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: 214.02 E-value: 2.50e-65

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 497 SFTKIPHDIAIRTGTTARLECAATGHPNPQIAWQKDGGTDFPAARERRMHVMPDDDVFFITDVKIDDMGVYSCTAQNSAG 576
Cdd:cd05763     1 SFTKTPHDITIRAGSTARLECAATGHPTPQIAWQKDGGTDFPAARERRMHVMPEDDVFFIVDVKIEDTGVYSCTAQNSAG 80

                          90
                  ....*....|.
gi 1907171115 577 SVSANATLTVL 587
Cdd:cd05763    81 SISANATLTVL 91

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 111.97 E-value: 2.49e-29

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 496 PSFTKIPHDIAIRTGTTARLECAATGHPNPQIAWQKDGgTDFPAARERRMHVMPDDDVFFITDVKIDDMGVYSCTAQNSA 575
Cdd:pfam07679   1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDG-QPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSA 79

                          90
                  ....*....|.
gi 1907171115 576 GSVSANATLTV 586
Cdd:pfam07679  80 GEAEASAELTV 90

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

Pssm-ID: 443914 [Multi-domain] Cd Length: 414 Bit Score: 119.27 E-value: 1.67e-28

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115  22 NKILSVDGSQLKSYLSLEVLDLSSNNITEIRSSCFPNGLRIRELNLASNRISILESGAFDGLSRSLLTLRLSKNRITQLP 101
Cdd:COG4886    10 LKLLLLLLLELLTTLILLLLLLLLLLALLLLSLLSLLLLLTLLLSLLLRDLLLSSLLLLLSLLLLLLLSLLLLSLLLLGL 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 102 VKAFKLPRLTQLDLNRNRirlieglTFQGLDSLEVLRLQRNNISRLTDgAFWGLSKMHVLHLEYNSLVEVNSgSLYGLTA 181
Cdd:COG4886    90 TDLGDLTNLTELDLSGNE-------ELSNLTNLESLDLSGNQLTDLPE-ELANLTNLKELDLSNNQLTDLPE-PLGNLTN 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 182 LHQLHLSNNSISRIqRDGWSFCQKLHELILSFNNLTRLDEEslaelsslsilrlshnaishiaegaFKGLKSLRVLDLDH 261
Cdd:COG4886   161 LKSLDLSNNQLTDL-PEELGNLTNLKELDLSNNQITDLPEP-------------------------LGNLTNLEELDLSG 214

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907171115 262 NEISgtieDTSGAFTGLDNLSKLTLFGNKIKSVAkrAFSGLESLEHLNLGENAIRSvqFDAFAKMKNLKELYIS 335
Cdd:COG4886   215 NQLT----DLPEPLANLTNLETLDLSNNQLTDLP--ELGNLTNLEELDLSNNQLTD--LPPLANLTNLKTLDLS 280

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

Pssm-ID: 443914 [Multi-domain] Cd Length: 414 Bit Score: 109.64 E-value: 3.38e-25

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115  23 KILSVDGSQLKSYLS-LEVLDLSSNNITEIrSSCFPNGLRIRELNLASNRISILESG----------AFDGlsrslltlr 91
Cdd:COG4886    99 TELDLSGNEELSNLTnLESLDLSGNQLTDL-PEELANLTNLKELDLSNNQLTDLPEPlgnltnlkslDLSN--------- 168

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115  92 lskNRITQLPVKAFKLPRLTQLDLNRNRIRLIeGLTFQGLDSLEVLRLQRNNISRLTDgAFWGLSKMHVLHLEYNSLVEV 171
Cdd:COG4886   169 ---NQLTDLPEELGNLTNLKELDLSNNQITDL-PEPLGNLTNLEELDLSGNQLTDLPE-PLANLTNLETLDLSNNQLTDL 243

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 172 nsGSLYGLTALHQLHLSNNSISRIqrDGWSFCQKLHELILSFNNLTRLDEESLAELSSLSILRLSHNAISHIAEgaFKGL 251
Cdd:COG4886   244 --PELGNLTNLEELDLSNNQLTDL--PPLANLTNLKTLDLSNNQLTDLKLKELELLLGLNSLLLLLLLLNLLEL--LILL 317

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907171115 252 KSLRVLDLDHNEISGTIEDTSGAFTGLDNLSKLTLFGNKIKSVAKRAFSGLESLEHLNLGENAIRSVQFDAFAK 325
Cdd:COG4886   318 LLLTTLLLLLLLLKGLLVTLTTLALSLSLLALLTLLLLLNLLSLLLTLLLTLGLLGLLEATLLTLALLLLTLLL 391

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 95.02 E-value: 2.56e-23

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 590 PSLAVPLEDRVVTVGETVAFQCKATGSPTPRITWLKGGRPLSLTERH--HFTPGNQLLVVQNVMIDDAGRYTCEMSNPLG 667
Cdd:pfam07679   1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFkvTYEGGTYTLTISNVQPDDSGKYTCVATNSAG 80

                          90
                  ....*....|
gi 1907171115 668 TERAHSQLSI 677
Cdd:pfam07679  81 EAEASAELTV 90

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

Pssm-ID: 443914 [Multi-domain] Cd Length: 414 Bit Score: 100.01 E-value: 5.38e-22

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115  65 LNLASNRISILESGAFDGLSRSLLTLRLSKNRITQLPVKAFKLPRLTQLDLNRNRIRLIEGLTFQGLDSLEVLRLQRNNI 144
Cdd:COG4886     5 LLSLTLKLLLLLLLELLTTLILLLLLLLLLLALLLLSLLSLLLLLTLLLSLLLRDLLLSSLLLLLSLLLLLLLSLLLLSL 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 145 SRLTDGAFWGLSKMHVLHLEYNSlvevnsgSLYGLTALHQLHLSNNSISRIQRDGWSFcQKLHELILSFNNLTRLDEEsl 224
Cdd:COG4886    85 LLLGLTDLGDLTNLTELDLSGNE-------ELSNLTNLESLDLSGNQLTDLPEELANL-TNLKELDLSNNQLTDLPEP-- 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 225 aelsslsilrlshnaishiaegaFKGLKSLRVLDLDHNEISgtieDTSGAFTGLDNLSKLTLFGNKIKSVAKrAFSGLES 304
Cdd:COG4886   155 -----------------------LGNLTNLKSLDLSNNQLT----DLPEELGNLTNLKELDLSNNQITDLPE-PLGNLTN 206

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*
gi 1907171115 305 LEHLNLGENAIRSVQfDAFAKMKNLKELYISsesflcDCQLKWLP 349
Cdd:COG4886   207 LEELDLSGNQLTDLP-EPLANLTNLETLDLS------NNQLTDLP 244

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

Pssm-ID: 443914 [Multi-domain] Cd Length: 414 Bit Score: 83.06 E-value: 1.85e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 163 LEYNSLVEVNSGSLYGLTALHQLHLSNNsisriqrDGWSFCQKLHELILSFNNLTRLDEEslaelsslsilrlshnaish 242
Cdd:COG4886    79 LLLLSLLLLGLTDLGDLTNLTELDLSGN-------EELSNLTNLESLDLSGNQLTDLPEE-------------------- 131

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 243 iaegaFKGLKSLRVLDLDHNEISgtieDTSGAFTGLDNLSKLTLFGNKIKSVAKrAFSGLESLEHLNLGENAIRSVQfDA 322
Cdd:COG4886   132 -----LANLTNLKELDLSNNQLT----DLPEPLGNLTNLKSLDLSNNQLTDLPE-ELGNLTNLKELDLSNNQITDLP-EP 200

                         170       180       190
                  ....*....|....*....|....*....|
gi 1907171115 323 FAKMKNLKELYISsesflcDCQLKWLPPWL 352
Cdd:COG4886   201 LGNLTNLEELDLS------GNQLTDLPEPL 224

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 74.14 E-value: 3.96e-16

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907171115 590 PSLAVPLEDRVVTVGETVAFQCKATGSPTPRITWLKGGRPL--SLTERHHFTPGNQLLVVQNVMIDDAGRYTCEMSN 664
Cdd:pfam13927   2 PVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPIssGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

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: 74.46 E-value: 4.12e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 598 DRVVTVGETVAFQCKATGSPTPRITWLKGGRPLSLTERHHFTPGNQLLVVQNVMIDDAGRYTCEMSNPLGTERAHSQLSI 677
Cdd:cd20952     8 NQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDERITTLENGSLQIKGAEKSDTGEYTCVALNLSGEATWSAVLDV 87

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: 78.29 E-value: 4.89e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115  20 QHNKILSVDGsqLKSYLSLEVLDLSSNNITEIRS-SCFPNglrIRELNLASNRISILESgaFDGlsrslltlrlsknrit 98
Cdd:cd21340    10 NDKNITKIDN--LSLCKNLKVLYLYDNKITKIENlEFLTN---LTHLYLQNNQIEKIEN--LEN---------------- 66

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115  99 qlpvkafkLPRLTQLDLNRNRIRLIEGLtfQGLDSLEVLRLQRNNISR---LT--DGAFWGLSK-MHVLHLEYNSLVEVN 172
Cdd:cd21340    67 --------LVNLKKLYLGGNRISVVEGL--ENLTNLEELHIENQRLPPgekLTfdPRSLAALSNsLRVLNISGNNIDSLE 136

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*...
gi 1907171115 173 sgSLYGLTALHQLHLSNNSISRIqrdgwsfcQKLHELILSFNNLTRLD 220
Cdd:cd21340   137 --PLAPLRNLEQLDASNNQISDL--------EELLDLLSSWPSLRELD 174

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: 77.90 E-value: 5.48e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 109 RLTQLDLNRNRIRLIEGLTFqgLDSLEVLRLQRNNISRLTDgaFWGLSKMHVLHLEYNSLVEVNSgsLYGLTALHQLHLS 188
Cdd:cd21340     3 RITHLYLNDKNITKIDNLSL--CKNLKVLYLYDNKITKIEN--LEFLTNLTHLYLQNNQIEKIEN--LENLVNLKKLYLG 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 189 NNSISRIqrDGWSFCQKLHELILSFNNLTR-----LDEESLAELSSL-SILRLSHNAISHIAEgaFKGLKSLRVLDLDHN 262
Cdd:cd21340    77 GNRISVV--EGLENLTNLEELHIENQRLPPgekltFDPRSLAALSNSlRVLNISGNNIDSLEP--LAPLRNLEQLDASNN 152

                         170       180       190
                  ....*....|....*....|....*....|....
gi 1907171115 263 EISGtIEDTSGAFTGLDNLSKLTLFGNKIKSVAK 296
Cdd:cd21340   153 QISD-LEELLDLLSSWPSLRELDLTGNPVCKKPK 185

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: 72.43 E-value: 1.61e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 502 PHDIAIRTGTTARLECAATGHPNPQIAWQKDGGtDFPaarERRMHVMpDDDVFFITDVKIDDMGVYSCTAQNSAGSVSAN 581
Cdd:cd05725     4 PQNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDG-ELP---KGRYEIL-DDHSLKIRKVTAGDMGSYTCVAENMVGKIEAS 78


                  ....*
gi 1907171115 582 ATLTV 586
Cdd:cd05725    79 ATLTV 83

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: 70.88 E-value: 7.10e-15

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907171115 595 PLEDRVVTVGETVAFQCKATGSPTPRITWLKGGRPLS-LTERHHFTPGNqlLVVQNVMIDDAGRYTCEMSNPLGTER 670
Cdd:cd20978     7 PEKNVVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQgPMERATVEDGT--LTIINVQPEDTGYYGCVATNEIGDIY 81

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: 69.67 E-value: 1.07e-14

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907171115 607 VAFQCKATGSPTPRITWLKGGRPLSLT--ERHHFTPGNQLLVVQNVMIDDAGRYTCEMSNPLGTERAHS 673
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSsrDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASAS 69

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: 70.23 E-value: 1.09e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115  502 PHDIAIRTGTTARLECAATGHPNPQIAWQKDGGTdfPAARERRMHVMPDDDVF--FITDVKIDDMGVYSCTAQNSAGSVS 579
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGK--LLAESGRFSVSRSGSTStlTISNVTPEDSGTYTCAATNSSGSAS 78


                   ....*..
gi 1907171115  580 ANATLTV 586
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: 69.58 E-value: 1.34e-14

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907171115 604 GETVAFQCKATGSPTPRITWLKGGRPLSLtERHHFTPGNQLLVVQNVMIDDAGRYTCEMSNPLGTERAHSQLSI 677
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: 70.27 E-value: 1.69e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 496 PSFTKIPHDIAIRTGTTARLECAATGHPNPQIAWQKDG---GTDFPAARERRMhVMPDDDVFFITDV----KIDDMGVYS 568
Cdd:cd07693     1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGqplETDKDDPRSHRI-VLPSGSLFFLRVVhgrkGRSDEGVYV 79

                          90
                  ....*....|....*....
gi 1907171115 569 CTAQNSAG-SVSANATLTV 586
Cdd:cd07693    80 CVAHNSLGeAVSRNASLEV 98

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 68.75 E-value: 2.47e-14

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907171115 496 PSFTKIPHDIAIRTGTTARLECAATGHPNPQIAWQKDGGTDFPaARERRMHVMPDDDVFFITDVKIDDMGVYSCTAQN 573
Cdd:pfam13927   2 PVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISS-GSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 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: 69.07 E-value: 2.76e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115  597 EDRVVTVGETVAFQCKATGSPTPRITWLK-GGRPLSLTERHHFTPGNQL--LVVQNVMIDDAGRYTCEMSNPLGTERAHS 673
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPEVTWYKqGGKLLAESGRFSVSRSGSTstLTISNVTPEDSGTYTCAATNSSGSASSGT 81


                   ....
gi 1907171115  674 QLSI 677
Cdd:smart00410  82 TLTV 85

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: 67.92 E-value: 7.23e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 586 VLETPSlavPLEDRVVTVGETVAFQCKATGSPTPRITWL-KGGRPLSLTERHHFTPGNQLLVVQNVMIDDAGRYTCEMSN 664
Cdd:cd20970     2 VISTPQ---PSFTVTAREGENATFMCRAEGSPEPEISWTrNGNLIIEFNTRYIVRENGTTLTIRNIRRSDMGIYLCIASN 78

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: 66.08 E-value: 2.66e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 500 KIPHDIAIRTGTTARLECAATGHPNPQIAWQKDGGtdfPAARERRMHVMPDDdvFFITDVKIDDMGVYSCTAQNSAGSVS 579
Cdd:cd05728     4 KVISDTEADIGSSLRWECKASGNPRPAYRWLKNGQ---PLASENRIEVEAGD--LRITKLSLSDSGMYQCVAENKHGTIY 78


                  ....*..
gi 1907171115 580 ANATLTV 586
Cdd:cd05728    79 ASAELAV 85

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: 66.12 E-value: 3.76e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 496 PSFTKIPHDIAIRTGTTARLECAATGHPNPQIAWQKDGgTDFPAARERrMHVMPDDDVFFITDVKIDDMGVYSCTAQNSA 575
Cdd:cd20976     2 PSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNA-QPLQYAADR-STCEAGVGELHIQDVLPEDHGTYTCLAKNAA 79

                          90
                  ....*....|.
gi 1907171115 576 GSVSANATLTV 586
Cdd:cd20976    80 GQVSCSAWVTV 90

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: 4.13e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 495 LPSFTKIphdiaIRTGTTARLECAATGHPNPQIAWQKDGGTdfPAARERRMHVMPDDDVFFITDVKIDDMGVYSCTAQNS 574
Cdd:cd20970     7 QPSFTVT-----AREGENATFMCRAEGSPEPEISWTRNGNL--IIEFNTRYIVRENGTTLTIRNIRRSDMGIYLCIASNG 79

                          90
                  ....*....|...
gi 1907171115 575 A-GSVSANATLTV 586
Cdd:cd20970    80 VpGSVEKRITLQV 92

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: 65.21 E-value: 6.17e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 496 PSFTKIPHDIAIRTGTTARLECAATGHPNPQIAWQKDGGTDFPAARERRMHVMPDDDVFFITDVKIDDMGVYSCTAQNSA 575
Cdd:cd05744     1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVRENGRHSLIIEPVTKRDAGIYTCIARNRA 80

                          90
                  ....*....|.
gi 1907171115 576 GSVSANATLTV 586
Cdd:cd05744    81 GENSFNAELVV 91

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: 65.21 E-value: 6.21e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 498 FTKIPHDIAIRTGTTARLECAATGHPNPQIAWQKDGGTDfpAARERRMHVMPDDdVFFITDVKIDDMGVYSCTAQNSAGS 577
Cdd:cd20952     2 ILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPL--LGKDERITTLENG-SLQIKGAEKSDTGEYTCVALNLSGE 78


                  ....*....
gi 1907171115 578 VSANATLTV 586
Cdd:cd20952    79 ATWSAVLDV 87

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: 65.27 E-value: 6.80e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 510 GTTARLECAATGHPNPQIAWQKDGgtdFPAARERRM----HVMPDDDV---FFITDVKIDDMGVYSCTAQNSAGSVSANA 582
Cdd:cd20956    16 GPSVSLKCVASGNPLPQITWTLDG---FPIPESPRFrvgdYVTSDGDVvsyVNISSVRVEDGGEYTCTATNDVGSVSHSA 92


                  ....
gi 1907171115 583 TLTV 586
Cdd:cd20956    93 RINV 96

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: 64.58 E-value: 1.13e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 590 PSLAVPLEDRVVTVGETVAFQCKATGSPTPRITWLKGGRPLSLT-ERHHFTPGNQLLVVQNVMIDDAGRYTCEMSNPLGT 668
Cdd:cd20976     2 PSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQYAaDRSTCEAGVGELHIQDVLPEDHGTYTCLAKNAAGQ 81


                  ....*....
gi 1907171115 669 ERAHSQLSI 677
Cdd:cd20976    82 VSCSAWVTV 90

Leucine rich repeat;

Pssm-ID: 404697 [Multi-domain] Cd Length: 61 Bit Score: 63.70 E-value: 1.16e-12

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907171115 108 PRLTQLDLNRNRIRLIEGLTFQGLDSLEVLRLQRNNISRLTDGAFWGLSKMHVLHLEYNSL 168
Cdd:pfam13855   1 PNLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 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: 64.59 E-value: 1.40e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 498 FTKIPHDIAIRTGTTARLECAATGHPNPQIAWQKDGGTDF-----PAARERRMHVMPDDDVfFITDVKIDDMGVYSCTAQ 572
Cdd:cd05726     2 FVVKPRDQVVALGRTVTFQCETKGNPQPAIFWQKEGSQNLlfpyqPPQPSSRFSVSPTGDL-TITNVQRSDVGYYICQAL 80

                          90
                  ....*....|....
gi 1907171115 573 NSAGSVSANATLTV 586
Cdd:cd05726    81 NVAGSILAKAQLEV 94

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: 64.13 E-value: 1.54e-12

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907171115 595 PLEDRVVTVGETVAFQCKATGSPTPRITWLKGGRPlsLTERHHFT-----PGNQLLVVQNVMIDDAGRYTCEMSNPLG 667
Cdd:cd20973     3 TLRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNP--IVESRRFQidqdeDGLCSLIISDVCGDDSGKYTCKAVNSLG 78

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: 63.75 E-value: 1.85e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 504 DIAIRTGTTARLECAATGHPNPQIAWQKDGGtdfPAARERRMHVMPDDD---VFFITDVKIDDMGVYSCTAQNSAGSVSA 580
Cdd:cd20973     6 DKEVVEGSAARFDCKVEGYPDPEVKWMKDDN---PIVESRRFQIDQDEDglcSLIISDVCGDDSGKYTCKAVNSLGEATC 82


                  ....*.
gi 1907171115 581 NATLTV 586
Cdd:cd20973    83 SAELTV 88

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

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 63.12 E-value: 2.05e-12

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907171115 513 ARLECAATGHPNPQIAWQKDGGTDFPAARERRMHVmPDDDVFFITDVKIDDMGVYSCTAQNSA-GSVSANA 582
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSE-LGNGTLTISNVTLEDSGTYTCVASNSAgGSASASV 70

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: 62.03 E-value: 9.50e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 502 PHDIAIRTGTTARLECAA-TGHPNPQIAWQKDGGTdfpaARERRMHV-MPDDDVFFITDVKIDDMGVYSCTAQNSAGS-V 578
Cdd:cd05724     4 PSDTQVAVGEMAVLECSPpRGHPEPTVSWRKDGQP----LNLDNERVrIVDDGNLLIAEARKSDEGTYKCVATNMVGErE 79


                  ....*...
gi 1907171115 579 SANATLTV 586
Cdd:cd05724    80 SRAARLSV 87

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: 61.71 E-value: 9.92e-12

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907171115 600 VVTVGETVAFQCKATGSPTPRITWLKGGRPLSLTERHHFTPgNQLLVVQNVMIDDAGRYTCEMSNPLGTERAHSQLSI 677
Cdd:cd04969    13 LAAKGGDVIIECKPKASPKPTISWSKGTELLTNSSRICILP-DGSLKIKNVTKSDEGKYTCFAVNFFGKANSTGSLSV 89

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: 61.43 E-value: 1.55e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 595 PLEDRVVTVGETVAFQCKATGSPTPRITWLKGGRPLSLTERHHFTPgNQLLVVQNV-MIDDAGRYTCEMSNPLGtERAHS 673
Cdd:cd20958     6 PMGNLTAVAGQTLRLHCPVAGYPISSITWEKDGRRLPLNHRQRVFP-NGTLVIENVqRSSDEGEYTCTARNQQG-QSASR 83


                  ....
gi 1907171115 674 QLSI 677
Cdd:cd20958    84 SVFV 87

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: 61.47 E-value: 1.64e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 587 LETPSLAVPledrvvtVGETVAFQCKATGSPTPRITWLKGGRPL--------SLTERHHFTpgnqlLVVQNVMIDDAGRY 658
Cdd:cd05729     9 MEEREHALP-------AANKVRLECGAGGNPMPNITWLKDGKEFkkehriggTKVEEKGWS-----LIIERAIPRDKGKY 76

                          90
                  ....*....|
gi 1907171115 659 TCEMSNPLGT 668
Cdd:cd05729    77 TCIVENEYGS 86

Leucine rich repeat;

Pssm-ID: 404697 [Multi-domain] Cd Length: 61 Bit Score: 59.85 E-value: 2.17e-11

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 133 SLEVLRLQRNNISRLTDGAFWGLSKMHVLHLEYNSLVEVNSGSLYGLTALHQLHLSNNSI 192
Cdd:pfam13855   2 NLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

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: 61.01 E-value: 2.21e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 597 EDRVVTVGETVAFQCKATGSPTPRITWLKGGRPLSLTERHHFTPGNQlLVVQNVMIDDAGRYTCEMSNPLGTERAHSQLS 676
Cdd:cd20957     9 PVQTVDFGRTAVFNCSVTGNPIHTVLWMKDGKPLGHSSRVQILSEDV-LVIPSVKREDKGMYQCFVRNDGDSAQATAELK 87


                  .
gi 1907171115 677 I 677
Cdd:cd20957    88 L 88

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: 60.93 E-value: 2.43e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 502 PHDIAIRTGTTARLECAATGHPNPQIAWQKDGGTDFPAARERRMHVMPDDDVFfiTDVKIDDMGVYSCTAQNSAGSVSAN 581
Cdd:cd04978     6 PPSLVLSPGETGELICEAEGNPQPTITWRLNGVPIEPAPEDMRRTVDGRTLIF--SNLQPNDTAVYQCNASNVHGYLLAN 83


                  ....*.
gi 1907171115 582 ATLTVL 587
Cdd:cd04978    84 AFLHVL 89

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: 64.42 E-value: 2.62e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 179 LTALHQLHLSNNSISRIqrDGWSFCQKLHELILSFNNLTRLdeESLAELSSLSILRLSHNAISHIaEGaFKGLKSLRVLD 258
Cdd:cd21340     1 LKRITHLYLNDKNITKI--DNLSLCKNLKVLYLYDNKITKI--ENLEFLTNLTHLYLQNNQIEKI-EN-LENLVNLKKLY 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 259 LDHNEISgTIEdtsgaftGLDNLSKL---------------------------------TLFGNKIKSVAkrAFSGLESL 305
Cdd:cd21340    75 LGGNRIS-VVE-------GLENLTNLeelhienqrlppgekltfdprslaalsnslrvlNISGNNIDSLE--PLAPLRNL 144

                         170       180       190
                  ....*....|....*....|....*....|..
gi 1907171115 306 EHLNLGENAIRSVQ--FDAFAKMKNLKELYIS 335
Cdd:cd21340   145 EQLDASNNQISDLEelLDLLSSWPSLRELDLT 176

Leucine rich repeat;

Pssm-ID: 404697 [Multi-domain] Cd Length: 61 Bit Score: 59.46 E-value: 3.53e-11

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1907171115 280 NLSKLTLFGNKIKSVAKRAFSGLESLEHLNLGENAIRSVQFDAFAKMKNLKELYISS 336
Cdd:pfam13855   2 NLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSG 58

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: 60.64 E-value: 3.93e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 585 TVLETPSlavpleDRVVTVGETVAFQCKATGSPTPRITWLKGGRPLSLTE-----RHHFTPGNQLLVVQNV----MIDDA 655
Cdd:cd07693     2 RIVEHPS------DLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLETDKddprsHRIVLPSGSLFFLRVVhgrkGRSDE 75

                          90
                  ....*....|....*..
gi 1907171115 656 GRYTCEMSNPLGTERAH 672
Cdd:cd07693    76 GVYVCVAHNSLGEAVSR 92

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: 60.45 E-value: 4.01e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 599 RVVTV--GETVAFQCKATGSPTPRITWLKGGRPLSLTERHHFTPGN--QLLVVQNVMIDDAGRYTCEMSNPLGTERAHSQ 674
Cdd:cd05747    11 RSLTVseGESARFSCDVDGEPAPTVTWMREGQIIVSSQRHQITSTEykSTFEISKVQMSDEGNYTVVVENSEGKQEAQFT 90


                  ..
gi 1907171115 675 LS 676
Cdd:cd05747    91 LT 92

leucine-rich repeat receptor-like protein kinase; Provisional

Pssm-ID: 215061 [Multi-domain] Cd Length: 968 Bit Score: 66.80 E-value: 5.36e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115  34 SYLSLEVLDLSSNNITEIRSSCFPNGLRIRELNLASNRIsilesgafdglsrslltlrlsknrITQLPVKAFKLPRLTQL 113
Cdd:PLN00113  162 SFSSLKVLDLGGNVLVGKIPNSLTNLTSLEFLTLASNQL------------------------VGQIPRELGQMKSLKWI 217

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 114 DLNRNRirLIEGLTFQ--GLDSLEVLRLQRNNISRLTDGAFWGLSKMHVLHLEYNSLVEVNSGSLYGLTALHQLHLSNNS 191
Cdd:PLN00113  218 YLGYNN--LSGEIPYEigGLTSLNHLDLVYNNLTGPIPSSLGNLKNLQYLFLYQNKLSGPIPPSIFSLQKLISLDLSDNS 295

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 192 ISRIQRDGWSFCQKLHELILSFNNLTRLDEESLAELSSLSILRLSHNAISHIAEGAFKGLKSLRVLDLDHNEISGTIEDT 271
Cdd:PLN00113  296 LSGEIPELVIQLQNLEILHLFSNNFTGKIPVALTSLPRLQVLQLWSNKFSGEIPKNLGKHNNLTVLDLSTNNLTGEIPEG 375

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 272 ---SGaftgldNLSKLTLFGNKIKSVAKRAFSGLESLEHLNLGENAIRSVQFDAFAKMKNLKELYISSESFLCDCQ-LKW 347
Cdd:PLN00113  376 lcsSG------NLFKLILFSNSLEGEIPKSLGACRSLRRVRLQDNSFSGELPSEFTKLPLVYFLDISNNNLQGRINsRKW 449

                         330       340       350
                  ....*....|....*....|....*....|....*..
gi 1907171115 348 LPPWLmgRMLqafvtatcahpeSLKGQSIFSVLPDSF 384
Cdd:PLN00113  450 DMPSL--QML------------SLARNKFFGGLPDSF 472

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 59.12 E-value: 6.38e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 391 KPQIITQPETTMAVVGKDIRFTCsaASSSSSPMTFAWKKDNEVLanadmenfAHVRAQDGEVMEYTTILHLRHVTFGHEG 470
Cdd:pfam13927   1 KPVITVSPSSVTVREGETVTLTC--EATGSPPPTITWYKNGEPI--------SSGSTRSRSLSGSNSTLTISNVTRSDAG 70


                  ....*...
gi 1907171115 471 RYQCIITN 478
Cdd:pfam13927  71 TYTCVASN 78

Leucine rich repeat;

Pssm-ID: 404697 [Multi-domain] Cd Length: 61 Bit Score: 58.30 E-value: 7.07e-11

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1907171115 237 HNAISHIAEGAFKGLKSLRVLDLDHNEISgTIEDtsGAFTGLDNLSKLTLFGNKI 291
Cdd:pfam13855  10 NNRLTSLDDGAFKGLSNLKVLDLSNNLLT-TLSP--GAFSGLPSLRYLDLSGNRL 61

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: 59.67 E-value: 7.56e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 496 PSFTKIPHDIAIRTGTTARLECAATGHPNPQIAWQKDG-GTDFPAARERRMHVMPDDDVFFITDVKIDDMGVYSCTAQNS 574
Cdd:cd20974     1 PVFTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFRDGqVISTSTLPGVQISFSDGRAKLSIPAVTKANSGRYSLTATNG 80

                          90
                  ....*....|...
gi 1907171115 575 AGSVSANATLTVL 587
Cdd:cd20974    81 SGQATSTAELLVL 93

leucine-rich repeat receptor-like protein kinase; Provisional

Pssm-ID: 215061 [Multi-domain] Cd Length: 968 Bit Score: 66.02 E-value: 8.49e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115  37 SLEVLDLSSNNIT-EIrsscfPNGLrirelnLASNRIS--ILESGAFDGLSRSLLTLRLSKNRIT--------QLPVKAF 105
Cdd:PLN00113  357 NLTVLDLSTNNLTgEI-----PEGL------CSSGNLFklILFSNSLEGEIPKSLGACRSLRRVRlqdnsfsgELPSEFT 425

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 106 KLPRLTQLDLNRNRIR-LIEGLTFQgLDSLEVLRLQRNNIS-RLTDgaFWGLSKMHVLHLEYNSLVEVNSGSLYGLTALH 183
Cdd:PLN00113  426 KLPLVYFLDISNNNLQgRINSRKWD-MPSLQMLSLARNKFFgGLPD--SFGSKRLENLDLSRNQFSGAVPRKLGSLSELM 502

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 184 QLHLSNNSISRIQRDGWSFCQKLHELILSFNNLTRLDEESLAELSSLSILRLSHNAISHIAEGAFKGLKSLRVLDLDHNE 263
Cdd:PLN00113  503 QLKLSENKLSGEIPDELSSCKKLVSLDLSHNQLSGQIPASFSEMPVLSQLDLSQNQLSGEIPKNLGNVESLVQVNISHNH 582

                         250
                  ....*....|..
gi 1907171115 264 ISGTIEDTsGAF 275
Cdd:PLN00113  583 LHGSLPST-GAF 593

Leucine rich repeat;

Pssm-ID: 404697 [Multi-domain] Cd Length: 61 Bit Score: 57.92 E-value: 9.95e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115  37 SLEVLDLSSNNITEIRSSCFPNGLRIRELNLASNRISILESGAFDGlsrslltlrlsknritqlpvkafkLPRLTQLDLN 116
Cdd:pfam13855   2 NLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSG------------------------LPSLRYLDLS 57


                  ....
gi 1907171115 117 RNRI 120
Cdd:pfam13855  58 GNRL 61

leucine-rich repeat receptor-like protein kinase; Provisional

Pssm-ID: 215061 [Multi-domain] Cd Length: 968 Bit Score: 65.64 E-value: 1.11e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115  31 QLKSYLSLEVLDLSSNNITEIRSSCFPNGLRIRELNLASNRISilesgafdglsrslltlrlsknriTQLPVKAFKLPRL 110
Cdd:PLN00113  231 EIGGLTSLNHLDLVYNNLTGPIPSSLGNLKNLQYLFLYQNKLS------------------------GPIPPSIFSLQKL 286

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 111 TQLDLNRNRIR-LIEGLTFQgLDSLEVLRLQRNNISRLTDGAFWGLSKMHVLHLEYNSL---VEVNSGSLYGLTALHqlh 186
Cdd:PLN00113  287 ISLDLSDNSLSgEIPELVIQ-LQNLEILHLFSNNFTGKIPVALTSLPRLQVLQLWSNKFsgeIPKNLGKHNNLTVLD--- 362

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 187 LSNNSISRIQRDGWSFCQKLHELILSFNNLTRLDEESLAELSSLSILRLSHNAISHIAEGAFKGLKSLRVLDLDHNEISG 266
Cdd:PLN00113  363 LSTNNLTGEIPEGLCSSGNLFKLILFSNSLEGEIPKSLGACRSLRRVRLQDNSFSGELPSEFTKLPLVYFLDISNNNLQG 442

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 267 TIEDT-----------------SGA---FTGLDNLSKLTLFGNKIKSVAKRAFSGLESLEHLNLGENAIRSVQFDAFAKM 326
Cdd:PLN00113  443 RINSRkwdmpslqmlslarnkfFGGlpdSFGSKRLENLDLSRNQFSGAVPRKLGSLSELMQLKLSENKLSGEIPDELSSC 522

                         330
                  ....*....|...
gi 1907171115 327 KNLKELYISSESF 339
Cdd:PLN00113  523 KKLVSLDLSHNQL 535

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: 58.71 E-value: 1.34e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 590 PSLAVPLEDRVVTVGETVAFQCKATGSPTPRITWLK---GGRPLSLTERHHFtpGNQL------LVVQNVMIDDAGRYTC 660
Cdd:cd05765     1 PALVNSPTHQTVKVGETASFHCDVTGRPQPEITWEKqvpGKENLIMRPNHVR--GNVVvtnigqLVIYNAQPQDAGLYTC 78

                          90
                  ....*....|....*..
gi 1907171115 661 EMSNPLGTERAHSQLSI 677
Cdd:cd05765    79 TARNSGGLLRANFPLSV 95

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: 58.71 E-value: 1.44e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 500 KIPHDIAIRTGTTARLECAATGHPNPQIAWQKDGGTDFPAARERRmhvmpDDDVFFITDVKIDDMGVYSCTAQNSAGSVS 579
Cdd:cd04968     6 RFPADTYALKGQTVTLECFALGNPVPQIKWRKVDGSPSSQWEITT-----SEPVLEIPNVQFEDEGTYECEAENSRGKDT 80


                  ....*..
gi 1907171115 580 ANATLTV 586
Cdd:cd04968    81 VQGRIIV 87

Leucine rich repeat C-terminal domain;

Pssm-ID: 214507 [Multi-domain] Cd Length: 51 Bit Score: 57.05 E-value: 1.58e-10

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1907171115  339 FLCDCQLKWLPPWLMG-RMLQAFVTATCAHPESLKGQsIFSVLPDSFVCD 387
Cdd:smart00082   3 FICDCELRWLLRWLQAnEHLQDPVDLRCASPSSLRGP-LLELLHSEFKCP 51

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: 58.43 E-value: 1.97e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 597 EDRVVTVGETVAFQCKATGSPTPRITWLKGG--------RPLSLTERHHFTPGNQlLVVQNVMIDDAGRYTCEMSNPLGT 668
Cdd:cd05726     7 RDQVVALGRTVTFQCETKGNPQPAIFWQKEGsqnllfpyQPPQPSSRFSVSPTGD-LTITNVQRSDVGYYICQALNVAGS 85


                  ....*....
gi 1907171115 669 ERAHSQLSI 677
Cdd:cd05726    86 ILAKAQLEV 94

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: 58.33 E-value: 2.20e-10

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 603 VGETVAFQCKATGSPTPRITWLKGGRPLSLTE-----RHHFTpgnqlLVVQNVMIDDAGRYTCEMSNPLG 667
Cdd:cd05856    18 VGSSVRLKCVASGNPRPDITWLKDNKPLTPPEigenkKKKWT-----LSLKNLKPEDSGKYTCHVSNRAG 82

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: 57.98 E-value: 2.34e-10

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907171115 510 GTTARLECAATGHPNPQIAWQKDGGTDFPAARERRMHVmpDDDVFFITDVKIDDMGVYSCTAQNSAGSVSANATLTVL 587
Cdd:cd05867    14 GETARLDCQVEGIPTPNITWSINGAPIEGTDPDPRRHV--SSGALILTDVQPSDTAVYQCEARNRHGNLLANAHVHVV 89

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: 57.02 E-value: 3.70e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 598 DRVVTVGETVAFQCKATGSPTPRITWLK--GGRPLSlteRHHFTPGNQLLvVQNVMIDDAGRYTCEMSNPLGTERAHSQL 675
Cdd:cd05725     6 NQVVLVDDSAEFQCEVGGDPVPTVRWRKedGELPKG---RYEILDDHSLK-IRKVTAGDMGSYTCVAENMVGKIEASATL 81


                  ..
gi 1907171115 676 SI 677
Cdd:cd05725    82 TV 83

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: 57.56 E-value: 3.88e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 496 PSFTKIPHDIAIRTGTTARLECAATGHPNPQIAWQKDggtdfpaARERRMHVMPDDDV-----------FFITDVKIDDM 564
Cdd:cd05765     1 PALVNSPTHQTVKVGETASFHCDVTGRPQPEITWEKQ-------VPGKENLIMRPNHVrgnvvvtnigqLVIYNAQPQDA 73

                          90       100
                  ....*....|....*....|..
gi 1907171115 565 GVYSCTAQNSAGSVSANATLTV 586
Cdd:cd05765    74 GLYTCTARNSGGLLRANFPLSV 95

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: 57.43 E-value: 4.18e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 496 PSFTKIPHDIAIRTGTTARLECAATGHPNPQIAWQKDGGTDFPAARERRMHVMPDDDV--FFITDVKIDDMGVYSCTAQN 573
Cdd:cd20951     1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDPSSIPGKYKIESEYGVhvLHIRRVTVEDSAVYSAVAKN 80

                          90
                  ....*....|...
gi 1907171115 574 SAGSVSANATLTV 586
Cdd:cd20951    81 IHGEASSSASVVV 93

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: 57.03 E-value: 4.99e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 496 PSFTKIPHDIAIRTGTTARLECAATGHPNPQIAWQKDGGTDFPAARERRMHVMPDDDVFFITDVKIDDMGVYSCTAQNSA 575
Cdd:cd20990     1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSAHKMLVRENGVHSLIIEPVTSRDAGIYTCIATNRA 80

                          90
                  ....*....|.
gi 1907171115 576 GSVSANATLTV 586
Cdd:cd20990    81 GQNSFNLELVV 91

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: 57.07 E-value: 5.24e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 600 VVTVGETVAFQCKATGSPTPRITWLKGGRPLsltERHHFTPGN----QLLVVQNVMIDDAGRYTCEMSNPLGTERAHSQL 675
Cdd:cd04978    10 VLSPGETGELICEAEGNPQPTITWRLNGVPI---EPAPEDMRRtvdgRTLIFSNLQPNDTAVYQCNASNVHGYLLANAFL 86


                  ...
gi 1907171115 676 SIL 678
Cdd:cd04978    87 HVL 89

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: 56.77 E-value: 5.26e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 497 SFTKIPHDIAIRTGTTARLECAATGHPNPQIAWQKDGGtdfPAARERRMHVMpDDDVFFITDVKIDDMGVYSCTAQNSAG 576
Cdd:cd20957     3 SATIDPPVQTVDFGRTAVFNCSVTGNPIHTVLWMKDGK---PLGHSSRVQIL-SEDVLVIPSVKREDKGMYQCFVRNDGD 78


                  ....*...
gi 1907171115 577 SVSANATL 584
Cdd:cd20957    79 SAQATAEL 86

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: 56.44 E-value: 5.95e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 505 IAIRTGTTARLECAATGHPNPQIAWQKDGgTDFPAARERRMHVMPDDDVFFITDVKIDDMGVYSCTAQNSAGSVSANATL 584
Cdd:cd05748     2 IVVRAGESLRLDIPIKGRPTPTVTWSKDG-QPLKETGRVQIETTASSTSLVIKNAKRSDSGKYTLTLKNSAGEKSATINV 80


                  ..
gi 1907171115 585 TV 586
Cdd:cd05748    81 KV 82

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: 56.80 E-value: 6.79e-10

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907171115 604 GETVAFQCKATGSPTPRITWLKGGRPLSLTER----HHFTPGNQL---LVVQNVMIDDAGRYTCEMSNPLGT 668
Cdd:cd20956    16 GPSVSLKCVASGNPLPQITWTLDGFPIPESPRfrvgDYVTSDGDVvsyVNISSVRVEDGGEYTCTATNDVGS 87

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: 56.64 E-value: 6.82e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 598 DRVVTVGETVAFQCKA-TGSPTPRITWLKGGRPLSLTE--RHHFTPGNqlLVVQNVMIDDAGRYTCEMSNPLGT-ERAHS 673
Cdd:cd05724     6 DTQVAVGEMAVLECSPpRGHPEPTVSWRKDGQPLNLDNerVRIVDDGN--LLIAEARKSDEGTYKCVATNMVGErESRAA 83


                  ....
gi 1907171115 674 QLSI 677
Cdd:cd05724    84 RLSV 87

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: 56.74 E-value: 6.83e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 590 PSLAVPLEDRVVTVGETVAFQCKATGSPTPRITWLKGGRPLSLTERHHF---TPGNQLLVVQNVMIDDAGRYTCEMSNPL 666
Cdd:cd05744     1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMlvrENGRHSLIIEPVTKRDAGIYTCIARNRA 80

                          90
                  ....*....|.
gi 1907171115 667 GTERAHSQLSI 677
Cdd:cd05744    81 GENSFNAELVV 91

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: 56.01 E-value: 1.19e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907171115 601 VTVGETVAFQCKATGSPTPRITWLKGGRPLSLTER---HHFTPGNQLLVVQNVMIDDAGRYTCEMSNPLGT 668
Cdd:cd05857    16 VPAANTVKFRCPAAGNPTPTMRWLKNGKEFKQEHRiggYKVRNQHWSLIMESVVPSDKGNYTCVVENEYGS 86

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: 55.27 E-value: 1.21e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 607 VAFQCKATGSPTPRITWLKGGRPLSLTERHHFTPGNQlLVVQNVMIDDAGRYTCEMSNPLGTERAHSQLS 676
Cdd:cd05746     1 VQIPCSAQGDPEPTITWNKDGVQVTESGKFHISPEGY-LAIRDVGVADQGRYECVARNTIGYASVSMVLS 69

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: 56.02 E-value: 1.30e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 597 EDRVVTVGETVAFQCKATGSPTPRITWLK-GGRPLSLTERHHFTPgnqLLVVQNVMIDDAGRYTCEMSNPLGTERAHSQL 675
Cdd:cd04968     9 ADTYALKGQTVTLECFALGNPVPQIKWRKvDGSPSSQWEITTSEP---VLEIPNVQFEDEGTYECEAENSRGKDTVQGRI 85


                  ..
gi 1907171115 676 SI 677
Cdd:cd04968    86 IV 87

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: 55.68 E-value: 1.52e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 596 LEDRVVTVGETVAFQCKATGSPTPRITWLKGGRPLSLTERHHFTPGNqlLVVQNVMIDDAGRYTCEMSNPLGTERAHSQL 675
Cdd:cd05728     6 ISDTEADIGSSLRWECKASGNPRPAYRWLKNGQPLASENRIEVEAGD--LRITKLSLSDSGMYQCVAENKHGTIYASAEL 83


                  ..
gi 1907171115 676 SI 677
Cdd:cd05728    84 AV 85

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: 55.67 E-value: 1.64e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 496 PSFTKIPHDIAIRTGTTARLECAATGHPNPQIAWQKDG-----GTDFPAARERRMHVMpdddvfFITDVKIDDMGVYSCT 570
Cdd:cd20972     2 PQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGkelqnSPDIQIHQEGDLHSL------IIAEAFEEDTGRYSCL 75

                          90
                  ....*....|....*.
gi 1907171115 571 AQNSAGSVSANATLTV 586
Cdd:cd20972    76 ATNSVGSDTTSAEIFV 91

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: 55.73 E-value: 1.74e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 590 PSLAVPLEDRVVTVGETVAFQCKATGSPTPRITWLKGGRPLS--LTERHHFTPGNQLLVVQNVMIDDAGRYTCEMSNPLG 667
Cdd:cd05736     1 PVIRVYPEFQAKEPGVEASLRCHAEGIPLPRVQWLKNGMDINpkLSKQLTLIANGSELHISNVRYEDTGAYTCIAKNEGG 80

                          90
                  ....*....|
gi 1907171115 668 TERAHSQLSI 677
Cdd:cd05736    81 VDEDISSLFV 90

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: 54.94 E-value: 2.00e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907171115 510 GTTARLECAATGHPNPQIAWQKDGGtdfPAARERRmHVMPDDDVFFITDVKIDDMGVYSCTAQNSAGSVSANATLTV 586
Cdd:cd05745     2 GQTVDFLCEAQGYPQPVIAWTKGGS---QLSVDRR-HLVLSSGTLRISRVALHDQGQYECQAVNIVGSQRTVAQLTV 74

Leucine rich repeat;

Pssm-ID: 404697 [Multi-domain] Cd Length: 61 Bit Score: 54.45 E-value: 2.00e-09

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1907171115  95 NRITQLPVKAFK-LPRLTQLDLNRNRIRLIEGLTFQGLDSLEVLRLQRNNI 144
Cdd:pfam13855  11 NRLTSLDDGAFKgLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

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: 55.28 E-value: 2.33e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 590 PSLAVPLEDRVVTVGETVAFQCKATGSPTPRITWLKGGRPLSLTERHHFTPGNQL--LVVQNVMIDDAGRYTCEMSNPLG 667
Cdd:cd20972     2 PQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSPDIQIHQEGDLhsLIIAEAFEEDTGRYSCLATNSVG 81

                          90
                  ....*....|
gi 1907171115 668 TERAHSQLSI 677
Cdd:cd20972    82 SDTTSAEIFV 91

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: 54.92 E-value: 3.38e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 505 IAIRTGTTARLECAATGHPNPQIAWQKDGGTDFPAARERRMHVMPDDDVFFITDVKIDDMGVYSCTAQNSAGSVSANATL 584
Cdd:cd05729    14 HALPAANKVRLECGAGGNPMPNITWLKDGKEFKKEHRIGGTKVEEKGWSLIIERAIPRDKGKYTCIVENEYGSINHTYDV 93


                  ..
gi 1907171115 585 TV 586
Cdd:cd05729    94 DV 95

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: 54.11 E-value: 3.55e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907171115 514 RLECAATGHPNPQIAWQKDGgtdFPAARERRMHVMPdDDVFFITDVKIDDMGVYSCTAQNSAGSVSANATLT 585
Cdd:cd05746     2 QIPCSAQGDPEPTITWNKDG---VQVTESGKFHISP-EGYLAIRDVGVADQGRYECVARNTIGYASVSMVLS 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: 54.13 E-value: 4.28e-09

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907171115 614 TGSPTPRITWLKGGRPLSLTERHHF--TPGNQLLVVQNVMIDDAGRYTCEMSNPLGTERAH 672
Cdd:cd05748    17 KGRPTPTVTWSKDGQPLKETGRVQIetTASSTSLVIKNAKRSDSGKYTLTLKNSAGEKSAT 77

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: 53.72 E-value: 7.78e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907171115 601 VTVGETVAFQCKA-TGSPTPRITWLKGGRPLSlTERHHFtpgNQLLVVQNVMIDDAGRYTCEMSNPLGTERAHSQLS 676
Cdd:cd05754    13 VRPGADVSFICRAkSKSPAYTLVWTRVNGTLP-SRAMDF---NGILTIRNVQLSDAGTYVCTGSNMLDTDEATATLY 85

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: 8.57e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 497 SFTKIPHDIAIRTGTTARLECAATGHPNPQIAWQKDGGTDFPAARERRmhVMPDDDVFFITDV---KID--DMGVYSCTA 571
Cdd:cd05722     3 YFLSEPSDIVAMRGGPVVLNCSAESDPPPKIEWKKDGVLLNLVSDERR--QQLPNGSLLITSVvhsKHNkpDEGFYQCVA 80

                          90
                  ....*....|....*..
gi 1907171115 572 QN-SAGS-VSANATLTV 586
Cdd:cd05722    81 QNeSLGSiVSRTARVTV 97

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: 53.17 E-value: 1.04e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907171115 595 PLEDRvvtvgETVAFQCKATGsPTPRITWLKGGRPLSLTERHHFTPGNQLLVVQNVMIDDAGRYTCEMSNPLGTER 670
Cdd:cd05740    11 PVEDK-----DAVTLTCEPET-QNTSYLWWFNGQSLPVTPRLTLSNGNRTLTLLNVTREDAGAYQCEISNPVSANR 80

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: 52.85 E-value: 1.39e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 496 PSFTKIP--HDIAIRTGTTARLECAATGHPNPQIAWQKDGGTdfpAARERRMHVMPDDDVFfITDVKIDDMGVYSCTAQN 573
Cdd:cd04969     1 PDFELNPvkKKILAAKGGDVIIECKPKASPKPTISWSKGTEL---LTNSSRICILPDGSLK-IKNVTKSDEGKYTCFAVN 76

                          90
                  ....*....|...
gi 1907171115 574 SAGSVSANATLTV 586
Cdd:cd04969    77 FFGKANSTGSLSV 89

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: 52.78 E-value: 1.67e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 597 EDRVVTVGETVAFQCKATGSPTPRITWLKGGRPL-----SLTERHHFTPGNQLLVVqNVMIDDAGRYTCEMSNPLGTERA 671
Cdd:cd20977     8 KDMMAKAGDVTMIYCMYGSNPTAHPNYFKNGKDVngnpeDRITRHNRTSGKRLLFK-TTLPEDEGVYTCEVDNGVGKPQK 86


                  ....*..
gi 1907171115 672 HS-QLSI 677
Cdd:cd20977    87 HSlKLTV 93

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: 52.71 E-value: 1.81e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907171115 512 TARLECAATGHPNPQIAWQKDGGTDFPAARERRMHvMPDDDVFFITDVKIDDMGVYSCTAQNSAGS-VSANATLTV 586
Cdd:cd05738    16 TATMLCAASGNPDPEISWFKDFLPVDTATSNGRIK-QLRSGALQIENSEESDQGKYECVATNSAGTrYSAPANLYV 90

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: 2.00e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 496 PSFTKIPHDIAIRTGT-TARLECAATGHPNPQIAWQKDGGTdFPAARERRmHVmpDDDVFFITDVKIDDMGVYSCTAQNS 574
Cdd:cd20978     1 PKFIQKPEKNVVVKGGqDVTLPCQVTGVPQPKITWLHNGKP-LQGPMERA-TV--EDGTLTIINVQPEDTGYYGCVATNE 76

                          90
                  ....*....|..
gi 1907171115 575 AGSVSANATLTV 586
Cdd:cd20978    77 IGDIYTETLLHV 88

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: 52.53 E-value: 2.29e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 596 LEDRVVTVGETVAFQCKATGSPTPRITWLKGGRPLSLTER----------HHftpGNQLLVVQNVMIDDAGRYTCEMSNP 665
Cdd:cd05732     8 LENQTAVELEQITLTCEAEGDPIPEITWRRATRGISFEEGdldgrivvrgHA---RVSSLTLKDVQLTDAGRYDCEASNR 84


                  ..
gi 1907171115 666 LG 667
Cdd:cd05732    85 IG 86

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: 52.51 E-value: 2.39e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 590 PSLAvPLEDRVVTVGETVAFQCKATG-SPTPRITWLKGGRPLSLTERHHF----TPGNQLLVVQNVMIDDAGRYTCEMSN 664
Cdd:cd05750     1 PKLK-EMKSQTVQEGSKLVLKCEATSeNPSPRYRWFKDGKELNRKRPKNIkirnKKKNSELQINKAKLEDSGEYTCVVEN 79

                          90
                  ....*....|...
gi 1907171115 665 PLGTERAHSQLSI 677
Cdd:cd05750    80 ILGKDTVTGNVTV 92

Leucine rich repeat;

Pssm-ID: 404697 [Multi-domain] Cd Length: 61 Bit Score: 51.37 E-value: 2.63e-08

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907171115 204 QKLHELILSFNNLTRLDEESLAELSSLSILRLSHNAISHIAEGAFKGLKSLRVLDLDHNEI 264
Cdd:pfam13855   1 PNLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

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: 56.59 E-value: 2.70e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115  29 GSQLKSYLSLEVLDLSSNNITEIRS------SCFPNGLRIRELNLASNRISILESGAFdglsrslltlrlsknritqlpv 102
Cdd:cd00116    44 ASALRPQPSLKELCLSLNETGRIPRglqsllQGLTKGCGLQELDLSDNALGPDGCGVL---------------------- 101

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 103 KAF-KLPRLTQLDLNRNRI------RLIEGLTFQGLDsLEVLRLQRNNISrltdgafwglskmhvlhleyNSLVEVNSGS 175
Cdd:cd00116   102 ESLlRSSSLQELKLNNNGLgdrglrLLAKGLKDLPPA-LEKLVLGRNRLE--------------------GASCEALAKA 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 176 LYGLTALHQLHLSNNSIS-----RIQRDGWSFCQkLHELILSFNNLTRLDEESLAElsslsilrlshnaishiaegAFKG 250
Cdd:cd00116   161 LRANRDLKELNLANNGIGdagirALAEGLKANCN-LEVLDLNNNGLTDEGASALAE--------------------TLAS 219

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907171115 251 LKSLRVLDLDHNEIS--GTIEDTSGAFTGLDNLSKLTLFGNKIKSVAKRAFSGL----ESLEHLNLGEN 313
Cdd:cd00116   220 LKSLEVLNLGDNNLTdaGAAALASALLSPNISLLTLSLSCNDITDDGAKDLAEVlaekESLLELDLRGN 288

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 51.24 E-value: 3.87e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 502 PHDIAIRTGTTARLECAATGHPNPQIAWQKDGgtdfpaarerrmHVMPDDDVFFITDVKIDDMGVYSCTAQNSAGS-VSA 580
Cdd:pfam13895   6 PSPTVVTEGEPVTLTCSAPGNPPPSYTWYKDG------------SAISSSPNFFTLSVSAEDSGTYTCVARNGRGGkVSN 73


                  ....*.
gi 1907171115 581 NATLTV 586
Cdd:pfam13895  74 PVELTV 79

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 51.49 E-value: 4.37e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 392 PQIITQPETTMAVVGKDIRFTCSAASSSssPMTFAWKKDNEVLANADmenfaHVRAQdgeVMEYTTILHLRHVTFGHEGR 471
Cdd:pfam07679   1 PKFTQKPKDVEVQEGESARFTCTVTGTP--DPEVSWFKDGQPLRSSD-----RFKVT---YEGGTYTLTISNVQPDDSGK 70

                          90       100
                  ....*....|....*....|.
gi 1907171115 472 YQCIITNHFGStYSHKARLTV 492
Cdd:pfam07679  71 YTCVATNSAGE-AEASAELTV 90

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: 51.54 E-value: 4.46e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 502 PHDIAIRTGTTARLECAATGHPNPQIAWQKDGGT------DFpaARERRMHVMPDDDVFFiTDVKIDDMGVYSCTAQNSA 575
Cdd:cd20954     8 PVDANVAAGQDVMLHCQADGFPTPTVTWKKATGStpgeykDL--LYDPNVRILPNGTLVF-GHVQKENEGHYLCEAKNGI 84

                          90
                  ....*....|..
gi 1907171115 576 GS-VSANATLTV 586
Cdd:cd20954    85 GSgLSKVIFLKV 96

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: 51.59 E-value: 5.01e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 495 LPS--FTKiPHDIAIRTGTTARLECAATGHPNPQIAWQKDGGtdfPAARERRMHVMPDD--DVFFITDVKIDDMGVYSCT 570
Cdd:cd05747     2 LPAtiLTK-PRSLTVSEGESARFSCDVDGEPAPTVTWMREGQ---IIVSSQRHQITSTEykSTFEISKVQMSDEGNYTVV 77

                          90
                  ....*....|....*
gi 1907171115 571 AQNSAGSVSANATLT 585
Cdd:cd05747    78 VENSEGKQEAQFTLT 92

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 50.86 E-value: 5.14e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907171115 600 VVTVGETVAFQCKATGSPTPRITWLKGGRPLslterhhftPGNQLLVVQNVMIDDAGRYTCEMSNPLGTERAHS 673
Cdd:pfam13895  10 VVTEGEPVTLTCSAPGNPPPSYTWYKDGSAI---------SSSPNFFTLSVSAEDSGTYTCVARNGRGGKVSNP 74

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: 51.07 E-value: 5.35e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907171115 600 VVTVGETVAFQCKATGSPTPRITWLKGGRPLSlTERHHFTPGNQLLVVQNVMIDDAGRYTCEMSNPLGTERAH 672
Cdd:cd05876     6 VALRGQSLVLECIAEGLPTPTVKWLRPSGPLP-PDRVKYQNHNKTLQLLNVGESDDGEYVCLAENSLGSARHA 77

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: 50.87 E-value: 5.39e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 505 IAIRtGTTARLECAATGHPNPQIAWQKDGGtDFPAARERRMHVmpdDDVFFITDVKIDDMGVYSCTAQNSAGSVSANATL 584
Cdd:cd05731     6 MVLR-GGVLLLECIAEGLPTPDIRWIKLGG-ELPKGRTKFENF---NKTLKIENVSEADSGEYQCTASNTMGSARHTISV 80


                  ..
gi 1907171115 585 TV 586
Cdd:cd05731    81 TV 82

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: 51.49 E-value: 5.43e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907171115 502 PHDIAIRTGTTARLECAATGHPNPQIAWQKDgGTDFPAARERRMHVMPDDDVFFITDVKIDDMGVYSCTAQNSAG 576
Cdd:cd05736     7 PEFQAKEPGVEASLRCHAEGIPLPRVQWLKN-GMDINPKLSKQLTLIANGSELHISNVRYEDTGAYTCIAKNEGG 80

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: 51.32 E-value: 6.62e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 590 PSLAVPLEDRVVTVGETVAFQCKATGSPTPRITWLKGGRPLSlTERHHFTPGNQL----LVVQNVMID-DAGRYTCEMSN 664
Cdd:cd20971     2 PHFKEELRNLNVRYQSNATLVCKVTGHPKPIVKWYRQGKEII-ADGLKYRIQEFKggyhQLIIASVTDdDATVYQVRATN 80


                  ...
gi 1907171115 665 PLG 667
Cdd:cd20971    81 QGG 83

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: 50.49 E-value: 7.37e-08

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907171115 604 GETVAFQCKATGSPTPRITWLKGGRPLsLTERHHFTPGNQLLVVQNVMIDDAGRYTCEMSNPLGTER 670
Cdd:cd05731    10 GGVLLLECIAEGLPTPDIRWIKLGGEL-PKGRTKFENFNKTLKIENVSEADSGEYQCTASNTMGSAR 75

leucine-rich repeat receptor-like protein kinase; Provisional

Pssm-ID: 215061 [Multi-domain] Cd Length: 968 Bit Score: 56.39 E-value: 8.54e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115  37 SLEVLDLSSNNITeirsSCFPNGL----RIRELNLASNRISilesgafdglsrslltlrlsknriTQLPVKAFKLPRLTQ 112
Cdd:PLN00113  309 NLEILHLFSNNFT----GKIPVALtslpRLQVLQLWSNKFS------------------------GEIPKNLGKHNNLTV 360

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 113 LDLNRNRI--RLIEGLTFQG-----------LD-----------SLEVLRLQRNNISRLTDGAFWGLSKMHVLHLEYNSL 168
Cdd:PLN00113  361 LDLSTNNLtgEIPEGLCSSGnlfklilfsnsLEgeipkslgacrSLRRVRLQDNSFSGELPSEFTKLPLVYFLDISNNNL 440

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 169 VEVNSGSLYGLTALHQLHLSNNSISRIQRDgwSF-CQKLHELILSFNNLTRLDEESLAELSSLSILRLSHNAISHIAEGA 247
Cdd:PLN00113  441 QGRINSRKWDMPSLQMLSLARNKFFGGLPD--SFgSKRLENLDLSRNQFSGAVPRKLGSLSELMQLKLSENKLSGEIPDE 518

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907171115 248 FKGLKSLRVLDLDHNEISGTIEDTsgaFTGLDNLSKLTLFGNKIKSVAKRAFSGLESLEHLNLGEN 313
Cdd:PLN00113  519 LSSCKKLVSLDLSHNQLSGQIPAS---FSEMPVLSQLDLSQNQLSGEIPKNLGNVESLVQVNISHN 581

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: 50.28 E-value: 9.16e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 593 AVPLEDRVVTVGETVAFQCKATGSPTPRITWLKGGRPLslterhhfTPGNQLLVVQNVM----IDDAGRYTCEMSNPLGT 668
Cdd:cd05739     1 SIPPSNHEVMPGGSVNLTCVAVGAPMPYVKWMKGGEEL--------TKEDEMPVGRNVLeltnIYESANYTCVAISSLGM 72


                  ....*....
gi 1907171115 669 ERAHSQLSI 677
Cdd:cd05739    73 IEATAQVTV 81

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: 50.70 E-value: 1.08e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907171115 603 VGETVAFQCKATGSPTPRITWLKGGRPL-SLTERHHFTPGNQLLVVQNVMIDDAGRYTCEMSNPLGTERAHSQLSI 677
Cdd:cd05730    17 LGQSVTLACDADGFPEPTMTWTKDGEPIeSGEEKYSFNEDGSEMTILDVDKLDEAEYTCIAENKAGEQEAEIHLKV 92

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: 50.39 E-value: 1.13e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907171115 597 EDRVVTVGETVAFQCKATGSPTPRITWLK--GGRP-----LSLTERHHFTPgNQLLVVQNVMIDDAGRYTCEMSNPLGT 668
Cdd:cd20954     9 VDANVAAGQDVMLHCQADGFPTPTVTWKKatGSTPgeykdLLYDPNVRILP-NGTLVFGHVQKENEGHYLCEAKNGIGS 86

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: 50.24 E-value: 1.32e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 505 IAIRTGTTARLECAATGHPNPQIAWQKDGG--TDFPAARERRMHVmpdddVFFITDVKIDDMGVYSCTAQNSAGSVsaNA 582
Cdd:cd05856    14 IARPVGSSVRLKCVASGNPRPDITWLKDNKplTPPEIGENKKKKW-----TLSLKNLKPEDSGKYTCHVSNRAGEI--NA 86


                  ....
gi 1907171115 583 TLTV 586
Cdd:cd05856    87 TYKV 90

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: 49.84 E-value: 1.39e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 501 IPHDIAIRTGTTARLECAATGHPNPQIAWQKdgGTDFPAARERRMHV--MPDDDVFFITDVKIDDMGVYSCTAQNSAGSV 578
Cdd:cd05894     1 AENTIVVVAGNKLRLDVPISGEPAPTVTWSR--GDKAFTATEGRVRVesYKDLSSFVIEGAEREDEGVYTITVTNPVGED 78


                  ....*...
gi 1907171115 579 SANATLTV 586
Cdd:cd05894    79 HASLFVKV 86

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: 50.15 E-value: 1.41e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 496 PSFTKIPHDIAIRTGTTARLECAATGHPNPQIAWQKDG-----GTDfpaarerRMHVMPDDD---VFFITDVKIDDMGVY 567
Cdd:cd05892     1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKKNNemlqyNTD-------RISLYQDNCgriCLLIQNANKKDAGWY 73

                          90
                  ....*....|....*....
gi 1907171115 568 SCTAQNSAGSVSANATLTV 586
Cdd:cd05892    74 TVSAVNEAGVVSCNARLDV 92

Leucine rich repeat;

Pssm-ID: 404697 [Multi-domain] Cd Length: 61 Bit Score: 49.06 E-value: 1.53e-07

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907171115 156 SKMHVLHLEYNSLVEVNSGSLYGLTALHQLHLSNNSISRIQRDGWSFCQKLHELILSFNNL 216
Cdd:pfam13855   1 PNLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

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: 49.41 E-value: 1.56e-07

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907171115 604 GETVAFQCKATGSPTPRITWLKGGRPLSLTERHHFTP--GNQLLVVQNVMIDDAGRYTCEMSNPLGT 668
Cdd:cd05743     1 GETVEFTCVATGVPTPIINWRLNWGHVPDSARVSITSegGYGTLTIRDVKESDQGAYTCEAINTRGM 67

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

Pssm-ID: 443914 [Multi-domain] Cd Length: 414 Bit Score: 54.55 E-value: 1.92e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115  21 HNKI--LSVDGSQLKSylsLEVLDLSSNNITEIrsscfPNGL----RIRELNLASNRISI---------LESGAFDGlsr 85
Cdd:COG4886   191 NNQItdLPEPLGNLTN---LEELDLSGNQLTDL-----PEPLanltNLETLDLSNNQLTDlpelgnltnLEELDLSN--- 259

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115  86 slltlrlskNRITQLPvKAFKLPRLTQLDLNRNRI---RLIEGLTFQGLDSLEVLRLQRNNISRLTDGAFWGLSKMHVLH 162
Cdd:COG4886   260 ---------NQLTDLP-PLANLTNLKTLDLSNNQLtdlKLKELELLLGLNSLLLLLLLLNLLELLILLLLLTTLLLLLLL 329

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907171115 163 LEYNSLVEVNSGSLYGLTALHQLHLSNNSISRIQRDGWSFCQKLHELILSFNNLTRLDEESLAELSSLSILRLSHNA 239
Cdd:COG4886   330 LKGLLVTLTTLALSLSLLALLTLLLLLNLLSLLLTLLLTLGLLGLLEATLLTLALLLLTLLLLLLTTTAGVLLLTLA 406

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: 49.66 E-value: 2.60e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 590 PSLAVPLEDRVVTVGETVAFQCKATGSPTPRITWLKGGRPLSLTE----RHHFTPGNQLLVVQNVMIDDAGRYTCEMSNP 665
Cdd:cd20974     1 PVFTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFRDGQVISTSTlpgvQISFSDGRAKLSIPAVTKANSGRYSLTATNG 80

                          90
                  ....*....|...
gi 1907171115 666 LGTERAHSQLSIL 678
Cdd:cd20974    81 SGQATSTAELLVL 93

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: 54.70 E-value: 3.24e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115  309 NLGENAIRSVQFDAFAKMKNLKELYISSESFLCDCQLKWLPPWLMGRMLQAFV--TATCAHPESLKGQSIFSVLPDSFVC 386
Cdd:TIGR00864    1 DISNNKISTIEEGICANLCNLSEIDLSGNPFECDCGLARLPRWAEEKGVKVRQpeAALCAGPGALAGQPLLGIPLLDSGC 80


                   .
gi 1907171115  387 D 387
Cdd:TIGR00864   81 D 81

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: 49.13 E-value: 3.38e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 600 VVTV--GETVAFQCKATGSPTPRITWLKGGRPLSLTERHH--FTPGNQL-LVVQNVMIDDAGRYTCEMSNPLGTERAHSQ 674
Cdd:cd05737    10 VVTImeGKTLNLTCNVWGDPPPEVSWLKNDQALAFLDHCNlkVEAGRTVyFTINGVSSEDSGKYGLVVKNKYGSETSDVT 89


                  ...
gi 1907171115 675 LSI 677
Cdd:cd05737    90 VSV 92

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: 48.86 E-value: 3.54e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 589 TPSLAVPLEDRVVTVGETVAFQCKATGSPTPRITWLKGGRPLSLTErhHFTPGNQLLVVQNVMIDDAGRYTCEMSNPLGT 668
Cdd:cd05851     1 PADINVKFKDTYALKGQNVTLECFALGNPVPVIRWRKILEPMPATA--EISMSGAVLKIFNIQPEDEGTYECEAENIKGK 78


                  ....*....
gi 1907171115 669 ERAHSQLSI 677
Cdd:cd05851    79 DKHQARVYV 87

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: 48.82 E-value: 4.08e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 502 PHDIAIRTGTTARLECAATGHPNPQIAWQKDGGTD--FPAARERRMhvmpDDDVFFITDVKIDDMGVYSCTAQNSAGSVS 579
Cdd:cd05868     6 PTNLVLSPGEDGTLICRANGNPKPSISWLTNGVPIeiAPTDPSRKV----DGDTIIFSKVQERSSAVYQCNASNEYGYLL 81


                  ....*...
gi 1907171115 580 ANATLTVL 587
Cdd:cd05868    82 ANAFVNVL 89

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: 48.54 E-value: 5.14e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 595 PLEDRVVTV--GETVAFQCKATGSPTPRITWL-KGGRPLSL--TERHHFTPGNQlLVVQNVMIDDAGRYTCEMSNPLGTE 669
Cdd:cd20969     6 DRKAQQVFVdeGHTVQFVCRADGDPPPAILWLsPRKHLVSAksNGRLTVFPDGT-LEVRYAQVQDNGTYLCIAANAGGND 84


                  ....*...
gi 1907171115 670 RAHSQLSI 677
Cdd:cd20969    85 SMPAHLHV 92

leucine-rich repeat receptor-like protein kinase; Provisional

Pssm-ID: 215061 [Multi-domain] Cd Length: 968 Bit Score: 53.31 E-value: 7.39e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115  40 VLDLSSNNIT-EIRSSCFpnGL-RIRELNLASNRISILESGAFDGLSRSLLTLRLSKNRITQlPVKAFKLPRLTQLDLNR 117
Cdd:PLN00113   73 SIDLSGKNISgKISSAIF--RLpYIQTINLSNNQLSGPIPDDIFTTSSSLRYLNLSNNNFTG-SIPRGSIPNLETLDLSN 149

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 118 NrirLIEGLTFQGL---DSLEVLRLQRNNISRLTDGAFWGLSKMHVLHLEYNSLVEVNSGSLYGLTALHQLHLSNNSIS- 193
Cdd:PLN00113  150 N---MLSGEIPNDIgsfSSLKVLDLGGNVLVGKIPNSLTNLTSLEFLTLASNQLVGQIPRELGQMKSLKWIYLGYNNLSg 226

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 194 --RIQRDGWSfcqKLHELILSFNNLTRLDEESLAELSSLSILRLSHNAISHIAEGAFKGLKSLRVLDLDHNEISGTIEDT 271
Cdd:PLN00113  227 eiPYEIGGLT---SLNHLDLVYNNLTGPIPSSLGNLKNLQYLFLYQNKLSGPIPPSIFSLQKLISLDLSDNSLSGEIPEL 303

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907171115 272 sgaFTGLDNLSKLTLFGNKIKSVAKRAFSGLESLEHLNLGENAIRSVQFDAFAKMKNLKELYISSESF-------LCD 342
Cdd:PLN00113  304 ---VIQLQNLEILHLFSNNFTGKIPVALTSLPRLQVLQLWSNKFSGEIPKNLGKHNNLTVLDLSTNNLtgeipegLCS 378

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: 48.00 E-value: 7.70e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907171115 509 TGTTARLECAATGHPNPQIAWQKDGGtdfPAARERRMHVMPDDDV-FFITDVKIDDMGVYSCTAQNSAGSVSANATLTV 586
Cdd:cd05730    17 LGQSVTLACDADGFPEPTMTWTKDGE---PIESGEEKYSFNEDGSeMTILDVDKLDEAEYTCIAENKAGEQEAEIHLKV 92

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: 48.09 E-value: 7.82e-07

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1907171115 618 TPRITWLKGGRPLSLTERhhFTPGNQLLVVQNVMIDDAGRYTCEMS 663
Cdd:cd05757    29 LPPIQWYKDCKPLQGDKR--FIPKGSKLLIQNVTEEDAGNYTCKFT 72

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: 47.57 E-value: 1.03e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 500 KIPHDIAIRTGTTARLEC-AATGHPNPQIAWQKDGGTdfpaaRERRMHVMPDDD-----VFFITDVKIDDMGVYSCTAQN 573
Cdd:pfam00047   1 SAPPTVTVLEGDSATLTCsASTGSPGPDVTWSKEGGT-----LIESLKVKHDNGrttqsSLLISNVTKEDAGTYTCVVNN 75

                          90
                  ....*....|.
gi 1907171115 574 SAGSVSANATL 584
Cdd:pfam00047  76 PGGSATLSTSL 86

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: 51.59 E-value: 1.07e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 133 SLEVLRLQRNNISRLTDG------AFWGLSKMHVLHLEYNSLVEVNSGSLYGLT---ALHQLHLSNNSIS----RIQRDG 199
Cdd:cd00116    52 SLKELCLSLNETGRIPRGlqsllqGLTKGCGLQELDLSDNALGPDGCGVLESLLrssSLQELKLNNNGLGdrglRLLAKG 131

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 200 WSFCQ-KLHELILSFNNLTRLDEESLAElsslsilrlshnaishiaegAFKGLKSLRVLDLDHNEISGT-IEDTSGAFTG 277
Cdd:cd00116   132 LKDLPpALEKLVLGRNRLEGASCEALAK--------------------ALRANRDLKELNLANNGIGDAgIRALAEGLKA 191

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*
gi 1907171115 278 LDNLSKLTLFGNKIKSVAKRAFSG----LESLEHLNLGENAIRSV 318
Cdd:cd00116   192 NCNLEVLDLNNNGLTDEGASALAEtlasLKSLEVLNLGDNNLTDA 236

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: 47.57 E-value: 1.07e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907171115 600 VVTVGETVAFQCKA-TGSPTPRITWLKGG--RPLSLTERHHFTPGNQL-LVVQNVMIDDAGRYTCEMSNPLG 667
Cdd:pfam00047   7 TVLEGDSATLTCSAsTGSPGPDVTWSKEGgtLIESLKVKHDNGRTTQSsLLISNVTKEDAGTYTCVVNNPGG 78

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: 47.46 E-value: 1.10e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 601 VTVGETVAFQCKATGSPTPRITWLKGGRPLSL-TER---HHFTPGNQLLVVQNVMIDDAGRYTCEMSNPLGTERAHSQLS 676
Cdd:cd05892    12 VLEGDPVRLECQISAIPPPQIFWKKNNEMLQYnTDRislYQDNCGRICLLIQNANKKDAGWYTVSAVNEAGVVSCNARLD 91


                  .
gi 1907171115 677 I 677
Cdd:cd05892    92 V 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: 47.46 E-value: 1.11e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 590 PSLAVPLEDRVVTVGETVAFQCKATGSPTPRITWLKGGRPLSLTERHHFTPGNQLLVVQNVMI---DDAGRYTCEMSNPL 666
Cdd:cd20975     1 PTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGGLCRLRILAaerGDAGFYTCKAVNEY 80

                          90
                  ....*....|.
gi 1907171115 667 GTERAHSQLSI 677
Cdd:cd20975    81 GARQCEARLEV 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: 47.20 E-value: 1.27e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907171115 604 GETVAFQCKATGSPTPRITWLKGGRPLSLT---ERHHFTPGNqlLVVQNVMIDDAGRYTCEMSNPLG 667
Cdd:cd05867    14 GETARLDCQVEGIPTPNITWSINGAPIEGTdpdPRRHVSSGA--LILTDVQPSDTAVYQCEARNRHG 78

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: 47.24 E-value: 1.38e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 499 TKIPHDIAIRTGTTARLECAATGHPNPQIAWQKdgGTDfpAARERRMHVMPDDDVFFITDVKIDDMGVYSCTAQNSAGSV 578
Cdd:cd20968     3 TRPPTNVTIIEGLKAVLPCTTMGNPKPSVSWIK--GDD--LIKENNRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLGIA 78


                  ....*....
gi 1907171115 579 -SANATLTV 586
Cdd:cd20968    79 ySKPVTIEV 87

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: 47.19 E-value: 1.52e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 500 KIPHDIAIRTGTTARLECAATGHPNPQIAWQKDGGTDFPAareRRMHVMPDDDVFFITDVKIDDmGVYSCTAQNSAGSVS 579
Cdd:cd05723     2 KKPSNIYAHESMDIVFECEVTGKPTPTVKWVKNGDVVIPS---DYFKIVKEHNLQVLGLVKSDE-GFYQCIAENDVGNAQ 77


                  ....*..
gi 1907171115 580 ANATLTV 586
Cdd:cd05723    78 ASAQLII 84

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: 46.76 E-value: 1.67e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907171115 600 VVTVGETVAFQCKATGSPTPRITWLKGGRPLSLTE---RHHFTPGNQLLVVQNVMIDDAGRYTCEMSNPLGTERA 671
Cdd:cd05894     6 VVVAGNKLRLDVPISGEPAPTVTWSRGDKAFTATEgrvRVESYKDLSSFVIEGAEREDEGVYTITVTNPVGEDHA 80

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: 47.28 E-value: 1.86e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 580 ANATLTVLETPSlAVPLEDRVVtvgetvaFQCKATGSPTPRITWLKGGRPLSLTE---------RHHFTPGNqlLVVQNV 650
Cdd:cd05869     1 AKPKITYVENQT-AMELEEQIT-------LTCEASGDPIPSITWRTSTRNISSEEktldghivvRSHARVSS--LTLKYI 70

                          90
                  ....*....|....*....
gi 1907171115 651 MIDDAGRYTCEMSNPLGTE 669
Cdd:cd05869    71 QYTDAGEYLCTASNTIGQD 89

Leucine rich repeat;

Pssm-ID: 404697 [Multi-domain] Cd Length: 61 Bit Score: 45.98 E-value: 2.08e-06

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1907171115  20 QHNKILSVDGSQLKSYLSLEVLDLSSNNITEIRSSCFpNGLR-IRELNLASNRI 72
Cdd:pfam13855   9 SNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAF-SGLPsLRYLDLSGNRL 61

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: 46.56 E-value: 2.34e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 497 SFTKIPHDIAIRTGTTARLECAATGHPNPQIAWQKDGG-TDFPAARERRMHVMpdDDVFFITDVKIDDMGVYSCTAQNSA 575
Cdd:cd20949     1 TFTENAYVTTVKEGQSATILCEVKGEPQPNVTWHFNGQpISASVADMSKYRIL--ADGLLINKVTQDDTGEYTCRAYQVN 78

                          90
                  ....*....|.
gi 1907171115 576 GSVSANATLTV 586
Cdd:cd20949    79 SIASDMQERTV 89

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: 46.46 E-value: 3.04e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907171115 602 TVGETVAFQCKATGSPTPRITWLKGGRPLSltERHHFTPGnQLLVVQNVMIDDAGRYTCEMSNPLGTERAHSQLSIL 678
Cdd:cd05864    15 KVGERVRIPVKYLGYPPPEIKWYKNGIPIE--SNHTIKAG-HVLTIMEVTEKDAGNYTVVLTNPISKEKQRHTFSLV 88

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: 46.13 E-value: 3.43e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 595 PLEDRVVTVGETVAFQCKATGSPTPRITWLKGGRPLSL--TERHHFTPGNQlLVVQNVMIDDAGRYTCEMSNPLGTERAH 672
Cdd:cd05868     5 APTNLVLSPGEDGTLICRANGNPKPSISWLTNGVPIEIapTDPSRKVDGDT-IIFSKVQERSSAVYQCNASNEYGYLLAN 83


                  ....*.
gi 1907171115 673 SQLSIL 678
Cdd:cd05868    84 AFVNVL 89

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: 46.17 E-value: 3.53e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907171115 600 VVTVGE--TVAFQCKATGSPTPRITWLKGGRPLSLTERH--HFTPGNQLLVVQNVMIDDAGRYTCEMSNPLGT 668
Cdd:cd20949     8 VTTVKEgqSATILCEVKGEPQPNVTWHFNGQPISASVADmsKYRILADGLLINKVTQDDTGEYTCRAYQVNSI 80

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: 46.19 E-value: 4.90e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 499 TKI---PHDIAIRTGTTARLECAATGHPNPQIA--WQKDG---GTDFPAARERRMHVMPDDDVFFITDVKIDDMGVYSCT 570
Cdd:cd05854     3 TKItlaPSSADINQGENLTLQCHASHDPTMDLTftWSLDDfpiDLDKPNGHYRRMEVKETIGDLVIVNAQLSHAGTYTCT 82

                          90       100
                  ....*....|....*....|
gi 1907171115 571 AQNSAGSVSANATLTVLETP 590
Cdd:cd05854    83 AQTVVDSASASATLVVRGPP 102

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: 45.86 E-value: 5.40e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 590 PSLAVPLEDRVVTVGETVAFQCKATGSPTPRITWLKGGRPLSLTERHHFTP----GNQLLVVQNVMIDDAGRYTCEMSNP 665
Cdd:cd05893     1 PFFEMKLKHYKIFEGMPVTFTCRVAGNPKPKIYWFKDGKQISPKSDHYTIQrdldGTCSLHTTASTLDDDGNYTIMAANP 80


                  ..
gi 1907171115 666 LG 667
Cdd:cd05893    81 QG 82

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: 45.29 E-value: 6.97e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 503 HDIAIRtGTTARLECAATGHPNPQIAWQKDGGTDFPaareRRMHVMPDDDVFFITDVKIDDMGVYSCTAQNSAGSVSANA 582
Cdd:cd05876     4 SLVALR-GQSLVLECIAEGLPTPTVKWLRPSGPLPP----DRVKYQNHNKTLQLLNVGESDDGEYVCLAENSLGSARHAY 78


                  ....
gi 1907171115 583 TLTV 586
Cdd:cd05876    79 YVTV 82

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: 9.01e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907171115 602 TVGE-TVAFQCKATGSPTPRITWLKGGRPLSLTERHHfTPgnQLLVVQNVMIDDAGRYTCEMSNPLGTERAHSQLSIL 678
Cdd:cd04976    15 TAGKrSVRLPMKVKAYPPPEVVWYKDGLPLTEKARYL-TR--HSLIIKEVTEEDTGNYTILLSNKQSNVFKNLTATLV 89

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: 45.11 E-value: 1.06e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 599 RVVTVGETVAFQCKATGSPTPRITWLK-----GGR--PLSLTE--------RHHFTPGNQLLvVQNVMIDDAGRYTCEMS 663
Cdd:cd04974    11 QTVVLGSDVEFHCKVYSDAQPHIQWLKhvevnGSKygPDGLPYvtvlkvagVNTTGEENTLT-ISNVTFDDAGEYICLAG 89


                  ....
gi 1907171115 664 NPLG 667
Cdd:cd04974    90 NSIG 93

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: 44.56 E-value: 1.47e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907171115 607 VAFQCKATGSPTPRITWLKGGRPLSLTERHHFTPGNQLLVVQNVMIDDAGRYTCEMSNPLGTERA 671
Cdd:cd05849    22 VSVNCRARANPFPIYKWRKNNLDIDLTNDRYSMVGGNLVINNPDKYKDAGRYVCIVSNIYGKVRS 86

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: 44.03 E-value: 1.91e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115  398 PETTMAVVGKDIRFTCSAASSSSSPMTfaWKKDNEVLANADmENFaHVRAQDGevmeyTTILHLRHVTFGHEGRYQCIIT 477
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVT--WYKQGGKLLAES-GRF-SVSRSGS-----TSTLTISNVTPEDSGTYTCAAT 71

                           90
                   ....*....|....*
gi 1907171115  478 NHFGSTYSHkARLTV 492
Cdd:smart00410  72 NSSGSASSG-TTLTV 85

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: 43.94 E-value: 1.98e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907171115 598 DRVVTVGETVAFQCKATGSPTPRITWLKGGRPLSLTERHHF---TPGNQLLVVQNVMIDDAGRYTCEMSNPLG 667
Cdd:cd20990     9 DLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSAHKMlvrENGVHSLIIEPVTSRDAGIYTCIATNRAG 81

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: 43.72 E-value: 2.09e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907171115 607 VAFQCKATGSPTPRITWLKGGRPLSLTERHHFTPGNQLLVVqNVMIDDAGRYTCEMSNPLGTERAHSQLSI 677
Cdd:cd05723    15 IVFECEVTGKPTPTVKWVKNGDVVIPSDYFKIVKEHNLQVL-GLVKSDEGFYQCIAENDVGNAQASAQLII 84

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: 44.02 E-value: 2.19e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 590 PSLAVPLEDRVVTVGETVAFQCKATGSPTPRITWlKGGRPLSLTERHHFTP--------GNQLLVVQNVMIDDAGRYTCE 661
Cdd:cd05734     2 PRFVVQPNDQDGIYGKAVVLNCSADGYPPPTIVW-KHSKGSGVPQFQHIVPlngriqllSNGSLLIKHVLEEDSGYYLCK 80

                          90
                  ....*....|..
gi 1907171115 662 MSNPLGTERAHS 673
Cdd:cd05734    81 VSNDVGADISKS 92

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: 44.08 E-value: 2.22e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 499 TKI---PHDIAIRTGTTARLECAATGHPNPQIA--WQKDG-GTDF--PAARERRMHVMPDDDVFFITDVKIDDMGVYSCT 570
Cdd:cd04970     3 TRItlaPSNADITVGENATLQCHASHDPTLDLTftWSFNGvPIDLekIEGHYRRRYGKDSNGDLEIVNAQLKHAGRYTCT 82

                          90       100
                  ....*....|....*....|
gi 1907171115 571 AQNSAGSVSANATLTVLETP 590
Cdd:cd04970    83 AQTVVDSDSASATLVVRGPP 102

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: 2.32e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 507 IRTGTTARLECAATGHPNPQIAWQKDG-------GTDFPAARERRMHVMPdddvffitdVKIDDMGVYSCTAQNSAGSV- 578
Cdd:cd05760    13 IQPSSRVTLRCHIDGHPRPTYQWFRDGtplsdgqGNYSVSSKERTLTLRS---------AGPDDSGLYYCCAHNAFGSVc 83

                          90
                  ....*....|.
gi 1907171115 579 -SANATLTVLE 588
Cdd:cd05760    84 sSQNFTLSIID 94

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: 43.25 E-value: 2.37e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 510 GTTARLECAATGHPNPQIAWQKDGGtdfPAARERRMHVMPDDD--VFFITDVKIDDMGVYSCTAQNSAGSVSAN--ATLT 585
Cdd:cd05743     1 GETVEFTCVATGVPTPIINWRLNWG---HVPDSARVSITSEGGygTLTIRDVKESDQGAYTCEAINTRGMVFGIpdGILT 77


                  .
gi 1907171115 586 V 586
Cdd:cd05743    78 V 78

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: 43.71 E-value: 2.77e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 510 GTTARLECAATGHPNPQIAWQKDGgtdfpaaRE----RRMHVMPdDDVFFITDV-KIDDMGVYSCTAQNSAG-SVSANAT 583
Cdd:cd20958    15 GQTLRLHCPVAGYPISSITWEKDG-------RRlplnHRQRVFP-NGTLVIENVqRSSDEGEYTCTARNQQGqSASRSVF 86


                  ...
gi 1907171115 584 LTV 586
Cdd:cd20958    87 VKV 89

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: 43.78 E-value: 2.99e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907171115 510 GTTARLECA-ATGHPNPQIAWQKDGGTDFPAAR---ERRMHVMPDDDVFF--ITDVKIDDMGVYSCTAQNSA 575
Cdd:cd20965    17 GKPFKLDCNvPPGYPKPTIEWKKQLVSDSSKADtilDRRITISPNGDLYFtnVTKEDVSTDYKYVCVAKTPA 88

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: 43.55 E-value: 3.48e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 496 PSFTKIPHD-IAIRTGTTARLECAATGHPNPQIAWQKDGGT---DFPAARErrmhvMPDDDVFFITDVKIDD------MG 565
Cdd:cd20955     2 PVFLKEPTNrIDFSNSTGAEIECKASGNPMPEIIWIRSDGTavgDVPGLRQ-----ISSDGKLVFPPFRAEDyrqevhAQ 76

                          90
                  ....*....|...
gi 1907171115 566 VYSCTAQNSAGSV 578
Cdd:cd20955    77 VYACLARNQFGSI 89

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: 43.62 E-value: 3.54e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 395 ITQPETTMAVVGKDIRFTCSAASSSssPMTFAWKKDNEVLANADMENfaHVRAQDGEVMeYTTILHLRHVTfGHEGRYQC 474
Cdd:cd05722     5 LSEPSDIVAMRGGPVVLNCSAESDP--PPKIEWKKDGVLLNLVSDER--RQQLPNGSLL-ITSVVHSKHNK-PDEGFYQC 78

                          90
                  ....*....|....*....
gi 1907171115 475 IITN-HFGSTYSHKARLTV 492
Cdd:cd05722    79 VAQNeSLGSIVSRTARVTV 97

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: 42.84 E-value: 3.69e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 498 FTKIPHDIAIRTGTTARLECAATGHPNP-QIAWQKDGG--TDFPAARERRMHVmpdddvffitdVKIDDMGVYSCTAQNS 574
Cdd:cd05749     2 FTVEPEDLAVTANTPFNLTCQAVGPPEPvEILWWQGGSplGGPPAPSPSVLNV-----------PGLNETTKFSCEAHNA 70

                          90
                  ....*....|..
gi 1907171115 575 AG-SVSANATLT 585
Cdd:cd05749    71 KGlTSSRTATVT 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: 44.18 E-value: 3.75e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 498 FTKIPHDIAIRTGTTARLECAATGHPNPQIAWQKDGGTD-------FPAARERRMHV-----MPDDDVFFITDVKIDDMG 565
Cdd:cd20940     3 FIKSPLSQQRLVGDSVELHCEAVGSPIPEIQWWFEGQEPneicsqlWDGARLDRVHInatyhQHATSTISIDNLTEEDTG 82


                  ....*...
gi 1907171115 566 VYSCTAQN 573
Cdd:cd20940    83 TYECRASN 90

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: 43.08 E-value: 3.98e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907171115 599 RVVTVGETVAFQCKATGSPTPRITWLKGGRPLSLTERH----HFTPGnqLLVVQNVMIDDAGRYTCEMSNPLGT 668
Cdd:cd05738     9 KVVEKARTATMLCAASGNPDPEISWFKDFLPVDTATSNgrikQLRSG--ALQIENSEESDQGKYECVATNSAGT 80

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: 43.30 E-value: 4.27e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 506 AIRTGTTARLECAATGHPNPQIAWQKDGGtdfPAARERRM---HVMPDDDVFFITDVKIDDMGVYSCTAQNSAGSVSANA 582
Cdd:cd05857    15 AVPAANTVKFRCPAAGNPTPTMRWLKNGK---EFKQEHRIggyKVRNQHWSLIMESVVPSDKGNYTCVVENEYGSINHTY 91


                  ....
gi 1907171115 583 TLTV 586
Cdd:cd05857    92 HLDV 95

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: 44.07 E-value: 4.35e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 243 IAEGAFKGLKSLRVLDLDHN--EISgtiedtSGAFTGLdNLSKLTlFGNKIKSVAKRAFSGLESLEHLNLGENaIRSVQF 320
Cdd:pfam13306  25 IGEYAFSNCTSLKSITLPSSltSIG------SYAFYNC-SLTSIT-IPSSLTSIGEYAFSNCSNLKSITLPSN-LTSIGS 95

                          90
                  ....*....|....*.
gi 1907171115 321 DAFAKMkNLKELYISS 336
Cdd:pfam13306  96 YAFSNC-SLKSITIPS 110

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: 43.06 E-value: 4.47e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 496 PSFTKIPHDIAIRTGTTAR--LECAATGHPNPQIAWQKdgGTDFpAARERRMHVMpDDDVFFITDVKIDDMGVYSCTAQN 573
Cdd:cd05852     1 PTFEFNPMKKKILAAKGGRviIECKPKAAPKPKFSWSK--GTEL-LVNNSRISIW-DDGSLEILNITKLDEGSYTCFAEN 76

                          90
                  ....*....|...
gi 1907171115 574 SAGSVSANATLTV 586
Cdd:cd05852    77 NRGKANSTGVLSV 89

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: 42.54 E-value: 5.05e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 502 PHDIAIRTGTTARLECAA-TGHPNPQIAWQKDGGTdFPAareRRMHVMpddDVFFITDVKIDDMGVYSCTAQNSAGSVSA 580
Cdd:cd05754     8 PRSQEVRPGADVSFICRAkSKSPAYTLVWTRVNGT-LPS---RAMDFN---GILTIRNVQLSDAGTYVCTGSNMLDTDEA 80


                  ....
gi 1907171115 581 NATL 584
Cdd:cd05754    81 TATL 84

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: 42.85 E-value: 5.27e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907171115 600 VVTVGETVAFQCKATGSPTPRITWLK-GGRPLSLTERHHFTPgNQLLVVQNVMIDDAGRYTCEMSNPLGTERAHSQLSI 677
Cdd:cd05764    11 RVLEGQRATLRCKARGDPEPAIHWISpEGKLISNSSRTLVYD-NGTLDILITTVKDTGAFTCIASNPAGEATARVELHI 88

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: 42.78 E-value: 5.31e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 515 LECAATGHPNPQIAWQKDgGTDFPAARERRMHVMPDDDVFFIT--DVKIDDM-GVYSCTAQNSAGSVSAN 581
Cdd:cd05733    21 IKCEAKGNPQPTFRWTKD-GKFFDPAKDPRVSMRRRSGTLVIDnhNGGPEDYqGEYQCYASNELGTAISN 89

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: 43.02 E-value: 5.58e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 501 IPHDIAIRTGTTARLECAATGHPNPQIAW----QKDG---GTD-FPAARERRMHVMPDDD----VFFITDVKIDDMGVYS 568
Cdd:cd05858     7 LPANTSVVVGTDAEFVCKVYSDAQPHIQWlkhvEKNGskyGPDgLPYVEVLKTAGVNTTDkeieVLYLRNVTFEDAGEYT 86

                          90
                  ....*....|....*....
gi 1907171115 569 CTAQNSAGSVSANATLTVL 587
Cdd:cd05858    87 CLAGNSIGISHHSAWLTVL 105

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: 42.62 E-value: 6.76e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907171115 607 VAFQCKATGSPTPRITWLKGGRPLSLTE--RHHFTPGNQLLVVQNVMIdDAGRYTCEMSNPLGT 668
Cdd:cd05848    22 VILNCEARGNPVPTYRWLRNGTEIDTESdyRYSLIDGNLIISNPSEVK-DSGRYQCLATNSIGS 84

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: 8.17e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 605 ETVAFQCKATGSPTPRITWLKGGRPLSLT--ERHHFTPGNqlLVVQN-VMIDDAGRYTCEMSNPLGTERA 671
Cdd:cd04967    20 KKVALNCRARANPVPSYRWLMNGTEIDLEsdYRYSLVDGT--LVISNpSKAKDAGHYQCLATNTVGSVLS 87

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: 42.20 E-value: 8.34e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 600 VVTV--GETVAFQCKATGSPTPRITWLKGGRPLSLTErHHFTPGNQ----LLVVQNVMIDDAGRYTCEMSNPLGTERAHS 673
Cdd:cd05891    10 VVTImeGKTLNLTCTVFGNPDPEVIWFKNDQDIELSE-HYSVKLEQgkyaSLTIKGVTSEDSGKYSINVKNKYGGETVDV 88


                  ....
gi 1907171115 674 QLSI 677
Cdd:cd05891    89 TVSV 92

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: 42.14 E-value: 8.99e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 511 TTARLECAATGHPNPQIAWQKdggtdFPAARERRMHVMPDDDV------FFITDVKIDDMGVYSCTAQNSAGSVSANATL 584
Cdd:cd20953    19 SSIALLCPAQGYPAPSFRWYK-----FIEGTTRKQAVVLNDRVkqvsgtLIIKDAVVEDSGKYLCVVNNSVGGESVETVL 93


                  ..
gi 1907171115 585 TV 586
Cdd:cd20953    94 TV 95

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: 41.91 E-value: 9.68e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 595 PLEDRVVTV-GETVAFQCKATGSPTPRITWLKGGRPLSLTERHHFTPGNQLLVVqNVMIDDAGRYTCEMSNPLGTERAHS 673
Cdd:cd05852     7 PMKKKILAAkGGRVIIECKPKAAPKPKFSWSKGTELLVNNSRISIWDDGSLEIL-NITKLDEGSYTCFAENNRGKANSTG 85


                  ....
gi 1907171115 674 QLSI 677
Cdd:cd05852    86 VLSV 89

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: 45.94 E-value: 1.06e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115  29 GSQLKSYLSLEVLDLSSNNITEIRSSCFPNGLR----IRELNLASNRISilESGAfdglsrslltlrlsknritQLPVKA 104
Cdd:COG5238   229 AEALKGNKSLTTLDLSNNQIGDEGVIALAEALKnnttVETLYLSGNQIG--AEGA-------------------IALAKA 287

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 105 FK-LPRLTQLDLNRNRIR------LIEGLtfQGLDSLEVLRLQRNNISrlTDGAfwglskmhvlhleyNSLVEvnsgSLY 177
Cdd:COG5238   288 LQgNTTLTSLDLSVNRIGdegaiaLAEGL--QGNKTLHTLNLAYNGIG--AQGA--------------IALAK----ALQ 345

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1907171115 178 GLTALHQLHLSNNSISRIQRDGwsFCQ------KLHELILSFNNLTRLDEESLAE 226
Cdd:COG5238   346 ENTTLHSLDLSDNQIGDEGAIA--LAKylegntTLRELNLGKNNIGKQGAEALID 398

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: 41.93 E-value: 1.18e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907171115 510 GTTARLECAATGHPNPQIAWQKDgGTDFPAARERRMhvmpDDDVFFITDVKIDDMGVYSCTAQNSAG 576
Cdd:cd05851    16 GQNVTLECFALGNPVPVIRWRKI-LEPMPATAEISM----SGAVLKIFNIQPEDEGTYECEAENIKG 77

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: 41.86 E-value: 1.42e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 597 EDRVVTVGETVAFQCKATGSPTPRITWLKGGRPLSltERHHF----TPGNQLLVVQNVMIDDAGRYTCEMSNPLGTERAH 672
Cdd:cd05762     9 EDMKVRAGESVELFCKVTGTQPITCTWMKFRKQIQ--EGEGIkienTENSSKLTITEGQQEHCGCYTLEVENKLGSRQAQ 86


                  ....*....
gi 1907171115 673 SQLSILPTP 681
Cdd:cd05762    87 VNLTVVDKP 95

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: 1.60e-04

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1907171115 619 PRITWLKGGRPLSLTERHhFTPGNQLLVVQNVMIDDAGRYTCEMSNP 665
Cdd:cd20994    31 PKVQWYKDCKPLLLDDKR-FAGLESDLLIFNVTVQDQGNYTCHTSYT 76

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: 41.62 E-value: 1.60e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 595 PLEDRVVTVGETVAFQCKATGSPTPRITWLKGGRplslterhHFTPGNQL----------LVVQN---VMIDDAGRYTCE 661
Cdd:cd05733     7 SPKDYIVDPRDNITIKCEAKGNPQPTFRWTKDGK--------FFDPAKDPrvsmrrrsgtLVIDNhngGPEDYQGEYQCY 78

                          90
                  ....*....|.
gi 1907171115 662 MSNPLGTERAH 672
Cdd:cd05733    79 ASNELGTAISN 89

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: 41.71 E-value: 1.68e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 496 PSFTKIPHDIAIRTGTTARLECAATGHPNPQIAWQKDGGTDFP-----AARERRMHVMPDDDVfFITDVKIDDMGVYSCT 570
Cdd:cd05734     2 PRFVVQPNDQDGIYGKAVVLNCSADGYPPPTIVWKHSKGSGVPqfqhiVPLNGRIQLLSNGSL-LIKHVLEEDSGYYLCK 80

                          90
                  ....*....|....*..
gi 1907171115 571 AQNSAGS-VSANATLTV 586
Cdd:cd05734    81 VSNDVGAdISKSMYLTV 97

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: 41.38 E-value: 1.81e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 392 PQIITQPETTMAVVGKDIRFTCSAASSSSSpmTFAWKKDNEVLANADMENFAHVRAQDGEVMEYTTILHLRHVTfGHEGR 471
Cdd:cd07693     1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTP--TIQWLKNGQPLETDKDDPRSHRIVLPSGSLFFLRVVHGRKGR-SDEGV 77

                          90       100
                  ....*....|....*....|.
gi 1907171115 472 YQCIITNHFGSTYSHKARLTV 492
Cdd:cd07693    78 YVCVAHNSLGEAVSRNASLEV 98

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: 41.50 E-value: 1.92e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 604 GETVAFQCKATGSPTPRITWLKGGRPLSLTE-------------RHhftpGNQLLVVQNVMIDDAGRYTCEMSNPLGTER 670
Cdd:cd05870    16 NGAATLSCKAEGEPIPEITWKRASDGHTFSEgdkspdgrievkgQH----GESSLHIKDVKLSDSGRYDCEAASRIGGHQ 91


                  ....*..
gi 1907171115 671 AHSQLSI 677
Cdd:cd05870    92 KSMYLDI 98

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: 41.45 E-value: 1.99e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907171115 605 ETVAFQCKATGSPTPRITWLKGGRPLSLTE--RHHFTPGNqlLVVQN-VMIDDAGRYTCEMSNPLGT 668
Cdd:cd05850    21 EKVTLACRARASPPATYRWKMNGTELKMEPdsRYRLVAGN--LVISNpVKAKDAGSYQCLASNRRGT 85

Immunoglobulin I-set domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1); The members here are composed of the immunoglobulin I-set (IgI) domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1). Human Lingo-1 is a central nervous system-specific transmembrane glycoprotein also known as LERN-1, which functions as a negative regulator of neuronal survival, axonal regeneration, and oligodendrocyte differentiation and myelination. Lingo-1 is a key component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors. The ligand-binding ectodomain of human Lingo-1 contains a bimodular, kinked structure composed of leucine-rich repeat (LRR) and immunoglobulin (Ig)-like modules. Diseases associated with Lingo-1 include mental retardation, autosomal recessive 64 and essential tremor. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the Lingo-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409561 Cd Length: 92 Bit Score: 41.22 E-value: 2.06e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907171115 510 GTTARLECAATGHPNPQIAWQKDGGTDFPAARERRMHVMPDDDVFFiTDVKIDDMGVYSCTAQNSAGSVSANATLTV 586
Cdd:cd20969    17 GHTVQFVCRADGDPPPAILWLSPRKHLVSAKSNGRLTVFPDGTLEV-RYAQVQDNGTYLCIAANAGGNDSMPAHLHV 92

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: 41.46 E-value: 2.10e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 496 PSFTKIPHDIAIRTGTTAR---LECAATGHPNPQIAWQKDGgTDFPAARERRmHVMPDDDVFFITDVKIDDMGVYSCTAQ 572
Cdd:cd04967     2 PVFEEQPDDTIFPEDSDEKkvaLNCRARANPVPSYRWLMNG-TEIDLESDYR-YSLVDGTLVISNPSKAKDAGHYQCLAT 79

                          90
                  ....*....|...
gi 1907171115 573 NSAGSV-SANATL 584
Cdd:cd04967    80 NTVGSVlSREATL 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: 41.36 E-value: 2.26e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 502 PHDIAIRTGTTARLE-----CAATGHPNPQIAWQK--DGGTDFPAARERRMHVMPDDDVFFIT--DVKIDDMGVYSCTAQ 572
Cdd:cd05732     3 PKITYLENQTAVELEqitltCEAEGDPIPEITWRRatRGISFEEGDLDGRIVVRGHARVSSLTlkDVQLTDAGRYDCEAS 82


                  ....
gi 1907171115 573 NSAG 576
Cdd:cd05732    83 NRIG 86

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: 40.74 E-value: 3.18e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 496 PSFT-KIPHDIAIRTGTTARLECAATGHPNPQIAWQKDgGTDFPAARERRMHVMPDDDVFFI---TDVKIDDM-GVYSCT 570
Cdd:cd05874     1 PTIThQSPKDYIVDPRENIVIQCEAKGKPPPSFSWTRN-GTHFDIDKDPKVTMKPNTGTLVInimNGEKAEAYeGVYQCT 79

                          90
                  ....*....|.
gi 1907171115 571 AQNSAGSVSAN 581
Cdd:cd05874    80 ARNERGAAVSN 90

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: 40.46 E-value: 3.31e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 397 QPETTMAVVGKDIRFTCSAASSSSSPmTFAWKKDNEVLANADMenfaHVR-AQDGEVMeyttilhLRHVTFGHEGRYQCI 475
Cdd:cd05724     3 EPSDTQVAVGEMAVLECSPPRGHPEP-TVSWRKDGQPLNLDNE----RVRiVDDGNLL-------IAEARKSDEGTYKCV 70

                          90
                  ....*....|....*..
gi 1907171115 476 ITNHFGSTYSHKARLTV 492
Cdd:cd05724    71 ATNMVGERESRAARLSV 87

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: 41.00 E-value: 3.45e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 601 VTVGETVAFQCKATGSPTPRIT--WLKGGRPLSLTE------RHHFTPGNQLLVVQNVMIDDAGRYTCEMSNPLGTERAH 672
Cdd:cd04970    14 ITVGENATLQCHASHDPTLDLTftWSFNGVPIDLEKieghyrRRYGKDSNGDLEIVNAQLKHAGRYTCTAQTVVDSDSAS 93


                  ....*....
gi 1907171115 673 SQLSILPTP 681
Cdd:cd04970    94 ATLVVRGPP 102

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: 40.70 E-value: 3.55e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 496 PSFTKIPHDIAIRTGTTAR---LECAATGHPNPQIAWQKDGgTDFPAARERRMHVMpdDDVFFITDV-KIDDMGVYSCTA 571
Cdd:cd05848     2 PVFVQEPDDAIFPTDSDEKkviLNCEARGNPVPTYRWLRNG-TEIDTESDYRYSLI--DGNLIISNPsEVKDSGRYQCLA 78

                          90
                  ....*....|....
gi 1907171115 572 QNSAGSV-SANATL 584
Cdd:cd05848    79 TNSIGSIlSREALL 92

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: 3.72e-04

                          10        20
                  ....*....|....*....|....*
gi 1907171115 363 ATCAHPESLKGQSIFSVLPDSFVCD 387
Cdd:pfam01463   2 ARCASPPRLRGQPLLDLLPSDFSCS 26

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: 40.48 E-value: 4.04e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 604 GETVAFQCKATGSPTPRITWLKGGRPLSlterHHFTPGN---------QLLVVQNVMIDDAGRYTCEMSNPLGTERAHSQ 674
Cdd:cd20951    15 KSDAKLRVEVQGKPDPEVKWYKNGVPID----PSSIPGKykieseygvHVLHIRRVTVEDSAVYSAVAKNIHGEASSSAS 90


                  .
gi 1907171115 675 L 675
Cdd:cd20951    91 V 91

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: 39.79 E-value: 4.25e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 502 PHDIAIRTGTTARLECAATGHPNPQIAWQKDGGtdfpaaRERRMHVMpdddvfFITDVKIDDMGVYSCTAQNSAGSVSAN 581
Cdd:cd20948     2 PSDTYYLSGENLNLSCHAASNPPAQYSWTINGT------FQTSSQEL------FLPAITENNEGTYTCSAHNSLTGKNIS 69


                  ....*
gi 1907171115 582 ATLTV 586
Cdd:cd20948    70 LVLSV 74

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: 39.92 E-value: 4.86e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907171115 611 CKATGSPTPRITWLKGGRPLSLTER-HHFTPGNqlLVVQNVMIDDAGRYTCEMSNPLGTerAHSQLSIL 678
Cdd:cd20968    21 CTTMGNPKPSVSWIKGDDLIKENNRiAVLESGS--LRIHNVQKEDAGQYRCVAKNSLGI--AYSKPVTI 85

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: 40.33 E-value: 5.17e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 398 PETTMAVVGKDIRFTCSAASSSSSPMTfaWKKDNEV---------LANADMENFAHVRAQDGEVmeytTILHLRHVTFGH 468
Cdd:cd05858     8 PANTSVVVGTDAEFVCKVYSDAQPHIQ--WLKHVEKngskygpdgLPYVEVLKTAGVNTTDKEI----EVLYLRNVTFED 81

                          90       100
                  ....*....|....*....|....
gi 1907171115 469 EGRYQCIITNHFGSTYsHKARLTV 492
Cdd:cd05858    82 AGEYTCLAGNSIGISH-HSAWLTV 104

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: 40.17 E-value: 5.21e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 509 TGTTARLECAATGHPNP-QIAWQKDGG--TDFPAARERRmhVMPDDDVFFITDVKIDDMGVYSCTAQNSAGSVSANATLT 585
Cdd:cd20959    16 VGMRAQLHCGVPGGDLPlNIRWTLDGQpiSDDLGITVSR--LGRRSSILSIDSLEASHAGNYTCHARNSAGSASYTAPLT 93


                  .
gi 1907171115 586 V 586
Cdd:cd20959    94 V 94

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: 39.98 E-value: 5.63e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 601 VTVGETVAFQCKATGS-PTPRITWLKGGRPLSLTERHHFT-----PGNQLLVVQNVMIDDAGRYTCEMSNPLGTERAHSQ 674
Cdd:cd05895    11 VAAGSKLVLRCETSSEyPSLRFKWFKNGKEINRKNKPENIkiqkkKKKSELRINKASLADSGEYMCKVSSKLGNDSASAN 90


                  ...
gi 1907171115 675 LSI 677
Cdd:cd05895    91 VTI 93

Leucine-rich repeat;

Pssm-ID: 405295 [Multi-domain] Cd Length: 175 Bit Score: 41.67 E-value: 6.07e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115  52 RSSCFPNGLRIRELNLASNRISILES-GA----FDglsrsllTLRLSKNRITQLPVKAFkLPRLTQLDLNRNRI-RLIEG 125
Cdd:pfam14580  11 QSAQYTNPVRERELDLRGYKIPIIENlGAtldqFD-------TIDFSDNEIRKLDGFPL-LRRLKTLLLNNNRIcRIGEG 82

                          90       100
                  ....*....|....*....|....
gi 1907171115 126 LTfQGLDSLEVLRLQRNNISRLTD 149
Cdd:pfam14580  83 LG-EALPNLTELILTNNNLQELGD 105

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: 39.23 E-value: 6.82e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 409 IRFTCSAASSSssPMTFAWKKDNEVLANADMENFAHVraqdgevmEYTTILHLRHVTFGHEGRYQCIITNHFGSTYSHKA 488
Cdd:cd00096     1 VTLTCSASGNP--PPTITWYKNGKPLPPSSRDSRRSE--------LGNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

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: 39.88 E-value: 7.00e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 501 IPHDIAIRTGTTARLECAATGHPNPQIAWQKDgGTDFPAARERRMHVMPDDDVFF-ITDVKIDDMGVYSCTAQNSAGSVS 579
Cdd:cd05737     7 LPDVVTIMEGKTLNLTCNVWGDPPPEVSWLKN-DQALAFLDHCNLKVEAGRTVYFtINGVSSEDSGKYGLVVKNKYGSET 85


                  ....*..
gi 1907171115 580 ANATLTV 586
Cdd:cd05737    86 SDVTVSV 92

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: 39.57 E-value: 7.91e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 502 PHDIAIRTGTT-----ARLECAATGHPNPQIAWQK--DGGT--DFPAARERRMHVMPD--DDVFFITDVKIDDMGVYSCT 570
Cdd:cd05870     3 PHIIQLKNETTvengaATLSCKAEGEPIPEITWKRasDGHTfsEGDKSPDGRIEVKGQhgESSLHIKDVKLSDSGRYDCE 82


                  ....*.
gi 1907171115 571 AQNSAG 576
Cdd:cd05870    83 AASRIG 88

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: 39.00 E-value: 1.05e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 496 PSFTKIPHDIAIRTGTTARLECAATGHPNPQIAWQKDGGTDFPAAreRRMHVMPDDDV-FFITDVKidDMGVYSCTAQNS 574
Cdd:cd05764     1 PLITRHTHELRVLEGQRATLRCKARGDPEPAIHWISPEGKLISNS--SRTLVYDNGTLdILITTVK--DTGAFTCIASNP 76

                          90
                  ....*....|..
gi 1907171115 575 AGSVSANATLTV 586
Cdd:cd05764    77 AGEATARVELHI 88

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: 37.61 E-value: 1.07e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1907171115 108 PRLTQLDLNRNRIRLIEGLtfQGLDSLEVLRLQRNN-ISRLTD 149
Cdd:pfam12799   1 PNLEVLDLSNNQITDIPPL--AKLPNLETLDLSGNNkITDLSD 41

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: 42.08 E-value: 1.40e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 103 KAFKLPRLTQLDLNRNRI------RLIEGLTfQGlDSLEVLRLQRNNIsrlTDGAFWGLSKMhvlhleynslvevnsgsL 176
Cdd:COG5238   175 KALQNNSVETVYLGCNQIgdegieELAEALT-QN-TTVTTLWLKRNPI---GDEGAEILAEA-----------------L 232

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 177 YGLTALHQLHLSNNSISriqrdgwsfCQKLHELI--LSFN-NLTRLDeeslaelsslsilrLSHNAISH-----IAEgAF 248
Cdd:COG5238   233 KGNKSLTTLDLSNNQIG---------DEGVIALAeaLKNNtTVETLY--------------LSGNQIGAegaiaLAK-AL 288

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 249 KGLKSLRVLDLDHNEISG--------------TIEDTSGAFTGLDN---------------LSKLTLFGNKI-----KSV 294
Cdd:COG5238   289 QGNTTLTSLDLSVNRIGDegaialaeglqgnkTLHTLNLAYNGIGAqgaialakalqenttLHSLDLSDNQIgdegaIAL 368

                         250       260       270
                  ....*....|....*....|....*....|..
gi 1907171115 295 AKrAFSGLESLEHLNLGENAIRSVQFDAFAKM 326
Cdd:COG5238   369 AK-YLEGNTTLRELNLGKNNIGKQGAEALIDA 399

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: 38.63 E-value: 1.50e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 584 LTVLETPSlavpleDRVVTVGETVAFQCKATGSPT--PRITWLKGGRplSLTERHHFTpgnqlLVVQNVMIDDAGRYTCE 661
Cdd:cd20937     3 LEIKVTPS------DAIVREGDSVTMTCEVSSSNPeyTTVSWLKDGT--SLKKQNTFT-----LNLREVTKDQSGKYCCQ 69

                          90
                  ....*....|
gi 1907171115 662 MSNPLGTERA 671
Cdd:cd20937    70 VSNDVGPGRS 79

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: 37.22 E-value: 1.56e-03

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1907171115 304 SLEHLNLGENAIRSVqfDAFAKMKNLKELYISSESFLCD 342
Cdd:pfam12799   2 NLEVLDLSNNQITDI--PPLAKLPNLETLDLSGNNKITD 38

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: 1.62e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 594 VPLEDRVVTVGETVAFQCKATGS-PTPRITWLKGGRPLSL-TERHHFTPGNQLLVVQNVMI-----DDAGR-YTCEMSNP 665
Cdd:pfam08205   4 EPPASLLEGEGPEVVATCSSAGGkPAPRITWYLDGKPLEAaETSSEQDPESGLVTVTSELKlvpsrSDHGQsLTCQVSYG 83


                  ....*.
gi 1907171115 666 LGTERA 671
Cdd:pfam08205  84 ALRGSI 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: 38.25 E-value: 1.64e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907171115 603 VGETVAFQCKATGSPTPRITWLKGGRPLSLTerhhftpgnQLLVVQNVMIDDAGRYTCEMSNPLGTERAHSQLSI 677
Cdd:cd20948     9 SGENLNLSCHAASNPPAQYSWTINGTFQTSS---------QELFLPAITENNEGTYTCSAHNSLTGKNISLVLSV 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: 38.33 E-value: 1.66e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 405 VGKDIRFTCSAASSSSSPmTFAWKKDNEVLANADmenfahvRAQDGEVMEYTTILHLRHVTFGHEGRYQCIITNHFGSTY 484
Cdd:pfam00047  10 EGDSATLTCSASTGSPGP-DVTWSKEGGTLIESL-------KVKHDNGRTTQSSLLISNVTKEDAGTYTCVVNNPGGSAT 81


                  .
gi 1907171115 485 S 485
Cdd:pfam00047  82 L 82

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: 38.21 E-value: 1.85e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907171115 594 VPLEDRVVTVGETVAFQCkATGSPTPRITWLKGGRPL--SLTERHHFTpGNQLLVVQNVMIDDAGRYTCEMSN-PLGT 668
Cdd:cd04979     1 TSFKQISVKEGDTVILSC-SVKSNNAPVTWIHNGKKVprYRSPRLVLK-TERGLLIRSAQEADAGVYECHSGErVLGS 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: 38.76 E-value: 2.03e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907171115 608 AFQCKATGSPTPRITWLKGGRPLSL-------TERHHFTPGNQLLVVQNV-MIDDAGRYTCEMSNPLGTERAHSQL 675
Cdd:cd05773    27 NLVCQAQGVPRVQFRWAKNGVPLDLgnpryeeTTEHTGTVHTSILTIINVsAALDYALFTCTAHNSLGEDSLDIQL 102

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: 38.15 E-value: 2.44e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 507 IRTGTTARLECAATGHPNPQIAWQKDGGTDFPAARERRMHVMPDDDV-FFITDVKIDDMGVYSCTAQNSAGSVSANATLT 585
Cdd:cd05893    12 IFEGMPVTFTCRVAGNPKPKIYWFKDGKQISPKSDHYTIQRDLDGTCsLHTTASTLDDDGNYTIMAANPQGRISCTGRLM 91


                  .
gi 1907171115 586 V 586
Cdd:cd05893    92 V 92

First Ig-like domain of Junctional adhesion molecule-1 (JAM1)and similar domains; a member of the V-set of IgSF domains; The members here are composed of the first Ig-like domain of Junctional Adhesion Molecule-1 (JAM1)and similar domains. 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 first Ig-like domain of JAM1 is a member of the V-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C'-C" in the other.

Pssm-ID: 409538 Cd Length: 102 Bit Score: 37.90 E-value: 3.89e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 594 VPLEDRVVTVGE--TVAFQCKATGSPT-PRITWLKGGRPLS------------LTERHHFTPGNqlLVVQNVMIDDAGRY 658
Cdd:cd20946     2 VPSSQQVVTVVEnqEVILSCKTPKKTSsPRVEWKKLQRDVTfvvfqnnkiqgdYKGRAEILGTN--ITIKNVTRSDSGKY 79


                  ....*..
gi 1907171115 659 TCEMSNP 665
Cdd:cd20946    80 RCEVSAR 86

Leucine-rich repeat;

Pssm-ID: 405295 [Multi-domain] Cd Length: 175 Bit Score: 39.36 E-value: 4.32e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 109 RLTQLDLNRNRIRLIEGLTfQGLDSLEVLRLQRNNISRLtDGAFWglskmhvlhleynslvevnsgslygLTALHQLHLS 188
Cdd:pfam14580  20 RERELDLRGYKIPIIENLG-ATLDQFDTIDFSDNEIRKL-DGFPL-------------------------LRRLKTLLLN 72

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907171115 189 NNSISRIQRDGWSFCQKLHELILSFNNLTRL-DEESLAELSSLSILRLSHNAIS---HIAEGAFKGLKSLRVLD 258
Cdd:pfam14580  73 NNRICRIGEGLGEALPNLTELILTNNNLQELgDLDPLASLKKLTFLSLLRNPVTnkpHYRLYVIYKVPQLRLLD 146

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: 37.20 E-value: 4.57e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 501 IPHDIAIRTGTTARLECAATGHPNPQIAWQKDggtDFPAARERRMHVMPDDDVFF---ITDVKIDDMGVYSCTAQNSAGS 577
Cdd:cd05891     7 LPDVVTIMEGKTLNLTCTVFGNPDPEVIWFKN---DQDIELSEHYSVKLEQGKYAsltIKGVTSEDSGKYSINVKNKYGG 83


                  ....*....
gi 1907171115 578 VSANATLTV 586
Cdd:cd05891    84 ETVDVTVSV 92

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: 37.14 E-value: 5.15e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907171115 601 VTVGETVAFQCKATGSPTPRITWLK------GGRPLSLTERHHFTPGNqlLVVQNVMIDDAGRYTCEMSNPLGTERAHSQ 674
Cdd:cd20953    15 VSSASSIALLCPAQGYPAPSFRWYKfiegttRKQAVVLNDRVKQVSGT--LIIKDAVVEDSGKYLCVVNNSVGGESVETV 92


                  ...
gi 1907171115 675 LSI 677
Cdd:cd20953    93 LTV 95

Leucine-rich repeats, outliers;

Pssm-ID: 197688 [Multi-domain] Cd Length: 24 Bit Score: 35.02 E-value: 5.84e-03

                           10        20
                   ....*....|....*....|....
gi 1907171115  131 LDSLEVLRLQRNNISRLTDGAFWG 154
Cdd:smart00370   1 LPNLRELDLSNNQLSSLPPGAFQG 24

Leucine-rich repeats, typical (most populated) subfamily;

Pssm-ID: 197687 [Multi-domain] Cd Length: 24 Bit Score: 35.02 E-value: 5.84e-03

                           10        20
                   ....*....|....*....|....
gi 1907171115  131 LDSLEVLRLQRNNISRLTDGAFWG 154
Cdd:smart00369   1 LPNLRELDLSNNQLSSLPPGAFQG 24

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: 35.30 E-value: 6.76e-03

                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 1907171115 180 TALHQLHLSNNSISRIqrDGWSFCQKLHELILSFNNL 216
Cdd:pfam12799   1 PNLEVLDLSNNQITDI--PPLAKLPNLETLDLSGNNK 35

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: 36.16 E-value: 9.69e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907171115 601 VTVGETVAFQCKATGSPTPR--ITWLKGG-----RPLSLTERH---HFTPGNQLLVVQNVMIDDAGRYTCEMSNPLGT 668
Cdd:cd23997     5 VAEGSTLWLPCLVPPSDGPRgpLTWSRGHpktplLSLELGSPGlwvLVGPLGILLLLPNVSAQMGGFYLCELGNLSWT 82

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: 34.91 E-value: 9.73e-03

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 1907171115  37 SLEVLDLSSNNITEIRS-SCFPNglrIRELNLASN 70
Cdd:pfam12799   2 NLEVLDLSNNQITDIPPlAKLPN---LETLDLSGN 33

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: 37.14 E-value: 9.80e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907171115 272 SGAFTGLdNLSKLTlFGNKIKSVAKRAFSGLESLEHLNLGENaIRSVQFDAFAKMkNLKELYISS 336
Cdd:pfam13306   5 SYAFYNC-SLTSIT-IPSSLTSIGEYAFSNCTSLKSITLPSS-LTSIGSYAFYNC-SLTSITIPS 65