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 51858934 125 PVSRIPSSVTTSSNVRLTCFDPVGSPPSTYKWYKDNTPLPEDPTKFPAFKNLTYKMNVFNGNLEFPSVSKMDTGSYFCEA 204
Cdd:cd20950   1 PTVNIPSSATIGNRAVLTCSEPDGSPPSEYTWFKDGVVMPTNPKSTRAFSNSSYSLDPTTGELVFDPLSASDTGEYSCEA 80

                        90
                ....*....|....*..
gi 51858934 205 SNGEGVPQRGDEVKMEV 221
Cdd:cd20950  81 RNGYGTPMRSNAVRMEA 97

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 51858934 125 PVSRIPSSVTTSSNVRLTCFDPVGSPPSTYKWYKDNTPLPEDPTKFPAFKNLTYKMNVFNGNLEFPSVSKMDTGSYFCEA 204
Cdd:cd20950   1 PTVNIPSSATIGNRAVLTCSEPDGSPPSEYTWFKDGVVMPTNPKSTRAFSNSSYSLDPTTGELVFDPLSASDTGEYSCEA 80

                        90
                ....*....|....*..
gi 51858934 205 SNGEGVPQRGDEVKMEV 221
Cdd:cd20950  81 RNGYGTPMRSNAVRMEA 97

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 51858934   124 KPVSRIPSSVTT---SSNVRLTCfDPVGSPPSTYKWYKDNTPLPEDPTkfpafknLTYKMNVFNGNLEFPSVSKMDTGSY 200
Cdd:pfam13927   1 KPVITVSPSSVTvreGETVTLTC-EATGSPPPTITWYKNGEPISSGST-------RSRSLSGSNSTLTISNVTRSDAGTY 72

                  ....*.
gi 51858934   201 FCEASN 206
Cdd:pfam13927  73 TCVASN 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 51858934    130 PSSVTTS--SNVRLTCFdPVGSPPSTYKWYKDNTPLPEDPTKFpafknlTYKMNVFNGNLEFPSVSKMDTGSYFCEASNG 207
Cdd:smart00410   1 PPSVTVKegESVTLSCE-ASGSPPPEVTWYKQGGKLLAESGRF------SVSRSGSTSTLTISNVTPEDSGTYTCAATNS 73

                   ...
gi 51858934    208 EGV 210
Cdd:smart00410  74 SGS 76

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 51858934 125 PVSRIPSSVTTSSNVRLTCFDPVGSPPSTYKWYKDNTPLPEDPTKFPAFKNLTYKMNVFNGNLEFPSVSKMDTGSYFCEA 204
Cdd:cd20950   1 PTVNIPSSATIGNRAVLTCSEPDGSPPSEYTWFKDGVVMPTNPKSTRAFSNSSYSLDPTTGELVFDPLSASDTGEYSCEA 80

                        90
                ....*....|....*..
gi 51858934 205 SNGEGVPQRGDEVKMEV 221
Cdd:cd20950  81 RNGYGTPMRSNAVRMEA 97

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 51858934   124 KPVSRIPSSVTT---SSNVRLTCfDPVGSPPSTYKWYKDNTPLPEDPTkfpafknLTYKMNVFNGNLEFPSVSKMDTGSY 200
Cdd:pfam13927   1 KPVITVSPSSVTvreGETVTLTC-EATGSPPPTITWYKNGEPISSGST-------RSRSLSGSNSTLTISNVTRSDAGTY 72

                  ....*.
gi 51858934   201 FCEASN 206
Cdd:pfam13927  73 TCVASN 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 51858934     25 SPVKVKENEGVDLQCSYTSDfgATPRVEWkfkdLKGSQTLVYFDGKptgqYTGRVTMYDKGLRFNKVTRADTGDYDCEVS 104
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGS--PPPEVTW----YKQGGKLLAESGR----FSVSRSGSTSTLTISNVTPEDSGTYTCAAT 71

                           90
                   ....*....|....
gi 51858934    105 GSGGYGENTIKLTV 118
Cdd:smart00410  72 NSSGSASSGTTLTV 85

Immunoglobulin (Ig) constant domain of the complement receptor of the immunoglobulin superfamily (CRIg); The members here are composed of the Immunoglobulin (Ig) constant domain of the complement receptor of the immunoglobulin superfamily (CRIg). The N-terminal domain of CRIg (also referred to as Z39Ig and V-set and Ig domain-containing 4 (VSIG4)) belongs to the IgV family of immunoglobulin-like domains while the C-terminal domain of CRIg belongs to the IgC family of immunoglobulin-like domains. CRIg plays a role in the complement system, an inhibitor of the alternative pathway convertases, and a negative regulator of T cell activation. 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 such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins such as butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 51858934 148 GSPPSTYKWYKDNTPLPEdPTKFPAFKNLTYKmnvfngnlefPSVSKmDTGSYFCEASNGEGVPQRGDEVKMEVR 222
Cdd:cd16082  24 GSPPISYVWYKEQTNNQE-PIKVAALSTLLFK----------PAVVA-DSGSYFCTAKGRVGSEQRSDIVKFVVK 86

Immunoglobulin V-set domain; This domain is found in antibodies as well as neural protein P0 and CTL4 amongst others.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 51858934    25 SPVKVKENEGVDLQCSYT-SDFGATPRVEWKFKDLKGSQT---LVYFDGKPTGQYTGRVT-----MYDKG-LRFNKVTRA 94
Cdd:pfam07686   4 REVTVALGGSVTLPCTYSsSMSEASTSVYWYRQPPGKGPTfliAYYSNGSEEGVKKGRFSgrgdpSNGDGsLTIQNLTLS 83

                          90       100
                  ....*....|....*....|....*.
gi 51858934    95 DTGDYDCEVSGSG-GYGENTIKLTVL 119
Cdd:pfam07686  84 DSGTYTCAVIPSGeGVFGKGTRLTVL 109

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 51858934    21 VTVTSPVKVKENEGVDLQCSYTSDfgATPRVEWkfkdlkgsqtlvYFDGKPTGQyTGRVTMYDKG----LRFNKVTRADT 96
Cdd:pfam07679   4 TQKPKDVEVQEGESARFTCTVTGT--PDPEVSW------------FKDGQPLRS-SDRFKVTYEGgtytLTISNVQPDDS 68

                          90       100
                  ....*....|....*....|..
gi 51858934    97 GDYDCEVSGSGGYGENTIKLTV 118
Cdd:pfam07679  69 GKYTCVATNSAGEAEASAELTV 90

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 51858934   136 SSNVRLTCFDPVGSPPSTYKWYKDNTPLPEDPTKFPAFKNltykmnVFNGNLEFPSVSKMDTGSYFCEASNGEGVPQR 213
Cdd:pfam00047  11 GDSATLTCSASTGSPGPDVTWSKEGGTLIESLKVKHDNGR------TTQSSLLISNVTKEDAGTYTCVVNNPGGSATL 82

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 51858934 121 PPAKPVSRIPSSVTTSSNVRLTCfDPVGSPPSTYKWYKDNTPLPEDptkfpaFKNLTYKMNVF---NGNLEFPSVSKMDT 197
Cdd:cd20954   1 PPRWIVEPVDANVAAGQDVMLHC-QADGFPTPTVTWKKATGSTPGE------YKDLLYDPNVRilpNGTLVFGHVQKENE 73

                        90
                ....*....|..
gi 51858934 198 GSYFCEASNGEG 209
Cdd:cd20954  74 GHYLCEAKNGIG 85

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 51858934 139 VRLTCFDPVGSPPSTYKWYKDNTPLPEDptkfPAFKnlTYKMNVFNGNLEFPSVSKMDTGSYFCEASNGEG 209
Cdd:cd20959  20 AQLHCGVPGGDLPLNIRWTLDGQPISDD----LGIT--VSRLGRRSSILSIDSLEASHAGNYTCHARNSAG 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 51858934 127 SRIPSSVTTSSNVRLTCfDPVGSPPSTYKWYKDNTPLPEDPTKFpAFKNLTYKMNVFNgnlefpsVSKMDTGSYFCEASN 206
Cdd:cd05730   9 SEVNATANLGQSVTLAC-DADGFPEPTMTWTKDGEPIESGEEKY-SFNEDGSEMTILD-------VDKLDEAEYTCIAEN 79

                ...
gi 51858934 207 GEG 209
Cdd:cd05730  80 KAG 82

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 51858934 128 RIPSSVT--TSSNVRLTCFdPVGSPPSTYKWYKDNTPLPedPTKfpafknltyKMNVFNGNLEFPSVSKMDTGSYFCEAS 205
Cdd:cd04968   6 RFPADTYalKGQTVTLECF-ALGNPVPQIKWRKVDGSPS--SQW---------EITTSEPVLEIPNVQFEDEGTYECEAE 73

                ....
gi 51858934 206 NGEG 209
Cdd:cd04968  74 NSRG 77

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
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 51858934 148 GSPPSTYKWYKDNTPLPEDPTKFPAFknltykmnvfNGNLEFPSVSKMDTGSYFCEASNGEG 209
Cdd:cd05731  21 GLPTPDIRWIKLGGELPKGRTKFENF----------NKTLKIENVSEADSGEYQCTASNTMG 72

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 51858934 125 PVSRIPSSVTTS-----SNVRLTCFdPVGSPPSTYKWYKDNTPLPEDPTKfpafknltYKMNVFNGNLEFPSVSKMDTGS 199
Cdd:cd20970   1 PVISTPQPSFTVtaregENATFMCR-AEGSPEPEISWTRNGNLIIEFNTR--------YIVRENGTTLTIRNIRRSDMGI 71

                ....*...
gi 51858934 200 YFCEASNG 207
Cdd:cd20970  72 YLCIASNG 79

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 51858934 137 SNVRLTCfDPVGSPPSTYKWYKDNTPLPEDPtkfpafknltyKMNVFNGNLEFPSVSKMDTGSYFCEASNGEG 209
Cdd:cd05728  15 SSLRWEC-KASGNPRPAYRWLKNGQPLASEN-----------RIEVEAGDLRITKLSLSDSGMYQCVAENKHG 75

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 51858934 124 KPVSRIPSSVTTSSNVRLTCfDPVGSPPSTYKWYKDNTPLPEDPtkfpafknlTYKMNVFNGNLEFPSVSKM-DTGSYFC 202
Cdd:cd04967   7 QPDDTIFPEDSDEKKVALNC-RARANPVPSYRWLMNGTEIDLES---------DYRYSLVDGTLVISNPSKAkDAGHYQC 76

                ....*..
gi 51858934 203 EASNGEG 209
Cdd:cd04967  77 LATNTVG 83

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 51858934 130 PSSVTTS--SNVRLTCfDPVGSPPSTYKWYKDNTPLPEDPTKfpafknltYKMNVFNGNLEFPSVSKMDTGSYFCEASNG 207
Cdd:cd04978   6 PPSLVLSpgETGELIC-EAEGNPQPTITWRLNGVPIEPAPED--------MRRTVDGRTLIFSNLQPNDTAVYQCNASNV 76

                ..
gi 51858934 208 EG 209
Cdd:cd04978  77 HG 78

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 51858934 130 PSSVTTSSN--VRLTCfDPVGSPPSTYKWYKDNTPLPEDPTKFPafknlTYKMNVFNGNLEFPSV-----SKMDTGSYFC 202
Cdd:cd07693   7 PSDLIVSKGdpATLNC-KAEGRPTPTIQWLKNGQPLETDKDDPR-----SHRIVLPSGSLFFLRVvhgrkGRSDEGVYVC 80

                ....*...
gi 51858934 203 EASNGEGV 210
Cdd:cd07693  81 VAHNSLGE 88

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
                ....*....|....*....|....*....|....*....|....*.
gi 51858934 119 LVPPAKPV-SRIPSSVTTSSNVRLTCFDPVGSPPSTYKWYKDNTPL 163
Cdd:cd05761   1 LGVPEKPViTGFTSPVVEGDEITLTCTTSGSKPAADIRWFKNDKEL 46

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 51858934 125 PVSRIpSSVTTSSNVRLTCfDPVGSPPSTYKWYKDNtplpedptkfpafKNLTYKMNVF---NGNLEFPSVSKMDTGSYF 201
Cdd:cd04969   7 PVKKK-ILAAKGGDVIIEC-KPKASPKPTISWSKGT-------------ELLTNSSRICilpDGSLKIKNVTKSDEGKYT 71

                ....*
gi 51858934 202 CEASN 206
Cdd:cd04969  72 CFAVN 76