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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38372919  23 AGFVQAPLSQQRWVGGSVELHCEAVGSPVPEIQWWFEGQGPNDTCSQLWDGARLDRVHIHATYHQHAASTISIDTLVEED 102
Cdd:cd20940   1 AGFIKSPLSQQRLVGDSVELHCEAVGSPIPEIQWWFEGQEPNEICSQLWDGARLDRVHINATYHQHATSTISIDNLTEED 80

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 38372919 103 TGTYECRASNDPDRNHLTRAPRVKWVRAQAVVLVLE 138
Cdd:cd20940  81 TGTYECRASNDPDRNHLTRAPKVKWIRSQANVLVLE 116

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38372919  23 AGFVQAPLSQQRWVGGSVELHCEAVGSPVPEIQWWFEGQGPNDTCSQLWDGARLDRVHIHATYHQHAASTISIDTLVEED 102
Cdd:cd20940   1 AGFIKSPLSQQRLVGDSVELHCEAVGSPIPEIQWWFEGQEPNEICSQLWDGARLDRVHINATYHQHATSTISIDNLTEED 80

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 38372919 103 TGTYECRASNDPDRNHLTRAPRVKWVRAQAVVLVLE 138
Cdd:cd20940  81 TGTYECRASNDPDRNHLTRAPKVKWIRSQANVLVLE 116

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38372919    228 SSEHINEGETAMLVCKSESVPPVTDWaWYKitdseDKALMNGSESRFFVSSSQGRSELHIENLNMEaDPGQYRCNGTSSK 307
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPEVT-WYK-----QGGKLLAESGRFSVSRSGSTSTLTISNVTPE-DSGTYTCAATNSS 74

                           90
                   ....*....|.
gi 38372919    308 GSDQAIITLRV 318
Cdd:smart00410  75 GSASSGTTLTV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38372919   220 PPRVKAVKSSEHINEGETAMLVCKSESVPPVTDWaWYKitdsEDKALMNGSESRFFVSSSQGRseLHIENLNMEaDPGQY 299
Cdd:pfam13927   1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTIT-WYK----NGEPISSGSTRSRSLSGSNST--LTISNVTRS-DAGTY 72

                  ..
gi 38372919   300 RC 301
Cdd:pfam13927  73 TC 74

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38372919  23 AGFVQAPLSQQRWVGGSVELHCEAVGSPVPEIQWWFEGQGPNDTCSQLWDGARLDRVHIHATYHQHAASTISIDTLVEED 102
Cdd:cd20940   1 AGFIKSPLSQQRLVGDSVELHCEAVGSPIPEIQWWFEGQEPNEICSQLWDGARLDRVHINATYHQHATSTISIDNLTEED 80

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 38372919 103 TGTYECRASNDPDRNHLTRAPRVKWVRAQAVVLVLE 138
Cdd:cd20940  81 TGTYECRASNDPDRNHLTRAPKVKWIRSQANVLVLE 116

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 38372919  40 VELHCEAVGSPVPEIQWWfegqgpndtcsqlWDGARLDRVHIHATYHQHAASTISIDTLVEEDTGTYECRASND 113
Cdd:cd00096   1 VTLTCSASGNPPPTITWY-------------KNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNS 61

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38372919    228 SSEHINEGETAMLVCKSESVPPVTDWaWYKitdseDKALMNGSESRFFVSSSQGRSELHIENLNMEaDPGQYRCNGTSSK 307
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPEVT-WYK-----QGGKLLAESGRFSVSRSGSTSTLTISNVTPE-DSGTYTCAATNSS 74

                           90
                   ....*....|.
gi 38372919    308 GSDQAIITLRV 318
Cdd:smart00410  75 GSASSGTTLTV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38372919   220 PPRVKAVKSSEHINEGETAMLVCKSESVPPVTDWaWYKitdsEDKALMNGSESRFFVSSSQGRseLHIENLNMEaDPGQY 299
Cdd:pfam13927   1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTIT-WYK----NGEPISSGSTRSRSLSGSNST--LTISNVTRS-DAGTY 72

                  ..
gi 38372919   300 RC 301
Cdd:pfam13927  73 TC 74

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 38372919  37 GGSVELHCEAVGSPVPEIQWWFEGQgpndtcsQLWDGARLdRVHIHATYHQHAASTISIDTLVEEDTGTYECRASND 113
Cdd:cd20956  16 GPSVSLKCVASGNPLPQITWTLDGF-------PIPESPRF-RVGDYVTSDGDVVSYVNISSVRVEDGGEYTCTATND 84

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 38372919    35 WVGGSVELHCEAV-GSPVPEIQWWFEGQGPNDTcsqlwdgarlDRVHIHATYHqhAASTISIDTLVEEDTGTYECRASN 112
Cdd:pfam00047   9 LEGDSATLTCSAStGSPGPDVTWSKEGGTLIES----------LKVKHDNGRT--TQSSLLISNVTKEDAGTYTCVVNN 75

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38372919   232 INEGETAMLVCKSESVPP--VTdwaWYKitdsEDKALmnGSESRFFVSSSQGRSELHIENLNMEaDPGQYRCNGTSSKGS 309
Cdd:pfam07679  12 VQEGESARFTCTVTGTPDpeVS---WFK----DGQPL--RSSDRFKVTYEGGTYTLTISNVQPD-DSGKYTCVATNSAGE 81

                  ....*....
gi 38372919   310 DQAIITLRV 318
Cdd:pfam07679  82 AEASAELTV 90

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 38372919  26 VQAPLSQQRWVGGSVELHCEAVGSPVPEIQWwfegqgpndtcsQLWDGARLDRVHIHAtyhqhAASTISIDTLVEEDTGT 105
Cdd:cd04968   5 VRFPADTYALKGQTVTLECFALGNPVPQIKW------------RKVDGSPSSQWEITT-----SEPVLEIPNVQFEDEGT 67

                        90
                ....*....|..
gi 38372919 106 YECRASNDPDRN 117
Cdd:cd04968  68 YECEAENSRGKD 79

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38372919  26 VQAPLSQQRWVGGSVELHCEAVGSPVPEIQWWFE-GQGPndtcsqlwdgarLDRVHIhatYHQHaasTISIDTLVEEDTG 104
Cdd:cd05725   1 VKRPQNQVVLVDDSAEFQCEVGGDPVPTVRWRKEdGELP------------KGRYEI---LDDH---SLKIRKVTAGDMG 62

                ....*...
gi 38372919 105 TYECRASN 112
Cdd:cd05725  63 SYTCVAEN 70

Fifth 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 fifth 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 (also known as Neph1), Kirrel2 (also known as Neph3), and Drosophila RST (also known as 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 38372919 219 GPPRVKAVKSSEHInEGETAMLVCKSESVPPVTD--WAWykitdsEDKALMNGSESRFFV---SSSQGR-SELHIENLNM 292
Cdd:cd05758   1 GPPIITAEATQPAI-LGEKARLECLVFSSPPPDRivWSW------DEGFLESGSSGRFSVetfPTEPGViSVLHISGTQR 73

                        90       100
                ....*....|....*....|....*
gi 38372919 293 EADPGQYRCNGTSSKGSDQAIITLR 317
Cdd:cd05758  74 SDFQTSFNCSAWNRFGEGTAIVSLG 98

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 38372919  36 VGGSVELHCEAVGSPVPEIQWWFEGQgpndtcsQLWdgaRLDRVHIHATYHQHAasTISIDTLVEEDTGTYECRASN 112
Cdd:cd05729  18 AANKVRLECGAGGNPMPNITWLKDGK-------EFK---KEHRIGGTKVEEKGW--SLIIERAIPRDKGKYTCIVEN 82

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 38372919 221 PRVKAVKSSEhINEGETAMLVCKSESVPPVTDWAWYKitdsEDKALMNGSESRFFVSSSQGRSELHIENLNMEaDPGQYR 300
Cdd:cd05750   1 PKLKEMKSQT-VQEGSKLVLKCEATSENPSPRYRWFK----DGKELNRKRPKNIKIRNKKKNSELQINKAKLE-DSGEYT 74

                        90
                ....*....|....*...
gi 38372919 301 CNGTSSKGSDQAIITLRV 318
Cdd:cd05750  75 CVVENILGKDTVTGNVTV 92

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 38372919  37 GGSVELHCEAVGSPVPEIQWWFEGQGPNDTCSQLwDGarldRVHIHAtyhQHAASTISIDTLVEEDTGTYECRASN 112
Cdd:cd05732  16 LEQITLTCEAEGDPIPEITWRRATRGISFEEGDL-DG----RIVVRG---HARVSSLTLKDVQLTDAGRYDCEASN 83

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 38372919  36 VGGSVELHCEAVGSPVPEIQWWFEGQGPNDTcsqlwdgarlDRVHIHATyhqHAASTISIDTLVEEDTGTYECRASND 113
Cdd:cd05748   6 AGESLRLDIPIKGRPTPTVTWSKDGQPLKET----------GRVQIETT---ASSTSLVIKNAKRSDSGKYTLTLKNS 70

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        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 38372919  37 GGSVELHCEAVGSPVPEIQWwfegQGPNDTCSQlwdgarlDRVhihaTYHQHaASTISIDTLVEEDTGTYECRASN 112
Cdd:cd05876  10 GQSLVLECIAEGLPTPTVKW----LRPSGPLPP-------DRV----KYQNH-NKTLQLLNVGESDDGEYVCLAEN 69

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 38372919 219 GPPRVKAvKSSEHINEGETAMLVCKSESVPPVTD--WAWykitdsEDKALMNGSESRFFV----SSSQGRSELHIENLnM 292
Cdd:cd05898   1 GPPIISS-EQVQYAVRGERGKVKCFIGSTPPPDRiaWAW------KENVLESGTLERYTVertsTGSGVLSTLTINNI-M 72

                        90       100
                ....*....|....*....|....*.
gi 38372919 293 EAD-PGQYRCNGTSSKGSDQAIITLR 317
Cdd:cd05898  73 EADfQTHYNCTAWNSFGSGTAIIQLE 98

Third immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the third 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 38372919  37 GGSVELHCEAVGSPVPEIQWWFEGqgpndtcSQLwdgaRLDRVHIHATyhqhaASTISIDTLVEEDTGTYECRASN 112
Cdd:cd05745   2 GQTVDFLCEAQGYPQPVIAWTKGG-------SQL----SVDRRHLVLS-----SGTLRISRVALHDQGQYECQAVN 61

Third immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F (also known as LAR), type IIa; member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains. Included in this group is Drosophila LAR (DLAR).

                        10        20
                ....*....|....*....|....*...
gi 38372919  29 PLSQQRWVGGSVELHCEAVGSPVPEIQW 56
Cdd:cd05739   4 PSNHEVMPGGSVNLTCVAVGAPMPYVKW 31

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 38372919  31 SQQRWV--GGSVELHCEAVGSPVPEIQWWF-EGQ-GPNDTCSQLWDGARLDrvhihatyhqhaastISIDTLveEDTGTY 106
Cdd:cd05764   7 THELRVleGQRATLRCKARGDPEPAIHWISpEGKlISNSSRTLVYDNGTLD---------------ILITTV--KDTGAF 69

                ....*.
gi 38372919 107 ECRASN 112
Cdd:cd05764  70 TCIASN 75

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 38372919  37 GGSVELHCEAVGSPVPEIQWWFEGQgpndTCSQlwDGARLDRVHIHatyhqhaASTISIDTLVEEDTGTYECRASN 112
Cdd:cd20949  14 GQSATILCEVKGEPQPNVTWHFNGQ----PISA--SVADMSKYRIL-------ADGLLINKVTQDDTGEYTCRAYQ 76

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 38372919  40 VELHCEAVGSPVPEIQWWFEGQGPNDTCSQLwDGARLDRVHIHatyhqhaASTISIDTLVEEDTGTYECRASN 112
Cdd:cd05869  20 ITLTCEASGDPIPSITWRTSTRNISSEEKTL-DGHIVVRSHAR-------VSSLTLKYIQYTDAGEYLCTASN 84

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. 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 38372919  25 FVQAPLSQQRWVGGSVELHCEAVGSPVPEIQWWFEGQgpndtcsqlwdGARLDRVHiHATYHQHAASTISIDTLVEEDTG 104
Cdd:cd20990   3 FLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDGK-----------PIRPDSAH-KMLVRENGVHSLIIEPVTSRDAG 70

                        90
                ....*....|....*.
gi 38372919 105 TYECRASNDPDRNHLT 120
Cdd:cd20990  71 IYTCIATNRAGQNSFN 86

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 38372919  42 LHCEAVGSPVPEIQWWFEGQGPNDTCSQLWDGARLDRVHIHatyhqhaastisidTLVEEDTGTYECRASN 112
Cdd:cd20976  21 AQCSARGKPVPRITWIRNAQPLQYAADRSTCEAGVGELHIQ--------------DVLPEDHGTYTCLAKN 77

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 38372919    36 VGGSVELHCEA---VGSPVPEIQWWFEGQGPNDTC-----SQLWD-GARLDRVHIHATYHQHAAStISIDTLVEEDTGTY 106
Cdd:pfam07686  10 LGGSVTLPCTYsssMSEASTSVYWYRQPPGKGPTFliayySNGSEeGVKKGRFSGRGDPSNGDGS-LTIQNLTLSDSGTY 88

                  ....*...
gi 38372919   107 ECRASNDP 114
Cdd:pfam07686  89 TCAVIPSG 96