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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7709992     112 KSEHASEGEFVKLICksEASHPPVDEWVWFKTsdtGDQTISNgteaNSKYVIISTPELSELIISDLDMNvDPGTYVCNAT 191
Cdd:smart00410   2 PSVTVKEGESVTLSC--EASGSPPPEVTWYKQ---GGKLLAE----SGRFSVSRSGSTSTLTISNVTPE-DSGTYTCAAT 71

                           90
                   ....*....|....
gi 7709992     192 NSQGSARETISLRV 205
Cdd:smart00410  72 NSSGSASSGTTLTV 85

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7709992     112 KSEHASEGEFVKLICksEASHPPVDEWVWFKTsdtGDQTISNgteaNSKYVIISTPELSELIISDLDMNvDPGTYVCNAT 191
Cdd:smart00410   2 PSVTVKEGESVTLSC--EASGSPPPEVTWYKQ---GGKLLAE----SGRFSVSRSGSTSTLTISNVTPE-DSGTYTCAAT 71

                           90
                   ....*....|....
gi 7709992     192 NSQGSARETISLRV 205
Cdd:smart00410  72 NSSGSASSGTTLTV 85

Fifth 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 fifth 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 7709992  134 PVDEWVWFKtsdtGDQTI---------SNGTeanskyviistpelseLIISDLDMNVDPGTYVCNATNSQG-SARETISL 203
Cdd:cd20958  28 PISSITWEK----DGRRLplnhrqrvfPNGT----------------LVIENVQRSSDEGEYTCTARNQQGqSASRSVFV 87

                ..
gi 7709992  204 RV 205
Cdd:cd20958  88 KV 89

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7709992     112 KSEHASEGEFVKLICksEASHPPVDEWVWFKTsdtGDQTISNgteaNSKYVIISTPELSELIISDLDMNvDPGTYVCNAT 191
Cdd:smart00410   2 PSVTVKEGESVTLSC--EASGSPPPEVTWYKQ---GGKLLAE----SGRFSVSRSGSTSTLTISNVTPE-DSGTYTCAAT 71

                           90
                   ....*....|....
gi 7709992     192 NSQGSARETISLRV 205
Cdd:smart00410  72 NSSGSASSGTTLTV 85

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7709992    116 ASEGEFVKLICKSEASHPPvdEWVWFKtsdtGDQTISNGteanSKYVIISTPELSELIISDLDMNvDPGTYVCNATNSQG 195
Cdd:pfam07679  12 VQEGESARFTCTVTGTPDP--EVSWFK----DGQPLRSS----DRFKVTYEGGTYTLTISNVQPD-DSGKYTCVATNSAG 80

                          90
                  ....*....|
gi 7709992    196 SARETISLRV 205
Cdd:pfam07679  81 EAEASAELTV 90

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7709992  114 EHASEGEfVKLICKSEASHPPVDEWvwfktsdtgdqtISNGTE----ANSKYVIIStpelSELIISDLDMNVDPGTYVCN 189
Cdd:cd04967  15 EDSDEKK-VALNCRARANPVPSYRW------------LMNGTEidleSDYRYSLVD----GTLVISNPSKAKDAGHYQCL 77

                        90       100
                ....*....|....*....|...
gi 7709992  190 ATNSQGSaretislrVRSRLAAL 212
Cdd:cd04967  78 ATNTVGS--------VLSREATL 92

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 7709992  122 VKLICKSEASHPPvdEWVWFKtsdtGDQTISNGTEANSKYVIIStpelSELIISDLDMNvDPGTYVCNATNSQGSARETI 201
Cdd:cd00096   1 VTLTCSASGNPPP--TITWYK----NGKPLPPSSRDSRRSELGN----GTLTISNVTLE-DSGTYTCVASNSAGGSASAS 69

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7709992  118 EGEFVKLICKSEASHPPVDEWvwfktsDTGDQTISNGTEANSKYVIIStpelSELIISDLDMNvDPGTYVCNATNSQGSA 197
Cdd:cd20949  13 EGQSATILCEVKGEPQPNVTW------HFNGQPISASVADMSKYRILA----DGLLINKVTQD-DTGEYTCRAYQVNSIA 81

                ....*...
gi 7709992  198 RETISLRV 205
Cdd:cd20949  82 SDMQERTV 89

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. 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 telokin Ig domain 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 7709992  117 SEGEFVKLICKSEAShpPVDEWVWFKTsdtgDQTIsngTEANSKYVIISTPELSELIISDLdMNVDPGTYVCNATNSQGS 196
Cdd:cd20973  10 VEGSAARFDCKVEGY--PDPEVKWMKD----DNPI---VESRRFQIDQDEDGLCSLIISDV-CGDDSGKYTCKAVNSLGE 79

                ....*....
gi 7709992  197 ARETISLRV 205
Cdd:cd20973  80 ATCSAELTV 88

Immunoglobulin I-set domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1); The members here are composed of the immunoglobulin I-set (IgI) domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1). Human Lingo-1 is a central nervous system-specific transmembrane glycoprotein also known as LERN-1, which functions as a negative regulator of neuronal survival, axonal regeneration, and oligodendrocyte differentiation and myelination. Lingo-1 is a key component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors. The ligand-binding ectodomain of human Lingo-1 contains a bimodular, kinked structure composed of leucine-rich repeat (LRR) and immunoglobulin (Ig)-like modules. Diseases associated with Lingo-1 include mental retardation, autosomal recessive 64 and essential tremor. 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 Lingo-1 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 7709992  118 EGEFVKLICKSEASHPPVDEWVWfktsdTGDQTISngTEANSKYVIIS--TPELSELIISdldmnvDPGTYVCNATNSQG 195
Cdd:cd20969  16 EGHTVQFVCRADGDPPPAILWLS-----PRKHLVS--AKSNGRLTVFPdgTLEVRYAQVQ------DNGTYLCIAANAGG 82

                        90
                ....*....|
gi 7709992  196 SARETISLRV 205
Cdd:cd20969  83 NDSMPAHLHV 92

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM), and similar domains; The members here are composed of the third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, and spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM and human neurofascin.

                        10        20
                ....*....|....*....|....*
gi 7709992  182 DPGTYVCNATNSQGSARETISLRVR 206
Cdd:cd05731  59 DSGEYQCTASNTMGSARHTISVTVE 83

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 7709992  116 ASEGEFVKLICKSEASHPPVDEW----VWFKTSDTGDQTISNGTEanskYVIIStpelseliISDLDMnvdpGTYVCNAT 191
Cdd:cd20970  14 AREGENATFMCRAEGSPEPEISWtrngNLIIEFNTRYIVRENGTT----LTIRN--------IRRSDM----GIYLCIAS 77

                        90
                ....*....|....*
gi 7709992  192 N-SQGSARETISLRV 205
Cdd:cd20970  78 NgVPGSVEKRITLQV 92

Fourth immunoglobulin (Ig)-like domain of stem cell factor receptor (SCFR); member of the I-set of IgSF domains; The members here are composed of the fourth Immunoglobulin (Ig)-like domain in stem cell factor receptor (SCFR). SCFR is organized as an extracellular component having five IG-like domains, a transmembrane segment, and a cytoplasmic portion having protein tyrosine kinase activity. SCFR and its ligand SCF are critical for normal hematopoiesis, mast cell development, melanocytes, and gametogenesis. SCF binds to the second and third Ig-like domains of SCFR. This fourth Ig-like domain participates in SCFR dimerization, which follows ligand binding. Deletion of this fourth domain abolishes the ligand-induced dimerization of SCFR and completely inhibits signal transduction. 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 7709992  119 GEFVKLICKSEA-SHPPVDEWVWF--KTSDTGDQTISNGTEANSKYViistpelSELIISDLDmNVDPGTYVCNATNSQG 195
Cdd:cd05860  18 GENLDLRVEYEAyPKPEHQVWIYMneTLTNTSDHYVKSKTEGNNRYV-------SELHLTRLK-GTEGGIYTFLVSNSDA 89

                        90
                ....*....|..
gi 7709992  196 SARETISLRVRS 207
Cdd:cd05860  90 SASVTFNVYVKT 101