409394 [Multi-domain] Cd Length: 83 Bit Score: 42.01 E-value: 1.57e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958664483  845 DIVLPCKAVGDPSPAVKWMKDSNGTPSlvtidGRRSIFS-NGSFVIRTVKAEDSGYYSCVANNNWGS 910
Cdd:cd05731     12 VLLLECIAEGLPTPDIRWIKLGGELPK-----GRTKFENfNKTLKIENVSEADSGEYQCTASNTMGS 73

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1(FGFRL1); member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 is comprised of a signal peptide, three extracellular Ig-like modules, a transmembrane segment, and a short intracellular domain. FGFRL1 is expressed preferentially in skeletal tissues. Similar to FGF receptors, the expressed protein interacts specifically with heparin and with FGF2. FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409442 Cd Length: 92 Bit Score: 42.15 E-value: 1.64e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958664483  848 LPCKAVGDPSPAVKWMKDSNGTPSLVTIDGRRSIFsngSFVIRTVKAEDSGYYSCVANNNWG 909
Cdd:cd05856     24 LKCVASGNPRPDITWLKDNKPLTPPEIGENKKKKW---TLSLKNLKPEDSGKYTCHVSNRAG 82

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 41.61 E-value: 1.74e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958664483  153 GQRVFIPCVVvSGDLPITITWQKDGRPIPASLGVTIDNidftSSLRISNLSLMHNGNYTCIARNEAAAVEHQSQLIV 229
Cdd:cd05725     12 DDSAEFQCEV-GGDPVPTVRWRKEDGELPKGRYEILDD----HSLKIRKVTAGDMGSYTCVAENMVGKIEASATLTV 83

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three IG-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans.

Pssm-ID: 409443 [Multi-domain] Cd Length: 95 Bit Score: 42.15 E-value: 1.82e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958664483  850 CKAVGDPSPAVKWMKDSNGTPSLVTIDGRRSIFSNGSFVIRTVKAEDSGYYSCVANNNWGS 910
Cdd:cd05857     26 CPAAGNPTPTMRWLKNGKEFKQEHRIGGYKVRNQHWSLIMESVVPSDKGNYTCVVENEYGS 86

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409582 Cd Length: 91 Bit Score: 42.01 E-value: 1.87e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  832 LTFSGTVTTPWMKDIVLPCKAVGDPSPAVKWMKDsnGTPSLVTIDGRRSIFSNG--SFVIRTVKAEDSGYYSCVANNNWG 909
Cdd:cd20990      4 LQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLD--GKPIRPDSAHKMLVRENGvhSLIIEPVTSRDAGIYTCIATNRAG 81

                           90
                   ....*....|
gi 1958664483  910 SDEIILNLQV 919
Cdd:cd20990     82 QNSFNLELVV 91

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 41.80 E-value: 1.98e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958664483  846 IVLPCKAVGDPSPAVKWMKDSNGTPSLVTIdgrrSIFSNG---SFVIRTVKAEDSGYYSCVANNNWGSD 911
Cdd:cd20972     19 VRLECRVTGNPTPVVRWFCEGKELQNSPDI----QIHQEGdlhSLIIAEAFEEDTGRYSCLATNSVGSD 83

IL-beta-binding protein; Provisional

Pssm-ID: 165149 [Multi-domain] Cd Length: 326 Bit Score: 45.39 E-value: 2.09e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  250 VILNCS-----AEGYPVPTIVWKfSKGAGvpqfqpialNGRIQVLSNGS-LLIKHVVEEDSGYYLCKVSNDVGADVsksM 323
Cdd:PHA02785    44 VILPCPqintlSSGYNILDILWE-KRGAD---------NDRIIPIDNGSnMLILNPTQSDSGIYICITKNETYCDM---M 110

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  324 YLTVKIPAM------ITSYPNttLATQGQRKEMSC-------TAHGEKPIIvrWEKEDRIINpemarylvstKEVGEEVI 390
Cdd:PHA02785   111 SLNLTIVSVsesnidLISYPQ--IVNERSTGEMVCpninafiASNVNADII--WSGHRRLRN----------KRLKQRTP 176

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1958664483  391 STLQILPTVREDSGFFSCHAINSYGED----RGIIQLTVQEPPDPPEIEIKDV 439
Cdd:PHA02785   177 GIITIEDVRKNDAGYYTCVLKYIYGDKtynvTRIVKLEVRDRIIPPTMQLPEG 229

Phage-related protein, tail protein J [Mobilome: prophages, transposons];

Pssm-ID: 443767 [Multi-domain] Cd Length: 978 Bit Score: 46.09 E-value: 2.13e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  443 TITLRWTMGFDGNSpitgYDIECKNKSDSWDSAQRTkdvspqlnSATIIDIH--PSSTYSIRMYAKNRIGKS---EPSNE 517
Cdd:COG4733    553 TLTVSWDAPAGAVA----YEVEWRRDDGNWVSVPRT--------SGTSFEVPgiYAGDYEVRVRAINALGVSsawAASSE 620

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  518 ITITADEAAPdGPPQEVHLEPTSSQsIRVTWKAPkkhlQNGIIRGYQIGYREYSTGGNFQFniISIDTTGDSevYTLDNL 597
Cdd:COG4733    621 TTVTGKTAPP-PAPTGLTATGGLGG-ITLSWSFP----VDADTLRTEIRYSTTGDWASATV--AQALYPGNT--YTLAGL 690

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*...
gi 1958664483  598 NKFTQYGLVVQACNRAGTgPSSQEIITTTLEDVPSYPPENVQAIATSP 645
Cdd:COG4733    691 KAGQTYYYRARAVDRSGN-VSAWWVSGQASADAAGILDAITGQILETE 737

Fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule); The members here are composed of the fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule). NrCAM belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six IG-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. NrCAM is primarily expressed in the nervous system.

Pssm-ID: 409454 Cd Length: 89 Bit Score: 41.51 E-value: 2.40e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958664483  844 KDIVLPCKAVGDPSPAVKWMkdSNGTPSLVT-------IDGRRSIFSNgsfvirtVKAEDSGYYSCVANNNWG 909
Cdd:cd05868     15 EDGTLICRANGNPKPSISWL--TNGVPIEIAptdpsrkVDGDTIIFSK-------VQERSSAVYQCNASNEYG 78

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 41.77 E-value: 2.68e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  830 RILTFSGTVTTPWMKDIVLPCKAVGDPSPAVKWMKdsNGTPsLVT----IDGRRSIFSNGS-FVIRTVKA----EDSGYY 900
Cdd:cd07693      2 RIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLK--NGQP-LETdkddPRSHRIVLPSGSlFFLRVVHGrkgrSDEGVY 78


                   ....*....
gi 1958664483  901 SCVANNNWG 909
Cdd:cd07693     79 VCVAHNSLG 87

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 41.48 E-value: 2.75e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  136 VKVPPFIQPFEfprfsIGQRVFIPCVVVSGDLPiTITWQKDGRPIPASLGVTIDNIDFTSSLRISNLSLMHNGNYTCIAR 215
Cdd:cd05736      3 IRVYPEFQAKE-----PGVEASLRCHAEGIPLP-RVQWLKNGMDINPKLSKQLTLIANGSELHISNVRYEDTGAYTCIAK 76

                           90
                   ....*....|....
gi 1958664483  216 NEAAAVEHQSQLIV 229
Cdd:cd05736     77 NEGGVDEDISSLFV 90

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains, five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

Pssm-ID: 409460 [Multi-domain] Cd Length: 83 Bit Score: 41.05 E-value: 2.77e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958664483  846 IVLPCKAVGDPSPAVKWMKDSNGTPSLVTIDGrrsiFSNGSFVIRTVKAEDSGYYSCVANNNWGS 910
Cdd:cd05876     13 LVLECIAEGLPTPTVKWLRPSGPLPPDRVKYQ----NHNKTLQLLNVGESDDGEYVCLAENSLGS 73

Immunoglobulin V-set domain; This domain is found in antibodies as well as neural protein P0 and CTL4 amongst others.

Pssm-ID: 462230 Cd Length: 109 Bit Score: 41.67 E-value: 2.93e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  237 VQPRDQDGIYGKAVILNC---SAEGYPVPTIVWKFSKGAGVPQF---------QPIALNGRIQVL-----SNGSLLIKHV 299
Cdd:pfam07686    1 QTPREVTVALGGSVTLPCtysSSMSEASTSVYWYRQPPGKGPTFliayysngsEEGVKKGRFSGRgdpsnGDGSLTIQNL 80

                           90       100
                   ....*....|....*....|....*...
gi 1958664483  300 VEEDSGYYLCKVSNDVGADVSKSMYLTV 327
Cdd:pfam07686   81 TLSDSGTYTCAVIPSGEGVFGKGTRLTV 108

Sixth immunoglobulin (Ig) domain of contactin-4; The members here are composed of the sixth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-4. Contactins are neural cell adhesion molecules, and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The different contactins show different expression patterns in the central nervous system. Highest expression of contactin-4 is in testes, thyroid, small intestine, uterus, and brain. Contactin-4 plays a role in the response of neuroblastoma cells to differentiating agents, such as retinoids. The contactin 4 gene is associated with cerebellar degeneration in spinocerebellar ataxia type 16.

Pssm-ID: 409439 Cd Length: 102 Bit Score: 41.53 E-value: 3.02e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  136 VKVPPFIQPFefprfSIGQRVFIPCVVVSG-DLPITITWQKDGRPIPASL-GVTIDNI---DFTSSLRISNLSLMHNGNY 210
Cdd:cd05853      5 VMVPPSSMDV-----TVGESIVLPCQVSHDhSLDIVFTWSFNGHLIDFQKdGDHFERVggqDSAGDLMIRSIQLKHAGKY 79

                           90       100
                   ....*....|....*....|...
gi 1958664483  211 TCIARNEAAAVEHQSQLIVRVPP 233
Cdd:cd05853     80 VCMVQTSVDKLSAAADLIVRGPP 102

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 41.08 E-value: 3.19e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483   47 PASIRPMKNITAIAGRDTYIHCRVIGYPYYSIKWYKNANLLPFNHRQVAFE-NNGTLKLSDVQKEvDEGEYTCnvLVQPQ 125
Cdd:cd20976      2 PSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQYAADRSTCEaGVGELHIQDVLPE-DHGTYTC--LAKNA 78

                           90
                   ....*....|..
gi 1958664483  126 LST-SQSVHVTV 136
Cdd:cd20976     79 AGQvSCSAWVTV 90

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 41.04 E-value: 3.33e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958664483  258 GYPVPTIVWKfsKGAgvpqfQPIALNGRIQV---LSNGSLLIKHVVEEDSGYYLCKVSNDVGadvSKSMYLTVKI 329
Cdd:cd05748     18 GRPTPTVTWS--KDG-----QPLKETGRVQIettASSTSLVIKNAKRSDSGKYTLTLKNSAG---EKSATINVKV 82

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409582 Cd Length: 91 Bit Score: 41.24 E-value: 3.46e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  233 PKFVVQPRDQDGIYGKAVILNCSAEGYPVPTIVWKFSkgaGVPqFQPIALNgRIQVLSNG--SLLIKHVVEEDSGYYLCK 310
Cdd:cd20990      1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLD---GKP-IRPDSAH-KMLVRENGvhSLIIEPVTSRDAGIYTCI 75

                           90
                   ....*....|....*..
gi 1958664483  311 VSNDVGADvSKSMYLTV 327
Cdd:cd20990     76 ATNRAGQN-SFNLELVV 91

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143223 Cd Length: 69 Bit Score: 40.24 E-value: 3.51e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958664483  250 VILNCSAEGYPVPTIVWKfSKGAGVPQfqpialNGRIQVLSNGSLLIKHVVEEDSGYYLCKVSNDVGAdVSKSMYLT 326
Cdd:cd05746      1 VQIPCSAQGDPEPTITWN-KDGVQVTE------SGKFHISPEGYLAIRDVGVADQGRYECVARNTIGY-ASVSMVLS 69

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.

Pssm-ID: 409541 [Multi-domain] Cd Length: 89 Bit Score: 40.78 E-value: 3.91e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958664483  844 KDIVLPCKAVGDPSPAVKWMKDSNGTPSLVTIDGRRSIFSNGsFVIRTVKAEDSGYYSCVANNNWGSDEIILNLQV 919
Cdd:cd20949     15 QSATILCEVKGEPQPNVTWHFNGQPISASVADMSKYRILADG-LLINKVTQDDTGEYTCRAYQVNSIASDMQERTV 89

C-terminal immunoglobulin (Ig)-like domain of M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of M-protein (also known as myomesin-2). M-protein is a structural protein localized to the M-band, a transverse structure in the center of the sarcomere, and is a candidate for M-band bridges. M-protein is modular consisting mainly of repetitive IG-like and fibronectin type III (FnIII) domains and has a muscle-type specific expression pattern. M-protein is present in fast fibers.

Pssm-ID: 143299 Cd Length: 92 Bit Score: 41.05 E-value: 4.01e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  838 VTTPWMKDIVLPCKAVGDPSPAVKWMK-DSNGTPS---LVTIDGRRSIfsngSFVIRTVKAEDSGYYSCVANNNWGSDEI 913
Cdd:cd05891     11 VTIMEGKTLNLTCTVFGNPDPEVIWFKnDQDIELSehySVKLEQGKYA----SLTIKGVTSEDSGKYSINVKNKYGGETV 86


                   ....*.
gi 1958664483  914 ILNLQV 919
Cdd:cd05891     87 DVTVSV 92

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.

Pssm-ID: 409408 [Multi-domain] Cd Length: 92 Bit Score: 40.96 E-value: 4.02e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  240 RDQDGIYGKAVILNCSAEG-YPVPTIVWkFSKGAGVPQFQPIAL---NGRiqvlSNGSLLIKHVVEEDSGYYLCKVSNDV 315
Cdd:cd05750      7 KSQTVQEGSKLVLKCEATSeNPSPRYRW-FKDGKELNRKRPKNIkirNKK----KNSELQINKAKLEDSGEYTCVVENIL 81


                   ....*..
gi 1958664483  316 GADVSKS 322
Cdd:cd05750     82 GKDTVTG 88

First immunoglobulin (Ig) domain of contactin; member of the I-set of (Ig) superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409356 [Multi-domain] Cd Length: 96 Bit Score: 41.07 E-value: 4.16e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  233 PKFVVQPRD----QDGIYGKaVILNCSAEGYPVPTIVWKFSKGAgvpqfQPIALNGRIQvLSNGSLLIKHVVE-EDSGYY 307
Cdd:cd04967      2 PVFEEQPDDtifpEDSDEKK-VALNCRARANPVPSYRWLMNGTE-----IDLESDYRYS-LVDGTLVISNPSKaKDAGHY 74

                           90
                   ....*....|....*...
gi 1958664483  308 LCKVSNDVGADVSKSMYL 325
Cdd:cd04967     75 QCLATNTVGSVLSREATL 92

Immunoglobulin (Ig)-like domain found in Perlecan and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain found in Perlecan. Perlecan is a large multi-domain heparin sulfate proteoglycan, important in tissue development and organogenesis. Perlecan can be represented as 5 major portions; its fourth major portion (domain IV) is a tandem repeat of immunoglobulin-like domains (Ig2-Ig15) which can vary in size due to alternative splicing. Perlecan binds many cellular and extracellular ligands. Its domain IV region has many binding sites. Some of these have been mapped at the level of individual Ig-like domains, including a site restricted to the Ig5 domain for heparin/sulfatide, a site restricted to the Ig3 domain for nidogen-1 and nidogen-2, a site restricted to Ig4-5 for fibronectin, and sites restricted to Ig2 and to Ig13-15 for fibulin-2. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409412 Cd Length: 85 Bit Score: 40.62 E-value: 4.49e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958664483  837 TVTTPWMKDIVLPCKAVG-DPSPAVKWMKdSNGT-PSlvtidgrRSIFSNGSFVIRTVKAEDSGYYSCVANNNWGSDE 912
Cdd:cd05754     10 SQEVRPGADVSFICRAKSkSPAYTLVWTR-VNGTlPS-------RAMDFNGILTIRNVQLSDAGTYVCTGSNMLDTDE 79

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 40.71 E-value: 5.23e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  333 ITSYPNTTLATQGQRKEMSCTAHGEKPIIVRWEKEDRIINPEMARYLVSTKEVGEEVISTLQIlptvrEDSGFFSCHAIN 412
Cdd:cd05736      3 IRVYPEFQAKEPGVEASLRCHAEGIPLPRVQWLKNGMDINPKLSKQLTLIANGSELHISNVRY-----EDTGAYTCIAKN 77

                           90
                   ....*....|....*
gi 1958664483  413 SYGEDRGIIQLTVQE 427
Cdd:cd05736     78 EGGVDEDISSLFVED 92

Immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan, also known as HSPG2, and similar proteins. Perlecan consists of five domains: domain I has three putative heparan sulfate attachment sites, domain II has four LDL receptor-like repeats, and one Ig-like repeat, domain III resembles the short arm of laminin chains, domain IV has multiple Ig-like repeats (21 repeats in human perlecan), and domain V resembles the globular G domain of the laminin A chain and internal repeats of EGF. Perlecan may participate in a variety of biological functions including cell binding, LDL-metabolism, basement membrane assembly and selective permeability, calcium binding, and growth- and neurite-promoting activities.

Pssm-ID: 143220 Cd Length: 78 Bit Score: 40.17 E-value: 5.25e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958664483  153 GQRVFIPCVVVSGDLPItITWQKDGRPIPASLGVTIDNIDFTSSLRISNLSLMHNGNYTCIARNEAAAVEHQSQLIVRV 231
Cdd:cd05743      1 GETVEFTCVATGVPTPI-INWRLNWGHVPDSARVSITSEGGYGTLTIRDVKESDQGAYTCEAINTRGMVFGIPDGILTV 78

Immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins; member of the I-set of IgSF domains; This group contains the immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins. The SALM (for synaptic adhesion-like molecules; also known as Lrfn for leucine-rich repeat and fibronectin type III domain containing) family of adhesion molecules consists of five known members: SALM1/Lrfn2, SALM2/Lrfn1, SALM3/Lrfn4, SALM4/Lrfn3, and SALM5/Lrfn5. SALMs share a similar domain structure, containing leucine-rich repeats (LRRs), an immunoglobulin (Ig) domain, and a fibronectin III (FNIII) domain, followed by a transmembrane domain and a C-terminal PDZ-binding motif. SALM5 is implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons. SALM5 interacts with the Ig domains of LAR (Leukocyte common Antigen-Related) family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPdelta, and PTPsigma). In addition, PTPdelta is implicated in ASDs, ADHD, bipolar disorder, and restless leg syndrome. Studies have shown that LAR-RPTPs are novel and splicing-dependent presynaptic ligands for SALM5, and that they mediate SALM5-dependent presynaptic differentiation. Furthermore, SALM5 maintains AMPA receptor (AMPAR)-mediated excitatory synaptic transmission through mechanisms involving the interaction of SALM5 with LAR-RPTPs. This group belongs to the I-set of immunoglobulin superfamily (IgSF) domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409421 [Multi-domain] Cd Length: 88 Bit Score: 40.54 E-value: 5.27e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  227 LIVRVPPKFVVqprdqdgIYGKAVILNCSAEGYPVPTIVWKFSKGAGVPQfqpialNGRIQVLSNGSLLIKHVVEEDSGY 306
Cdd:cd05764      2 LITRHTHELRV-------LEGQRATLRCKARGDPEPAIHWISPEGKLISN------SSRTLVYDNGTLDILITTVKDTGA 68

                           90
                   ....*....|
gi 1958664483  307 YLCKVSNDVG 316
Cdd:cd05764     69 FTCIASNPAG 78

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.

Pssm-ID: 409408 [Multi-domain] Cd Length: 92 Bit Score: 40.57 E-value: 5.39e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958664483  140 PFIQPFEFPRFSIGQRVFIPCVVVSGDLPITITWQKDGRPIPA--SLGVTIDNIDFTSSLRISNLSLMHNGNYTCIARN 216
Cdd:cd05750      1 PKLKEMKSQTVQEGSKLVLKCEATSENPSPRYRWFKDGKELNRkrPKNIKIRNKKKNSELQINKAKLEDSGEYTCVVEN 79

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 40.17 E-value: 5.87e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958664483  152 IGQRVFIPCVVVSGDLPiTITWQKDGRPIPA--SLGVTIDNidftSSLRISNLSLMHNGNYTCIARN 216
Cdd:cd20952     13 VGGTVVLNCQATGEPVP-TISWLKDGVPLLGkdERITTLEN----GSLQIKGAEKSDTGEYTCVALN 74

Immunoglobulin V-set domain; This domain is found in antibodies as well as neural protein P0 and CTL4 amongst others.

Pssm-ID: 462230 Cd Length: 109 Bit Score: 40.90 E-value: 6.18e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483   56 ITAIAGRDTYIHCRV---IGYPYYSIKWYKN-------------ANLLPFNHRQVAFE-------NNGTLKLSDVQKEvD 112
Cdd:pfam07686    6 VTVALGGSVTLPCTYsssMSEASTSVYWYRQppgkgptfliayySNGSEEGVKKGRFSgrgdpsnGDGSLTIQNLTLS-D 84

                           90       100
                   ....*....|....*....|....
gi 1958664483  113 EGEYTCNVLVQPQLSTSQSVHVTV 136
Cdd:pfam07686   85 SGTYTCAVIPSGEGVFGKGTRLTV 108

First immunoglobulin (Ig)-like domain of Tyro3 receptor tyrosine kinase (RTK), and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain of Tyro3 receptor tyrosine kinase (RTK). Tyro3 together with Axl and Mer form the Axl/Tyro3 family of receptor tyrosine kinases (RTKs). This family includes Axl (also known as Ark, Ufo, and Tyro7), Tyro3 (also known as Sky, Rse, Brt, Dtk, and Tif), and Mer (also known as Nyk, c-Eyk, and Tyro12). Axl/Tyro3 family receptors have an extracellular portion with two Ig-like domains followed by two fibronectin-types III (FNIII) domains, a membrane-spanning single helix, and a cytoplasmic tyrosine kinase domain. Axl, Tyro3 and Mer are widely expressed in adult tissues, though they show higher expression in the brain, in the lymphatic and vascular systems, and in the testis. Axl, Tyro3, and Mer bind the vitamin K dependent protein Gas6 with high affinity, and in doing so activate their tyrosine kinase activity. Axl/Gas6 signaling may play a part in cell adhesion processes, prevention of apoptosis, and cell proliferation.

Pssm-ID: 409553 Cd Length: 87 Bit Score: 40.12 E-value: 7.01e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  247 GKAVILNCSAEGYPVPTIVWkFSKGAGVPQ----FQPIALNGRIQVLSngsllIKHVVEEDSGYYLCKVSNDVGADVSKS 322
Cdd:cd20961      8 GQPVKLNCSVEGMEEPDIQW-VKDGAVVQNldqlYIPVSEQHWIGFLS-----LKSVERSDAGRYWCQVEDGGETEISQP 81


                   ....*.
gi 1958664483  323 MYLTVK 328
Cdd:cd20961     82 VWLTVE 87

Sixth immunoglobulin (Ig) domain of contactin; The members here are composed of the sixth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409359 Cd Length: 102 Bit Score: 40.61 E-value: 7.53e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  151 SIGQRVFIPCVVvSGD--LPITITWQKDGRPI----PASLGVTIDNIDFTSSLRISNLSLMHNGNYTCIARNEAAAVEHQ 224
Cdd:cd04970     15 TVGENATLQCHA-SHDptLDLTFTWSFNGVPIdlekIEGHYRRRYGKDSNGDLEIVNAQLKHAGRYTCTAQTVVDSDSAS 93


                   ....*....
gi 1958664483  225 SQLIVRVPP 233
Cdd:cd04970     94 ATLVVRGPP 102

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 40.14 E-value: 7.91e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958664483  153 GQRVFIPCVVVSGDLPiTITWQKDGRPIPASLGVTI-DNidftSSLRISNLSLMHNGNYTCIARN 216
Cdd:cd04969     17 GGDVIIECKPKASPKP-TISWSKGTELLTNSSRICIlPD----GSLKIKNVTKSDEGKYTCFAVN 76

Immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan, also known as HSPG2, and similar proteins. Perlecan consists of five domains: domain I has three putative heparan sulfate attachment sites, domain II has four LDL receptor-like repeats, and one Ig-like repeat, domain III resembles the short arm of laminin chains, domain IV has multiple Ig-like repeats (21 repeats in human perlecan), and domain V resembles the globular G domain of the laminin A chain and internal repeats of EGF. Perlecan may participate in a variety of biological functions including cell binding, LDL-metabolism, basement membrane assembly and selective permeability, calcium binding, and growth- and neurite-promoting activities.

Pssm-ID: 143220 Cd Length: 78 Bit Score: 39.78 E-value: 8.49e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958664483  848 LPCKAVGDPSPAVKWMKDSNGTPS----LVTIDGRRsifsnGSFVIRTVKAEDSGYYSCVANNNWG 909
Cdd:cd05743      6 FTCVATGVPTPIINWRLNWGHVPDsarvSITSEGGY-----GTLTIRDVKESDQGAYTCEAINTRG 66

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM and human neurofascin.

Pssm-ID: 409394 [Multi-domain] Cd Length: 83 Bit Score: 39.70 E-value: 8.53e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  171 ITWQKDGRPIPASLGVTiDNidFTSSLRISNLSLMHNGNYTCIARNEAAAVEHQSQLIVR 230
Cdd:cd05731     27 IRWIKLGGELPKGRTKF-EN--FNKTLKIENVSEADSGEYQCTASNTMGSARHTISVTVE 83

Immunoglobulin-like domain of human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin I-set (IgI) domain of the Human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins. APEG-1 is a novel specific smooth muscle differentiation marker predicted to play a role in the growth and differentiation of arterial smooth muscle cells (SMCs). The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the human APEG-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409567 Cd Length: 91 Bit Score: 39.76 E-value: 9.52e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  844 KDIVLPCKAVGDPSPAVKWMKdsNGTPslVTIDGRR--SIFSNGSFVIRTVKAE--DSGYYSCVANNNWGSDEIILNLQV 919
Cdd:cd20975     16 QDVIMSIRVQGEPKPVVSWLR--NRQP--VRPDQRRfaEEAEGGLCRLRILAAErgDAGFYTCKAVNEYGARQCEARLEV 91

Fifth immunoglobulin (Ig) domain of contactin-1; The members here are composed of the fifth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409438 Cd Length: 89 Bit Score: 39.60 E-value: 9.97e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  233 PKFVVQPRDQDGIYGKA--VILNCSAEGYPVPTIVWkfSKGAgvpqfQPIALNGRIQVLSNGSLLIKHVVEEDSGYYLCK 310
Cdd:cd05852      1 PTFEFNPMKKKILAAKGgrVIIECKPKAAPKPKFSW--SKGT-----ELLVNNSRISIWDDGSLEILNITKLDEGSYTCF 73


                   ....*.
gi 1958664483  311 VSNDVG 316
Cdd:cd05852     74 AENNRG 79

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 39.74 E-value: 1.08e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  229 VRVPPKFVVQPrdqdgiyGKAVILNCSAEGYPVPTIVWKFSkgaGVP-QFQPIA----LNGRIQVLSNgsllikhVVEED 303
Cdd:cd04978      3 IIEPPSLVLSP-------GETGELICEAEGNPQPTITWRLN---GVPiEPAPEDmrrtVDGRTLIFSN-------LQPND 65

                           90
                   ....*....|...
gi 1958664483  304 SGYYLCKVSNDVG 316
Cdd:cd04978     66 TAVYQCNASNVHG 78

Immunoglobulin (Ig)-like domain of human carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) domains 2, 4, and 6, and similar domains; The members here are composed of the second, fourth, and sixth immunoglobulin (Ig)-like domains in human carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) protein subfamily. The CEA family is a group of anchored or secreted glycoproteins expressed by epithelial cells, leukocytes, endothelial cells, and placenta. The CEA family is divided into the CEACAM and pregnancy-specific glycoprotein (PSG) subfamilies. This group represents the CEACAM subfamily. CEACAM1 has many important cellular functions; it is a cell adhesion molecule and a signaling molecule that regulates the growth of tumor cells, an angiogenic factor, and a receptor for bacterial and viral pathogens, including mouse hepatitis virus (MHV). In mice, four isoforms of CEACAM1 generated by alternative splicing have either two [D1, D4] or four [D1-D4] Ig-like domains on the cell surface.

Pssm-ID: 409402 [Multi-domain] Cd Length: 89 Bit Score: 39.69 E-value: 1.20e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  249 AVILNCSAEGyPVPTIVWKFSKgagvpqfQPIALNGRIQvLSNG--SLLIKHVVEEDSGYYLCKVSNDVGADVSKSMYLT 326
Cdd:cd05740     17 AVTLTCEPET-QNTSYLWWFNG-------QSLPVTPRLT-LSNGnrTLTLLNVTREDAGAYQCEISNPVSANRSDPVTLD 87


                   .
gi 1958664483  327 V 327
Cdd:cd05740     88 V 88

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 39.30 E-value: 1.25e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958664483  844 KDIVLPCKAVGDPSPAVKWMKDSNGTPSlvtidgrrsifsNGSFVIRTVKAEDSGYYSCVANNNWGS 910
Cdd:pfam13895   15 EPVTLTCSAPGNPPPSYTWYKDGSAISS------------SPNFFTLSVSAEDSGTYTCVARNGRGG 69

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 39.48 E-value: 1.30e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  142 IQPFEFPRFSIGQRVFIPCVVVSGDLPiTITWQKDGRPIPASLGVTID-NIDFTSSLRISNLSLMHNGNYTCIARNEAAA 220
Cdd:cd20973      1 IQTLRDKEVVEGSAARFDCKVEGYPDP-EVKWMKDDNPIVESRRFQIDqDEDGLCSLIISDVCGDDSGKYTCKAVNSLGE 79


                   ....*....
gi 1958664483  221 VEHQSQLIV 229
Cdd:cd20973     80 ATCSAELTV 88

Second immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of this group show that the second Ig domain lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules, including vascular (VCAM), intercellular (ICAM), neural (NCAM) and mucosal addressin (MADCAM) cell adhesion molecules, as well as junction adhesion molecules (JAM).

Pssm-ID: 409557 Cd Length: 101 Bit Score: 39.54 E-value: 1.37e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958664483  245 IYGKAVILNCS-AEGYPVPTIVWKFSKGAGVPQFQPIaLNGRIQVLSNGSLLIKHVVEED---SGYYLCKVSN 313
Cdd:cd20965     15 VEGKPFKLDCNvPPGYPKPTIEWKKQLVSDSSKADTI-LDRRITISPNGDLYFTNVTKEDvstDYKYVCVAKT 86

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409422 [Multi-domain] Cd Length: 95 Bit Score: 39.45 E-value: 1.40e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  233 PKFVVQPRDQDGIYGKAVILNCSAEGYPVPTIVW-KFSKGAGVPQFQPIALNGRIQVLSNGSLLIKHVVEEDSGYYLCKV 311
Cdd:cd05765      1 PALVNSPTHQTVKVGETASFHCDVTGRPQPEITWeKQVPGKENLIMRPNHVRGNVVVTNIGQLVIYNAQPQDAGLYTCTA 80


                   ....*
gi 1958664483  312 SNDVG 316
Cdd:cd05765     81 RNSGG 85

Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409357 [Multi-domain] Cd Length: 88 Bit Score: 39.45 E-value: 1.41e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958664483  153 GQRVFIPCVVVSGDLPiTITWQK-DGRPIPASLGVTIDNIdftssLRISNLSLMHNGNYTCIARNEAAAVEHQSQLIV 229
Cdd:cd04968     16 GQTVTLECFALGNPVP-QIKWRKvDGSPSSQWEITTSEPV-----LEIPNVQFEDEGTYECEAENSRGKDTVQGRIIV 87

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 39.48 E-value: 1.41e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958664483   50 IRPMKNITAIAGRDTYIHCRVIGYPYYSIKWYKNAN-LLPFNHRQVAFENNG--TLKLSDVQKEvDEGEYTC 118
Cdd:cd20973      1 IQTLRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNpIVESRRFQIDQDEDGlcSLIISDVCGD-DSGKYTC 71

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.

Pssm-ID: 409408 [Multi-domain] Cd Length: 92 Bit Score: 39.42 E-value: 1.47e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483   49 SIRPMKNITAIAGRDTYIHCRVIG-YPYYSIKWYKNANLL----PFNHRQVAFENNGTLKLSDVQKEvDEGEYTCnvLVQ 123
Cdd:cd05750      2 KLKEMKSQTVQEGSKLVLKCEATSeNPSPRYRWFKDGKELnrkrPKNIKIRNKKKNSELQINKAKLE-DSGEYTC--VVE 78

                           90
                   ....*....|....
gi 1958664483  124 PQL---STSQSVHV 134
Cdd:cd05750     79 NILgkdTVTGNVTV 92

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 38.92 E-value: 1.53e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  337 PNTTLATQGQRKEMSCTAHGEKPIIVRWEKEDRIINPEMaRYLVSTKEVgeevistlqilptvrEDSGFFSCHAINS-YG 415
Cdd:pfam13895    6 PSPTVVTEGEPVTLTCSAPGNPPPSYTWYKDGSAISSSP-NFFTLSVSA---------------EDSGTYTCVARNGrGG 69

                           90
                   ....*....|
gi 1958664483  416 EDRGIIQLTV 425
Cdd:pfam13895   70 KVSNPVELTV 79

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

Pssm-ID: 143223 Cd Length: 69 Bit Score: 38.70 E-value: 1.55e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958664483  156 VFIPCVVvSGDLPITITWQKDGRPIPASLGVTIDNIDFtssLRISNLSLMHNGNYTCIARN 216
Cdd:cd05746      1 VQIPCSA-QGDPEPTITWNKDGVQVTESGKFHISPEGY---LAIRDVGVADQGRYECVARN 57

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 39.33 E-value: 1.61e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  233 PKFVVQPRDQDGIYGKAVILNCSAEGYPVPTIVWKFSkgaGVPqFQPIALNGRIQVLSNG---SLLIKHVVEEDSGYYLC 309
Cdd:cd20951      1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKN---GVP-IDPSSIPGKYKIESEYgvhVLHIRRVTVEDSAVYSA 76


                   ....*..
gi 1958664483  310 KVSNDVG 316
Cdd:cd20951     77 VAKNIHG 83

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409422 [Multi-domain] Cd Length: 95 Bit Score: 39.45 E-value: 1.62e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958664483  850 CKAVGDPSPAVKWMKDSNGTPSLVT----IDGRRSIFSNGSFVIRTVKAEDSGYYSCVANNNWGS 910
Cdd:cd05765     22 CDVTGRPQPEITWEKQVPGKENLIMrpnhVRGNVVVTNIGQLVIYNAQPQDAGLYTCTARNSGGL 86

Fourth immunoglobulin (Ig)-like domain of platelet-derived growth factor receptor (PDGFR); The members here are composed of the fourth immunoglobulin (Ig)-like domain of platelet-derived growth factor receptor (PDGFR; also known as cluster of differentiation (CD) 140a) alpha and beta. PDGF is a potent mitogen for connective tissue cells. PDGF-stimulated processes are mediated by three different PDGFs (PDGF-A,PDGF-B, and PDGF-C). PDGFR alpha binds to all three PDGFs, whereas the PDGFR beta binds only to PDGF-B. PDGF alpha is organized as an extracellular component having five Ig-like domains, a transmembrane segment, and a cytoplasmic portion having protein tyrosine kinase activity. In mice, PDGFR alpha and PDGFR beta are essential for normal development.

Pssm-ID: 409445 Cd Length: 101 Bit Score: 39.46 E-value: 1.68e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958664483  161 VVVSGDLPITITWQKDGRPIPASLGVTIDNIDFTSSLR-ISNLSLMH-----NGNYTCIARNEAAAVEHQSQLIVRV 231
Cdd:cd05859     25 VEVEAYPPPQIRWLKDNRTLIENLTEITTSTRNVQETRyVSKLKLIRakeedSGLYTALAQNEDAVKSYTFALQIQV 101

N-terminal immunoglobulin (Ig)-like domain of T-cell surface antigen CD2, and similar domains; The members here are composed of the N-terminal immunoglobulin (Ig)-like domain (or domain 1) of T-cell surface antigen Clusters of Differentiation (CD) 2 and similar proteins. CD2 is a T-cell specific surface glycoprotein and is critically important for mediating adhesion between T cells and antigen-presenting cells or between cytolytic T cells and target cells. CD2 is located on chromosome 1 at 1p13 in humans and on chromosome 3 in mice. CD2 contains an extracellular domain with two or Ig-like domains, a single transmembrane segment, and a cytoplasmic region rich in proline and basic residues.

Pssm-ID: 409431 Cd Length: 98 Bit Score: 39.25 E-value: 1.76e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  244 GIYGKAVILNCSAEGYPVPTIVWKFSK--------GAGVPQFQPiaLNGRIQVL-SNGSLLIKHVVEEDSGYYLCKVSND 314
Cdd:cd05775      7 GALGGNVTLTISSLQDDIDEIKWKKTKdkivewenNIGPTYFGS--FKDRVLLDkESGSLTIKNLTKEDSGTYELEITST 84

                           90
                   ....*....|....
gi 1958664483  315 VGADVSKSMYLTVK 328
Cdd:cd05775     85 NGKVLSSKFTLEVL 98

First immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409436 [Multi-domain] Cd Length: 95 Bit Score: 39.17 E-value: 1.78e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958664483  846 IVLPCKAVGDPSPAVKWMKDsNGTPSLVTidgRRSIFSNGSFVIRTV-KAEDSGYYSCVANNNWG---SDEIILNL 917
Cdd:cd05849     22 VSVNCRARANPFPIYKWRKN-NLDIDLTN---DRYSMVGGNLVINNPdKYKDAGRYVCIVSNIYGkvrSREATLSF 93

Immunoglobulin Variable (IgV) domain in HERV-H LTR-associating 2 (HHLA2); The members here are composed of the immunoglobulin variable (IgV) region in HERV-H LTR-associating 2 (HHLA2; also known as B7-H7/B7 homolog 7). HHLA2 is a member of the B7 family of immune regulatory proteins. Mature human HHLA2 consists of an extracellular domain (ECD) with three immunoglobulin-like domains, a transmembrane segment, and a cytoplasmic domain. HHLA2 is widely expressed in human cancers including non-small cell lung carcinoma (NSCLS), triple negative breast cancer (TNBC), and melanoma, but has limited expression on normal tissues. Interestingly, unlike other members of B7 family, HHLA2 is not expressed in mice or rats. HHLA2 functions as a T cell coinhibitory molecules as it inhibits the proliferation of activated CD4(+) and CD8(+) T cells and their cytokine production. Furthermore, HHLA2 is constitutively expressed on the surface of human monocytes and is induced on B cells after stimulation, however it is not inducible on T cells.

Pssm-ID: 409512 Cd Length: 107 Bit Score: 39.68 E-value: 1.82e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  838 VTTPWMKDIVLPCKAVGDPSPAVKWMKDSN---------GTPSLVTID----GRRSIFS------NGSFVIRTVKAEDSG 898
Cdd:cd16091      7 VVCLLSEDCILPCSFTPGSEVVIHWYKQDSdikvhsyyyGKDQLESQDqryrNRTSLFKdqisngNASLLLRRVQLQDEG 86

                           90       100
                   ....*....|....*....|.
gi 1958664483  899 YYSCVANNNWGSDEIILNLQV 919
Cdd:cd16091     87 RYKCYTSTIIGNQESFVNLKV 107

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 2 (NCAM-2); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule NCAM-2 (also known as OCAM/mamFas II and RNCAM). NCAM-2 is organized similarly to NCAM, including five N-terminal Ig-like domains and two fibronectin type III domains. NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE), and may function like NCAM, as an adhesion molecule. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 143278 [Multi-domain] Cd Length: 98 Bit Score: 39.19 E-value: 1.88e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  846 IVLPCKAVGDPSPAVKWMKDSNG---TPSLVTIDGR---RSIFSNGSFVIRTVKAEDSGYYSCVANNNWG 909
Cdd:cd05870     19 ATLSCKAEGEPIPEITWKRASDGhtfSEGDKSPDGRievKGQHGESSLHIKDVKLSDSGRYDCEAASRIG 88

C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C); The members here are composed of the C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C). MyBP-C consists of repeated domains, Ig and fibronectin type 3, and various linkers. Three isoforms of MYBP-C exist: slow-skeletal (ssMyBP-C), fast-skeletal (fsMyBP-C), and cardiac (cMyBP-C). cMYBP-C has insertions between and inside domains and an additional cardiac-specific Ig domain at the N-terminus. For cMYBP_C an interaction has been demonstrated between this C5 domain and the Ig C8 domain.

Pssm-ID: 409475 Cd Length: 86 Bit Score: 38.67 E-value: 1.97e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958664483  854 GDPSPAVKWMKdsnGTPSLVTIDGRRSIFSN---GSFVIRTVKAEDSGYYSCVANNNWGSDEIILNLQV 919
Cdd:cd05894     21 GEPAPTVTWSR---GDKAFTATEGRVRVESYkdlSSFVIEGAEREDEGVYTITVTNPVGEDHASLFVKV 86

Immunoglobulin-like Ig0 domain of basigin-1 (BSG1) and similar proteins; The members here are composed of the immunoglobulin (Ig) domain of the collagenase stimulatory factor, basigin-1 (BSG1; also known as Cluster of Differentiation 147 (CD147) and Extracellular Matrix Metalloproteinase Inducer (EMMPRIN)) and similar proteins. CD147 is a transmembrane glycoprotein that belongs to the immunoglobulin superfamily. It is expressed in nearly all cells including platelets and fibroblasts and is involved in inflammatory diseases, and cancer progression. CD147 is highly expressed in several cancers and used as a prognostic marker. The two primary isoforms of CD147 that are related to cancer progression have been identified: CD147 Ig1-Ig2 (also called Basigin-2) that is ubiquitously expressed in most tissues and CD147 Ig0-Ig1-Ig2 (also called Basigin-1) that is retinal specific and implicated in retinoblastoma. Studies showed that CD147 Ig0 domain is a potent stimulator of interleukin-6 and suggest that the CD147 Ig0 dimer is the functional unit required for activity.

Pssm-ID: 409534 Cd Length: 116 Bit Score: 39.56 E-value: 2.33e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  835 SGTVTTP-----WMKDIV-LPCKAVGDPSPAVKWMKDSNGTPSLVT--IDGRR----------SIFSNGSFVIRTVKAED 896
Cdd:cd20940      1 AGFIKSPlsqqrLVGDSVeLHCEAVGSPIPEIQWWFEGQEPNEICSqlWDGARldrvhinatyHQHATSTISIDNLTEED 80

                           90
                   ....*....|.
gi 1958664483  897 SGYYSCVANNN 907
Cdd:cd20940     81 TGTYECRASND 91

Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues, and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409388 Cd Length: 84 Bit Score: 38.33 E-value: 2.66e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958664483  250 VILNCSAEGYPVPTIVWKFSKGAGVPqfqpialNGRIQVLSNGSLLIKHVVEEDSGYYLCKVSNDVG 316
Cdd:cd05723     15 IVFECEVTGKPTPTVKWVKNGDVVIP-------SDYFKIVKEHNLQVLGLVKSDEGFYQCIAENDVG 74

Immunoglobulin variable domain (IgV); The members here are composed of the immunoglobulin variable domain (IgV). The IgV family contains the standard Ig superfamily V-set AGFCC'C"/DEB domain topology, and are components of immunoglobulin (Ig) and T cell receptors. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. In Ig, each chain is composed of one variable domain (IgV) and one or more constant domains (IgC); these names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. Within the variable domain, there are regions of even more variability called the hypervariable or complementarity-determining regions (CDRs) which are responsible for antigen binding. A predominant feature of most Ig domains is the disulfide bridge connecting 2 beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E and, D strands in one sheet and A', G, F, C, C', and C" strands in the other.

Pssm-ID: 409355 [Multi-domain] Cd Length: 111 Bit Score: 39.24 E-value: 2.70e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  247 GKAVILNCSAEG-YPVPTIVWKFSKGAGVPQF----------QPIALNGRIQVLSNG----SLLIKHVVEEDSGYYLCKV 311
Cdd:cd00099     13 GESVTLSCEVSSsFSSTYIYWYRQKPGQGPEFliylssskgkTKGGVPGRFSGSRDGtssfSLTISNLQPEDSGTYYCAV 92


                   .
gi 1958664483  312 S 312
Cdd:cd00099     93 S 93

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.

Pssm-ID: 143207 [Multi-domain] Cd Length: 95 Bit Score: 38.76 E-value: 2.90e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  170 TITWQKDGRPIPASLGVTIDNIDfTSSLRISNLSLMHNGNYTCIARNEAAAVEHQSQLIV 229
Cdd:cd05730     34 TMTWTKDGEPIESGEEKYSFNED-GSEMTILDVDKLDEAEYTCIAENKAGEQEAEIHLKV 92

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.

Pssm-ID: 143207 [Multi-domain] Cd Length: 95 Bit Score: 38.76 E-value: 3.04e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958664483   47 PASIRPMK---NITAIAGRDTYIHCRVIGYPYYSIKWYKNANLLPFNHRQVAFENNGT-LKLSDVQKEvDEGEYTC 118
Cdd:cd05730      1 PPTIRARQsevNATANLGQSVTLACDADGFPEPTMTWTKDGEPIESGEEKYSFNEDGSeMTILDVDKL-DEAEYTC 75

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; depending on isoform composition it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 143224 [Multi-domain] Cd Length: 92 Bit Score: 38.49 E-value: 3.34e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958664483  163 VSGDLPITITWQKDGRPIPASLGVTIDNIDFTSSLRISNLSLMHNGNYTCIARNEAAAVEHQSQL 227
Cdd:cd05747     27 VDGEPAPTVTWMREGQIIVSSQRHQITSTEYKSTFEISKVQMSDEGNYTVVVENSEGKQEAQFTL 91

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 38.20 E-value: 3.70e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  847 VLPCKAVGDPSPAVKWMkdSNGTP-------SLVTIDGRRSIFSNgsfvirtVKAEDSGYYSCVANNNWG 909
Cdd:cd04978     18 ELICEAEGNPQPTITWR--LNGVPiepapedMRRTVDGRTLIFSN-------LQPNDTAVYQCNASNVHG 78

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 37.98 E-value: 3.95e-03

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958664483  1029 SINTTRVRLNligW-----NDGGCPITSFTLEYRPFGTTvWTTAQRTSLSKSYILYDLQEATWYELQMRVCNSAG 1098
Cdd:smart00060   11 DVTSTSVTLS---WepppdDGITGYIVGYRVEYREEGSE-WKEVNVTPSSTSYTLTGLKPGTEYEFRVRAVNGAG 81

First immunoglobulin (Ig) domain of Cluster of Differentiation (CD) 4; member of the V-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig) domain of Cluster of Differentiation (CD) 4. CD4 and CD8 are the two primary co-receptor proteins found on the surface of T cells, and the presence of either CD4 or CD8 determines the function of the T cell. CD4 is found on helper T cells, where it is required for the binding of MHC (major histocompatibility complex) class II molecules, while CD8 is found on cytotoxic T cells, where it is required for the binding of MHC class I molecules. CD4 contains four immunoglobulin domains, with the first three included in this hierarchy. The fourth domain has a general Ig architecture, but has slight topological changes in the arrangement of beta strands relative to the other structures in this family and is not specifically included in the hierarchy.

Pssm-ID: 409487 Cd Length: 97 Bit Score: 38.30 E-value: 3.96e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958664483  848 LPCKAVGDPSPAVKWmKDSNGT------PSLVT---------IDGRRSIFSNGSF--VIRTVKAEDSGYYSC 902
Cdd:cd07690     14 LPCTASQKKSIQFHW-KNSNQIkilgnqGSFLTkgpsklndrADSRRNLWDQGSFplIIKNLKIEDSDTYIC 84

Second immunoglobulin (Ig)-like domain of protein tyrosine kinase (PTK) 7; The members here are composed of the second immunoglobulin (Ig)-like domain in protein tyrosine kinase (PTK) 7, also known as CCK4. PTK7 is a subfamily of the receptor protein tyrosine kinase family, and is referred to as an RPTK-like molecule. RPTKs transduce extracellular signals across the cell membrane and play important roles in regulating cell proliferation, migration, and differentiation. PTK7 is organized as an extracellular portion having seven Ig-like domains, a single transmembrane region, and a cytoplasmic tyrosine kinase-like domain. PTK7 is considered a pseudokinase as it has several unusual residues in some of the highly conserved tyrosine kinase (TK) motifs; it is predicted to lack TK activity. PTK7 may function as a cell-adhesion molecule. PTK7 mRNA is expressed at high levels in placenta, melanocytes, liver, lung, pancreas, and kidney. PTK7 is overexpressed in several cancers, including melanoma and colon cancer lines.

Pssm-ID: 409417 Cd Length: 95 Bit Score: 38.37 E-value: 4.05e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958664483  846 IVLPCKAVGDPSPAVKWMKDsnGTPsLVTIDGRRSIFSNG-SFVIRTVKAEDSGYYSCVANNNWGS 910
Cdd:cd05760     19 VTLRCHIDGHPRPTYQWFRD--GTP-LSDGQGNYSVSSKErTLTLRSAGPDDSGLYYCCAHNAFGS 81

First immunoglobulin (Ig)-like domain of carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM); The members here are composed of the immunoglobulin (Ig)-like domain 1 in carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) proteins. The CEA family is a group of anchored or secreted glycoproteins, expressed by epithelial cells, leukocytes, endothelial cells, and placenta. The CEA family is divided into the CEACAM and pregnancy-specific glycoprotein (PSG) subfamilies. This group represents the CEACAM subfamily. CEACAM1 has many important cellular functions: it is a cell adhesion molecule and a signaling molecule that regulates the growth of tumor cells, an angiogenic factor, and a receptor for bacterial and viral pathogens, including mouse hepatitis virus (MHV). In mice, four isoforms of CEACAM1 generated by alternative splicing have either two (D1, D4) or four (D1-D4) Ig-like domains on the cell surface.

Pssm-ID: 409430 Cd Length: 105 Bit Score: 38.40 E-value: 4.24e-03

                           10        20
                   ....*....|....*....|....
gi 1958664483  284 GRIQVLSNGSLLIKHVVEEDSGYY 307
Cdd:cd05774     62 GRETIYPNGSLLIQNVTQKDTGFY 85

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 38.17 E-value: 4.54e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483   47 PASIRPMKNITAIAGRDTYIHCRVIGYPYYSIKWYKNANLL-----PFNHRQVAFENNGTLKLSDVQKEvDEGEYTCNVL 121
Cdd:cd20951      1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIdpssiPGKYKIESEYGVHVLHIRRVTVE-DSAVYSAVAK 79

                           90
                   ....*....|....
gi 1958664483  122 -VQPQLSTSQSVHV 134
Cdd:cd20951     80 nIHGEASSSASVVV 93

Second immunoglobulin (Ig)-like domain of interleukin-1 receptor (IL1R), and similar domains; The members here are composed of the second immunoglobulin (Ig)-like domain of interleukin-1 receptor (IL1R; also known as cluster of differentiation (CD) 121). IL-1 alpha and IL-1 beta are cytokines which participate in the regulation of inflammation, immune responses, and hematopoiesis. These cytokines bind to the IL-1 receptor type 1 (IL1R1), which is activated on additional association with interleukin-1 receptor accessory protein (IL1RAP). IL-1 also binds a second receptor designated type II (IL1R2). Mature IL1R1 consists of three IG-like domains, a transmembrane domain, and a large cytoplasmic domain. Mature IL1R2 is organized similarly except that it has a short cytoplasmic domain. The latter does not initiate signal transduction. A naturally occurring cytokine IL-1RA (IL-1 receptor antagonist) is widely expressed and binds to IL-1 receptors, inhibiting the binding of IL-1 alpha and IL-1 beta. This group also contains ILIR-like 1 (IL1R1L) which maps to the same chromosomal location as IL1R1 and IL1R2.

Pssm-ID: 409415 Cd Length: 92 Bit Score: 37.69 E-value: 5.16e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1958664483  281 ALNGRIQVLSNGS-LLIKHVVEEDSGYYLCKVS---NDVGADVSKSMYLTVK 328
Cdd:cd05757     40 PLQGDKRFIPKGSkLLIQNVTEEDAGNYTCKFTythNGKQYNVTRTISLTVT 91

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1(FGFRL1); member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 is comprised of a signal peptide, three extracellular Ig-like modules, a transmembrane segment, and a short intracellular domain. FGFRL1 is expressed preferentially in skeletal tissues. Similar to FGF receptors, the expressed protein interacts specifically with heparin and with FGF2. FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409442 Cd Length: 92 Bit Score: 37.53 E-value: 6.20e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  139 PPFIQPFEFPRFSI----GQRVFIPCVVvSGDLPITITWQKDGRPI-PASLGvtiDNIDFTSSLRISNLSLMHNGNYTCI 213
Cdd:cd05856      1 PRFTQPAKMRRRVIarpvGSSVRLKCVA-SGNPRPDITWLKDNKPLtPPEIG---ENKKKKWTLSLKNLKPEDSGKYTCH 76


                   ....*...
gi 1958664483  214 ARNEAAAV 221
Cdd:cd05856     77 VSNRAGEI 84

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409566 [Multi-domain] Cd Length: 93 Bit Score: 37.72 E-value: 6.72e-03

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                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1958664483  854 GDPSPAVKWMKDSNGTpSLVTIDGRRSIFSNGS--FVIRTVKAEDSGYYSCVANNNWGS 910
Cdd:cd20974     26 GKPVPEVSWFRDGQVI-STSTLPGVQISFSDGRakLSIPAVTKANSGRYSLTATNGSGQ 83

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409473 Cd Length: 92 Bit Score: 37.44 E-value: 7.07e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  233 PKFVVQPRDQDGIYGKAVILNCSAEGYPVPTIVWKfsKGAGVPQFQPialnGRIQVLSNGS----LLIKHVVEEDSGYYL 308
Cdd:cd05892      1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWK--KNNEMLQYNT----DRISLYQDNCgricLLIQNANKKDAGWYT 74


                   ....*...
gi 1958664483  309 CKVSNDVG 316
Cdd:cd05892     75 VSAVNEAG 82

Fifth immunoglobulin (Ig) domain of contactin-1; The members here are composed of the fifth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409438 Cd Length: 89 Bit Score: 37.29 E-value: 7.18e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958664483   52 PM-KNITAIAGRDTYIHCRVIGYPYYSIKWYKNANLLpFNHRQVAFENNGTLKLSDVQKeVDEGEYTC 118
Cdd:cd05852      7 PMkKKILAAKGGRVIIECKPKAAPKPKFSWSKGTELL-VNNSRISIWDDGSLEILNITK-LDEGSYTC 72

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 37.49 E-value: 7.48e-03

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958664483  153 GQRVFIPCVVVSGDLPiTITWQKDG-RPIPASLGVTIDNIDFTssLRISNLSLMHNGNYTCIARNEAA-AVEHQSQLIV 229
Cdd:cd20970     17 GENATFMCRAEGSPEP-EISWTRNGnLIIEFNTRYIVRENGTT--LTIRNIRRSDMGIYLCIASNGVPgSVEKRITLQV 92

Interferon-alpha/beta receptor, fibronectin type III; Members of this family adopt a secondary structure consisting of seven beta-strands arranged in an immunoglobulin-like beta-sandwich, in a Greek-key topology. They are required for binding to interferon-alpha.

Pssm-ID: 462746 Cd Length: 103 Bit Score: 37.71 E-value: 7.85e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958664483  667 FRVIYWANlidGELGEIKNVTTTQPSLELDGLEKYTNYSIQVLAFTRAGD--GVRSEQIFTRTK 728
Cdd:pfam09294   43 YRVSYWKN---SSNGEKKNTTSTNSFVVLSDLEPGTTYCVSVQAFSPLDNksSQRSPPQCIRTT 103

Fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

Pssm-ID: 409453 [Multi-domain] Cd Length: 89 Bit Score: 37.18 E-value: 7.95e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958664483  240 RDQDGIY--GKAVILNCSAEGYPVPTIVWKFSkgaGVPqFQPIALNGRIQVlSNGSLLIKHVVEEDSGYYLCKVSNDVG 316
Cdd:cd05867      5 RPQSHLYgpGETARLDCQVEGIPTPNITWSIN---GAP-IEGTDPDPRRHV-SSGALILTDVQPSDTAVYQCEARNRHG 78

Second immunoglobulin (Ig)-like domain of interleukin-1 receptor (IL1R), and similar domains; The members here are composed of the second immunoglobulin (Ig)-like domain of interleukin-1 receptor (IL1R). IL-1 alpha and IL-1 beta are cytokines which participate in the regulation of inflammation, immune responses, and hematopoiesis. These cytokines bind to the IL-1 receptor type 1 (IL1R1), which is activated on additional association with interleukin-1 receptor accessory protein (IL1RAP). IL-1 also binds a second receptor designated type II (IL1R2). Mature IL1R1 consists of three IG-like domains, a transmembrane domain, and a large cytoplasmic domain. Mature IL1R2 is organized similarly except that it has a short cytoplasmic domain. The latter does not initiate signal transduction. A naturally occurring cytokine IL-1RA (IL-1 receptor antagonist) is widely expressed and binds to IL-1 receptors, inhibiting the binding of IL-1 alpha and IL-1 beta. This group also contains ILIR-like 1 (IL1R1L) which maps to the same chromosomal location as IL1R1 and IL1R2.

Pssm-ID: 409586 Cd Length: 94 Bit Score: 37.06 E-value: 8.55e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1958664483  278 QPIALNGRIQVLSNGSLLIKHVVEEDSGYYLCKVS-NDVGA--DVSKSMYLTVK 328
Cdd:cd20994     40 KPLLLDDKRFAGLESDLLIFNVTVQDQGNYTCHTSyTYMGKqyNISRTISLIVL 93

Immunoglobulin-like domain of human nephrin and similar proteins; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin-like domain in human nephrin and similar proteins. Nephrin is an integral component of the slit diaphragm and is a central component of the glomerular ultrafilter. Nephrin plays a structural role and has a role in signaling. Nephrin is a transmembrane protein having a short intracellular portion, an extracellular portion comprised of eight Ig-like domains, and one fibronectin type III-like domain. The extracellular portions of nephrin from neighboring foot processes of separate podocyte cells may interact with each other, and in association with other components of the slit diaphragm form a porous molecular sieve within the slit pore. The intracellular portion of nephrin is associated with linker proteins, which connect nephrin to the actin cytoskeleton. The intracellular portion is tyrosine phosphorylated, and mediates signaling from the slit diaphragm into the podocytes.

Pssm-ID: 143250 Cd Length: 109 Bit Score: 37.60 E-value: 8.99e-03

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958664483  352 CTAHGEKPIIVRWEKEDRIINPEMARYLVSTKEVGEEVISTLQILP-TVREDSGFFSCHAINSYGEDRGIIQLTVQEPPD 430
Cdd:cd05773     30 CQAQGVPRVQFRWAKNGVPLDLGNPRYEETTEHTGTVHTSILTIINvSAALDYALFTCTAHNSLGEDSLDIQLVSTSRPD 109