NCBI Conserved Domain Search

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup 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. 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. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin 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. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 212.48 E-value: 1.22e-64

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  552 SFTKTPHDITIRTTTMARLECAATGHPNPQIAWQKDGGTDFPAARERRMHVMPDDDVFFITDVKIDDAGVYSCTAQNSAG 631
Cdd:cd05763     1 SFTKTPHDITIRAGSTARLECAATGHPTPQIAWQKDGGTDFPAARERRMHVMPEDDVFFIVDVKIEDTGVYSCTAQNSAG 80

                          90
                  ....*....|.
gi 767922909  632 SISANATLTVL 642
Cdd:cd05763    81 SISANATLTVL 91

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 101.95 E-value: 9.48e-26

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909   551 PSFTKTPHDITIRTTTMARLECAATGHPNPQIAWQKDGgTDFPAARERRMHVMPDDDVFFITDVKIDDAGVYSCTAQNSA 630
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDG-QPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSA 79

                           90
                   ....*....|.
gi 767922909   631 GSISANATLTV 641
Cdd:pfam07679   80 GEAEASAELTV 90

Leucine-rich repeat (LRR) protein [Transcription];

Pssm-ID: 443914 [Multi-domain] Cd Length: 414 Bit Score: 107.71 E-value: 1.31e-24

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909   68 SWTRSLNLSYNKLSEIDPAGFEDLPNLQEVYLNNNELTAVPSLGAASS--HVVSLFLQHNKIRSVEGSQLKAYLSLEVLD 145
Cdd:COG4886    23 TLILLLLLLLLLLALLLLSLLSLLLLLTLLLSLLLRDLLLSSLLLLLSllLLLLLSLLLLSLLLLGLTDLGDLTNLTELD 102

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  146 LSLNN-ITEVRNtcfphgppIKELNLAGNRIgtlelgafdglsrslltlrlsknriTQLPVRAFKLPRLTQLDLNRNRIR 224
Cdd:COG4886   103 LSGNEeLSNLTN--------LESLDLSGNQL-------------------------TDLPEELANLTNLKELDLSNNQLT 149

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  225 LIeGLTFQGLNSLEVLKLQRNNISKLTDgAFWGLSKMHVLVLSFNNLTRLDEEsLAELSSLSVLRLSHNSISHIAEgAFK 304
Cdd:COG4886   150 DL-PEPLGNLTNLKSLDLSNNQLTDLPE-ELGNLTNLKELDLSNNQITDLPEP-LGNLTNLEELDLSGNQLTDLPE-PLA 225

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  305 GLRSLRVLDLDHNEISgTIEDtsgaFSGLDSLSKLTLFGNKIKSVAKraFSGLEGLEHLNLGGNAIRSVQ 374
Cdd:COG4886   226 NLTNLETLDLSNNQLT-DLPE----LGNLTNLEELDLSNNQLTDLPP--LANLTNLKTLDLSNNQLTDLK 288

Leucine-rich repeat (LRR) protein [Transcription];

Pssm-ID: 443914 [Multi-domain] Cd Length: 414 Bit Score: 107.71 E-value: 1.56e-24

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909   62 LPGDLPSWTRSLNLSYNKLSEIDPAGFEDLPNLQEVYL-NNNELTAVPSLgaasshvVSLFLQHNKIRSVeGSQLKAYLS 140
Cdd:COG4886    66 LLLLSLLLLLLLSLLLLSLLLLGLTDLGDLTNLTELDLsGNEELSNLTNL-------ESLDLSGNQLTDL-PEELANLTN 137

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  141 LEVLDLSLNNITEVrntcfphGPPIKEL-NLAgnrigTLELGAfdglsrslltlrlskNRITQLPVRAFKLPRLTQLDLN 219
Cdd:COG4886   138 LKELDLSNNQLTDL-------PEPLGNLtNLK-----SLDLSN---------------NQLTDLPEELGNLTNLKELDLS 190

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  220 RNRIRLIeGLTFQGLNSLEVLKLQRNNISKLTDgAFWGLSKMHVLVLSFNNLTRLDEeslaelsslsvlrlshnsishia 299
Cdd:COG4886   191 NNQITDL-PEPLGNLTNLEELDLSGNQLTDLPE-PLANLTNLETLDLSNNQLTDLPE----------------------- 245

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767922909  300 egaFKGLRSLRVLDLDHNEISgtiedTSGAFSGLDSLSKLTLFGNKIKSVAKRAFSGLEGLEHLNLGGNAI 370
Cdd:COG4886   246 ---LGNLTNLEELDLSNNQLT-----DLPPLANLTNLKTLDLSNNQLTDLKLKELELLLGLNSLLLLLLLL 308

Leucine-rich repeat (LRR) protein [Transcription];

Pssm-ID: 443914 [Multi-domain] Cd Length: 414 Bit Score: 106.94 E-value: 2.38e-24

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  139 LSLEVLDLSLNNITEVRNTCFPHGPPIKELNLAGNRIGTLELGAFDGLSRSLLTLRLSKNRITQLPVRAFKLPRLTQLDL 218
Cdd:COG4886    24 LILLLLLLLLLLALLLLSLLSLLLLLTLLLSLLLRDLLLSSLLLLLSLLLLLLLSLLLLSLLLLGLTDLGDLTNLTELDL 103

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  219 NRNRirlieglTFQGLNSLEVLKLQRNNISKLTDgAFWGLSKMHVLVLSFNNLTRLDEEsLAELSSLSVLRLSHNSISHI 298
Cdd:COG4886   104 SGNE-------ELSNLTNLESLDLSGNQLTDLPE-ELANLTNLKELDLSNNQLTDLPEP-LGNLTNLKSLDLSNNQLTDL 174

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  299 AEgAFKGLRSLRVLDLDHNEISgtieDTSGAFSGLDSLSKLTLFGNKIKSVAKrAFSGLEGLEHLNLGGNAIRSvqFDAF 378
Cdd:COG4886   175 PE-ELGNLTNLKELDLSNNQIT----DLPEPLGNLTNLEELDLSGNQLTDLPE-PLANLTNLETLDLSNNQLTD--LPEL 246

                         250       260
                  ....*....|....*....|....*..
gi 767922909  379 VKMKNLKELHISsdsflcDCQLKWLPP 405
Cdd:COG4886   247 GNLTNLEELDLS------NNQLTDLPP 267

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 94.63 E-value: 3.50e-23

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909   645 PSLVVPLEDRVVSVGETVALQCKATGNPPPRITWFKGDRPLSLTERHHLT--PDNQLLVVQNVVAEDAGRYTCEMSNTLG 722
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTyeGGTYTLTISNVQPDDSGKYTCVATNSAG 80

                           90
                   ....*....|
gi 767922909   723 TERAHSQLSV 732
Cdd:pfam07679   81 EAEASAELTV 90

Leucine-rich repeat (LRR) protein [Transcription];

Pssm-ID: 443914 [Multi-domain] Cd Length: 414 Bit Score: 103.09 E-value: 5.73e-23

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909   51 SLDCGGRGLAALPGDLPSWT--RSLNLSYNKLSEIdPAGFEDLPNLQEVYLNNNELTAVPSLGAASSHVVSLFLQHNKIR 128
Cdd:COG4886   117 SLDLSGNQLTDLPEELANLTnlKELDLSNNQLTDL-PEPLGNLTNLKSLDLSNNQLTDLPEELGNLTNLKELDLSNNQIT 195

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  129 SVEG--SQLKaylSLEVLDLSLNNITEVrntcfphGPPI------KELNLAGNRIGTL-ELGA--------FDGlsrsll 191
Cdd:COG4886   196 DLPEplGNLT---NLEELDLSGNQLTDL-------PEPLanltnlETLDLSNNQLTDLpELGNltnleeldLSN------ 259

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  192 tlrlskNRITQLPVRAfKLPRLTQLDLNRNRirlIEGLTFQGLNSLEVLKLQRNNISKLTDGAFWGLSKMHVLVLSFNNL 271
Cdd:COG4886   260 ------NQLTDLPPLA-NLTNLKTLDLSNNQ---LTDLKLKELELLLGLNSLLLLLLLLNLLELLILLLLLTTLLLLLLL 329

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 767922909  272 TRLDEESLAELSSLSVLRLSHNSISHIAEGAFKGLRSLRVLDLDHNEISGTIEDT 326
Cdd:COG4886   330 LKGLLVTLTTLALSLSLLALLTLLLLLNLLSLLLTLLLTLGLLGLLEATLLTLAL 384

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.

Pssm-ID: 411060 [Multi-domain] Cd Length: 220 Bit Score: 85.99 E-value: 9.93e-19

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909   73 LNLSYNKLSEIDpaGFEDLPNLQEVYLNNNELTAVPSLGAASsHVVSLFLQHNKIRSVEGsqlkaylslevldlsLNNit 152
Cdd:cd21340     7 LYLNDKNITKID--NLSLCKNLKVLYLYDNKITKIENLEFLT-NLTHLYLQNNQIEKIEN---------------LEN-- 66

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  153 evrntcfphgppikelnlagnrigtlelgafdglsrslltlrlsknritqlpvrafkLPRLTQLDLNRNRIRLIEGLtfQ 232
Cdd:cd21340    67 ---------------------------------------------------------LVNLKKLYLGGNRISVVEGL--E 87

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  233 GLNSLEVLKLQRNNI---SKLT--DGAFWGLSK-MHVLVLSFNNLTRLDEeslaelsslsvlrlshnsishiaegaFKGL 306
Cdd:cd21340    88 NLTNLEELHIENQRLppgEKLTfdPRSLAALSNsLRVLNISGNNIDSLEP--------------------------LAPL 141

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*
gi 767922909  307 RSLRVLDLDHNEISGtIEDTSGAFSGLDSLSKLTLFGNKIKSVAK 351
Cdd:cd21340   142 RNLEQLDASNNQISD-LEELLDLLSSWPSLRELDLTGNPVCKKPK 185

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 80.30 E-value: 2.71e-18

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767922909   645 PSLVVPLEDRVVSVGETVALQCKATGNPPPRITWFKGDRPL--SLTERHHLTPDNQLLVVQNVVAEDAGRYTCEMSN 719
Cdd:pfam13927    2 PVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPIssGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

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

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 78.32 E-value: 1.41e-17

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909    652 EDRVVSVGETVALQCKATGNPPPRITWFK-GDRPLSLTERHHLTPDNQL--LVVQNVVAEDAGRYTCEMSNTLGTERAHS 728
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKqGGKLLAESGRFSVSRSGSTstLTISNVTPEDSGTYTCAATNSSGSASSGT 81


                    ....
gi 767922909    729 QLSV 732
Cdd:smart00410   82 TLTV 85

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.

Pssm-ID: 411060 [Multi-domain] Cd Length: 220 Bit Score: 77.13 E-value: 1.19e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  212 RLTQLDLNRNRIRLIEGLTFqgLNSLEVLKLQRNNISKLTDgafwglskmhvlvLSFN-NLTRLDEEslaelsslsvlrl 290
Cdd:cd21340     3 RITHLYLNDKNITKIDNLSL--CKNLKVLYLYDNKITKIEN-------------LEFLtNLTHLYLQ------------- 54

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  291 sHNSISHIaEGaFKGLRSLRVLDLDHNEISgTIE--------------------------DTSGAFSGLDSLSKLTLFGN 344
Cdd:cd21340    55 -NNQIEKI-EN-LENLVNLKKLYLGGNRIS-VVEglenltnleelhienqrlppgekltfDPRSLAALSNSLRVLNISGN 130

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*...
gi 767922909  345 KIKSVAKraFSGLEGLEHLNLGGNAIRSVQ--FDAFVKMKNLKELHIS 390
Cdd:cd21340   131 NIDSLEP--LAPLRNLEQLDASNNQISDLEelLDLLSSWPSLRELDLT 176

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.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 70.44 E-value: 6.88e-15

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767922909  662 VALQCKATGNPPPRITWFKGDRPLSLT--ERHHLTPDNQLLVVQNVVAEDAGRYTCEMSNTLGTERAHS 728
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSsrDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASAS 69

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

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 69.83 E-value: 1.53e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  653 DRVVSVGETVALQCKATGNPPPRITWFKGDRPLSLTERHHLTPDNQLLVVQNVVAEDAGRYTCEMSNTLGTERAHSQLSV 732
Cdd:cd20952     8 NQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDERITTLENGSLQIKGAEKSDTGEYTCVALNLSGEATWSAVLDV 87

Leucine rich repeat;

Pssm-ID: 404697 [Multi-domain] Cd Length: 61 Bit Score: 68.71 E-value: 1.99e-14

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767922909   211 PRLTQLDLNRNRIRLIEGLTFQGLNSLEVLKLQRNNISKLTDGAFWGLSKMHVLVLSFNNL 271
Cdd:pfam13855    1 PNLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

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.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 68.96 E-value: 2.89e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  650 PLEDRVVSVGETVALQCKATGNPPPRITWFKGDRPLS-LTERHHLTpdNQLLVVQNVVAEDAGRYTCEMSNTLGTERAHS 728
Cdd:cd20978     7 PEKNVVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQgPMERATVE--DGTLTIINVQPEDTGYYGCVATNEIGDIYTET 84


                  ....
gi 767922909  729 QLSV 732
Cdd:cd20978    85 LLHV 88

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.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 68.19 E-value: 4.55e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  653 DRVVSVGETVALQCKATGNPPPRITWFK--GDRPLSlteRHHLTPDNQLLvVQNVVAEDAGRYTCEMSNTLGTERAHSQL 730
Cdd:cd05725     6 NQVVLVDDSAEFQCEVGGDPVPTVRWRKedGELPKG---RYEILDDHSLK-IRKVTAGDMGSYTCVAENMVGKIEASATL 81


                  ..
gi 767922909  731 SV 732
Cdd:cd05725    82 TV 83

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.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 68.19 E-value: 4.87e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  555 KTPHDITIRTTTMARLECAATGHPNPQIAWQKDGGtDFPaarERRMHVMpDDDVFFITDVKIDDAGVYSCTAQNSAGSIS 634
Cdd:cd05725     2 KRPQNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDG-ELP---KGRYEIL-DDHSLKIRKVTAGDMGSYTCVAENMVGKIE 76


                  ....*..
gi 767922909  635 ANATLTV 641
Cdd:cd05725    77 ASATLTV 83

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

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 68.30 E-value: 5.80e-14

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909    557 PHDITIRTTTMARLECAATGHPNPQIAWQKDGGTdfPAARERRMHVMPDDDVF--FITDVKIDDAGVYSCTAQNSAGSIS 634
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGK--LLAESGRFSVSRSGSTStlTISNVTPEDSGTYTCAATNSSGSAS 78


                    ....*..
gi 767922909    635 ANATLTV 641
Cdd:smart00410   79 SGTTLTV 85

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.

Pssm-ID: 143222 [Multi-domain] Cd Length: 74 Bit Score: 67.66 E-value: 6.38e-14

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767922909  659 GETVALQCKATGNPPPRITWFKGDRPLSLtERHHLTPDNQLLVVQNVVAEDAGRYTCEMSNTLGTERAHSQLSV 732
Cdd:cd05745     2 GQTVDFLCEAQGYPQPVIAWTKGGSQLSV-DRRHLVLSSGTLRISRVALHDQGQYECQAVNIVGSQRTVAQLTV 74

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) 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, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), 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 Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 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.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 68.35 E-value: 6.75e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  551 PSFTKTPHDITIRTTTMARLECAATGHPNPQIAWQKDG---GTDFPAARERRMhVMPDDDVFFITDV----KIDDAGVYS 623
Cdd:cd07693     1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGqplETDKDDPRSHRI-VLPSGSLFFLRVVhgrkGRSDEGVYV 79

                          90
                  ....*....|....*....
gi 767922909  624 CTAQNSAG-SISANATLTV 641
Cdd:cd07693    80 CVAHNSLGeAVSRNASLEV 98

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.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 67.52 E-value: 1.07e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  551 PSFTKTPHDITIRTTTMARLECAATGHPNPQIAWQKDGGTDFPAARERRMHVMPDDDVFFITDVKIDDAGVYSCTAQNSA 630
Cdd:cd05744     1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVRENGRHSLIIEPVTKRDAGIYTCIARNRA 80

                          90
                  ....*....|.
gi 767922909  631 GSISANATLTV 641
Cdd:cd05744    81 GENSFNAELVV 91

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 66.82 E-value: 1.25e-13

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767922909   551 PSFTKTPHDITIRTTTMARLECAATGHPNPQIAWQKDGGTDFPaARERRMHVMPDDDVFFITDVKIDDAGVYSCTAQN 628
Cdd:pfam13927    2 PVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISS-GSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

Leucine-rich repeat (LRR) protein [Transcription];

Pssm-ID: 443914 [Multi-domain] Cd Length: 414 Bit Score: 73.43 E-value: 2.51e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  213 LTQLDLNRNRIRLIEGLTFQGLNSLEVLKLQRNNISKLTDGAFWGLSKMhvlvlsfNNLTRLD---EESLAELSSLSVLR 289
Cdd:COG4886    47 LLLTLLLSLLLRDLLLSSLLLLLSLLLLLLLSLLLLSLLLLGLTDLGDL-------TNLTELDlsgNEELSNLTNLESLD 119

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  290 LSHNSISHIAEgAFKGLRSLRVLDLDHNEISgtieDTSGAFSGLDSLSKLTLFGNKIKSVAKrAFSGLEGLEHLNLGGNA 369
Cdd:COG4886   120 LSGNQLTDLPE-ELANLTNLKELDLSNNQLT----DLPEPLGNLTNLKSLDLSNNQLTDLPE-ELGNLTNLKELDLSNNQ 193

                         170       180       190
                  ....*....|....*....|....*....|....*...
gi 767922909  370 IRSVQfDAFVKMKNLKELHISsdsflcDCQLKWLPPWL 407
Cdd:COG4886   194 ITDLP-EPLGNLTNLEELDLS------GNQLTDLPEPL 224

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.

Pssm-ID: 409548 [Multi-domain] Cd Length: 96 Bit Score: 66.04 E-value: 3.72e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  644 TPSLVVPLEDRVVSVGETVALQCKATGNPPPRITWFKGDRPLSLTER----HHLTPDNQL---LVVQNVVAEDAGRYTCE 716
Cdd:cd20956     1 APVLLETFSEQTLQPGPSVSLKCVASGNPLPQITWTLDGFPIPESPRfrvgDYVTSDGDVvsyVNISSVRVEDGGEYTCT 80


                  ....*..
gi 767922909  717 MSNTLGT 723
Cdd:cd20956    81 ATNDVGS 87

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.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 65.99 E-value: 4.18e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  641 VLETPSlvvPLEDRVVSVGETVALQCKATGNPPPRITWF-KGDRPLSLTERHHLTPDNQLLVVQNVVAEDAGRYTCEMSN 719
Cdd:cd20970     2 VISTPQ---PSFTVTAREGENATFMCRAEGSPEPEISWTrNGNLIIEFNTRYIVRENGTTLTIRNIRRSDMGIYLCIASN 78

leucine-rich repeat receptor-like protein kinase; Provisional

Pssm-ID: 215061 [Multi-domain] Cd Length: 968 Bit Score: 73.73 E-value: 4.59e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909   73 LNLSYNKLSEIDPAGFEDLPNLQEVYLNNNELTA-VPSLGAASSHVVSLFLQHNKIrSVEGSQLKAYL-SLEVLDLSLNN 150
Cdd:PLN00113  241 LDLVYNNLTGPIPSSLGNLKNLQYLFLYQNKLSGpIPPSIFSLQKLISLDLSDNSL-SGEIPELVIQLqNLEILHLFSNN 319

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  151 ITEVRNTCFPHGPPIKELNLAGNRigtlelgaFDGlsrslltlrlsknritQLPVRAFKLPRLTQLDLNRNRI--RLIEG 228
Cdd:PLN00113  320 FTGKIPVALTSLPRLQVLQLWSNK--------FSG----------------EIPKNLGKHNNLTVLDLSTNNLtgEIPEG 375

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  229 LTFQG----------------------LNSLEVLKLQRNNISKLTDGAFWGLSKMHVLVLSFNNLTRLDEESLAELSSLS 286
Cdd:PLN00113  376 LCSSGnlfklilfsnslegeipkslgaCRSLRRVRLQDNSFSGELPSEFTKLPLVYFLDISNNNLQGRINSRKWDMPSLQ 455

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  287 VLRLSHNSISHIAEGAFkGLRSLRVLDLDHNEISGTIEDTSGAFSgldSLSKLTLFGNKIKSVAKRAFSGLEGLEHLNLG 366
Cdd:PLN00113  456 MLSLARNKFFGGLPDSF-GSKRLENLDLSRNQFSGAVPRKLGSLS---ELMQLKLSENKLSGEIPDELSSCKKLVSLDLS 531

                         330       340
                  ....*....|....*....|....
gi 767922909  367 GNAIRSVQFDAFVKMKNLKELHIS 390
Cdd:PLN00113  532 HNQLSGQIPASFSEMPVLSQLDLS 555

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.

Pssm-ID: 409357 [Multi-domain] Cd Length: 88 Bit Score: 65.65 E-value: 5.65e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  645 PSLVVPL-EDRVVSVGETVALQCKATGNPPPRITWFKGDRPlsLTERHHLTPDNQLLVVQNVVAEDAGRYTCEMSNTLGT 723
Cdd:cd04968     1 PSIKVRFpADTYALKGQTVTLECFALGNPVPQIKWRKVDGS--PSSQWEITTSEPVLEIPNVQFEDEGTYECEAENSRGK 78


                  ....*....
gi 767922909  724 ERAHSQLSV 732
Cdd:cd04968    79 DTVQGRIIV 87

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.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 64.66 E-value: 6.25e-13

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767922909  568 ARLECAATGHPNPQIAWQKDGGTDFPAARERRMHVmPDDDVFFITDVKIDDAGVYSCTAQNSA-GSISANA 637
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSE-LGNGTLTISNVTLEDSGTYTCVASNSAgGSASASV 70

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.

Pssm-ID: 409550 [Multi-domain] Cd Length: 89 Bit Score: 64.51 E-value: 1.04e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  645 PSLVVPLEDRVVSVGETVALQCKATGNPPPRITWFKGDRPLSLTERHHLTPdNQLLVVQNVV-AEDAGRYTCEMSNTLG- 722
Cdd:cd20958     1 PPFIRPMGNLTAVAGQTLRLHCPVAGYPISSITWEKDGRRLPLNHRQRVFP-NGTLVIENVQrSSDEGEYTCTARNQQGq 79

                          90
                  ....*....|
gi 767922909  723 TERAHSQLSV 732
Cdd:cd20958    80 SASRSVFVKV 89

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 64.16 E-value: 1.38e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  555 KTPHDITIRTTTMARLECAATGHPNPQIAWQKDGGtdfPAARERRMHVMPDDdvFFITDVKIDDAGVYSCTAQNSAGSIS 634
Cdd:cd05728     4 KVISDTEADIGSSLRWECKASGNPRPAYRWLKNGQ---PLASENRIEVEAGD--LRITKLSLSDSGMYQCVAENKHGTIY 78


                  ....*..
gi 767922909  635 ANATLTV 641
Cdd:cd05728    79 ASAELAV 85

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

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 64.02 E-value: 1.62e-12

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767922909  655 VVSVGETVALQCKATGNPPPRITWFKGDRPLSLTERHHLTPDNQlLVVQNVVAEDAGRYTCEMSNTLGTERAHSQLSV 732
Cdd:cd04969    13 LAAKGGDVIIECKPKASPKPTISWSKGTELLTNSSRICILPDGS-LKIKNVTKSDEGKYTCFAVNFFGKANSTGSLSV 89

Leucine rich repeat;

Pssm-ID: 404697 [Multi-domain] Cd Length: 61 Bit Score: 62.54 E-value: 2.57e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 767922909   292 HNSISHIAEGAFKGLRSLRVLDLDHNEISgTIEDtsGAFSGLDSLSKLTLFGNKI 346
Cdd:pfam13855   10 NNRLTSLDDGAFKGLSNLKVLDLSNNLLT-TLSP--GAFSGLPSLRYLDLSGNRL 61

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.

Pssm-ID: 409548 [Multi-domain] Cd Length: 96 Bit Score: 63.35 E-value: 3.24e-12

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767922909  570 LECAATGHPNPQIAWQKDGgtdFPAARERRM----HVMPDDDV---FFITDVKIDDAGVYSCTAQNSAGSISANATLTV 641
Cdd:cd20956    21 LKCVASGNPLPQITWTLDG---FPIPESPRFrvgdYVTSDGDVvsyVNISSVRVEDGGEYTCTATNDVGSVSHSARINV 96

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.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 62.59 E-value: 5.48e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  554 TKTPHDITIRTTTMARLECAATGHPNPQIAWQKDGGtdfPAARERRMHVMPDDD---VFFITDVKIDDAGVYSCTAQNSA 630
Cdd:cd20973     1 IQTLRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDN---PIVESRRFQIDQDEDglcSLIISDVCGDDSGKYTCKAVNSL 77

                          90
                  ....*....|.
gi 767922909  631 GSISANATLTV 641
Cdd:cd20973    78 GEATCSAELTV 88

Leucine rich repeat;

Pssm-ID: 404697 [Multi-domain] Cd Length: 61 Bit Score: 61.77 E-value: 5.79e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909   236 SLEVLKLQRNNISKLTDGAFWGLSKMHVLVLSfnnltrldeeslaelsslsvlrlsHNSISHIAEGAFKGLRSLRVLDLD 315
Cdd:pfam13855    2 NLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLS------------------------NNLLTTLSPGAFSGLPSLRYLDLS 57


                   ....
gi 767922909   316 HNEI 319
Cdd:pfam13855   58 GNRL 61

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.

Pssm-ID: 409391 [Multi-domain] Cd Length: 98 Bit Score: 63.05 E-value: 5.85e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  553 FTKTPHDITIRTTTMARLECAATGHPNPQIAWQKDGGTDF-----PAARERRMHVMPDDDVFfITDVKIDDAGVYSCTAQ 627
Cdd:cd05726     2 FVVKPRDQVVALGRTVTFQCETKGNPQPAIFWQKEGSQNLlfpyqPPQPSSRFSVSPTGDLT-ITNVQRSDVGYYICQAL 80

                          90
                  ....*....|....
gi 767922909  628 NSAGSISANATLTV 641
Cdd:cd05726    81 NVAGSILAKAQLEV 94

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band 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. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. 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 I1 domain of the titin I-band 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, 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.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 62.44 E-value: 7.92e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  551 PSFTKTPHDITIRTTTMARLECAATGHPNPQIAWQKDGGTDFPAARERRMHVMPDDDV--FFITDVKIDDAGVYSCTAQN 628
Cdd:cd20951     1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDPSSIPGKYKIESEYGVhvLHIRRVTVEDSAVYSAVAKN 80

                          90
                  ....*....|...
gi 767922909  629 SAGSISANATLTV 641
Cdd:cd20951    81 IHGEASSSASVVV 93

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.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 62.22 E-value: 9.73e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  645 PSLVVPLEDRVVSVGETVALQCKATGNPPPRITWFKGDRPLslterhHLTPDNQL--------LVVQNVVAEDAGRYTCE 716
Cdd:cd20972     2 PQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKEL------QNSPDIQIhqegdlhsLIIAEAFEEDTGRYSCL 75

                          90
                  ....*....|....*.
gi 767922909  717 MSNTLGTERAHSQLSV 732
Cdd:cd20972    76 ATNSVGSDTTSAEIFV 91

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.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 61.74 E-value: 1.16e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  645 PSLVVPLEDRVVSVGETVALQCKATGNPPPRITWFKGDRPLSLTERHHLTPDN---QLLVVQNVVAEDAGRYTCEMSNTL 721
Cdd:cd05744     1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVREngrHSLIIEPVTKRDAGIYTCIARNRA 80

                          90
                  ....*....|.
gi 767922909  722 GTERAHSQLSV 732
Cdd:cd05744    81 GENSFNAELVV 91

Leucine-rich repeat (LRR) protein [Transcription];

Pssm-ID: 443914 [Multi-domain] Cd Length: 414 Bit Score: 67.65 E-value: 1.56e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  213 LTQLDLNRNRIRLIEGLTFQGLNSLEVLKLQRNNISKLTDGAFWGLSKMHVLVLSFNNLTRLDEESLAELSSLSVLRLSH 292
Cdd:COG4886    21 LTTLILLLLLLLLLLALLLLSLLSLLLLLTLLLSLLLRDLLLSSLLLLLSLLLLLLLSLLLLSLLLLGLTDLGDLTNLTE 100

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  293 NSISHIAEgaFKGLRSLRVLDLDHNEISgtieDTSGAFSGLDSLSKLTLFGNKIKSVAKrAFSGLEGLEHLNLGGNAIRS 372
Cdd:COG4886   101 LDLSGNEE--LSNLTNLESLDLSGNQLT----DLPEELANLTNLKELDLSNNQLTDLPE-PLGNLTNLKSLDLSNNQLTD 173

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 767922909  373 VQfDAFVKMKNLKELHISsdsflcDCQLKWLPPWL 407
Cdd:COG4886   174 LP-EELGNLTNLKELDLS------NNQITDLPEPL 201

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1(FGFRL1); 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 like-1(FGFRL1). FGFRL1 is comprised of a signal peptide, three extracellular Ig-like modules, a transmembrane segment, and a short intracellular domain. FGFRL1 is expressed preferentially in skeletal tissues. Similar to FGF receptors, the expressed protein interacts specifically with heparin and with FGF2. 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.

Pssm-ID: 409442 Cd Length: 92 Bit Score: 61.41 E-value: 1.94e-11

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 767922909  658 VGETVALQCKATGNPPPRITWFKGDRPLSLTERHHLTPDNQLLVVQNVVAEDAGRYTCEMSNTLG 722
Cdd:cd05856    18 VGSSVRLKCVASGNPRPDITWLKDNKPLTPPEIGENKKKKWTLSLKNLKPEDSGKYTCHVSNRAG 82

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as 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. 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.

Pssm-ID: 409422 [Multi-domain] Cd Length: 95 Bit Score: 61.03 E-value: 2.52e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  645 PSLVVPLEDRVVSVGETVALQCKATGNPPPRITWfkgDRPLSLTERHHLTPDNQL----------LVVQNVVAEDAGRYT 714
Cdd:cd05765     1 PALVNSPTHQTVKVGETASFHCDVTGRPQPEITW---EKQVPGKENLIMRPNHVRgnvvvtnigqLVIYNAQPQDAGLYT 77

                          90
                  ....*....|....*...
gi 767922909  715 CEMSNTLGTERAHSQLSV 732
Cdd:cd05765    78 CTARNSGGLLRANFPLSV 95

Second 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 second 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 the 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, and 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, 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 Slit-2 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.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 60.49 E-value: 2.78e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  557 PHDITIRTTTMARLECAA-TGHPNPQIAWQKDGGTdfpaARERRMHV-MPDDDVFFITDVKIDDAGVYSCTAQNSAGS-I 633
Cdd:cd05724     4 PSDTQVAVGEMAVLECSPpRGHPEPTVSWRKDGQP----LNLDNERVrIVDDGNLLIAEARKSDEGTYKCVATNMVGErE 79


                  ....*...
gi 767922909  634 SANATLTV 641
Cdd:cd05724    80 SRAARLSV 87

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) 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, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), 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 Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 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.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 61.03 E-value: 2.94e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  640 TVLETPSlvvpleDRVVSVGETVALQCKATGNPPPRITWFKGDRPLSLTE-----RHHLTPDNQLLVVQNV----VAEDA 710
Cdd:cd07693     2 RIVEHPS------DLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLETDKddprsHRIVLPSGSLFFLRVVhgrkGRSDE 75

                          90
                  ....*....|....*..
gi 767922909  711 GRYTCEMSNTLGTERAH 727
Cdd:cd07693    76 GVYVCVAHNSLGEAVSR 92

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.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 60.34 E-value: 3.37e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  551 PSFTKTPHDITIRTTTMARLECAATGHPNPQIAWQKDGgTDFPAARERrMHVMPDDDVFFITDVKIDDAGVYSCTAQNSA 630
Cdd:cd20976     2 PSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNA-QPLQYAADR-STCEAGVGELHIQDVLPEDHGTYTCLAKNAA 79

                          90
                  ....*....|.
gi 767922909  631 GSISANATLTV 641
Cdd:cd20976    80 GQVSCSAWVTV 90

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 60.10 E-value: 3.66e-11

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767922909   655 VVSVGETVALQCKATGNPPPRITWFKGDRPLslterhhltPDNQLLVVQNVVAEDAGRYTCEMSNTLGTERAHS 728
Cdd:pfam13895   10 VVTEGEPVTLTCSAPGNPPPSYTWYKDGSAI---------SSSPNFFTLSVSAEDSGTYTCVARNGRGGKVSNP 74

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.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 59.57 E-value: 6.23e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  645 PSLVVPLEDRVVSVGETVALQCKATGNPPPRITWFKGDRPLSLT-ERHHLTPDNQLLVVQNVVAEDAGRYTCEMSNTLGT 723
Cdd:cd20976     2 PSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQYAaDRSTCEAGVGELHIQDVLPEDHGTYTCLAKNAAGQ 81


                  ....*....
gi 767922909  724 ERAHSQLSV 732
Cdd:cd20976    82 VSCSAWVTV 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

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 59.43 E-value: 7.11e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  553 FTKTPHDITIRTTTMARLECAATGHPNPQIAWQKDGGTDfpAARERRMHVMPDDdVFFITDVKIDDAGVYSCTAQNSAGS 632
Cdd:cd20952     2 ILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPL--LGKDERITTLENG-SLQIKGAEKSDTGEYTCVALNLSGE 78


                  ....*....
gi 767922909  633 ISANATLTV 641
Cdd:cd20952    79 ATWSAVLDV 87

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 59.12 E-value: 8.24e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909   446 KPQIITQPETTMAMVGKDIRFTCsaASSSSSPMTFAWKKDNEVLTnadmenfvHVHAQDGEVMEYTTILHLRQVTFGHEG 525
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVTLTC--EATGSPPPTITWYKNGEPIS--------SGSTRSRSLSGSNSTLTISNVTRSDAG 70


                   ....*...
gi 767922909   526 RYQCVITN 533
Cdd:pfam13927   71 TYTCVASN 78

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third 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. 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. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 59.08 E-value: 1.00e-10

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767922909  652 EDRVVSVGETVALQCKATGNPPPRITWFKGDRPLSLTERHHLTPDNQlLVVQNVVAEDAGRYTCEMSNTLGTERAHSQL 730
Cdd:cd20957     9 PVQTVDFGRTAVFNCSVTGNPIHTVLWMKDGKPLGHSSRVQILSEDV-LVIPSVKREDKGMYQCFVRNDGDSAQATAEL 86

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. 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.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 59.00 E-value: 1.08e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  554 TKTPHDITIRTTTMARLECAATGHPNPQIAWQKDGGTDFPAARERRMHVMPDDDVFfiTDVKIDDAGVYSCTAQNSAGSI 633
Cdd:cd04978     3 IIEPPSLVLSPGETGELICEAEGNPQPTITWRLNGVPIEPAPEDMRRTVDGRTLIF--SNLQPNDTAVYQCNASNVHGYL 80


                  ....*....
gi 767922909  634 SANATLTVL 642
Cdd:cd04978    81 LANAFLHVL 89

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.

Pssm-ID: 409582 Cd Length: 91 Bit Score: 58.96 E-value: 1.08e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  551 PSFTKTPHDITIRTTTMARLECAATGHPNPQIAWQKDGGTDFPAARERRMHVMPDDDVFFITDVKIDDAGVYSCTAQNSA 630
Cdd:cd20990     1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSAHKMLVRENGVHSLIIEPVTSRDAGIYTCIATNRA 80

                          90
                  ....*....|.
gi 767922909  631 GSISANATLTV 641
Cdd:cd20990    81 GQNSFNLELVV 91

Leucine rich repeat;

Pssm-ID: 404697 [Multi-domain] Cd Length: 61 Bit Score: 57.92 E-value: 1.15e-10

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909   335 SLSKLTLFGNKIKSVAKRAFSGLEGLEHLNLGGNAIRSVQFDAFVKMKNLKELHISSDSF 394
Cdd:pfam13855    2 NLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

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.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 58.67 E-value: 1.32e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  557 PHDITIRTTTMARLECAATGHPNPQIAWQKDGGTdfPAARERRMHVMPDDDVFFITDVKIDDAGVYSCTAQNSA-GSISA 635
Cdd:cd20970     9 SFTVTAREGENATFMCRAEGSPEPEISWTRNGNL--IIEFNTRYIVRENGTTLTIRNIRRSDMGIYLCIASNGVpGSVEK 86


                  ....*.
gi 767922909  636 NATLTV 641
Cdd:cd20970    87 RITLQV 92

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.

Pssm-ID: 409391 [Multi-domain] Cd Length: 98 Bit Score: 59.20 E-value: 1.39e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  648 VVPLEDRVVSVGETVALQCKATGNPPPRITWFK--------GDRPLSLTERHHLTPDNQlLVVQNVVAEDAGRYTCEMSN 719
Cdd:cd05726     3 VVKPRDQVVALGRTVTFQCETKGNPQPAIFWQKegsqnllfPYQPPQPSSRFSVSPTGD-LTITNVQRSDVGYYICQALN 81

                          90
                  ....*....|...
gi 767922909  720 TLGTERAHSQLSV 732
Cdd:cd05726    82 VAGSILAKAQLEV 94

C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein (also known as myomesin-2). Myomesin and M-protein are both structural proteins localized to the M-band, a transverse structure in the center of the sarcomere, and are candidates for M-band bridges. Both proteins are modular, consisting mainly of repetitive Ig-like and fibronectin type III (FnIII) domains. Myomesin is expressed in all types of vertebrate striated muscle; M-protein has a muscle-type specific expression pattern. Myomesin is present in both slow and fast fibers; M-protein is present only in fast fibers. It has been suggested that myomesin acts as a molecular spring with alternative splicing as a means of modifying its elasticity.

Pssm-ID: 319300 Cd Length: 92 Bit Score: 58.76 E-value: 1.47e-10

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767922909  659 GETVALQCKATGNPPPRITWFKGDRPLSLTERHHLTPDNQLLV---VQNVVAEDAGRYTCEMSNTLGTERAHSQLSV 732
Cdd:cd05737    16 GKTLNLTCNVWGDPPPEVSWLKNDQALAFLDHCNLKVEAGRTVyftINGVSSEDSGKYGLVVKNKYGSETSDVTVSV 92

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.

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 57.98 E-value: 1.87e-10

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 767922909  655 VVSVGETVALQCKATGNPPPRITWFKGDRPLSLTERH--HLTPDNQLLVVQNVVAEDAGRYTCEMSNTLGTERAH 727
Cdd:cd05748     3 VVRAGESLRLDIPIKGRPTPTVTWSKDGQPLKETGRVqiETTASSTSLVIKNAKRSDSGKYTLTLKNSAGEKSAT 77

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.

Pssm-ID: 409393 [Multi-domain] Cd Length: 95 Bit Score: 58.39 E-value: 2.37e-10

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767922909  656 VSVGETVALQCKATGNPPPRITWFKGDRPLSLTERHHLTPDNQ---LLVVQNVVAEDAGRYTCEMSNTLGT 723
Cdd:cd05729    16 LPAANKVRLECGAGGNPMPNITWLKDGKEFKKEHRIGGTKVEEkgwSLIIERAIPRDKGKYTCIVENEYGS 86

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.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 57.58 E-value: 2.93e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  650 PLEDRVVSVGETVALQCKATGNPPPRITWFKGDRPlsLTERHHLT-----PDNQLLVVQNVVAEDAGRYTCEMSNTLGTE 724
Cdd:cd20973     3 TLRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNP--IVESRRFQidqdeDGLCSLIISDVCGDDSGKYTCKAVNSLGEA 80


                  ....*...
gi 767922909  725 RAHSQLSV 732
Cdd:cd20973    81 TCSAELTV 88

Leucine-rich repeats (LRRs), ribonuclease inhibitor (RI)-like subfamily. LRRs are 20-29 residue sequence motifs present in many proteins that participate in protein-protein interactions and have different functions and cellular locations. LRRs correspond to structural units consisting of a beta strand (LxxLxLxxN/CxL conserved pattern) and an alpha helix. This alignment contains 12 strands corresponding to 11 full repeats, consistent with the extent observed in the subfamily acting as Ran GTPase Activating Proteins (RanGAP1).

Pssm-ID: 238064 [Multi-domain] Cd Length: 319 Bit Score: 62.37 E-value: 3.68e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909   73 LNLSYNKLSEIDPA------GFEDLPNLQEVYLNNNeltavpSLGAASSHVVSLFLQ----------HNKIrSVEGSQLK 136
Cdd:cd00116    56 LCLSLNETGRIPRGlqsllqGLTKGCGLQELDLSDN------ALGPDGCGVLESLLRssslqelklnNNGL-GDRGLRLL 128

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  137 A------YLSLEVLDLSLNNITevrNTC-------FPHGPPIKELNLAGNRIGtlelgafdglsrslltlrlskNRITQL 203
Cdd:cd00116   129 AkglkdlPPALEKLVLGRNRLE---GAScealakaLRANRDLKELNLANNGIG---------------------DAGIRA 184

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  204 PVRAFK-LPRLTQLDLNRNRIRLIEGL----TFQGLNSLEVLKLQRNNI-----SKLTDGAFWGLSKMHVLVLSFNNLTR 273
Cdd:cd00116   185 LAEGLKaNCNLEVLDLNNNGLTDEGASalaeTLASLKSLEVLNLGDNNLtdagaAALASALLSPNISLLTLSLSCNDITD 264

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*..
gi 767922909  274 LDEESLAELsslsvlrlshnsishIAEGAfkglrSLRVLDLDHNEIS 320
Cdd:cd00116   265 DGAKDLAEV---------------LAEKE-----SLLELDLRGNKFG 291

Leucine rich repeat;

Pssm-ID: 404697 [Multi-domain] Cd Length: 61 Bit Score: 56.38 E-value: 3.91e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909   140 SLEVLDLSLNNITEVRNTCFPHGPPIKELNLAGNRIGTLELGAFDGlsrslltlrlsknritqlpvrafkLPRLTQLDLN 219
Cdd:pfam13855    2 NLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSG------------------------LPSLRYLDLS 57


                   ....
gi 767922909   220 RNRI 223
Cdd:pfam13855   58 GNRL 61

Leucine rich repeat;

Pssm-ID: 404697 [Multi-domain] Cd Length: 61 Bit Score: 56.38 E-value: 4.03e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 767922909   198 NRITQLPVRAFK-LPRLTQLDLNRNRIRLIEGLTFQGLNSLEVLKLQRNNI 247
Cdd:pfam13855   11 NRLTSLDDGAFKgLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

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.

Pssm-ID: 409546 [Multi-domain] Cd Length: 96 Bit Score: 57.32 E-value: 4.49e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  645 PSLVVPLEDRVVSVGETVALQCKATGNPPPRITWFK--GDRP-----LSLTERHHLTPdNQLLVVQNVVAEDAGRYTCEM 717
Cdd:cd20954     2 PRWIVEPVDANVAAGQDVMLHCQADGFPTPTVTWKKatGSTPgeykdLLYDPNVRILP-NGTLVFGHVQKENEGHYLCEA 80


                  ....*.
gi 767922909  718 SNTLGT 723
Cdd:cd20954    81 KNGIGS 86

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 56.89 E-value: 7.24e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  645 PSLVVPLEDRVVSVGETVALQCKATGNPPPRITWFKGDRPLS--LTERHHLTPDNQLLVVQNVVAEDAGRYTCEMSNTLG 722
Cdd:cd05736     1 PVIRVYPEFQAKEPGVEASLRCHAEGIPLPRVQWLKNGMDINpkLSKQLTLIANGSELHISNVRYEDTGAYTCIAKNEGG 80

                          90
                  ....*....|
gi 767922909  723 TERAHSQLSV 732
Cdd:cd05736    81 VDEDISSLFV 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.

Pssm-ID: 409357 [Multi-domain] Cd Length: 88 Bit Score: 56.79 E-value: 7.26e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  557 PHDITIRTTTMARLECAATGHPNPQIAWQKDGGTDFPAARERRmhvmpDDDVFFITDVKIDDAGVYSCTAQNSAGSISAN 636
Cdd:cd04968     8 PADTYALKGQTVTLECFALGNPVPQIKWRKVDGSPSSQWEITT-----SEPVLEIPNVQFEDEGTYECEAENSRGKDTVQ 82


                  ....*
gi 767922909  637 ATLTV 641
Cdd:cd04968    83 GRIIV 87

Leucine rich repeat C-terminal domain;

Pssm-ID: 214507 [Multi-domain] Cd Length: 51 Bit Score: 55.13 E-value: 8.00e-10

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|
gi 767922909    394 FLCDCQLKWLPPWLIG-RMLQAFVTATCAHPESLKGQsIFSVPPESFVCD 442
Cdd:smart00082    3 FICDCELRWLLRWLQAnEHLQDPVDLRCASPSSLRGP-LLELLHSEFKCP 51

Third immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 143259 Cd Length: 88 Bit Score: 56.18 E-value: 9.56e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  644 TPSLVVPLEDRVVSVGETVALQCKATGNPPPRITWFKGDRPLSLTErhHLTPDNQLLVVQNVVAEDAGRYTCEMSNTLGT 723
Cdd:cd05851     1 PADINVKFKDTYALKGQNVTLECFALGNPVPVIRWRKILEPMPATA--EISMSGAVLKIFNIQPEDEGTYECEAENIKGK 78


                  ....*....
gi 767922909  724 ERAHSQLSV 732
Cdd:cd05851    79 DKHQARVYV 87

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 55.73 E-value: 1.43e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909   447 PQIITQPETTMAMVGKDIRFTCSAASSSssPMTFAWKKDNEVLTNADmenFVHVHAQDGEvmeYTtiLHLRQVTFGHEGR 526
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTP--DPEVSWFKDGQPLRSSD---RFKVTYEGGT---YT--LTISNVQPDDSGK 70

                           90       100
                   ....*....|....*....|.
gi 767922909   527 YQCVITNHFGStYSHKARLTV 547
Cdd:pfam07679   71 YTCVATNSAGE-AEASAELTV 90

C-terminal immunoglobulin (Ig)-like domain of M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of M-protein (also known as myomesin-2). M-protein is a structural protein localized to the M-band, a transverse structure in the center of the sarcomere, and is a candidate for M-band bridges. M-protein is modular consisting mainly of repetitive IG-like and fibronectin type III (FnIII) domains and has a muscle-type specific expression pattern. M-protein is present in fast fibers.

Pssm-ID: 143299 Cd Length: 92 Bit Score: 55.69 E-value: 1.59e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  655 VVSV--GETVALQCKATGNPPPRITWFKGDRPLSLTERHHLTPDN---QLLVVQNVVAEDAGRYTCEMSNTLGTERAHSQ 729
Cdd:cd05891    10 VVTImeGKTLNLTCTVFGNPDPEVIWFKNDQDIELSEHYSVKLEQgkyASLTIKGVTSEDSGKYSINVKNKYGGETVDVT 89


                  ...
gi 767922909  730 LSV 732
Cdd:cd05891    90 VSV 92

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. 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.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 55.53 E-value: 1.92e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  655 VVSVGETVALQCKATGNPPPRITWFKGDRPLS-LTERHHLTPDNQLLVVQNVVAEDAGRYTCEMSNTLGTERAHSQLSVL 733
Cdd:cd04978    10 VLSPGETGELICEAEGNPQPTITWRLNGVPIEpAPEDMRRTVDGRTLIFSNLQPNDTAVYQCNASNVHGYLLANAFLHVL 89

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.

Pssm-ID: 143223 Cd Length: 69 Bit Score: 54.88 E-value: 1.95e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767922909  569 RLECAATGHPNPQIAWQKDGgtdFPAARERRMHVMPdDDVFFITDVKIDDAGVYSCTAQNSAGSISANATLT 640
Cdd:cd05746     2 QIPCSAQGDPEPTITWNKDG---VQVTESGKFHISP-EGYLAIRDVGVADQGRYECVARNTIGYASVSMVLS 69

Third 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 third 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 third 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 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, including vascular (VCAM), intercellular (ICAM), neural (NCAM) and mucosal addressin (MADCAM) cell adhesion molecules, as well as junction adhesion molecules (JAM).

Pssm-ID: 409569 Cd Length: 93 Bit Score: 55.47 E-value: 2.07e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  645 PSLVVPLEDRVVSVGETVALQCKATGNPPPRITWFKGDRPL-----SLTERHHLTPDNQLLVVqNVVAEDAGRYTCEMSN 719
Cdd:cd20977     1 PVPQYVSKDMMAKAGDVTMIYCMYGSNPTAHPNYFKNGKDVngnpeDRITRHNRTSGKRLLFK-TTLPEDEGVYTCEVDN 79

                          90
                  ....*....|....
gi 767922909  720 TLGTERAHS-QLSV 732
Cdd:cd20977    80 GVGKPQKHSlKLTV 93

Immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

Pssm-ID: 409397 [Multi-domain] Cd Length: 97 Bit Score: 55.58 E-value: 2.26e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  645 PSLVVPLEDRVVSVGETVALQCKATGNPPPRITW--FKG------DRPLSLTERHHLTPDNQLLvVQNVVAEDAGRYTCE 716
Cdd:cd05734     2 PRFVVQPNDQDGIYGKAVVLNCSADGYPPPTIVWkhSKGsgvpqfQHIVPLNGRIQLLSNGSLL-IKHVLEEDSGYYLCK 80

                          90
                  ....*....|..
gi 767922909  717 MSNTLGTERAHS 728
Cdd:cd05734    81 VSNDVGADISKS 92

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three IG-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans.

Pssm-ID: 409443 [Multi-domain] Cd Length: 95 Bit Score: 55.24 E-value: 2.35e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  656 VSVGETVALQCKATGNPPPRITWFKGDRPLSLTER---HHLTPDNQLLVVQNVVAEDAGRYTCEMSNTLGTERAHSQLSV 732
Cdd:cd05857    16 VPAANTVKFRCPAAGNPTPTMRWLKNGKEFKQEHRiggYKVRNQHWSLIMESVVPSDKGNYTCVVENEYGSINHTYHLDV 95

Second 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 second 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 the 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, and 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, 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 Slit-2 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.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 55.10 E-value: 2.45e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  653 DRVVSVGETVALQCKA-TGNPPPRITWFKGDRPLSLTERHHLTPDNQLLVVQNVVAEDAGRYTCEMSNTLGT-ERAHSQL 730
Cdd:cd05724     6 DTQVAVGEMAVLECSPpRGHPEPTVSWRKDGQPLNLDNERVRIVDDGNLLIAEARKSDEGTYKCVATNMVGErESRAARL 85


                  ..
gi 767922909  731 SV 732
Cdd:cd05724    86 SV 87

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.

Pssm-ID: 409566 [Multi-domain] Cd Length: 93 Bit Score: 55.05 E-value: 2.96e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  551 PSFTKTPHDITIRTTTMARLECAATGHPNPQIAWQKDG-GTDFPAARERRMHVMPDDDVFFITDVKIDDAGVYSCTAQNS 629
Cdd:cd20974     1 PVFTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFRDGqVISTSTLPGVQISFSDGRAKLSIPAVTKANSGRYSLTATNG 80

                          90
                  ....*....|...
gi 767922909  630 AGSISANATLTVL 642
Cdd:cd20974    81 SGQATSTAELLVL 93

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; 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 and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. 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.

Pssm-ID: 143224 [Multi-domain] Cd Length: 92 Bit Score: 55.05 E-value: 3.30e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767922909  656 VSVGETVALQCKATGNPPPRITWFKGDRPLSLTERHHLTPDN--QLLVVQNVVAEDAGRYTCEMSNTLGTERAHSQLS 731
Cdd:cd05747    15 VSEGESARFSCDVDGEPAPTVTWMREGQIIVSSQRHQITSTEykSTFEISKVQMSDEGNYTVVVENSEGKQEAQFTLT 92

C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C); The members here are composed of the C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C). MyBP-C consists of repeated domains, Ig and fibronectin type 3, and various linkers. Three isoforms of MYBP-C exist: slow-skeletal (ssMyBP-C), fast-skeletal (fsMyBP-C), and cardiac (cMyBP-C). cMYBP-C has insertions between and inside domains and an additional cardiac-specific Ig domain at the N-terminus. For cMYBP_C an interaction has been demonstrated between this C5 domain and the Ig C8 domain.

Pssm-ID: 409475 Cd Length: 86 Bit Score: 54.46 E-value: 3.48e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  655 VVSVGETVALQCKATGNPPPRITWFKGDRPLSLTE---RHHLTPDNQLLVVQNVVAEDAGRYTCEMSNTLGTERAHSQLS 731
Cdd:cd05894     6 VVVAGNKLRLDVPISGEPAPTVTWSRGDKAFTATEgrvRVESYKDLSSFVIEGAEREDEGVYTITVTNPVGEDHASLFVK 85


                  .
gi 767922909  732 V 732
Cdd:cd05894    86 V 86

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as 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. 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.

Pssm-ID: 409422 [Multi-domain] Cd Length: 95 Bit Score: 54.86 E-value: 3.92e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  551 PSFTKTPHDITIRTTTMARLECAATGHPNPQIAWQKDggtdfpaARERRMHVMPDDDV-----------FFITDVKIDDA 619
Cdd:cd05765     1 PALVNSPTHQTVKVGETASFHCDVTGRPQPEITWEKQ-------VPGKENLIMRPNHVrgnvvvtnigqLVIYNAQPQDA 73

                          90       100
                  ....*....|....*....|..
gi 767922909  620 GVYSCTAQNSAGSISANATLTV 641
Cdd:cd05765    74 GLYTCTARNSGGLLRANFPLSV 95

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.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 54.51 E-value: 3.99e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  551 PSFTKTPHDITIRTTTMARLECAATGHPNPQIAWQKDG-----GTDFPAARERRMHVMpdddvfFITDVKIDDAGVYSCT 625
Cdd:cd20972     2 PQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGkelqnSPDIQIHQEGDLHSL------IIAEAFEEDTGRYSCL 75

                          90
                  ....*....|....*.
gi 767922909  626 AQNSAGSISANATLTV 641
Cdd:cd20972    76 ATNSVGSDTTSAEIFV 91

Fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 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.

Pssm-ID: 409453 [Multi-domain] Cd Length: 89 Bit Score: 54.52 E-value: 4.16e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 767922909  568 ARLECAATGHPNPQIAWQKDGGTDFPAARERRMHVmpDDDVFFITDVKIDDAGVYSCTAQNSAGSISANATLTVL 642
Cdd:cd05867    17 ARLDCQVEGIPTPNITWSINGAPIEGTDPDPRRHV--SSGALILTDVQPSDTAVYQCEARNRHGNLLANAHVHVV 89

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.

Pssm-ID: 409408 [Multi-domain] Cd Length: 92 Bit Score: 54.44 E-value: 4.80e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  645 PSLVvPLEDRVVSVGETVALQCKATG-NPPPRITWFKGDRPLSLTERHHL----TPDNQLLVVQNVVAEDAGRYTCEMSN 719
Cdd:cd05750     1 PKLK-EMKSQTVQEGSKLVLKCEATSeNPSPRYRWFKDGKELNRKRPKNIkirnKKKNSELQINKAKLEDSGEYTCVVEN 79

                          90
                  ....*....|...
gi 767922909  720 TLGTERAHSQLSV 732
Cdd:cd05750    80 ILGKDTVTGNVTV 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.

Pssm-ID: 409395 [Multi-domain] Cd Length: 96 Bit Score: 54.07 E-value: 6.11e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  651 LEDRVVSVGETVALQCKATGNPPPRITWFKGDRPLSLTERhhlTPDNQLLV----------VQNVVAEDAGRYTCEMSNT 720
Cdd:cd05732     8 LENQTAVELEQITLTCEAEGDPIPEITWRRATRGISFEEG---DLDGRIVVrgharvssltLKDVQLTDAGRYDCEASNR 84


                  ..
gi 767922909  721 LG 722
Cdd:cd05732    85 IG 86

Second immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F; member of the I-set of IgSF domains; The members here are composed of the second 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.

Pssm-ID: 409400 [Multi-domain] Cd Length: 91 Bit Score: 54.25 E-value: 6.34e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  563 RTTTMArleCAATGHPNPQIAWQKDGGTDFPAARERRMHvMPDDDVFFITDVKIDDAGVYSCTAQNSAGS-ISANATLTV 641
Cdd:cd05738    15 RTATML---CAASGNPDPEISWFKDFLPVDTATSNGRIK-QLRSGALQIENSEESDQGKYECVATNSAGTrYSAPANLYV 90

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.

Pssm-ID: 143223 Cd Length: 69 Bit Score: 53.34 E-value: 7.18e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  662 VALQCKATGNPPPRITWFKGDRPLSLTERHHLTPDNQlLVVQNVVAEDAGRYTCEMSNTLGTERAHSQLS 731
Cdd:cd05746     1 VQIPCSAQGDPEPTITWNKDGVQVTESGKFHISPEGY-LAIRDVGVADQGRYECVARNTIGYASVSMVLS 69

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.

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 53.36 E-value: 7.71e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  560 ITIRTTTMARLECAATGHPNPQIAWQKDGgTDFPAARERRMHVMPDDDVFFITDVKIDDAGVYSCTAQNSAGSISANATL 639
Cdd:cd05748     2 IVVRAGESLRLDIPIKGRPTPTVTWSKDG-QPLKETGRVQIETTASSTSLVIKNAKRSDSGKYTLTLKNSAGEKSATINV 80


                  ..
gi 767922909  640 TV 641
Cdd:cd05748    81 KV 82

Leucine rich repeat;

Pssm-ID: 404697 [Multi-domain] Cd Length: 61 Bit Score: 52.53 E-value: 8.87e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 767922909    71 RSLNLSYNKLSEIDPAGFEDLPNLQEVYLNNNELTAVpSLGAAS--SHVVSLFLQHNKI 127
Cdd:pfam13855    4 RSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTL-SPGAFSglPSLRYLDLSGNRL 61

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.

Pssm-ID: 409460 [Multi-domain] Cd Length: 83 Bit Score: 53.38 E-value: 1.02e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767922909  659 GETVALQCKATGNPPPRITWFKGDRPLSlTERHHLTPDNQLLVVQNVVAEDAGRYTCEMSNTLGTERAHSQLSV 732
Cdd:cd05876    10 GQSLVLECIAEGLPTPTVKWLRPSGPLP-PDRVKYQNHNKTLQLLNVGESDDGEYVCLAENSLGSARHAYYVTV 82

First immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. 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.

Pssm-ID: 409387 Cd Length: 97 Bit Score: 53.64 E-value: 1.07e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  552 SFTKTPHDITIRTTTMARLECAATGHPNPQIAWQKDGGTDFPAARERRmhVMPDDDVFFITDV---KID--DAGVYSCTA 626
Cdd:cd05722     3 YFLSEPSDIVAMRGGPVVLNCSAESDPPPKIEWKKDGVLLNLVSDERR--QQLPNGSLLITSVvhsKHNkpDEGFYQCVA 80

                          90
                  ....*....|....*..
gi 767922909  627 QN-SAGSI-SANATLTV 641
Cdd:cd05722    81 QNeSLGSIvSRTARVTV 97

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 53.17 E-value: 1.08e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909   556 TPHDITIRTTTMARLECAATGHPNPQIAWQKDGgtdfpaarerrmHVMPDDDVFFITDVKIDDAGVYSCTAQNSAGSI-S 634
Cdd:pfam13895    5 TPSPTVVTEGEPVTLTCSAPGNPPPSYTWYKDG------------SAISSSPNFFTLSVSAEDSGTYTCVARNGRGGKvS 72


                   ....*..
gi 767922909   635 ANATLTV 641
Cdd:pfam13895   73 NPVELTV 79

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.

Pssm-ID: 409473 Cd Length: 92 Bit Score: 53.23 E-value: 1.09e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  645 PSLVVPLEDRVVSVGETVALQCKATGNPPPRITWFKGDRPLSL-TERHHLTPDNQ---LLVVQNVVAEDAGRYTCEMSNT 720
Cdd:cd05892     1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKKNNEMLQYnTDRISLYQDNCgriCLLIQNANKKDAGWYTVSAVNE 80

                          90
                  ....*....|..
gi 767922909  721 LGTERAHSQLSV 732
Cdd:cd05892    81 AGVVSCNARLDV 92

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

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 53.23 E-value: 1.13e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  551 PSFTKTP-HDITIRTTTMARL-ECAATGHPNPQIAWQKDGGTdfpAARERRMHVMPDDDVFfITDVKIDDAGVYSCTAQN 628
Cdd:cd04969     1 PDFELNPvKKKILAAKGGDVIiECKPKASPKPTISWSKGTEL---LTNSSRICILPDGSLK-IKNVTKSDEGKYTCFAVN 76

                          90
                  ....*....|...
gi 767922909  629 SAGSISANATLTV 641
Cdd:cd04969    77 FFGKANSTGSLSV 89

Second immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F; member of the I-set of IgSF domains; The members here are composed of the second 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.

Pssm-ID: 409400 [Multi-domain] Cd Length: 91 Bit Score: 53.09 E-value: 1.27e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  654 RVVSVGETVALQCKATGNPPPRITWFKGDRPLSLTE---RHHLTpDNQLLVVQNVVAEDAGRYTCEMSNTLGTE-RAHSQ 729
Cdd:cd05738     9 KVVEKARTATMLCAASGNPDPEISWFKDFLPVDTATsngRIKQL-RSGALQIENSEESDQGKYECVATNSAGTRySAPAN 87


                  ...
gi 767922909  730 LSV 732
Cdd:cd05738    88 LYV 90

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third 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. 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. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 52.92 E-value: 1.56e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  557 PHDITIRTTTMARLECAATGHPNPQIAWQKDGGtdfPAARERRMHVMpDDDVFFITDVKIDDAGVYSCTAQNSAGSISAN 636
Cdd:cd20957     8 PPVQTVDFGRTAVFNCSVTGNPIHTVLWMKDGK---PLGHSSRVQIL-SEDVLVIPSVKREDKGMYQCFVRNDGDSAQAT 83


                  ...
gi 767922909  637 ATL 639
Cdd:cd20957    84 AEL 86

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 52.60 E-value: 1.89e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  651 LEDRVVSVGETVALQCKATGNPPPRITWFKGDRPLSLTERHHLtpDNQLLVVQNVVAEDAGRYTCEMSNTLGTERAHSQL 730
Cdd:cd05728     6 ISDTEADIGSSLRWECKASGNPRPAYRWLKNGQPLASENRIEV--EAGDLRITKLSLSDSGMYQCVAENKHGTIYASAEL 83


                  ..
gi 767922909  731 SV 732
Cdd:cd05728    84 AV 85

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.

Pssm-ID: 409393 [Multi-domain] Cd Length: 95 Bit Score: 52.99 E-value: 1.94e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  551 PSFTKTPH----DITIRTTTMARLECAATGHPNPQIAWQKDGGTDFPAARERRMHVMPDDDVFFITDVKIDDAGVYSCTA 626
Cdd:cd05729     1 PRFTDTEKmeerEHALPAANKVRLECGAGGNPMPNITWLKDGKEFKKEHRIGGTKVEEKGWSLIIERAIPRDKGKYTCIV 80

                          90
                  ....*....|....*
gi 767922909  627 QNSAGSISANATLTV 641
Cdd:cd05729    81 ENEYGSINHTYDVDV 95

Leucine rich repeat;

Pssm-ID: 404697 [Multi-domain] Cd Length: 61 Bit Score: 51.76 E-value: 2.00e-08

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767922909   115 SHVVSLFLQHNKIRSVEGSQLKAYLSLEVLDLSLNNITEVRNTCFpHGPP-IKELNLAGNRI 175
Cdd:pfam13855    1 PNLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAF-SGLPsLRYLDLSGNRL 61

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.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 52.39 E-value: 2.09e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  551 PSFTKTPHDITIR----TTTMarlECAATGHPNPQIAWQKDGGTdFPAARERRmHVmpDDDVFFITDVKIDDAGVYSCTA 626
Cdd:cd20978     1 PKFIQKPEKNVVVkggqDVTL---PCQVTGVPQPKITWLHNGKP-LQGPMERA-TV--EDGTLTIINVQPEDTGYYGCVA 73

                          90
                  ....*....|....*
gi 767922909  627 QNSAGSISANATLTV 641
Cdd:cd20978    74 TNEIGDIYTETLLHV 88

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.

Pssm-ID: 409394 [Multi-domain] Cd Length: 83 Bit Score: 51.64 E-value: 3.06e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  564 TTTMA------RLECAATGHPNPQIAWQKDGGtDFPAARERRMHVmpdDDVFFITDVKIDDAGVYSCTAQNSAGSISANA 637
Cdd:cd05731     3 SSTMVlrggvlLLECIAEGLPTPDIRWIKLGG-ELPKGRTKFENF---NKTLKIENVSEADSGEYQCTASNTMGSARHTI 78


                  ....
gi 767922909  638 TLTV 641
Cdd:cd05731    79 SVTV 82

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.

Pssm-ID: 143207 [Multi-domain] Cd Length: 95 Bit Score: 52.24 E-value: 3.24e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767922909  658 VGETVALQCKATGNPPPRITWFKGDRPL-SLTERHHLTPDNQLLVVQNVVAEDAGRYTCEMSNTLGTERAHSQLSV 732
Cdd:cd05730    17 LGQSVTLACDADGFPEPTMTWTKDGEPIeSGEEKYSFNEDGSEMTILDVDKLDEAEYTCIAENKAGEQEAEIHLKV 92

leucine-rich repeat receptor-like protein kinase; Provisional

Pssm-ID: 215061 [Multi-domain] Cd Length: 968 Bit Score: 57.55 E-value: 4.47e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909   62 LPGDLPSWTR--SLNLSYNKLSEIDPAGFEDLPNLQEVYLNNNELTA-VPSLGAASSHVVSLFLQHNKIRSVEGSQLKAY 138
Cdd:PLN00113  324 IPVALTSLPRlqVLQLWSNKFSGEIPKNLGKHNNLTVLDLSTNNLTGeIPEGLCSSGNLFKLILFSNSLEGEIPKSLGAC 403

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  139 LSLEVLDLSLNNITEVRNTCFPHGPPIKELNLAGNrigtlelgafdglsrslltlrlskNRITQLPVRAFKLPRLTQLDL 218
Cdd:PLN00113  404 RSLRRVRLQDNSFSGELPSEFTKLPLVYFLDISNN------------------------NLQGRINSRKWDMPSLQMLSL 459

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  219 NRNRirLIEGL-TFQGLNSLEVLKLQRNNISKLTDGAFWGLSKMHVLVLSFNNLTRLDEESLAELSSLSVLRLSHNSISH 297
Cdd:PLN00113  460 ARNK--FFGGLpDSFGSKRLENLDLSRNQFSGAVPRKLGSLSELMQLKLSENKLSGEIPDELSSCKKLVSLDLSHNQLSG 537

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*..
gi 767922909  298 IAEGAFKGLRSLRVLDLDHNEISGTIEDTSGafsGLDSLSKLTLFGN 344
Cdd:PLN00113  538 QIPASFSEMPVLSQLDLSQNQLSGEIPKNLG---NVESLVQVNISHN 581

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.

Pssm-ID: 409561 Cd Length: 92 Bit Score: 51.62 E-value: 4.90e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  645 PSLVVPLEDRVVSV--GETVALQCKATGNPPPRITW-FKGDRPLSL--TERHHLTPDNQlLVVQNVVAEDAGRYTCEMSN 719
Cdd:cd20969     1 RAAIRDRKAQQVFVdeGHTVQFVCRADGDPPPAILWlSPRKHLVSAksNGRLTVFPDGT-LEVRYAQVQDNGTYLCIAAN 79

                          90
                  ....*....|...
gi 767922909  720 TLGTERAHSQLSV 732
Cdd:cd20969    80 AGGNDSMPAHLHV 92

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.

Pssm-ID: 188093 [Multi-domain] Cd Length: 2740 Bit Score: 57.40 E-value: 5.10e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909   364 NLGGNAIRSVQFDAFVKMKNLKELHISSDSFLCDCQLKWLPPWLigRMLQAFV----TATCAHPESLKGQSIFSVPPESF 439
Cdd:TIGR00864    1 DISNNKISTIEEGICANLCNLSEIDLSGNPFECDCGLARLPRWA--EEKGVKVrqpeAALCAGPGALAGQPLLGIPLLDS 78


                   ...
gi 767922909   440 VCD 442
Cdd:TIGR00864   79 GCD 81

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.

Pssm-ID: 143222 [Multi-domain] Cd Length: 74 Bit Score: 50.71 E-value: 6.01e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  572 CAATGHPNPQIAWQKDGGtdfPAARERRmHVMPDDDVFFITDVKIDDAGVYSCTAQNSAGSISANATLTV 641
Cdd:cd05745     9 CEAQGYPQPVIAWTKGGS---QLSVDRR-HLVLSSGTLRISRVALHDQGQYECQAVNIVGSQRTVAQLTV 74

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.

Pssm-ID: 395002 Cd Length: 86 Bit Score: 50.66 E-value: 9.05e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767922909   655 VVSVGETVALQCKA-TGNPPPRITWFKGDRPLSLTERHHLTPDNQ---LLVVQNVVAEDAGRYTCEMSNTLG 722
Cdd:pfam00047    7 TVLEGDSATLTCSAsTGSPGPDVTWSKEGGTLIESLKVKHDNGRTtqsSLLISNVTKEDAGTYTCVVNNPGG 78

Immunoglobulin (Ig)-like domain of human carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) domains 2, 4, and 6, and similar domains; The members here are composed of the second, fourth, and sixth immunoglobulin (Ig)-like domains in human carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) protein subfamily. The CEA family is a group of anchored or secreted glycoproteins expressed by epithelial cells, leukocytes, endothelial cells, and placenta. The CEA family is divided into the CEACAM and pregnancy-specific glycoprotein (PSG) subfamilies. This group represents the CEACAM subfamily. CEACAM1 has many important cellular functions; it is a cell adhesion molecule and a signaling molecule that regulates the growth of tumor cells, an angiogenic factor, and a receptor for bacterial and viral pathogens, including mouse hepatitis virus (MHV). In mice, four isoforms of CEACAM1 generated by alternative splicing have either two [D1, D4] or four [D1-D4] Ig-like domains on the cell surface.

Pssm-ID: 409402 [Multi-domain] Cd Length: 89 Bit Score: 50.09 E-value: 1.46e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  650 PLEDRvvsvgETVALQCKATgNPPPRITWFKGDRPLSLTERHHLTPDNQLLVVQNVVAEDAGRYTCEMSN 719
Cdd:cd05740    11 PVEDK-----DAVTLTCEPE-TQNTSYLWWFNGQSLPVTPRLTLSNGNRTLTLLNVTREDAGAYQCEISN 74

First immunoglobulin-like domains A168 within the A-band segment of human cardiac titin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domain A168 within the A-band segment of human cardiac titin. 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 structures of the titin-A168169 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.

Pssm-ID: 409563 Cd Length: 93 Bit Score: 50.16 E-value: 1.58e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  645 PSLVVPLEDRVVSVGETVALQCKATGNPPPRITWFKGDRPLSlTERHHLTPDNQL----LVVQNV-VAEDAGRYTCEMSN 719
Cdd:cd20971     2 PHFKEELRNLNVRYQSNATLVCKVTGHPKPIVKWYRQGKEII-ADGLKYRIQEFKggyhQLIIASvTDDDATVYQVRATN 80


                  ...
gi 767922909  720 TLG 722
Cdd:cd20971    81 QGG 83

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.

Pssm-ID: 409560 [Multi-domain] Cd Length: 88 Bit Score: 49.93 E-value: 1.64e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 767922909  659 GETVALQCKATGNPPPRITWFKGDRPLSLTERHHLTpDNQLLVVQNVVAEDAGRYTCEMSNTLGTerAHSQLSVL 733
Cdd:cd20968    14 GLKAVLPCTTMGNPKPSVSWIKGDDLIKENNRIAVL-ESGSLRIHNVQKEDAGQYRCVAKNSLGI--AYSKPVTI 85

Fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule); The members here are composed of the fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule). NrCAM 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. NrCAM is primarily expressed in the nervous system.

Pssm-ID: 409454 Cd Length: 89 Bit Score: 49.59 E-value: 2.12e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  648 VVPLEDRVVSVGETVALQCKATGNPPPRITWFKGDRPLSLT-ERHHLTPDNQLLVVQNVVAEDAGRYTCEMSNTLGTERA 726
Cdd:cd05868     3 ITAPTNLVLSPGEDGTLICRANGNPKPSISWLTNGVPIEIApTDPSRKVDGDTIIFSKVQERSSAVYQCNASNEYGYLLA 82


                  ....*..
gi 767922909  727 HSQLSVL 733
Cdd:cd05868    83 NAFVNVL 89

type III secretion system effector E3 ubiquitin transferase SlrP;

Pssm-ID: 185268 [Multi-domain] Cd Length: 754 Bit Score: 54.70 E-value: 2.50e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909   62 LPGDLPSWTRSLNLSYNKLSEIDpagfEDLPN-LQEVYLNNNELTAVPSlgAASSHVVSLFLQHNKIrsvegSQLKAYL- 139
Cdd:PRK15370  256 LPERLPSALQSLDLFHNKISCLP----ENLPEeLRYLSVYDNSIRTLPA--HLPSGITHLNVQSNSL-----TALPETLp 324

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  140 -SLEVLDLSLNNItevrnTCFPHG--PPIKELNLAGNRIGTLElgafdglsrslltlrlsknriTQLPvrafklPRLTQL 216
Cdd:PRK15370  325 pGLKTLEAGENAL-----TSLPASlpPELQVLDVSKNQITVLP---------------------ETLP------PTITTL 372

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 767922909  217 DLNRNR-IRLIEGLTfqglNSLEVLKLQRNNISKLTD 252
Cdd:PRK15370  373 DVSRNAlTNLPENLP----AALQIMQASRNNLVRLPE 405

Leucine-rich repeats (LRRs), ribonuclease inhibitor (RI)-like subfamily. LRRs are 20-29 residue sequence motifs present in many proteins that participate in protein-protein interactions and have different functions and cellular locations. LRRs correspond to structural units consisting of a beta strand (LxxLxLxxN/CxL conserved pattern) and an alpha helix. This alignment contains 12 strands corresponding to 11 full repeats, consistent with the extent observed in the subfamily acting as Ran GTPase Activating Proteins (RanGAP1).

Pssm-ID: 238064 [Multi-domain] Cd Length: 319 Bit Score: 53.51 E-value: 3.26e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909   53 DCGGRGLAALPGDLPSWTRSLNLSYNKLSEidpAGFEDL-------PNLQEVYLNNNELT--AVPSL---GAASSHVVSL 120
Cdd:cd00116   122 DRGLRLLAKGLKDLPPALEKLVLGRNRLEG---ASCEALakalranRDLKELNLANNGIGdaGIRALaegLKANCNLEVL 198

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 767922909  121 FLQHNKIRSVEGSQLKAYL----SLEVLDLSLNNITEV----RNTCFPHGPP-IKELNLAGNRIG 176
Cdd:cd00116   199 DLNNNGLTDEGASALAETLaslkSLEVLNLGDNNLTDAgaaaLASALLSPNIsLLTLSLSCNDIT 263

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1(FGFRL1); 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 like-1(FGFRL1). FGFRL1 is comprised of a signal peptide, three extracellular Ig-like modules, a transmembrane segment, and a short intracellular domain. FGFRL1 is expressed preferentially in skeletal tissues. Similar to FGF receptors, the expressed protein interacts specifically with heparin and with FGF2. 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.

Pssm-ID: 409442 Cd Length: 92 Bit Score: 49.09 E-value: 3.31e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 767922909  569 RLECAATGHPNPQIAWQKDGG--TDFPAARERRMHVmpdddVFFITDVKIDDAGVYSCTAQNSAGSIsaNATLTV 641
Cdd:cd05856    23 RLKCVASGNPRPDITWLKDNKplTPPEIGENKKKKW-----TLSLKNLKPEDSGKYTCHVSNRAGEI--NATYKV 90

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).

Pssm-ID: 409401 Cd Length: 82 Bit Score: 48.74 E-value: 3.61e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  649 VPLEDRVVSVGETVALQCKATGNPPPRITWFKGDRplslterhHLTPDNQLLVVQNVVA----EDAGRYTCEMSNTLGTE 724
Cdd:cd05739     2 IPPSNHEVMPGGSVNLTCVAVGAPMPYVKWMKGGE--------ELTKEDEMPVGRNVLEltniYESANYTCVAISSLGMI 73


                  ....*...
gi 767922909  725 RAHSQLSV 732
Cdd:cd05739    74 EATAQVTV 81

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.

Pssm-ID: 409394 [Multi-domain] Cd Length: 83 Bit Score: 48.94 E-value: 3.67e-07

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767922909  659 GETVALQCKATGNPPPRITWFK--GDRPlslTERHHLTPDNQLLVVQNVVAEDAGRYTCEMSNTLGTER 725
Cdd:cd05731    10 GGVLLLECIAEGLPTPDIRWIKlgGELP---KGRTKFENFNKTLKIENVSEADSGEYQCTASNTMGSAR 75

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; 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 and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. 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.

Pssm-ID: 143224 [Multi-domain] Cd Length: 92 Bit Score: 48.89 E-value: 4.05e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  550 LPS--FTKtPHDITIRTTTMARLECAATGHPNPQIAWQKDGGtdfPAARERRMHVMPDD--DVFFITDVKIDDAGVYSCT 625
Cdd:cd05747     2 LPAtiLTK-PRSLTVSEGESARFSCDVDGEPAPTVTWMREGQ---IIVSSQRHQITSTEykSTFEISKVQMSDEGNYTVV 77

                          90
                  ....*....|....*
gi 767922909  626 AQNSAGSISANATLT 640
Cdd:cd05747    78 VENSEGKQEAQFTLT 92

Immunoglobulin-like domain of human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin I-set (IgI) domain of the Human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins. APEG-1 is a novel specific smooth muscle differentiation marker predicted to play a role in the growth and differentiation of arterial smooth muscle cells (SMCs). 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 human APEG-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.

Pssm-ID: 409567 Cd Length: 91 Bit Score: 49.01 E-value: 4.31e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  645 PSLVVPLEDRVVSVGETVALQCKATGNPPPRITWFKGDRPLSLTERHHL-TPDNQLLVVQNVVAE--DAGRYTCEMSNTL 721
Cdd:cd20975     1 PTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAeEAEGGLCRLRILAAErgDAGFYTCKAVNEY 80

                          90
                  ....*....|.
gi 767922909  722 GTERAHSQLSV 732
Cdd:cd20975    81 GARQCEARLEV 91

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.

Pssm-ID: 409541 [Multi-domain] Cd Length: 89 Bit Score: 48.87 E-value: 4.73e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  656 VSVGETVALQCKATGNPPPRITWFKGDRPLSLT----ERHHLTPDNqlLVVQNVVAEDAGRYTCEMSNTLGTERAHSQLS 731
Cdd:cd20949    11 VKEGQSATILCEVKGEPQPNVTWHFNGQPISASvadmSKYRILADG--LLINKVTQDDTGEYTCRAYQVNSIASDMQERT 88


                  .
gi 767922909  732 V 732
Cdd:cd20949    89 V 89

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.

Pssm-ID: 409560 [Multi-domain] Cd Length: 88 Bit Score: 48.39 E-value: 5.46e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  554 TKTPHDITIRTTTMARLECAATGHPNPQIAWQKdgGTDfpAARERRMHVMPDDDVFFITDVKIDDAGVYSCTAQNSAGS- 632
Cdd:cd20968     3 TRPPTNVTIIEGLKAVLPCTTMGNPKPSVSWIK--GDD--LIKENNRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLGIa 78


                  ....*....
gi 767922909  633 ISANATLTV 641
Cdd:cd20968    79 YSKPVTIEV 87

Immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM) and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains NrCAM [Ng(neuronglia)CAM-related cell adhesion molecule], which is primarily expressed in the nervous system, and human neurofascin. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lacks a C" strand.

Pssm-ID: 409396 [Multi-domain] Cd Length: 94 Bit Score: 48.56 E-value: 5.93e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  650 PLEDRVVSVGETVALQCKATGNPPPRITWFKGDRPLSLTERHHLT--PDNQLLVVQ--NVVAED-AGRYTCEMSNTLGTE 724
Cdd:cd05733     7 SPKDYIVDPRDNITIKCEAKGNPQPTFRWTKDGKFFDPAKDPRVSmrRRSGTLVIDnhNGGPEDyQGEYQCYASNELGTA 86


                  ...
gi 767922909  725 RAH 727
Cdd:cd05733    87 ISN 89

First immunoglobulin (Ig) domain of contactin-1; 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-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409436 [Multi-domain] Cd Length: 95 Bit Score: 48.41 E-value: 7.03e-07

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 767922909  662 VALQCKATGNPPPRITWFKGDRPLSLTERHHLTPDNQLLVVQNVVAEDAGRYTCEMSNTLGTERA 726
Cdd:cd05849    22 VSVNCRARANPFPIYKWRKNNLDIDLTNDRYSMVGGNLVINNPDKYKDAGRYVCIVSNIYGKVRS 86

Immunoglobulin (Ig)-like domain found in Perlecan and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain found in Perlecan. Perlecan is a large multi-domain heparin sulfate proteoglycan, important in tissue development and organogenesis. Perlecan can be represented as 5 major portions; its fourth major portion (domain IV) is a tandem repeat of immunoglobulin-like domains (Ig2-Ig15) which can vary in size due to alternative splicing. Perlecan binds many cellular and extracellular ligands. Its domain IV region has many binding sites. Some of these have been mapped at the level of individual Ig-like domains, including a site restricted to the Ig5 domain for heparin/sulfatide, a site restricted to the Ig3 domain for nidogen-1 and nidogen-2, a site restricted to Ig4-5 for fibronectin, and sites restricted to Ig2 and to Ig13-15 for fibulin-2. 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.

Pssm-ID: 409412 Cd Length: 85 Bit Score: 47.55 E-value: 1.01e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  648 VVPLEDRVVSVGETVALQCKA-TGNPPPRITWFKGDRPLSLTERHHltpdNQLLVVQNVVAEDAGRYTCEMSNTLGTERA 726
Cdd:cd05754     5 VEEPRSQEVRPGADVSFICRAkSKSPAYTLVWTRVNGTLPSRAMDF----NGILTIRNVQLSDAGTYVCTGSNMLDTDEA 80


                  ....*
gi 767922909  727 HSQLS 731
Cdd:cd05754    81 TATLY 85

Second immunoglobulin (Ig)-like domain of interleukin-1 receptor (IL1R), and similar domains; The members here are composed of the second immunoglobulin (Ig)-like domain of interleukin-1 receptor (IL1R; also known as cluster of differentiation (CD) 121). IL-1 alpha and IL-1 beta are cytokines which participate in the regulation of inflammation, immune responses, and hematopoiesis. These cytokines bind to the IL-1 receptor type 1 (IL1R1), which is activated on additional association with interleukin-1 receptor accessory protein (IL1RAP). IL-1 also binds a second receptor designated type II (IL1R2). Mature IL1R1 consists of three IG-like domains, a transmembrane domain, and a large cytoplasmic domain. Mature IL1R2 is organized similarly except that it has a short cytoplasmic domain. The latter does not initiate signal transduction. A naturally occurring cytokine IL-1RA (IL-1 receptor antagonist) is widely expressed and binds to IL-1 receptors, inhibiting the binding of IL-1 alpha and IL-1 beta. This group also contains ILIR-like 1 (IL1R1L) which maps to the same chromosomal location as IL1R1 and IL1R2.

Pssm-ID: 409415 Cd Length: 92 Bit Score: 47.70 E-value: 1.06e-06

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 767922909  674 PRITWFKGDRPLSLTERHHLTPDNqlLVVQNVVAEDAGRYTCEMSNT 720
Cdd:cd05757    30 PPIQWYKDCKPLQGDKRFIPKGSK--LLIQNVTEEDAGNYTCKFTYT 74

Immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan, also known as HSPG2, and similar proteins. Perlecan consists of five domains: domain I has three putative heparan sulfate attachment sites, domain II has four LDL receptor-like repeats, and one Ig-like repeat, domain III resembles the short arm of laminin chains, domain IV has multiple Ig-like repeats (21 repeats in human perlecan), and domain V resembles the globular G domain of the laminin A chain and internal repeats of EGF. Perlecan may participate in a variety of biological functions including cell binding, LDL-metabolism, basement membrane assembly and selective permeability, calcium binding, and growth- and neurite-promoting activities.

Pssm-ID: 143220 Cd Length: 78 Bit Score: 47.10 E-value: 1.10e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767922909  659 GETVALQCKATGNPPPRITWFKGDRPLSLTERHHLTPDN--QLLVVQNVVAEDAGRYTCEMSNTLGT 723
Cdd:cd05743     1 GETVEFTCVATGVPTPIINWRLNWGHVPDSARVSITSEGgyGTLTIRDVKESDQGAYTCEAINTRGM 67

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.

Pssm-ID: 409356 [Multi-domain] Cd Length: 96 Bit Score: 48.01 E-value: 1.11e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 767922909  657 SVGETVALQCKATGNPPPRITWFK--GDRPLSLTERHHLTPDNqlLVVQN-VVAEDAGRYTCEMSNTLGTERA 726
Cdd:cd04967    17 SDEKKVALNCRARANPVPSYRWLMngTEIDLESDYRYSLVDGT--LVISNpSKAKDAGHYQCLATNTVGSVLS 87

C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C); The members here are composed of the C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C). MyBP-C consists of repeated domains, Ig and fibronectin type 3, and various linkers. Three isoforms of MYBP-C exist: slow-skeletal (ssMyBP-C), fast-skeletal (fsMyBP-C), and cardiac (cMyBP-C). cMYBP-C has insertions between and inside domains and an additional cardiac-specific Ig domain at the N-terminus. For cMYBP_C an interaction has been demonstrated between this C5 domain and the Ig C8 domain.

Pssm-ID: 409475 Cd Length: 86 Bit Score: 47.53 E-value: 1.25e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  557 PHDITIRTTTMARLECAATGHPNPQIAWQKdgGTDFPAARERRMHV--MPDDDVFFITDVKIDDAGVYSCTAQNSAGSIS 634
Cdd:cd05894     2 ENTIVVVAGNKLRLDVPISGEPAPTVTWSR--GDKAFTATEGRVRVesYKDLSSFVIEGAEREDEGVYTITVTNPVGEDH 79


                  ....*..
gi 767922909  635 ANATLTV 641
Cdd:cd05894    80 ASLFVKV 86

Fifth immunoglobulin (Ig) domain of contactin-1; The members here are composed of the fifth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409438 Cd Length: 89 Bit Score: 47.30 E-value: 1.28e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  650 PLEDRVVSV-GETVALQCKATGNPPPRITWFKGDRPLSLTERHHLTPDNQLLVVqNVVAEDAGRYTCEMSNTLGTERAHS 728
Cdd:cd05852     7 PMKKKILAAkGGRVIIECKPKAAPKPKFSWSKGTELLVNNSRISIWDDGSLEIL-NITKLDEGSYTCFAENNRGKANSTG 85


                  ....
gi 767922909  729 QLSV 732
Cdd:cd05852    86 VLSV 89

First 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 first 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.

Pssm-ID: 409547 Cd Length: 99 Bit Score: 47.79 E-value: 1.28e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  551 PSFTKTPHD-ITIRTTTMARLECAATGHPNPQIAWQKDGGT---DFPAARErrmhvMPDDDVFFITDVKIDD------AG 620
Cdd:cd20955     2 PVFLKEPTNrIDFSNSTGAEIECKASGNPMPEIIWIRSDGTavgDVPGLRQ-----ISSDGKLVFPPFRAEDyrqevhAQ 76

                          90
                  ....*....|...
gi 767922909  621 VYSCTAQNSAGSI 633
Cdd:cd20955    77 VYACLARNQFGSI 89

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.

Pssm-ID: 409566 [Multi-domain] Cd Length: 93 Bit Score: 47.73 E-value: 1.32e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  645 PSLVVPLEDRVVSVGETVALQCKATGNPPPRITWFKGDRPLSLTE----RHHLTPDNQLLVVQNVVAEDAGRYTCEMSNT 720
Cdd:cd20974     1 PVFTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFRDGQVISTSTlpgvQISFSDGRAKLSIPAVTKANSGRYSLTATNG 80

                          90
                  ....*....|...
gi 767922909  721 LGTERAHSQLSVL 733
Cdd:cd20974    81 SGQATSTAELLVL 93

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 2 (VEGFR-2); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 2 (VEGFR-2). The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. VEGFRs bind VEGFs with high affinity at the Ig-like domains. VEGFR-2 (KDR/Flk-1) is a major mediator of the mitogenic, angiogenic and microvascular permeability-enhancing effects of VEGF-A; VEGF-A is important to the growth and maintenance of vascular endothelial cells and to the development of new blood- and lymphatic-vessels in physiological and pathological states. VEGF-A also interacts with VEGFR-1, which it binds more strongly than VEGFR-2. VEGFR-1 and VEGFR-2 may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. 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.

Pssm-ID: 409450 Cd Length: 89 Bit Score: 47.23 E-value: 1.37e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767922909  658 VGETVALQCKATGNPPPRITWFKGDRPLsltERHHLTPDNQLLVVQNVVAEDAGRYTCEMSNTLGTERAHSQLSVL 733
Cdd:cd05864    16 VGERVRIPVKYLGYPPPEIKWYKNGIPI---ESNHTIKAGHVLTIMEVTEKDAGNYTVVLTNPISKEKQRHTFSLV 88

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.

Pssm-ID: 395002 Cd Length: 86 Bit Score: 47.19 E-value: 1.38e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909   555 KTPHDITIRTTTMARLEC-AATGHPNPQIAWQKDGGTdfpaaRERRMHVMPDDD-----VFFITDVKIDDAGVYSCTAQN 628
Cdd:pfam00047    1 SAPPTVTVLEGDSATLTCsASTGSPGPDVTWSKEGGT-----LIESLKVKHDNGrttqsSLLISNVTKEDAGTYTCVVNN 75

                           90
                   ....*....|.
gi 767922909   629 SAGSISANATL 639
Cdd:pfam00047   76 PGGSATLSTSL 86

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.

Pssm-ID: 409546 [Multi-domain] Cd Length: 96 Bit Score: 47.31 E-value: 1.42e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  551 PSFTKTPHDITIRTTTMARLECAATGHPNPQIAWQKDGGT------DFpaARERRMHVMPDDDVFFiTDVKIDDAGVYSC 624
Cdd:cd20954     2 PRWIVEPVDANVAAGQDVMLHCQADGFPTPTVTWKKATGStpgeykDL--LYDPNVRILPNGTLVF-GHVQKENEGHYLC 78

                          90
                  ....*....|....*...
gi 767922909  625 TAQNSAGS-ISANATLTV 641
Cdd:cd20954    79 EAKNGIGSgLSKVIFLKV 96

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.

Pssm-ID: 143277 [Multi-domain] Cd Length: 97 Bit Score: 47.67 E-value: 1.45e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767922909  656 VSVGETVALQCKATGNPPPRITWFKGDRPLSLTERhhlTPDNQLLV----------VQNVVAEDAGRYTCEMSNTLGTE 724
Cdd:cd05869    14 MELEEQITLTCEASGDPIPSITWRTSTRNISSEEK---TLDGHIVVrsharvssltLKYIQYTDAGEYLCTASNTIGQD 89

Fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell adhesion molecule 5 (CEACAM5) and similar domains; member of the C2-set IgSF domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell adhesion molecule 5 (CEACAM5) and similar domains. The CEA family is a group of anchored or secreted glycoproteins, expressed by epithelial cells, leukocytes, endothelial cells and placenta. The CEA family is divided into the CEACAM and pregnancy-specific glycoprotein (PSG) subfamilies. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), also known as CD66e (Cluster of Differentiation 66e), is a cell surface glycoprotein that plays a role in cell adhesion, intracellular signaling and tumor progression. Diseases associated with CEACAM5 include lung cancer and rectum cancer. 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. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409540 Cd Length: 76 Bit Score: 46.72 E-value: 1.71e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 767922909  658 VGETVALQCKATGNPPPRITWFKGDRPLSLTerhhltpdnQLLVVQNVVAEDAGRYTCEMSNTLGTERAHSQLSV 732
Cdd:cd20948     9 SGENLNLSCHAASNPPAQYSWTINGTFQTSS---------QELFLPAITENNEGTYTCSAHNSLTGKNISLVLSV 74

Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues, and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. 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.

Pssm-ID: 409388 Cd Length: 84 Bit Score: 46.42 E-value: 2.45e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  555 KTPHDITIRTTTMARLECAATGHPNPQIAWQKDGGTDFPAareRRMHVMPDDDVFFITDVKIDDaGVYSCTAQNSAGSIS 634
Cdd:cd05723     2 KKPSNIYAHESMDIVFECEVTGKPTPTVKWVKNGDVVIPS---DYFKIVKEHNLQVLGLVKSDE-GFYQCIAENDVGNAQ 77


                  ....*..
gi 767922909  635 ANATLTV 641
Cdd:cd05723    78 ASAQLII 84

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.

Pssm-ID: 143207 [Multi-domain] Cd Length: 95 Bit Score: 46.85 E-value: 2.56e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 767922909  570 LECAATGHPNPQIAWQKDGGtdfPAARERRMHVMPDDDV-FFITDVKIDDAGVYSCTAQNSAGSISANATLTV 641
Cdd:cd05730    23 LACDADGFPEPTMTWTKDGE---PIESGEEKYSFNEDGSeMTILDVDKLDEAEYTCIAENKAGEQEAEIHLKV 92

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.

Pssm-ID: 409473 Cd Length: 92 Bit Score: 46.69 E-value: 2.69e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  551 PSFTKTPHDITIRTTTMARLECAATGHPNPQIAWQKDG-----GTDfpaarerRMHVMPDDD---VFFITDVKIDDAGVY 622
Cdd:cd05892     1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKKNNemlqyNTD-------RISLYQDNCgriCLLIQNANKKDAGWY 73

                          90
                  ....*....|....*....
gi 767922909  623 SCTAQNSAGSISANATLTV 641
Cdd:cd05892    74 TVSAVNEAGVVSCNARLDV 92

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

Pssm-ID: 409419 Cd Length: 99 Bit Score: 46.87 E-value: 2.76e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  652 EDRVVSVGETVALQCKATGNPPPRITWFKGDRPLSltERHHL----TPDNQLLVVQNVVAEDAGRYTCEMSNTLGTERAH 727
Cdd:cd05762     9 EDMKVRAGESVELFCKVTGTQPITCTWMKFRKQIQ--EGEGIkienTENSSKLTITEGQQEHCGCYTLEVENKLGSRQAQ 86


                  ....*.
gi 767922909  728 SQLSVL 733
Cdd:cd05762    87 VNLTVV 92

leucine-rich repeat receptor-like protein kinase; Provisional

Pssm-ID: 215061 [Multi-domain] Cd Length: 968 Bit Score: 51.00 E-value: 4.03e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909   72 SLNLSYNKLS-EIDPAGFEdLPNLQEVYLNNNELTA-VP-SLGAASSHVVSLFLQHNkirSVEGSQLKAYLS-LEVLDLS 147
Cdd:PLN00113   73 SIDLSGKNISgKISSAIFR-LPYIQTINLSNNQLSGpIPdDIFTTSSSLRYLNLSNN---NFTGSIPRGSIPnLETLDLS 148

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  148 LNNIT-EVRNT--CFPHgppIKELNLAGNRIgtlelgafdglsrslltlrlsknrITQLPVRAFKLPRLTQLDLNRNriR 224
Cdd:PLN00113  149 NNMLSgEIPNDigSFSS---LKVLDLGGNVL------------------------VGKIPNSLTNLTSLEFLTLASN--Q 199

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  225 LIEGLTFQ--GLNSLEVLKLQRNNISKLTDGAFWGLSKMHVLVLSFNNLTRLDEESLAELSSLSVLRLSHNSISHIAEGA 302
Cdd:PLN00113  200 LVGQIPRElgQMKSLKWIYLGYNNLSGEIPYEIGGLTSLNHLDLVYNNLTGPIPSSLGNLKNLQYLFLYQNKLSGPIPPS 279

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  303 FKGLRSLRVLDLDHNEISGTIEDTsgaFSGLDSLSKLTLFGNKIKSVAKRAFSGLEGLEHLNLGGNAIRSVQFDAFVKMK 382
Cdd:PLN00113  280 IFSLQKLISLDLSDNSLSGEIPEL---VIQLQNLEILHLFSNNFTGKIPVALTSLPRLQVLQLWSNKFSGEIPKNLGKHN 356

                         330       340
                  ....*....|....*....|..
gi 767922909  383 NLKELHISSDSF-------LCD 397
Cdd:PLN00113  357 NLTVLDLSTNNLtgeipegLCS 378

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 46.10 E-value: 4.44e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  551 PSFTKTPHDITIRTTTMARLECAATGHPNPQIAWQKDgGTDFPAARERRMHVMPDDDVFFITDVKIDDAGVYSCTAQNSA 630
Cdd:cd05736     1 PVIRVYPEFQAKEPGVEASLRCHAEGIPLPRVQWLKN-GMDINPKLSKQLTLIANGSELHISNVRYEDTGAYTCIAKNEG 79


                  .
gi 767922909  631 G 631
Cdd:cd05736    80 G 80

type III secretion system effector E3 ubiquitin transferase SlrP;

Pssm-ID: 185268 [Multi-domain] Cd Length: 754 Bit Score: 50.85 E-value: 4.61e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909   58 GLAALPGDLPSWTRSLNLSYNKLSEIDpagfEDL-PNLQEVYLNNNELTAVPSlgAASSHVVSLFLQHNKIrsvegSQLK 136
Cdd:PRK15370  189 GLTTIPACIPEQITTLILDNNELKSLP----ENLqGNIKTLYANSNQLTSIPA--TLPDTIQEMELSINRI-----TELP 257

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  137 AYL--SLEVLDLSLNNItevrnTCFPHGPP--IKELNLAGNRIGTL---------ELGAFDGLSRSLLTL--------RL 195
Cdd:PRK15370  258 ERLpsALQSLDLFHNKI-----SCLPENLPeeLRYLSVYDNSIRTLpahlpsgitHLNVQSNSLTALPETlppglktlEA 332

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  196 SKNRITQLPvrAFKLPRLTQLDLNRNRIRLI-EGLTfqglNSLEVLKLQRNNISKLTDGAFWGLSKMHVlvlSFNNLTRL 274
Cdd:PRK15370  333 GENALTSLP--ASLPPELQVLDVSKNQITVLpETLP----PTITTLDVSRNALTNLPENLPAALQIMQA---SRNNLVRL 403

                         250       260
                  ....*....|....*....|....*
gi 767922909  275 DE---ESLAELSSLSVLRLSHNSIS 296
Cdd:PRK15370  404 PEslpHFRGEGPQPTRIIVEYNPFS 428

Fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule); The members here are composed of the fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule). NrCAM 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. NrCAM is primarily expressed in the nervous system.

Pssm-ID: 409454 Cd Length: 89 Bit Score: 45.74 E-value: 4.84e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  557 PHDITIRTTTMARLECAATGHPNPQIAWQKDGGTD--FPAARERRMhvmpDDDVFFITDVKIDDAGVYSCTAQNSAGSIS 634
Cdd:cd05868     6 PTNLVLSPGEDGTLICRANGNPKPSISWLTNGVPIeiAPTDPSRKV----DGDTIIFSKVQERSSAVYQCNASNEYGYLL 81


                  ....*...
gi 767922909  635 ANATLTVL 642
Cdd:cd05868    82 ANAFVNVL 89

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

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 45.19 E-value: 6.72e-06

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909    453 PETTMAMVGKDIRFTCSAASSSSSPMTFAWKKDNEVLTNADMEnfvhvhaqdGEVMEYTTILHLRQVTFGHEGRYQCVIT 532
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFS---------VSRSGSTSTLTISNVTPEDSGTYTCAAT 71

                            90
                    ....*....|....*
gi 767922909    533 NHFGSTYSHkARLTV 547
Cdd:smart00410   72 NSSGSASSG-TTLTV 85

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.

Pssm-ID: 409541 [Multi-domain] Cd Length: 89 Bit Score: 45.40 E-value: 6.94e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  552 SFTKTPHDITIRTTTMARLECAATGHPNPQIAWQKDGG-TDFPAARERRMHVMpdDDVFFITDVKIDDAGVYSCTAQNSA 630
Cdd:cd20949     1 TFTENAYVTTVKEGQSATILCEVKGEPQPNVTWHFNGQpISASVADMSKYRIL--ADGLLINKVTQDDTGEYTCRAYQVN 78

                          90
                  ....*....|.
gi 767922909  631 GSISANATLTV 641
Cdd:cd20949    79 SIASDMQERTV 89

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor (VEGFR); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor (VEGFR). The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. The VEGFR family consists of three members, VEGFR-1 (Flt-1), VEGFR-2 (KDR/Flk-1), and VEGFR-3 (Flt-4). VEGFRs bind VEGFs with high affinity at the Ig-like domains. VEGF-A is important to the growth and maintenance of vascular endothelial cells and to the development of new blood- and lymphatic-vessels in physiological and pathological states. VEGFR-2 is a major mediator of the mitogenic, angiogenic, and microvascular permeability-enhancing effects of VEGF-A. VEGFR-1 may play an inhibitory part in these processes by binding VEGF and interfering with its interaction with VEGFR-2. VEGFR-1 has a signaling role in mediating monocyte chemotaxis. VEGFR-1 and VEGFR-2 may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. VEGFR-3 has been shown to be involved in tumor angiogenesis and growth. 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.

Pssm-ID: 409365 Cd Length: 90 Bit Score: 44.90 E-value: 9.30e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767922909  660 ETVALQCKATGNPPPRITWFKGDRPLSLTERHHlTPdnQLLVVQNVVAEDAGRYTCEMSNTLGTERAHSQLSVL 733
Cdd:cd04976    19 RSVRLPMKVKAYPPPEVVWYKDGLPLTEKARYL-TR--HSLIIKEVTEEDTGNYTILLSNKQSNVFKNLTATLV 89

Fifth immunoglobulin (Ig) domain of contactin-1; The members here are composed of the fifth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409438 Cd Length: 89 Bit Score: 44.99 E-value: 1.03e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  551 PSFTKTPHDITIRTTTMAR--LECAATGHPNPQIAWQKdgGTDFpAARERRMHVMpDDDVFFITDVKIDDAGVYSCTAQN 628
Cdd:cd05852     1 PTFEFNPMKKKILAAKGGRviIECKPKAAPKPKFSWSK--GTEL-LVNNSRISIW-DDGSLEILNITKLDEGSYTCFAEN 76

                          90
                  ....*....|...
gi 767922909  629 SAGSISANATLTV 641
Cdd:cd05852    77 NRGKANSTGVLSV 89

Leucine Rich repeats (2 copies); Leucine rich repeats are short sequence motifs present in a number of proteins with diverse functions and cellular locations. These repeats are usually involved in protein-protein interactions. Each Leucine Rich Repeat is composed of a beta-alpha unit. These units form elongated non-globular structures. Leucine Rich Repeats are often flanked by cysteine rich domains.

Pssm-ID: 463713 [Multi-domain] Cd Length: 44 Bit Score: 43.39 E-value: 1.12e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 767922909    71 RSLNLSYNKLSEIDPagFEDLPNLQEVYL-NNNELTAVPSL 110
Cdd:pfam12799    4 EVLDLSNNQITDIPP--LAKLPNLETLDLsGNNKITDLSDL 42

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.

Pssm-ID: 409421 [Multi-domain] Cd Length: 88 Bit Score: 44.77 E-value: 1.23e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 767922909  659 GETVALQCKATGNPPPRITW-FKGDRPLSLTERhHLTPDNQLLVVQNVVAEDAGRYTCEMSNTLGTERAHSQLSV 732
Cdd:cd05764    15 GQRATLRCKARGDPEPAIHWiSPEGKLISNSSR-TLVYDNGTLDILITTVKDTGAFTCIASNPAGEATARVELHI 88

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band 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. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. 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 I1 domain of the titin I-band 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, 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.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 44.72 E-value: 1.28e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  645 PSLVVPLEDRVVSVGETVALQCKATGNPPPRITWFKGDRPLsltERHHLTPDNQL--------LVVQNVVAEDAGRYTCE 716
Cdd:cd20951     1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPI---DPSSIPGKYKIeseygvhvLHIRRVTVEDSAVYSAV 77

                          90
                  ....*....|....*.
gi 767922909  717 MSNTLGTERAHSQLSV 732
Cdd:cd20951    78 AKNIHGEASSSASVVV 93

Second immunoglobulin (Ig)-like domain of protein tyrosine kinase (PTK) 7; The members here are composed of the second immunoglobulin (Ig)-like domain in protein tyrosine kinase (PTK) 7, also known as CCK4. PTK7 is a subfamily of the receptor protein tyrosine kinase family, and is referred to as an RPTK-like molecule. RPTKs transduce extracellular signals across the cell membrane and play important roles in regulating cell proliferation, migration, and differentiation. PTK7 is organized as an extracellular portion having seven Ig-like domains, a single transmembrane region, and a cytoplasmic tyrosine kinase-like domain. PTK7 is considered a pseudokinase as it has several unusual residues in some of the highly conserved tyrosine kinase (TK) motifs; it is predicted to lack TK activity. PTK7 may function as a cell-adhesion molecule. PTK7 mRNA is expressed at high levels in placenta, melanocytes, liver, lung, pancreas, and kidney. PTK7 is overexpressed in several cancers, including melanoma and colon cancer lines.

Pssm-ID: 409417 Cd Length: 95 Bit Score: 44.15 E-value: 2.11e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  562 IRTTTMARLECAATGHPNPQIAWQKDG-------GTDFPAARERRMHVMPdddvffitdVKIDDAGVYSCTAQNSAGSI- 633
Cdd:cd05760    13 IQPSSRVTLRCHIDGHPRPTYQWFRDGtplsdgqGNYSVSSKERTLTLRS---------AGPDDSGLYYCCAHNAFGSVc 83

                          90
                  ....*....|.
gi 767922909  634 -SANATLTVLE 643
Cdd:cd05760    84 sSQNFTLSIID 94

leucine-rich repeat receptor-like protein kinase; Provisional

Pssm-ID: 215061 [Multi-domain] Cd Length: 968 Bit Score: 47.92 E-value: 3.31e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909   62 LPGD---LPSWTRSLNLSYNKLSEIDPAGFedLPNLQEVYLNNNELTAvpslgaasshvvslflqhnKIRSVEGSqlkaY 138
Cdd:PLN00113  109 IPDDiftTSSSLRYLNLSNNNFTGSIPRGS--IPNLETLDLSNNMLSG-------------------EIPNDIGS----F 163

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  139 LSLEVLDL-----------SLNNITEvrntcfphgppIKELNLAGNR-IGTL--ELGAFdglSRSLLTLRLSKNRITQLP 204
Cdd:PLN00113  164 SSLKVLDLggnvlvgkipnSLTNLTS-----------LEFLTLASNQlVGQIprELGQM---KSLKWIYLGYNNLSGEIP 229

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  205 VRAFKLPRLTQLDLNRNRIRLIEGLTFQGLNSLEVLKLQRNNISKLTDGAFWGLSKMHVLVLSFNNLTRLDEESLAELSS 284
Cdd:PLN00113  230 YEIGGLTSLNHLDLVYNNLTGPIPSSLGNLKNLQYLFLYQNKLSGPIPPSIFSLQKLISLDLSDNSLSGEIPELVIQLQN 309

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  285 LSVLRLSHNSISHIAEGAFKGLRSLRVLDLDHNEISGTIEDTSGA---FSGLD------------------SLSKLTLFG 343
Cdd:PLN00113  310 LEILHLFSNNFTGKIPVALTSLPRLQVLQLWSNKFSGEIPKNLGKhnnLTVLDlstnnltgeipeglcssgNLFKLILFS 389

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|..
gi 767922909  344 NKIKSVAKRAFSGLEGLEHLNLGGNAIRSVQFDAFVKMKNLKELHISSDSFL 395
Cdd:PLN00113  390 NSLEGEIPKSLGACRSLRRVRLQDNSFSGELPSEFTKLPLVYFLDISNNNLQ 441

Second 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 second immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. 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.

Pssm-ID: 409545 Cd Length: 95 Bit Score: 43.30 E-value: 3.78e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  656 VSVGETVALQCKATGNPPPRITWFK------GDRPLSLTERhhLTPDNQLLVVQNVVAEDAGRYTCEMSNTLGTERAHSQ 729
Cdd:cd20953    15 VSSASSIALLCPAQGYPAPSFRWYKfiegttRKQAVVLNDR--VKQVSGTLIIKDAVVEDSGKYLCVVNNSVGGESVETV 92


                  ...
gi 767922909  730 LSV 732
Cdd:cd20953    93 LTV 95

Immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM) and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. L1 is primarily expressed in the nervous system and is involved in its development and function. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains NrCAM [Ng(neuronglia)CAM-related cell adhesion molecule], which is primarily expressed in the nervous system, and human neurofascin. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lacks a C" strand.

Pssm-ID: 409396 [Multi-domain] Cd Length: 94 Bit Score: 43.55 E-value: 3.82e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  551 PSFTK-TPHDITIRTTTMARLECAATGHPNPQIAWQKDgGTDFPAARERRMHVMPDDDVFFIT--DVKIDD-AGVYSCTA 626
Cdd:cd05733     1 PTITEqSPKDYIVDPRDNITIKCEAKGNPQPTFRWTKD-GKFFDPAKDPRVSMRRRSGTLVIDnhNGGPEDyQGEYQCYA 79

                          90
                  ....*....|....
gi 767922909  627 QNSAGS-ISANATL 639
Cdd:cd05733    80 SNELGTaISNEIRL 93

First immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. 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.

Pssm-ID: 409387 Cd Length: 97 Bit Score: 43.24 E-value: 4.22e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767922909  653 DRVVSVGETVALQCKATGNPPPRITWFKGDRPLSL--TERHHLTPDNQLLvVQNVV-----AEDAGRYTCEMSN-TLGT 723
Cdd:cd05722    10 DIVAMRGGPVVLNCSAESDPPPKIEWKKDGVLLNLvsDERRQQLPNGSLL-ITSVVhskhnKPDEGFYQCVAQNeSLGS 87

Sixth immunoglobulin (Ig) domain of contactin-2; The members here are composed of the sixth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-2-like. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. It may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module by contacts between IG domains 1 and 4, and domains 2 and 3. 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-2 is also expressed in retinal amacrine cells (AC) in the developing chick retina, corresponding to the period of formation and maturation of AC processes.

Pssm-ID: 409440 Cd Length: 102 Bit Score: 43.49 E-value: 5.03e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  554 TKTPHDITIRTTTMARLECAATGHPNPQIA--WQKDG---GTDFPAARERRMHVMPDDDVFFITDVKIDDAGVYSCTAQN 628
Cdd:cd05854     6 TLAPSSADINQGENLTLQCHASHDPTMDLTftWSLDDfpiDLDKPNGHYRRMEVKETIGDLVIVNAQLSHAGTYTCTAQT 85

                          90
                  ....*....|....*..
gi 767922909  629 SAGSISANATLTVLETP 645
Cdd:cd05854    86 VVDSASASATLVVRGPP 102

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.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 42.32 E-value: 5.80e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  464 IRFTCSAASSSssPMTFAWKKDNEVLTNADMENFVHVHaqdgevmeYTTILHLRQVTFGHEGRYQCVITNHFGSTYSHKA 543
Cdd:cd00096     1 VTLTCSASGNP--PPTITWYKNGKPLPPSSRDSRRSEL--------GNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

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.

Pssm-ID: 409395 [Multi-domain] Cd Length: 96 Bit Score: 42.90 E-value: 6.14e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  557 PHDITIRTTTMARLE-----CAATGHPNPQIAWQK--DGGTDFPAARERRMHVMPDDDVFFIT--DVKIDDAGVYSCTAQ 627
Cdd:cd05732     3 PKITYLENQTAVELEqitltCEAEGDPIPEITWRRatRGISFEEGDLDGRIVVRGHARVSSLTlkDVQLTDAGRYDCEAS 82


                  ....
gi 767922909  628 NSAG 631
Cdd:cd05732    83 NRIG 86

Second 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 second 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. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of this group show that the second Ig domain lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules, including vascular (VCAM), intercellular (ICAM), neural (NCAM) and mucosal addressin (MADCAM) cell adhesion molecules, as well as junction adhesion molecules (JAM).

Pssm-ID: 409557 Cd Length: 101 Bit Score: 43.01 E-value: 7.19e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767922909  569 RLECA-ATGHPNPQIAWQKDGGTDFPAAR---ERRMHVMPDDDVFF--ITDVKIDDAGVYSCTAQNSA 630
Cdd:cd20965    21 KLDCNvPPGYPKPTIEWKKQLVSDSSKADtilDRRITISPNGDLYFtnVTKEDVSTDYKYVCVAKTPA 88

Leucine-rich repeat;

Pssm-ID: 405295 [Multi-domain] Cd Length: 175 Bit Score: 44.37 E-value: 7.83e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909   199 RITQLPVRAFKLPRLTQL----------DLNRNRIRLIEGLTFqgLNSLEVLKLQRNNISKLTDGAFWGLSKMHVLVLSF 268
Cdd:pfam14580   20 RERELDLRGYKIPIIENLgatldqfdtiDFSDNEIRKLDGFPL--LRRLKTLLLNNNRICRIGEGLGEALPNLTELILTN 97

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 767922909   269 NNLTRL-DEESLAELSSLSVLRLSHNSIS---HIAEGAFKGLRSLRVLD 313
Cdd:pfam14580   98 NNLQELgDLDPLASLKKLTFLSLLRNPVTnkpHYRLYVIYKVPQLRLLD 146

Second 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 second immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. 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.

Pssm-ID: 409545 Cd Length: 95 Bit Score: 42.53 E-value: 8.09e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  565 TTMARLeCAATGHPNPQIAWQKdggtdFPAARERRMHVMPDDDV------FFITDVKIDDAGVYSCTAQNSAGSISANAT 638
Cdd:cd20953    19 SSIALL-CPAQGYPAPSFRWYK-----FIEGTTRKQAVVLNDRVkqvsgtLIIKDAVVEDSGKYLCVVNNSVGGESVETV 92


                  ...
gi 767922909  639 LTV 641
Cdd:cd20953    93 LTV 95

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.

Pssm-ID: 409356 [Multi-domain] Cd Length: 96 Bit Score: 42.62 E-value: 8.85e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  551 PSFTKTPHDITIRTTTMAR---LECAATGHPNPQIAWQKDGgTDFPAARERRmHVMPDDDVFFITDVKIDDAGVYSCTAQ 627
Cdd:cd04967     2 PVFEEQPDDTIFPEDSDEKkvaLNCRARANPVPSYRWLMNG-TEIDLESDYR-YSLVDGTLVISNPSKAKDAGHYQCLAT 79

                          90
                  ....*....|...
gi 767922909  628 NSAGSI-SANATL 639
Cdd:cd04967    80 NTVGSVlSREATL 92

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.

Pssm-ID: 409550 [Multi-domain] Cd Length: 89 Bit Score: 42.17 E-value: 8.89e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767922909  569 RLECAATGHPNPQIAWQKDGgtdfpaaRE----RRMHVMPDDdVFFITDV-KIDDAGVYSCTAQNSAGsISANATLTV 641
Cdd:cd20958    19 RLHCPVAGYPISSITWEKDG-------RRlplnHRQRVFPNG-TLVIENVqRSSDEGEYTCTARNQQG-QSASRSVFV 87

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.

Pssm-ID: 409435 Cd Length: 96 Bit Score: 42.24 E-value: 9.07e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  551 PSFTKTPHDITIRTTTMAR---LECAATGHPNPQIAWQKDGgTDFPAARERRMHVMpdDDVFFITDV-KIDDAGVYSCTA 626
Cdd:cd05848     2 PVFVQEPDDAIFPTDSDEKkviLNCEARGNPVPTYRWLRNG-TEIDTESDYRYSLI--DGNLIISNPsEVKDSGRYQCLA 78

                          90
                  ....*....|....
gi 767922909  627 QNSAGSI-SANATL 639
Cdd:cd05848    79 TNSIGSIlSREALL 92

First immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. 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.

Pssm-ID: 409387 Cd Length: 97 Bit Score: 42.47 E-value: 9.87e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  450 ITQPETTMAMVGKDIRFTCSAASSSssPMTFAWKKDNEVLTNADMENFVHVhaQDGEVMeYTTILHLRqvtfgH----EG 525
Cdd:cd05722     5 LSEPSDIVAMRGGPVVLNCSAESDP--PPKIEWKKDGVLLNLVSDERRQQL--PNGSLL-ITSVVHSK-----HnkpdEG 74

                          90       100
                  ....*....|....*....|...
gi 767922909  526 RYQCVITN-HFGSTYSHKARLTV 547
Cdd:cd05722    75 FYQCVAQNeSLGSIVSRTARVTV 97

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.

Pssm-ID: 409534 Cd Length: 116 Bit Score: 42.64 E-value: 1.02e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  553 FTKTPHDITIRTTTMARLECAATGHPNPQIAWQKDGGTD-------FPAARERRMHV-----MPDDDVFFITDVKIDDAG 620
Cdd:cd20940     3 FIKSPLSQQRLVGDSVELHCEAVGSPIPEIQWWFEGQEPneicsqlWDGARLDRVHInatyhQHATSTISIDNLTEEDTG 82


                  ....*...
gi 767922909  621 VYSCTAQN 628
Cdd:cd20940    83 TYECRASN 90

Sixth 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 sixth 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.

Pssm-ID: 409551 Cd Length: 94 Bit Score: 42.09 E-value: 1.04e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767922909  567 MARLECAATGHPNP-QIAWQKDGG--TDFPAARERRmhVMPDDDVFFITDVKIDDAGVYSCTAQNSAGSISANATLTV 641
Cdd:cd20959    19 RAQLHCGVPGGDLPlNIRWTLDGQpiSDDLGITVSR--LGRRSSILSIDSLEASHAGNYTCHARNSAGSASYTAPLTV 94

Sixth immunoglobulin (Ig) domain of contactin; The members here are composed of the sixth 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.

Pssm-ID: 409359 Cd Length: 102 Bit Score: 42.54 E-value: 1.09e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  554 TKTPHDITIRTTTMARLECAATGHPNPQIA--WQKDG-GTDF--PAARERRMHVMPDDDVFFITDVKIDDAGVYSCTAQN 628
Cdd:cd04970     6 TLAPSNADITVGENATLQCHASHDPTLDLTftWSFNGvPIDLekIEGHYRRRYGKDSNGDLEIVNAQLKHAGRYTCTAQT 85

                          90
                  ....*....|....*..
gi 767922909  629 SAGSISANATLTVLETP 645
Cdd:cd04970    86 VVDSDSASATLVVRGPP 102

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) 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, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), 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 Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 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.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 42.15 E-value: 1.21e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  447 PQIITQPETTMAMVGKDIRFTCSAASSSSSpmTFAWKKDNEVL-TNADMENFVHVHAQDGEVMeYTTILHLRQVTfGHEG 525
Cdd:cd07693     1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTP--TIQWLKNGQPLeTDKDDPRSHRIVLPSGSLF-FLRVVHGRKGR-SDEG 76

                          90       100
                  ....*....|....*....|..
gi 767922909  526 RYQCVITNHFGSTYSHKARLTV 547
Cdd:cd07693    77 VYVCVAHNSLGEAVSRNASLEV 98

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.

Pssm-ID: 409460 [Multi-domain] Cd Length: 83 Bit Score: 41.44 E-value: 1.46e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767922909  570 LECAATGHPNPQIAWQKDGGTDFPaareRRMHVMPDDDVFFITDVKIDDAGVYSCTAQNSAGSISANATLTV 641
Cdd:cd05876    15 LECIAEGLPTPTVKWLRPSGPLPP----DRVKYQNHNKTLQLLNVGESDDGEYVCLAENSLGSARHAYYVTV 82

Third immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 143259 Cd Length: 88 Bit Score: 41.55 E-value: 1.49e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767922909  570 LECAATGHPNPQIAWQKDgGTDFPAARERRMhvmpDDDVFFITDVKIDDAGVYSCTAQNSAG 631
Cdd:cd05851    21 LECFALGNPVPVIRWRKI-LEPMPATAEISM----SGAVLKIFNIQPEDEGTYECEAENIKG 77

Ran GTPase-activating protein (RanGAP) involved in mRNA processing and transport [Translation, ribosomal structure and biogenesis];

Pssm-ID: 444072 [Multi-domain] Cd Length: 434 Bit Score: 45.55 E-value: 1.59e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909   93 NLQEVYLNNNEL--TAVPSLGAA---SSHVVSLFLQHNKI--RSVE--GSQLKAYLSLEVLDLSLNNITE--VRN--TCF 159
Cdd:COG5238   181 SVETVYLGCNQIgdEGIEELAEAltqNTTVTTLWLKRNPIgdEGAEilAEALKGNKSLTTLDLSNNQIGDegVIAlaEAL 260

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  160 PHGPPIKELNLAGNRIGtlELGAfdglsrslltlrlsKNRITQLPVRafklPRLTQLDLNRNRIR------LIEGLtfQG 233
Cdd:COG5238   261 KNNTTVETLYLSGNQIG--AEGA--------------IALAKALQGN----TTLTSLDLSVNRIGdegaiaLAEGL--QG 318

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  234 LNSLEVLKLQRNNISklTDGAfwglskmhvlvlsfnnltrldeESLAElsslsvlrlshnsishiaegAFKGLRSLRVLD 313
Cdd:COG5238   319 NKTLHTLNLAYNGIG--AQGA----------------------IALAK--------------------ALQENTTLHSLD 354

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  314 LDHNEISGtiedtsgafSGLDSLSKLtLFGNKiksvakrafsgleGLEHLNLGGNAIRSVQFDAFVKMKNLKELHissds 393
Cdd:COG5238   355 LSDNQIGD---------EGAIALAKY-LEGNT-------------TLRELNLGKNNIGKQGAEALIDALQTNRLH----- 406

                         330       340       350
                  ....*....|....*....|....*....|...
gi 767922909  394 flcdcQLKwLPPWLIGRMLQAFVTATCAHPESL 426
Cdd:COG5238   407 -----TLI-LDGNLIGAEAQQRLEQLLERIKSV 433

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.

Pssm-ID: 395002 Cd Length: 86 Bit Score: 41.41 E-value: 1.65e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909   460 VGKDIRFTCSAASSSSSPmTFAWKKDNEVLTNADmenfvhvHAQDGEVMEYTTILHLRQVTFGHEGRYQCVITNHFGSTY 539
Cdd:pfam00047   10 EGDSATLTCSASTGSPGP-DVTWSKEGGTLIESL-------KVKHDNGRTTQSSLLISNVTKEDAGTYTCVVNNPGGSAT 81


                   .
gi 767922909   540 S 540
Cdd:pfam00047   82 L 82

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.

Pssm-ID: 409534 Cd Length: 116 Bit Score: 42.26 E-value: 1.74e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  650 PLEDRVVsVGETVALQCKATGNPPPRIT-WFKGDRPLSLT---------ERHHLTPDNQL-----LVVQNVVAEDAGRYT 714
Cdd:cd20940     7 PLSQQRL-VGDSVELHCEAVGSPIPEIQwWFEGQEPNEICsqlwdgarlDRVHINATYHQhatstISIDNLTEEDTGTYE 85


                  ....*
gi 767922909  715 CEMSN 719
Cdd:cd20940    86 CRASN 90

Second immunoglobulin (Ig)-like domain of interleukin-1 receptor (IL1R), and similar domains; The members here are composed of the second immunoglobulin (Ig)-like domain of interleukin-1 receptor (IL1R). IL-1 alpha and IL-1 beta are cytokines which participate in the regulation of inflammation, immune responses, and hematopoiesis. These cytokines bind to the IL-1 receptor type 1 (IL1R1), which is activated on additional association with interleukin-1 receptor accessory protein (IL1RAP). IL-1 also binds a second receptor designated type II (IL1R2). Mature IL1R1 consists of three IG-like domains, a transmembrane domain, and a large cytoplasmic domain. Mature IL1R2 is organized similarly except that it has a short cytoplasmic domain. The latter does not initiate signal transduction. A naturally occurring cytokine IL-1RA (IL-1 receptor antagonist) is widely expressed and binds to IL-1 receptors, inhibiting the binding of IL-1 alpha and IL-1 beta. This group also contains ILIR-like 1 (IL1R1L) which maps to the same chromosomal location as IL1R1 and IL1R2.

Pssm-ID: 409586 Cd Length: 94 Bit Score: 41.68 E-value: 1.75e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 767922909  671 NPPPRITWFKGDRPLSLTERHhLTPDNQLLVVQNVVAEDAGRYTCEMSNT 720
Cdd:cd20994    28 NNLPKVQWYKDCKPLLLDDKR-FAGLESDLLIFNVTVQDQGNYTCHTSYT 76

Immunoglobulin-like domain of human nephrin and similar proteins; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin-like domain in human nephrin and similar proteins. Nephrin is an integral component of the slit diaphragm and is a central component of the glomerular ultrafilter. Nephrin plays a structural role and has a role in signaling. Nephrin is a transmembrane protein having a short intracellular portion, an extracellular portion comprised of eight Ig-like domains, and one fibronectin type III-like domain. The extracellular portions of nephrin from neighboring foot processes of separate podocyte cells may interact with each other, and in association with other components of the slit diaphragm form a porous molecular sieve within the slit pore. The intracellular portion of nephrin is associated with linker proteins, which connect nephrin to the actin cytoskeleton. The intracellular portion is tyrosine phosphorylated, and mediates signaling from the slit diaphragm into the podocytes.

Pssm-ID: 143250 Cd Length: 109 Bit Score: 41.84 E-value: 1.80e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767922909  663 ALQCKATGNPPPRITWFKGDRPLSL-------TERHHLTPDNQLLVVQNV-VAEDAGRYTCEMSNTLGTERAHSQL 730
Cdd:cd05773    27 NLVCQAQGVPRVQFRWAKNGVPLDLgnpryeeTTEHTGTVHTSILTIINVsAALDYALFTCTAHNSLGEDSLDIQL 102

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.

Pssm-ID: 409582 Cd Length: 91 Bit Score: 41.24 E-value: 1.82e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  653 DRVVSVGETVALQCKATGNPPPRITWFKGDRPLSLTERHH-LTPDNQL--LVVQNVVAEDAGRYTCEMSNTLGTERAHSQ 729
Cdd:cd20990     9 DLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSAHKmLVRENGVhsLIIEPVTSRDAGIYTCIATNRAGQNSFNLE 88


                  ...
gi 767922909  730 LSV 732
Cdd:cd20990    89 LVV 91

BspA type Leucine rich repeat region (6 copies); This family includes a number of leucine rich repeats. This family contains a large number of BSPA-like surface antigens from Trichomonas vaginalis.

Pssm-ID: 463839 [Multi-domain] Cd Length: 127 Bit Score: 42.15 E-value: 1.97e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909   293 NSISHIAEGAFKGLRSLRVLDLDHN--EISgtiedtSGAFSGLdSLSKLTlFGNKIKSVAKRAFSGLEGLEHLNLGGNaI 370
Cdd:pfam13306   20 SSLTSIGEYAFSNCTSLKSITLPSSltSIG------SYAFYNC-SLTSIT-IPSSLTSIGEYAFSNCSNLKSITLPSN-L 90

                           90       100
                   ....*....|....*....|..
gi 767922909   371 RSVQFDAFVKMkNLKELHISSD 392
Cdd:pfam13306   91 TSIGSYAFSNC-SLKSITIPSS 111

Immunoglobulin (Ig)-like domain of NrCAM (Ng (neuronglia) CAM-related cell adhesion molecule); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of NrCAM (Ng (neuronglia) CAM-related cell adhesion molecule). NrCAM 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. NrCAM is primarily expressed in the nervous system.

Pssm-ID: 409458 Cd Length: 95 Bit Score: 41.51 E-value: 2.07e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  551 PSFT-KTPHDITIRTTTMARLECAATGHPNPQIAWQKDgGTDFPAARERRMHVMPDDDVFFI---TDVKIDD-AGVYSCT 625
Cdd:cd05874     1 PTIThQSPKDYIVDPRENIVIQCEAKGKPPPSFSWTRN-GTHFDIDKDPKVTMKPNTGTLVInimNGEKAEAyEGVYQCT 79

                          90
                  ....*....|.
gi 767922909  626 AQNSAGSISAN 636
Cdd:cd05874    80 ARNERGAAVSN 90

IL-beta-binding protein; Provisional

Pssm-ID: 165149 [Multi-domain] Cd Length: 326 Bit Score: 44.62 E-value: 2.14e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  525 GRYQCVITNHfgsTYSHKARLTVNV---------LPSFTKTPHDITIRTTTMARLECAATGHPNPQIAWqkdggTDFPAA 595
Cdd:PHA02785   95 GIYICITKNE---TYCDMMSLNLTIvsvsesnidLISYPQIVNERSTGEMVCPNINAFIASNVNADIIW-----SGHRRL 166

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  596 RERRMHVMPDDdVFFITDVKIDDAGVYSCTAQNSAGSISANATLTV-LETPSLVVP----LEDRVV-SVGETVALQCKAT 669
Cdd:PHA02785  167 RNKRLKQRTPG-IITIEDVRKNDAGYYTCVLKYIYGDKTYNVTRIVkLEVRDRIIPptmqLPEGVVtSIGSNLTIACRVS 245

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767922909  670 GNPP---PRITWFK-----------GDRPLSLTERHHLTPDNQL----LVVQNVVAEDAGRYTC 715
Cdd:PHA02785  246 LRPPttdADVFWISngmyyeeddedGDGRISVANKIYTTDKRRVitsrLNINPVKEEDATTFTC 309

Leucine Rich repeats (2 copies); Leucine rich repeats are short sequence motifs present in a number of proteins with diverse functions and cellular locations. These repeats are usually involved in protein-protein interactions. Each Leucine Rich Repeat is composed of a beta-alpha unit. These units form elongated non-globular structures. Leucine Rich Repeats are often flanked by cysteine rich domains.

Pssm-ID: 463713 [Multi-domain] Cd Length: 44 Bit Score: 39.54 E-value: 2.40e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 767922909   211 PRLTQLDLNRNRIRLIEGLtfQGLNSLEVLKLQRNN-ISKLTD 252
Cdd:pfam12799    1 PNLEVLDLSNNQITDIPPL--AKLPNLETLDLSGNNkITDLSD 41

First immunoglobulin (Ig) domain of contactin-2; 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-2-like. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. It may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module by contacts between IG domains 1 and 4, and domains 2 and 3. 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-2 is also expressed in retinal amacrine cells in the developing chick retina, corresponding to the period of formation and maturation of AC processes. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409437 [Multi-domain] Cd Length: 97 Bit Score: 41.06 E-value: 2.42e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  657 SVGETVALQCKATGNPPPRITWFKGDRPLSLTE--RHHLTPDNqlLVVQNVV-AEDAGRYTCEMSNTLGT 723
Cdd:cd05850    18 SAEEKVTLACRARASPPATYRWKMNGTELKMEPdsRYRLVAGN--LVISNPVkAKDAGSYQCLASNRRGT 85

Fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 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.

Pssm-ID: 409453 [Multi-domain] Cd Length: 89 Bit Score: 40.65 E-value: 2.74e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  652 EDRVVSVGETVALQCKATGNPPPRITWFKGDRPLSLT---ERHHLTpdNQLLVVQNVVAEDAGRYTCEMSNTLGTERAHS 728
Cdd:cd05867     7 QSHLYGPGETARLDCQVEGIPTPNITWSINGAPIEGTdpdPRRHVS--SGALILTDVQPSDTAVYQCEARNRHGNLLANA 84


                  ....*
gi 767922909  729 QLSVL 733
Cdd:cd05867    85 HVHVV 89

Immunoglobulin (Ig)-like domain at the C-terminus of semaphorins; The members here are composed of the immunoglobulin (Ig)-like domain in semaphorins. Semaphorins are transmembrane protein that have important roles in a variety of tissues. Functionally, semaphorins were initially characterized for their importance in the development of the nervous system and in axonal guidance. Later they have been found to be important for the formation and functioning of the cardiovascular, endocrine, gastrointestinal, hepatic, immune, musculoskeletal, renal, reproductive, and respiratory systems. Semaphorins function through binding to their receptors and transmembrane semaphorins also serves as receptors themselves. Although molecular mechanism of semaphorins is poorly understood, the Ig-like domains may be involved in ligand binding or dimerization.

Pssm-ID: 409368 Cd Length: 88 Bit Score: 40.52 E-value: 2.95e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  649 VPLEDRVVSVGETVALQCKATGNPPPrITWF--KGDRPLSLTERHHLTPDnQLLVVQNVVAEDAGRYTCEMSN-TLGTER 725
Cdd:cd04979     1 TSFKQISVKEGDTVILSCSVKSNNAP-VTWIhnGKKVPRYRSPRLVLKTE-RGLLIRSAQEADAGVYECHSGErVLGSTL 78


                  ....*....
gi 767922909  726 AHSQLSVLP 734
Cdd:cd04979    79 RSVTLHVLE 87

Third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor 2 (FGFR2); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain of human fibroblast growth factor receptor 2 (FGFR2). Fibroblast growth factors (FGFs) participate in morphogenesis, development, angiogenesis, and wound healing. These FGF-stimulated processes are mediated by four FGFR tyrosine kinases (FGRF1-4). FGFRs are comprised of an extracellular portion consisting of three Ig-like domains, a transmembrane helix, and a cytoplasmic portion having protein tyrosine kinase activity. The highly conserved Ig-like domains 2 and 3, and the linker region between D2 and D3 define a general binding site for FGFs. FGFR2 is required for male sex determination. 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.

Pssm-ID: 409444 Cd Length: 105 Bit Score: 41.10 E-value: 3.34e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  557 PHDITIRTTTMARLECAATGHPNPQIAW----QKDG---GTD-FPAARERRMHVMPDDD----VFFITDVKIDDAGVYSC 624
Cdd:cd05858     8 PANTSVVVGTDAEFVCKVYSDAQPHIQWlkhvEKNGskyGPDgLPYVEVLKTAGVNTTDkeieVLYLRNVTFEDAGEYTC 87

                          90
                  ....*....|....*...
gi 767922909  625 TAQNSAGSISANATLTVL 642
Cdd:cd05858    88 LAGNSIGISHHSAWLTVL 105

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 2 (NCAM-2); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule NCAM-2 (also known as OCAM/mamFas II and RNCAM). NCAM-2 is organized similarly to NCAM, including five N-terminal Ig-like domains and two fibronectin type III domains. NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE), and may function like NCAM, as an adhesion molecule. 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.

Pssm-ID: 143278 [Multi-domain] Cd Length: 98 Bit Score: 40.73 E-value: 3.64e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  648 VVPLEDRVVSVGETVALQCKATGNPPPRITWFKGDRPLSLTERHHlTPDNQL----------LVVQNVVAEDAGRYTCEM 717
Cdd:cd05870     5 IIQLKNETTVENGAATLSCKAEGEPIPEITWKRASDGHTFSEGDK-SPDGRIevkgqhgessLHIKDVKLSDSGRYDCEA 83


                  ....*
gi 767922909  718 SNTLG 722
Cdd:cd05870    84 ASRIG 88

Leucine rich repeat C-terminal domain; Leucine Rich Repeats pfam00560 are short sequence motifs present in a number of proteins with diverse functions and cellular locations. Leucine Rich Repeats are often flanked by cysteine rich domains. This domain is often found at the C-terminus of tandem leucine rich repeats.

Pssm-ID: 279765 Cd Length: 26 Bit Score: 38.57 E-value: 3.90e-04

                           10        20
                   ....*....|....*....|....*
gi 767922909   418 ATCAHPESLKGQSIFSVPPESFVCD 442
Cdd:pfam01463    2 ARCASPPRLRGQPLLDLLPSDFSCS 26

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three IG-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans.

Pssm-ID: 409443 [Multi-domain] Cd Length: 95 Bit Score: 40.61 E-value: 3.92e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767922909  569 RLECAATGHPNPQIAWQKDGGtdfPAARERRM---HVMPDDDVFFITDVKIDDAGVYSCTAQNSAGSISANATLTV 641
Cdd:cd05857    23 KFRCPAAGNPTPTMRWLKNGK---EFKQEHRIggyKVRNQHWSLIMESVVPSDKGNYTCVVENEYGSINHTYHLDV 95

Second 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 second 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 the 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, and 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, 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 Slit-2 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.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 40.08 E-value: 4.07e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  452 QPETTMAMVGKDIRFTCSAASSSSSPmTFAWKKDNEVLTNADMenfvHVH-AQDGEVMeyttilhLRQVTFGHEGRYQCV 530
Cdd:cd05724     3 EPSDTQVAVGEMAVLECSPPRGHPEP-TVSWRKDGQPLNLDNE----RVRiVDDGNLL-------IAEARKSDEGTYKCV 70

                          90
                  ....*....|....*..
gi 767922909  531 ITNHFGSTYSHKARLTV 547
Cdd:cd05724    71 ATNMVGERESRAARLSV 87

Immunoglobulin (Ig) domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig) domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

Pssm-ID: 409398 Cd Length: 101 Bit Score: 40.55 E-value: 4.20e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  659 GETVALQCKATGNPPPRITWFKGDRPLSLTE--RHHLT----PD--NQLLVVQNVVAEDAGRYTCEMSNTLGTERAHSQL 730
Cdd:cd05735    18 GQKKEMSCTAHGEKPIIVRWEKEDTIINPSEmsRYLVTtkevGDevISTLQILPTVREDSGFFSCHAINSYGEDRGIIQL 97


                  ..
gi 767922909  731 SV 732
Cdd:cd05735    98 TV 99

Sixth immunoglobulin (Ig) domain of contactin; The members here are composed of the sixth 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.

Pssm-ID: 409359 Cd Length: 102 Bit Score: 40.61 E-value: 4.24e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  656 VSVGETVALQCKATGNPPPRIT--WFKGDRPLSLTE------RHHLTPDNQLLVVQNVVAEDAGRYTCEMSNTLGTERAH 727
Cdd:cd04970    14 ITVGENATLQCHASHDPTLDLTftWSFNGVPIDLEKieghyrRRYGKDSNGDLEIVNAQLKHAGRYTCTAQTVVDSDSAS 93


                  ....*
gi 767922909  728 SQLSV 732
Cdd:cd04970    94 ATLVV 98

Third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR). Fibroblast growth factors (FGFs) participate in morphogenesis, development, angiogenesis, and wound healing. These FGF-stimulated processes are mediated by four FGFR tyrosine kinases (FGRF1-4). FGFRs are comprised of an extracellular portion consisting of three Ig-like domains, a transmembrane helix, and a cytoplasmic portion having protein tyrosine kinase activity. The highly conserved Ig-like domains 2 and 3, and the linker region between D2 and D3 define a general binding site for FGFs. 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.

Pssm-ID: 409363 Cd Length: 102 Bit Score: 40.48 E-value: 4.55e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  654 RVVSVGETVALQCKATGNPPPRITWFK-----GDR--PLSLTE--------RHHLTPDNQLLVvQNVVAEDAGRYTCEMS 718
Cdd:cd04974    11 QTVVLGSDVEFHCKVYSDAQPHIQWLKhvevnGSKygPDGLPYvtvlkvagVNTTGEENTLTI-SNVTFDDAGEYICLAG 89


                  ....
gi 767922909  719 NTLG 722
Cdd:cd04974    90 NSIG 93

Ran GTPase-activating protein (RanGAP) involved in mRNA processing and transport [Translation, ribosomal structure and biogenesis];

Pssm-ID: 444072 [Multi-domain] Cd Length: 434 Bit Score: 43.63 E-value: 6.48e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909   69 WTRSLNLSYNklsEIDPAGFEDL-------PNLQEVYLNNNELT--AVPSLGAASSH---VVSLFLQHNKIRSVEGSQLK 136
Cdd:COG5238   181 SVETVYLGCN---QIGDEGIEELaealtqnTTVTTLWLKRNPIGdeGAEILAEALKGnksLTTLDLSNNQIGDEGVIALA 257

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  137 AYL----SLEVLDLSLNNITEvrntcfPHGPPIKELnLAGNrigtlelgafdglsrslltlrlsknritqlpvrafklPR 212
Cdd:COG5238   258 EALknntTVETLYLSGNQIGA------EGAIALAKA-LQGN-------------------------------------TT 293

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  213 LTQLDLNRNRIR------LIEGLtfQGLNSLEVLKLQRNNISklTDG------AFWGLSKMHVLVLSFNNLTRLDEESLA 280
Cdd:COG5238   294 LTSLDLSVNRIGdegaiaLAEGL--QGNKTLHTLNLAYNGIG--AQGaialakALQENTTLHSLDLSDNQIGDEGAIALA 369

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767922909  281 ElsslsvlrlshnsishiaegAFKGLRSLRVLDLDHNEISgtiedTSGAFSGLDSL-----SKLTLFGNKIKSVAKRA 353
Cdd:COG5238   370 K--------------------YLEGNTTLRELNLGKNNIG-----KQGAEALIDALqtnrlHTLILDGNLIGAEAQQR 422

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.

Pssm-ID: 409435 Cd Length: 96 Bit Score: 39.93 E-value: 7.17e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767922909  662 VALQCKATGNPPPRITWFKGDRPLSLTE--RHHLTpDNQLLVVQNVVAEDAGRYTCEMSNTLGT 723
Cdd:cd05848    22 VILNCEARGNPVPTYRWLRNGTEIDTESdyRYSLI-DGNLIISNPSEVKDSGRYQCLATNSIGS 84

Leucine Rich repeats (2 copies); Leucine rich repeats are short sequence motifs present in a number of proteins with diverse functions and cellular locations. These repeats are usually involved in protein-protein interactions. Each Leucine Rich Repeat is composed of a beta-alpha unit. These units form elongated non-globular structures. Leucine Rich Repeats are often flanked by cysteine rich domains.

Pssm-ID: 463713 [Multi-domain] Cd Length: 44 Bit Score: 38.00 E-value: 7.96e-04

                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 767922909   360 LEHLNLGGNAIRSVqfDAFVKMKNLKELHISSDSFLCD 397
Cdd:pfam12799    3 LEVLDLSNNQITDI--PPLAKLPNLETLDLSGNNKITD 38

Second Ig-like domain of Junctional adhesion molecule-1 (JAM1); a member of the I-set of IgSF domains; The members here are composed of the second Ig-like domain of Junctional adhesion molecule-1 (JAM1). JAM1 is an immunoglobulin superfamily (IgSF) protein with two Ig-like domains in its extracellular region; it plays a role in the formation of endothelial and epithelial tight junction and acts as a receptor for mammalian reovirus sigma-1. The IgSF is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. 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 second Ig-like domain of JAM1 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, the A strand of the I-set is discontinuous but lacks 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.

Pssm-ID: 409542 Cd Length: 97 Bit Score: 39.61 E-value: 8.11e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767922909  656 VSVGETVALQC-KATGNPPPRITWFKGDRPLSLTER---------HHLTPDNQLLVVQNVVAEDAGRYTCEMSNTLGT 723
Cdd:cd20950     9 ATIGNRAVLTCsEPDGSPPSEYTWFKDGVVMPTNPKstrafsnssYSLDPTTGELVFDPLSASDTGEYSCEARNGYGT 86

BspA type Leucine rich repeat region (6 copies); This family includes a number of leucine rich repeats. This family contains a large number of BSPA-like surface antigens from Trichomonas vaginalis.

Pssm-ID: 463839 [Multi-domain] Cd Length: 127 Bit Score: 40.61 E-value: 8.25e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909   322 TIEDtsGAFSGLDSLSKLTlFGNKIKSVAKRAFSGLEgLEHLNLGGNaIRSVQFDAFVKMKNLKELHISS------DSFL 395
Cdd:pfam13306   24 SIGE--YAFSNCTSLKSIT-LPSSLTSIGSYAFYNCS-LTSITIPSS-LTSIGEYAFSNCSNLKSITLPSnltsigSYAF 98


                   ....*.
gi 767922909   396 CDCQLK 401
Cdd:pfam13306   99 SNCSLK 104

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 39.30 E-value: 8.35e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909   446 KPQIitQPETTMAMVGKDIRFTCSAASSSssPMTFAWKKDNEVLtnadmenfvhvhaqdgevmEYTTILHLRQVTFGHEG 525
Cdd:pfam13895    1 KPVL--TPSPTVVTEGEPVTLTCSAPGNP--PPSYTWYKDGSAI-------------------SSSPNFFTLSVSAEDSG 57

                           90       100
                   ....*....|....*....|..
gi 767922909   526 RYQCVITNHFGSTYSHKARLTV 547
Cdd:pfam13895   58 TYTCVARNGRGGKVSNPVELTV 79

Immunoglobulin (Ig)-like domain found in Perlecan and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain found in Perlecan. Perlecan is a large multi-domain heparin sulfate proteoglycan, important in tissue development and organogenesis. Perlecan can be represented as 5 major portions; its fourth major portion (domain IV) is a tandem repeat of immunoglobulin-like domains (Ig2-Ig15) which can vary in size due to alternative splicing. Perlecan binds many cellular and extracellular ligands. Its domain IV region has many binding sites. Some of these have been mapped at the level of individual Ig-like domains, including a site restricted to the Ig5 domain for heparin/sulfatide, a site restricted to the Ig3 domain for nidogen-1 and nidogen-2, a site restricted to Ig4-5 for fibronectin, and sites restricted to Ig2 and to Ig13-15 for fibulin-2. 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.

Pssm-ID: 409412 Cd Length: 85 Bit Score: 39.46 E-value: 8.47e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  557 PHDITIRTTTMARLECAA-TGHPNPQIAWQKDGGTdFPAarerrmHVMPDDDVFFITDVKIDDAGVYSCTAQNSAGSISA 635
Cdd:cd05754     8 PRSQEVRPGADVSFICRAkSKSPAYTLVWTRVNGT-LPS------RAMDFNGILTIRNVQLSDAGTYVCTGSNMLDTDEA 80


                  ....
gi 767922909  636 NATL 639
Cdd:cd05754    81 TATL 84

Immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan, also known as HSPG2, and similar proteins. Perlecan consists of five domains: domain I has three putative heparan sulfate attachment sites, domain II has four LDL receptor-like repeats, and one Ig-like repeat, domain III resembles the short arm of laminin chains, domain IV has multiple Ig-like repeats (21 repeats in human perlecan), and domain V resembles the globular G domain of the laminin A chain and internal repeats of EGF. Perlecan may participate in a variety of biological functions including cell binding, LDL-metabolism, basement membrane assembly and selective permeability, calcium binding, and growth- and neurite-promoting activities.

Pssm-ID: 143220 Cd Length: 78 Bit Score: 38.62 E-value: 1.22e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767922909  570 LECAATGHPNPQIAWQKDGGtdfPAARERRMHVMPDDD--VFFITDVKIDDAGVYSCTAQNSAGSISAN--ATLTV 641
Cdd:cd05743     6 FTCVATGVPTPIINWRLNWG---HVPDSARVSITSEGGygTLTIRDVKESDQGAYTCEAINTRGMVFGIpdGILTV 78

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 2 (NCAM-2); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule NCAM-2 (also known as OCAM/mamFas II and RNCAM). NCAM-2 is organized similarly to NCAM, including five N-terminal Ig-like domains and two fibronectin type III domains. NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE), and may function like NCAM, as an adhesion molecule. 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.

Pssm-ID: 143278 [Multi-domain] Cd Length: 98 Bit Score: 39.19 E-value: 1.30e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  557 PHDITIRTTTM-----ARLECAATGHPNPQIAWQK--DGGT--DFPAARERRMHVMPD--DDVFFITDVKIDDAGVYSCT 625
Cdd:cd05870     3 PHIIQLKNETTvengaATLSCKAEGEPIPEITWKRasDGHTfsEGDKSPDGRIEVKGQhgESSLHIKDVKLSDSGRYDCE 82


                  ....*.
gi 767922909  626 AQNSAG 631
Cdd:cd05870    83 AASRIG 88

Sixth 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 sixth 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.

Pssm-ID: 409551 Cd Length: 94 Bit Score: 39.01 E-value: 1.35e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  658 VGETVALQCKAT-GNPPPRITWFKGDRPLSltERHHLT-----PDNQLLVVQNVVAEDAGRYTCEMSNTLGTERAHSQLS 731
Cdd:cd20959    16 VGMRAQLHCGVPgGDLPLNIRWTLDGQPIS--DDLGITvsrlgRRSSILSIDSLEASHAGNYTCHARNSAGSASYTAPLT 93


                  .
gi 767922909  732 V 732
Cdd:cd20959    94 V 94

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

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 38.60 E-value: 1.45e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767922909  479 TFAWKKDNEVLTNADMENFVhvhaQDGEvmeyttiLHLRQVTFGHEGRYQCVITNHFGSTYS 540
Cdd:cd04969    33 TISWSKGTELLTNSSRICIL----PDGS-------LKIKNVTKSDEGKYTCFAVNFFGKANS 83

Immunoglobulin (Ig)-like domain found in neuregulin (NRG)-1; The members here are composed of the immunoglobulin (Ig)-like domain found in neuregulin (NRG)-1. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. NRG-1 belongs to the neuregulin gene family which is comprised of four genes. This group represents NRG-1. NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, and heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. The NRG-1 protein binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. NRG-1 has multiple functions, for example, in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival.

Pssm-ID: 409476 Cd Length: 93 Bit Score: 38.82 E-value: 1.45e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  656 VSVGETVALQCKATGNPPP-RITWFKGDRPLSLTER-HHLT----PDNQLLVVQNVVAEDAGRYTCEMSNTLGTERAHSQ 729
Cdd:cd05895    11 VAAGSKLVLRCETSSEYPSlRFKWFKNGKEINRKNKpENIKiqkkKKKSELRINKASLADSGEYMCKVSSKLGNDSASAN 90


                  ...
gi 767922909  730 LSV 732
Cdd:cd05895    91 VTI 93

Immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

Pssm-ID: 409397 [Multi-domain] Cd Length: 97 Bit Score: 39.01 E-value: 1.45e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767922909  570 LECAATGHPNPQIAWQKDGGTDFP-----AARERRMHVMPDDDVfFITDVKIDDAGVYSCTAQNSAGS-ISANATLTV 641
Cdd:cd05734    21 LNCSADGYPPPTIVWKHSKGSGVPqfqhiVPLNGRIQLLSNGSL-LIKHVLEEDSGYYLCKVSNDVGAdISKSMYLTV 97

Immunoglobulin V-set domain; This domain is found in antibodies as well as neural protein P0 and CTL4 amongst others.

Pssm-ID: 462230 Cd Length: 109 Bit Score: 39.36 E-value: 1.47e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909   656 VSVGETVALQCKATG---NPPPRITWFKGDRPLSLT----------------ERHHLTPD----NQLLVVQNVVAEDAGR 712
Cdd:pfam07686    8 VALGGSVTLPCTYSSsmsEASTSVYWYRQPPGKGPTfliayysngseegvkkGRFSGRGDpsngDGSLTIQNLTLSDSGT 87

                           90       100
                   ....*....|....*....|..
gi 767922909   713 YTCEM-SNTLGTERAHSQLSVL 733
Cdd:pfam07686   88 YTCAViPSGEGVFGKGTRLTVL 109

First immunoglobulin (Ig)-like domain of neural cell adhesion molecule NCAM-1, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of neural cell adhesion molecule NCAM-1. NCAM-1 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-nonNCAM) 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 the Ig1, Ig2, and Ig3 domains. 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). 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.

Pssm-ID: 409366 Cd Length: 95 Bit Score: 38.77 E-value: 1.60e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767922909  656 VSVGETVALQCKATGNPPpRITWF--KGDRPLSLTER---HHLTPDNQLLVVQNVVAEDAGRYTCEMSNTLGTE 724
Cdd:cd04977    12 ISVGESKFFLCKVSGDAK-NINWVspNGEKVLTKHGNlkvVNHGSVLSSLTIYNANINDAGIYKCVATNGKGTE 84

CD80-like C2-set immunoglobulin domain; These domains belong to the immunoglobulin superfamily.

Pssm-ID: 400489 Cd Length: 89 Bit Score: 38.55 E-value: 1.79e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909   648 VVPLEDRVVSVGETVALQCKAT-GNPPPRITWFKGDRPLSLTERHHLT-PDNQLLVVQ-----NVVAEDAGR-YTCEMSN 719
Cdd:pfam08205    3 IEPPASLLEGEGPEVVATCSSAgGKPAPRITWYLDGKPLEAAETSSEQdPESGLVTVTselklVPSRSDHGQsLTCQVSY 82


                   ....*..
gi 767922909   720 TLGTERA 726
Cdd:pfam08205   83 GALRGSI 89

Immunoglobulin (Ig)-like domain of NrCAM (Ng (neuronglia) CAM-related cell adhesion molecule); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of NrCAM (Ng (neuronglia) CAM-related cell adhesion molecule). NrCAM 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. NrCAM is primarily expressed in the nervous system.

Pssm-ID: 409458 Cd Length: 95 Bit Score: 38.81 E-value: 1.90e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767922909  652 EDRVVSVGETVALQCKATGNPPPRITWFKGDRPLSLTERHHLT--PDNQLLVVQNVVAEDA----GRYTCEMSNTLGT 723
Cdd:cd05874     9 KDYIVDPRENIVIQCEAKGKPPPSFSWTRNGTHFDIDKDPKVTmkPNTGTLVINIMNGEKAeayeGVYQCTARNERGA 86

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.

Pssm-ID: 409561 Cd Length: 92 Bit Score: 38.52 E-value: 2.03e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767922909  570 LECAATGHPNPQIAWQKDGGTDFPAARERRMHVMPDDDVFFiTDVKIDDAGVYSCTAQNSAGSISANATLTV 641
Cdd:cd20969    22 FVCRADGDPPPAILWLSPRKHLVSAKSNGRLTVFPDGTLEV-RYAQVQDNGTYLCIAANAGGNDSMPAHLHV 92

Third immunoglobulin domain in Cluster of Differentiation (CD) 22; member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain in Cluster of Differentiation (CD) 22 (also known as Siglec-2). CD22, a sialic-acid binding immunoglobulin type-lectin (Siglec) family member, is an inhibitory co-receptor of the B-cell receptor (BCR). The inhibitory function of CD22 and its restricted expression on B cells makes CD22 an attractive target against dysregulated B cells that cause autoimmune diseases and B-cell-derived cancers. CD22 plays a vital role in establishing a baseline level of B-cell inhibition, and thus is an important determinant of homeostasis in humoral immunity. Siglecs are primarily expressed on immune cells and recognize sialic acid-containing glycan ligands. Siglecs are organized as an extracellular module composed of Ig-like domains (an N-terminal variable set of Ig-like carbohydrate recognition domains, and 1 to 16 constant Ig-like domains), followed by transmembrane and short cytoplasmic domains. Human Siglecs are classified into two subgroups, one subgroup is comprised of sialoadhesin (Siglec-1), CD22 (Siglec-2), and MAG (Siglec-4, myelin-associated glycoprotein), the other subgroup is comprised of CD33-related Siglecs which include CD33 (Siglec-3) and human Siglecs 5-11. 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. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409531 Cd Length: 88 Bit Score: 38.24 E-value: 2.18e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  639 LTVLETPSlvvpleDRVVSVGETVALQCKATGNPP--PRITWFKGDRplSLTERHHLTpdnqlLVVQNVVAEDAGRYTCE 716
Cdd:cd20937     3 LEIKVTPS------DAIVREGDSVTMTCEVSSSNPeyTTVSWLKDGT--SLKKQNTFT-----LNLREVTKDQSGKYCCQ 69

                          90
                  ....*....|
gi 767922909  717 MSNTLGTERA 726
Cdd:cd20937    70 VSNDVGPGRS 79

Fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell adhesion molecule 5 (CEACAM5) and similar domains; member of the C2-set IgSF domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell adhesion molecule 5 (CEACAM5) and similar domains. The CEA family is a group of anchored or secreted glycoproteins, expressed by epithelial cells, leukocytes, endothelial cells and placenta. The CEA family is divided into the CEACAM and pregnancy-specific glycoprotein (PSG) subfamilies. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), also known as CD66e (Cluster of Differentiation 66e), is a cell surface glycoprotein that plays a role in cell adhesion, intracellular signaling and tumor progression. Diseases associated with CEACAM5 include lung cancer and rectum cancer. 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. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409540 Cd Length: 76 Bit Score: 37.86 E-value: 2.25e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  556 TPHDITIRTTTMARLECAATGHPNPQIAWQKDGGtdfpaaRERRMHVMpdddvfFITDVKIDDAGVYSCTAQNSAGS--I 633
Cdd:cd20948     1 SPSDTYYLSGENLNLSCHAASNPPAQYSWTINGT------FQTSSQEL------FLPAITENNEGTYTCSAHNSLTGknI 68


                  ....*...
gi 767922909  634 SANATLTV 641
Cdd:cd20948    69 SLVLSVTV 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.

Pssm-ID: 143277 [Multi-domain] Cd Length: 97 Bit Score: 38.42 E-value: 2.56e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767922909  570 LECAATGHPNPQIAWQKdgGTDFPAARER----RMHVMPDDDVFFIT--DVKIDDAGVYSCTAQNSAGSISANATLTV 641
Cdd:cd05869    22 LTCEASGDPIPSITWRT--STRNISSEEKtldgHIVVRSHARVSSLTlkYIQYTDAGEYLCTASNTIGQDSQSMYLEV 97

type III secretion system effector E3 ubiquitin transferase SlrP;

Pssm-ID: 185268 [Multi-domain] Cd Length: 754 Bit Score: 41.61 E-value: 2.85e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909   51 SLDCGGRGLAALPGDLPSWTRSLNLSYNKLSEIDpagfEDLPN-LQEVYLNNNELTAVPSlgAASSHVVSLFLQHNKIRS 129
Cdd:PRK15370  266 SLDLFHNKISCLPENLPEELRYLSVYDNSIRTLP----AHLPSgITHLNVQSNSLTALPE--TLPPGLKTLEAGENALTS 339

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 767922909  130 VEGSQLKAylsLEVLDLSLNNITEVRNTcFPhgPPIKELNLAGNRIGTL 178
Cdd:PRK15370  340 LPASLPPE---LQVLDVSKNQITVLPET-LP--PTITTLDVSRNALTNL 382

Second immunoglobulin (Ig)-like domain of Axl/Tyro3 family receptor tyrosine kinases (RTKs); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in the Axl/Tyro3 family of receptor tyrosine kinases (RTKs). This family includes Axl (also known as Ark, Ufo, and Tyro7), Tyro3 (also known as Sky, Rse, Brt, Dtk, and Tif), and Mer (also known as Nyk, c-Eyk, and Tyro12). Axl/Tyro3 family receptors have an extracellular portion with two Ig-like domains followed by two fibronectin-types III (FNIII) domains, a membrane-spanning single helix, and a cytoplasmic tyrosine kinase domain. Axl, Tyro3, and Mer are widely expressed in adult tissues, though they show higher expression in the brain, lymphatic and vascular systems, and testis. Axl, Tyro3, and Mer bind the vitamin K dependent protein Gas6 with high affinity, and in doing so activate their tyrosine kinase activity. Axl/Gas6 signaling may play a part in cell adhesion processes, prevention of apoptosis, and cell proliferation.

Pssm-ID: 409407 Cd Length: 82 Bit Score: 37.83 E-value: 2.86e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  553 FTKTPHDITIRTTTMARLECAATGHPNP-QIAWQKDGG--TDFPAARERRMHVmpdddvffitdVKIDDAGVYSCTAQNS 629
Cdd:cd05749     2 FTVEPEDLAVTANTPFNLTCQAVGPPEPvEILWWQGGSplGGPPAPSPSVLNV-----------PGLNETTKFSCEAHNA 70

                          90
                  ....*....|..
gi 767922909  630 AG-SISANATLT 640
Cdd:cd05749    71 KGlTSSRTATVT 82

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 3 (VEGFR-3); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 3 (VEGFR-3). The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. VEGFRs bind VEGFs with high affinity at the Ig-like domains. VEGFR-3 (Flt-4) binds two members of the VEGF family (VEGF-C and VEGF-D) and is involved in tumor angiogenesis and growth. 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.

Pssm-ID: 409449 Cd Length: 88 Bit Score: 37.99 E-value: 2.97e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767922909  660 ETVALQCKATGNPPPRITWFKGDRPLSLTERHHltpdnqLLVVQNVVAEDAGRYTCEMSNTL-GTER 725
Cdd:cd05863    20 ELVKLPVKVAAYPPPEFQWYKDGKLISGKHSPH------SLQIKDVTEASAGTYTLVLWNSAaGLEK 80

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).

Pssm-ID: 409401 Cd Length: 82 Bit Score: 37.57 E-value: 3.15e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 767922909  570 LECAATGHPNPQIAWQKdGGTDFPAARErrmhvMP-DDDVFFITDVKidDAGVYSCTAQNSAGSISANATLTV 641
Cdd:cd05739    17 LTCVAVGAPMPYVKWMK-GGEELTKEDE-----MPvGRNVLELTNIY--ESANYTCVAISSLGMIEATAQVTV 81

type III secretion system effector E3 ubiquitin transferase SspH2;

Pssm-ID: 185285 [Multi-domain] Cd Length: 788 Bit Score: 41.30 E-value: 3.80e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909   51 SLDCGGRGLAALPGdLPSWTRSLNLSYNKLSEID--PAGFEDL--------------PNLQEVYLNNNELTAVPSLgaaS 114
Cdd:PRK15387  246 TLEVSGNQLTSLPV-LPPGLLELSIFSNPLTHLPalPSGLCKLwifgnqltslpvlpPGLQELSVSDNQLASLPAL---P 321

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  115 SHVVSLFLQHNKIR------------SVEGSQLKAYLSL--EVLDL-SLNNitevRNTCFPHGPP-IKELNLAGNRIGTL 178
Cdd:PRK15387  322 SELCKLWAYNNQLTslptlpsglqelSVSDNQLASLPTLpsELYKLwAYNN----RLTSLPALPSgLKELIVSGNRLTSL 397

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 767922909  179 ELgafdgLSRSLLTLRLSKNRITQLPVrafkLPR-LTQLDLNRNRI-RLIEGLTFqgLNSLEVLKLQRNNISKLT 251
Cdd:PRK15387  398 PV-----LPSELKELMVSGNRLTSLPM----LPSgLLSLSVYRNQLtRLPESLIH--LSSETTVNLEGNPLSERT 461

CD19 (Cluster of Differentiation 19), a unique double immunoglobulin (Ig)-fold domain; CD19, also known as B-Lymphocyte Surface Antigen B4, T-Cell Surface Antigen Leu-12, and CVID3, is a transmembrane receptor present on various types of B cells, including progenitor, naive, and memory B cells, as well as plasmablasts. Until recently, it was believed to comprise two extracellular immunoglobulin (Ig) structural domains arranged in tandem with C2 topology. However, recent crystal structures have shown that the CD19 extracellular domain contains a unique double Ig domain that is responsible for its binding to proteins such as CD21, CD81, and CD225, which regulate B cell activation and survival. A recent analysis of the CD19 extracellular domain sequence reveals two "Ig domains", but the structure demonstrates that these two domains are not folded independently and connected in tandem. Rather, they fold together as one intertwined domain that can be referred to as a "double Ig" domain. Each of the two regular Ig domain sequences has a noticeably short linker that forms a loop between strands C' and D, rather than allowing the formation of a C" strand. Additionally, the two Ig-domain sequences are separated by a long linker that is structured as a small insertion domain, enabling both Ig sequences to fold together as a unique double Ig-domain. The CD19 domain comprises four "protodomains": two formed by A'B-CC' strands and two by DE-FG strands that interdigitate to form a novel double Ig fold. When analyzing this double Ig domain in terms of the usual Ig-fold, A'B-CC' protodomain of the first Ig sequence combines with DE-FG protodomain of the second, and vice versa. Hence, the second combined Ig fold is inverted, with DE-FG protodomain of the first Ig sequence combining with A'B-CC' protodomain of the second Ig sequence and in that order, as if it were a circular permutation, obtained only through structural folding.

Pssm-ID: 467824 Cd Length: 89 Bit Score: 37.32 E-value: 4.19e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767922909  656 VSVGETVALQCKATGNPPPR--ITWFKGD-----RPLSLTERH---HLTPDNQLLVVQNVVAEDAGRYTCEMSN 719
Cdd:cd23997     5 VAEGSTLWLPCLVPPSDGPRgpLTWSRGHpktplLSLELGSPGlwvLVGPLGILLLLPNVSAQMGGFYLCELGN 78

Fifth domain (immunoglobulin-like) of Trk receptors TrkA, TrkB, and TrkC; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth 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. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409360 Cd Length: 96 Bit Score: 37.38 E-value: 4.73e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767922909  669 TGNPPPRITWFKGDRPLS-----LTERHHLTPDNQL----LVVQNVVAEDAGRYTCEMSNTLGTERA 726
Cdd:cd04971    23 RGNPKPTLTWYHNGAVLNesdyiRTEIHYEAATPTEyhgcLKFDNPTHVNNGNYTLVASNEYGQDSK 89

C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein (also known as myomesin-2). Myomesin and M-protein are both structural proteins localized to the M-band, a transverse structure in the center of the sarcomere, and are candidates for M-band bridges. Both proteins are modular, consisting mainly of repetitive Ig-like and fibronectin type III (FnIII) domains. Myomesin is expressed in all types of vertebrate striated muscle; M-protein has a muscle-type specific expression pattern. Myomesin is present in both slow and fast fibers; M-protein is present only in fast fibers. It has been suggested that myomesin acts as a molecular spring with alternative splicing as a means of modifying its elasticity.

Pssm-ID: 319300 Cd Length: 92 Bit Score: 37.19 E-value: 5.14e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  557 PHDITIRTTTMARLECAATGHPNPQIAWQKDgGTDFPAARERRMHVMPDDDVFF-ITDVKIDDAGVYSCTAQNSAGSISA 635
Cdd:cd05737     8 PDVVTIMEGKTLNLTCNVWGDPPPEVSWLKN-DQALAFLDHCNLKVEAGRTVYFtINGVSSEDSGKYGLVVKNKYGSETS 86


                  ....*.
gi 767922909  636 NATLTV 641
Cdd:cd05737    87 DVTVSV 92

Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues, and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. 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.

Pssm-ID: 409388 Cd Length: 84 Bit Score: 37.18 E-value: 5.38e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767922909  662 VALQCKATGNPPPRITWFKGDRPLSLTERHHLTPDNQLLVVqNVVAEDAGRYTCEMSNTLGTERAHSQLSV 732
Cdd:cd05723    15 IVFECEVTGKPTPTVKWVKNGDVVIPSDYFKIVKEHNLQVL-GLVKSDEGFYQCIAENDVGNAQASAQLII 84

First 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.

Pssm-ID: 409474 Cd Length: 92 Bit Score: 37.00 E-value: 6.82e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767922909  572 CAATGHPNPQIAWQKDGGTDFPAARERRMHVMPDDDV-FFITDVKIDDAGVYSCTAQNSAGSISANATLTV 641
Cdd:cd05893    22 CRVAGNPKPKIYWFKDGKQISPKSDHYTIQRDLDGTCsLHTTASTLDDDGNYTIMAANPQGRISCTGRLMV 92

Third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor 2 (FGFR2); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain of human fibroblast growth factor receptor 2 (FGFR2). Fibroblast growth factors (FGFs) participate in morphogenesis, development, angiogenesis, and wound healing. These FGF-stimulated processes are mediated by four FGFR tyrosine kinases (FGRF1-4). FGFRs are comprised of an extracellular portion consisting of three Ig-like domains, a transmembrane helix, and a cytoplasmic portion having protein tyrosine kinase activity. The highly conserved Ig-like domains 2 and 3, and the linker region between D2 and D3 define a general binding site for FGFs. FGFR2 is required for male sex determination. 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.

Pssm-ID: 409444 Cd Length: 105 Bit Score: 36.86 E-value: 8.66e-03

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 767922909  513 ILHLRQVTFGHEGRYQCVITNHFGSTYsHKARLTV 547
Cdd:cd05858    71 VLYLRNVTFEDAGEYTCLAGNSIGISH-HSAWLTV 104

Immunoglobulin-like M1 domain from Titin; a member of the I-set of IgSF domains; The members here are composed of the Immunoglobulin-like M1 I-set domain from Titin 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-M1 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.

Pssm-ID: 409521 Cd Length: 90 Bit Score: 36.55 E-value: 9.21e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 767922909  675 RITWFKGDRPLSLTERHHLTPDN--QLLVVQNVVAEDAGRYTCEMSNTLGTERAHSQLSV 732
Cdd:cd20927    31 QVTWYFGVRQLENSEKYEITYEDgvAILYVKDITKFDDGTYRCKVVNDYGEDSSYAELFV 90