NCBI Conserved Domain Search

Second immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), 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 of the L1 cell adhesion molecule (CAM) and similar proteins. 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 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: 409432 Cd Length: 91 Bit Score: 190.01 E-value: 1.31e-56

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  135 KEKIDPLEVEEGDPIVLPCNPPKGLPPLHIYWMNIELEHIEQDERVYMSQKGDLYFANVEEKDSRNDYCCFAAFPRLRTI 214
Cdd:cd05845      1 KEKIDPVEVEEGDPVVLPCNPPKGAPPPRIYWMNSSLEHITQDERVSMGQNGDLYFSNVMEQDSHPDYICHAHFPGTRTI 80

                           90
                   ....*....|.
gi 1034630801  215 VQKMPMKLTVN 225
Cdd:cd05845     81 VQKEPITLKVL 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: 158.34 E-value: 1.46e-45

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  262 SESSITILKGEILLLECFAEGLPTPQVDWNKIGGDLPKGRETKENYGKTLKIENVSYQDKGNYRCTASNFLGTATHDFHV 341
Cdd:cd05731      1 SESSTMVLRGGVLLLECIAEGLPTPDIRWIKLGGELPKGRTKFENFNKTLKIENVSEADSGEYQCTASNTMGSARHTISV 80


                   ...
gi 1034630801  342 IVE 344
Cdd:cd05731     81 TVE 83

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: 151.06 E-value: 6.35e-43

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  348 RWTKKPQSAVYSTGSNGILLCEAEGEPQPTIKWRVNGSPVDNHPF-AGDVVFPREISFTNLQPNHTAVYQCEASNVHGTI 426
Cdd:cd04978      1 YWIIEPPSLVLSPGETGELICEAEGNPQPTITWRLNGVPIEPAPEdMRRTVDGRTLIFSNLQPNDTAVYQCNASNVHGYL 80


                   ....*....
gi 1034630801  427 LANANIDVV 435
Cdd:cd04978     81 LANAFLHVL 89

Bravo-like intracellular region; This is the very C-terminal intracellular region of neural adhesion molecule L1 proteins that are also known as Bravo or NrCAM. It lies upstream of the IG and Fn3 domains and has the highly conserved motif FIGEY. The function is not known.

Pssm-ID: 464016 Cd Length: 88 Bit Score: 141.30 E-value: 1.56e-39

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801 1067 KRNRGGKYSVKEKEDLHPDPEIQSVKDETFGEYSDSDEKPLKGSLRSLNRDMQP--TESADSLVEYGEGDHGLFSEDGSF 1144
Cdd:pfam13882    1 KRNKGGKYSVKEKEDAHGDPEDQPMDEDAFGEYSDLDEKPLKSSQPSLSSDSKLvdSDSTDSLDDYGDGDGGQFNEDGSF 80


                   ....*...
gi 1034630801 1145 IGAYAGSK 1152
Cdd:pfam13882   81 IGQYGGKK 88

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: 119.82 E-value: 6.10e-32

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801   35 PTIIKQSKVQVAFPFDEYFQIECEAKGNPEPTFSWTKDGNPFYFT-DHRIIPSNNSGTFRIPN-EGHISHFQGKYRCFAS 112
Cdd:cd05733      1 PTITEQSPKDYIVDPRDNITIKCEAKGNPQPTFRWTKDGKFFDPAkDPRVSMRRRSGTLVIDNhNGGPEDYQGEYQCYAS 80

                           90
                   ....*....|....
gi 1034630801  113 NKLGIAMSEEIEFI 126
Cdd:cd05733     81 NELGTAISNEIRLV 94

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: 94.98 E-value: 2.36e-23

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  262 SESSITILKGEILLLECFAEGLPTPQVDWNKIGGDLPKGRETKENYGKTLKIENVSYQDKGNYRCTASNFLGTATHDFHV 341
Cdd:cd05876      1 SSSSLVALRGQSLVLECIAEGLPTPTVKWLRPSGPLPPDRVKYQNHNKTLQLLNVGESDDGEYVCLAENSLGSARHAYYV 80


                   ...
gi 1034630801  342 IVE 344
Cdd:cd05876     81 TVE 83

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: 92.27 E-value: 2.46e-22

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  349 WTKKPQSAVYSTGSNGILLCEAEGEPQPTIKWRVNGSPVDnhpfAGDVVFPREIS-----FTNLQPNHTAVYQCEASNVH 423
Cdd:cd05867      2 WTRRPQSHLYGPGETARLDCQVEGIPTPNITWSINGAPIE----GTDPDPRRHVSsgaliLTDVQPSDTAVYQCEARNRH 77

                           90
                   ....*....|..
gi 1034630801  424 GTILANANIDVV 435
Cdd:cd05867     78 GNLLANAHVHVV 89

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: 85.24 E-value: 9.15e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  628 PDPPENLHLSERQNRSVRLTWEAGADHNSNISEYIVEFegNKEEPGRWEELTRVQGKKTTVILP-LAPFVRYQFRVIAVN 706
Cdd:cd00063      1 PSPPTNLRVTDVTSTSVTLSWTPPEDDGGPITGYVVEY--REKGSGDWKEVEVTPGSETSYTLTgLKPGTEYEFRVRAVN 78

                           90
                   ....*....|.
gi 1034630801  707 EVGRSQPSQPS 717
Cdd:cd00063     79 GGGESPPSESV 89

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: 84.26 E-value: 1.79e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801   35 PTIIKQS-KVQVAFPFDEYFqIECEAKGNPEPTFSWTKDGNPFYFT-DHRIIPSNNSGTFRI--PNEGHISHFQGKYRCF 110
Cdd:cd05875      1 PTITKQSaKDYIVDPRDNIL-IECEAKGNPVPTFHWTRNGKFFNVAkDPRVSMRRRSGTLVIdfRGGGRPEDYEGEYQCF 79

                           90
                   ....*....|...
gi 1034630801  111 ASNKLGIAMSEEI 123
Cdd:cd05875     80 ARNKFGTALSNKI 92

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: 83.11 E-value: 4.00e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  349 WTKKPQSAVYSTGSNGILLCEAEGEPQPTIKWRVNGSPVDNHP------FAGDVvfpreISFTNLQPNHTAVYQCEASNV 422
Cdd:cd05868      2 WITAPTNLVLSPGEDGTLICRANGNPKPSISWLTNGVPIEIAPtdpsrkVDGDT-----IIFSKVQERSSAVYQCNASNE 76

                           90
                   ....*....|...
gi 1034630801  423 HGTILANANIDVV 435
Cdd:cd05868     77 YGYLLANAFVNVL 89

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: 71.11 E-value: 5.96e-15

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801   628 PDPPENLHLSERQNRSVRLTWEAGADHNSNisEYIVEFE-GNKEEPGRWEELTRVQGKKTTVILPLAPFVRYQFRVIAVN 706
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTLSWEPPPDDGIT--GYIVGYRvEYREEGSEWKEVNVTPSSTSYTLTGLKPGTEYEFRVRAVN 78


                    ....*
gi 1034630801   707 EVGRS 711
Cdd:smart00060   79 GAGEG 83

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 69.75 E-value: 2.01e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  629 DPPENLHLSERQNRSVRLTWEAGADHNSNISEYIVEFEgNKEEPGRWEELTRVQGKKTTVILPLAPFVRYQFRVIAVNEV 708
Cdd:pfam00041    1 SAPSNLTVTDVTSTSLTVSWTPPPDGNGPITGYEVEYR-PKNSGEPWNEITVPGTTTSVTLTGLKPGTEYEVRVQAVNGG 79


                   ....*.
gi 1034630801  709 GRSQPS 714
Cdd:pfam00041   80 GEGPPS 85

Immunoglobulin (Ig)-like domain of NrCAM (Ng (neuronglia) CAM-related cell adhesion molecule); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of NrCAM (Ng (neuronglia) CAM-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: 409458 Cd Length: 95 Bit Score: 68.09 E-value: 8.86e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801   35 PTIIKQSKVQVAFPFDEYFQIECEAKGNPEPTFSWTKDGNPFYF-TDHRIIPSNNSGTF--RIPNEGHISHFQGKYRCFA 111
Cdd:cd05874      1 PTITHQSPKDYIVDPRENIVIQCEAKGKPPPSFSWTRNGTHFDIdKDPKVTMKPNTGTLviNIMNGEKAEAYEGVYQCTA 80

                           90
                   ....*....|..
gi 1034630801  112 SNKLGIAMSEEI 123
Cdd:cd05874     81 RNERGAAVSNNI 92

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: 67.74 E-value: 1.15e-13

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1034630801  269 LKGEILLLECFAEGLPTPQVDWNKIGGDLPKGRETKENyGKTLKIENVSYQDKGNYRCTASNFLGTATHDFHVIVE 344
Cdd:cd05851     14 LKGQNVTLECFALGNPVPVIRWRKILEPMPATAEISMS-GAVLKIFNIQPEDEGTYECEAENIKGKDKHQARVYVQ 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: 66.65 E-value: 2.39e-13

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1034630801  448 NYATVVGYSAFLHCEFFASPEAVVSWQKVEEVKPLegRRYHIYENGTLQINRTTEEDAGSYSCWVENAIGKTAVTANL 525
Cdd:cd05725      6 NQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGELPK--GRYEILDDHSLKIRKVTAGDMGSYTCVAENMVGKIEASATL 81

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: 66.75 E-value: 2.91e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  932 PEQPTFLKVIKVDKDTATLSWGLPKKLNGNLTGYLLQYQIINDtyeiGELNDINITTPSKPSWHLSNLNATTKYKFYLRA 1011
Cdd:cd00063      1 PSPPTNLRVTDVTSTSVTLSWTPPEDDGGPITGYVVEYREKGS----GDWKEVEVTPGSETSYTLTGLKPGTEYEFRVRA 76

                           90
                   ....*....|....*.
gi 1034630801 1012 CTSQGCGKPITEESST 1027
Cdd:cd00063     77 VNGGGESPPSESVTVT 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: 66.37 E-value: 2.93e-13

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801   264 SSITILKGEILLLECFAEGLPTPQVDWNKIGGDL----PKGRETKENYGKTLKIENVSYQDKGNYRCTASNFLGTATHDF 339
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLlaesGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGT 81


                    ....
gi 1034630801   340 HVIV 343
Cdd:smart00410   82 TLTV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 66.05 E-value: 3.25e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  250 KPKLLLPPtesgseSSITILKGEILLLECFAEGLPTPQVDWNKIGGDLPKGR---ETKENYGKTLKIENVSYQDKGNYRC 326
Cdd:pfam13927    1 KPVITVSP------SSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGStrsRSLSGSNSTLTISNVTRSDAGTYTC 74


                   ....
gi 1034630801  327 TASN 330
Cdd:pfam13927   75 VASN 78

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: 66.29 E-value: 4.06e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  347 PRWTKKPQSAVYSTGSNGILLCEAEGEPQPTIKWRVNGSPVDNHPFAGDVVFPREISFTNLQ-----PNHTAVYQCEASN 421
Cdd:cd20951      1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDPSSIPGKYKIESEYGVHVLHirrvtVEDSAVYSAVAKN 80

                           90
                   ....*....|...
gi 1034630801  422 VHGTILANANIDV 434
Cdd:cd20951     81 IHGEASSSASVVV 93

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 73.50 E-value: 4.83e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  616 AADITQVTVLDVPDPPENLHLSERQNRSVRLTWEAGAdhNSNISEYIVefEGNKEEPGRWEELTRVQGkkTTVILP-LAP 694
Cdd:COG3401    221 SNEVSVTTPTTPPSAPTGLTATADTPGSVTLSWDPVT--ESDATGYRV--YRSNSGDGPFTKVATVTT--TSYTDTgLTN 294

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  695 FVRYQFRVIAVNEVG-RSQPSQPS----DHheTPPAApdrnPQNIRVQASQPKEMIIKWEPlksmeQNGPGL-EYRVT-W 767
Cdd:COG3401    295 GTTYYYRVTAVDAAGnESAPSNVVsvttDL--TPPAA----PSGLTATAVGSSSITLSWTA-----SSDADVtGYNVYrS 363

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  768 KPQGAPVEW--EEETVTNHTLRVMTPAVyaPYDVKVQAINQLGSGPDP------QSVTLYSGEDYPDTAPVIHGVDVINS 839
Cdd:COG3401    364 TSGGGTYTKiaETVTTTSYTDTGLTPGT--TYYYKVTAVDAAGNESAPseevsaTTASAASGESLTASVDAVPLTDVAGA 441

                          250       260
                   ....*....|....*....|....*....
gi 1034630801  840 TLVkVTWSTVPKDRVHGRLKGYQINWWKT 868
Cdd:COG3401    442 TAA-ASAASNPGVSAAVLADGGDTGNAVP 469

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: 64.83 E-value: 8.98e-13

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801   447 ENYATVVGYSAFLHCEFFASPEAVVSWQKVEEVKPLEGRRYHIYENG---TLQINRTTEEDAGSYSCWVENAIGKTAVTA 523
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSGstsTLTISNVTPEDSGTYTCAATNSSGSASSGT 81


                    ..
gi 1034630801   524 NL 525
Cdd:smart00410   82 TL 83

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 64.97 E-value: 1.04e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  264 SSITILKGEILLLECFAEGLPTPQVDWNKIGGDLPKGRE---TKENYGKTLKIENVSYQDKGNYRCTASNFLGTATHDFH 340
Cdd:pfam07679    8 KDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRfkvTYEGGTYTLTISNVQPDDSGKYTCVATNSAGEAEASAE 87


                   ...
gi 1034630801  341 VIV 343
Cdd:pfam07679   88 LTV 90

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: 64.34 E-value: 1.33e-12

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1034630801  264 SSITILKGEILLLECFAEGLPTPQVDWNKIGGDLPKGR-ETKENygKTLKIENVSYQDKGNYRCTASNFLGTAT 336
Cdd:cd05725      5 QNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGELPKGRyEILDD--HSLKIRKVTAGDMGSYTCVAENMVGKIE 76

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 62.97 E-value: 3.88e-12

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1034630801  346 PPRWTKKPQSAVYSTGSNGILLCEAEGEPQPTIKWRVNGSPVDN--HPFAGDVVFPREISFTNLQPNHTAVYQCEASN 421
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSgsTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 62.82 E-value: 5.02e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  934 QPTFLKVIKVDKDTATLSWGLPKKLNGNLTGYLLQYQIINDTyeiGELNDINItTPSKPSWHLSNLNATTKYKFYLRACT 1013
Cdd:pfam00041    2 APSNLTVTDVTSTSLTVSWTPPPDGNGPITGYEVEYRPKNSG---EPWNEITV-PGTTTSVTLTGLKPGTEYEVRVQAVN 77


                   ....*..
gi 1034630801 1014 SQGCGKP 1020
Cdd:pfam00041   78 GGGEGPP 84

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: 62.62 E-value: 5.16e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  349 WTKKPQSAVYSTGSNGILLCEAEGEPQPTIKWRVNGSPVdnhPFAGDV-VFPREISFTNLQPNHTAVYQCEASNVHGTIL 427
Cdd:cd05728      2 WLKVISDTEADIGSSLRWECKASGNPRPAYRWLKNGQPL---ASENRIeVEAGDLRITKLSLSDSGMYQCVAENKHGTIY 78


                   ....*..
gi 1034630801  428 ANANIDV 434
Cdd:cd05728     79 ASAELAV 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: 61.79 E-value: 1.11e-11

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1034630801  269 LKGEILLLECFAEGLPTPQVDWNKIGGDLPKGRETKENYGkTLKIENVSYQDKGNYRCTASNFLGTATHDFHVIV 343
Cdd:cd04968     14 LKGQTVTLECFALGNPVPQIKWRKVDGSPSSQWEITTSEP-VLEIPNVQFEDEGTYECEAENSRGKDTVQGRIIV 87

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: 61.19 E-value: 1.42e-11

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1034630801  457 AFLHCEFFASPEAVVSWQKVEEVKPLE--GRRYHIYENGTLQINRTTEEDAGSYSCWVENAIGKTA 520
Cdd:cd00096      1 VTLTCSASGNPPPTITWYKNGKPLPPSsrDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSA 66

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: 61.25 E-value: 1.62e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  347 PRWTKKPQSAV-YSTGSNGILLCEAEGEPQPTIKWRVNGSPVDNHPFAGDVvfpREISFT--NLQPNHTAVYQCEASNVH 423
Cdd:cd20978      1 PKFIQKPEKNVvVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMERATV---EDGTLTiiNVQPEDTGYYGCVATNEI 77

                           90
                   ....*....|.
gi 1034630801  424 GTILANANIDV 434
Cdd:cd20978     78 GDIYTETLLHV 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: 61.10 E-value: 2.47e-11

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1034630801  266 ITILKGEILLLECFAEGLPTPQVDWNKIGG-DLPKGRETKENYGKTLK---IENVSYQDKGNYRCTASNFLGT 334
Cdd:cd05763      9 ITIRAGSTARLECAATGHPTPQIAWQKDGGtDFPAARERRMHVMPEDDvffIVDVKIEDTGVYSCTAQNSAGS 81

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: 2.56e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  441 IQTKDGENYATVVGYSAFLHCEFFASPEAVVSWQKVEEVKPLEGRRYHIYENGTLQINRTTEEDAGSYSCWVENAIGKTA 520
Cdd:cd20952      1 IILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDERITTLENGSLQIKGAEKSDTGEYTCVALNLSGEAT 80


                   ....*..
gi 1034630801  521 VTANLDI 527
Cdd:cd20952     81 WSAVLDV 87

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: 59.65 E-value: 4.24e-11

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034630801  274 LLLECFAEGLPTPQVDWNKIGGDLP---KGRETKENYGKTLKIENVSYQDKGNYRCTASNFLGTATH 337
Cdd:cd00096      1 VTLTCSASGNPPPTITWYKNGKPLPpssRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSAS 67

Second Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the second 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: 409392 Cd Length: 88 Bit Score: 60.27 E-value: 4.53e-11

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1034630801  139 DPLEVEEGDPIVLPCNPPKGLPPLHIYWMNIELEH-IEQDERVYMSQ-KGDLYFANVEEKDsRNDYCCFAAFP 209
Cdd:cd05727      3 DEVKVKEGWGVVLFCDPPPHYPDLSYRWLLNEFPNfIPEDGRRFVSQtNGNLYIAKVEASD-RGNYSCFVSSP 74

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 58.73 E-value: 1.27e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801   35 PTIIKQSKVQVAFPfDEYFQIECEAKGNPEPTFSWTKDGNPFYFTDHRIIP-SNNSGTFRIPNeGHISHfQGKYRCFASN 113
Cdd:pfam13927    2 PVITVSPSSVTVRE-GETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSlSGSNSTLTISN-VTRSD-AGTYTCVASN 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: 58.72 E-value: 2.21e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  347 PRWTKKPQSAVYSTGSNGILLCEAEGEPQPTIKWRVNGSPVD-------NHPF---AGDVVFPREISFTNLQPnHTAVYQ 416
Cdd:cd07693      1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLEtdkddprSHRIvlpSGSLFFLRVVHGRKGRS-DEGVYV 79

                           90
                   ....*....|....*....
gi 1034630801  417 CEASNVHGTIL-ANANIDV 434
Cdd:cd07693     80 CVAHNSLGEAVsRNASLEV 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: 58.40 E-value: 2.35e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  349 WTKKPQSAVYSTGSNGILLCEAEGEPQPTIKWRVNGSpvDNHPFAGDV---VFPREISF--TNLQPNHTAVYQCEASNVH 423
Cdd:cd05763      2 FTKTPHDITIRAGSTARLECAATGHPTPQIAWQKDGG--TDFPAARERrmhVMPEDDVFfiVDVKIEDTGVYSCTAQNSA 79

                           90
                   ....*....|..
gi 1034630801  424 GTILANANIDVV 435
Cdd:cd05763     80 GSISANATLTVL 91

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: 58.43 E-value: 2.67e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  352 KPQSAVYSTGSNGILLCEAEGEPQPTIKWRVNGSPV------DNHPFAGDVVFPR-EISFTNLQPNHTAVYQCEASNVHG 424
Cdd:cd05726      5 KPRDQVVALGRTVTFQCETKGNPQPAIFWQKEGSQNllfpyqPPQPSSRFSVSPTgDLTITNVQRSDVGYYICQALNVAG 84

                           90
                   ....*....|...
gi 1034630801  425 TILANANIDVVDV 437
Cdd:cd05726     85 SILAKAQLEVTDV 97

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: 58.09 E-value: 2.90e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  346 PPRWTKKPQSAVYSTGSNGILLCEAEGEPQPTIKWR--VNGSPVDNHPFAGDV---VFPR-EISFTNLQPNHTAVYQCEA 419
Cdd:cd20954      1 PPRWIVEPVDANVAAGQDVMLHCQADGFPTPTVTWKkaTGSTPGEYKDLLYDPnvrILPNgTLVFGHVQKENEGHYLCEA 80


                   ..
gi 1034630801  420 SN 421
Cdd:cd20954     81 KN 82

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: 57.86 E-value: 3.30e-10

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1034630801  452 VVGYSAFLHCEFFASPEAVVSWQKVEEVKpLEGRRYHIYENGTLQINRTTEEDAGSYSCWVENAIGKTAVTANLDI 527
Cdd:cd04969     15 AKGGDVIIECKPKASPKPTISWSKGTELL-TNSSRICILPDGSLKIKNVTKSDEGKYTCFAVNFFGKANSTGSLSV 89

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: 55.78 E-value: 1.53e-09

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1034630801  454 GYSAFLHCEFFASPEAVVSWQKVEEVKpLEGRRYHIYENGTLQINRTTEEDAGSYSCWVENAIGKTAVTANLDI 527
Cdd:cd05852     17 GGRVIIECKPKAAPKPKFSWSKGTELL-VNNSRISIWDDGSLEILNITKLDEGSYTCFAENNRGKANSTGVLSV 89

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 55.50 E-value: 1.82e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  731 PQNIRVQASQPKEMIIKWEPLKSmeQNGPGLEYRVTWKPQGAPVEWEEETVTNHTLRVM----TPavYAPYDVKVQAINQ 806
Cdd:pfam00041    3 PSNLTVTDVTSTSLTVSWTPPPD--GNGPITGYEVEYRPKNSGEPWNEITVPGTTTSVTltglKP--GTEYEVRVQAVNG 78


                   ....*
gi 1034630801  807 LGSGP 811
Cdd:pfam00041   79 GGEGP 83

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: 54.64 E-value: 2.38e-09

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034630801  366 LLCEAEGEPQPTIKWRVNGSPVDNHPFAGDVVFPR--EISFTNLQPNHTAVYQCEASNVHGT 425
Cdd:cd00096      3 LTCSASGNPPPTITWYKNGKPLPPSSRDSRRSELGngTLTISNVTLEDSGTYTCVASNSAGG 64

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: 55.20 E-value: 2.46e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  350 TKKPQSAVYSTGSNGILLCEAEGEPQPTIKWRVNGSPV---DNHPFAGDVvfpREISFTNLQPNHTAVYQCEASNVHGTI 426
Cdd:cd20952      3 LQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLlgkDERITTLEN---GSLQIKGAEKSDTGEYTCVALNLSGEA 79


                   ....*...
gi 1034630801  427 LANANIDV 434
Cdd:cd20952     80 TWSAVLDV 87

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: 54.95 E-value: 3.44e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  256 PPTESGSESSITILKGEILLLECFAEGLPTPQVDWNKIGGDLPKG--RETKENYGKTLKIENVSYQDKGNYRCTASNFLG 333
Cdd:cd20976      1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQYAadRSTCEAGVGELHIQDVLPEDHGTYTCLAKNAAG 80

                           90
                   ....*....|
gi 1034630801  334 TATHDFHVIV 343
Cdd:cd20976     81 QVSCSAWVTV 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: 54.54 E-value: 3.58e-09

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801   932 PEQPTFLKVIKVDKDTATLSWGLPKklNGNLTGYLLQYQIINDtyEIGELNDINITTPSKPSWHLSNLNATTKYKFYLRA 1011
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTLSWEPPP--DDGITGYIVGYRVEYR--EEGSEWKEVNVTPSSTSYTLTGLKPGTEYEFRVRA 76


                    ....*..
gi 1034630801  1012 CTSQGCG 1018
Cdd:smart00060   77 VNGAGEG 83

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: 54.81 E-value: 3.85e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801   37 IIKQSKVQVAFPFDEYFQIECEAKGNPEPTFSWTKDGNPFYFTDHRIIPSNNsGTFRIPNeGHISHfQGKYRCFASNKLG 116
Cdd:cd20952      1 IILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDERITTLEN-GSLQIKG-AEKSD-TGEYTCVALNLSG 77


                   ..
gi 1034630801  117 IA 118
Cdd:cd20952     78 EA 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: 54.11 E-value: 4.06e-09

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034630801   54 QIECEAKGNPEPTFSWTKDGnpfyftdhriIPSNNSGTFRIPNEGHIS------HFQGKYRCFASNKLGIA 118
Cdd:cd05746      2 QIPCSAQGDPEPTITWNKDG----------VQVTESGKFHISPEGYLAirdvgvADQGRYECVARNTIGYA 62

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 53.72 E-value: 5.89e-09

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  447 ENYATVVGYSAFLHCEFFASPEAVVSWQKVEEVKP--LEGRRYHIYENGTLQINRTTEEDAGSYSCWVEN 514
Cdd:pfam13927    9 SSVTVREGETVTLTCEATGSPPPTITWYKNGEPISsgSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

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: 54.19 E-value: 6.70e-09

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1034630801  271 GEILLLECFAEGLPTPQVDWNK----IGGDLPKGRETKENyGKTLKIENVSYQDKGNYRCTASNFLGTATHDFHVIVEE 345
Cdd:cd05736     15 GVEASLRCHAEGIPLPRVQWLKngmdINPKLSKQLTLIAN-GSELHISNVRYEDTGAYTCIAKNEGGVDEDISSLFVED 92

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: 53.10 E-value: 9.93e-09

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1034630801   53 FQIECEAKGNPEPTFSWTKDGNPFYFTDH-RIIPSNNSGTFRIPN--EGHishfQGKYRCFASNKLGIAMSEEI 123
Cdd:cd00096      1 VTLTCSASGNPPPTITWYKNGKPLPPSSRdSRRSELGNGTLTISNvtLED----SGTYTCVASNSAGGSASASV 70

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 53.42 E-value: 1.07e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1034630801  453 VGYSAFLHCEFFASPEAVVSWQKvEEVKPLEGRRYHIYENG---TLQINRTTEEDAGSYSCWVENAIGKTAVTANL 525
Cdd:pfam07679   14 EGESARFTCTVTGTPDPEVSWFK-DGQPLRSSDRFKVTYEGgtyTLTISNVQPDDSGKYTCVATNSAGEAEASAEL 88

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: 53.62 E-value: 1.08e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034630801  265 SITILKGEILLLECFAEGLPTPQVDWNKIGGDLPKGRETKENYGKTLKIENVSYQDKGNYRCTASNFLGTA 335
Cdd:cd04969     11 KILAAKGGDVIIECKPKASPKPTISWSKGTELLTNSSRICILPDGSLKIKNVTKSDEGKYTCFAVNFFGKA 81

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: 53.67 E-value: 1.11e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  264 SSITILKGEILLLECFAEGLPTPQVDWNKIGGdLPKGRETKENY---GKTLKIENVSYQDKGNYRCTASN 330
Cdd:cd20970     10 FTVTAREGENATFMCRAEGSPEPEISWTRNGN-LIIEFNTRYIVrenGTTLTIRNIRRSDMGIYLCIASN 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: 53.71 E-value: 1.28e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801   35 PTIIKQSKvQVAFPFDEYFQIECEAKGNPEPTFSWTKDGNPFYfTD------HRII-PSNNSGTFRI-PNEGHISHfQGK 106
Cdd:cd07693      1 PRIVEHPS-DLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLE-TDkddprsHRIVlPSGSLFFLRVvHGRKGRSD-EGV 77

                           90
                   ....*....|....
gi 1034630801  107 YRCFASNKLGIAMS 120
Cdd:cd07693     78 YVCVAHNSLGEAVS 91

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: 52.63 E-value: 1.45e-08

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801   57 CEAKGNPEPTFSWTKDGNPFYFTDHRIIPSnnSGTFRIpnEGHISHFQGKYRCFASNKLG 116
Cdd:cd05745      9 CEAQGYPQPVIAWTKGGSQLSVDRRHLVLS--SGTLRI--SRVALHDQGQYECQAVNIVG 64

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: 52.50 E-value: 2.77e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  730 NPQNIRVQASQPKEMIIKWEPLKSMeqNGPGLEYRVTWKPQGAP----VEWEEETVTNHTLRVMTPavYAPYDVKVQAIN 805
Cdd:cd00063      3 PPTNLRVTDVTSTSVTLSWTPPEDD--GGPITGYVVEYREKGSGdwkeVEVTPGSETSYTLTGLKP--GTEYEFRVRAVN 78

                           90
                   ....*....|..
gi 1034630801  806 QLGSGPDPQSVT 817
Cdd:cd00063     79 GGGESPPSESVT 90

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: 52.41 E-value: 3.09e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  341 VIVEEPPRwtkkpQSAVYSTgSNGILLCEAEGEPQPTIKWRVNGSPVDNHPFAGDVVFPR----EISFTNLQP-NHTAVY 415
Cdd:cd05733      2 TITEQSPK-----DYIVDPR-DNITIKCEAKGNPQPTFRWTKDGKFFDPAKDPRVSMRRRsgtlVIDNHNGGPeDYQGEY 75

                           90
                   ....*....|....
gi 1034630801  416 QCEASNVHGTILAN 429
Cdd:cd05733     76 QCYASNELGTAISN 89

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: 52.17 E-value: 3.32e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1034630801  361 GSNGILLCEAEGEPQPTIKWRVNGSPVDNHPFAGDVVFPREISFTNLQPNHTAVYQCEASNVHGTILANANIDV 434
Cdd:cd05856     19 GSSVRLKCVASGNPRPDITWLKDNKPLTPPEIGENKKKKWTLSLKNLKPEDSGKYTCHVSNRAGEINATYKVDV 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: 51.74 E-value: 4.47e-08

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801   353 PQSAVYSTGSNGILLCEAEGEPQPTIKWRVNGSPVDNHPFAGDVVFPREIS---FTNLQPNHTAVYQCEASNVHGTILAN 429
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSGSTStltISNVTPEDSGTYTCAATNSSGSASSG 80


                    ....*
gi 1034630801   430 ANIDV 434
Cdd:smart00410   81 TTLTV 85

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 51.10 E-value: 7.14e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  347 PRWTKKPQSAVYSTGSNGILLCEAEGEPQPTIKWRVNGSPV--DNHpfaGDVVFPREISF---TNLQPNHTAVYQCEASN 421
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLrsSDR---FKVTYEGGTYTltiSNVQPDDSGKYTCVATN 77

                           90
                   ....*....|...
gi 1034630801  422 VHGTILANANIDV 434
Cdd:pfam07679   78 SAGEAEASAELTV 90

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: 50.41 E-value: 8.39e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  548 LELHCESKCDshlkHSLKLSWSKDGEAFEINGTEDGRIIIDGANLTISNVTLEDQGIYCCSAHTALDSAA 617
Cdd:cd00096      1 VTLTCSASGN----PPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSA 66

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 50.33 E-value: 1.23e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1034630801   56 ECEAKGNPEPTFSWTKDGNPFYFTDH-RIIPSNNSGTFRIPNEGhiSHFQGKYRCFASNKLGIAmSEEIEFIV 127
Cdd:pfam07679   21 TCTVTGTPDPEVSWFKDGQPLRSSDRfKVTYEGGTYTLTISNVQ--PDDSGKYTCVATNSAGEA-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: 50.31 E-value: 1.33e-07

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801   730 NPQNIRVQASQPKEMIIKWEPLKSMEQNGPGLEYRVTWKPQGApvEWEEETV----TNHTLRVMTPavYAPYDVKVQAIN 805
Cdd:smart00060    3 PPSNLRVTDVTSTSVTLSWEPPPDDGITGYIVGYRVEYREEGS--EWKEVNVtpssTSYTLTGLKP--GTEYEFRVRAVN 78


                    ....*
gi 1034630801   806 QLGSG 810
Cdd:smart00060   79 GAGEG 83

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: 50.26 E-value: 1.45e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  437 VRPLiqtkdgENYATVVGYSAFLHCEFFASPEAVVSWQKveEVKPL-EGRRYHIYENGTLQI-NRTTEEDAGSYSCWVEN 514
Cdd:cd20958      4 IRPM------GNLTAVAGQTLRLHCPVAGYPISSITWEK--DGRRLpLNHRQRVFPNGTLVIeNVQRSSDEGEYTCTARN 75


                   ....*.
gi 1034630801  515 AIGKTA 520
Cdd:cd20958     76 QQGQSA 81

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: 50.30 E-value: 1.54e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034630801  276 LECFAEGLPTPQVDWNKIGGDLPKGRETK----ENYGKTLKIENVSYQDKGNYRCTASNFLGTATHDFHVIV 343
Cdd:cd05729     24 LECGAGGNPMPNITWLKDGKEFKKEHRIGgtkvEEKGWSLIIERAIPRDKGKYTCIVENEYGSINHTYDVDV 95

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: 49.81 E-value: 1.69e-07

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801   548 LELHCESKCDSHLKhslkLSWSKDGEAFEIngtEDGRIIIDG----ANLTISNVTLEDQGIYCCSAHTALDSAADITQVT 623
Cdd:smart00410   12 VTLSCEASGSPPPE----VTWYKQGGKLLA---ESGRFSVSRsgstSTLTISNVTPEDSGTYTCAATNSSGSASSGTTLT 84


                    .
gi 1034630801   624 V 624
Cdd:smart00410   85 V 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: 49.17 E-value: 2.41e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1034630801  270 KGEILLLECFAEGLPTPQVDWNKIGGDLPKGRETKENYGKTLKIENVSYQDKGNYRCTASNFLGTATHDFHVIV 343
Cdd:cd05745      1 EGQTVDFLCEAQGYPQPVIAWTKGGSQLSVDRRHLVLSSGTLRISRVALHDQGQYECQAVNIVGSQRTVAQLTV 74

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: 49.17 E-value: 2.48e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1034630801  454 GYSAFLHCEFFASPEAVVSWQKVEEVKPLEgRRYHIYENGTLQINRTTEEDAGSYSCWVENAIGKTAVTANLDI 527
Cdd:cd05745      2 GQTVDFLCEAQGYPQPVIAWTKGGSQLSVD-RRHLVLSSGTLRISRVALHDQGQYECQAVNIVGSQRTVAQLTV 74

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 55.01 E-value: 2.68e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  797 YDVKVQAINQLGSGPDPQSVTLYSGEDYPdTAPVIHGVDVINSTLVKVTWSTVPKDRVhgrlKGYQINWWKTKSlldgrT 876
Cdd:COG3401    205 YYYRVAATDTGGESAPSNEVSVTTPTTPP-SAPTGLTATADTPGSVTLSWDPVTESDA----TGYRVYRSNSGD-----G 274

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  877 HPKEVNilrfSGQRNSGMVPSLDAFSEFHLTVLAYNSKG-AGPESEPYIFQTPEGVPEQPTFLKVIKVDKDTATLSWGlp 955
Cdd:COG3401    275 PFTKVA----TVTTTSYTDTGLTNGTTYYYRVTAVDAAGnESAPSNVVSVTTDLTPPAAPSGLTATAVGSSSITLSWT-- 348

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  956 KKLNGNLTGYLLQYqiinDTYEIGELNDINiTTPSKPSWHLSNLNATTKYKFYLRACTSQGCGKPITEESSTLGEGKYAG 1035
Cdd:COG3401    349 ASSDADVTGYNVYR----STSGGGTYTKIA-ETVTTTSYTDTGLTPGTTYYYKVTAVDAAGNESAPSEEVSATTASAASG 423

                          250
                   ....*....|
gi 1034630801 1036 LYDDISTQGW 1045
Cdd:COG3401    424 ESLTASVDAV 433

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: 49.55 E-value: 2.94e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801   35 PTI-IKQSKVQVAFPFDEYFQIECEAKGNPEPTFSWTKDGNPFYFTDHRIIPSNNSGTFRIPNEGHIShfQGKYRCFASN 113
Cdd:cd05730      2 PTIrARQSEVNATANLGQSVTLACDADGFPEPTMTWTKDGEPIESGEEKYSFNEDGSEMTILDVDKLD--EAEYTCIAEN 79


                   ...
gi 1034630801  114 KLG 116
Cdd:cd05730     80 KAG 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: 49.40 E-value: 3.06e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  439 PLIQTKDGENYAtVVGYSAFLHCEFFASPEAVVSWqkveeVKPlEGR------RYHIYENGTLQINRTTEEDAGSYSCWV 512
Cdd:cd05764      1 PLITRHTHELRV-LEGQRATLRCKARGDPEPAIHW-----ISP-EGKlisnssRTLVYDNGTLDILITTVKDTGAFTCIA 73

                           90
                   ....*....|....*
gi 1034630801  513 ENAIGKTAVTANLDI 527
Cdd:cd05764     74 SNPAGEATARVELHI 88

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: 49.04 E-value: 3.12e-07

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034630801    55 IECEAKGNPEPTFSWTKDGNPFYFTDHRIIPSNNSGTFRIpnegHISHFQ----GKYRCFASNKLGIAMSE 121
Cdd:smart00410   14 LSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSGSTSTL----TISNVTpedsGTYTCAATNSSGSASSG 80

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: 48.79 E-value: 5.17e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801   40 QSKVQVAFPFD---EYFQIECEAKGNPEPTFSWTKDGNPFYF-TDHRIipSNNSGTFRIPNEGHISHFqGKYRCFASNKL 115
Cdd:cd05848      6 QEPDDAIFPTDsdeKKVILNCEARGNPVPTYRWLRNGTEIDTeSDYRY--SLIDGNLIISNPSEVKDS-GRYQCLATNSI 82


                   ....*..
gi 1034630801  116 GIAMSEE 122
Cdd:cd05848     83 GSILSRE 89

First 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 first 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 first 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 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, including vascular (VCAM), intercellular (ICAM), neural (NCAM) and mucosal addressin (MADCAM) cell adhesion molecules, as well as junction adhesion molecules (JAM).

Pssm-ID: 409571 Cd Length: 91 Bit Score: 48.72 E-value: 5.41e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801   37 IIKQSKVQVAFPFDEYFQIECEAKGNPEPT-FSWTKDGNPFYFTDHRIIPSNNSGT--FRIPNEGHishfQGKYRCFASN 113
Cdd:cd20979      2 VLKEQPAEVLFREGQPTVLECVTEGGDQGVkYSWLKDGKSFNWQEHNVAQRKDEGSlvFLKPQASD----EGQYQCFAET 77

                           90
                   ....*....|..
gi 1034630801  114 KLGIAMSEEIEF 125
Cdd:cd20979     78 PAGVASSRVISF 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: 48.78 E-value: 5.57e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  252 KLLLPPTesgsesSITILKGEILLLECFAEGLPTPQVDWNKiGGDLpkgreTKENY------GKTLKIENVSYQDKGNYR 325
Cdd:cd20968      1 KITRPPT------NVTIIEGLKAVLPCTTMGNPKPSVSWIK-GDDL-----IKENNriavleSGSLRIHNVQKEDAGQYR 68

                           90
                   ....*....|
gi 1034630801  326 CTASNFLGTA 335
Cdd:cd20968     69 CVAKNSLGIA 78

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: 48.25 E-value: 6.21e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034630801  366 LLCEAEGEPQPTIKWRVNGSPVDNHPFA--------GDVVFPreisftNLQPNHTAVYQCEASNVHGTILAN 429
Cdd:cd05743      6 FTCVATGVPTPIINWRLNWGHVPDSARVsitseggyGTLTIR------DVKESDQGAYTCEAINTRGMVFGI 71

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: 48.33 E-value: 7.40e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1034630801  366 LLCEAEGEPQPTIKWRVNGSPV-DNHPF-AGDVVFPRE--ISF---TNLQPNHTAVYQCEASNVHGTILANANIDV 434
Cdd:cd20956     21 LKCVASGNPLPQITWTLDGFPIpESPRFrVGDYVTSDGdvVSYvniSSVRVEDGGEYTCTATNDVGSVSHSARINV 96

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: 48.46 E-value: 8.17e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  454 GYSAFLHCEFFASPEAVVSWQKVEEVKP------LEGRRYHIYENGTLQINRTTEEDAGSYSCWVENAIG 517
Cdd:cd20954     16 GQDVMLHCQADGFPTPTVTWKKATGSTPgeykdlLYDPNVRILPNGTLVFGHVQKENEGHYLCEAKNGIG 85

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: 47.78 E-value: 9.01e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  351 KKPQSAVYSTGSNGILLCEAEGEPQPTIKWRVNGS--PVDNHPFAGDvvfpREISFTNLQPNHTAVYQCEASNVHGTILA 428
Cdd:cd05725      2 KRPQNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGelPKGRYEILDD----HSLKIRKVTAGDMGSYTCVAENMVGKIEA 77


                   ....*.
gi 1034630801  429 NANIDV 434
Cdd:cd05725     78 SATLTV 83

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: 48.08 E-value: 1.08e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  251 PKLLLPPTEsgsessITILKGEILLLECFAEGLPTPQVDWNKIGGDLP------KGRETKENYGK-TLKIENVSYQDKGN 323
Cdd:cd20954      2 PRWIVEPVD------ANVAAGQDVMLHCQADGFPTPTVTWKKATGSTPgeykdlLYDPNVRILPNgTLVFGHVQKENEGH 75

                           90
                   ....*....|.
gi 1034630801  324 YRCTASNFLGT 334
Cdd:cd20954     76 YLCEAKNGIGS 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: 47.20 E-value: 1.22e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1034630801  282 GLPTPQVDWNKIGGDL-PKGRETKENYGK--TLKIENVSYQDKGNYRCTASNFLGTATHDFHVIV 343
Cdd:cd05748     18 GRPTPTVTWSKDGQPLkETGRVQIETTASstSLVIKNAKRSDSGKYTLTLKNSAGEKSATINVKV 82

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: 46.79 E-value: 1.58e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034630801  459 LHCEFFASPEAVVSWQKvEEVKPLEGRRYHIYENGTLQINRTTEEDAGSYSCWVENAIGKTAVTANL 525
Cdd:cd05746      3 IPCSAQGDPEPTITWNK-DGVQVTESGKFHISPEGYLAIRDVGVADQGRYECVARNTIGYASVSMVL 68

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: 47.11 E-value: 1.90e-06

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801   140 PLEVEEGDPIVLPCnPPKGLPPLHIYWMNIELEHIEQDERVYMSQKGD---LYFANVEEKDSRNdYCCFAafpRLRTIVQ 216
Cdd:smart00410    3 SVTVKEGESVTLSC-EASGSPPPEVTWYKQGGKLLAESGRFSVSRSGStstLTISNVTPEDSGT-YTCAA---TNSSGSA 77


                    ....*...
gi 1034630801   217 KMPMKLTV 224
Cdd:smart00410   78 SSGTTLTV 85

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: 47.11 E-value: 1.96e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034630801  267 TILKGEILLLECFAEGLPTPQVDWNKIGGDLPKG--RETKENYGkTLKIENVSYQDKGNYRCTASNFLGTAT 336
Cdd:cd20952     10 TVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKdeRITTLENG-SLQIKGAEKSDTGEYTCVALNLSGEAT 80

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: 46.80 E-value: 2.05e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1034630801  264 SSITILKGEILLLECFA-EGLPTPQVDWNKIGGDLPKGRETKENYGK----TLKIENVSYQDKGNYRCTASNFLG 333
Cdd:pfam00047    4 PTVTVLEGDSATLTCSAsTGSPGPDVTWSKEGGTLIESLKVKHDNGRttqsSLLISNVTKEDAGTYTCVVNNPGG 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: 47.11 E-value: 2.07e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  834 VDVINSTLVKVTWSTVPKDrvHGRLKGYQINWWKTkslldGRTHPKEVNilRFSGQRNSGMVPSLDAFSEFHLTVLAYNS 913
Cdd:cd00063      9 VTDVTSTSVTLSWTPPEDD--GGPITGYVVEYREK-----GSGDWKEVE--VTPGSETSYTLTGLKPGTEYEFRVRAVNG 79

                           90
                   ....*....|....
gi 1034630801  914 KGAGPESEPYIFQT 927
Cdd:cd00063     80 GGESPPSESVTVTT 93

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: 47.12 E-value: 2.18e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1034630801   55 IECEAKGNPEPTFSWTKDGNPFYFTDHRIIPSNNSGTFRIPNEghISHFQGKYRCFASNKLGIAMSEEIEFIV 127
Cdd:cd20970     22 FMCRAEGSPEPEISWTRNGNLIIEFNTRYIVRENGTTLTIRNI--RRSDMGIYLCIASNGVPGSVEKRITLQV 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: 46.33 E-value: 2.35e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034630801  271 GEILLLECFAEGLPTPQVDWNKIGGDLP-KGRETKENYGK--TLKIENVSYQDKGNYRCTASNFLGT 334
Cdd:cd05743      1 GETVEFTCVATGVPTPIINWRLNWGHVPdSARVSITSEGGygTLTIRDVKESDQGAYTCEAINTRGM 67

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: 46.63 E-value: 2.38e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1034630801  264 SSITILKGEILLLECFA-EGLPTPQVDWNKIG---GDLPKGRETKEnyGKTLKIENVSYQDKGNYRCTASNFLGT 334
Cdd:cd05724      5 SDTQVAVGEMAVLECSPpRGHPEPTVSWRKDGqplNLDNERVRIVD--DGNLLIAEARKSDEGTYKCVATNMVGE 77

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 46.40 E-value: 2.85e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1034630801  532 KLRVSPKNPRIPKLHMLELHCESKCDShlkhSLKLSWSKDGEAFEINGTEDGRIIIDGANLTISNVTLEDQGIYCCSAH 610
Cdd:pfam13927    3 VITVSPSSVTVREGETVTLTCEATGSP----PPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVAS 77

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: 46.63 E-value: 2.89e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034630801  452 VVGYSAFLHCEF-FASPEAVVSWQKVEEVKPLEGRRYHIYENGTLQINRTTEEDAGSYSCWVENAIG 517
Cdd:cd05724     10 AVGEMAVLECSPpRGHPEPTVSWRKDGQPLNLDNERVRIVDDGNLLIAEARKSDEGTYKCVATNMVG 76

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: 3.27e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1034630801  265 SITILKGEILLLECFAEGLPTPQVDWNKIGGDLPKGRETK----ENYGKTLKIENVSYQDKGNYRCTASNFLGTAT 336
Cdd:cd05744      9 DLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKmlvrENGRHSLIIEPVTKRDAGIYTCIARNRAGENS 84

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: 46.64 E-value: 3.34e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  454 GYSAFLHCEFFASPEAVVSWQKVEEvkPLEG----RRYHIYENG---TLQINRTTEEDAGSYSCWVENAIGKTAVTANLD 526
Cdd:cd20951     15 KSDAKLRVEVQGKPDPEVKWYKNGV--PIDPssipGKYKIESEYgvhVLHIRRVTVEDSAVYSAVAKNIHGEASSSASVV 92


                   ..
gi 1034630801  527 IR 528
Cdd:cd20951     93 VE 94

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: 46.47 E-value: 3.46e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  448 NYATVVGYSAFLHCEFFASPEAVVSWQKVEEVKPlEGRRYHIYENGTLQINRTTEEDAGSYSCWVENAIG 517
Cdd:cd20968      8 NVTIIEGLKAVLPCTTMGNPKPSVSWIKGDDLIK-ENNRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLG 76

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: 46.42 E-value: 3.63e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  346 PPRWTKKPQSAVYSTGSNGILLCEAEGEPQPTIKWRVNGSPVDNHPfagDVVFPREISFTNL-----QPNHTAVYQCEAS 420
Cdd:cd20972      1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSP---DIQIHQEGDLHSLiiaeaFEEDTGRYSCLAT 77

                           90
                   ....*....|....
gi 1034630801  421 NVHGTILANANIDV 434
Cdd:cd20972     78 NSVGSDTTSAEIFV 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: 46.04 E-value: 4.64e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  256 PPTESGSESSITILKGEILLLECFAEGLPTPQVDWNKIGGDL---PKGRETKENYGKTLKIENVSYQDKGNYRCTASNFL 332
Cdd:cd20972      1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELqnsPDIQIHQEGDLHSLIIAEAFEEDTGRYSCLATNSV 80

                           90
                   ....*....|.
gi 1034630801  333 GTATHDFHVIV 343
Cdd:cd20972     81 GSDTTSAEIFV 91

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: 46.06 E-value: 4.71e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1034630801   39 KQSKVQVAFPFDEYFQIECEAKGNPEPTFSWTKDGNPFYfTDHRIIPSNNSGT-FRIPNEGHISHFQGKYRCFASNKLG 116
Cdd:cd05729      8 KMEEREHALPAANKVRLECGAGGNPMPNITWLKDGKEFK-KEHRIGGTKVEEKgWSLIIERAIPRDKGKYTCIVENEYG 85

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: 45.84 E-value: 5.01e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  266 ITILKGEILLLECFAEGLPTPQVDWNKIGGDLPKGRETKENY---GKTLKIENVSYQDKGNYRCTASNFLGTATHDFHVI 342
Cdd:cd20969     12 VFVDEGHTVQFVCRADGDPPPAILWLSPRKHLVSAKSNGRLTvfpDGTLEVRYAQVQDNGTYLCIAANAGGNDSMPAHLH 91


                   .
gi 1034630801  343 V 343
Cdd:cd20969     92 V 92

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: 46.08 E-value: 5.34e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  347 PRWTKKPQSAVYSTGSNG---ILLCEAEGEPQPTIKWRVNGSPVDNHP------FAGDVVfpreISFTNLQPNhTAVYQC 417
Cdd:cd04967      2 PVFEEQPDDTIFPEDSDEkkvALNCRARANPVPSYRWLMNGTEIDLESdyryslVDGTLV----ISNPSKAKD-AGHYQC 76

                           90
                   ....*....|.
gi 1034630801  418 EASNVHGTILA 428
Cdd:cd04967     77 LATNTVGSVLS 87

Sixth immunoglobulin (Ig) domain of contactin-2; The members here are composed of the sixth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-2-like. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. It may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. 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. 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-2 is also expressed in retinal amacrine cells (AC) in the developing chick retina, corresponding to the period of formation and maturation of AC processes.

Pssm-ID: 409440 Cd Length: 102 Bit Score: 45.80 E-value: 7.12e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  529 NATKLRVSPKNPRIPKLHMLELHCESKCDSHLkhSLKLSWSKDGEAFEINGTE------DGRIIIdgANLTISNVTLEDQ 602
Cdd:cd05854      1 DATKITLAPSSADINQGENLTLQCHASHDPTM--DLTFTWSLDDFPIDLDKPNghyrrmEVKETI--GDLVIVNAQLSHA 76

                           90       100
                   ....*....|....*....|....*.
gi 1034630801  603 GIYCCSAHTALDSAADITQVTVLDVP 628
Cdd:cd05854     77 GTYTCTAQTVVDSASASATLVVRGPP 102

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: 45.48 E-value: 7.42e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  266 ITILKGEILLLECFAEGLPTPQVDWNKIGG----DLPKGRETKENYGKTLKIENVSYQDKGNYRCTASNFLGTATHDFHV 341
Cdd:cd20990     10 LTVQEGKLCRMDCKVSGLPTPDLSWQLDGKpirpDSAHKMLVRENGVHSLIIEPVTSRDAGIYTCIATNRAGQNSFNLEL 89


                   ..
gi 1034630801  342 IV 343
Cdd:cd20990     90 VV 91

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 45.10 E-value: 8.05e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  834 VDVINSTLVKVTWStvPKDRVHGRLKGYQINWWKTKSLldgrTHPKEVNIlrfSGQRNSGMVPSLDAFSEFHLTVLAYNS 913
Cdd:pfam00041    8 VTDVTSTSLTVSWT--PPPDGNGPITGYEVEYRPKNSG----EPWNEITV---PGTTTSVTLTGLKPGTEYEVRVQAVNG 78


                   ....*..
gi 1034630801  914 KGAGPES 920
Cdd:pfam00041   79 GGEGPPS 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: 45.42 E-value: 9.40e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  255 LPPTESGSESSITILKGEILLLECFAEGLPTPQVDWNKIGGDLPKGRE---TKENYGKTLKIENVSYQDKGNYRCTASNF 331
Cdd:cd05747      2 LPATILTKPRSLTVSEGESARFSCDVDGEPAPTVTWMREGQIIVSSQRhqiTSTEYKSTFEISKVQMSDEGNYTVVVENS 81


                   ....*...
gi 1034630801  332 LGTATHDF 339
Cdd:cd05747     82 EGKQEAQF 89

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: 45.14 E-value: 1.01e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1034630801   55 IECEAKGNPEPTFSWTKdGNPFYFTDHRIIPSNNsGTFRIPNEGHiSHfQGKYRCFASNKLGIAMS 120
Cdd:cd04969     22 IECKPKASPKPTISWSK-GTELLTNSSRICILPD-GSLKIKNVTK-SD-EGKYTCFAVNFFGKANS 83

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: 44.87 E-value: 1.08e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  266 ITILKGEILLLECFAEGLPTPQVDWNKIGGDLPKGRETKENYGKTLKIENV-SYQDKGNYRCTASNFLG-TATHDFHVIV 343
Cdd:cd20958     10 LTAVAGQTLRLHCPVAGYPISSITWEKDGRRLPLNHRQRVFPNGTLVIENVqRSSDEGEYTCTARNQQGqSASRSVFVKV 89

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: 44.92 E-value: 1.20e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  439 PLIQTKDGENYATV-VGYSAFLHCEFFASPEAVVSWQKVEEVKPLEGRRYHIYENGT-LQINRTTEEDAGSYSCWVENAI 516
Cdd:cd05730      2 PTIRARQSEVNATAnLGQSVTLACDADGFPEPTMTWTKDGEPIESGEEKYSFNEDGSeMTILDVDKLDEAEYTCIAENKA 81

                           90
                   ....*....|.
gi 1034630801  517 GKTAVTANLDI 527
Cdd:cd05730     82 GEQEAEIHLKV 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: 44.92 E-value: 1.21e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  256 PPTESGSESSI--TILKGEILLLECFAEGLPTPQVDWNKIGGDLPKGRETKE-NY-GKTLKIENVSYQDKGNYRCTASNF 331
Cdd:cd05730      1 PPTIRARQSEVnaTANLGQSVTLACDADGFPEPTMTWTKDGEPIESGEEKYSfNEdGSEMTILDVDKLDEAEYTCIAENK 80

                           90
                   ....*....|..
gi 1034630801  332 LGTATHDFHVIV 343
Cdd:cd05730     81 AGEQEAEIHLKV 92

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: 44.82 E-value: 1.23e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1034630801  267 TILKGEILLLECFAEGLPTPQVDWNKI-------GGDLPKGRETKENYGKT-LKIENVSYQDKGNYRCTASNFLG 333
Cdd:cd05732     12 TAVELEQITLTCEAEGDPIPEITWRRAtrgisfeEGDLDGRIVVRGHARVSsLTLKDVQLTDAGRYDCEASNRIG 86

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: 45.00 E-value: 1.29e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1034630801   55 IECEAKGNPEPTFSWTKDGNPF-YFTDHRIIPSNNSGTFRIPNEGHIShfQGKYRCFASNKLGIAMSEEIEFIV 127
Cdd:cd05738     19 MLCAASGNPDPEISWFKDFLPVdTATSNGRIKQLRSGALQIENSEESD--QGKYECVATNSAGTRYSAPANLYV 90

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: 44.93 E-value: 1.34e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  347 PRWTKKPQSAVYSTGSNG---ILLCEAEGEPQPTIKWRVNGSPVDnhpFAGDVVFPR-EISFTNLQPNH---TAVYQCEA 419
Cdd:cd05848      2 PVFVQEPDDAIFPTDSDEkkvILNCEARGNPVPTYRWLRNGTEID---TESDYRYSLiDGNLIISNPSEvkdSGRYQCLA 78


                   ....*....
gi 1034630801  420 SNVHGTILA 428
Cdd:cd05848     79 TNSIGSILS 87

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: 44.46 E-value: 1.79e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  264 SSITILKGEILLLECFAEGLPTPQVDWNKIG------GDLPKGRETKENYGKTLKIENV----SYQDKGNYRCTASNFLG 333
Cdd:cd07693      8 SDLIVSKGDPATLNCKAEGRPTPTIQWLKNGqpletdKDDPRSHRIVLPSGSLFFLRVVhgrkGRSDEGVYVCVAHNSLG 87


                   ...
gi 1034630801  334 TAT 336
Cdd:cd07693     88 EAV 90

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: 44.31 E-value: 1.87e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801   51 EYFQIECEA-KGNPEPTFSWTKDGNPFYFTDHRIipsnnsgtfRIPNEGH--ISHFQ----GKYRCFASNKLGIAMSEEI 123
Cdd:cd05724     13 EMAVLECSPpRGHPEPTVSWRKDGQPLNLDNERV---------RIVDDGNllIAEARksdeGTYKCVATNMVGERESRAA 83


                   ....
gi 1034630801  124 EFIV 127
Cdd:cd05724     84 RLSV 87

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: 44.08 E-value: 1.87e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  439 PLIQTKDGENYATVVGYSAFLHCEFFASPEAVVSWQKVEEvkPLEGRRYHIYENGTLQINRTTEEDAGSYSCWVENAIGK 518
Cdd:cd04968      1 PSIKVRFPADTYALKGQTVTLECFALGNPVPQIKWRKVDG--SPSSQWEITTSEPVLEIPNVQFEDEGTYECEAENSRGK 78


                   ....*..
gi 1034630801  519 TAVTANL 525
Cdd:cd04968     79 DTVQGRI 85

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: 44.46 E-value: 2.08e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801   39 KQSKVQVAFPFDEYFQIECEAKGNPEPTFSWTKDGNPFYfTDHRIipsnnsGTFRIPN-------EGHISHFQGKYRCFA 111
Cdd:cd05857      8 KMEKKLHAVPAANTVKFRCPAAGNPTPTMRWLKNGKEFK-QEHRI------GGYKVRNqhwslimESVVPSDKGNYTCVV 80


                   ....*
gi 1034630801  112 SNKLG 116
Cdd:cd05857     81 ENEYG 85

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: 44.04 E-value: 2.50e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1034630801  271 GEILLLECFAEGL-PTPQVDWNKIGGDLPKGRETKENYGKT-----LKIENVSYQDKGNYRCTASNFLGTATHDFHVIV 343
Cdd:cd05750     14 GSKLVLKCEATSEnPSPRYRWFKDGKELNRKRPKNIKIRNKkknseLQINKAKLEDSGEYTCVVENILGKDTVTGNVTV 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: 44.04 E-value: 2.65e-05

                           10        20        30
                   ....*....|....*....|....*....|....*.
gi 1034630801  492 NGTLQINRTTEEDAGSYSCWVENAIGKTAVTANLDI 527
Cdd:cd05750     57 NSELQINKAKLEDSGEYTCVVENILGKDTVTGNVTV 92

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: 43.72 E-value: 2.85e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  267 TILKGEILLLECFAEGLPTPQVDWNKIGGDLPKGRETK----ENYGKTLKIENVSYQDKGNYRCTASNFLGTATHDFHVI 342
Cdd:cd20973      8 EVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQidqdEDGLCSLIISDVCGDDSGKYTCKAVNSLGEATCSAELT 87


                   .
gi 1034630801  343 V 343
Cdd:cd20973     88 V 88

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: 43.86 E-value: 2.92e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1034630801  454 GYSAFLHCEFFASPEAVVSWQKveEVKPL-----EGRRYHIYENGtLQINRTTEEDAGSYSCWVENAIG 517
Cdd:cd20949     14 GQSATILCEVKGEPQPNVTWHF--NGQPIsasvaDMSKYRILADG-LLINKVTQDDTGEYTCRAYQVNS 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: 43.53 E-value: 3.05e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801   35 PTIIKQSKVQVAFPFDEYFQIECEAKGNPEPTFSWTKDGNP-------FYFTDHR--IIPSNNSGTfripneghishfqG 105
Cdd:cd20978      1 PKFIQKPEKNVVVKGGQDVTLPCQVTGVPQPKITWLHNGKPlqgpmerATVEDGTltIINVQPEDT-------------G 67

                           90
                   ....*....|....*.
gi 1034630801  106 KYRCFASNKLGIAMSE 121
Cdd:cd20978     68 YYGCVATNEIGDIYTE 83

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 43.15 E-value: 3.66e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034630801  353 PQSAVYSTGSNGILLCEAEGEPQPTIKWRVNGSPVDNHPfagdvvfprEISFTNLQPNHTAVYQCEASNVHGTILAN 429
Cdd:pfam13895    6 PSPTVVTEGEPVTLTCSAPGNPPPSYTWYKDGSAISSSP---------NFFTLSVSAEDSGTYTCVARNGRGGKVSN 73

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: 43.54 E-value: 3.71e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1034630801  142 EVEEGDPIVLPCNPPKGLPPLHIYWMNIELEHIEQDERVYMSQKGDLYFANVEEKDSRNdYCCFA 206
Cdd:cd05724      8 QVAVGEMAVLECSPPRGHPEPTVSWRKDGQPLNLDNERVRIVDDGNLLIAEARKSDEGT-YKCVA 71

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: 43.62 E-value: 3.76e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  346 PPRWTKKPQSAVYSTGSNGILLCEAEGEPQPTIKWRVNGSpvdnhpFAGDVVFPREISFTN--------LQPNH----TA 413
Cdd:cd05722      1 ELYFLSEPSDIVAMRGGPVVLNCSAESDPPPKIEWKKDGV------LLNLVSDERRQQLPNgsllitsvVHSKHnkpdEG 74

                           90
                   ....*....|....*.
gi 1034630801  414 VYQCEASN-VHGTILA 428
Cdd:cd05722     75 FYQCVAQNeSLGSIVS 90

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: 43.59 E-value: 3.77e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801   51 EYFQIECEAKGNPEPTFSWTKDGNPfyFTDHRIIPSNN----SGTFRIPNEGHIshfqGKYRCFASNKLG 116
Cdd:cd04978     15 ETGELICEAEGNPQPTITWRLNGVP--IEPAPEDMRRTvdgrTLIFSNLQPNDT----AVYQCNASNVHG 78

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: 43.65 E-value: 3.89e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  352 KPQSAVYSTGSNGILLCEAEGEPQPTIKWRVNG----SPVDNHPFAGDvvfPREISFTNLQPNHTAVYQCEASN-VHGTI 426
Cdd:cd20970      8 PSFTVTAREGENATFMCRAEGSPEPEISWTRNGnliiEFNTRYIVREN---GTTLTIRNIRRSDMGIYLCIASNgVPGSV 84

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: 43.36 E-value: 3.96e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1034630801  271 GEILLLECFAEGLPTPQVDWNKIGGDLPKGRETKENYGKtLKIENVSYQDKGNYRCTASNFLGT 334
Cdd:cd05728     14 GSSLRWECKASGNPRPAYRWLKNGQPLASENRIEVEAGD-LRITKLSLSDSGMYQCVAENKHGT 76

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: 42.95 E-value: 4.63e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1034630801  453 VGYSAFLHCE-FFASPEAVVSWQKvEEVKPLEGRRYHIYENG----TLQINRTTEEDAGSYSCWVENAIGKTAVTANL 525
Cdd:pfam00047   10 EGDSATLTCSaSTGSPGPDVTWSK-EGGTLIESLKVKHDNGRttqsSLLISNVTKEDAGTYTCVVNNPGGSATLSTSL 86

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: 43.32 E-value: 4.85e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  264 SSITILKGEILLLECFAEGLPTPQVDWNKIGGDLPK-GRETKENY----GKT---LKIENVSYQDKGNYRCTASNFLGTA 335
Cdd:cd20956      9 SEQTLQPGPSVSLKCVASGNPLPQITWTLDGFPIPEsPRFRVGDYvtsdGDVvsyVNISSVRVEDGGEYTCTATNDVGSV 88


                   ..
gi 1034630801  336 TH 337
Cdd:cd20956     89 SH 90

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: 5.23e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  262 SESSITILKGEILLLECFAEGLPTPQVDWNKIGG--DLPKG-RETKENYGKTLKIENVS-----YQdkGNYRCTASNFLG 333
Cdd:cd05733      7 SPKDYIVDPRDNITIKCEAKGNPQPTFRWTKDGKffDPAKDpRVSMRRRSGTLVIDNHNggpedYQ--GEYQCYASNELG 84

                           90
                   ....*....|
gi 1034630801  334 TA-THDFHVI 342
Cdd:cd05733     85 TAiSNEIRLV 94

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: 43.30 E-value: 5.57e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034630801  276 LECFAEGLPTPQVDWNKIGGDLPK----GRETKENYGKTLKIENVSYQDKGNYRCTASNFLGTATHDFHVIV 343
Cdd:cd05857     24 FRCPAAGNPTPTMRWLKNGKEFKQehriGGYKVRNQHWSLIMESVVPSDKGNYTCVVENEYGSINHTYHLDV 95

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: 43.00 E-value: 5.60e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1034630801  355 SAVYSTGSNGILLCEAEGEPQPTIKWRVNGSPVDN----HPFAGDvvfPREISFTNLQPNHTAVYQCEASNVHG 424
Cdd:cd05730     12 NATANLGQSVTLACDADGFPEPTMTWTKDGEPIESgeekYSFNED---GSEMTILDVDKLDEAEYTCIAENKAG 82

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: 42.92 E-value: 5.65e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801   42 KVQVAFPFDEY------FQIECEAKGNPEPTFSWTK-DGNPFyftdHRIIPSNNSGTFRIPNeghishFQ----GKYRCF 110
Cdd:cd04968      2 SIKVRFPADTYalkgqtVTLECFALGNPVPQIKWRKvDGSPS----SQWEITTSEPVLEIPN------VQfedeGTYECE 71


                   ....*.
gi 1034630801  111 ASNKLG 116
Cdd:cd04968     72 AENSRG 77

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: 42.76 E-value: 5.88e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  256 PPTESGSESSITILKGEILLLECFAEGLPTPQVDWnkiggdLPKGRETKENYGK------TLKIENVSYQDKGNYRCTAS 329
Cdd:cd20978      1 PKFIQKPEKNVVVKGGQDVTLPCQVTGVPQPKITW------LHNGKPLQGPMERatvedgTLTIINVQPEDTGYYGCVAT 74

                           90
                   ....*....|....
gi 1034630801  330 NFLGTATHDFHVIV 343
Cdd:cd20978     75 NEIGDIYTETLLHV 88

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: 42.59 E-value: 6.15e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1034630801  453 VGYSAFLHCEFFASPEAVVSWQKVEEVKPLEGRRYhiYENGTLQINRTTEEDAGSYSCWVENAIGKTAVTANLDI 527
Cdd:cd05728     13 IGSSLRWECKASGNPRPAYRWLKNGQPLASENRIE--VEAGDLRITKLSLSDSGMYQCVAENKHGTIYASAELAV 85

Fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell adhesion molecule 5 (CEACAM5) and similar domains; member of the C2-set IgSF domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell adhesion molecule 5 (CEACAM5) and similar domains. 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. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), also known as CD66e (Cluster of Differentiation 66e), is a cell surface glycoprotein that plays a role in cell adhesion, intracellular signaling and tumor progression. Diseases associated with CEACAM5 include lung cancer and rectum cancer. 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' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409540 Cd Length: 76 Bit Score: 42.48 E-value: 6.15e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034630801  264 SSITILKGEILLLECFAEGLPTPQVDWNKIGGDLPKGREtkenygktLKIENVSYQDKGNYRCTASNFLGT 334
Cdd:cd20948      3 SDTYYLSGENLNLSCHAASNPPAQYSWTINGTFQTSSQE--------LFLPAITENNEGTYTCSAHNSLTG 65

First Ig-like domain of Junctional adhesion molecule-1 (JAM1)and similar domains; a member of the V-set of IgSF domains; The members here are composed of the first Ig-like domain of Junctional Adhesion Molecule-1 (JAM1)and similar domains. JAM1 is an immunoglobulin superfamily (IgSF) protein with two Ig-like domains in its extracellular region; it plays a role in the formation of endothelial and epithelial tight junction and acts as a receptor for mammalian reovirus sigma-1. The 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 first Ig-like domain of JAM1 is a member of the V-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C'-C" in the other.

Pssm-ID: 409538 Cd Length: 102 Bit Score: 42.91 E-value: 6.89e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  536 SPKNPRIPKLHMLELHCESkcdSHLKHSLKLSWSKDG--------EAFEINGTEDGRIIIDGANLTISNVTLEDQGIYCC 607
Cdd:cd20946      5 SQQVVTVVENQEVILSCKT---PKKTSSPRVEWKKLQrdvtfvvfQNNKIQGDYKGRAEILGTNITIKNVTRSDSGKYRC 81

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: 42.59 E-value: 7.19e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1034630801   54 QIECEAKGNPEPTFSWTKDGNPFYfTDHRIIPSNnsGTFRIpNEGHISHfQGKYRCFASNKLG 116
Cdd:cd05728     18 RWECKASGNPRPAYRWLKNGQPLA-SENRIEVEA--GDLRI-TKLSLSD-SGMYQCVAENKHG 75

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: 42.61 E-value: 7.98e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034630801   57 CEAKGNPEPTFSWTKdGNPFYFTDHRIiPSNNSGTFRIPNEGhiSHFQGKYRCFASNKLGIAMSEEIEFIV 127
Cdd:cd20968     21 CTTMGNPKPSVSWIK-GDDLIKENNRI-AVLESGSLRIHNVQ--KEDAGQYRCVAKNSLGIAYSKPVTIEV 87

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: 42.41 E-value: 8.27e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  265 SITILKGEILLLECFAEGLPTPQVDWNKIG-----GDLPKGRETKENYGK-TLKIENVSYQDKGNYRCTASNFLGTATHD 338
Cdd:cd20951      9 SHTVWEKSDAKLRVEVQGKPDPEVKWYKNGvpidpSSIPGKYKIESEYGVhVLHIRRVTVEDSAVYSAVAKNIHGEASSS 88


                   ....*.
gi 1034630801  339 FHVIVE 344
Cdd:cd20951     89 ASVVVE 94

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: 42.62 E-value: 8.59e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  130 VPKFPKEKIDPLEveeGDPIVLPCNPPKGLPPLHIYWMN--IELEHIEQ---DERVYMSQKGDLYFANVEEKDSRND--Y 202
Cdd:cd20965      4 DPQVKTKEKKPVE---GKPFKLDCNVPPGYPKPTIEWKKqlVSDSSKADtilDRRITISPNGDLYFTNVTKEDVSTDykY 80


                   ....*..
gi 1034630801  203 CCFAAFP 209
Cdd:cd20965     81 VCVAKTP 87

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: 42.40 E-value: 1.02e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  347 PRWTKKPQSAV-YSTGSNGILLCEAEGEPQPTIKW-RVNGSPVDNHP------FAGDVVFPREISFTNLQPNHTAVYQCE 418
Cdd:cd20955      2 PVFLKEPTNRIdFSNSTGAEIECKASGNPMPEIIWiRSDGTAVGDVPglrqisSDGKLVFPPFRAEDYRQEVHAQVYACL 81

                           90
                   ....*....|
gi 1034630801  419 ASNVHGTILA 428
Cdd:cd20955     82 ARNQFGSIIS 91

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: 41.99 E-value: 1.05e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1034630801  459 LHCEFFASPEAVVSWqkVEEVKPLEGRRYHI-YENGTLQINRTTEEDAGSYSCWVENAIGKTAVTANL 525
Cdd:cd20978     21 LPCQVTGVPQPKITW--LHNGKPLQGPMERAtVEDGTLTIINVQPEDTGYYGCVATNEIGDIYTETLL 86

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: 42.15 E-value: 1.08e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  351 KKPQSAVYSTGSNGILLCEAEGEPQPTIKWRvngsPVDNHPFAGDVVFPRE--ISFTNLQPNHTAVYQCEASNVHGTILA 428
Cdd:cd04968      6 RFPADTYALKGQTVTLECFALGNPVPQIKWR----KVDGSPSSQWEITTSEpvLEIPNVQFEDEGTYECEAENSRGKDTV 81


                   ....*.
gi 1034630801  429 NANIDV 434
Cdd:cd04968     82 QGRIIV 87

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: 42.20 E-value: 1.22e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  266 ITILKGEILLLECFAEGLPTPQVDWNKIGGDLpkgrETKENY------GK--TLKIENVSYQDKGNYRCTASNFLGTATH 337
Cdd:cd05891     11 VTIMEGKTLNLTCTVFGNPDPEVIWFKNDQDI----ELSEHYsvkleqGKyaSLTIKGVTSEDSGKYSINVKNKYGGETV 86


                   ....*.
gi 1034630801  338 DFHVIV 343
Cdd:cd05891     87 DVTVSV 92

First immunoglobulin (Ig) domain of contactin-2; 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-2-like. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. It may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. 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. 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-2 is also expressed in retinal amacrine cells in the developing chick retina, corresponding to the period of formation and maturation of AC processes. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409437 [Multi-domain] Cd Length: 97 Bit Score: 42.22 E-value: 1.30e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  347 PRWTKKPQSAVYSTGSNG---ILLCEAEGEPQPTIKWRVNGSPVDNHP------FAGDVVfpreisFTNLQPNHTA-VYQ 416
Cdd:cd05850      3 PVFEEQPSSTLFPEGSAEekvTLACRARASPPATYRWKMNGTELKMEPdsryrlVAGNLV------ISNPVKAKDAgSYQ 76

                           90
                   ....*....|..
gi 1034630801  417 CEASNVHGTILA 428
Cdd:cd05850     77 CLASNRRGTVVS 88

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: 42.27 E-value: 1.37e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1034630801  265 SITILKGEILLLECFAEGLPTPQVDWNKI--------GGDLPKGR-ETKENYGKT-LKIENVSYQDKGNYRCTASNFLG 333
Cdd:cd05870     10 NETTVENGAATLSCKAEGEPIPEITWKRAsdghtfseGDKSPDGRiEVKGQHGESsLHIKDVKLSDSGRYDCEAASRIG 88

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: 41.81 E-value: 1.72e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1034630801   50 DEYFQIECEAKGNPEPTFSWTKDGNPFYFTDHRIIPSNNSGTFRIPNEGHISHFQGKYRCFASNKLGiamSEEIEFIV 127
Cdd:cd05737     16 GKTLNLTCNVWGDPPPEVSWLKNDQALAFLDHCNLKVEAGRTVYFTINGVSSEDSGKYGLVVKNKYG---SETSDVTV 90

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: 41.78 E-value: 1.83e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034630801   57 CEAKGNPEPTFSWTKDGNPFYfTDHRIipsnNSGTFRIPNeGH------ISHFQ----GKYRCFASNKLGIA 118
Cdd:cd20956     23 CVASGNPLPQITWTLDGFPIP-ESPRF----RVGDYVTSD-GDvvsyvnISSVRvedgGEYTCTATNDVGSV 88

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: 41.77 E-value: 1.91e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  529 NATKLRVSPKNPRIPKLHMLELHCESKCDSHLkhSLKLSWSKDGEAF---EINGTEDGRIIIDGA-NLTISNVTLEDQGI 604
Cdd:cd04970      1 DATRITLAPSNADITVGENATLQCHASHDPTL--DLTFTWSFNGVPIdleKIEGHYRRRYGKDSNgDLEIVNAQLKHAGR 78

                           90       100       110
                   ....*....|....*....|....*....|
gi 1034630801  605 YCCSAHTALDS---AADitqvtvLDVPDPP 631
Cdd:cd04970     79 YTCTAQTVVDSdsaSAT------LVVRGPP 102

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: 41.44 E-value: 2.16e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  347 PRWT-----KKPQSAVYStGSNGILLCEAEGEPQPTIKWRVNGSPVDNHPFAGdVVFPREISFT----NLQPNHTAVYQC 417
Cdd:cd05729      1 PRFTdtekmEEREHALPA-ANKVRLECGAGGNPMPNITWLKDGKEFKKEHRIG-GTKVEEKGWSliieRAIPRDKGKYTC 78

                           90
                   ....*....|....*..
gi 1034630801  418 EASNVHGTILANANIDV 434
Cdd:cd05729     79 IVENEYGSINHTYDVDV 95

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: 41.36 E-value: 2.22e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  435 VDVRPLIQTKDgenyatvVGYSAFLHCEFFASPEAVVSWQKVEEVKPLEGRRYHIYENgTLQINRTTEEDAGSYSCWVEN 514
Cdd:cd20957      4 ATIDPPVQTVD-------FGRTAVFNCSVTGNPIHTVLWMKDGKPLGHSSRVQILSED-VLVIPSVKREDKGMYQCFVRN 75

                           90
                   ....*....|...
gi 1034630801  515 AIGKTAVTANLDI 527
Cdd:cd20957     76 DGDSAQATAELKL 88

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: 41.33 E-value: 2.31e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  347 PRWTKKPQSAVYSTGSNGILLCEAEGEPQPTIKWRVNGSPVdnHPFAGDVVFPRE-----ISFTNLQPNHTAVYQCEASN 421
Cdd:cd05744      1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPV--RPDSAHKMLVREngrhsLIIEPVTKRDAGIYTCIARN 78

                           90
                   ....*....|...
gi 1034630801  422 VHGTILANANIDV 434
Cdd:cd05744     79 RAGENSFNAELVV 91

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: 41.03 E-value: 2.37e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  535 VSPKNPRIPKLHMLELHCESKCDSHLkhsLKLSWSKDGEAFEIN---GTEDGRIIIdgANLTISNVTLEDQGIYCCSAHT 611
Cdd:pfam00047    1 SAPPTVTVLEGDSATLTCSASTGSPG---PDVTWSKEGGTLIESlkvKHDNGRTTQ--SSLLISNVTKEDAGTYTCVVNN 75


                   ....*
gi 1034630801  612 ALDSA 616
Cdd:pfam00047   76 PGGSA 80

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: 41.16 E-value: 2.58e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  348 RWTKKPQSAVYSTGSNGILLCEAEGEPQPTIKWRVNGSPV-----DNHPFAGDvvfPREISFTNLQPNHTAVYQCEASNV 422
Cdd:cd20949      1 TFTENAYVTTVKEGQSATILCEVKGEPQPNVTWHFNGQPIsasvaDMSKYRIL---ADGLLINKVTQDDTGEYTCRAYQV 77


                   ...
gi 1034630801  423 HGT 425
Cdd:cd20949     78 NSI 80

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: 2.81e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1034630801  276 LECFAEGLPTPQVDWNKIGGDLPKGRETKENYGKTLKIENVSYQDKGNYRCTASNFLGTATHD 338
Cdd:cd05746      3 IPCSAQGDPEPTITWNKDGVQVTESGKFHISPEGYLAIRDVGVADQGRYECVARNTIGYASVS 65

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 44.99 E-value: 2.94e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  692 LAPFVRYQFRVIAVNEVGRSQPSQPSD--HHETPPAApdrnPQNIRVQASQPKEMIIKWEPLKSMEQNGpgleYRVTWK- 768
Cdd:COG3401    199 IEPGTTYYYRVAATDTGGESAPSNEVSvtTPTTPPSA----PTGLTATADTPGSVTLSWDPVTESDATG----YRVYRSn 270

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  769 -PQGAPVEWEEETVTNHTLRVMTPAVyaPYDVKVQAINQLGSGPDP-QSVTLYSGEDYPdTAPVIHGVDVINSTLVKVTW 846
Cdd:COG3401    271 sGDGPFTKVATVTTTSYTDTGLTNGT--TYYYRVTAVDAAGNESAPsNVVSVTTDLTPP-AAPSGLTATAVGSSSITLSW 347

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  847 STVPKDRVhgrlKGYQI--------NWWKTKSLLDGrthpkevnilrfsgqrNSGMVPSLDAFSEFHLTVLAYNSKGAGP 918
Cdd:COG3401    348 TASSDADV----TGYNVyrstsgggTYTKIAETVTT----------------TSYTDTGLTPGTTYYYKVTAVDAAGNES 407

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034630801  919 ESEPYIFQTPEGVPEQPTFLKVIKVDKDTATLSWGLPKKLNGNLTGYLLQYQIINDTYEIGELNDINITTPS 990
Cdd:COG3401    408 APSEEVSATTASAASGESLTASVDAVPLTDVAGATAAASAASNPGVSAAVLADGGDTGNAVPFTTTSSTVTA 479

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: 40.78 E-value: 3.04e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1034630801  361 GSNGILLCEAEGEPQPTIKWRVNGSPVdnhPFAGDVVFPREI-SFTNLQPNHTAVYQCEASNVHG 424
Cdd:cd05851     16 GQNVTLECFALGNPVPVIRWRKILEPM---PATAEISMSGAVlKIFNIQPEDEGTYECEAENIKG 77

First immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR). Fibroblast growth factors (FGFs) participate in morphogenesis, development, angiogenesis, and wound healing. These FGF-stimulated processes are mediated by four FGFR tyrosine kinases (FGRF1-4). FGFRs are comprised of an extracellular portion consisting of three Ig-like domains, a transmembrane helix, and a cytoplasmic portion having protein tyrosine kinase activity. The highly conserved Ig-like domains 2 and 3, and the linker region between D2 and D3 define a general binding site for all FGFs.

Pssm-ID: 409362 Cd Length: 94 Bit Score: 41.03 E-value: 3.06e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1034630801  548 LELHCESKCDSHLkhslkLSWSKDGeafeINGTEDGRIIIDGANLTISNVTLEDQGIYCCSAHTALDS 615
Cdd:cd04973     27 LQLRCRLRDDVQS-----INWTKDG----VQLGENNRTRITGEEVQIKDAVPRDSGLYACVTSSPSGS 85

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 40.70 E-value: 3.24e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034630801  565 KLSWSKDGEafEINGTEDGRIIIDGAN--LTISNVTLEDQGIYCCSAHTALDSAADITQVTV 624
Cdd:pfam07679   31 EVSWFKDGQ--PLRSSDRFKVTYEGGTytLTISNVQPDDSGKYTCVATNSAGEAEASAELTV 90

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: 40.56 E-value: 3.48e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034630801  454 GYSAFLHCEFFASPEAVVSWQKVEE-VKPLEGRRYHIYENG--TLQINRTTEEDAGSYSCWVENAIGKTAVTANLDI 527
Cdd:cd05744     15 GRLCRFDCKVSGLPTPDLFWQLNGKpVRPDSAHKMLVRENGrhSLIIEPVTKRDAGIYTCIARNRAGENSFNAELVV 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: 40.47 E-value: 3.67e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1034630801   54 QIECEAKGNPEPTFSWTKDGNPFYftDHRIIPSNNSGTFRIPNeghISHF-QGKYRCFASNKLGIA 118
Cdd:cd05731     14 LLECIAEGLPTPDIRWIKLGGELP--KGRTKFENFNKTLKIEN---VSEAdSGEYQCTASNTMGSA 74

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: 40.69 E-value: 4.18e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801   37 IIKQSKVQVAFPFD---EYFQIECEAKGNPEPTFSWTKDGnpfyfTDHRIIPSNN----SGTFRIPNEGHISHfQGKYRC 109
Cdd:cd04967      3 VFEEQPDDTIFPEDsdeKKVALNCRARANPVPSYRWLMNG-----TEIDLESDYRyslvDGTLVISNPSKAKD-AGHYQC 76

                           90
                   ....*....|...
gi 1034630801  110 FASNKLGIAMSEE 122
Cdd:cd04967     77 LATNTVGSVLSRE 89

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: 40.23 E-value: 4.19e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1034630801  264 SSITILKGEILLLECFAEG-LPTPQVDWNKIGGDLPKgreTKENYGKTLKIENVSYQDKGNYRCTASNFLGTA 335
Cdd:cd05754      9 RSQEVRPGADVSFICRAKSkSPAYTLVWTRVNGTLPS---RAMDFNGILTIRNVQLSDAGTYVCTGSNMLDTD 78

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: 40.65 E-value: 4.48e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  266 ITILKGEILLLECFAEGLPTPQVDWNKIGGDLP-------KGRETKENYgktLKIENVSYQDKGNYRCTASNFLGTATHD 338
Cdd:cd05737     11 VTIMEGKTLNLTCNVWGDPPPEVSWLKNDQALAfldhcnlKVEAGRTVY---FTINGVSSEDSGKYGLVVKNKYGSETSD 87


                   ....*
gi 1034630801  339 FHVIV 343
Cdd:cd05737     88 VTVSV 92

Immunoglobulin (Ig)-like domain of NrCAM (Ng (neuronglia) CAM-related cell adhesion molecule); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of NrCAM (Ng (neuronglia) CAM-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: 409458 Cd Length: 95 Bit Score: 40.35 E-value: 5.50e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  351 KKPQSAVYSTGSNGILLCEAEGEPQPTIKWRVNGSPVD--------NHPFAGDVVFprEISFTNLQPNHTAVYQCEASNV 422
Cdd:cd05874      6 QSPKDYIVDPRENIVIQCEAKGKPPPSFSWTRNGTHFDidkdpkvtMKPNTGTLVI--NIMNGEKAEAYEGVYQCTARNE 83


                   ....*..
gi 1034630801  423 HGTILAN 429
Cdd:cd05874     84 RGAAVSN 90

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: 39.98 E-value: 6.03e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1034630801   55 IECEAKGNPEPTFSWTKdGNPFYFTDHRIIPSNNsGTFRIPNEGHIShfQGKYRCFASNKLGIAMS 120
Cdd:cd05852     22 IECKPKAAPKPKFSWSK-GTELLVNNSRISIWDD-GSLEILNITKLD--EGSYTCFAENNRGKANS 83

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: 40.03 E-value: 6.90e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1034630801  346 PPRWTKKPQSAVYSTGSNGILLCEAEGEPQPTIKWRVNGSPV 387
Cdd:cd05747      3 PATILTKPRSLTVSEGESARFSCDVDGEPAPTVTWMREGQII 44

Third immunoglobulin domain of the hematopoietic colony-stimulating factor 1 receptor (CSF-1R), and similar domains; member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the hematopoietic colony-stimulating factor 1 receptor (CSF-1R) and similar proteins. CSF-1R, a class III receptor tyrosine kinase (RTKIII), is critical to the survival, proliferation, and differentiation of mononuclear phagocytic cells such as monocytes, tissue macrophages, muscularis macrophages, microglia, osteoclasts, Paneth cells, and myeloid dendritic cells. Human colony-stimulating factor 1 receptor (hCSF-1R) is unique among the hematopoietic receptors because it is activated by two distinct cytokines, CSF-1 and interleukin-34 (IL-34). The Ig superfamily (IgSF) 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, 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. 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 I-set of IgSF domains.

Pssm-ID: 409530 Cd Length: 93 Bit Score: 39.94 E-value: 6.97e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  251 PKLLLPPTEsgsessITILKGEILLLECFAEGLptpQVDWNKI--GGD----LPKGRETKENYGK---TLKIENVSYQDK 321
Cdd:cd20936      1 PALTLEPAE------LVRIRGEAAQIVCSASNV---DVNFDVFlqHGDtklaIPQQSDFHDNRYQkvlTLNLDQVDFQDA 71

                           90       100
                   ....*....|....*....|..
gi 1034630801  322 GNYRCTASNFLG--TATHDFHV 341
Cdd:cd20936     72 GNYSCVASNVQGkhSASMFFRV 93

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: 39.80 E-value: 7.29e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  439 PLIQT-KDGENYATVVGYSAFLHCEFFASPEAVVSWQKvEEVKPLEG-RRYHIYENGT-LQINRTTEEDAGSYSCWVENA 515
Cdd:cd20970      1 PVISTpQPSFTVTAREGENATFMCRAEGSPEPEISWTR-NGNLIIEFnTRYIVRENGTtLTIRNIRRSDMGIYLCIASNG 79


                   ....*
gi 1034630801  516 IGKTA 520
Cdd:cd20970     80 VPGSV 84

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: 39.84 E-value: 7.62e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  347 PRWT-----KKPQSAVySTGSNGILLCEAEGEPQPTIKWRVNGSPV-DNHPFAGDVVFPR--EISFTNLQPNHTAVYQCE 418
Cdd:cd05857      1 PYWTnpekmEKKLHAV-PAANTVKFRCPAAGNPTPTMRWLKNGKEFkQEHRIGGYKVRNQhwSLIMESVVPSDKGNYTCV 79

                           90
                   ....*....|....*.
gi 1034630801  419 ASNVHGTILANANIDV 434
Cdd:cd05857     80 VENEYGSINHTYHLDV 95

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: 39.84 E-value: 8.43e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034630801  276 LECFAEGLPTPQVDWNKIGGDL---PKGRETKENYgkTLKIENVSYQDKGNYRCTASNFLG--TATHDFHV 341
Cdd:cd05856     24 LKCVASGNPRPDITWLKDNKPLtppEIGENKKKKW--TLSLKNLKPEDSGKYTCHVSNRAGeiNATYKVDV 92

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: 39.53 E-value: 9.14e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  341 VIVEEPPRWTK-KPQSAVystgsngILLCEAEGEPQPTIKWRVNGSPVDNHPFAGDVVFP-REISFTNLQPNHTAVYQCE 418
Cdd:cd05760      2 VVLKHPASAAEiQPSSRV-------TLRCHIDGHPRPTYQWFRDGTPLSDGQGNYSVSSKeRTLTLRSAGPDDSGLYYCC 74

                           90
                   ....*....|....
gi 1034630801  419 ASNVHGTILANANI 432
Cdd:cd05760     75 AHNAFGSVCSSQNF 88

Second immunoglobulin (Ig)-like domain of Axl/Tyro3 family receptor tyrosine kinases (RTKs); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in 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, lymphatic and vascular systems, and 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: 409407 Cd Length: 82 Bit Score: 39.37 E-value: 9.62e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1034630801  350 TKKPQSAVYSTGSNGILLCEAEGEPQP-TIKWRVNGSPVDNHPFAGdvvfPREISFTNLqpNHTAVYQCEASNVHG 424
Cdd:cd05749      3 TVEPEDLAVTANTPFNLTCQAVGPPEPvEILWWQGGSPLGGPPAPS----PSVLNVPGL--NETTKFSCEAHNAKG 72

Third 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 third 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 third 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 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, including vascular (VCAM), intercellular (ICAM), neural (NCAM) and mucosal addressin (MADCAM) cell adhesion molecules, as well as junction adhesion molecules (JAM).

Pssm-ID: 409569 Cd Length: 93 Bit Score: 39.68 E-value: 1.02e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  447 ENYATVVGYSAFLHCEFFASPEAVVSWQKveEVKPLEGR------RYHIYENGTLQINRTTEEDAGSYSCWVENAIGKTA 520
Cdd:cd20977      8 KDMMAKAGDVTMIYCMYGSNPTAHPNYFK--NGKDVNGNpedritRHNRTSGKRLLFKTTLPEDEGVYTCEVDNGVGKPQ 85

                           90
                   ....*....|....*
gi 1034630801  521 vtanldiRNATKLRV 535
Cdd:cd20977     86 -------KHSLKLTV 93

Third 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 third 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 third 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 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, including vascular (VCAM), intercellular (ICAM), neural (NCAM) and mucosal addressin (MADCAM) cell adhesion molecules, as well as junction adhesion molecules (JAM).

Pssm-ID: 409569 Cd Length: 93 Bit Score: 39.68 E-value: 1.03e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034630801  359 STGSNGILLCEAEGEPQPTIKWRVNGSPVDNHP----FAGDVVFPREISFTNLQPNHTAVYQCEASN 421
Cdd:cd20977     13 KAGDVTMIYCMYGSNPTAHPNYFKNGKDVNGNPedriTRHNRTSGKRLLFKTTLPEDEGVYTCEVDN 79

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: 39.16 E-value: 1.13e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1034630801   53 FQIECEAKGNPEPTFSWTKDGNPFYFTDHRIIPSNNSGTFRIPNEGHISHfqGKYRCFASNKLGIA 118
Cdd:cd20976     19 FVAQCSARGKPVPRITWIRNAQPLQYAADRSTCEAGVGELHIQDVLPEDH--GTYTCLAKNAAGQV 82

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: 39.22 E-value: 1.32e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034630801  278 CFAEGLPTPQVDWNK----IGGDLPKGRETKENYGkTLKIENVSYQDKGNYRCTASNFLGT 334
Cdd:cd05738     21 CAASGNPDPEISWFKdflpVDTATSNGRIKQLRSG-ALQIENSEESDQGKYECVATNSAGT 80

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: 38.72 E-value: 1.39e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034630801   56 ECEAKGNPEPTFSWTKDGNpfyftdhRIIPSNnsgTFRIPNE------GHISHFQGKYRCFASNKLGIAMS 120
Cdd:cd05723     18 ECEVTGKPTPTVKWVKNGD-------VVIPSD---YFKIVKEhnlqvlGLVKSDEGFYQCIAENDVGNAQA 78

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: 38.74 E-value: 1.46e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1034630801  454 GYSAFLHC--EFFASPEavVSWQKVEEVKPLEGRRYHiYENGTLQINRTTEEDAGSYSCWVENAIG 517
Cdd:cd05876     10 GQSLVLECiaEGLPTPT--VKWLRPSGPLPPDRVKYQ-NHNKTLQLLNVGESDDGEYVCLAENSLG 72

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 38.53 E-value: 1.64e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  264 SSITILKGEILLLECFAEGLPTPQVDWNKiggdlpKGRETKENYGKTLKieNVSYQDKGNYRCTASNF-LGTATHDFHVI 342
Cdd:pfam13895    7 SPTVVTEGEPVTLTCSAPGNPPPSYTWYK------DGSAISSSPNFFTL--SVSAEDSGTYTCVARNGrGGKVSNPVELT 78


                   .
gi 1034630801  343 V 343
Cdd:pfam13895   79 V 79

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: 38.65 E-value: 1.68e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034630801   55 IECEAKG-NPEPTFSWTKDGNPFyftdHRIIPSNnsgtFRIPNEGHISHFQ---------GKYRCFASNKLG 116
Cdd:cd05750     19 LKCEATSeNPSPRYRWFKDGKEL----NRKRPKN----IKIRNKKKNSELQinkakledsGEYTCVVENILG 82

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: 38.77 E-value: 1.85e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  346 PPRWTKKPQSAVYSTGSNGILLCEAEGEPQPTIKWRVNGSP--VDNHPFAGDVVFPrEISFTNLQPNHTAVYQCEASNVH 423
Cdd:cd20976      1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPlqYAADRSTCEAGVG-ELHIQDVLPEDHGTYTCLAKNAA 79

                           90
                   ....*....|.
gi 1034630801  424 GTILANANIDV 434
Cdd:cd20976     80 GQVSCSAWVTV 90

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: 38.67 E-value: 1.91e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  271 GEILLLECFAEGLPTPQVDWNKIGGDLPKGRETKENYGKTLKIENVSYQDKGNYRCTASN 330
Cdd:cd20957     16 GRTAVFNCSVTGNPIHTVLWMKDGKPLGHSSRVQILSEDVLVIPSVKREDKGMYQCFVRN 75

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: 38.61 E-value: 2.01e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  264 SSITILKGEILLLECFAEGLPTPQVDWNKIGGDLPKGREtkENY----GKTLKIENVSYQ-----DKGNYRCTASNF-LG 333
Cdd:cd05722      9 SDIVAMRGGPVVLNCSAESDPPPKIEWKKDGVLLNLVSD--ERRqqlpNGSLLITSVVHSkhnkpDEGFYQCVAQNEsLG 86


                   .
gi 1034630801  334 T 334
Cdd:cd05722     87 S 87

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: 38.60 E-value: 2.02e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034630801  265 SITILKGEILLLECFAEGLPTPQVDWNK----IGGDLPKGRETKENYGK-TLKIENVSYQDKGNYRCTASNFLGTAT 336
Cdd:cd05892      9 NKKVLEGDPVRLECQISAIPPPQIFWKKnnemLQYNTDRISLYQDNCGRiCLLIQNANKKDAGWYTVSAVNEAGVVS 85

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: 38.54 E-value: 2.06e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1034630801  353 PQSAVYSTGSNGILLCEA-EGEPQPTIKWRVNGSPVDNHPFAGDVVFPREISFTNLQPNHTAVYQCEASNVHGT 425
Cdd:cd05724      4 PSDTQVAVGEMAVLECSPpRGHPEPTVSWRKDGQPLNLDNERVRIVDDGNLLIAEARKSDEGTYKCVATNMVGE 77

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: 38.53 E-value: 2.09e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1034630801  276 LECFAEGlPTPQVDWNKIGGDLPKG-RETKENYGKTLKIENVSYQDKGNYRCTASN 330
Cdd:cd05740     20 LTCEPET-QNTSYLWWFNGQSLPVTpRLTLSNGNRTLTLLNVTREDAGAYQCEISN 74

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: 38.60 E-value: 2.10e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1034630801  565 KLSWSKDGEAFeingTEDGRI-IIDGANLTISNVTLEDQGIYCCSAHTALDSA 616
Cdd:cd04969     33 TISWSKGTELL----TNSSRIcILPDGSLKIKNVTKSDEGKYTCFAVNFFGKA 81

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 38.14 E-value: 2.14e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034630801  438 RPLIQtkdGENYATVVGYSAFLHCEFFASPEAVVSWQKVEEVkplegrryhIYENGTLQINRTTEEDAGSYSCWVEN 514
Cdd:pfam13895    1 KPVLT---PSPTVVTEGEPVTLTCSAPGNPPPSYTWYKDGSA---------ISSSPNFFTLSVSAEDSGTYTCVARN 65

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: 38.35 E-value: 2.14e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1034630801   55 IECEAKGNPEPTFSWTKDGNPfyFTDHRIIPSNNSGTFRIPNEGHIShfQGKYRCFASNKLGIA 118
Cdd:cd05876     15 LECIAEGLPTPTVKWLRPSGP--LPPDRVKYQNHNKTLQLLNVGESD--DGEYVCLAENSLGSA 74

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: 38.16 E-value: 2.36e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034630801  366 LLCEAEGEPQPTIKW-RVNGSPVDNHPFAGDvvFPREISFTNLQPNHTAVYQCEASNVHGTI 426
Cdd:cd05731     15 LECIAEGLPTPDIRWiKLGGELPKGRTKFEN--FNKTLKIENVSEADSGEYQCTASNTMGSA 74

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: 38.76 E-value: 2.36e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  276 LECFAEGLPTPQVDWNKIGGDL----PKGRETKENYG----KTLKIENVS-YQDKGNYRCTASNFLGTATHDFHVIVEEP 346
Cdd:cd05773     28 LVCQAQGVPRVQFRWAKNGVPLdlgnPRYEETTEHTGtvhtSILTIINVSaALDYALFTCTAHNSLGEDSLDIQLVSTSR 107


                   .
gi 1034630801  347 P 347
Cdd:cd05773    108 P 108

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: 38.23 E-value: 2.39e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1034630801  268 ILKGEILLLECFAEGLPTPQVDWNKIGGDL--PKGRETKENYGkTLKIENVSYQDKGNYRCTASNFLGTATHDFHVIV 343
Cdd:cd05764     12 VLEGQRATLRCKARGDPEPAIHWISPEGKLisNSSRTLVYDNG-TLDILITTVKDTGAFTCIASNPAGEATARVELHI 88

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: 37.96 E-value: 2.49e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1034630801  568 WSKDGEAFeingTEDGRIIIDGANLTISNVTLEDQGIYCCSAH 610
Cdd:cd05728     33 WLKNGQPL----ASENRIEVEAGDLRITKLSLSDSGMYQCVAE 71

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: 38.14 E-value: 2.75e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1034630801  454 GYSAFLHCEFFASPEAVVSW--QKVEEVKPLEGRRYHIYENGTLQINRTTEEDAGSYSCWVENAIGKTAVTANLDI 527
Cdd:cd20969     17 GHTVQFVCRADGDPPPAILWlsPRKHLVSAKSNGRLTVFPDGTLEVRYAQVQDNGTYLCIAANAGGNDSMPAHLHV 92

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: 37.94 E-value: 2.77e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  356 AVYSTGSNGILLCEAEGEPQPTIKWRVNGSPV--DNH-PFAGDVVFPREISFTNLQPNHTAVYQCEASNVHGTILANANI 432
Cdd:cd20973      7 KEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIveSRRfQIDQDEDGLCSLIISDVCGDDSGKYTCKAVNSLGEATCSAEL 86


                   ..
gi 1034630801  433 DV 434
Cdd:cd20973     87 TV 88

Third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor 2 (FGFR2); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain of human fibroblast growth factor receptor 2 (FGFR2). Fibroblast growth factors (FGFs) participate in morphogenesis, development, angiogenesis, and wound healing. These FGF-stimulated processes are mediated by four FGFR tyrosine kinases (FGRF1-4). FGFRs are comprised of an extracellular portion consisting of three Ig-like domains, a transmembrane helix, and a cytoplasmic portion having protein tyrosine kinase activity. The highly conserved Ig-like domains 2 and 3, and the linker region between D2 and D3 define a general binding site for FGFs. FGFR2 is required for male sex determination. 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: 409444 Cd Length: 105 Bit Score: 38.40 E-value: 2.79e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  439 PLIQTKDGENYATVVGYSAFLHCEFFASPEAVVSW-QKVE--------------EVKPLEGRRYHIYENGTLQINRTTEE 503
Cdd:cd05858      1 PILQAGLPANTSVVVGTDAEFVCKVYSDAQPHIQWlKHVEkngskygpdglpyvEVLKTAGVNTTDKEIEVLYLRNVTFE 80

                           90       100
                   ....*....|....*....|....
gi 1034630801  504 DAGSYSCWVENAIGKTAVTANLDI 527
Cdd:cd05858     81 DAGEYTCLAGNSIGISHHSAWLTV 104

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: 37.90 E-value: 2.97e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  262 SESSITILKGEILLLECFAEGLPTPQVDWNKigGD----LPKGRETKENYG--KTLKIENVSYQDKGNYRCTASNFLGTA 335
Cdd:cd05894      1 AENTIVVVAGNKLRLDVPISGEPAPTVTWSR--GDkaftATEGRVRVESYKdlSSFVIEGAEREDEGVYTITVTNPVGED 78


                   ....*...
gi 1034630801  336 THDFHVIV 343
Cdd:cd05894     79 HASLFVKV 86

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: 38.24 E-value: 3.00e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1034630801  346 PPRWTKKP--QSAVYstGSNGILLCEAEGEPQPTIKW---RVNGSPVDNHP 391
Cdd:cd05734      1 PPRFVVQPndQDGIY--GKAVVLNCSADGYPPPTIVWkhsKGSGVPQFQHI 49

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: 38.01 E-value: 3.05e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034630801  565 KLSWSKDGEAFEINGTEDGRIIIDGANLTISNVTLEDQGIYCCSAHTALDSAADITQVTVLD 626
Cdd:cd05736     31 RVQWLKNGMDINPKLSKQLTLIANGSELHISNVRYEDTGAYTCIAKNEGGVDEDISSLFVED 92

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 37.76 E-value: 3.11e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034630801   51 EYFQIECEAKGNPEPTFSWTKDGNPfyftdhriIPSNNSGTFRIPNEGHishfQGKYRCFASNKLGIAMSEEIEFIV 127
Cdd:pfam13895   15 EPVTLTCSAPGNPPPSYTWYKDGSA--------ISSSPNFFTLSVSAED----SGTYTCVARNGRGGKVSNPVELTV 79

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: 3.18e-03

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801   828 APVIHGVDVINSTLVKVTWSTVPKDRVHGRLKGYQINWWKTKSlldgrthpkEVNILRFSGQRNSGMVPSLDAFSEFHLT 907
Cdd:smart00060    3 PPSNLRVTDVTSTSVTLSWEPPPDDGITGYIVGYRVEYREEGS---------EWKEVNVTPSSTSYTLTGLKPGTEYEFR 73

                            90
                    ....*....|
gi 1034630801   908 VLAYNSKGAG 917
Cdd:smart00060   74 VRAVNGAGEG 83

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: 37.95 E-value: 3.23e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  351 KKPqSAVYSTGSNGILL-CEAEGEPQPTIKWRVNgspvdnhpfaGDVVFPRE----ISFTNLQ-----PNHTAVYQCEAS 420
Cdd:cd05723      2 KKP-SNIYAHESMDIVFeCEVTGKPTPTVKWVKN----------GDVVIPSDyfkiVKEHNLQvlglvKSDEGFYQCIAE 70

                           90
                   ....*....|..
gi 1034630801  421 NVHGTILANANI 432
Cdd:cd05723     71 NDVGNAQASAQL 82

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: 38.07 E-value: 3.45e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  529 NATKLRVSPKNPRIPKLHMLELHCESKCDshlkHSLKL--SWS---------KDGEAFEINGTEDgriiiDGANLTISNV 597
Cdd:cd05853      1 DPTRVMVPPSSMDVTVGESIVLPCQVSHD----HSLDIvfTWSfnghlidfqKDGDHFERVGGQD-----SAGDLMIRSI 71

                           90       100
                   ....*....|....*....|....*
gi 1034630801  598 TLEDQGIYCCSAHTALD---SAADI 619
Cdd:cd05853     72 QLKHAGKYVCMVQTSVDklsAAADL 96

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor(R); member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor(R). The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. The VEGFR family consists of three members, VEGFR-1 (also known as Flt-1), VEGFR-2 (also known as KDR or Flk-1) and VEGFR-3 (also known as Flt-4). VEGF_A interacts with both VEGFR-1 and VEGFR-2. VEGFR-1 binds strongest to VEGF, VEGF-2 binds more weakly. VEGFR-3 appears not to bind VEGF, but binds other members of the VEGF family (VEGF-C and -D). VEGFRs bind VEGFs with high affinity with the IG-like domains. VEGF-A is important to the growth and maintenance of vascular endothelial cells and to the development of new blood- and lymphatic-vessels in physiological and pathological states. VEGFR-2 is a major mediator of the mitogenic, angiogenic and microvascular permeability-enhancing effects of VEGF-A. VEGFR-1 may play an inhibitory part in these processes by binding VEGF and interfering with its interaction with VEGFR-2. VEGFR-1 has a signaling role in mediating monocyte chemotaxis. VEGFR-2 and -1 may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. VEGFR-3 has been shown to be involved in tumor angiogenesis and growth.

Pssm-ID: 409448 Cd Length: 102 Bit Score: 38.19 E-value: 3.53e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  263 ESSITILKGEILLLECFAEglpTP-----QVDW------NKIGGDLPKGRETKENYGK----TLKIENVSYQDKGNYRCT 327
Cdd:cd05862      8 PKPVELLVGEKLVLNCTAR---TElnvgvDFQWdypgkkEQRRASVRRRRKQQSSEATefssTLTIDNVTLSDKGLYTCA 84

                           90
                   ....*....|....*...
gi 1034630801  328 ASNFLGTATHDFHVIVEE 345
Cdd:cd05862     85 ASSGPMFKKNSTSVIVHE 102

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: 37.99 E-value: 3.82e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 1034630801  566 LSWSKDGEAFEiNGTEDGRIIIDGANLTISNVTLEDQGIYCCSA 609
Cdd:cd05730     35 MTWTKDGEPIE-SGEEKYSFNEDGSEMTILDVDKLDEAEYTCIA 77

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: 38.21 E-value: 3.98e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  546 HMLELHCESKcDSHLKHSLKLSWSKD----GEAFEI--------NGTEDGRIIIDG------ANLTISNVTLEDQGIYCC 607
Cdd:pfam07686   12 GSVTLPCTYS-SSMSEASTSVYWYRQppgkGPTFLIayysngseEGVKKGRFSGRGdpsngdGSLTIQNLTLSDSGTYTC 90

                           90
                   ....*....|....*....
gi 1034630801  608 SAHTA-LDSAADITQVTVL 625
Cdd:pfam07686   91 AVIPSgEGVFGKGTRLTVL 109

Immunoglobulin (Ig)-like domain of class III semaphorin Sema3; The members here are composed of the immunoglobulin (Ig)-like domain of Sema3 and similar proteins. Semaphorins are classified based on structural features additional to the Sema domain. Sema3 is a Class III semaphorin that is secreted. It is a vertebrate class having a Sema domain, an Ig domain, a short basic domain. They have been shown to be axonal guidance cues and have a part in the regulation of the cardiovascular, immune, and respiratory systems. Sema3A, the prototype member of this class III subfamily, induces growth cone collapse and is an inhibitor of axonal sprouting. In perinatal rat cortex, it acts as a chemoattractant and functions to direct the orientated extension of apical dendrites. It may play a role, prior to the development of apical dendrites, in signaling the radial migration of newborn cortical neurons towards the upper layers. Sema3A selectively inhibits vascular endothelial growth factor receptor (VEGF)-induced angiogenesis and induces microvascular permeability. This group also includes Sema3B, -C, -D, -E, -G.

Pssm-ID: 409455 Cd Length: 92 Bit Score: 37.71 E-value: 4.00e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  452 VVGYSAFLHCEFfASPEAVVSW-------QKVEEVKPlEGRRYHIyENGTLqINRTTEEDAGSYSCW-VENAIGKTAVTA 523
Cdd:cd05871     10 VEGNSTFLECLP-KSPQATVKWlfqrggdQRKEEVKS-EERLIVT-DRGLL-LRSLQRSDAGVYTCQaVEHGFSQTLVKI 85


                   ..
gi 1034630801  524 NL 525
Cdd:cd05871     86 RL 87

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: 37.23 E-value: 4.29e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034630801  366 LLCEAEGEPQPTIKWRVNGS--PVDNHPFagdVVFPREISFTNLQPNHTAVYQCEASNVHGTILANANIDV 434
Cdd:cd05745      7 FLCEAQGYPQPVIAWTKGGSqlSVDRRHL---VLSSGTLRISRVALHDQGQYECQAVNIVGSQRTVAQLTV 74

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: 37.91 E-value: 4.36e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034630801  453 VGYSAFLHCEFFASPEAVVSWQK-VEEVKPLEGRRYHIYEN------GTLQINRTTEEDAGSYSCWVENAIG 517
Cdd:cd05765     14 VGETASFHCDVTGRPQPEITWEKqVPGKENLIMRPNHVRGNvvvtniGQLVIYNAQPQDAGLYTCTARNSGG 85

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: 36.99 E-value: 5.21e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034630801  549 ELHCESKCDShlkhSLKLSWSK-DGEafeingTEDGRI-IIDGANLTISNVTLEDQGIYCCSAHTALDSA 616
Cdd:cd05725     16 EFQCEVGGDP----VPTVRWRKeDGE------LPKGRYeILDDHSLKIRKVTAGDMGSYTCVAENMVGKI 75

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: 37.48 E-value: 5.27e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1034630801   54 QIECEAKGNPEPTFSWTKDGNPFYFTDHRIIPSNNSGTFRIPNEGHISHFQGKYRCFASNKLGIA 118
Cdd:cd05744     19 RFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVRENGRHSLIIEPVTKRDAGIYTCIARNRAGEN 83

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: 37.00 E-value: 6.42e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 1034630801  566 LSWSKDGEafEINGTEDGRIIIDGANLTISNVTLEDQGIYCCSA 609
Cdd:cd05724     30 VSWRKDGQ--PLNLDNERVRIVDDGNLLIAEARKSDEGTYKCVA 71

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: 37.12 E-value: 6.63e-03

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gi 1034630801  366 LLCEAEGEPQPTIKWRvngSPVDNHPFA-----GDVVFP---REISFT--NLQPNHTAVYQCEASN 421
Cdd:cd05732     21 LTCEAEGDPIPEITWR---RATRGISFEegdldGRIVVRghaRVSSLTlkDVQLTDAGRYDCEASN 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: 37.06 E-value: 7.12e-03

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gi 1034630801  454 GYSAFLHCEFFASPEAVVSWQKVEEVKPLEGRRYHIYENGT----LQINRTTEEDAGSYSCWVENAIGKTAVTANLDI 527
Cdd:cd05892     15 GDPVRLECQISAIPPPQIFWKKNNEMLQYNTDRISLYQDNCgricLLIQNANKKDAGWYTVSAVNEAGVVSCNARLDV 92

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: 36.41 E-value: 9.03e-03

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gi 1034630801   60 KGNPEPTFSWTKDGNPFYFTDH-RIIPSNNSGTFRIPNeGHISHfQGKYRCFASNKLGIAmSEEIEFIV 127
Cdd:cd05748     17 KGRPTPTVTWSKDGQPLKETGRvQIETTASSTSLVIKN-AKRSD-SGKYTLTLKNSAGEK-SATINVKV 82