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 1242768283 412 GPPEIKSKATQFAEPDLDGKVSCLVRSVPYPDQILWVRDNKIIDYAQSGRYSITQTQMADGVENILHISHLTPSDF-GQY 490
Cdd:cd05898     1 GPPIISSEQVQYAVRGERGKVKCFIGSTPPPDRIAWAWKENVLESGTLERYTVERTSTGSGVLSTLTINNIMEADFqTHY 80

                          90
                  ....*....|....*..
gi 1242768283 491 ICTVFNGYGNDTMSITL 507
Cdd:cd05898    81 NCTAWNSFGSGTAIIQL 97

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 1242768283 327 PKFIGVNQYIPVDLDKSVTLTCNATGNPPPQIRWRRSDSQTPLS---------ETTTLTIPGIQRADLGLYICEASALYG 397
Cdd:pfam07679   1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSdrfkvtyegGTYTLTISNVQPDDSGKYTCVATNSAG 80

                  ....*
gi 1242768283 398 AFTTK 402
Cdd:pfam07679  81 EAEAS 85

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1242768283 239 KPIITMSHNITRpmkENDYVRFSCDGDANPrEVQWRWLRDGHLIRGQTRSYldIPQISSDyHQNTIACEATNTIG---SS 315
Cdd:pfam13895   1 KPVLTPSPTVVT---EGEPVTLTCSAPGNP-PPSYTWYKDGSAISSSPNFF--TLSVSAE-DSGTYTCVARNGRGgkvSN 73

                  ....*
gi 1242768283 316 MAEIT 320
Cdd:pfam13895  74 PVELT 78

Fifth immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3 protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3 protein (also known as Neph2). This protein has five Ig-like domains, one transmembrane domain, and a cytoplasmic tail. Included in this group is mammalian Kirrel (Neph1). These proteins contain multiple Ig domains, have properties of cell adhesion molecules, and are important in organ development. Neph1 and 2 may mediate axonal guidance and synapse formation in certain areas of the CNS. In the kidney they participate in the formation of the slit diaphragm.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1242768283 412 GPPEIKSKATQFAEPDLDGKVSCLVRSVPYPDQILWVRDNKIIDYAQSGRYSITQTQMADGVENILHISHLTPSDF-GQY 490
Cdd:cd05898     1 GPPIISSEQVQYAVRGERGKVKCFIGSTPPPDRIAWAWKENVLESGTLERYTVERTSTGSGVLSTLTINNIMEADFqTHY 80

                          90
                  ....*....|....*..
gi 1242768283 491 ICTVFNGYGNDTMSITL 507
Cdd:cd05898    81 NCTAWNSFGSGTAIIQL 97

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1242768283 327 PKFIGVNQYIPVDLDKSVTLTCNATGNPPPQIRWRRSDSQTPLS---------ETTTLTIPGIQRADLGLYICEASALYG 397
Cdd:pfam07679   1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSdrfkvtyegGTYTLTISNVQPDDSGKYTCVATNSAG 80

                  ....*
gi 1242768283 398 AFTTK 402
Cdd:pfam07679  81 EAEAS 85

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1242768283  338 VDLDKSVTLTCNATGNPPPQIRWRRSDSQTPL----------SETTTLTIPGIQRADLGLYICEASALYG 397
Cdd:smart00410   6 VKEGESVTLSCEASGSPPPEVTWYKQGGKLLAesgrfsvsrsGSTSTLTISNVTPEDSGTYTCAATNSSG 75

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1242768283 132 IAPPKPPLidGGQVKSLVLgvptniTCRADGGKPAPQMLWYKEGTGRIANNTYTiaTTDEVTKVTDVIGIVTLKATSDDH 211
Cdd:pfam08205   3 IEPPASLL--EGEGPEVVA------TCSSAGGKPAPRITWYLDGKPLEAAETSS--EQDPESGLVTVTSELKLVPSRSDH 72

                          90
                  ....*....|....
gi 1242768283 212 EKRIECQAKNEALR 225
Cdd:pfam08205  73 GQSLTCQVSYGALR 86

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1242768283 433 SCLVRSVPYPdQILWVRDNKIIdyAQSGRYSITqtqmADGVENILHISHLTPSDFGQYICTVFNGYGNDTMSITLA 508
Cdd:pfam07679  21 TCTVTGTPDP-EVSWFKDGQPL--RSSDRFKVT----YEGGTYTLTISNVQPDDSGKYTCVATNSAGEAEASAELT 89

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1242768283 239 KPIITMSHNITRpmkENDYVRFSCDGDANPrEVQWRWLRDGHLIRGQTRSYldIPQISSDyHQNTIACEATNTIG---SS 315
Cdd:pfam13895   1 KPVLTPSPTVVT---EGEPVTLTCSAPGNP-PPSYTWYKDGSAISSSPNFF--TLSVSAE-DSGTYTCVARNGRGgkvSN 73

                  ....*
gi 1242768283 316 MAEIT 320
Cdd:pfam13895  74 PVELT 78

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1) and similar proteins; The members here are composed of the fourth immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. Also included in this group is NCAM-2 (also known as OCAM/mamFas II and RNCAM) NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE). One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1242768283 239 KPIITMSHNITrpMKENDYVRFSCDGDANP-REVQWRWLRDGH-----------LIRGQTR-SYLDIPQIS-SDYHQntI 304
Cdd:cd05732     2 QPKITYLENQT--AVELEQITLTCEAEGDPiPEITWRRATRGIsfeegdldgriVVRGHARvSSLTLKDVQlTDAGR--Y 77

                          90
                  ....*....|....*....
gi 1242768283 305 ACEATNTIGSSMAEITLDI 323
Cdd:cd05732    78 DCEASNRIGGDQQSMYLEV 96

Fifth immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3 protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3 protein (also known as Neph2). This protein has five Ig-like domains, one transmembrane domain, and a cytoplasmic tail. Included in this group is mammalian Kirrel (Neph1). These proteins contain multiple Ig domains, have properties of cell adhesion molecules, and are important in organ development. Neph1 and 2 may mediate axonal guidance and synapse formation in certain areas of the CNS. In the kidney they participate in the formation of the slit diaphragm.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1242768283 412 GPPEIKSKATQFAEPDLDGKVSCLVRSVPYPDQILWVRDNKIIDYAQSGRYSITQTQMADGVENILHISHLTPSDF-GQY 490
Cdd:cd05898     1 GPPIISSEQVQYAVRGERGKVKCFIGSTPPPDRIAWAWKENVLESGTLERYTVERTSTGSGVLSTLTINNIMEADFqTHY 80

                          90
                  ....*....|....*..
gi 1242768283 491 ICTVFNGYGNDTMSITL 507
Cdd:cd05898    81 NCTAWNSFGSGTAIIQL 97

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1242768283 138 PLIDGGQVKSLVLGVPTNITCRADGGKPAPQMLWYKEGTgRIANNTYTIATTDEVTKVTdVIGIVTLKATSDDHEKRIEC 217
Cdd:cd05759     2 PVIEGGPVISLQAGVPYNLTCRARGAKPAAEIIWFRDGE-QLEGAVYSKELLKDGKRET-TVSTLLITPSDLDTGRTFTC 79

                          90
                  ....*....|....*....
gi 1242768283 218 QAKNEALRDPLSTSVILNV 236
Cdd:cd05759    80 RARNEAIPNGKETSITLDV 98

Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; Members here are composed the fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1, Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1242768283 338 VDLDKSVTLTCNATGNPPPQIRWRRSDSQTPL--------------SETTTLTIPGIQRADLGLYICEASALYGAFTTKK 403
Cdd:cd05726    11 VALGRTVTFQCETKGNPQPAIFWQKEGSQNLLfpyqppqpssrfsvSPTGDLTITNVQRSDVGYYICQALNVAGSILAKA 90

                  .
gi 1242768283 404 L 404
Cdd:cd05726    91 Q 91

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
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1242768283 344 VTLTCNATGNPPPQIRWRRSD-SQTPLSETTT----LTIPGIQRADLGLYICEA 392
Cdd:cd04968    19 VTLECFALGNPVPQIKWRKVDgSPSSQWEITTsepvLEIPNVQFEDEGTYECEA 72

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1242768283 340 LDKSVTLTCNATGNPPPQIRWRRSDSQTPLS-----ETTTLTIPGIQRADLGLYICEASALYGAFTTK 402
Cdd:cd05725    11 VDDSAEFQCEVGGDPVPTVRWRKEDGELPKGryeilDDHSLKIRKVTAGDMGSYTCVAENMVGKIEAS 78

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1242768283 344 VTLTCNATGNPPPQIRWRRSDSQTPLSETT---------TLTIPGIQRADLGLYICEAS 393
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDsrrselgngTLTISNVTLEDSGTYTCVAS 59

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1242768283 340 LDKSVTLTCNATGNPPPQIRWRRSDSQTPLS-ETTT----LTIPGIQRADLGLYICEASALYG 397
Cdd:cd05851    15 KGQNVTLECFALGNPVPVIRWRKILEPMPATaEISMsgavLKIFNIQPEDEGTYECEAENIKG 77

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1242768283 132 IAPPKPPLidGGQVKSLVLgvptniTCRADGGKPAPQMLWYKEGTGRIANNTYTiaTTDEVTKVTDVIGIVTLKATSDDH 211
Cdd:pfam08205   3 IEPPASLL--EGEGPEVVA------TCSSAGGKPAPRITWYLDGKPLEAAETSS--EQDPESGLVTVTSELKLVPSRSDH 72

                          90
                  ....*....|....
gi 1242768283 212 EKRIECQAKNEALR 225
Cdd:pfam08205  73 GQSLTCQVSYGALR 86

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1242768283 134 PPKPPLIDGgQVKSLVLGVPTNITCRADGGKPAPQMLWYK-----EGTGRI----ANNTYTIATTdevtkvtdvigiVTL 204
Cdd:cd05761     3 VPEKPVITG-FTSPVVEGDEITLTCTTSGSKPAADIRWFKndkelKGVKEVqesgAGKTFTVTST------------LRF 69

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1242768283 205 KATSDDHEKRIECQAKNEALRD-PLSTSVILNV 236
Cdd:cd05761    70 RVDRDDDGVAVICRVDHESLTStPKQTQQVLEV 102

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1242768283   31 PENEKSIIGGRIQLKCVVK-NRSGIVQWTKDGFGLgndrdLPPYPRYRMVGGRTEvnndiieeFSLEITDVQLEDDGKYN 109
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASgSPPPEVTWYKQGGKL-----LAESGRFSVSRSGST--------STLTISNVTPEDSGTYT 67

                           90       100
                   ....*....|....*....|..
gi 1242768283  110 CQVTPTdddpRVLLSQEVTVTV 131
Cdd:smart00410  68 CAATNS----SGSASSGTTLTV 85

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1242768283 344 VTLTCNATGNPPPQIRWR---------RSDSQTPLSETTTLTIPGIQRADLGLYICEA 392
Cdd:cd05743     4 VEFTCVATGVPTPIINWRlnwghvpdsARVSITSEGGYGTLTIRDVKESDQGAYTCEA 61

First immunoglobulin (Ig)-like domain of Axl receptor tyrosine kinase (RTK), and similar domains; member of the I-set Ig domains; The members here are composed of the first immunoglobulin (Ig)-like domain of Axl receptor tyrosine kinase (RTK). Axl together with Tyro3 and Mer form the Axl/Tyro3 family of receptor tyrosine kinases (RTKs). This family includes Axl (also known as Ark, Ufo, and Tyro7), Tyro3 (also known as Sky, Rse, Brt, Dtk, and Tif), and Mer (also known as Nyk, c-Eyk, and Tyro12). Axl/Tyro3 family receptors have an extracellular portion with two Ig-like domains followed by two fibronectin-types III (FNIII) domains, a membrane-spanning single helix, and a cytoplasmic tyrosine kinase domain. Axl, Tyro3 and Mer are widely expressed in adult tissues, though they show higher expression in the brain, in the lymphatic and vascular systems, and in the testis. Axl, Tyro3, and Mer bind the vitamin K dependent protein Gas6 with high affinity, and in doing so activate their tyrosine kinase activity. Axl/Gas6 signaling may play a part in cell adhesion processes, prevention of apoptosis, and cell proliferation. Ig superfamily 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 Axl 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 1242768283 428 LDGKVSCLVRSVPYPDQILWVRDNKIIDYAQSgrysiTQTQMADG--------VENILHISHLTPSDFGQYICTVFNGYG 499
Cdd:cd20966    16 LTGTLRCQLQVQGEPPEVHWLRDGQILELADS-----TQTQVPLGedeqddwiVVSQLRITSLQLSDTGQYQCLVFLGHQ 90

                  .
gi 1242768283 500 N 500
Cdd:cd20966    91 T 91

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 1242768283 332 VNQYIPVDLDKSVTLTCNA-TGNPPPQIRWRRSDSQTPLSE----------TTTLTIPGIQRADLGLYICEAS 393
Cdd:pfam00047   2 APPTVTVLEGDSATLTCSAsTGSPGPDVTWSKEGGTLIESLkvkhdngrttQSSLLISNVTKEDAGTYTCVVN 74

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 1242768283  39 GGRIQLKCVVKNRSGI----VQWTKDGFGLGNDRDLPPYPRYRMV---GGRTEVNNDIIE-EFSLEITDVQLEDDGKYNC 110
Cdd:pfam07686  11 GGSVTLPCTYSSSMSEastsVYWYRQPPGKGPTFLIAYYSNGSEEgvkKGRFSGRGDPSNgDGSLTIQNLTLSDSGTYTC 90

                          90       100
                  ....*....|....*....|.
gi 1242768283 111 QVTPtddDPRVLLSQEVTVTV 131
Cdd:pfam07686  91 AVIP---SGEGVFGKGTRLTV 108

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 1242768283 432 VSCLVRSVPYPdQILWVRDNKIIDYAQSGRYSItqtqmaDGVENILHISHLTPSDFGQYICTVFNGYG 499
Cdd:cd00096     3 LTCSASGNPPP-TITWYKNGKPLPPSSRDSRRS------ELGNGTLTISNVTLEDSGTYTCVASNSAG 63

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1242768283  31 PENEKSIIGGRIQLKCVVknrSG----IVQWTKDGfglgndRDLPPYPRYRMvggrTEVNNDiieeFSLEITDVQLEDDG 106
Cdd:pfam07679   7 PKDVEVQEGESARFTCTV---TGtpdpEVSWFKDG------QPLRSSDRFKV----TYEGGT----YTLTISNVQPDDSG 69

                  ....*..
gi 1242768283 107 KYNCQVT 113
Cdd:pfam07679  70 KYTCVAT 76

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1242768283 239 KPIITMSHNITRpmkENDYVRFSCDGDANPrEVQWRWLRDGHLIRGQTRSYldIPQISSDyHQNTIACEATNTIG---SS 315
Cdd:pfam13895   1 KPVLTPSPTVVT---EGEPVTLTCSAPGNP-PPSYTWYKDGSAISSSPNFF--TLSVSAE-DSGTYTCVARNGRGgkvSN 73

                  ....*
gi 1242768283 316 MAEIT 320
Cdd:pfam13895  74 PVELT 78

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1242768283 338 VDLDKSVTLTCNATGNPPPQIRWRR------SDSQTPLSETTTLTIPGIQRADLGLYIC 390
Cdd:cd20957    13 VDFGRTAVFNCSVTGNPIHTVLWMKdgkplgHSSRVQILSEDVLVIPSVKREDKGMYQC 71

Second immunoglobulin (Ig) domain of poliovirus receptor (PVR, also known as CD155 and Necl-5), and similar domains; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig) domain of poliovirus receptor (PVR, also known as CD155 and nectin-like protein 5 (Necl-5)) and similar proteins. Poliovirus (PV) binds to its cellular receptor (PVR/CD155) to initiate infection. CD155 is a membrane-anchored, single-span glycoprotein; its extracellular region has three Ig-like domains. There are four different isotypes of CD155 (referred to as alpha, beta, gamma, and delta), these result from alternate splicing of the CD155 mRNA, and have identical extracellular domains. CD155-beta and CD155-gamma are secreted, while CD155-alpha and CD155-delta are membrane-bound and function as PV receptors. The virus recognition site is contained in the amino-terminal domain, D1. Having the virus attachment site on the receptor distal from the plasma membrane may be important for successful initiation of infection of cells by the virus. CD155 binds in the poliovirus "canyon" and has a footprint similar to that of the intercellular adhesion molecule-1 receptor on human rhinoviruses. This group also includes the second Ig-like domain of nectin-1, also known as poliovirus receptor related protein(PVRL)1 or CD111.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1242768283 135 PKPPLIdgGQVKSLVLGVPTNI-TCRADGGKPAPQMLWYKEgTGRIANNTYTIATTDEVTkvtdVIGIVTLKATSDDHEK 213
Cdd:cd05719     1 PTNSLE--GGPALLIGGEPTLVaTCISANGKPPASVTWETD-LKGEASTTQVRGSNGTVT----VTSRYRLVPSREADGQ 73

                          90       100
                  ....*....|....*....|...
gi 1242768283 214 RIECQAKNEALRDPLSTSVILNV 236
Cdd:cd05719    74 PLTCVVEHPSLEKDQRISVTLNV 96

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1242768283 337 PVDLD----KSVTLTCNATGNPPPQIRWRRSDSQTP-------------LSETTTLTIPGIQRADLGLYICEAS 393
Cdd:cd20954     8 PVDANvaagQDVMLHCQADGFPTPTVTWKKATGSTPgeykdllydpnvrILPNGTLVFGHVQKENEGHYLCEAK 81

First immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR). Fibroblast growth factors (FGFs) participate in morphogenesis, development, angiogenesis, and wound healing. These FGF-stimulated processes are mediated by four FGFR tyrosine kinases (FGRF1-4). FGFRs are comprised of an extracellular portion consisting of three Ig-like domains, a transmembrane helix, and a cytoplasmic portion having protein tyrosine kinase activity. The highly conserved Ig-like domains 2 and 3, and the linker region between D2 and D3 define a general binding site for all FGFs.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1242768283  30 EPENEKSIIGGRIQLKCVVKNRSGIVQWTKDGFglgndrDLPPYPRYRMVGgrtevnndiiEEfsLEITDVQLEDDGKYN 109
Cdd:cd04973    15 EVESYSAHPGDLLQLRCRLRDDVQSINWTKDGV------QLGENNRTRITG----------EE--VQIKDAVPRDSGLYA 76

                          90
                  ....*....|....*...
gi 1242768283 110 CQVTPTDDDPRVLLSQEV 127
Cdd:cd04973    77 CVTSSPSGSDTTYFSVNV 94

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); 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, 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 the chicken neuron-glia cell adhesion molecule, Ng-CAM.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1242768283 342 KSVTLTCNATGNPPPQIRWRRSDSQTPLSETT------TLTIPGIQRADLGLYICEA 392
Cdd:cd05876    11 QSLVLECIAEGLPTPTVKWLRPSGPLPPDRVKyqnhnkTLQLLNVGESDDGEYVCLA 67

Fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell adhesion molecule 5 (CEACAM5) and similar domains; member of the C2-set IgSF domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell adhesion molecule 5 (CEACAM5) and similar domains. The CEA family is a group of anchored or secreted glycoproteins, expressed by epithelial cells, leukocytes, endothelial cells and placenta. The CEA family is divided into the CEACAM and pregnancy-specific glycoprotein (PSG) subfamilies. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), also known as CD66e (Cluster of Differentiation 66e), is a cell surface glycoprotein that plays a role in cell adhesion, intracellular signaling and tumor progression. Diseases associated with CEACAM5 include lung cancer and rectum cancer. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1242768283 341 DKSVTLTCNATGNPPPQIRWRRSDsqTPLSETTTLTIPGIQRADLGLYICEAS 393
Cdd:cd20948    10 GENLNLSCHAASNPPAQYSWTING--TFQTSSQELFLPAITENNEGTYTCSAH 60

C-terminal immunoglobulin (Ig)-like domain of M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of M-protein (also known as myomesin-2). M-protein is a structural protein localized to the M-band, a transverse structure in the center of the sarcomere, and is a candidate for M-band bridges. M-protein is modular consisting mainly of repetitive IG-like and fibronectin type III (FnIII) domains and has a muscle-type specific expression pattern. M-protein is present in fast fibers.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1242768283 342 KSVTLTCNATGNPPPQIRWRRSDSQTPLSET----------TTLTIPGIQRADLGLYICEASALYGAfttKKLDV 406
Cdd:cd05891    17 KTLNLTCTVFGNPDPEVIWFKNDQDIELSEHysvkleqgkyASLTIKGVTSEDSGKYSINVKNKYGG---ETVDV 88