Immunoglobulin domain; This family contains immunoglobulin-like domains.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 386769058   316 PPIVFIESKTHEAEEGETVLIRCNVTANPSPiNVEWLKEGAP---------DFRYTGELLTLGSVRAEHAGNYICRSVN 385
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVTLTCEATGSPPP-TITWYKNGEPissgstrsrSLSGSNSTLTISNVTRSDAGTYTCVASN 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386769058  523 DYAVTCSAKGKPTPQIRWIKDGTEIlptrkMFDIRTTPTDAGGGVVAVQSIlrfrgkarpngnqlLPNDRGLYTCLYEND 602
Cdd:cd20976    18 DFVAQCSARGKPVPRITWIRNAQPL-----QYAADRSTCEAGVGELHIQDV--------------LPEDHGTYTCLAKNA 78

                          90
                  ....*....|..
gi 386769058  603 VNSANSSMHLRI 614
Cdd:cd20976    79 AGQVSCSAWVTV 90

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386769058   416 ITPNKPVVHVGNGVTLTCSAnpPGWPVPQYRWFRDmdgdigntQKILAQGPQYSIPKAHLGSEGKYHCHAVNELGIGKIA 495
Cdd:pfam13895    4 LTPSPTVVTEGEPVTLTCSA--PGNPPPSYTWYKD--------GSAISSSPNFFTLSVSAEDSGTYTCVARNGRGGKVSN 73

                   ....*.
gi 386769058   496 TIILEV 501
Cdd:pfam13895   74 PVELTV 79

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 386769058   316 PPIVFIESKTHEAEEGETVLIRCNVTANPSPiNVEWLKEGAP---------DFRYTGELLTLGSVRAEHAGNYICRSVN 385
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVTLTCEATGSPPP-TITWYKNGEPissgstrsrSLSGSNSTLTISNVTRSDAGTYTCVASN 78

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.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 386769058   139 LAVATEEKPLELTCSSIGGSPDPMITWYREGSTVPLQSYalKGGSKNHYTNATLQIVPRRADDGAKYKCVVWNR 212
Cdd:pfam00047    5 TVTVLEGDSATLTCSASTGSPGPDVTWSKEGGTLIESLK--VKHDNGRTTQSSLLISNVTKEDAGTYTCVVNNP 76

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386769058  523 DYAVTCSAKGKPTPQIRWIKDGTEIlptrkMFDIRTTPTDAGGGVVAVQSIlrfrgkarpngnqlLPNDRGLYTCLYEND 602
Cdd:cd20976    18 DFVAQCSARGKPVPRITWIRNAQPL-----QYAADRSTCEAGVGELHIQDV--------------LPEDHGTYTCLAKNA 78

                          90
                  ....*....|..
gi 386769058  603 VNSANSSMHLRI 614
Cdd:cd20976    79 AGQVSCSAWVTV 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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 386769058  635 AEVVCRVQAYPKPEFQWQYGNNPSPLTMSSDGHyeistrmenNDVYTSILRIAHLQHSDYGEYICRAVNPL 705
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRR---------SELGNGTLTISNVTLEDSGTYTCVASNSA 62

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386769058   416 ITPNKPVVHVGNGVTLTCSAnpPGWPVPQYRWFRDmdgdigntQKILAQGPQYSIPKAHLGSEGKYHCHAVNELGIGKIA 495
Cdd:pfam13895    4 LTPSPTVVTEGEPVTLTCSA--PGNPPPSYTWYKD--------GSAISSSPNFFTLSVSAEDSGTYTCVARNGRGGKVSN 73

                   ....*.
gi 386769058   496 TIILEV 501
Cdd:pfam13895   74 PVELTV 79

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386769058  238 PQNP--LKVERDHVAKLDCRVDAKPMvSNVRWSRNG----------QYVSATPTHTIYRVNRHHAGKYTCSADNGLGKTG 305
Cdd:cd20970     6 PQPSftVTAREGENATFMCRAEGSPE-PEISWTRNGnliiefntryIVRENGTTLTIRNIRRSDMGIYLCIASNGVPGSV 84

                  ....*...
gi 386769058  306 EKDIVLDV 313
Cdd:cd20970    85 EKRITLQV 92

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386769058  323 SKTHEAEEGETVLIRCNVTANPSPInVEWLKEG----APDFRYT----GELLTLGSVRAEHAGNYICRSVNIMQPFSSKR 394
Cdd:cd20970     9 SFTVTAREGENATFMCRAEGSPEPE-ISWTRNGnliiEFNTRYIvrenGTTLTIRNIRRSDMGIYLCIASNGVPGSVEKR 87

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 386769058   232 PRVEVGPQNPLKVERDHVaKLDCRVDAKPmVSNVRWSRNGQYVSATPTH-----------TIYRVNRHHAGKYTCSADN 299
Cdd:pfam13927    2 PVITVSPSSVTVREGETV-TLTCEATGSP-PPTITWYKNGEPISSGSTRsrslsgsnstlTISNVTRSDAGTYTCVASN 78

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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 386769058  425 VGNGVTLTCSAnpPGWPVPQYRWfRDMDGDIGNTQKILAQGPQYSIPKAHLGSEGKYHCHAVNELG 490
Cdd:cd04968    15 KGQTVTLECFA--LGNPVPQIKW-RKVDGSPSSQWEITTSEPVLEIPNVQFEDEGTYECEAENSRG 77

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

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386769058    418 PNKPVVHVGNGVTLTCSANppGWPVPQYRWFRDMDGDIGNTQKILAQGPQYS----IPKAHLGSEGKYHCHAVNELGIGK 493
Cdd:smart00410    1 PPSVTVKEGESVTLSCEAS--GSPPPEVTWYKQGGKLLAESGRFSVSRSGSTstltISNVTPEDSGTYTCAATNSSGSAS 78

                    ....*...
gi 386769058    494 iATIILEV 501
Cdd:smart00410   79 -SGTTLTV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 386769058   316 PPIVFIESKTHEAEEGETVLIRCNVTANPSPiNVEWLKEGAP---------DFRYTGELLTLGSVRAEHAGNYICRSVN 385
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVTLTCEATGSPPP-TITWYKNGEPissgstrsrSLSGSNSTLTISNVTRSDAGTYTCVASN 78

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.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 386769058   139 LAVATEEKPLELTCSSIGGSPDPMITWYREGSTVPLQSYalKGGSKNHYTNATLQIVPRRADDGAKYKCVVWNR 212
Cdd:pfam00047    5 TVTVLEGDSATLTCSASTGSPGPDVTWSKEGGTLIESLK--VKHDNGRTTQSSLLISNVTKEDAGTYTCVVNNP 76

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386769058   131 PPMVT-PGNLAVATEEKPLELTCSsIGGSPDPMITWYREGSTVPLQSYALKGGSKNhytNATLQIVPRRADDGAKYKCVV 209
Cdd:pfam13927    1 KPVITvSPSSVTVREGETVTLTCE-ATGSPPPTITWYKNGEPISSGSTRSRSLSGS---NSTLTISNVTRSDAGTYTCVA 76

                   ..
gi 386769058   210 WN 211
Cdd:pfam13927   77 SN 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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 386769058  148 LELTCSSIGgSPDPMITWYREGSTVPLQSYalkGGSKNHYTNATLQIVPRRADDGAKYKCVVWNRA 213
Cdd:cd00096     1 VTLTCSASG-NPPPTITWYKNGKPLPPSSR---DSRRSELGNGTLTISNVTLEDSGTYTCVASNSA 62

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

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 386769058    323 SKTHEAEEGETVLIRCNVTANPSPiNVEWLKEG----APDFRYTGEL------LTLGSVRAEHAGNYICRSVN 385
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPP-EVTWYKQGgkllAESGRFSVSRsgststLTISNVTPEDSGTYTCAATN 72

CD80-like C2-set immunoglobulin domain; These domains belong to the immunoglobulin superfamily.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386769058   132 PMVTPGNLAVATEEKPLELTCSSIGGSPDPMITWYREGSTV--PLQSYALKGGSKNHYTNATLQIVPRRADDGAKYKCVV 209
Cdd:pfam08205    1 PTIEPPASLLEGEGPEVVATCSSAGGKPAPRITWYLDGKPLeaAETSSEQDPESGLVTVTSELKLVPSRSDHGQSLTCQV 80

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386769058   416 ITPNKPVVHVGNGVTLTCSAnpPGWPVPQYRWFRDmdgdigntQKILAQGPQYSIPKAHLGSEGKYHCHAVNELGIGKIA 495
Cdd:pfam13895    4 LTPSPTVVTEGEPVTLTCSA--PGNPPPSYTWYKD--------GSAISSSPNFFTLSVSAEDSGTYTCVARNGRGGKVSN 73

                   ....*.
gi 386769058   496 TIILEV 501
Cdd:pfam13895   74 PVELTV 79

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386769058  528 CSAKGKPTPQIRWIKDGTEILPTRKmfdIRTTPTDAGGGVVAVQSilrfrgkarpngnqLLPNDRGLYTCLYENDVNSAN 607
Cdd:cd05729    26 CGAGGNPMPNITWLKDGKEFKKEHR---IGGTKVEEKGWSLIIER--------------AIPRDKGKYTCIVENEYGSIN 88

                  ....*..
gi 386769058  608 SSMHLRI 614
Cdd:cd05729    89 HTYDVDV 95

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 386769058   416 ITPNKPVVHVGNGVTLTCSANppGWPVPQYRWFRDMDGDIGNTQKILAQGPQYS---IPKAHLGSEGKYHCHAVN 487
Cdd:pfam13927    6 VSPSSVTVREGETVTLTCEAT--GSPPPTITWYKNGEPISSGSTRSRSLSGSNStltISNVTRSDAGTYTCVASN 78

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386769058  238 PQNP--LKVERDHVAKLDCRVDAKPMvSNVRWSRNG----------QYVSATPTHTIYRVNRHHAGKYTCSADNGLGKTG 305
Cdd:cd20970     6 PQPSftVTAREGENATFMCRAEGSPE-PEISWTRNGnliiefntryIVRENGTTLTIRNIRRSDMGIYLCIASNGVPGSV 84

                  ....*...
gi 386769058  306 EKDIVLDV 313
Cdd:cd20970    85 EKRITLQV 92

Fibronectin type III domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386769058   722 KPTNLKILEVGHNYAVLNWTPGFNGGFMSTKYLVSYRrvatpreqtlsDCSGNGYIPSYQISSSssnsnhewiefncfkE 801
Cdd:pfam00041    2 APSNLTVTDVTSTSLTVSWTPPPDGNGPITGYEVEYR-----------PKNSGEPWNEITVPGT---------------T 55

                           90       100       110
                   ....*....|....*....|....*....|
gi 386769058   802 NPCKLAPLDQHQSYMFKVYALNSKGTSGYS 831
Cdd:pfam00041   56 TSVTLTGLKPGTEYEVRVQAVNGGGEGPPS 85

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

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386769058    526 VTCSAKGKPTPQIRWIKDGTEILPTRKMFDIRTTPTdagggvvavQSILRFrgkarpngNQLLPNDRGLYTCLYENDVNS 605
Cdd:smart00410   14 LSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSGS---------TSTLTI--------SNVTPEDSGTYTCAATNSSGS 76

                    ....*....
gi 386769058    606 ANSSMHLRI 614
Cdd:smart00410   77 ASSGTTLTV 85

Second immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 - Necl-4; member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 (also known as cell adhesion molecule 3 or CADM3), Necl-2 (also known as CADM1), Necl-3 (also known as CADM2) and Necl-4 (also known as CADM4). These nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. The N-terminal Ig-like domain of the extracellular region belongs to the V-type subfamily of Ig domains, is essential to cell-cell adhesion, and plays a part in the interaction with the envelope glycoprotein D of various viruses. Necl-1 and Necl-2 have Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is specifically expressed in neural tissue and is important to the formation of synapses, axon bundles, and myelinated axons. Necl-2 is expressed in a wide variety of tissues, and is a putative tumour suppressor gene, which is downregulated in aggressive neuroblastoma. Necl-3 has been shown to accumulate in tissues of the central and peripheral nervous system, where it is expressed in ependymal cells and myelinated axons. It is observed at the interface between the axon shaft and the myelin sheath. Necl-4 is expressed on Schwann cells, and plays a key part in initiating peripheral nervous system (PNS) myelination. Necl-4 participates in cell-cell adhesion and is proposed to play a role in tumor suppression.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386769058  126 LTAPHPPMVTpGNLAVATEEKPLELTCSSIGGSPDPMITWYREGSTVPLQSYALKGGSKNHYT-NATLQIVPRRADDGAK 204
Cdd:cd05761     1 LGVPEKPVIT-GFTSPVVEGDEITLTCTTSGSKPAADIRWFKNDKELKGVKEVQESGAGKTFTvTSTLRFRVDRDDDGVA 79

                          90       100
                  ....*....|....*....|....
gi 386769058  205 YKCVVWNRAMPeGHMLETSVTLNV 228
Cdd:cd05761    80 VICRVDHESLT-STPKQTQQVLEV 102

Immunoglobulin I-set domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386769058   232 PRVEVGPQnPLKVERDHVAKLDCRVDAKPmVSNVRWSRNGQYVSATPTH-----------TIYRVNRHHAGKYTCSADNG 300
Cdd:pfam07679    1 PKFTQKPK-DVEVQEGESARFTCTVTGTP-DPEVSWFKDGQPLRSSDRFkvtyeggtytlTISNVQPDDSGKYTCVATNS 78

                           90
                   ....*....|...
gi 386769058   301 LGKTgEKDIVLDV 313
Cdd:pfam07679   79 AGEA-EASAELTV 90

Immunoglobulin I-set domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386769058   416 ITPNKPV-VHVGNGVTLTCSANppGWPVPQYRWFRDmDGDIGNTQ--KILAQGPQYS--IPKAHLGSEGKYHCHAVNELG 490
Cdd:pfam07679    4 TQKPKDVeVQEGESARFTCTVT--GTPDPEVSWFKD-GQPLRSSDrfKVTYEGGTYTltISNVQPDDSGKYTCVATNSAG 80

Immunoglobulin I-set domain;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 386769058   327 EAEEGETVLIRCNVTANPSPInVEWLKEGAP-------DFRYTGEL--LTLGSVRAEHAGNYICRSVN 385
Cdd:pfam07679   11 EVQEGESARFTCTVTGTPDPE-VSWFKDGQPlrssdrfKVTYEGGTytLTISNVQPDDSGKYTCVATN 77

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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 386769058  425 VGNGVTLTCSAnpPGWPVPQYRWfRDMDGDIGNTQKILAQGPQYSIPKAHLGSEGKYHCHAVNELG 490
Cdd:cd04968    15 KGQTVTLECFA--LGNPVPQIKW-RKVDGSPSSQWEITTSEPVLEIPNVQFEDEGTYECEAENSRG 77

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386769058  525 AVTCSAKGKPTPQIRWIKDGTEILPTRKmFDIrttptdAGGGVVAVQSilrfrgkarpngnqLLPNDRGLYTCLYENDVN 604
Cdd:cd05746     2 QIPCSAQGDPEPTITWNKDGVQVTESGK-FHI------SPEGYLAIRD--------------VGVADQGRYECVARNTIG 60

                  ....*...
gi 386769058  605 SANSSMHL 612
Cdd:cd05746    61 YASVSMVL 68