Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568922990  132 PPKIYDISNDMTINEGTNVTLTCLATGKPEPVISWRH--------ISPSAKPFENGQYLDIYGITRDQAGEYECSAEN 201
Cdd:pfam13927   1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKngepissgSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568922990  219 PTIQEIKSGT-VTPGRSGLIRCEGAGVPPPAFEWYKGEKRLFNGQQGIIIQNFSTrSILTVTNVTQEHFGNYTCVAAN 295
Cdd:pfam13927   2 PVITVSPSSVtVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSGSN-STLTISNVTRSDAGTYTCVASN 78

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922990 219 PTIQEIKSGTVTPGRSGLIRCEGAGV-PPPAFEWYKGEKRLFNGQ-QGIIIQNFSTRSILTVTNVTQEHFGNYTCVAANK 296
Cdd:cd05750    1 PKLKEMKSQTVQEGSKLVLKCEATSEnPSPRYRWFKDGKELNRKRpKNIKIRNKKKNSELQINKAKLEDSGEYTCVVENI 80

                 ....*..
gi 568922990 297 LGTTNAS 303
Cdd:cd05750   81 LGKDTVT 87

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922990   139 SNDMTINEGTNVTLTCLATGKPEPVISWRHISP---------SAKPFENGQYLDIYGITRDQAGEYECSAENDvSFPDVK 209
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGkllaesgrfSVSRSGSTSTLTISNVTPEDSGTYTCAATNS-SGSASS 79

                   ....*.
gi 568922990   210 KVRVIV 215
Cdd:smart00410  80 GTTLTV 85

First (N-terminal) immunoglobulin (Ig)-like domain of the nectin-like molecules; member of the V-set of Ig superfamily (IgSF) domains; The members here are composed of the N-terminal immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 (also known as cell adhesion molecule 3 (CADM3)), Necl-2 (CADM1), Necl-3 (CADM2), and similar proteins. At least five nectin-like molecules have been identified (Necl-1 to Necl-5). They all have an extracellular region containing three Ig-like domains, a transmembrane region, and a 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, Necl-2, and Necl-3 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 accumulates in central and peripheral nervous system tissue and has been shown to selectively interact with oligodendrocytes. This group also contains Class-I MHC-restricted T-cell-associated molecule (CRTAM), whose expression pattern is consistent with its expression in Class-I MHC-restricted T-cells.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922990  38 AVDNMLVRKGDTAVLRCYLEDGA-SKGAWLNRSS-IIFAGGDKWSVDPRVSISTLNKRDYSLQIQNVDVTDDGPYTCSVQ 115
Cdd:cd05717    2 HTQDVTVVEGETLTLKCQVSLRDdSSLQWLNPNGqTIYFNDKRALRDSRYQLLNHSASELSISVSNVTLSDEGVYTCLHY 81

                         90
                 ....*....|....
gi 568922990 116 TQhTPRTMQVHLTV 129
Cdd:cd05717   82 TD-PVSTKKVTVTV 94

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568922990  219 PTIQEIKSGT-VTPGRSGLIRCEGAGVPPPAFEWYKGEKRLFNGQQGIIIQNFSTrSILTVTNVTQEHFGNYTCVAAN 295
Cdd:pfam13927   2 PVITVSPSSVtVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSGSN-STLTISNVTRSDAGTYTCVASN 78

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922990 219 PTIQEIKSGTVTPGRSGLIRCEGAGV-PPPAFEWYKGEKRLFNGQ-QGIIIQNFSTRSILTVTNVTQEHFGNYTCVAANK 296
Cdd:cd05750    1 PKLKEMKSQTVQEGSKLVLKCEATSEnPSPRYRWFKDGKELNRKRpKNIKIRNKKKNSELQINKAKLEDSGEYTCVVENI 80

                 ....*..
gi 568922990 297 LGTTNAS 303
Cdd:cd05750   81 LGKDTVT 87

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922990  221 IQEIKSGTVTPGRSGLIRCEGAGVPPPAFEWYKGEKRLfNGQQGIIIQNFSTRSILTVTNVTQEHFGNYTCVAANKLG-- 298
Cdd:pfam07679   4 TQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPL-RSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSAGea 82

                  ....*.
gi 568922990  299 TTNASL 304
Cdd:pfam07679  83 EASAEL 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568922990 237 IRCEGAGVPPPAFEWYKGEKRLFNGQQGIIiQNFSTRSILTVTNVTQEHFGNYTCVAANKLGTTNAS 303
Cdd:cd00096    3 LTCSASGNPPPTITWYKNGKPLPPSSRDSR-RSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASA 68

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 568922990 132 PPKIYDISNDMTINEGTNVTLTCLATGKPEPVISWRHI----SPSAKPFENGQYLDIYGITRDQAGEYECSAENdVSFPD 207
Cdd:cd05851    1 PADINVKFKDTYALKGQNVTLECFALGNPVPVIRWRKIlepmPATAEISMSGAVLKIFNIQPEDEGTYECEAEN-IKGKD 79

                 ....*...
gi 568922990 208 VKKVRVIV 215
Cdd:cd05851   80 KHQARVYV 87

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922990   139 SNDMTINEGTNVTLTCLATGKPEPVISWRHISP---------SAKPFENGQYLDIYGITRDQAGEYECSAENDvSFPDVK 209
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGkllaesgrfSVSRSGSTSTLTISNVTPEDSGTYTCAATNS-SGSASS 79

                   ....*.
gi 568922990   210 KVRVIV 215
Cdd:smart00410  80 GTTLTV 85

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 568922990 219 PTI---QEIKSGTVTPGRSGLIRCEGAGVPPPAFEWYKGEKRLFNGQQGIIIQNFStrSILTVTNVTQEHFGNYTCVAAN 295
Cdd:cd05730    2 PTIrarQSEVNATANLGQSVTLACDADGFPEPTMTWTKDGEPIESGEEKYSFNEDG--SEMTILDVDKLDEAEYTCIAEN 79

                         90
                 ....*....|....
gi 568922990 296 KLGTTNASLPLNLW 309
Cdd:cd05730   80 KAGEQEAEIHLKVF 93

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922990  222 QEIKSGTVTPGRSGLIRCEG-AGVPPPAFEWYKGEKRLFNGQQGIIIQNFSTRSILTVTNVTQEHFGNYTCVAANKLGTT 300
Cdd:pfam00047   1 SAPPTVTVLEGDSATLTCSAsTGSPGPDVTWSKEGGTLIESLKVKHDNGRTTQSSLLISNVTKEDAGTYTCVVNNPGGSA 80

                  ....*.
gi 568922990  301 NASLPL 306
Cdd:pfam00047  81 TLSTSL 86

Fourth 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 fourth 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 568922990 132 PPKIYDISNDMTINEGTNVTLTCLATGKPEPVISW----RHISPSAKpFENGQY----------LDIYGITRDQAGEYEC 197
Cdd:cd20956    1 APVLLETFSEQTLQPGPSVSLKCVASGNPLPQITWtldgFPIPESPR-FRVGDYvtsdgdvvsyVNISSVRVEDGGEYTC 79

                 ....*..
gi 568922990 198 SAENDVS 204
Cdd:cd20956   80 TATNDVG 86

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 568922990 132 PP--KIYDISNDMTINEGTNVTLTCLATGKPEPVISWRHispSAKPFENGQ----------YLDIYGITRDQAGEYECSA 199
Cdd:cd05730    1 PPtiRARQSEVNATANLGQSVTLACDADGFPEPTMTWTK---DGEPIESGEekysfnedgsEMTILDVDKLDEAEYTCIA 77

                 ..
gi 568922990 200 EN 201
Cdd:cd05730   78 EN 79

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 568922990 150 VTLTCLATGKPEPVISWRH--------ISPSAKPFENGQYLDIYGITRDQAGEYECSAENDV 203
Cdd:cd00096    1 VTLTCSASGNPPPTITWYKngkplppsSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSA 62

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568922990 141 DMTINEGTNVTLTCLATGKPEPVISWRH-------ISPSAKPFENGQyLDIYGITRDQAGEYECSAEN 201
Cdd:cd20952    8 NQTVAVGGTVVLNCQATGEPVPTISWLKdgvpllgKDERITTLENGS-LQIKGAEKSDTGEYTCVALN 74

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922990 219 PTI--QEIKSGTVTPGRSGLIRCEGAGVPPPAFEWYKgEKRLFNGQQG--IIIQNFSTRSILTVTNVTQEHF-GNYTCVA 293
Cdd:cd05733    1 PTIteQSPKDYIVDPRDNITIKCEAKGNPQPTFRWTK-DGKFFDPAKDprVSMRRRSGTLVIDNHNGGPEDYqGEYQCYA 79

                 ....*.
gi 568922990 294 ANKLGT 299
Cdd:cd05733   80 SNELGT 85

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568922990  143 TINEGTNVTLTCLATGKPEPVISWR----HISPSAKPFengqyldIYGITRDQAGEYECSAENDVSFPDVKKVRVIV 215
Cdd:pfam13895  10 VVTEGEPVTLTCSAPGNPPPSYTWYkdgsAISSSPNFF-------TLSVSAEDSGTYTCVARNGRGGKVSNPVELTV 79

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568922990 243 GVPPPAFEWYKGEKRLFNGQQgIIIQNFSTRSILTVTNVTQEHFGNYTCVAANKLGTTNASL 304
Cdd:cd05748   18 GRPTPTVTWSKDGQPLKETGR-VQIETTASSTSLVIKNAKRSDSGKYTLTLKNSAGEKSATI 78

Fifth immunoglobulin (Ig) domain of contactin-1; The members here are composed of the fifth 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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568922990 236 LIRCEGAGVPPPAFEWYKGEKRLFNGQQGIIIQNFStrsiLTVTNVTQEHFGNYTCVAANKLGTTNAS 303
Cdd:cd05852   21 IIECKPKAAPKPKFSWSKGTELLVNNSRISIWDDGS----LEILNITKLDEGSYTCFAENNRGKANST 84

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted, and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568922990 150 VTLTCLATGKPEPVISWR------------HISPSAkpfengqYLDIYGITRDQAGEYECSAENDVSFPDVKKV 211
Cdd:cd05746    1 VQIPCSAQGDPEPTITWNkdgvqvtesgkfHISPEG-------YLAIRDVGVADQGRYECVARNTIGYASVSMV 67

Eighth immunoglobulin (Ig)-like domain of human myosin light-chain kinase (MLCK) and similar protein; member of the I-set of IgSF domains; The members here are composed of the eighth immunoglobulin (Ig)-like domain of human myosin light-chain kinase (MLCK) and similar proteins. Myosin light-chain kinase (MLCK) is a key regulator of different forms of cell motility involving actin and myosin II. Agonist stimulation of smooth muscle cells increases cytosolic Ca2+ which binds calmodulin. This Ca2+-calmodulin complex in turn binds to and activates MLCK. Activated MLCK leads to the phosphorylation of the 20 kDa myosin regulatory light chain (RLC) of myosin II and the stimulation of actin-activated myosin MgATPase activity. MLCK is widely present in vertebrate tissues; it phosphorylates the 20 kDa RLC of both smooth and nonmuscle myosin II. Phosphorylation leads to the activation of the myosin motor domain and altered structural properties of myosin II. In smooth muscle MLCK it is involved in initiating contraction. In nonmuscle cells, MLCK may participate in cell division and cell motility; it has been suggested MLCK plays a role in cardiomyocyte differentiation and contraction through regulation of nonmuscle myosin II.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922990 205 FPDVKKVRVivnfaptiqeiksgtvtpGRSGLIRCEGAGVPPPAFEWYKGEKRLFNGQqGIIIQNFSTRSILTVTNVTQE 284
Cdd:cd05762    7 FPEDMKVRA------------------GESVELFCKVTGTQPITCTWMKFRKQIQEGE-GIKIENTENSSKLTITEGQQE 67

                         90       100
                 ....*....|....*....|....
gi 568922990 285 HFGNYTCVAANKLGTTNASLPLNL 308
Cdd:cd05762   68 HCGCYTLEVENKLGSRQAQVNLTV 91

First (N-terminal) immunoglobulin (Ig)-like domain of nectin-like molecule-3; member of the V-set of Ig superfamily (IgSF) domains; The members here are composed of the N-terminal immunoglobulin (Ig)-like domain of nectin-like molecule-3, Necl-3 (also known as cell adhesion molecule 2 (CADM2), SynCAM2, IGSF4D). Nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 - Necl-5). They all have an extracellular region containing three Ig-like domains, a transmembrane region, and a 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-3 accumulates in central and peripheral nervous system tissue, and has been shown to selectively interact with oligodendrocytes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922990  39 VDNMLVRKGDTAVLRCYLEDGASKG-AWLNRSSIIFAGGDKWSV-DPRVSISTLNKRDYSLQIQNVDVTDDGPYTCSVQT 116
Cdd:cd07701    4 TQNVTVVEGGTANLTCRVDQNDNTSlQWSNPAQQTLYFDDKKALrDNRIELVRASWHELSISISDVSLSDEGQYTCSLFT 83

                         90
                 ....*....|...
gi 568922990 117 QHTpRTMQVHLTV 129
Cdd:cd07701   84 MPV-KTSKAYLTV 95

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 568922990 131 VPPKIYDISNDMTInEGTNVTLTCLATGKPEPVISW----RHISPSAKPFE-----NGQY----LDIYGITRDQAGEYEC 197
Cdd:cd05732    1 VQPKITYLENQTAV-ELEQITLTCEAEGDPIPEITWrratRGISFEEGDLDgrivvRGHArvssLTLKDVQLTDAGRYDC 79

                 ....
gi 568922990 198 SAEN 201
Cdd:cd05732   80 EASN 83

First (N-terminal) immunoglobulin (Ig)-like domain of nectin-like molecule-1 (Necl-1); member of the V-set of Ig superfamily (IgSF) domains; The members here are composed of the N-terminal immunoglobulin (Ig)-like domain of nectin-like molecule-1, Necl-1 (also known as celll adhesion molecule 3 (CADM3), SynCAM2, or IGSF4). Nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 - Necl-5). They all have an extracellular region containing three Ig-like domains, a transmembrane region, and a 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 has 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922990  35 PWAAvdNMLVRKGDTAVLRCYLEDGA-SKGAWLNRSSIIFAGGDKWSV-DPRVSISTLNKRDYSLQIQNVDVTDDGPYTC 112
Cdd:cd05882    2 PVTQ--DETVAVGGTVTLKCGVKEHDnSSLQWSNTAQQTLYFGEKRALrDNRIQLVKSTPTELIISISNVQLSDEGEYTC 79

                         90
                 ....*....|....*..
gi 568922990 113 SVQTQHTpRTMQVHLTV 129
Cdd:cd05882   80 SIFTMPV-RTAKATVTV 95

Immunoglobulin (Ig)-like domain of human neurofascin (NF); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of human neurofascin (NF). NF 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 a cytoplasmic domain. NF has many alternatively spliced isoforms having different temporal expression patterns during development. NF participates in axon subcellular targeting and synapse formation, however little is known of the functions of the different isoforms. 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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922990 219 PTI--QEIKSGTVTPGRSGLIRCEGAGVPPPAFEWYKgEKRLFN----------GQQGIIIQNFSTRSiltvtnVTQEHF 286
Cdd:cd05875    1 PTItkQSAKDYIVDPRDNILIECEAKGNPVPTFHWTR-NGKFFNvakdprvsmrRRSGTLVIDFRGGG------RPEDYE 73

                         90
                 ....*....|...
gi 568922990 287 GNYTCVAANKLGT 299
Cdd:cd05875   74 GEYQCFARNKFGT 86

Immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins; member of the I-set of IgSF domains; This group contains the immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins. The SALM (for synaptic adhesion-like molecules; also known as Lrfn for leucine-rich repeat and fibronectin type III domain containing) family of adhesion molecules consists of five known members: SALM1/Lrfn2, SALM2/Lrfn1, SALM3/Lrfn4, SALM4/Lrfn3, and SALM5/Lrfn5. SALMs share a similar domain structure, containing leucine-rich repeats (LRRs), an immunoglobulin (Ig) domain, and a fibronectin III (FNIII) domain, followed by a transmembrane domain and a C-terminal PDZ-binding motif. SALM5 is implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons. SALM5 interacts with the Ig domains of LAR (Leukocyte common Antigen-Related) family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPdelta, and PTPsigma). In addition, PTPdelta is implicated in ASDs, ADHD, bipolar disorder, and restless leg syndrome. Studies have shown that LAR-RPTPs are novel and splicing-dependent presynaptic ligands for SALM5, and that they mediate SALM5-dependent presynaptic differentiation. Furthermore, SALM5 maintains AMPA receptor (AMPAR)-mediated excitatory synaptic transmission through mechanisms involving the interaction of SALM5 with LAR-RPTPs. This group belongs to the I-set of immunoglobulin superfamily (IgSF) domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568922990 133 PKIYDISNDMTINEGTNVTLTCLATGKPEPVISWrhISPSAK---------PFENGQyLDIYGITRDQAGEYECSAEN 201
Cdd:cd05764    1 PLITRHTHELRVLEGQRATLRCKARGDPEPAIHW--ISPEGKlisnssrtlVYDNGT-LDILITTVKDTGAFTCIASN 75

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922990 141 DMTINEGTNVTLTCLATGKPEPVISWRHISPSAKP------FENGQyLDIYGITRDQAGEYECSAENDVSFPDVKKVRVI 214
Cdd:cd20968    8 NVTIIEGLKAVLPCTTMGNPKPSVSWIKGDDLIKEnnriavLESGS-LRIHNVQKEDAGQYRCVAKNSLGIAYSKPVTIE 86

                 .
gi 568922990 215 V 215
Cdd:cd20968   87 V 87

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922990 131 VPPKIYDISNDMTINEGTNVTLTCLATGKPEPVISWR---------------------HISPSAKPFENGQYLDiygitr 189
Cdd:cd05869    1 AKPKITYVENQTAMELEEQITLTCEASGDPIPSITWRtstrnisseektldghivvrsHARVSSLTLKYIQYTD------ 74

                         90
                 ....*....|....
gi 568922990 190 dqAGEYECSAENDV 203
Cdd:cd05869   75 --AGEYLCTASNTI 86

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922990 220 TIQEIKSGTVTPGRSGLIRCEGAGVPPPAFEWYKGEKRLFNGQQGIIIQNFSTrsiLTVTNVTQEHFGNYTCVAANKLGT 299
Cdd:cd20952    2 ILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDERITTLENGS---LQIKGAEKSDTGEYTCVALNLSGE 78

                 ....
gi 568922990 300 TNAS 303
Cdd:cd20952   79 ATWS 82

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor; 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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568922990 238 RCEGAGVPPPAFEWYK------GEKRLfnGQQGIIIQNFStrsiLTVTNVTQEHFGNYTCVAANKLGTTNASLPLNL 308
Cdd:cd05857   25 RCPAAGNPTPTMRWLKngkefkQEHRI--GGYKVRNQHWS----LIMESVVPSDKGNYTCVVENEYGSINHTYHLDV 95