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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340045   25 GTLIAKEGESLTLRCEVE-DPSVAIIWRKNtevvavDDEILDTYGGYEISMEGSTSVLTIKRVEPINSANYSCALAEPEV 103
Cdd:smart00410   2 PSVTVKEGESVTLSCEASgSPPPEVTWYKQ------GGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSG 75

                           90
                   ....*....|
gi 1734340045  104 SVTFVIKVQV 113
Cdd:smart00410  76 SASSGTTLTV 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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340045 229 VRKNQNASFWCTYDGTPVPQVEWLFNGYKINfNDEKFKKTSETaqrlngySKSTLTVGDISEEAFGDYACRISNKLGSVT 308
Cdd:pfam07679  12 VQEGESARFTCTVTGTPDPEVSWFKDGQPLR-SSDRFKVTYEG-------GTYTLTISNVQPDDSGKYTCVATNSAGEAE 83

                  ....*
gi 1734340045 309 AVVHV 313
Cdd:pfam07679  84 ASAEL 88

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340045   25 GTLIAKEGESLTLRCEVE-DPSVAIIWRKNtevvavDDEILDTYGGYEISMEGSTSVLTIKRVEPINSANYSCALAEPEV 103
Cdd:smart00410   2 PSVTVKEGESVTLSCEASgSPPPEVTWYKQ------GGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSG 75

                           90
                   ....*....|
gi 1734340045  104 SVTFVIKVQV 113
Cdd:smart00410  76 SASSGTTLTV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340045 114 KPLVVISPDTgvYHARVGEkNLVITCHVkEGNPKPGVVWTKQFKAAKLPEDIKREH--GGARIVITEVKKHHAGKYNCLA 191
Cdd:pfam13927   1 KPVITVSPSS--VTVREGE-TVTLTCEA-TGSPPPTITWYKNGEPISSGSTRSRSLsgSNSTLTISNVTRSDAGTYTCVA 76

                  ..
gi 1734340045 192 EN 193
Cdd:pfam13927  77 SN 78

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1734340045 239 CTYDGTPVPQVEWLFNGYKINFNDEKFKKTSETAQrlngyskstLTVGDISEEAFGDYACRISNKLGSVTAVVHVS 314
Cdd:cd20976    23 CSARGKPVPRITWIRNAQPLQYAADRSTCEAGVGE---------LHIQDVLPEDHGTYTCLAKNAAGQVSCSAWVT 89

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340045  229 VRKNQNASFWCTYDGTPVPQVEWLFNGYKINFNDEKFKktsetaqRLNGYSKSTLTVGDISEEAFGDYACRISNKLGSVT 308
Cdd:smart00410   6 VKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFS-------VSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSAS 78

                   ....*.
gi 1734340045  309 AVVHVS 314
Cdd:smart00410  79 SGTTLT 84

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 1734340045  23 KGGTLIAKEGESLTLRCEVE-DPSVAIIWRKNTEVVAVDDEildtygGYEISMEGSTsvLTIKRVEPINSANYSCAL--- 98
Cdd:cd20970     8 PSFTVTAREGENATFMCRAEgSPEPEISWTRNGNLIIEFNT------RYIVRENGTT--LTIRNIRRSDMGIYLCIAsng 79

                          90
                  ....*....|...
gi 1734340045  99 AEPEVSVTFVIKV 111
Cdd:cd20970    80 VPGSVEKRITLQV 92

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340045   25 GTLIAKEGESLTLRCEVE-DPSVAIIWRKNtevvavDDEILDTYGGYEISMEGSTSVLTIKRVEPINSANYSCALAEPEV 103
Cdd:smart00410   2 PSVTVKEGESVTLSCEASgSPPPEVTWYKQ------GGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSG 75

                           90
                   ....*....|
gi 1734340045  104 SVTFVIKVQV 113
Cdd:smart00410  76 SASSGTTLTV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340045 114 KPLVVISPDTgvYHARVGEkNLVITCHVkEGNPKPGVVWTKQFKAAKLPEDIKREH--GGARIVITEVKKHHAGKYNCLA 191
Cdd:pfam13927   1 KPVITVSPSS--VTVREGE-TVTLTCEA-TGSPPPTITWYKNGEPISSGSTRSRSLsgSNSTLTISNVTRSDAGTYTCVA 76

                  ..
gi 1734340045 192 EN 193
Cdd:pfam13927  77 SN 78

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340045 229 VRKNQNASFWCTYDGTPVPQVEWLFNGYKINfNDEKFKKTSETaqrlngySKSTLTVGDISEEAFGDYACRISNKLGSVT 308
Cdd:pfam07679  12 VQEGESARFTCTVTGTPDPEVSWFKDGQPLR-SSDRFKVTYEG-------GTYTLTISNVQPDDSGKYTCVATNSAGEAE 83

                  ....*
gi 1734340045 309 AVVHV 313
Cdd:pfam07679  84 ASAEL 88

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1734340045  19 QIRTKGGTLIAKEGESLTLRCEVE-DPSVAIIWRKNtevvavdDEILDTYGGYEISMEGSTSVLTIKRVEPINSANYSC 96
Cdd:pfam13927   3 VITVSPSSVTVREGETVTLTCEATgSPPPTITWYKN-------GEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTC 74

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1734340045 229 VRKNQNASFWCTYDGTPVPQVEWLFNGykinfndeKFKKTSETAQRLNGYSKSTLTVGDISEEAFGDYACRISN 302
Cdd:pfam13927  13 VREGETVTLTCEATGSPPPTITWYKNG--------EPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340045  27 LIAKEGESLTLRCEVE---DPSVAiiWRKNTEVVAVDDEildtyggYEISMEGSTSVLTIKRVEPINSANYSCaLAEPEV 103
Cdd:pfam07679  10 VEVQEGESARFTCTVTgtpDPEVS--WFKDGQPLRSSDR-------FKVTYEGGTYTLTISNVQPDDSGKYTC-VATNSA 79

                          90
                  ....*....|.
gi 1734340045 104 -SVTFVIKVQV 113
Cdd:pfam07679  80 gEAEASAELTV 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340045 125 VYHARVGEkNLVITCHVKeGNPKPGVVWTKQFKAAKLPEDIKREHGGAR--IVITEVKKHHAGKYNCLAENIAGSDRATI 202
Cdd:cd05748     1 TIVVRAGE-SLRLDIPIK-GRPTPTVTWSKDGQPLKETGRVQIETTASStsLVIKNAKRSDSGKYTLTLKNSAGEKSATI 78

                  ....
gi 1734340045 203 DIHV 206
Cdd:cd05748    79 NVKV 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340045 115 PLVVISPDTGVyhARVGEKNLVITCHVKeGNPKPGVVWT---KQFKAAklPEDIKREHGGarIVITEVKKHHAGKYNCLA 191
Cdd:cd20978     1 PKFIQKPEKNV--VVKGGQDVTLPCQVT-GVPQPKITWLhngKPLQGP--MERATVEDGT--LTIINVQPEDTGYYGCVA 73

                          90
                  ....*....|....*
gi 1734340045 192 ENIAGSDRATIDIHV 206
Cdd:cd20978    74 TNEIGDIYTETLLHV 88

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 1734340045 235 ASFWCTYDGTPVPQVEWLFNGYKInfndekfkKTSETAQRLNGYSKSTLTVGDISEEAFGDYACRISNKLGSVTA 309
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPL--------PPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSAS 67

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 1734340045  35 LTLRCEVE-DPSVAIIWRKNtevvavdDEILDTYGGYEISMEGSTSVLTIKRVEPINSANYSC 96
Cdd:cd00096     1 VTLTCSASgNPPPTITWYKN-------GKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTC 56

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1734340045 128 ARVGEkNLVITCHVkEGNPKPGVVWTKQfkaAKLPEDIKREH----GGARIVITEVKKHHAGKYNCLAENIAG 196
Cdd:cd20970    14 AREGE-NATFMCRA-EGSPEPEISWTRN---GNLIIEFNTRYivreNGTTLTIRNIRRSDMGIYLCIASNGVP 81

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340045 233 QNASFWCTYDGTPVPQVEWLFNGYKINFNDEKFKKTsetaqrlngYSKSTLTVGDISEEAFGDYACRISNKLGSVTAVVH 312
Cdd:cd05730    19 QSVTLACDADGFPEPTMTWTKDGEPIESGEEKYSFN---------EDGSEMTILDVDKLDEAEYTCIAENKAGEQEAEIH 89

                  .
gi 1734340045 313 V 313
Cdd:cd05730    90 L 90

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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1734340045 135 LVITChVKEGNPKPGVVWTKqfKAAKLPED-IKREHGGARIVITEVKKHHAGKYNCLAENIAGSDRATIDIHV 206
Cdd:cd05731    13 LLLEC-IAEGLPTPDIRWIK--LGGELPKGrTKFENFNKTLKIENVSEADSGEYQCTASNTMGSARHTISVTV 82

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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340045 134 NLVITCHVKeGNPKPGVVWTKQ---FKAAKLPEDIKREHGGArIVITE---VKKHHAGKYNCLAENIAGS 197
Cdd:cd05733    18 NITIKCEAK-GNPQPTFRWTKDgkfFDPAKDPRVSMRRRSGT-LVIDNhngGPEDYQGEYQCYASNELGT 85

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1734340045 243 GTPVPQVEWLFNGYKINfndekfKKTSETAQRLNGYSKSTLTVGDISEEAFGDYACRISNKLG--SVTAVVHV 313
Cdd:cd05750    26 ENPSPRYRWFKDGKELN------RKRPKNIKIRNKKKNSELQINKAKLEDSGEYTCVVENILGkdTVTGNVTV 92

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340045  29 AKEGESLTLRCEVE--DPSVAIIWRKNTEVVAVDDeildtygGYEISMEGS-TSVLTIKRVEPINSANYSCALAEPEVSV 105
Cdd:cd20959    14 AQVGMRAQLHCGVPggDLPLNIRWTLDGQPISDDL-------GITVSRLGRrSSILSIDSLEASHAGNYTCHARNSAGSA 86

                  ....*...
gi 1734340045 106 TFVIKVQV 113
Cdd:cd20959    87 SYTAPLTV 94

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1734340045 144 GNPKPGVVWTKQFKAAKLPEDIK-REHGGARIviTEVKKHHAGKYNCLAEN---IAGSDRATIDI 204
Cdd:cd20968    25 GNPKPSVSWIKGDDLIKENNRIAvLESGSLRI--HNVQKEDAGQYRCVAKNslgIAYSKPVTIEV 87

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340045 106 TFVIKVQvkPLVVISPDTGVYHARVgeknlvitchvkEGNPKPGVVWTKQFKA---AKLPE-DIKREHGGARIVITEVKK 181
Cdd:cd20974     2 VFTQPLQ--SVVVLEGSTATFEAHV------------SGKPVPEVSWFRDGQVistSTLPGvQISFSDGRAKLSIPAVTK 67

                          90       100
                  ....*....|....*....|....*
gi 1734340045 182 HHAGKYNCLAENIAGSDRATIDIHV 206
Cdd:cd20974    68 ANSGRYSLTATNGSGQATSTAELLV 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340045 108 VIKVQVKplvvispDTgvyHARVGEkNLVITCHVKeGNPKPGVVWTKQFKAakLPEDIKREHGGARIVITEVKKHHAGKY 187
Cdd:cd05851     3 DINVKFK-------DT---YALKGQ-NVTLECFAL-GNPVPVIRWRKILEP--MPATAEISMSGAVLKIFNIQPEDEGTY 68

                          90
                  ....*....|....*....
gi 1734340045 188 NCLAENIAGSDRATIDIHV 206
Cdd:cd05851    69 ECEAENIKGKDKHQARVYV 87

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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1734340045 233 QNASFWCTYDGTPVPQVEWLFNGYKINFNDEkfkktsETAQRLNGyskSTLTVGDISEEAFGDYACRISNKLGSVTA 309
Cdd:cd05868    15 EDGTLICRANGNPKPSISWLTNGVPIEIAPT------DPSRKVDG---DTIIFSKVQERSSAVYQCNASNEYGYLLA 82

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340045 225 TFIPVRKNQNASFWCTYDGTPVPQVEWlfngykiNFNDEKFKKTSETAQRLNGYSKStLTVGDISEEAFGDYACRISNKL 304
Cdd:cd20949     7 YVTTVKEGQSATILCEVKGEPQPNVTW-------HFNGQPISASVADMSKYRILADG-LLINKVTQDDTGEYTCRAYQVN 78

                  ....*..
gi 1734340045 305 GSVTAVV 311
Cdd:cd20949    79 SIASDMQ 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340045 229 VRKNQNASFWCTYDGTPVPQVEWLFNGYKINFNDEKFKKTSETAqrlngysKSTLTVGDISEEAFGDYACRISNKLGSVT 308
Cdd:cd05744    12 VQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVRENG-------RHSLIIEPVTKRDAGIYTCIARNRAGENS 84

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340045 115 PLVVISPDTGVYHARVGEKNLVITCHVKeGNPKPGVVWTKQFKAAKLPEDIKREHGGARIVI---TEVKKhhAGKYNCLA 191
Cdd:cd05848     2 PVFVQEPDDAIFPTDSDEKKVILNCEAR-GNPVPTYRWLRNGTEIDTESDYRYSLIDGNLIIsnpSEVKD--SGRYQCLA 78

                  ....*.
gi 1734340045 192 ENIAGS 197
Cdd:cd05848    79 TNSIGS 84

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340045  17 SAQIRTKGGTLIAKEGESLTLRCEVED-PSVAIIWRKNTEVVAVDDEildtyggyEISMEGSTSVLTIKRVEPINSANYS 95
Cdd:cd05730     3 TIRARQSEVNATANLGQSVTLACDADGfPEPTMTWTKDGEPIESGEE--------KYSFNEDGSEMTILDVDKLDEAEYT 74

                          90       100
                  ....*....|....*....|..
gi 1734340045  96 CaLAEP---EVSVTFVIKVQVK 114
Cdd:cd05730    75 C-IAENkagEQEAEIHLKVFAK 95

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 1734340045 127 HARVGEKNLVITChVKEGNPKPGVVWTK---QFKAAKLPEDIKREHGGARIVITEVKKHHAGKYNCLAENIAGSDRATID 203
Cdd:cd05729    14 HALPAANKVRLEC-GAGGNPMPNITWLKdgkEFKKEHRIGGTKVEEKGWSLIIERAIPRDKGKYTCIVENEYGSINHTYD 92

                  ...
gi 1734340045 204 IHV 206
Cdd:cd05729    93 VDV 95

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1734340045 234 NASFWCTYDGTPVPQVEWLFNGYKIN------FNDEKFKKTSETAQrLNGYSKSTLTVGDISEEAFGDYACRISN 302
Cdd:cd20940    17 SVELHCEAVGSPIPEIQWWFEGQEPNeicsqlWDGARLDRVHINAT-YHQHATSTISIDNLTEEDTGTYECRASN 90

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734340045  33 ESLTLRCEVE-DPSVAIIWRKNTEVVAVDDEILDtyGGYEISMEGSTSVLTIKRVEPINSANYSCALAEP 101
Cdd:cd05869    18 EQITLTCEASgDPIPSITWRTSTRNISSEEKTLD--GHIVVRSHARVSSLTLKYIQYTDAGEYLCTASNT 85