NCBI Conserved Domain Search

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: 157.31 E-value: 3.06e-45

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  531 ADNTVTVIAGNKLRLEIPISGEPPPKAMWSRGDKAIMEGSGRIRTESYPDSSTLVIDIAERDDSGVYHINLKNEAGEAHA 610
Cdd:cd05894    1 AENTIVVVAGNKLRLDVPISGEPAPTVTWSRGDKAFTATEGRVRVESYKDLSSFVIEGAEREDEGVYTITVTNPVGEDHA 80


                 ....*.
gi 46049110  611 SIKVKV 616
Cdd:cd05894   81 SLFVKV 86

Immunoglobulin Domain C1 of human cardiac Myosin Binding Protein C and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain C1 of human cardiac Myosin Binding Protein C (MyBP-C). MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. 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 C1 domain of the MyBP-C 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: 409554 Cd Length: 101 Bit Score: 130.17 E-value: 1.70e-35

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110   59 LFIEKPQGGTVKVGEDITFIAKVKAEDLLRKPTIKWFKGKWMDLASKAGKHLQLKETFERHSRVYTFEMQIIKAKDNFAG 138
Cdd:cd20962    1 LFVMRPQDGEVTVGGSITFSARVAGASLLKPPVVKWFKGKWVDLSSKVGQHLQLHDSYDRASKVYLFELHITDAQPAFAG 80

                         90       100
                 ....*....|....*....|.
gi 46049110  139 NYRCEVTYKDKFDSCSFDLEV 159
Cdd:cd20962   81 GYRCEVSTKDKFDCSNFNLTV 101

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: 116.92 E-value: 3.68e-31

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  534 TVTVIAGNKLRLEIPISGEPPPKAMWSRGDKAIMEgSGRIRTESYPDSSTLVIDIAERDDSGVYHINLKNEAGEAHASIK 613
Cdd:cd05748    1 TIVVRAGESLRLDIPIKGRPTPTVTWSKDGQPLKE-TGRVQIETTASSTSLVIKNAKRSDSGKYTLTLKNSAGEKSATIN 79


                 ...
gi 46049110  614 VKV 616
Cdd:cd05748   80 VKV 82

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. 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 the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. 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: 409559 Cd Length: 82 Bit Score: 103.86 E-value: 1.76e-26

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  256 KILDPAYQVDKGGRVRFVVELADPKLEVKWYKNGQEIRPSTKYIFEHKGCQRILFINNCQMTDDSEYYVTAGDEKCSTEL 335
Cdd:cd20967    1 KKAQPAVQVSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFEL 80


                 ..
gi 46049110  336 FV 337
Cdd:cd20967   81 FV 82

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 89.24 E-value: 3.15e-21

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110   1029 PMFTQPLVNTYAIAGYNATLNCSVRGNPKPKITWMKNKVAIVDDPRYRMFSNQGVCTLEIRKPSPYDGGTYCCKAVNDLG 1108
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSAG 80

                           90
                   ....*....|
gi 46049110   1109 TVEIECKLEV 1118
Cdd:pfam07679   81 EAEASAELTV 90

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

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 88.03 E-value: 6.53e-21

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  830 TYIRRVGEAVNLVIPFQGKPRPELTWKKDGAEIDKNQ-INIRNSETDTIIFIRKAERSHSGKYDLQVKVDKFVETASIDI 908
Cdd:cd05748    1 TIVVRAGESLRLDIPIKGRPTPTVTWSKDGQPLKETGrVQIETTASSTSLVIKNAKRSDSGKYTLTLKNSAGEKSATINV 80


                 ..
gi 46049110  909 QI 910
Cdd:cd05748   81 KV 82

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: 84.09 E-value: 2.15e-19

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  620 PDPPVAPTVTEVGDDWCIMNWEPPAYDGGsPILGYFIERKKKQSSRWMRLNFDLCKETTFEPKKMIEGVAYEVRIFAVNA 699
Cdd:cd00063    1 PSPPTNLRVTDVTSTSVTLSWTPPEDDGG-PITGYVVEYREKGSGDWKEVEVTPGSETSYTLTGLKPGTEYEFRVRAVNG 79

                         90
                 ....*....|.
gi 46049110  700 IGISKPSMPSR 710
Cdd:cd00063   80 GGESPPSESVT 90

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 92.76 E-value: 4.11e-19

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  575 TESYPDSSTLVIDIAERDDSGVYHINLKNEAGEAHASIKVKVVDFPDPPVAPT---VTEVGDDWCIMNWEPPAYDGgspI 651
Cdd:COG3401  185 LTVTSTTLVDGGGDIEPGTTYYYRVAATDTGGESAPSNEVSVTTPTTPPSAPTgltATADTPGSVTLSWDPVTESD---A 261

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  652 LGYFIERKKKQSSRWMRLNFDlcKETTFEPKKMIEGVAYEVRIFAVNAIGI-SKPSMPSRPFVPLAVTSPPTLLTVDSVT 730
Cdd:COG3401  262 TGYRVYRSNSGDGPFTKVATV--TTTSYTDTGLTNGTTYYYRVTAVDAAGNeSAPSNVVSVTTDLTPPAAPSGLTATAVG 339

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  731 DTTVTMRWRPPDhigAAGLDGYVLEYCFEGTEDWIVANKdLIDKTKFTITGLPTDAKIFVRVKAVNAAGASEPkyYSQPI 810
Cdd:COG3401  340 SSSITLSWTASS---DADVTGYNVYRSTSGGGTYTKIAE-TVTTTSYTDTGLTPGTTYYYKVTAVDAAGNESA--PSEEV 413

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

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 81.77 E-value: 1.30e-18

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  719 SPPTLLTVDSVTDTTVTMRWRPPDHIGAAgLDGYVLEYCFEGTEDWIVANKDLIDKTKFTITGLPTDAKIFVRVKAVNAA 798
Cdd:cd00063    2 SPPTNLRVTDVTSTSVTLSWTPPEDDGGP-ITGYVVEYREKGSGDWKEVEVTPGSETSYTLTGLKPGTEYEFRVRAVNGG 80


                 ....*
gi 46049110  799 GASEP 803
Cdd:cd00063   81 GESPP 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 77.22 E-value: 3.14e-17

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 46049110   1029 PMFTQPLVNTYAIAGYNATLNCSVRGNPKPKITWMKNKVAIVDDPRYRMFSNQGVCTLEIRKPSPYDGGTYCCKAVN 1105
Cdd:pfam13927    2 PVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

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: 76.21 E-value: 6.80e-17

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 46049110 1046 ATLNCSVRGNPKPKITWMKNKVAIVDDPRYRMFSNQGVCTLEIRKPSPYDGGTYCCKAVNDLGTVE 1111
Cdd:cd00096    1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSA 66

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: 75.23 E-value: 1.99e-16

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110    1037 NTYAIAGYNATLNCSVRGNPKPKITWMKNK-VAIVDDPRYRMFSNQGVCTLEIRKPSPYDGGTYCCKAVNDLGTVEIECK 1115
Cdd:smart00410    3 SVTVKEGESVTLSCEASGSPPPEVTWYKQGgKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGTT 82


                    ...
gi 46049110    1116 LEV 1118
Cdd:smart00410   83 LTV 85

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

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 75.23 E-value: 2.28e-16

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  914 PGPPQIVKIEDVWGENVALTWTPPKDDGnAAITGYTIQKADKKSMEWFTVIEHYH-RTSATITELVIGNEYYFRVFSENM 992
Cdd:cd00063    1 PSPPTNLRVTDVTSTSVTLSWTPPEDDG-GPITGYVVEYREKGSGDWKEVEVTPGsETSYTLTGLKPGTEYEFRVRAVNG 79


                 ....*
gi 46049110  993 CGLSE 997
Cdd:cd00063   80 GGESP 84

Tri-helix bundle domain; This domain can be found in the myosin-binding motif (m-domain) region present in myosin-binding protein C (MyBP-C). MyBP-C is a sarcomeric assembly protein necessary for the regulation of sarcomere structure and function. The MyBP-C family of proteins consists mainly of modules with immunoglobulin (Ig) or fibronectin folds. This domain exhibits a three-helix bundle fold and there is a known actin-binding motif, LK(R/K)XK positioned in the third helix (alpha3), similar to that found in villin and related proteins.

Pssm-ID: 465725 Cd Length: 34 Bit Score: 72.77 E-value: 4.03e-16

                           10        20        30
                   ....*....|....*....|....*....|....
gi 46049110    209 DVWELLKNAKPSEYEKIAFQYGITDLRGMLKRLK 242
Cdd:pfam18362    1 DVWEILSNAPPKDYEKIAFQYGITDLRGMLKKLK 34

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: 73.22 E-value: 1.45e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110 1042 AGYNATLNCSVRGNPKPKITWMKNKVAI---VDDPRYRMFSNQGVCTLEIRKPSPYDGGTYCCKAVNDLGTVEIECKLEV 1118
Cdd:cd20951   14 EKSDAKLRVEVQGKPDPEVKWYKNGVPIdpsSIPGKYKIESEYGVHVLHIRRVTVEDSAVYSAVAKNIHGEASSSASVVV 93


                 .
gi 46049110 1119 K 1119
Cdd:cd20951   94 E 94

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: 71.88 E-value: 2.62e-15

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110     914 PGPPQIVKIEDVWGENVALTWTPPKDDGNAA-ITGYTIQKaDKKSMEWFTVIEHYHRTSATITELVIGNEYYFRVFSENM 992
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTLSWEPPPDDGITGyIVGYRVEY-REEGSEWKEVNVTPSSTSYTLTGLKPGTEYEFRVRAVNG 79


                    ....
gi 46049110     993 CGLS 996
Cdd:smart00060   80 AGEG 83

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 71.52 E-value: 4.12e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110    535 VTVIAGNKLRLEIPISGEPPPKAMWSRGDKAIMEgSGRIRTESYPDSSTLVIDIAERDDSGVYHINLKNEAGEAHASIKV 614
Cdd:pfam07679   10 VEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRS-SDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSAGEAEASAEL 88


                   ..
gi 46049110    615 KV 616
Cdd:pfam07679   89 TV 90

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: 70.30 E-value: 1.36e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110 1032 TQPLVNTYAIAGYNATLNCSVRGNPKPKITWMKNKVAIVDDPRYRM-FSNQGVCTLEIRKPSPYDGGTYCCKAVNDLGTV 1110
Cdd:cd20973    1 IQTLRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIdQDEDGLCSLIISDVCGDDSGKYTCKAVNSLGEA 80


                 ....*...
gi 46049110 1111 EIECKLEV 1118
Cdd:cd20973   81 TCSAELTV 88

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: 69.59 E-value: 2.31e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110 1028 APMFTQPLVNTYAIAGYNATLNCSVRGNPKPKITWMKNKVAIVDDPRyRMFSNQGVCTLEIRKPSPYDGGTYCCKAVNDL 1107
Cdd:cd20976    1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQYAAD-RSTCEAGVGELHIQDVLPEDHGTYTCLAKNAA 79

                         90
                 ....*....|...
gi 46049110 1108 GTVeiECKLEVKV 1120
Cdd:cd20976   80 GQV--SCSAWVTV 90

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

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 68.02 E-value: 6.79e-14

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110     620 PDPPVAPTVTEVGDDWCIMNWEPPAYDGG-SPILGYFIERKKKqSSRWMRLNFDlCKETTFEPKKMIEGVAYEVRIFAVN 698
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTLSWEPPPDDGItGYIVGYRVEYREE-GSEWKEVNVT-PSSTSYTLTGLKPGTEYEFRVRAVN 78


                    ....*
gi 46049110     699 AIGIS 703
Cdd:smart00060   79 GAGEG 83

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: 67.53 E-value: 1.46e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110 1033 QPLVNTYAIAGYNATLNCSVRGNPKPKITWMKNKVAIVD-DPRYRMFSNQGvcTLEIRKPSPYDGGTYCCKAVNDL-GTV 1110
Cdd:cd20970    7 QPSFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEfNTRYIVRENGT--TLTIRNIRRSDMGIYLCIASNGVpGSV 84


                 ....*...
gi 46049110 1111 EIECKLEV 1118
Cdd:cd20970   85 EKRITLQV 92

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: 66.26 E-value: 2.88e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110 1029 PMFTQ-PLVNTYAIAGYNATLNCSVRGNPKPKITWMKNKVAIVDDPRYRMFSNQgvcTLEIRKPSPYDGGTYCCKAVNDL 1107
Cdd:cd20978    1 PKFIQkPEKNVVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMERATVEDG---TLTIINVQPEDTGYYGCVATNEI 77

                         90
                 ....*....|.
gi 46049110 1108 GTVEIECKLEV 1118
Cdd:cd20978   78 GDIYTETLLHV 88

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 73.50 E-value: 3.98e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  686 EGVAYEVRIFAVNAIGISKPSMPSRPFVPLAVTSPPTLLTVDSVTDTTVTMRWRPPDhigAAGLDGYVLEYCFEGTEDW- 764
Cdd:COG3401  201 PGTTYYYRVAATDTGGESAPSNEVSVTTPTTPPSAPTGLTATADTPGSVTLSWDPVT---ESDATGYRVYRSNSGDGPFt 277

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  765 IVANkdlIDKTKFTITGLPTDAKIFVRVKAVNAAGASEPkyYSQPILVKEIIEPpkiriprhlkqtyirrvgeavnlvip 844
Cdd:COG3401  278 KVAT---VTTTSYTDTGLTNGTTYYYRVTAVDAAGNESA--PSNVVSVTTDLTP-------------------------- 326

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  845 fqgkprpeltwkkdgaeidknqinirnsetdtiifirkaershsgkydlqvkvdkfvetasidiqiidrPGPPQIVKIED 924
Cdd:COG3401  327 ---------------------------------------------------------------------PAAPSGLTATA 337

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  925 VWGENVALTWTPPKDDGnaaITGYTIQKADKKSMEWFTVIEHYHRTSATITELVIGNEYYFRVFSENMCGL-SEDATMTK 1003
Cdd:COG3401  338 VGSSSITLSWTASSDAD---VTGYNVYRSTSGGGTYTKIAETVTTTSYTDTGLTPGTTYYYKVTAVDAAGNeSAPSEEVS 414

                        330
                 ....*....|....*....
gi 46049110 1004 ESAVIARDGKIYKNPVYED 1022
Cdd:COG3401  415 ATTASAASGESLTASVDAV 433

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 65.90 E-value: 4.41e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110    915 GPPQIVKIEDVWGENVALTWTPPkDDGNAAITGYTIQKADKKSME-WFTVIEHYHRTSATITELVIGNEYYFRVFSENMC 993
Cdd:pfam00041    1 SAPSNLTVTDVTSTSLTVSWTPP-PDGNGPITGYEVEYRPKNSGEpWNEITVPGTTTSVTLTGLKPGTEYEVRVQAVNGG 79


                   ....
gi 46049110    994 GLSE 997
Cdd:pfam00041   80 GEGP 83

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

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 65.33 E-value: 6.71e-13

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110     719 SPPTLLTVDSVTDTTVTMRWRPPDHIGAAG-LDGYVLEYCfEGTEDWIVANKDlIDKTKFTITGLPTDAKIFVRVKAVNA 797
Cdd:smart00060    2 SPPSNLRVTDVTSTSVTLSWEPPPDDGITGyIVGYRVEYR-EEGSEWKEVNVT-PSSTSYTLTGLKPGTEYEFRVRAVNG 79


                    ....
gi 46049110     798 AGAS 801
Cdd:smart00060   80 AGEG 83

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

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 63.68 E-value: 2.17e-12

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110     534 TVTVIAGNKLRLEIPISGEPPPKAMWSRGDKAIMEGSGRIRTESYPDSSTLVIDIAERDDSGVYHINLKNEAGEAHASIK 613
Cdd:smart00410    3 SVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGTT 82


                    ...
gi 46049110     614 VKV 616
Cdd:smart00410   83 LTV 85

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 63.59 E-value: 2.78e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110    719 SPPTLLTVDSVTDTTVTMRWRPPDHIGAAgLDGYVLEYCFEGTEDWIVANKDLIDKTKFTITGLPTDAKIFVRVKAVNAA 798
Cdd:pfam00041    1 SAPSNLTVTDVTSTSLTVSWTPPPDGNGP-ITGYEVEYRPKNSGEPWNEITVPGTTTSVTLTGLKPGTEYEVRVQAVNGG 79


                   ....*
gi 46049110    799 GASEP 803
Cdd:pfam00041   80 GEGPP 84

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

Pssm-ID: 409567 Cd Length: 91 Bit Score: 63.64 E-value: 3.09e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110 1029 PMFTQPLVNTYAIAGYNATLNCSVRGNPKPKITWMKNKVAI-VDDPRYRMFSNQGVCTLEIRKPSPYDGGTYCCKAVNDL 1107
Cdd:cd20975    1 PTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVrPDQRRFAEEAEGGLCRLRILAAERGDAGFYTCKAVNEY 80

                         90
                 ....*....|.
gi 46049110 1108 GTVEIECKLEV 1118
Cdd:cd20975   81 GARQCEARLEV 91

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 63.20 E-value: 3.19e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110    621 DPPVAPTVTEVGDDWCIMNWEPPAyDGGSPILGYFIERKKKQSSRWMRlNFDLCK-ETTFEPKKMIEGVAYEVRIFAVNA 699
Cdd:pfam00041    1 SAPSNLTVTDVTSTSLTVSWTPPP-DGNGPITGYEVEYRPKNSGEPWN-EITVPGtTTSVTLTGLKPGTEYEVRVQAVNG 78


                   ....*..
gi 46049110    700 IGISKPS 706
Cdd:pfam00041   79 GGEGPPS 85

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: 62.90 E-value: 5.11e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110 1029 PMFTQPLVNTYAIAGYNATLNCSVRGNPKPKITWMKNKVAIVDDPRYRMFSNQ-GVCTLEIRKPSPYDGGTYCCKAVNDL 1107
Cdd:cd05744    1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVREnGRHSLIIEPVTKRDAGIYTCIARNRA 80

                         90
                 ....*....|.
gi 46049110 1108 GTVEIECKLEV 1118
Cdd:cd05744   81 GENSFNAELVV 91

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 62.66 E-value: 5.86e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110    344 VTKQLEDTTAYCGERVELECEVSED-DANVKWFKNGEEIIPGpkSRYRIRVEGKKHILIIEGATKADAAEYSVMTT--GG 420
Cdd:pfam07679    3 FTQKPKDVEVQEGESARFTCTVTGTpDPEVSWFKDGQPLRSS--DRFKVTYEGGTYTLTISNVQPDDSGKYTCVATnsAG 80


                   ....*...
gi 46049110    421 QSSAKLSV 428
Cdd:pfam07679   81 EAEASAEL 88

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. 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 the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. 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: 409559 Cd Length: 82 Bit Score: 61.49 E-value: 1.24e-11

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 46049110  356 GERVELECEVSEDDANVKWFKNGEEIipGPKSRYRIRVEGKKHILIIEGATKADAAEYSVMTTGGQSSAKLSV 428
Cdd:cd20967   12 GHKIRLTVELADPDAEVKWYKDGQEL--QSSSKVIFESIGAKRTLTVQQASLADAGEYQCVAGGEKCSFELFV 82

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 59.19 E-value: 1.01e-10

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110    434 KILTPLTDQTVNLGKEICLKCEISENIPGK--WTKNGLPVQESDRLKVVHKGRIHKLVIANALTEDEGDY 501
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVTGTPDPEvsWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKY 71

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: 58.29 E-value: 1.95e-10

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110     441 DQTVNLGKEICLKCEISENIP--GKWTKNGL-PVQESDRLKVVHKGRIHKLVIANALTEDEGDYVFA--PDAYNVTLPAK 515
Cdd:smart00410    3 SVTVKEGESVTLSCEASGSPPpeVTWYKQGGkLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAatNSSGSASSGTT 82


                    ...
gi 46049110     516 VHV 518
Cdd:smart00410   83 LTV 85

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: 57.96 E-value: 2.96e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110 1025 FSEapMFTQPlvntyaiaGYNATLNCSVRGNPKPKITWMKNKVAIVDDPRYRM---FSNQG--VCTLEIRKPSPYDGGTY 1099
Cdd:cd20956    8 FSE--QTLQP--------GPSVSLKCVASGNPLPQITWTLDGFPIPESPRFRVgdyVTSDGdvVSYVNISSVRVEDGGEY 77

                         90
                 ....*....|....*....
gi 46049110 1100 CCKAVNDLGTVEIECKLEV 1118
Cdd:cd20956   78 TCTATNDVGSVSHSARINV 96

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: 57.52 E-value: 3.06e-10

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110     349 EDTTAYCGERVELECEVSED-DANVKWFKNGEEIIpGPKSRYRIRVEGKKHILIIEGATKADAAEY--SVMTTGGQ--SS 423
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSpPPEVTWYKQGGKLL-AESGRFSVSRSGSTSTLTISNVTPEDSGTYtcAATNSSGSasSG 80


                    ....*
gi 46049110     424 AKLSV 428
Cdd:smart00410   81 TTLTV 85

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

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 56.27 E-value: 1.17e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  345 TKQLEDTTAYCGERVELECEVS-EDDANVKWFKNGEEIIPGPKSR-YRIRVEGKKHILIIEGATKADAAEYSV--MTTGG 420
Cdd:cd20951    4 IIRLQSHTVWEKSDAKLRVEVQgKPDPEVKWYKNGVPIDPSSIPGkYKIESEYGVHVLHIRRVTVEDSAVYSAvaKNIHG 83

                         90
                 ....*....|.
gi 46049110  421 QSSAKLSVDLK 431
Cdd:cd20951   84 EASSSASVVVE 94

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

Pssm-ID: 409566 [Multi-domain] Cd Length: 93 Bit Score: 56.21 E-value: 1.46e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110 1029 PMFTQPLVNTYAIAGYNATLNCSVRGNPKPKITWMKNKVAI--VDDPRYRMFSNQGVCTLEIRKPSPYDGGTYCCKAVND 1106
Cdd:cd20974    1 PVFTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFRDGQVIstSTLPGVQISFSDGRAKLSIPAVTKANSGRYSLTATNG 80

                         90
                 ....*....|...
gi 46049110 1107 LGTVEIECKLEVK 1119
Cdd:cd20974   81 SGQATSTAELLVL 93

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

Pssm-ID: 409419 Cd Length: 99 Bit Score: 56.12 E-value: 1.83e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  521 PPKIILDGLDadntVTVIAGNKLRLEIPISGEPPPKAMWSRGDKAIMEGSGrIRTESYPDSSTLVIDIAERDDSGVYHIN 600
Cdd:cd05762    1 PPQIIQFPED----MKVRAGESVELFCKVTGTQPITCTWMKFRKQIQEGEG-IKIENTENSSKLTITEGQQEHCGCYTLE 75

                         90       100
                 ....*....|....*....|...
gi 46049110  601 LKNEAGEAHASIKVKVVDFPDPP 623
Cdd:cd05762   76 VENKLGSRQAQVNLTVVDKPDPP 98

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: 55.55 E-value: 1.87e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110 1029 PMFTQPLVNTYAIAGYNATLNCSVRGNPKPKITWMKNKVAIVDDP-RYRMF-SNQGVCTLEIRKPSPYDGGTYCCKAVND 1106
Cdd:cd05892    1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKKNNEMLQYNTdRISLYqDNCGRICLLIQNANKKDAGWYTVSAVNE 80

                         90
                 ....*....|..
gi 46049110 1107 LGTVEIECKLEV 1118
Cdd:cd05892   81 AGVVSCNARLDV 92

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

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 54.71 E-value: 3.68e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110 1033 QPlVNTYAIAGYNATLNCSV-RGNPKPKITWMKNKVAIV-DDPRYRMFSNQgvcTLEIRKPSPYDGGTYCCKAVNDLGTV 1110
Cdd:cd05724    3 EP-SDTQVAVGEMAVLECSPpRGHPEPTVSWRKDGQPLNlDNERVRIVDDG---NLLIAEARKSDEGTYKCVATNMVGER 78


                 .
gi 46049110 1111 E 1111
Cdd:cd05724   79 E 79

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: 54.13 E-value: 7.36e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110 1028 APMFTQPLVNTYAIAGYNATLNCSVRGNPKPKITWMKNKVAIVDDPRYRMFSNQGVCTLEIRKPSPYDGGTYCCKAVNDL 1107
Cdd:cd20972    1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSPDIQIHQEGDLHSLIIAEAFEEDTGRYSCLATNSV 80


                 ..
gi 46049110 1108 GT 1109
Cdd:cd20972   81 GS 82

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: 54.04 E-value: 7.52e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  536 TVIAGNKLRLEIPISGEPPPKAMWSRGDKAIMEGSGRIRTESYPDSSTLVIDIAERDDSGVYHINLKNEAGEAHASIKVK 615
Cdd:cd05744   11 EVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVRENGRHSLIIEPVTKRDAGIYTCIARNRAGENSFNAELV 90


                 .
gi 46049110  616 V 616
Cdd:cd05744   91 V 91

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: 53.65 E-value: 9.32e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110 1030 MFTQPLVNTYAIAGYNATLNCSVRGNPKPKITWMKNKVAI-VDDPRYRMFSNQgvcTLEIRKPSPYDGGTYCCKAVNDLG 1108
Cdd:cd20952    1 IILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLlGKDERITTLENG---SLQIKGAEKSDTGEYTCVALNLSG 77

                         90
                 ....*....|
gi 46049110 1109 TVEIECKLEV 1118
Cdd:cd20952   78 EATWSAVLDV 87

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: 53.18 E-value: 1.54e-08

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 46049110 1045 NATLNCSVRGNPKPKITWMKNKV--AIVDDPRYRMFSNQGVCTLEIRKPSPYD-GGTYCCKAVNDLGT 1109
Cdd:cd05733   18 NITIKCEAKGNPQPTFRWTKDGKffDPAKDPRVSMRRRSGTLVIDNHNGGPEDyQGEYQCYASNELGT 85

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

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 52.81 E-value: 1.96e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  264 VDKGGRVRFVVELA-DPKLEVKWYKNGQEIRPST---KYIFEHKGCQRILFINNCQMTDDSEYYVTA----GDEKCSTEL 335
Cdd:cd20951   12 VWEKSDAKLRVEVQgKPDPEVKWYKNGVPIDPSSipgKYKIESEYGVHVLHIRRVTVEDSAVYSAVAknihGEASSSASV 91


                 ...
gi 46049110  336 FVR 338
Cdd:cd20951   92 VVE 94

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 52.64 E-value: 2.12e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110    254 FAKILDPAyQVDKGGRVRFVVEL-ADPKLEVKWYKNGQEIRPSTKYIFEHKGCQRILFINNCQMTDDSEYYVTA----GD 328
Cdd:pfam07679    3 FTQKPKDV-EVQEGESARFTCTVtGTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVAtnsaGE 81


                   ....*....
gi 46049110    329 EKCSTELFV 337
Cdd:pfam07679   82 AEASAELTV 90

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 52.18 E-value: 2.33e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 46049110    521 PPKIILDGldadNTVTVIAGNKLRLEIPISGEPPPKAMWSRGDKAIMEGSGRIRTeSYPDSSTLVIDIAERDDSGVY 597
Cdd:pfam13927    1 KPVITVSP----SSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRS-LSGSNSTLTISNVTRSDAGTY 72

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 58.09 E-value: 2.36e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  597 YHINLKNEAG-EAHASIKVKVVDFPDPPVAP---TVTEVGDDWCIMNWEPPAydgGSPILGYFIERKKKQSSRWMRLNfD 672
Cdd:COG3401  300 YRVTAVDAAGnESAPSNVVSVTTDLTPPAAPsglTATAVGSSSITLSWTASS---DADVTGYNVYRSTSGGGTYTKIA-E 375

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  673 LCKETTFEPKKMIEGVAYEVRIFAVNAIGISkpSMPSRPFVPLAVTSPPTLLTVDSVTDTTVTMRWRPPDHIGAAGLDGY 752
Cdd:COG3401  376 TVTTTSYTDTGLTPGTTYYYKVTAVDAAGNE--SAPSEEVSATTASAASGESLTASVDAVPLTDVAGATAAASAASNPGV 453

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|..
gi 46049110  753 V-LEYCFEGTEDWIVANKDLIDKTKFTITGLPTDAKIFVRVKAVNAAGASEP 803
Cdd:COG3401  454 SaAVLADGGDTGNAVPFTTTSSTVTATTTDTTTANLSVTTGSLVGGSGASSV 505

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: 52.12 E-value: 2.45e-08

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110      64 PQGGTVKVGEDITFIAKVKAEDllrKPTIKWFKGKwmdlaskaGKHLQLKETFERHSRVYTFEMQIIKAKDNFAGNYRCE 143
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSP---PPEVTWYKQG--------GKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCA 69

                            90
                    ....*....|....*.
gi 46049110     144 VTYKDKFDSCSFDLEV 159
Cdd:smart00410   70 ATNSSGSASSGTTLTV 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: 52.01 E-value: 2.93e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110 1036 VNTYAIAGYNATLNCSVRGNPKPKITWMKNKVAIvDDPRYRMFSNQgvcTLEIRKPSPYDGGTYCCKAVNDLGTVEIECK 1115
Cdd:cd05725    5 QNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGEL-PKGRYEILDDH---SLKIRKVTAGDMGSYTCVAENMVGKIEASAT 80


                 ...
gi 46049110 1116 LEV 1118
Cdd:cd05725   81 LTV 83

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: 51.81 E-value: 3.36e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  536 TVIAGNKLRLEIPISGEPPPKAMWSRGDKAIMEgSGRIRTE-SYPDSSTLVIDIAERDDSGVYHINLKNEAGEAHASIKV 614
Cdd:cd20973    8 EVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVE-SRRFQIDqDEDGLCSLIISDVCGDDSGKYTCKAVNSLGEATCSAEL 86


                 ..
gi 46049110  615 KV 616
Cdd:cd20973   87 TV 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: 51.74 E-value: 3.69e-08

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110     829 QTYIRRVGEAVNLVIPFQGKPRPELTWKKDGAE--IDKNQINIRNSETDTIIFIRKAERSHSGKYDLQVKVDKFVETASI 906
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKllAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGT 81


                    ....
gi 46049110     907 DIQI 910
Cdd:smart00410   82 TLTV 85

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: 51.69 E-value: 3.88e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110 1024 DFSEAPMftqpLVNTYAIAGYNATLNCSVRGNPKPKITWMKNKVAIVDDPRYRMFSNQgvcTLEIRKPSPYDGGTYCCKA 1103
Cdd:cd04969    2 DFELNPV----KKKILAAKGGDVIIECKPKASPKPTISWSKGTELLTNSSRICILPDG---SLKIKNVTKSDEGKYTCFA 74

                         90
                 ....*....|....*
gi 46049110 1104 VNDLGTVEIECKLEV 1118
Cdd:cd04969   75 VNFFGKANSTGSLSV 89

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: 51.34 E-value: 4.24e-08

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 46049110 1043 GYNATLNCSVRGNPKPKITWMKNKVAIVDDPRYRMFSNQGVCTLEIRKPSPYDGGTYCCKAVNDLGTV 1110
Cdd:cd05743    1 GETVEFTCVATGVPTPIINWRLNWGHVPDSARVSITSEGGYGTLTIRDVKESDQGAYTCEAINTRGMV 68

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 51.41 E-value: 4.80e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 46049110    818 PPKIRIPrhlKQTYIRRVGEAVNLVIPFQGKPRPELTWKKDGAEIDKN-QINIRNSETDTIIFIRKAERSHSGKY 891
Cdd:pfam13927    1 KPVITVS---PSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGsTRSRSLSGSNSTLTISNVTRSDAGTY 72

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: 51.71 E-value: 5.73e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110 1031 FTQPLVNTYAIAGYNATLNCSVRGNPKPKITWMKNKV--AIVDDPRYRMFSNQGVCTLEI--RKPSPYDGGTYCCKAVN- 1105
Cdd:cd05722    4 FLSEPSDIVAMRGGPVVLNCSAESDPPPKIEWKKDGVllNLVSDERRQQLPNGSLLITSVvhSKHNKPDEGFYQCVAQNe 83


                 ....*
gi 46049110 1106 DLGTV 1110
Cdd:cd05722   84 SLGSI 88

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

Pssm-ID: 409566 [Multi-domain] Cd Length: 93 Bit Score: 51.20 E-value: 8.54e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  534 TVTVIAGNKLRLEIPISGEPPPKAMWSRGDKAI-MEGSGRIRTESYPDSSTLVIDIAERDDSGVYHINLKNEAGEAHASI 612
Cdd:cd20974    9 SVVVLEGSTATFEAHVSGKPVPEVSWFRDGQVIsTSTLPGVQISFSDGRAKLSIPAVTKANSGRYSLTATNGSGQATSTA 88


                 ....
gi 46049110  613 KVKV 616
Cdd:cd20974   89 ELLV 92

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: 50.64 E-value: 1.08e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110 1029 PMFTQPLVNTYAIAGYNATLNCSVRGNPKPKITWMKNKVAIVDDPRYRMFSNqGvcTLEIRK-PSPYDGGTYCCKAVNDL 1107
Cdd:cd20958    1 PPFIRPMGNLTAVAGQTLRLHCPVAGYPISSITWEKDGRRLPLNHRQRVFPN-G--TLVIENvQRSSDEGEYTCTARNQQ 77

                         90
                 ....*....|...
gi 46049110 1108 GTvEIECKLEVKV 1120
Cdd:cd20958   78 GQ-SASRSVFVKV 89

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: 50.47 E-value: 1.37e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110 1042 AGYNATLNCSVRGNPKPKITWM---KNKVAIVDDPRYRMFSNQgvcTLEIRKPSPYDGGTYCCKAVNDLGTVEIECKLEV 1118
Cdd:cd20969   16 EGHTVQFVCRADGDPPPAILWLsprKHLVSAKSNGRLTVFPDG---TLEVRYAQVQDNGTYLCIAANAGGNDSMPAHLHV 92

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: 50.32 E-value: 1.41e-07

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 46049110 1032 TQPLVNTYAIAGYNATLNCSVRGNPKPKITWMKNKVAIVDDPRYRMFSNQgvcTLEIRKPSPYDGGTYCCKAVNDLGT 1109
Cdd:cd20968    3 TRPPTNVTIIEGLKAVLPCTTMGNPKPSVSWIKGDDLIKENNRIAVLESG---SLRIHNVQKEDAGQYRCVAKNSLGI 77

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: 50.14 E-value: 1.50e-07

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 46049110 1043 GYNATLNCSVRGNPKPKITWMKNKVAIVDDP-RYRMFSNQGVCTLEIRkpSPYDGGTYCCKAVNDLGTV 1110
Cdd:cd04978   14 GETGELICEAEGNPQPTITWRLNGVPIEPAPeDMRRTVDGRTLIFSNL--QPNDTAVYQCNASNVHGYL 80

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: 50.15 E-value: 1.55e-07

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 46049110  537 VIAGNKLRLEIPISGEPPPKAMWSRGDKAIMEGSGRIRTesYPDSS---TLVIDIAERDDSGVYHINLKNEAG 606
Cdd:cd05892   12 VLEGDPVRLECQISAIPPPQIFWKKNNEMLQYNTDRISL--YQDNCgriCLLIQNANKKDAGWYTVSAVNEAG 82

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: 49.91 E-value: 2.01e-07

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 46049110 1042 AGYNATLNCSVRGNPKPKITWMKNKVAIVDDPRYRMFSNQGV-CTLEIRKPSPYDGGTYCCKAVNDLGTVEIECKLEV 1118
Cdd:cd05729   18 AANKVRLECGAGGNPMPNITWLKDGKEFKKEHRIGGTKVEEKgWSLIIERAIPRDKGKYTCIVENEYGSINHTYDVDV 95

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: 50.05 E-value: 2.12e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110 1028 APMFTQPLVNTYAiAGYNATLNCSVRGNPKPKITWMKNKVAIVDDPRYRMFSNQGVCTLEIRKPSPYDGGTYCCKAVNDL 1107
Cdd:cd05747    4 ATILTKPRSLTVS-EGESARFSCDVDGEPAPTVTWMREGQIIVSSQRHQITSTEYKSTFEISKVQMSDEGNYTVVVENSE 82


                 ....*....
gi 46049110 1108 GTVEIECKL 1116
Cdd:cd05747   83 GKQEAQFTL 91

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

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 49.86 E-value: 2.50e-07

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 46049110 1046 ATLNCSVRGNPKPKITWMKNKVAIV---DDPRYR--MFSNQGVCTLEI---RKPSPyDGGTYCCKAVNDLGT 1109
Cdd:cd07693   18 ATLNCKAEGRPTPTIQWLKNGQPLEtdkDDPRSHriVLPSGSLFFLRVvhgRKGRS-DEGVYVCVAHNSLGE 88

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

Pssm-ID: 143222 [Multi-domain] Cd Length: 74 Bit Score: 49.17 E-value: 2.50e-07

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 46049110 1043 GYNATLNCSVRGNPKPKITWMKNKVAIVDDPRYRMFSNQgvcTLEIRKPSPYDGGTYCCKAVNDLGTVEIECKLEV 1118
Cdd:cd05745    2 GQTVDFLCEAQGYPQPVIAWTKGGSQLSVDRRHLVLSSG---TLRISRVALHDQGQYECQAVNIVGSQRTVAQLTV 74

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 48.72 E-value: 3.74e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 46049110    340 PPImVTKQLEDTTAYCGERVELECEVS-EDDANVKWFKNGEEIIPGPKSryRIRVEGKKHILIIEGATKADAAEYS 414
Cdd:pfam13927    1 KPV-ITVSPSSVTVREGETVTLTCEATgSPPPTITWYKNGEPISSGSTR--SRSLSGSNSTLTISNVTRSDAGTYT 73

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: 49.12 E-value: 3.83e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 46049110   1033 QPLVNTYAIAGYNATLNCSVR-GNPKPKITWMKNKVAIVDDPRY-RMFSNQGVCTLEIRKPSPYDGGTYCCKAVNDLG 1108
Cdd:pfam00047    1 SAPPTVTVLEGDSATLTCSAStGSPGPDVTWSKEGGTLIESLKVkHDNGRTTQSSLLISNVTKEDAGTYTCVVNNPGG 78

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

Pssm-ID: 409419 Cd Length: 99 Bit Score: 49.18 E-value: 4.03e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  818 PPKI-RIPRHLKqtyIRRvGEAVNLVIPFQGKPRPELTWKKDGAEIDKNQ-INIRNSETDTIIFIRKAERSHSGKYDLQV 895
Cdd:cd05762    1 PPQIiQFPEDMK---VRA-GESVELFCKVTGTQPITCTWMKFRKQIQEGEgIKIENTENSSKLTITEGQQEHCGCYTLEV 76

                         90       100
                 ....*....|....*....|..
gi 46049110  896 KVDKFVETASIDIQIIDRPGPP 917
Cdd:cd05762   77 ENKLGSRQAQVNLTVVDKPDPP 98

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 48.79 E-value: 4.45e-07

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 46049110    834 RVGEAVNLVIPFQGKPRPELTWKKDGAEIDKNQ-INIRNSETDTIIFIRKAERSHSGKYDLQVK 896
Cdd:pfam07679   13 QEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDrFKVTYEGGTYTLTISNVQPDDSGKYTCVAT 76

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: 49.20 E-value: 4.49e-07

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 46049110 1045 NATLNCSVRGNPKPKITWMKNK--VAIVDDPRYRMFSNQGvcTLEIR---KPSPYD-GGTYCCKAVNDLGT 1109
Cdd:cd05875   18 NILIECEAKGNPVPTFHWTRNGkfFNVAKDPRVSMRRRSG--TLVIDfrgGGRPEDyEGEYQCFARNKFGT 86

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: 48.39 E-value: 6.73e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110 1029 PMFTQPLVNTYAIAGY---NATLNCSVRGNPKPKITWMKN--KVAIVDDPRYRMFSNqgvcTLEIRKPSPY-DGGTYCCK 1102
Cdd:cd04967    2 PVFEEQPDDTIFPEDSdekKVALNCRARANPVPSYRWLMNgtEIDLESDYRYSLVDG----TLVISNPSKAkDAGHYQCL 77


                 ....*...
gi 46049110 1103 AVNDLGTV 1110
Cdd:cd04967   78 ATNTVGSV 85

First 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: 409474 Cd Length: 92 Bit Score: 48.55 E-value: 7.15e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110 1029 PMFTQPLVNTYAIAGYNATLNCSVRGNPKPKITWMKNKVAIvdDPRYRMFSNQ----GVCTLEIRKPSPYDGGTYCCKAV 1104
Cdd:cd05893    1 PFFEMKLKHYKIFEGMPVTFTCRVAGNPKPKIYWFKDGKQI--SPKSDHYTIQrdldGTCSLHTTASTLDDDGNYTIMAA 78

                         90
                 ....*....|....
gi 46049110 1105 NDLGTVEIECKLEV 1118
Cdd:cd05893   79 NPQGRISCTGRLMV 92

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: 47.97 E-value: 9.09e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  339 EPPIMVTKQLEDTTAYCGERVELECEVSEDDANVKWFKNGEEIipGPKSRYRIRVEgkkhILIIEGATKADAAEYSVMTT 418
Cdd:cd04973    7 APPTYQISEVESYSAHPGDLLQLRCRLRDDVQSINWTKDGVQL--GENNRTRITGE----EVQIKDAVPRDSGLYACVTS 80


                 .
gi 46049110  419 G 419
Cdd:cd04973   81 S 81

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: 47.91 E-value: 9.20e-07

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110 1042 AGYNATLNCSVRGNPKPKITWMKNKVAIVDDPRYRMFSnqgVCTLEIRKPSPYDGGTYCCKAVNDLGTVE 1111
Cdd:cd20957   15 FGRTAVFNCSVTGNPIHTVLWMKDGKPLGHSSRVQILS---EDVLVIPSVKREDKGMYQCFVRNDGDSAQ 81

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: 47.55 E-value: 1.27e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110 1029 PMFTQP-LVNTYAIA---GYNATLNCSVRGNPKPKITWMKNKVAIVD----DPRYRMFsnqgvcTLEIRKPSPYDGGTYC 1100
Cdd:cd05856    1 PRFTQPaKMRRRVIArpvGSSVRLKCVASGNPRPDITWLKDNKPLTPpeigENKKKKW------TLSLKNLKPEDSGKYT 74

                         90
                 ....*....|....*...
gi 46049110 1101 CKAVNDLGTVEIECKLEV 1118
Cdd:cd05856   75 CHVSNRAGEINATYKVDV 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: 47.32 E-value: 1.44e-06

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 46049110 1037 NTYAIAGYNATLNCSVRGNPKPKITWMKNKVAIvddPRYRMFSNQGVcTLEIRKPSPYDGGTYCCKAVN 1105
Cdd:cd05851   10 DTYALKGQNVTLECFALGNPVPVIRWRKILEPM---PATAEISMSGA-VLKIFNIQPEDEGTYECEAEN 74

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: 47.58 E-value: 1.47e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  536 TVIAGNKLRLEIPISGEPPPKAMWSRGDKAImEGSGRIRTESYPDSSTLVIDIAERDDSGVYHINLKNEAGEAHASIKVK 615
Cdd:cd20972   12 EVAEGSKVRLECRVTGNPTPVVRWFCEGKEL-QNSPDIQIHQEGDLHSLIIAEAFEEDTGRYSCLATNSVGSDTTSAEIF 90


                 .
gi 46049110  616 V 616
Cdd:cd20972   91 V 91

Second Ig-like domain of Junctional adhesion molecule-1 (JAM1); a member of the I-set of IgSF domains; The members here are composed of the second Ig-like domain of Junctional adhesion molecule-1 (JAM1). 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 second Ig-like domain of JAM1 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, the A strand of the I-set is discontinuous but lacks 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: 409542 Cd Length: 97 Bit Score: 47.70 E-value: 1.56e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110 1034 PLVN--TYAIAGYNATLNCSVR-GNPKPKITWMKNKVAIVDDPR-YRMFSNQGVC------TLEIRKPSPYDGGTYCCKA 1103
Cdd:cd20950    1 PTVNipSSATIGNRAVLTCSEPdGSPPSEYTWFKDGVVMPTNPKsTRAFSNSSYSldpttgELVFDPLSASDTGEYSCEA 80


                 ....*.
gi 46049110 1104 VNDLGT 1109
Cdd:cd20950   81 RNGYGT 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: 47.49 E-value: 1.72e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110 1029 PMF-TQPLvNTYAIAGYNATLNCSVRGNPKPKITWMKNKVAIVD--------DPRYRMFSNQgvcTLEIRKPSPYDGGTY 1099
Cdd:cd05734    2 PRFvVQPN-DQDGIYGKAVVLNCSADGYPPPTIVWKHSKGSGVPqfqhivplNGRIQLLSNG---SLLIKHVLEEDSGYY 77

                         90
                 ....*....|
gi 46049110 1100 CCKAVNDLGT 1109
Cdd:cd05734   78 LCKVSNDVGA 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: 46.55 E-value: 1.83e-06

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 46049110  359 VELECEVSED-DANVKWFKNGEEIIPGPksRYRIRVEGKKHILIIEGATKADAAEYS 414
Cdd:cd00096    1 VTLTCSASGNpPPTITWYKNGKPLPPSS--RDSRRSELGNGTLTISNVTLEDSGTYT 55

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: 46.85 E-value: 2.41e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110 1033 QPLVNTYAIAGYNATLNCSVRGNPKPKITWMKNKVAIVDDPRYRMFSNQGvCTLEIRKPSPYDGGTYCCKAVNDLGtvEI 1112
Cdd:cd05730    8 QSEVNATANLGQSVTLACDADGFPEPTMTWTKDGEPIESGEEKYSFNEDG-SEMTILDVDKLDEAEYTCIAENKAG--EQ 84

                         90
                 ....*....|.
gi 46049110 1113 ECKLEVKVIAQ 1123
Cdd:cd05730   85 EAEIHLKVFAK 95

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: 46.02 E-value: 2.95e-06

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 46049110 1048 LNCSVRGNPKPKITWMKNKVAIVDDPRYRMfSNQGvcTLEIRKPSPYDGGTYCCKAVNDLG 1108
Cdd:cd05746    3 IPCSAQGDPEPTITWNKDGVQVTESGKFHI-SPEG--YLAIRDVGVADQGRYECVARNTIG 60

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 46.23 E-value: 3.09e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 46049110   1043 GYNATLNCSVRGNPKPKITWMKNKVAIvdDPRYRMFSNQgvctleirkPSPYDGGTYCCKAVNDlGTVEIECKLEVKV 1120
Cdd:pfam13895   14 GEPVTLTCSAPGNPPPSYTWYKDGSAI--SSSPNFFTLS---------VSAEDSGTYTCVARNG-RGGKVSNPVELTV 79

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: 46.34 E-value: 3.31e-06

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110     260 PAYQVDKGGRVRFVVEL-ADPKLEVKWYKNGQE-IRPSTKYIFEHKGCQRILFINNCQMTDDSEYYVTA----GDEKCST 333
Cdd:smart00410    2 PSVTVKEGESVTLSCEAsGSPPPEVTWYKQGGKlLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAAtnssGSASSGT 81


                    ....
gi 46049110     334 ELFV 337
Cdd:smart00410   82 TLTV 85

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: 46.09 E-value: 4.85e-06

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 46049110 1048 LNCSVRGNPKPKITWMKNKVAIVDDPRYRMFSNQGvcTLEIRKPSPY-DGGTYCCKAVNDLGTV 1110
Cdd:cd05848   24 LNCEARGNPVPTYRWLRNGTEIDTESDYRYSLIDG--NLIISNPSEVkDSGRYQCLATNSIGSI 85

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: 45.58 E-value: 6.88e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  534 TVTVIAGNKLRLEIPISGEPPPKAMWSRGDKAIMEGSGRIRTESypDSSTLVIDIAERDDSGVYHINLKNEA-GEAHASI 612
Cdd:cd20970   11 TVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNTRYIVRE--NGTTLTIRNIRRSDMGIYLCIASNGVpGSVEKRI 88


                 ....
gi 46049110  613 KVKV 616
Cdd:cd20970   89 TLQV 92

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: 45.40 E-value: 7.78e-06

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 46049110 1043 GYNATLNCSVRGNPKPKITWMKN----KVAIVDDPRYRMFSNqgvcTLEIRKPSPYDGGTYCCKAVNDLGTVE 1111
Cdd:cd20949   14 GQSATILCEVKGEPQPNVTWHFNgqpiSASVADMSKYRILAD----GLLINKVTQDDTGEYTCRAYQVNSIAS 82

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: 44.63 E-value: 8.04e-06

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 46049110  839 VNLVIPFQGKPRPELTWKKDGAEIDKNQINIRNSETDT-IIFIRKAERSHSGKY 891
Cdd:cd00096    1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSELGNgTLTISNVTLEDSGTY 54

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: 45.23 E-value: 8.61e-06

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 46049110 1038 TYAIAGYNATLNCSVRGNPKPKITWMKnkvaiVDD---PRYRMFSNQGVctLEIRKPSPYDGGTYCCKAVNDLG 1108
Cdd:cd04968   11 TYALKGQTVTLECFALGNPVPQIKWRK-----VDGspsSQWEITTSEPV--LEIPNVQFEDEGTYECEAENSRG 77

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: 44.88 E-value: 8.80e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110 1036 VNTYAIAGYNATLNCSVRGNPKPKITWMKNKVAIVDDPRYRMFSNQGVCTLEIRKPspyDGGTYCCKAVNDLGTVEIECK 1115
Cdd:cd05723    5 SNIYAHESMDIVFECEVTGKPTPTVKWVKNGDVVIPSDYFKIVKEHNLQVLGLVKS---DEGFYQCIAENDVGNAQASAQ 81


                 .
gi 46049110 1116 L 1116
Cdd:cd05723   82 L 82

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: 45.27 E-value: 8.88e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  340 PPIMVTKqLEDTTAYCGERVELECEVSEDDA-NVKWFKNGEEIIPGPKsrYRIRVEGKKHILIIEGATKADAAEYSVMTT 418
Cdd:cd20972    1 PPQFIQK-LRSQEVAEGSKVRLECRVTGNPTpVVRWFCEGKELQNSPD--IQIHQEGDLHSLIIAEAFEEDTGRYSCLAT 77

                         90
                 ....*....|..
gi 46049110  419 GGQSSAKLSVDL 430
Cdd:cd20972   78 NSVGSDTTSAEI 89

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

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 44.90 E-value: 9.45e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110 1037 NTYAIAGYNATLNCSVRGNPKPKITWMKNKVAIVDDPRYRMFSNqgvcTLEIRKPSPYDGGTYCCKAVNDLGTVEIECKL 1116
Cdd:cd05728    8 DTEADIGSSLRWECKASGNPRPAYRWLKNGQPLASENRIEVEAG----DLRITKLSLSDSGMYQCVAENKHGTIYASAEL 83


                 ..
gi 46049110 1117 EV 1118
Cdd:cd05728   84 AV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 44.48 E-value: 1.31e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 46049110    431 KPlKILTPLTDQTVNLGKEICLKCEISENIPGK--WTKNGLPVQESDRLKVVHKGRIHKLVIANALTEDEGDY 501
Cdd:pfam13927    1 KP-VITVSPSSVTVREGETVTLTCEATGSPPPTitWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTY 72

First immunoglobulin-like domains A168 within the A-band segment of human cardiac titin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domain A168 within the A-band segment of human cardiac titin. 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 structures of the titin-A168169 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: 409563 Cd Length: 93 Bit Score: 44.77 E-value: 1.32e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110 1028 APMFTQPLVNTYAIAGYNATLNCSVRGNPKPKITWMKNKVAIVDDPRYRMFSNQ-GVCTLEIRKPS-PYDGGTYCCKAVN 1105
Cdd:cd20971    1 APHFKEELRNLNVRYQSNATLVCKVTGHPKPIVKWYRQGKEIIADGLKYRIQEFkGGYHQLIIASVtDDDATVYQVRATN 80


                 ...
gi 46049110 1106 DLG 1108
Cdd:cd20971   81 QGG 83

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: 44.39 E-value: 1.73e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110 1029 PMFTQPLVNTYAIAGYNATLNCSVRGNPKPKITWMKNKVAIV-DDPRYRMFSNQgvcTLEIRKPSPYDGGTYCCKAVNDL 1107
Cdd:cd05764    1 PLITRHTHELRVLEGQRATLRCKARGDPEPAIHWISPEGKLIsNSSRTLVYDNG---TLDILITTVKDTGAFTCIASNPA 77


                 .
gi 46049110 1108 G 1108
Cdd:cd05764   78 G 78

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 44.17 E-value: 1.77e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110     60 FIEKPQGGTVKVGEDITFIAKVKAEDllrKPTIKWFKGkwmDLASKAGKHLQLKETferhSRVYTFEMQIIKAKDnfAGN 139
Cdd:pfam07679    3 FTQKPKDVEVQEGESARFTCTVTGTP---DPEVSWFKD---GQPLRSSDRFKVTYE----GGTYTLTISNVQPDD--SGK 70

                           90       100
                   ....*....|....*....|
gi 46049110    140 YRCEVTYKDKFDSCSFDLEV 159
Cdd:pfam07679   71 YTCVATNSAGEAEASAELTV 90

Immunoglobulin (Ig)-like domain found in neuregulin (NRG)-1; The members here are composed of the immunoglobulin (Ig)-like domain found in neuregulin (NRG)-1. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. NRG-1 belongs to the neuregulin gene family which is comprised of four genes. This group represents NRG-1. NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, and heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. The NRG-1 protein binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. NRG-1 has multiple functions, for example, in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival.

Pssm-ID: 409476 Cd Length: 93 Bit Score: 44.60 E-value: 1.81e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  346 KQLEDTTAYCGERVELECEVSEDDANV--KWFKNGEEIipGPKSR---YRIRVEGKKHILIIEGATKADAAEYSVMTTG- 419
Cdd:cd05895    4 KEMKSQEVAAGSKLVLRCETSSEYPSLrfKWFKNGKEI--NRKNKpenIKIQKKKKKSELRINKASLADSGEYMCKVSSk 81

                         90
                 ....*....|
gi 46049110  420 -GQSSAKLSV 428
Cdd:cd05895   82 lGNDSASANV 91

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: 44.23 E-value: 2.15e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 46049110 1046 ATLNCSVRGNPKPKITWMKNKVAIVDDPRYRMFSNQGVCTLEIRKPSPYDGGTYCCKAVNDLGT 1109
Cdd:cd05738   17 ATMLCAASGNPDPEISWFKDFLPVDTATSNGRIKQLRSGALQIENSEESDQGKYECVATNSAGT 80

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: 43.47 E-value: 2.32e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  543 LRLEIPISGEPPPKAMWSRGDKAImEGSGRIRTESYPDSSTLVIDIAERDDSGVYHINLKNEAGEAHASI 612
Cdd:cd00096    1 VTLTCSASGNPPPTITWYKNGKPL-PPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASAS 69

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

Pssm-ID: 319300 Cd Length: 92 Bit Score: 44.12 E-value: 2.55e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  533 NTVTVIAGNKLRLEIPISGEPPPKAMWSRGDKAIMEgSGRIRTESYPDSS-TLVIDIAERDDSGVYHINLKNEAGEAHAS 611
Cdd:cd05737    9 DVVTIMEGKTLNLTCNVWGDPPPEVSWLKNDQALAF-LDHCNLKVEAGRTvYFTINGVSSEDSGKYGLVVKNKYGSETSD 87


                 ....*
gi 46049110  612 IKVKV 616
Cdd:cd05737   88 VTVSV 92

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: 43.84 E-value: 3.25e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110 1036 VNTYAIAGYNATLNCSVRGNPKPKITWMKnkvAIVDDP-RYRMF-SNQGV-----CTLEIRKPSPYDGGTYCCKAVNDLG 1108
Cdd:cd20954    9 VDANVAAGQDVMLHCQADGFPTPTVTWKK---ATGSTPgEYKDLlYDPNVrilpnGTLVFGHVQKENEGHYLCEAKNGIG 85


                 .
gi 46049110 1109 T 1109
Cdd:cd20954   86 S 86

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: 43.38 E-value: 4.05e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  535 VTVIAGNKLRLEIPISGEPPPKAMWSRGDKAIMEGSGRIRTESYPDSSTLVIDIAERDDSGVYHINLKNEAG--EAHASI 612
Cdd:cd05763    9 ITIRAGSTARLECAATGHPTPQIAWQKDGGTDFPAARERRMHVMPEDDVFFIVDVKIEDTGVYSCTAQNSAGsiSANATL 88


                 ..
gi 46049110  613 KV 614
Cdd:cd05763   89 TV 90

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: 43.56 E-value: 4.16e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  536 TVIAGNKLRLEIPISGEPPPKAMWSRGDKAImEGSGRIRT---ESYPDSSTLVIDIAERDDSGVYHINLKNEAGEA--HA 610
Cdd:cd20951   11 TVWEKSDAKLRVEVQGKPDPEVKWYKNGVPI-DPSSIPGKykiESEYGVHVLHIRRVTVEDSAVYSAVAKNIHGEAssSA 89


                 ....*
gi 46049110  611 SIKVK 615
Cdd:cd20951   90 SVVVE 94

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: 43.02 E-value: 4.93e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 46049110 1043 GYNATLNCSVRGNPKPKITWMKNKVAIVDD--PRYRMFSNQGvcTLEIRKPSPYDGGTYCCKAVNDLGTVE 1111
Cdd:cd05736   15 GVEASLRCHAEGIPLPRVQWLKNGMDINPKlsKQLTLIANGS--ELHISNVRYEDTGAYTCIAKNEGGVDE 83

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: 42.58 E-value: 5.85e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 46049110 1042 AGYNATLNCSVRGNPKPKITWMKNKVAIVDDPRYRMFSNQGVCTLEIRKPSPYDGGTYCCKAVNDLGTVEIEckLEVKV 1120
Cdd:cd05748    6 AGESLRLDIPIKGRPTPTVTWSKDGQPLKETGRVQIETTASSTSLVIKNAKRSDSGKYTLTLKNSAGEKSAT--INVKV 82

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: 5.85e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  532 DNTVTVIAGNKLRLEIPISGEPPPKAMWSRGDKAIMEGSGRIRTEsypdSSTLVIDIAERDDSGVYHINLKNEAGEAHAS 611
Cdd:cd20978    8 EKNVVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMERATVE----DGTLTIINVQPEDTGYYGCVATNEIGDIYTE 83


                 ....*
gi 46049110  612 IKVKV 616
Cdd:cd20978   84 TLLHV 88

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: 42.66 E-value: 6.42e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 46049110 1043 GYNATLNCSVRGNPKPKITWMKNKVAIV---DDPRYRMFSNqgvcTLEIRKPSPYDGGTYCCKAVNDLG 1108
Cdd:cd05868   14 GEDGTLICRANGNPKPSISWLTNGVPIEiapTDPSRKVDGD----TIIFSKVQERSSAVYQCNASNEYG 78

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: 42.57 E-value: 6.95e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 46049110 1043 GYNATLNCSVRGNPKPKITWMKNKVAIVD---DPRYRMFSNqgvcTLEIRKPSPYDGGTYCCKAVNDLGTVEIECKLEV 1118
Cdd:cd05867   14 GETARLDCQVEGIPTPNITWSINGAPIEGtdpDPRRHVSSG----ALILTDVQPSDTAVYQCEARNRHGNLLANAHVHV 88

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: 42.59 E-value: 7.33e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  533 NTVTVIAGNKLRLEIPISGEPPPKAMWSRGDKAIMEGSGRIRTESYPDSSTLVIDIAERDDSGVYHINLKNEAGEAHASI 612
Cdd:cd05891    9 DVVTIMEGKTLNLTCTVFGNPDPEVIWFKNDQDIELSEHYSVKLEQGKYASLTIKGVTSEDSGKYSINVKNKYGGETVDV 88


                 ....
gi 46049110  613 KVKV 616
Cdd:cd05891   89 TVSV 92

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: 42.64 E-value: 8.20e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110 1043 GYNATLNCSVRGNPKPKITWMKnkvaivDDPRYRMFSNQ-----GVCT------LEIRKPSPYDGGTYCCKAVNDLGTVE 1111
Cdd:cd05726   14 GRTVTFQCETKGNPQPAIFWQK------EGSQNLLFPYQppqpsSRFSvsptgdLTITNVQRSDVGYYICQALNVAGSIL 87


                 ....*...
gi 46049110 1112 IECKLEVK 1119
Cdd:cd05726   88 AKAQLEVT 95

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: 42.34 E-value: 1.03e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  511 TLPAKVhvidppkiildgLDADNTVTVIAGNKLRLEIPISGEPPPKAMWSRGDKAIMEgSGRIRTESYPDSSTLVIDIAE 590
Cdd:cd05747    1 TLPATI------------LTKPRSLTVSEGESARFSCDVDGEPAPTVTWMREGQIIVS-SQRHQITSTEYKSTFEISKVQ 67

                         90       100
                 ....*....|....*....|....
gi 46049110  591 RDDSGVYHINLKNEAG--EAHASI 612
Cdd:cd05747   68 MSDEGNYTVVVENSEGkqEAQFTL 91

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: 42.15 E-value: 1.12e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110 1042 AGYNATLNCSVRGNPKPKITWMK---NKVAIVDDPRYrMFSNQGVCT---LEIRKPSPYDGGTYCCKAVNDLGTVEIECK 1115
Cdd:cd05765   14 VGETASFHCDVTGRPQPEITWEKqvpGKENLIMRPNH-VRGNVVVTNigqLVIYNAQPQDAGLYTCTARNSGGLLRANFP 92


                 ...
gi 46049110 1116 LEV 1118
Cdd:cd05765   93 LSV 95

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: 42.15 E-value: 1.34e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  835 VGEavNLVIPFQGKPRPEL----TWKKDGAEIDKNQINI---RNSETDTI--IFIRKAERSHSGKYD--LQVKVDKFVET 903
Cdd:cd04970   16 VGE--NATLQCHASHDPTLdltfTWSFNGVPIDLEKIEGhyrRRYGKDSNgdLEIVNAQLKHAGRYTctAQTVVDSDSAS 93

                         90
                 ....*....|....
gi 46049110  904 ASIDIQiidrpGPP 917
Cdd:cd04970   94 ATLVVR-----GPP 102

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

Pssm-ID: 409436 [Multi-domain] Cd Length: 95 Bit Score: 41.86 E-value: 1.37e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 46049110 1047 TLNCSVRGNPKPKITWMKNKVAI-VDDPRYRMFSNQgvctLEIRKPSPY-DGGTYCCKAVNDLGTV 1110
Cdd:cd05849   23 SVNCRARANPFPIYKWRKNNLDIdLTNDRYSMVGGN----LVINNPDKYkDAGRYVCIVSNIYGKV 84

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: 41.73 E-value: 1.72e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  346 KQLEDTTAYCGERVELECE-VSEDDA-NVKWFKNGEEIIPGPKSRYRIRVEGKKHILIIEGATKADAAEYSVMTTG--GQ 421
Cdd:cd05750    4 KEMKSQTVQEGSKLVLKCEaTSENPSpRYRWFKDGKELNRKRPKNIKIRNKKKNSELQINKAKLEDSGEYTCVVENilGK 83


                 ....*..
gi 46049110  422 SSAKLSV 428
Cdd:cd05750   84 DTVTGNV 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: 40.78 E-value: 1.77e-04

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 46049110  278 DPKLEVKWYKNGQEIRPSTKYIFEHKGCQRILFINNCQMTDDSEYYVTA 326
Cdd:cd00096   10 NPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVA 58

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: 41.23 E-value: 2.04e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 46049110  835 VGEAVNL-VIPFQGKPRPELTWKKDGAEIDKNQINIRNSETDTIIfIRKAERSHSGKY 891
Cdd:cd05724   11 VGEMAVLeCSPPRGHPEPTVSWRKDGQPLNLDNERVRIVDDGNLL-IAEARKSDEGTY 67

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: 41.42 E-value: 2.08e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 46049110 1048 LNCSVRGNPKPKITWMKNKVAIVDDPRYRMFSNQG-VCTLEIRKPSPYDGGTYCCKAVNDLGTVEIECKLEV 1118
Cdd:cd05737   21 LTCNVWGDPPPEVSWLKNDQALAFLDHCNLKVEAGrTVYFTINGVSSEDSGKYGLVVKNKYGSETSDVTVSV 92

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: 41.15 E-value: 2.31e-04

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 46049110  847 GKPRPELTWKKDGAEIDKNQINIRNSETDT-IIFIRKAERSHSGKYD 892
Cdd:cd05738   25 GNPDPEISWFKDFLPVDTATSNGRIKQLRSgALQIENSEESDQGKYE 71

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: 41.07 E-value: 2.37e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110 1031 FTQPLVNTYAIAGYNATLNCSVRGNPKPKITWMKNkvAIVDDP-----RYRMFSNQGVCTLEIRKPSpyDGGTYCCKAVN 1105
Cdd:cd05763    2 FTKTPHDITIRAGSTARLECAATGHPTPQIAWQKD--GGTDFPaarerRMHVMPEDDVFFIVDVKIE--DTGVYSCTAQN 77

                         90
                 ....*....|...
gi 46049110 1106 DLGTVEIECKLEV 1118
Cdd:cd05763   78 SAGSISANATLTV 90

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: 41.07 E-value: 2.44e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 46049110 1047 TLNCSVRGNPKPKITWMKNKVAIVDDPRYRMFSNQGVcTLEIRKPSPYDGGTYCCKAVNDLGTV 1110
Cdd:cd05760   20 TLRCHIDGHPRPTYQWFRDGTPLSDGQGNYSVSSKER-TLTLRSAGPDDSGLYYCCAHNAFGSV 82

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: 40.84 E-value: 2.51e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 46049110  341 PIMVTKQLEDTTAYCGERVELECEVSED-DANVKWFKNGEEIIpgpKSRYRIRVEgkKHILIIEGATKADAAEY 413
Cdd:cd20978    1 PKFIQKPEKNVVVKGGQDVTLPCQVTGVpQPKITWLHNGKPLQ---GPMERATVE--DGTLTIINVQPEDTGYY 69

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: 41.05 E-value: 2.56e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  539 AGNKLRLEIPISGEPPPKAMWSRGDKAIME----GSGRIRTESYpdssTLVIDIAERDDSGVYHINLKNEAGEAHASIKV 614
Cdd:cd05729   18 AANKVRLECGAGGNPMPNITWLKDGKEFKKehriGGTKVEEKGW----SLIIERAIPRDKGKYTCIVENEYGSINHTYDV 93


                 ..
gi 46049110  615 KV 616
Cdd:cd05729   94 DV 95

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

Pssm-ID: 409541 [Multi-domain] Cd Length: 89 Bit Score: 40.78 E-value: 2.92e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  336 FVREPPIMVTKQLEDTTAYCgeRVeleceVSEDDANVKWFKNGEEIIPGPK--SRYRIRVEGkkhiLIIEGATKADAAEY 413
Cdd:cd20949    2 FTENAYVTTVKEGQSATILC--EV-----KGEPQPNVTWHFNGQPISASVAdmSKYRILADG----LLINKVTQDDTGEY 70


                 ..
gi 46049110  414 SV 415
Cdd:cd20949   71 TC 72

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

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 40.95 E-value: 3.07e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 46049110  830 TYIRRVGEAVNLVIPFQGKPRPELTWKKDGAEIDKNQINIRNSETDTIIFIRKAERSHSGKY 891
Cdd:cd20970   11 TVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNTRYIVRENGTTLTIRNIRRSDMGIY 72

Fifth domain (immunoglobulin-like) of Trk receptors TrkA, TrkB, and TrkC; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth domain of Trk receptors TrkA, TrkB, and TrkC, an immunoglobulin (Ig)-like domain which binds to neurotrophin. The Trk family of receptors are tyrosine kinase receptors. They are activated by dimerization, leading to autophosphorylation of intracellular tyrosine residues, and triggering the signal transduction pathway. TrkA, TrkB, and TrkC share significant sequence homology and domain organization. The first three domains are leucine-rich domains while the fourth and fifth domains are Ig-like domains playing a part in ligand binding. TrkA, TrkB, and TrkC mediate the trophic effects of the neurotrophin Nerve Growth Factor (NGF) family. TrkA is recognized by NGF. TrkB is recognized by brain-derived neurotrophic factor (BDNF) and neurotrophin (NT)-4. TrkC is recognized by NT-3. NT-3 is promiscuous as in some cell systems it activates TrkA and TrkB receptors. TrkA is a receptor found in all major NGF targets, including the sympathetic, trigeminal, and dorsal root ganglia, cholinergic neurons of the basal forebrain, and the striatum. TrKB transcripts are found throughout multiple structures of the central and peripheral nervous systems. The TrkC gene is expressed throughout the mammalian nervous system. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409360 Cd Length: 96 Bit Score: 40.85 E-value: 3.26e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 46049110 1051 SVRGNPKPKITWMKN-KVAIVDDPRYRMFSNQGVCTLEIR------KPSPYDGGTYCCKAVNDLGTVE 1111
Cdd:cd04971   21 TVRGNPKPTLTWYHNgAVLNESDYIRTEIHYEAATPTEYHgclkfdNPTHVNNGNYTLVASNEYGQDS 88

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 40.24 E-value: 3.45e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 46049110    264 VDKGGRVRFVVE-LADPKLEVKWYKNGQEIRPSTKYIFEHKGCQRILFINNCQMTDDSEYYVTA 326
Cdd:pfam13927   13 VREGETVTLTCEaTGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVA 76

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: 3.91e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  534 TVTVIAGNKLRLEIPISGEPPPKAMWSR--GDKAimegSGRIRTESYpdSSTLVIDIAERDDSGVYHINLKNEAGEAHAS 611
Cdd:cd05731    4 STMVLRGGVLLLECIAEGLPTPDIRWIKlgGELP----KGRTKFENF--NKTLKIENVSEADSGEYQCTASNTMGSARHT 77


                 ....*
gi 46049110  612 IKVKV 616
Cdd:cd05731   78 ISVTV 82

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: 40.01 E-value: 4.07e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 46049110  452 LKCEISENIPG--KWTKNGLPVQESDRLKVVHKGRIHKLVIANALTEDEGDYV 502
Cdd:cd00096    3 LTCSASGNPPPtiTWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYT 55

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

Pssm-ID: 409421 [Multi-domain] Cd Length: 88 Bit Score: 40.54 E-value: 4.18e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  537 VIAGNKLRLEIPISGEPPPKAMWSRGDKAIMEGSGRirTESYPDSsTLVIDIAERDDSGVYHINLKNEAGEAHASIKVKV 616
Cdd:cd05764   12 VLEGQRATLRCKARGDPEPAIHWISPEGKLISNSSR--TLVYDNG-TLDILITTVKDTGAFTCIASNPAGEATARVELHI 88

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: 40.26 E-value: 4.29e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 46049110  432 PLKILTPLTDQTVNLGKEICLKCEISENIPG--KWTKNGLPVQESDRLKVVHKGRIHKLVIANALTEDEGDY 501
Cdd:cd20972    1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPvvRWFCEGKELQNSPDIQIHQEGDLHSLIIAEAFEEDTGRY 72

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: 40.37 E-value: 4.66e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110 1025 FSEAPMFTQPLvntyAIAGYNATLNCSVRGNPKPKITWMKNKVAIVDDPRYRMFSNQgvcTLEIRKPSPYDGGTYCCKAV 1104
Cdd:cd05852    3 FEFNPMKKKIL----AAKGGRVIIECKPKAAPKPKFSWSKGTELLVNNSRISIWDDG---SLEILNITKLDEGSYTCFAE 75

                         90
                 ....*....|....
gi 46049110 1105 NDLGTVEIECKLEV 1118
Cdd:cd05852   76 NNRGKANSTGVLSV 89

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: 39.87 E-value: 5.32e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110     64 PQGGTVKVGEDITFIAKVKAEDLLrkPTIKWFKGKwmdlaskaGKHLQLKETFERHSRVYTFEMQIIKAKDNFAGNYRCE 143
Cdd:pfam00047    3 PPTVTVLEGDSATLTCSASTGSPG--PDVTWSKEG--------GTLIESLKVKHDNGRTTQSSLLISNVTKEDAGTYTCV 72


                   ....*
gi 46049110    144 VTYKD 148
Cdd:pfam00047   73 VNNPG 77

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: 40.23 E-value: 5.68e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 46049110  817 EPPKIRiprhlKQTYIRRVGEAVNLVIPFQGKPRPELTWKKDGAEIDKNQINiRNSETDTIIFIRKAERSHSGKYDLQV 895
Cdd:cd05856    5 QPAKMR-----RRVIARPVGSSVRLKCVASGNPRPDITWLKDNKPLTPPEIG-ENKKKKWTLSLKNLKPEDSGKYTCHV 77

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: 40.17 E-value: 6.11e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 46049110  441 DQTVNLGKEICLKCEISENIPGK--WTKNGLPVQESDRLK-VVHKGRIHKLVIANALTEDEGDY 501
Cdd:cd05744    9 DLEVQEGRLCRFDCKVSGLPTPDlfWQLNGKPVRPDSAHKmLVRENGRHSLIIEPVTKRDAGIY 72

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

Pssm-ID: 409553 Cd Length: 87 Bit Score: 39.74 E-value: 6.13e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 46049110  836 GEAVNLVIPFQGKPRPELTWKKDGAEIDK-NQINIRNSETDTIIF--IRKAERSHSGKYDLQVK 896
Cdd:cd20961    8 GQPVKLNCSVEGMEEPDIQWVKDGAVVQNlDQLYIPVSEQHWIGFlsLKSVERSDAGRYWCQVE 71

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: 39.92 E-value: 6.64e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 46049110  818 PPKIRIpRHLKQTYIRRVGEAVNLVIPFQGKPRPELTWKKDGAEIDKNQINIRNSETDTIIFIRKAERSHSGKY 891
Cdd:cd05730    1 PPTIRA-RQSEVNATANLGQSVTLACDADGFPEPTMTWTKDGEPIESGEEKYSFNEDGSEMTILDVDKLDEAEY 73

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

Pssm-ID: 409566 [Multi-domain] Cd Length: 93 Bit Score: 40.03 E-value: 7.05e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  829 QTYIRRVGEAVNLVIPFQGKPRPELTWKKDGAEIDKNQ---INIRNSETDTIIFIRKAERSHSGKYDLQVK--VDKFVET 903
Cdd:cd20974    8 QSVVVLEGSTATFEAHVSGKPVPEVSWFRDGQVISTSTlpgVQISFSDGRAKLSIPAVTKANSGRYSLTATngSGQATST 87


                 ....*
gi 46049110  904 ASIDI 908
Cdd:cd20974   88 AELLV 92

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: 39.70 E-value: 7.28e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110 1029 PMFTQPLVNTYAIAGYNATLNCSVRGNPKPKITWMKNKVAIVDDPRYRMFSNQ-GVCTLEIRKPSPYDGGTYCCKAVNDL 1107
Cdd:cd20990    1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSAHKMLVREnGVHSLIIEPVTSRDAGIYTCIATNRA 80

                         90
                 ....*....|.
gi 46049110 1108 GTVEIECKLEV 1118
Cdd:cd20990   81 GQNSFNLELVV 91

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

Pssm-ID: 319310 Cd Length: 98 Bit Score: 39.82 E-value: 7.44e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  521 PPKIildglDADNTVTVIAGNKLRLEIPISGEPPP-KAMWSRGDKAIMEGS-GRIRTESYPDS----STLVIDIAERDD- 593
Cdd:cd05758    2 PPII-----TAEATQPAILGEKARLECLVFSSPPPdRIVWSWDEGFLESGSsGRFSVETFPTEpgviSVLHISGTQRSDf 76

                         90       100
                 ....*....|....*....|..
gi 46049110  594 SGVYHINLKNEAGEAHASIKVK 615
Cdd:cd05758   77 QTSFNCSAWNRFGEGTAIVSLG 98

First immunoglobulin (Ig)-like domain of neural cell adhesion molecule NCAM-1, 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 of neural cell adhesion molecule NCAM-1. NCAM-1 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-nonNCAM) 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 the Ig1, Ig2, and Ig3 domains. 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). 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: 409366 Cd Length: 95 Bit Score: 39.93 E-value: 7.62e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 46049110  356 GERVELECEVSEDDANVKWFK-NGEEIIPGPKSRYRIRVEGKKHILIIEGATKADAAEYSVMTT---GGQSSAKLSVDL 430
Cdd:cd04977   15 GESKFFLCKVSGDAKNINWVSpNGEKVLTKHGNLKVVNHGSVLSSLTIYNANINDAGIYKCVATngkGTESEATVKLDI 93

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: 39.88 E-value: 7.64e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110 1027 EAPMFTQPLVNTY-AIAGYNATLNCSVRGNPKpKITWMKNKVAIVDDPRYRMFSNQgvctLEIRKPSPYDGGTYCCKAVN 1105
Cdd:cd04973    7 APPTYQISEVESYsAHPGDLLQLRCRLRDDVQ-SINWTKDGVQLGENNRTRITGEE----VQIKDAVPRDSGLYACVTSS 81

                         90
                 ....*....|...
gi 46049110 1106 DLGTVEIECKLEV 1118
Cdd:cd04973   82 PSGSDTTYFSVNV 94

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: 39.62 E-value: 8.73e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 46049110  263 QVDKGGRVRFVVEL-ADPKLEVKWYKNGQEIRPSTKYIFEHKGCQRILFINNCQMTDDSEYYVTA 326
Cdd:cd20949   10 TVKEGQSATILCEVkGEPQPNVTWHFNGQPISASVADMSKYRILADGLLINKVTQDDTGEYTCRA 74

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: 39.30 E-value: 9.78e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 46049110  432 PLKILTPLTDQTVNLGKEICLKCEISENIPGK--WTKNGLPVQESDRLKVVHKGRihkLVIANALTEDEGDY 501
Cdd:cd20978    1 PKFIQKPEKNVVVKGGQDVTLPCQVTGVPQPKitWLHNGKPLQGPMERATVEDGT---LTIINVQPEDTGYY 69

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: 39.51 E-value: 1.01e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 46049110 1043 GYNATLNCSVRGNPKPKITWMKNKVAIVDDPRYRMFSNQG-VCTLEIRKPSPYDGGTYCCKAVNDLGTVEIECKLEV 1118
Cdd:cd05891   16 GKTLNLTCTVFGNPDPEVIWFKNDQDIELSEHYSVKLEQGkYASLTIKGVTSEDSGKYSINVKNKYGGETVDVTVSV 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: 39.42 E-value: 1.05e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 46049110  436 LTPLTDQTVNLGKEICLKCEISENIPG---KWTKNG--LPVQESDRLKVVHKGRIHKLVIANALTEDEGDYV 502
Cdd:cd05750    3 LKEMKSQTVQEGSKLVLKCEATSENPSpryRWFKDGkeLNRKRPKNIKIRNKKKNSELQINKAKLEDSGEYT 74

Third immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F (also known as LAR), type IIa; member of the I-set of IgSF domains; The members here are composed of the third 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. Included in this group is Drosophila LAR (DLAR).

Pssm-ID: 409401 Cd Length: 82 Bit Score: 39.11 E-value: 1.07e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110 1032 TQPLVNTYAIAGYNATLNCSVRGNPKPKITWMKNKVAIVDDPRYRMFSNqgvcTLEIRkpSPYDGGTYCCKAVNDLGTVE 1111
Cdd:cd05739    1 SIPPSNHEVMPGGSVNLTCVAVGAPMPYVKWMKGGEELTKEDEMPVGRN----VLELT--NIYESANYTCVAISSLGMIE 74


                 ....*...
gi 46049110 1112 IECKLEVK 1119
Cdd:cd05739   75 ATAQVTVK 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: 39.16 E-value: 1.13e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  536 TVIAGNKLRLEIPISGEPPPKAMWSRGDKAIMEGSGRIRTEsyPDSSTLVIDIAERDDSGVYHINLKNEAGEAHASIKVK 615
Cdd:cd20976   12 EAVEGQDFVAQCSARGKPVPRITWIRNAQPLQYAADRSTCE--AGVGELHIQDVLPEDHGTYTCLAKNAAGQVSCSAWVT 89


                 .
gi 46049110  616 V 616
Cdd:cd20976   90 V 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: 38.92 E-value: 1.15e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 46049110  534 TVTVIAGNKLRLEI-PISGEPPPKAMWSRGDKAIMEGSGRIRTEsypDSSTLVIDIAERDDSGVYHINLKNEAGE 607
Cdd:cd05724    6 DTQVAVGEMAVLECsPPRGHPEPTVSWRKDGQPLNLDNERVRIV---DDGNLLIAEARKSDEGTYKCVATNMVGE 77

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

Pssm-ID: 409567 Cd Length: 91 Bit Score: 39.38 E-value: 1.18e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  536 TVIAGNKLRLEIPISGEPPPKAMWSRGDKAIMEGSGRIRTESYPDSSTLVIDIAERDDSGVYHINLKNEAGEAHASIKVK 615
Cdd:cd20975   11 SVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGGLCRLRILAAERGDAGFYTCKAVNEYGARQCEARLE 90


                 .
gi 46049110  616 V 616
Cdd:cd20975   91 V 91

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: 39.07 E-value: 1.26e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110 1042 AGYNATLNCSVRGNPKPKITWMKNKVAIVDDPR---YRMFSNQGVCTLEIRKPSpyDGGTYCCKAVNDLGTVEIECKLEV 1118
Cdd:cd05857   18 AANTVKFRCPAAGNPTPTMRWLKNGKEFKQEHRiggYKVRNQHWSLIMESVVPS--DKGNYTCVVENEYGSINHTYHLDV 95

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: 39.04 E-value: 1.43e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110 1029 PMFTQpLVNTYAIAGYNATLNCSVRGNPKPKITWMKNKVAIVD-----DPRYRMFSNQGVCTLEIRKPSPYDGGTYCCKA 1103
Cdd:cd05732    3 PKITY-LENQTAVELEQITLTCEAEGDPIPEITWRRATRGISFeegdlDGRIVVRGHARVSSLTLKDVQLTDAGRYDCEA 81


                 ....*
gi 46049110 1104 VNDLG 1108
Cdd:cd05732   82 SNRIG 86

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: 38.91 E-value: 1.71e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  535 VTVIAGNKLRLEIPISGEPPPKAMWSRGDKAIMEGSGRIRTESYPDsSTLVIDIAERDDSGVYHINLKNEAGEAHASIKV 614
Cdd:cd20969   12 VFVDEGHTVQFVCRADGDPPPAILWLSPRKHLVSAKSNGRLTVFPD-GTLEVRYAQVQDNGTYLCIAANAGGNDSMPAHL 90


                 ..
gi 46049110  615 KV 616
Cdd:cd20969   91 HV 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: 38.81 E-value: 1.84e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110 1045 NATLNCSVRGNPKPKITWMKNKVA--IVDDPRYRMFSNQGVCTLEIR---KPSPYDgGTYCCKAVNDLGT 1109
Cdd:cd05874   18 NIVIQCEAKGKPPPSFSWTRNGTHfdIDKDPKVTMKPNTGTLVINIMngeKAEAYE-GVYQCTARNERGA 86

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

Pssm-ID: 409475 Cd Length: 86 Bit Score: 38.28 E-value: 2.00e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 46049110  836 GEAVNLVIPFQGKPRPELTWKKDGAEIDKNQINIR-NSETDTIIF-IRKAERSHSGKYDLQVKVDKFVETASIDIQI 910
Cdd:cd05894   10 GNKLRLDVPISGEPAPTVTWSRGDKAFTATEGRVRvESYKDLSSFvIEGAEREDEGVYTITVTNPVGEDHASLFVKV 86

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: 38.79 E-value: 2.09e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110 1037 NTYAIAGYNATLNCSVRGNPKPKITWMK------NKVAIVDDPRYRMFSNQGVCT-------LEIRKPSPYDGGTYCCKA 1103
Cdd:cd05858   10 NTSVVVGTDAEFVCKVYSDAQPHIQWLKhvekngSKYGPDGLPYVEVLKTAGVNTtdkeievLYLRNVTFEDAGEYTCLA 89


                 ....*
gi 46049110 1104 VNDLG 1108
Cdd:cd05858   90 GNSIG 94

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: 38.34 E-value: 2.19e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  443 TVNLGKEICLKCEISENIPGK--WTKNGLPVQESDRLKV-VHKGRIHKLVIANALTEDEGDY-VFAPDAY 508
Cdd:cd05737   12 TIMEGKTLNLTCNVWGDPPPEvsWLKNDQALAFLDHCNLkVEAGRTVYFTINGVSSEDSGKYgLVVKNKY 81

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: 38.28 E-value: 2.23e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 46049110  432 PLKILTPLTDQTVNLGKEICLKCEISENiPGK---WTKNGLPVQESDRLKVVHKGRihkLVIANALTEDEGDY 501
Cdd:cd20957    1 PLSATIDPPVQTVDFGRTAVFNCSVTGN-PIHtvlWMKDGKPLGHSSRVQILSEDV---LVIPSVKREDKGMY 69

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 37.55 E-value: 3.02e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110     63 KPQGGTVKVGEDITFIAKVKAEDllrKPTIKWFKGkwmdlaskaGKHLQLKETFERHSRVYTFEMQIIKAKDNFAGNYRC 142
Cdd:pfam13927    7 SPSSVTVREGETVTLTCEATGSP---PPTITWYKN---------GEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTC 74


                   ...
gi 46049110    143 EVT 145
Cdd:pfam13927   75 VAS 77

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: 3.07e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 46049110  540 GNKLRLEIPISGEPPPKAMWSRgDKAIMEGSGRIRTEsypdSSTLVIDIAERDDSGVYHINLKNEAGEAHASIKVKV 616
Cdd:cd05728   14 GSSLRWECKASGNPRPAYRWLK-NGQPLASENRIEVE----AGDLRITKLSLSDSGMYQCVAENKHGTIYASAELAV 85

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

Pssm-ID: 409398 Cd Length: 101 Bit Score: 38.24 E-value: 3.08e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110 1030 MFTQPLVNTYAIAGYNATLNCSVRGNPKPKITWMKNKVAI--VDDPRYRMFSNQG----VCTLEIRKPSPYDGGTYCCKA 1103
Cdd:cd05735    5 MITSYPNTTLATKGQKKEMSCTAHGEKPIIVRWEKEDTIInpSEMSRYLVTTKEVgdevISTLQILPTVREDSGFFSCHA 84


                 ....*
gi 46049110 1104 VNDLG 1108
Cdd:cd05735   85 INSYG 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: 37.61 E-value: 3.43e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 46049110  535 VTVIAGNKLRLEIPISGEPPPKAMWSRGDKAIMEGSgRIrteSYPDSSTLVIDIAERDDSGVYHINLKNEAGEAHA 610
Cdd:cd20968    9 VTIIEGLKAVLPCTTMGNPKPSVSWIKGDDLIKENN-RI---AVLESGSLRIHNVQKEDAGQYRCVAKNSLGIAYS 80

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: 37.86 E-value: 3.63e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  535 VTVIAGNKLRLEIPISGEPPPKAMWSRGDKAIMEGSGRIRTEsypDSSTLVIDIAERDDSGVYHINLKNEAGEAHASIKV 614
Cdd:cd20952    9 QTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDERITTL---ENGSLQIKGAEKSDTGEYTCVALNLSGEATWSAVL 85


                 ..
gi 46049110  615 KV 616
Cdd:cd20952   86 DV 87

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: 37.37 E-value: 4.25e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 46049110  359 VELECEVSEDDANVKWFKNGEEIIPGPksryRIRVEGKKHILIIEGATKADAAEY 413
Cdd:cd05740   18 VTLTCEPETQNTSYLWWFNGQSLPVTP----RLTLSNGNRTLTLLNVTREDAGAY 68

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: 37.70 E-value: 4.43e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110   60 FIEKPQGGTVKVGEDITFIAKVKAEDllrKPTIKWFKGkwmdlaskaGKHLQLKETFERHSRVYTFEMQIIKAKDNFAGN 139
Cdd:cd20949    2 FTENAYVTTVKEGQSATILCEVKGEP---QPNVTWHFN---------GQPISASVADMSKYRILADGLLINKVTQDDTGE 69


                 ...
gi 46049110  140 YRC 142
Cdd:cd20949   70 YTC 72

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: 37.55 E-value: 4.47e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  535 VTVIAGNKLRLEIPISGEPPPKAMWSRGDKAIMEGsgrIRTESYPDsSTLVIDIAERD-DSGVYHINLKNEAGE-AHASI 612
Cdd:cd20958   10 LTAVAGQTLRLHCPVAGYPISSITWEKDGRRLPLN---HRQRVFPN-GTLVIENVQRSsDEGEYTCTARNQQGQsASRSV 85


                 ....
gi 46049110  613 KVKV 616
Cdd:cd20958   86 FVKV 89

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 36.99 E-value: 4.95e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 46049110    815 IIEPPKIRIprhlkqtyirRVGEAVNLVIPFQGKPRPELTWKKDGAEIDKNQinirnsetdtIIFIRKAERSHSGKY 891
Cdd:pfam13895    3 VLTPSPTVV----------TEGEPVTLTCSAPGNPPPSYTWYKDGSAISSSP----------NFFTLSVSAEDSGTY 59

Third 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 third 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 FGFs. 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: 409363 Cd Length: 102 Bit Score: 37.79 E-value: 5.01e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110 1035 LVNTYAIAGYNATLNCSVRGNPKPKITWMK------NKVAIVDDPRYRMFSNQGVC------TLEIRKPSPYDGGTYCCK 1102
Cdd:cd04974    8 PANQTVVLGSDVEFHCKVYSDAQPHIQWLKhvevngSKYGPDGLPYVTVLKVAGVNttgeenTLTISNVTFDDAGEYICL 87


                 ....*.
gi 46049110 1103 AVNDLG 1108
Cdd:cd04974   88 AGNSIG 93

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: 5.40e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  535 VTVIAGNKLRLEIPISGEPPPKAMWSRGDKAIMEGSGRIRtesypDSSTLVIDIAERDDSGVYHINLKNEAGEAHASIKV 614
Cdd:cd05725    7 QVVLVDDSAEFQCEVGGDPVPTVRWRKEDGELPKGRYEIL-----DDHSLKIRKVTAGDMGSYTCVAENMVGKIEASATL 81


                 ..
gi 46049110  615 KV 616
Cdd:cd05725   82 TV 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: 37.18 E-value: 5.97e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46049110  346 KQLEDTTAYCGERVELECEVS-EDDANVKWFKNGEEIIPgpkSRYRIRVEGkkHILIIEGATKADAAEYSVMTT----GG 420
Cdd:cd05723    2 KKPSNIYAHESMDIVFECEVTgKPTPTVKWVKNGDVVIP---SDYFKIVKE--HNLQVLGLVKSDEGFYQCIAEndvgNA 76


                 ....*...
gi 46049110  421 QSSAKLSV 428
Cdd:cd05723   77 QASAQLII 84

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: 37.20 E-value: 7.49e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 46049110  833 RRVGEAVNLVIPFQGKPRPELTWKKDGAEIDK-NQINI-RNSETDTIIFIRKAERSHSGKYDLQV 895
Cdd:cd05729   16 LPAANKVRLECGAGGNPMPNITWLKDGKEFKKeHRIGGtKVEEKGWSLIIERAIPRDKGKYTCIV 80

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: 36.81 E-value: 8.87e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 46049110  356 GERVELECEVSED-DANVKWFKNGEEIipGPKSRYRIRVEGKKHI-LIIEGATKADAAEYSV 415
Cdd:cd05891   16 GKTLNLTCTVFGNpDPEVIWFKNDQDI--ELSEHYSVKLEQGKYAsLTIKGVTSEDSGKYSI 75

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: 36.15 E-value: 9.57e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 46049110   89 KPTIKWFKGkwmdlaskaGKHLQLKETFERHSRVYTFEMQIIKAKDNFAGNYRCEVTYK 147
Cdd:cd00096   12 PPTITWYKN---------GKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNS 61

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: 36.83 E-value: 9.90e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 46049110  551 GEPPPKAMWSRGDKAIMEGSGRIRTESypDSSTLVIDIAERDDSGVYHINLKNEAGEAHASIKVKV 616
Cdd:cd05730   29 GFPEPTMTWTKDGEPIESGEEKYSFNE--DGSEMTILDVDKLDEAEYTCIAENKAGEQEAEIHLKV 92