Immunoglobulin domain; This family contains immunoglobulin-like domains.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922764  1912 PRIeTASQKWTEVNLGEKLLLNCSATGDPKPTIIWKLPSKVVIDQWHRmgSRIHVYPNGSLVIGSVTEKDGGDYLCVARN 1991
Cdd:pfam13927    2 PVI-TVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTR--SRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568922764 1637 VLLPCEAVGDPKPTIHWTRvssgreisRGIQKT---RFHVLPNGTLSIQRVSIQDRGQYLCAASNPLGVDHLHVTLS 1710
Cdd:cd05746     1 VQIPCSAQGDPEPTITWNK--------DGVQVTesgKFHISPEGYLAIRDVGVADQGRYECVARNTIGYASVSMVLS 69

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922764  2402 KPVIlTYEPGMIKSAGGESLSLHCVSDGIPKPNVKWTTPGGLVIDRPQVGGkYILHENGTLVIKETTAHDRGNYICKAQN 2481
Cdd:pfam13927    1 KPVI-TVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSR-SLSGSNSTLTISNVTRSDAGTYTCVASN 78

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922764 1813 PVIIEQKRQAIVGVLGESLKLPCTAKGTPQPSVHWvLYDGtelKPLQLTHSRfFLYPNGTLYIRNIVSSVRGTYECIATS 1892
Cdd:cd20978     1 PKFIQKPEKNVVVKGGQDVTLPCQVTGVPQPKITW-LHNG---KPLQGPMER-ATVEDGTLTIINVQPEDTGYYGCVATN 75

                          90
                  ....*....|...
gi 568922764 1893 SSGSERRVVILRV 1905
Cdd:cd20978    76 EIGDIYTETLLHV 88

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

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568922764   2230 LDCRADGVPPPQITWIMPDNIFLTapyYGGRITVHQNG---TLEIRNIRLSDSADFTCVVRSEGGESVLVVQLKV 2301
Cdd:smart00410   14 LSCEASGSPPPEVTWYKQGGKLLA---ESGRFSVSRSGstsTLTISNVTPEDSGTYTCAATNSSGSASSGTTLTV 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 568922764   2024 GKDFQVDCKASGSPVPEVSWSLPDGTVVNNvaqaddsgyrTKRYTLFHNG---TLYFNKVGMAEEGDYICSAQNTLGKDE 2100
Cdd:smart00410    9 GESVTLSCEASGSPPPEVTWYKQGGKLLAE----------SGRFSVSRSGstsTLTISNVTPEDSGTYTCAATNSSGSAS 78

                    ....*..
gi 568922764   2101 MKVHLTV 2107
Cdd:smart00410   79 SGTTLTV 85

Leucine rich repeat C-terminal domain;

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*...
gi 568922764    219 NPWTCDCHLKWLSEWMQGNpdiikckkERIPssPQQCPLCMNPRISKGRSIAMVPSGS 276
Cdd:smart00082    1 NPFICDCELRWLLRWLQAN--------EHLQ--DPVDLRCASPSSLRGPLLELLHSEF 48

Leucine rich repeat;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568922764    81 SRLELLMLHSNGIHRVSDKTFSGLQSLQVLKMSYNKVQIIEKDTLYGLRSLTRLHLDHNNI 141
Cdd:pfam13855    1 PNLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

Immunoglobulin I-set domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922764  2120 SNVRIKAGDTAVLDCEVTGEPKPNVFWLLPsNNVISfSNDRFIFHANG---TLSINKVKPLDSGKYVCVAQNPSGDDTKT 2196
Cdd:pfam07679    8 KDVEVQEGESARFTCTVTGTPDPEVSWFKD-GQPLR-SSDRFKVTYEGgtyTLTISNVQPDDSGKYTCVATNSAGEAEAS 85

                   ...
gi 568922764  2197 YKL 2199
Cdd:pfam07679   86 AEL 88

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568922764 1637 VLLPCEAVGDPKPTIHWTRvssgreisRGIQKT---RFHVLPNGTLSIQRVSIQDRGQYLCAASNPLGVDHLHVTLS 1710
Cdd:cd05746     1 VQIPCSAQGDPEPTITWNK--------DGVQVTesgKFHISPEGYLAIRDVGVADQGRYECVARNTIGYASVSMVLS 69

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922764  2498 PPRIINYlPRSMLRRTGEAMQLHCVALGVPKPQITWETPGYSLLSTATERRPHRSEmlplQGTLVIQNLRASDSGVYKCR 2577
Cdd:pfam13927    1 KPVITVS-PSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSGS----NSTLTISNVTRSDAGTYTCV 75

                   ...
gi 568922764  2578 AQN 2580
Cdd:pfam13927   76 ASN 78

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922764  2402 KPVIlTYEPGMIKSAGGESLSLHCVSDGIPKPNVKWTTPGGLVIDRPQVGGkYILHENGTLVIKETTAHDRGNYICKAQN 2481
Cdd:pfam13927    1 KPVI-TVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSR-SLSGSNSTLTISNVTRSDAGTYTCVASN 78

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

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922764   2506 PRSMLRRTGEAMQLHCVALGVPKPQITWETPGYSLLSTATERRPHRSemlPLQGTLVIQNLRASDSGVYKCRAQNVLGAD 2585
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRS---GSTSTLTISNVTPEDSGTYTCAATNSSGSA 77

                    ....*...
gi 568922764   2586 YATTYIQV 2593
Cdd:smart00410   78 SSGTTLTV 85

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 568922764 1813 PVIIEQKRQAIVGVLGESLKLPCTAKGTPQPSVHWvLYDGtelKPLQLTHSRfFLYPNGTLYIRNIVSSVRGTYECIATS 1892
Cdd:cd20978     1 PKFIQKPEKNVVVKGGQDVTLPCQVTGVPQPKITW-LHNG---KPLQGPMER-ATVEDGTLTIINVQPEDTGYYGCVATN 75

                          90
                  ....*....|...
gi 568922764 1893 SSGSERRVVILRV 1905
Cdd:cd20978    76 EIGDIYTETLLHV 88

protein phosphatase 1 regulatory subunit 42; Protein phosphatase 1 regulatory subunit 42 (PPP1R42), also known as leucine-rich repeat-containing protein 67 (lrrc67) or testis leucine-rich repeat (TLRR) protein, plays a role in centrosome separation. PPP1R42 has been shown to interact with the well-conserved signaling protein phosphatase-1 (PP1) and thereby increasing PP1's activity, which counters centrosome separation. Inhibition of PPP1R42 expression increases the number of centrosomes per cell while its depletion reduces the activity of PP1 leading to activation of NEK2, the kinase responsible for phosphorylation of centrosomal linker proteins promoting centrosome separation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922764   80 LSRLELLMLHSNGIHRVSDktFSGLQSLQVLkmsY---NKVQIIEKdtLYGLRSLTRLHLDHNNIEFInpEAFYGLTLLR 156
Cdd:cd21340     1 LKRITHLYLNDKNITKIDN--LSLCKNLKVL---YlydNKITKIEN--LEFLTNLTHLYLQNNQIEKI--ENLENLVNLK 71

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922764  157 LVHLEGNR------------LTKLH---------------PDTFVSLSY-LQIFKTS--------------FIKYLYLSD 194
Cdd:cd21340    72 KLYLGGNRisvveglenltnLEELHienqrlppgekltfdPRSLAALSNsLRVLNISgnnidsleplaplrNLEQLDASN 151

                         170       180
                  ....*....|....*....|....*...
gi 568922764  195 NFLTSLP--KEMVSSMPNLESLYLHGNP 220
Cdd:cd21340   152 NQISDLEelLDLLSSWPSLRELDLTGNP 179

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

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922764   1630 TVPTNSDVLLPCEAVGDPKPTIHWTRvSSGREIsrgIQKTRFHVLPNG---TLSIQRVSIQDRGQYLCAASNPLGVDHLH 1706
Cdd:smart00410    5 TVKEGESVTLSCEASGSPPPEVTWYK-QGGKLL---AESGRFSVSRSGstsTLTISNVTPEDSGTYTCAATNSSGSASSG 80

                    ....*
gi 568922764   1707 VTLSV 1711
Cdd:smart00410   81 TTLTV 85

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 568922764 1715 PARILESHVKEITAHSGSTVKLKCRVEGMPRPTISWILANQTVVSETPEGSRKVWvtPDGTLIIHNLSLYDRGFYKCVAN 1794
Cdd:cd20969     1 RAAIRDRKAQQVFVDEGHTVQFVCRADGDPPPAILWLSPRKHLVSAKSNGRLTVF--PDGTLEVRYAQVQDNGTYLCIAA 78

                          90
                  ....*....|....
gi 568922764 1795 NPSGQDSLLVKIQV 1808
Cdd:cd20969    79 NAGGNDSMPAHLHV 92

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

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922764    583 HTVIMGEILDLPCLSTGIPDASISWILPRNTVFSQSSRdMQILNNG---TLRILQATPKDQGHYRCVAANPSGADFSSFQ 659
Cdd:smart00410    4 VTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGR-FSVSRSGstsTLTISNVTPEDSGTYTCAATNSSGSASSGTT 82

                    ...
gi 568922764    660 VSV 662
Cdd:smart00410   83 LTV 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 568922764   1919 QKWTEVNLGEKLLLNCSATGDPKPTIIWKLPSkvviDQWHRMGSRIHVYPNG---SLVIGSVTEKDGGDYLCVARNKMGD 1995
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQG----GKLLAESGRFSVSRSGstsTLTISNVTPEDSGTYTCAATNSSGS 76

                    .
gi 568922764   1996 D 1996
Cdd:smart00410   77 A 77

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922764 2409 EPGMIKSAGGESLSLHCVSDGIPKPNVKW-----TTPGGL--VIDRPQVGgkyiLHENGTLVIKETTAHDRGNYICKAQN 2481
Cdd:cd20954     7 EPVDANVAAGQDVMLHCQADGFPTPTVTWkkatgSTPGEYkdLLYDPNVR----ILPNGTLVFGHVQKENEGHYLCEAKN 82

                          90
                  ....*....|....
gi 568922764 2482 SVG---QAVISVPV 2492
Cdd:cd20954    83 GIGsglSKVIFLKV 96

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

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922764   2024 GKDFQVDCKASGSPVPEVSWSLPDGTVVNNvaqaddsgyrTKRYTLFHNG---TLYFNKVGMAEEGDYICSAQNTLGKDE 2100
Cdd:smart00410    9 GESVTLSCEASGSPPPEVTWYKQGGKLLAE----------SGRFSVSRSGstsTLTISNVTPEDSGTYTCAATNSSGSAS 78

                    ....*..
gi 568922764   2101 MKVHLTV 2107
Cdd:smart00410   79 SGTTLTV 85

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568922764  584 TVIMGEILDLPCLSTGIPDASISWIlPRNTVFSQSSRdMQILNNGTLRILQATPKDQGHYRCVAANPSGADFS 656
Cdd:cd20968    10 TIIEGLKAVLPCTTMGNPKPSVSWI-KGDDLIKENNR-IAVLESGSLRIHNVQKEDAGQYRCVAKNSLGIAYS 80

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568922764 2326 VAMNCSVDGNPTPEIIWILpDGTQFANGPQNSPYLMASNGSLIVYKATRNKSGKYRCTARNKVG 2389
Cdd:cd00096     1 VTLTCSASGNPPPTITWYK-NGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAG 63

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 568922764 2008 PAKIEHKQHFKKQVLHGKDFQVDCKASGSPVPEVSWSLPDGTVVnnvaqaddSGYRTKRYTLFHNGTLYFNKVGMAEEGD 2087
Cdd:cd20969     1 RAAIRDRKAQQVFVDEGHTVQFVCRADGDPPPAILWLSPRKHLV--------SAKSNGRLTVFPDGTLEVRYAQVQDNGT 72

                          90       100
                  ....*....|....*....|
gi 568922764 2088 YICSAQNTLGKDEMKVHLTV 2107
Cdd:cd20969    73 YLCIAANAGGNDSMPAHLHV 92

Immunoglobulin I-set domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922764  2030 DCKASGSPVPEVSWSLpDGTVVNNvaqaddsgyrTKRYTLFHNG---TLYFNKVGMAEEGDYICSAQNTLGKDEMKVHLT 2106
Cdd:pfam07679   21 TCTVTGTPDPEVSWFK-DGQPLRS----------SDRFKVTYEGgtyTLTISNVQPDDSGKYTCVATNSAGEAEASAELT 89

                   .
gi 568922764  2107 V 2107
Cdd:pfam07679   90 V 90

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568922764  483 LEHTVLVGGTIALDCPGKGDPSPHLEWvLADGSKVRApyvsEDGRILIDKKGKLELQMADTFDAGLYHCISTN 555
Cdd:cd20952     7 QNQTVAVGGTVVLNCQATGEPVPTISW-LKDGVPLLG----KDERITTLENGSLQIKGAEKSDTGEYTCVALN 74

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

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922764    485 HTVLVGGTIALDCPGKGDPSPHLEWVLADGSKvrapyVSEDGRILIDK-KGKLELQM--ADTFDAGLYHCISTNDADADI 561
Cdd:smart00410    4 VTVKEGESVTLSCEASGSPPPEVTWYKQGGKL-----LAESGRFSVSRsGSTSTLTIsnVTPEDSGTYTCAATNSSGSAS 78

                    ....*..
gi 568922764    562 LTYRITV 568
Cdd:smart00410   79 SGTTLTV 85

polycystin cation channel protein; The Polycystin Cation Channel (PCC) Family (TC 1.A.5) Polycystin is a huge protein of 4303aas. Its repeated leucine-rich (LRR) segment is found in many proteins. It contains 16 polycystic kidney disease (PKD) domains, one LDL-receptor class A domain, one C-type lectin family domain, and 16-18 putative TMSs in positions between residues 2200 and 4100. Polycystin-L has been shown to be a cation (Na+, K+ and Ca2+) channel that is activated by Ca2+. Two members of the PCC family (polycystin 1 and 2) are mutated in autosomal dominant polycystic kidney disease, and polycystin-L is deleted in mice with renal and retinal defects. Note: this model is restricted to the amino half.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922764   192 LSDNFLTSLPKEMVSSMPNLESLYLHGNPWTCDCHLKWLSEWMQGnpdiiKCKKERIPsspqQCPLCMNPRISKGRSIAM 271
Cdd:TIGR00864    2 ISNNKISTIEEGICANLCNLSEIDLSGNPFECDCGLARLPRWAEE-----KGVKVRQP----EAALCAGPGALAGQPLLG 72

                   ....*...
gi 568922764   272 VPSGSFLC 279
Cdd:TIGR00864   73 IPLLDSGC 80