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 1907116891 209 PAIMMPQKSFNATAERGEEMTLTCKASGSPDPTISWFRNGKLIEE-NEKYILKGSNTELTVRNIINKDGGSYVCKATNKA 287
Cdd:cd20970     1 PVISTPQPSFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEfNTRYIVRENGTTLTIRNIRRSDMGIYLCIASNGV 80

                          90
                  ....*....|..
gi 1907116891 288 -GEDQKQAFLQV 298
Cdd:cd20970    81 pGSVEKRITLQV 92

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907116891  122 SPQEFKQGEDAEVVCRVSSSPAPAVSWlYHNEEVTTIPDNRFAVLANNNLQI---LNINKSDEGIYRCE 187
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPEVTW-YKQGGKLLAESGRFSVSRSGSTSTltiSNVTPEDSGTYTCA 69

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 1907116891 209 PAIMMPQKSFNATAERGEEMTLTCKASGSPDPTISWFRNGKLIEE-NEKYILKGSNTELTVRNIINKDGGSYVCKATNKA 287
Cdd:cd20970     1 PVISTPQPSFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEfNTRYIVRENGTTLTIRNIRRSDMGIYLCIASNGV 80

                          90
                  ....*....|..
gi 1907116891 288 -GEDQKQAFLQV 298
Cdd:cd20970    81 pGSVEKRITLQV 92

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907116891  22 QVTISLSKVELSVGESKFFTCTAIGEPE-SIDWYNPqGEKIISTQRVMLQKEGVRSRLTIYNANIEDAGIYRCQATDAKG 100
Cdd:pfam07679   2 KFTQKPKDVEVQEGESARFTCTVTGTPDpEVSWFKD-GQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSAG 80

                          90
                  ....*....|.
gi 1907116891 101 QtQEATVVLEI 111
Cdd:pfam07679  81 E-AEASAELTV 90

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907116891  219 NATAERGEEMTLTCKASGSPDPTISWFRNG-KLIEENEKYILKGSNTE--LTVRNIINKDGGSYVCKATNKAGEDQKQAF 295
Cdd:smart00410   3 SVTVKEGESVTLSCEASGSPPPEVTWYKQGgKLLAESGRFSVSRSGSTstLTISNVTPEDSGTYTCAATNSSGSASSGTT 82

                   ...
gi 1907116891  296 LQV 298
Cdd:smart00410  83 LTV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907116891 302 PHI-LQLKNETTSENGHVTLVCEAEGEPVPEITWKRaidgvmfseGDKLLLSHGIRRLHGGNISSIFILSS 371
Cdd:pfam13927   2 PVItVSPSSVTVREGETVTLTCEATGSPPPTITWYK---------NGEPISSGSTRSRSLSGSNSTLTISN 63

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907116891  122 SPQEFKQGEDAEVVCRVSSSPAPAVSWlYHNEEVTTIPDNRFAVLANNNLQI---LNINKSDEGIYRCE 187
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPEVTW-YKQGGKLLAESGRFSVSRSGSTSTltiSNVTPEDSGTYTCA 69

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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907116891 129 GEDAEVVCRVSSSPAPAVSWlyhNEEVTTIPDNRFAVLANNNLQILNINKSDEGIYRCE-----GRVEARG 194
Cdd:cd05725    12 DDSAEFQCEVGGDPVPTVRW---RKEDGELPKGRYEILDDHSLKIRKVTAGDMGSYTCVaenmvGKIEASA 79

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907116891  21 LQVTISLSKVELSVGESKFFTCTAIGEPESIDWYNPQGEKIIS--TQRVMLQKEGVRSRLTIYNANIEDAGIYRCQATDA 98
Cdd:cd04977     1 LQVKIIPSYAEISVGESKFFLCKVSGDAKNINWVSPNGEKVLTkhGNLKVVNHGSVLSSLTIYNANINDAGIYKCVATNG 80

                          90
                  ....*....|....*
gi 1907116891  99 KGQTQEATVVLEIYQ 113
Cdd:cd04977    81 KGTESEATVKLDIIQ 95

First immunoglobulin (Ig)-like domain of neural cell adhesion molecule (NCAM-1); 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. 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907116891  21 LQVTISLSKVELSVGESKFFTCTAIGEPES--IDWYNPQGEKIISTQR--VMLQKEGVRSRLTIYNANIEDAGIYRCQAT 96
Cdd:cd05865     1 LQVDIVPSQGEISVGESKFFLCQVAGEAKDkdISWFSPNGEKLTPNQQriSVVRNDDYSSTLTIYNANIDDAGIYKCVVS 80

                          90
                  ....*....|....*..
gi 1907116891  97 DAKGQTQEATVVLEIYQ 113
Cdd:cd05865    81 NEDEGESEATVNVKIFQ 97

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1907116891 300 VQPHILQLKNETTSENGHVTLVCEAEGEPVPEITWKRAIDGVMFSEGDK 348
Cdd:cd05870     1 VQPHIIQLKNETTVENGAATLSCKAEGEPIPEITWKRASDGHTFSEGDK 49

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907116891 215 QKSFNATAERGEEMTLTCKASGSPDPTISWFRNGKLIEENEKYILK--GSNTELTVRNIINKDGGSYVCKATNKAGEDQK 292
Cdd:pfam07679   5 QKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTyeGGTYTLTISNVQPDDSGKYTCVATNSAGEAEA 84

                  ....*.
gi 1907116891 293 QAFLQV 298
Cdd:pfam07679  85 SAELTV 90

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907116891 208 PPAIMMPQKsfNATAERGEEMTLTCKASGSPDPTISWFRNGKLIEENE--KYILKGSNTELTVRNIINKDGGSYVCKATN 285
Cdd:pfam13927   1 KPVITVSPS--SVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGStrSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907116891  219 NATAERGEEMTLTCKASGSPDPTISWFRNG-KLIEENEKYILKGSNTE--LTVRNIINKDGGSYVCKATNKAGEDQKQAF 295
Cdd:smart00410   3 SVTVKEGESVTLSCEASGSPPPEVTWYKQGgKLLAESGRFSVSRSGSTstLTISNVTPEDSGTYTCAATNSSGSASSGTT 82

                   ...
gi 1907116891  296 LQV 298
Cdd:smart00410  83 LTV 85

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907116891 229 TLTCKASGSPDPTISWFRNGKLIEENEKYI--LKGSNTELTVRNIINKDGGSYVCKATNKAGE 289
Cdd:cd00096     2 TLTCSASGNPPPTITWYKNGKPLPPSSRDSrrSELGNGTLTISNVTLEDSGTYTCVASNSAGG 64

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907116891 215 QKSFNATAERGEEMTLTCKASGSPDPTISWFRNGKLIEENEKYILKGSNTELTVRNIINKDGGSYVCKATNKAGEDQKQA 294
Cdd:cd20952     4 QGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDERITTLENGSLQIKGAEKSDTGEYTCVALNLSGEATWSA 83

                  ....
gi 1907116891 295 FLQV 298
Cdd:cd20952    84 VLDV 87

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907116891 219 NATA-ERGEEMTLTCKASGSPDPTISWFRNGKLIEENEK----YILKGSN---TELTVRNIINKDGGSYVCKATNKAGED 290
Cdd:cd05869    10 NQTAmELEEQITLTCEASGDPIPSITWRTSTRNISSEEKtldgHIVVRSHarvSSLTLKYIQYTDAGEYLCTASNTIGQD 89

                  ....*...
gi 1907116891 291 QKQAFLQV 298
Cdd:cd05869    90 SQSMYLEV 97

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907116891 225 GEEMTLTCKASGSPDPTISWFRNGKLIEENEKYILKGSNT---ELTVRNIINKDGGSYVCKATNKAGEDQKQAFLQV 298
Cdd:cd05744    15 GRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVRENgrhSLIIEPVTKRDAGIYTCIARNRAGENSFNAELVV 91

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907116891 219 NATAERGEEMTLTCKASGSPDPTISWFRNGKLIEE-NEKYILKGSNTELTVRNIINKDGGSYVCKATNKAGEDQKQAFLQ 297
Cdd:cd04978     8 SLVLSPGETGELICEAEGNPQPTITWRLNGVPIEPaPEDMRRTVDGRTLIFSNLQPNDTAVYQCNASNVHGYLLANAFLH 87

                  ..
gi 1907116891 298 VF 299
Cdd:cd04978    88 VL 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907116891 215 QKSFNATAERGEEMTLTCKASGSPDPTISWFRNGK-LIEENEKYILKGsntELTVRNIINKDGGSYVCKATNKAGEDQKQ 293
Cdd:cd05728     4 KVISDTEADIGSSLRWECKASGNPRPAYRWLKNGQpLASENRIEVEAG---DLRITKLSLSDSGMYQCVAENKHGTIYAS 80

                  ....*
gi 1907116891 294 AFLQV 298
Cdd:cd05728    81 AELAV 85

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907116891  40 FTCTAIGEPE-SIDWYNpQGEKIISTQRVMLQKEGVRSRLTIYNANIEDAGIYRCQATDAKGQTQEATV 107
Cdd:cd00096     3 LTCSASGNPPpTITWYK-NGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907116891 221 TAERGEEMTLTCKASGSPDPTISWFRNGKLIEENE-----KYILKGSNTELTVRNIINK----DGGSYVCKATNKAGED- 290
Cdd:cd07693    11 IVSKGDPATLNCKAEGRPTPTIQWLKNGQPLETDKddprsHRIVLPSGSLFFLRVVHGRkgrsDEGVYVCVAHNSLGEAv 90

                  ....*...
gi 1907116891 291 QKQAFLQV 298
Cdd:cd07693    91 SRNASLEV 98

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907116891 219 NATAERGEEMTLTCKASGSPDPTISWFRNGKLIEENEKYIL---KGSNTELTVRNIINKDGGSYVCKATNKAGEDQKQAF 295
Cdd:cd20973     6 DKEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIdqdEDGLCSLIISDVCGDDSGKYTCKAVNSLGEATCSAE 85

                  ...
gi 1907116891 296 LQV 298
Cdd:cd20973    86 LTV 88

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907116891 225 GEEMTLTCKASGSPDPTISW-FRNGKLIEENEKYILKGSNT-ELTVRNIinKDGGSYVCKATNKAGEDQKQAFLQV 298
Cdd:cd05764    15 GQRATLRCKARGDPEPAIHWiSPEGKLISNSSRTLVYDNGTlDILITTV--KDTGAFTCIASNPAGEATARVELHI 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907116891 219 NATAERGEEMTLTCKASGSPDPTISWFRNGKLIE-ENEKYILKGSNTELTVRNIINKDGGSYVCKATNKAGEDQKQAFLQ 297
Cdd:cd20976    10 DLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQyAADRSTCEAGVGELHIQDVLPEDHGTYTCLAKNAAGQVSCSAWVT 89

                  .
gi 1907116891 298 V 298
Cdd:cd20976    90 V 90

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

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907116891 222 AERGEEMTLTCKASGSPDPTISWFRNGKLIEENeKYILKGSNTELTVRNIINKDGGSYVCKATNKAGEDQKQAFLQV 298
Cdd:cd04969    14 AAKGGDVIIECKPKASPKPTISWSKGTELLTNS-SRICILPDGSLKIKNVTKSDEGKYTCFAVNFFGKANSTGSLSV 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907116891 225 GEEMTLTCKASGSPDPTISWFRNGKLIEENEKYILKGSNTE--LTVRNIINKDGGSYVCKATNKAGedqkqaflQVFVQP 302
Cdd:cd05743     1 GETVEFTCVATGVPTPIINWRLNWGHVPDSARVSITSEGGYgtLTIRDVKESDQGAYTCEAINTRG--------MVFGIP 72

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907116891 224 RGEEMTLTCKASGSPDPTISWFRNGKLIEenekyilkgSNTELTVRNIINKDGGSYVCKATNKAG 288
Cdd:pfam13895  13 EGEPVTLTCSAPGNPPPSYTWYKDGSAIS---------SSPNFFTLSVSAEDSGTYTCVARNGRG 68

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907116891 204 IVNVPpaimmpqksfnATAERGEEMTLTC-KASGSPDPTISWFRNGKLIE---------ENEKYILKGSNTELTVRNIIN 273
Cdd:cd20950     2 TVNIP-----------SSATIGNRAVLTCsEPDGSPPSEYTWFKDGVVMPtnpkstrafSNSSYSLDPTTGELVFDPLSA 70

                          90
                  ....*....|....*....
gi 1907116891 274 KDGGSYVCKATNKAGEDQK 292
Cdd:cd20950    71 SDTGEYSCEARNGYGTPMR 89

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907116891 221 TAERGEEMTLTCKASGSPDPTISWFRNGKLIEENE---KYIL--KGSNTELTVRNIINKDGGSYVCKATNKAGEDQKQAF 295
Cdd:cd20951    11 TVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDPSSipgKYKIesEYGVHVLHIRRVTVEDSAVYSAVAKNIHGEASSSAS 90

                  ...
gi 1907116891 296 LQV 298
Cdd:cd20951    91 VVV 93

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907116891 222 AERGEEMTLTCKASGSPDPTISWFR-NGKLIEeneKYILKGSNTELTVRNIINKDGGSYVCKATNKAGEDQKQAFLQVF 299
Cdd:cd04968    13 ALKGQTVTLECFALGNPVPQIKWRKvDGSPSS---QWEITTSEPVLEIPNVQFEDEGTYECEAENSRGKDTVQGRIIVQ 88

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.