Leucine rich repeat C-terminal motif; This entry represents the Leucine Rich Repeat C-terminal (LRRCT) capping motif from TRK receptors.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 47220893    25 CGCNIRWIQLWTQRGEAGLHTQELYCKNGASKIRLHNMYIQKCD 68
Cdd:pfam16920   2 CSCDIRWLQLWQEEGLAGLGTQQLYCLNDGSKIPLQSMNIPNCG 45

Leucine rich repeat C-terminal motif; This entry represents the Leucine Rich Repeat C-terminal (LRRCT) capping motif from TRK receptors.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 47220893    25 CGCNIRWIQLWTQRGEAGLHTQELYCKNGASKIRLHNMYIQKCD 68
Cdd:pfam16920   2 CSCDIRWLQLWQEEGLAGLGTQQLYCLNDGSKIPLQSMNIPNCG 45

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47220893     77 GSVLVTEGDNVTVSCNGSGLPLPDVDWTISGLRSI--NTHMSdIQPTTHSINLTLFNVSRDDN-NYqlTCIAENVVGMTN 153
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLaeSGRFS-VSRSGSTSTLTISNVTPEDSgTY--TCAATNSSGSAS 78

                   ....*..
gi 47220893    154 ASVQLNV 160
Cdd:smart00410  79 SGTTLTV 85

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 47220893   205 TCiefTVRGYPHPKLRWFHEHKEIQQNDYIRteMDYYQDylEGCLTFQNPTHINNGNYTLEASNALGTVTKTVF 278
Cdd:pfam07679  21 TC---TVTGTPDPEVSWFKDGQPLRSSDRFK--VTYEGG--TYTLTISNVQPDDSGKYTCVATNSAGEAEASAE 87

Leucine rich repeat C-terminal domain;

                           10        20
                   ....*....|....*....|....*...
gi 47220893     23 FDCGCNIRWIQLWTQRGEAGLHTQELYC 50
Cdd:smart00082   3 FICDCELRWLLRWLQANEHLQDPVDLRC 30

Fifth domain (immunoglobulin-like) of Trk receptor TrkB; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth domain of Trk receptor, TrkB, an immunoglobulin (Ig)-like domain which binds to neurotrophin. The Trk family of receptors are tyrosine kinase receptors, which mediate the trophic effects of the neurotrophin Nerve Growth Factor (NGF) family. Trks are activated by dimerization, leading to autophosphorylation of intracellular tyrosine residues, and triggering the signal transduction pathway. TrkB shares significant sequence homology and domain organization with TrkA and TrkC. The first three domains are leucine-rich domains while the fourth and fifth domains are Ig-like domains playing a part in ligand binding. TrKB is recognized by brain-derived neurotrophic factor (BDNF) and neurotrophin (NT)-4. In some cell systems NT-3 can activate TrkA and TrkB receptors. TrKB transcripts are found throughout multiple structures of the central and peripheral nervous systems. This group belongs to the I-set of IgSF domains

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47220893 190 PPVILRLAEPEQRHDTCIEFTVRGYPHPKLRWFHEHKEIQQNDYIRTEM-DYYQDYLEGCLTFQNPTHINNGNYTLEASN 268
Cdd:cd05855   1 PPTITFLELPTRDHHWCIPFTVKGNPKPTLQWFHEGAILNESEYICTKIhVINNTEYHGCLQLDNPTHLNNGIYTLVAKN 80

                        90
                ....*....|....
gi 47220893 269 ALGTVTKTVFGHFL 282
Cdd:cd05855  81 EYGEDEKNVSAHFM 94

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 47220893    70 PDISVSHGSVLVTEGDNVTVSCNGSGLPLPDVDWTISGLRSINTHMSDIQPTTHSINLTLFNVSRDDN-NYqlTCIAEN 147
Cdd:pfam13927   2 PVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAgTY--TCVASN 78

Fourth domain (immunoglobulin-like) of Trk receptors TrkA, TrkB, and TrkC; The members here are composed of the fourth domain of Trk receptors TrkA, TrkB, and TrkC, an immunoglobulin (Ig)-like domain which binds to neurotrophin. The Trk family of receptors are tyrosine kinase receptors. They are activated by dimerization, leading to autophosphorylation of intracellular tyrosine residues, and triggering the signal transduction pathway. TrkA, TrkB, and TrkC share significant sequence homology and domain organization. The first three domains are leucine-rich domains while the fourth and fifth domains are Ig-like domains playing a part in ligand binding. TrkA, TrkB, and TrkC mediate the trophic effects of the neurotrophin Nerve Growth Factor (NGF) family. TrkA is recognized by NGF. TrKB is recognized by brain-derived neurotrophic factor (BDNF) and neurotrophin (NT)-4. TrkC is recognized by NT-3. NT-3 is promiscuous as in some cell systems it activates TrkA and TrkB receptors. TrkA is a receptor found in all major NGF targets, including the sympathetic, trigeminal, and dorsal root ganglia, cholinergic neurons of the basal forebrain, and the striatum. TrKB transcripts are found throughout multiple structures of the central and peripheral nervous systems. The TrkC gene is expressed throughout the mammalian nervous system.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47220893  72 ISVSHGSVLVteGDNVTVSCNGSGLPLPDVDWTISGLRSINTHMSdiQPTTHSINLTLFNVSRDDNNYQLTCIAENVVGM 151
Cdd:cd04972   4 IQMPNASVDV--GDDVLLQCQVEGQGLEQAGWILTELEQSATVMK--SGSLPSLGLTLANVTSDLNRKNVTCWAENDVGR 79

                ....*....
gi 47220893 152 TNASVQLNV 160
Cdd:cd04972  80 AEVSVQVNV 88

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). 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 47220893  77 GSVLVTEGDNVTVSCNGSGLPLPDVDWTISG--LRSINTHmSDIQPTTHSINLTLFNVSRDDNNYqLTCIAENVVGMTNA 154
Cdd:cd05744   8 GDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGkpVRPDSAH-KMLVRENGRHSLIIEPVTKRDAGI-YTCIARNRAGENSF 85

                ....*.
gi 47220893 155 SVQLNV 160
Cdd:cd05744  86 NAELVV 91

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. 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 fourth Ig-like domain of hemolin 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 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 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 47220893 200 EQRHDTCIEFTVRGYPHPKLRWFHEHKEIQQNDYIRTemdyyqdYLEGCLTFQNPTHINNGNYTLEASNALGTVTKTV 277
Cdd:cd20978  14 KGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMERAT-------VEDGTLTIINVQPEDTGYYGCVATNEIGDIYTET 84

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47220893  70 PDISVSHGSVLVTEGDNVTVSCNGSGLPLPDVDWTISGlRSINTHMSDIQPTTHSINLTLFNVSRDDN-NYqlTCIAENV 148
Cdd:cd20976   2 PSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNA-QPLQYAADRSTCEAGVGELHIQDVLPEDHgTY--TCLAKNA 78

                        90
                ....*....|..
gi 47220893 149 VGMTNASVQLNV 160
Cdd:cd20976  79 AGQVSCSAWVTV 90

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 47220893 205 TCIeftVRGYPHPKLRWFHEHKEIQQNDYIRTEMDyyQDYLegC-LTFQNPTHINNGNYTLEASNALGTVTKT 276
Cdd:cd20973  18 DCK---VEGYPDPEVKWMKDDNPIVESRRFQIDQD--EDGL--CsLIISDVCGDDSGKYTCKAVNSLGEATCS 83

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 47220893  84 GDNVTVSCNGSGLPLPDVDWTISGlRSINTHMSDIQPTTHSINLTLFNVSRDDNNyQLTCIAENVVGMTNASVQLNV 160
Cdd:cd05730  18 GQSVTLACDADGFPEPTMTWTKDG-EPIESGEEKYSFNEDGSEMTILDVDKLDEA-EYTCIAENKAGEQEAEIHLKV 92

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. 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 fourth Ig-like domain of hemolin 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 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 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 47220893  79 VLVTEGDNVTVSCNGSGLPLPDVDWTISGlRSINTHMSDIQPTTHSinLTLFNVSRDDNNYqLTCIAENVVGMTNASVQL 158
Cdd:cd20978  11 VVVKGGQDVTLPCQVTGVPQPKITWLHNG-KPLQGPMERATVEDGT--LTIINVQPEDTGY-YGCVATNEIGDIYTETLL 86

                ..
gi 47220893 159 NV 160
Cdd:cd20978  87 HV 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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 47220893 205 TCiefTVRGYPHPKLRWFHEHKEIQQNDYIRTEMDYYQdyleGCLTFQNPTHINNGNYTLEASNALGTVTKTVF 278
Cdd:cd00096   4 TC---SASGNPPPTITWYKNGKPLPPSSRDSRRSELGN----GTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 47220893   205 TCiefTVRGYPHPKLRWFHEHKEIQQNDYIRteMDYYQDylEGCLTFQNPTHINNGNYTLEASNALGTVTKTVF 278
Cdd:pfam07679  21 TC---TVTGTPDPEVSWFKDGQPLRSSDRFK--VTYEGG--TYTLTISNVQPDDSGKYTCVATNSAGEAEASAE 87

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 47220893   205 TCiefTVRGYPHPKLRWFHEHKEIQQNDYIRTEMDYYQdyleGCLTFQNPTHINNGNYTLEASN 268
Cdd:pfam13927  22 TC---EATGSPPPTITWYKNGEPISSGSTRSRSLSGSN----STLTISNVTRSDAGTYTCVASN 78

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. 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 titin Z1z2 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 47220893  78 SVLVTEGDNVTVSCNGSGLPLPDVDWTISGLRSINTHMSDIQPTTH--SINLTLFNVSRDDN-NYQLTciAENVVGMTNA 154
Cdd:cd20974   9 SVVVLEGSTATFEAHVSGKPVPEVSWFRDGQVISTSTLPGVQISFSdgRAKLSIPAVTKANSgRYSLT--ATNGSGQATS 86

                ....*.
gi 47220893 155 SVQLNV 160
Cdd:cd20974  87 TAELLV 92

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 47220893  80 LVTEGDNVTVSCNGSGLPLPDVDWTISGLRSI-NTHMSDIQPT-THSINLTlfnVSRDDNNYqlTCIAENVVGMTNASVQ 157
Cdd:cd05764  11 RVLEGQRATLRCKARGDPEPAIHWISPEGKLIsNSSRTLVYDNgTLDILIT---TVKDTGAF--TCIASNPAGEATARVE 85

                ...
gi 47220893 158 LNV 160
Cdd:cd05764  86 LHI 88

First immunoglobulin (Ig) domain of contactin-5; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-5. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains, anchored to the membrane by glycosylphosphatidylinositol. The different contactins show different expression patterns in the central nervous system. In rats, a lack of contactin-5 (NB-2) results in an impairment of the neuronal activity in the auditory system. Contactin-5 is expressed specifically in the postnatal nervous system, peaking at about 3 weeks postnatal. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala; lower levels of expression have been detected in the corpus callosum, caudate nucleus, and spinal cord. This group belongs to the I-set of IgSF domains.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 47220893 211 VRGYPHPKLRWFHEHKEIQqndyirTEMDYYQDYLEGCLTFQNPTH-INNGNYTLEASNALGTV 273
Cdd:cd05848  28 ARGNPVPTYRWLRNGTEID------TESDYRYSLIDGNLIISNPSEvKDSGRYQCLATNSIGSI 85

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 47220893  84 GDNVTVSCNGSGLPLPDVDWTISGL-------RSINTHMSDIQPTTHSINLTLFNVsRDDNNYqlTCIAENVVGMTNASV 156
Cdd:cd20956  16 GPSVSLKCVASGNPLPQITWTLDGFpipesprFRVGDYVTSDGDVVSYVNISSVRV-EDGGEY--TCTATNDVGSVSHSA 92

                ....
gi 47220893 157 QLNV 160
Cdd:cd20956  93 RINV 96

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 47220893  75 SHGSVLVTEGDNVTVSCNGSGLPLPDVDWtisglRSINTHMSDIQPTTHSIN--LTLFNVSR-DDNNYqlTCIAENVVG 150
Cdd:cd05876   1 SSSSLVALRGQSLVLECIAEGLPTPTVKW-----LRPSGPLPPDRVKYQNHNktLQLLNVGEsDDGEY--VCLAENSLG 72

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. 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 titin Z1z2 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47220893 207 IEFTVRGYPHPKLRWFHEHKEIQQNDYIRTEMDYYQDYLEgcLTFQNPTHINNGNYTLEASNALGTVTKT 276
Cdd:cd20974  20 FEAHVSGKPVPEVSWFRDGQVISTSTLPGVQISFSDGRAK--LSIPAVTKANSGRYSLTATNGSGQATST 87

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 47220893  81 VTEGDNVTVSCNGSGLPLPDVDWTISG--LRSINTHMSDIQPTThsinLTLFNVSRDDNNyQLTCIAENVVGMTNASVQL 158
Cdd:cd20952  11 VAVGGTVVLNCQATGEPVPTISWLKDGvpLLGKDERITTLENGS----LQIKGAEKSDTG-EYTCVALNLSGEATWSAVL 85

                ..
gi 47220893 159 NV 160
Cdd:cd20952  86 DV 87

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 47220893  80 LVTEGDNVTVSCNGSGLPLPDVDWTISGLRSINTHMSDIQPTTH-----SINLTLFNVSRDDNNYQLtCIAENVVGMTNA 154
Cdd:cd05726  10 VVALGRTVTFQCETKGNPQPAIFWQKEGSQNLLFPYQPPQPSSRfsvspTGDLTITNVQRSDVGYYI-CQALNVAGSILA 88

                ....*.
gi 47220893 155 SVQLNV 160
Cdd:cd05726  89 KAQLEV 94

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. 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 titin Z1z2 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 47220893  78 SVLVTEGDNVTVSCNGSGLPLPDVDWTISGLRSINThmSDIQPTT----HSInltLFNVSRDDNNYQLTCIAENVVGMTN 153
Cdd:cd20972  10 SQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNS--PDIQIHQegdlHSL---IIAEAFEEDTGRYSCLATNSVGSDT 84

                ....*..
gi 47220893 154 ASVQLNV 160
Cdd:cd20972  85 TSAEIFV 91

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 47220893 207 IEFTVRGYPHPKLRWFHEHKEIQQNDyirTEMDYYQD---YLegCLTFQNPTHINNGNYTLEASNALGTVTKT 276
Cdd:cd05892  20 LECQISAIPPPQIFWKKNNEMLQYNT---DRISLYQDncgRI--CLLIQNANKKDAGWYTVSAVNEAGVVSCN 87

Leucine rich repeat C-terminal domain;

                           10        20
                   ....*....|....*....|....*...
gi 47220893     23 FDCGCNIRWIQLWTQRGEAGLHTQELYC 50
Cdd:smart00082   3 FICDCELRWLLRWLQANEHLQDPVDLRC 30