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: 204.39 E-value: 9.22e-62

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  607 SFIKTPRDSTIRTGHTARLECAAEGHPTPQIAWQKDGGTDFPAARDRRMHVMPDDDVFFITDVKPVDMGVYSCTAKNTAG 686
Cdd:cd05763      1 SFTKTPHDITIRAGSTARLECAATGHPTPQIAWQKDGGTDFPAARERRMHVMPEDDVFFIVDVKIEDTGVYSCTAQNSAG 80

                           90
                   ....*....|.
gi 1779345322  687 TVSANATLTVL 697
Cdd:cd05763     81 SISANATLTVL 91

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

Pssm-ID: 443914 [Multi-domain] Cd Length: 414 Bit Score: 135.83 E-value: 5.37e-34

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322   39 NCTCSGDSVDCSNLELTATPLDLPVRTVSLNLGHNQLTSISPEAFANLPNLRELRLDHNELTSIPDLGQAASKIVSLYLH 118
Cdd:COG4886      1 LLLLLLSLTLKLLLLLLLELLTTLILLLLLLLLLLALLLLSLLSLLLLLTLLLSLLLRDLLLSSLLLLLSLLLLLLLSLL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  119 HNKIRSIDGRRTGELLSVETLDLSNND-ITELRgqcfpaglHIRDLYLSNNKISVL--ELGALDHlgetLQVLRLSRNRI 195
Cdd:COG4886     81 LLSLLLLGLTDLGDLTNLTELDLSGNEeLSNLT--------NLESLDLSGNQLTDLpeELANLTN----LKELDLSNNQL 148

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  196 SQIPVKAFQLPRLTQLELNRNRIRQVeGLTFQGLSSLEVLKLQRNSISKLTDgAFFDLSKMKVLHLDYNSLTEVnSGSLY 275
Cdd:COG4886    149 TDLPEPLGNLTNLKSLDLSNNQLTDL-PEELGNLTNLKELDLSNNQITDLPE-PLGNLTNLEELDLSGNQLTDL-PEPLA 225

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  276 GLTSLQQLFLSNNSIARInpDGWKFCQKLRELNLSYNNLTRLDEgsLAVLGDLHTLRLGHNSISHINEGAFRGLKALRIL 355
Cdd:COG4886    226 NLTNLETLDLSNNQLTDL--PELGNLTNLEELDLSNNQLTDLPP--LANLTNLKTLDLSNNQLTDLKLKELELLLGLNSL 301

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  356 ELDHNDISGTIEDTNGAFSGLDSLIKLTLFENKIKSVAKKAFSGLETLEHLNLGENAIRSIQPDAFTKMRNLKSLLIQSN 435
Cdd:COG4886    302 LLLLLLLNLLELLILLLLLTTLLLLLLLLKGLLVTLTTLALSLSLLALLTLLLLLNLLSLLLTLLLTLGLLGLLEATLLT 381

                          410       420
                   ....*....|....*....|....*..
gi 1779345322  436 SLLCDCQLHWLPDWLVARGLQVGINAT 462
Cdd:COG4886    382 LALLLLTLLLLLLTTTAGVLLLTLALL 408

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

Pssm-ID: 443914 [Multi-domain] Cd Length: 414 Bit Score: 129.28 E-value: 1.01e-31

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322   48 DCSNLELTATPLDLPVRTVSLNLGHNqltsispEAFANLPNLRELRLDHNELTSIPDLGQAASKIVSLYLHHNKIRSIdG 127
Cdd:COG4886     81 LLSLLLLGLTDLGDLTNLTELDLSGN-------EELSNLTNLESLDLSGNQLTDLPEELANLTNLKELDLSNNQLTDL-P 152

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  128 RRTGELLSVETLDLSNNDITELrgqcfPAGL----HIRDLYLSNNKISVL--ELGALdhlgETLQVLRLSRNRISQIPVK 201
Cdd:COG4886    153 EPLGNLTNLKSLDLSNNQLTDL-----PEELgnltNLKELDLSNNQITDLpePLGNL----TNLEELDLSGNQLTDLPEP 223

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  202 AFQLPRLTQLELNRNRIRQVEGLTfqGLSSLEVLKLQRNSISKLTDGAffDLSKMKVLHLDYNSLTEVNSGSLYGLTSLQ 281
Cdd:COG4886    224 LANLTNLETLDLSNNQLTDLPELG--NLTNLEELDLSNNQLTDLPPLA--NLTNLKTLDLSNNQLTDLKLKELELLLGLN 299

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  282 QLFLSNNSIARINP-DGWKFCQKLRELNLSYNNLTRLDEGSLAVLGDLHTLRLGHNSISHINEGAFRGLKALRILELDHN 360
Cdd:COG4886    300 SLLLLLLLLNLLELlILLLLLTTLLLLLLLLKGLLVTLTTLALSLSLLALLTLLLLLNLLSLLLTLLLTLGLLGLLEATL 379

                          330       340       350
                   ....*....|....*....|....*....|...
gi 1779345322  361 DISGTIEDTNGAFSGLDSLIKLTLFENKIKSVA 393
Cdd:COG4886    380 LTLALLLLTLLLLLLTTTAGVLLLTLALLDAVN 412

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

Pssm-ID: 443914 [Multi-domain] Cd Length: 414 Bit Score: 121.96 E-value: 2.38e-29

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  120 NKIRSIDGRRTGELLSVETLDLSNNDITELRGQCFPAGLHIRDLYLSNNKISVLELGALDHLGETLQVLRLSRNRISQIP 199
Cdd:COG4886     10 LKLLLLLLLELLTTLILLLLLLLLLLALLLLSLLSLLLLLTLLLSLLLRDLLLSSLLLLLSLLLLLLLSLLLLSLLLLGL 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  200 VKAFQLPRLTQLELNRNRirqveglTFQGLSSLEVLKLQRNSISKLTDgAFFDLSKMKVLHLDYNSLTEVNSgSLYGLTS 279
Cdd:COG4886     90 TDLGDLTNLTELDLSGNE-------ELSNLTNLESLDLSGNQLTDLPE-ELANLTNLKELDLSNNQLTDLPE-PLGNLTN 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  280 LQQLFLSNNSIARInPDGWKFCQKLRELNLSYNNLTRLDEgSLAVLGDLHTLRLGHNSISHINEgAFRGLKALRILELDH 359
Cdd:COG4886    161 LKSLDLSNNQLTDL-PEELGNLTNLKELDLSNNQITDLPE-PLGNLTNLEELDLSGNQLTDLPE-PLANLTNLETLDLSN 237

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  360 NDISgTIEDtngaFSGLDSLIKLTLFENKIKSVAKkaFSGLETLEHLNLGENAIRSIQPDAFTKMRNLKSLLIQSNSLLC 439
Cdd:COG4886    238 NQLT-DLPE----LGNLTNLEELDLSNNQLTDLPP--LANLTNLKTLDLSNNQLTDLKLKELELLLGLNSLLLLLLLLNL 310

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*....
gi 1779345322  440 DCQLHWLPDWLVARGLQVGINATCAHPESLKGKSVFEVPPSSFVCDDLP 488
Cdd:COG4886    311 LELLILLLLLTTLLLLLLLLKGLLVTLTTLALSLSLLALLTLLLLLNLL 359

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 104.26 E-value: 1.56e-26

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  606 PSFIKTPRDSTIRTGHTARLECAAEGHPTPQIAWQKDGgTDFPAARDRRMHVMPDDDVFFITDVKPVDMGVYSCTAKNTA 685
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDG-QPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSA 79

                           90
                   ....*....|.
gi 1779345322  686 GTVSANATLTV 696
Cdd:pfam07679   80 GEAEASAELTV 90

leucine-rich repeat receptor-like protein kinase; Provisional

Pssm-ID: 215061 [Multi-domain] Cd Length: 968 Bit Score: 100.69 E-value: 2.24e-21

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322   30 LSSDTPCAQNCTCSGdsVDCSNLEltatpldlpvRTVSLNL-GHNQLTSISPEAFaNLPNLRELRLDHNELT-SIP-DLG 106
Cdd:PLN00113    48 LSNWNSSADVCLWQG--ITCNNSS----------RVVSIDLsGKNISGKISSAIF-RLPYIQTINLSNNQLSgPIPdDIF 114

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  107 QAASKIVSLYLHHNKIR-SIDGrrtGELLSVETLDLSNNDITELRGQCFPAGLHIRDLYLSNNKISVLELGALDHLgETL 185
Cdd:PLN00113   115 TTSSSLRYLNLSNNNFTgSIPR---GSIPNLETLDLSNNMLSGEIPNDIGSFSSLKVLDLGGNVLVGKIPNSLTNL-TSL 190

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  186 QVLRLSRNR-ISQIPVKAFQLPRLTQLELNRNRIRQVEGLTFQGLSSLEVLKLQRNSISKLTDGAFFDLSKMKVLHLDYN 264
Cdd:PLN00113   191 EFLTLASNQlVGQIPRELGQMKSLKWIYLGYNNLSGEIPYEIGGLTSLNHLDLVYNNLTGPIPSSLGNLKNLQYLFLYQN 270

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  265 SLTEVNSGSLYGLTSLQQLFLSNNSIARINPDGWKFCQKLRELNLSYNNLTRLDEGSLAVLGDLHTLRLGHNSISHINEG 344
Cdd:PLN00113   271 KLSGPIPPSIFSLQKLISLDLSDNSLSGEIPELVIQLQNLEILHLFSNNFTGKIPVALTSLPRLQVLQLWSNKFSGEIPK 350

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  345 AFRGLKALRILELDHNDISGTIEDTNGAfSGldSLIKLTLFENKIKSVAKKAFSGLETLEHLNLGENAIRSIQPDAFTKM 424
Cdd:PLN00113   351 NLGKHNNLTVLDLSTNNLTGEIPEGLCS-SG--NLFKLILFSNSLEGEIPKSLGACRSLRRVRLQDNSFSGELPSEFTKL 427

                          410
                   ....*....|....
gi 1779345322  425 RNLKSLLIQSNSLL 438
Cdd:PLN00113   428 PLVYFLDISNNNLQ 441

leucine-rich repeat receptor-like protein kinase; Provisional

Pssm-ID: 215061 [Multi-domain] Cd Length: 968 Bit Score: 99.92 E-value: 4.26e-21

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322   68 LNLGHNQLTSISPEAFANLPNLRELRLDHNELT-SIP-DLGQAASkIVSLYLHHNKIRSIDGRRTGELLSVETLDLSNND 145
Cdd:PLN00113   169 LDLGGNVLVGKIPNSLTNLTSLEFLTLASNQLVgQIPrELGQMKS-LKWIYLGYNNLSGEIPYEIGGLTSLNHLDLVYNN 247

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  146 ITelrGQCFPAGLHIRDL---YLSNNKI------SVLELGALDHL--------GE---------TLQVLRL-SRNRISQI 198
Cdd:PLN00113   248 LT---GPIPSSLGNLKNLqylFLYQNKLsgpippSIFSLQKLISLdlsdnslsGEipelviqlqNLEILHLfSNNFTGKI 324

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  199 PVKAFQLPRLTQLELNRNRIRQVEGLTFQGLSSLEVLKLQRNSIS-KLTDGaFFDLSKMKVLHLDYNSLTEVNSGSLYGL 277
Cdd:PLN00113   325 PVALTSLPRLQVLQLWSNKFSGEIPKNLGKHNNLTVLDLSTNNLTgEIPEG-LCSSGNLFKLILFSNSLEGEIPKSLGAC 403

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  278 TSLQQLFLSNNSIARINPDGWKFCQKLRELNLSYNNLTRLDEGSLAVLGDLHTLRLGHNSISHINEGAFRGlKALRILEL 357
Cdd:PLN00113   404 RSLRRVRLQDNSFSGELPSEFTKLPLVYFLDISNNNLQGRINSRKWDMPSLQMLSLARNKFFGGLPDSFGS-KRLENLDL 482

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  358 DHNDISGTIEDTNGAFSgldSLIKLTLFENKIKSVAKKAFSGLETLEHLNLGENAIRSIQPDAFTKMRNLKSLLIQSNSL 437
Cdd:PLN00113   483 SRNQFSGAVPRKLGSLS---ELMQLKLSENKLSGEIPDELSSCKKLVSLDLSHNQLSGQIPASFSEMPVLSQLDLSQNQL 559

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 86.93 E-value: 1.44e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  700 PHLAQDLEDRSVTVGETVALQCKALGSPPPRITWLHNDQPLRPSDRH--HFTPGNQLLVIGSALLKDAGRYTCLMSNTLG 777
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFkvTYEGGTYTLTISNVQPDDSGKYTCVATNSAG 80

                           90
                   ....*....|
gi 1779345322  778 TERAHSQLVV 787
Cdd:pfam07679   81 EAEASAELTV 90

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: 89.46 E-value: 6.01e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322   68 LNLGHNQLTSIspEAFANLPNLRELRLDHNELTSIPDLGQAaSKIVSLYLHHNKIRSIDGrrTGELLSVETLDLSNNDIT 147
Cdd:cd21340      7 LYLNDKNITKI--DNLSLCKNLKVLYLYDNKITKIENLEFL-TNLTHLYLQNNQIEKIEN--LENLVNLKKLYLGGNRIS 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  148 ELrgqcfpAGLH----IRDLYLSNNKIS-----VLELGALDHLGETLQVLRLSRNRISQI-PVKAfqLPRLTQLELNRNR 217
Cdd:cd21340     82 VV------EGLEnltnLEELHIENQRLPpgeklTFDPRSLAALSNSLRVLNISGNNIDSLePLAP--LRNLEQLDASNNQ 153

                          170       180
                   ....*....|....*....|....*....
gi 1779345322  218 IRQVEGL--TFQGLSSLEVLKLQRNSISK 244
Cdd:cd21340    154 ISDLEELldLLSSWPSLRELDLTGNPVCK 182

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: 81.29 E-value: 1.30e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  609 IKTPRDSTIRTGHTARLECAAEGHPTPQIAWQKDGGtDFPaarDRRMHVMpDDDVFFITDVKPVDMGVYSCTAKNTAGTV 688
Cdd:cd05725      1 VKRPQNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDG-ELP---KGRYEIL-DDHSLKIRKVTAGDMGSYTCVAENMVGKI 75


                   ....*...
gi 1779345322  689 SANATLTV 696
Cdd:cd05725     76 EASATLTV 83

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: 83.30 E-value: 9.71e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  111 KIVSLYLHHNKIRSIDGRRTGELLSVetLDLSNNDITELRG-QCFPaglHIRDLYLSNNKISVLElgALDHlgetlqvlr 189
Cdd:cd21340      3 RITHLYLNDKNITKIDNLSLCKNLKV--LYLYDNKITKIENlEFLT---NLTHLYLQNNQIEKIE--NLEN--------- 66

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  190 lsrnrisqipvkafqLPRLTQLELNRNRIRQVEGLtfQGLSSLEVLKLQRNSI---SKLTdgafFD------LSK-MKVL 259
Cdd:cd21340     67 ---------------LVNLKKLYLGGNRISVVEGL--ENLTNLEELHIENQRLppgEKLT----FDprslaaLSNsLRVL 125

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1779345322  260 HLDYNSLTEVNsgSLYGLTSLQQLFLSNNSIARINPDGWKF--CQKLRELNLSYNNLTR 316
Cdd:cd21340    126 NISGNNIDSLE--PLAPLRNLEQLDASNNQISDLEELLDLLssWPSLRELDLTGNPVCK 182

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: 77.98 E-value: 2.76e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  606 PSFIKTPRDSTIRTGHTARLECAAEGHPTPQIAWQKDG---GTDFPAARDRRMhVMPDDDVFFITDV-----KPvDMGVY 677
Cdd:cd07693      1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGqplETDKDDPRSHRI-VLPSGSLFFLRVVhgrkgRS-DEGVY 78

                           90       100
                   ....*....|....*....|
gi 1779345322  678 SCTAKNTAGT-VSANATLTV 696
Cdd:cd07693     79 VCVAHNSLGEaVSRNASLEV 98

leucine-rich repeat receptor-like protein kinase; Provisional

Pssm-ID: 215061 [Multi-domain] Cd Length: 968 Bit Score: 86.06 E-value: 7.67e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322   66 VSLNLGHNQLTSISPEAFANLPNLRELRLDHNELT-SIPDLGQAASKIVSLYLHHNKIRSIDGRRTGELLSVETLDLSNN 144
Cdd:PLN00113   287 ISLDLSDNSLSGEIPELVIQLQNLEILHLFSNNFTgKIPVALTSLPRLQVLQLWSNKFSGEIPKNLGKHNNLTVLDLSTN 366

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  145 DITelrGQcFPAGL----HIRDLYLSNNKisvLELGALDHLG--ETLQVLRLSRNRIS-QIPVKAFQLPRLTQLELNRNR 217
Cdd:PLN00113   367 NLT---GE-IPEGLcssgNLFKLILFSNS---LEGEIPKSLGacRSLRRVRLQDNSFSgELPSEFTKLPLVYFLDISNNN 439

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  218 IRQVEGLTFQGLSSLEVLKLQRNSIS-KLTDgaFFDLSKMKVLHLDYNSLTEVNSGSLYGLTSLQQLFLSNNSIARINPD 296
Cdd:PLN00113   440 LQGRINSRKWDMPSLQMLSLARNKFFgGLPD--SFGSKRLENLDLSRNQFSGAVPRKLGSLSELMQLKLSENKLSGEIPD 517

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  297 GWKFCQKLRELNLSYNNLTRLDEGSLAVLGDLHTLRLGHNSISHINEGAFRGLKALRILELDHNDISGTIEDTnGAFSGL 376
Cdd:PLN00113   518 ELSSCKKLVSLDLSHNQLSGQIPASFSEMPVLSQLDLSQNQLSGEIPKNLGNVESLVQVNISHNHLHGSLPST-GAFLAI 596


                   ..
gi 1779345322  377 DS 378
Cdd:PLN00113   597 NA 598

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 73.37 E-value: 6.99e-16

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1779345322  606 PSFIKTPRDSTIRTGHTARLECAAEGHPTPQIAWQKDGGTDFPaARDRRMHVMPDDDVFFITDVKPVDMGVYSCTAKN 683
Cdd:pfam13927    2 PVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISS-GSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

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: 77.52 E-value: 7.96e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  207 RLTQLELNRNRIRQVEGLTFqgLSSLEVLKLQRNSISKLTDgaFFDLSKMKVLHLDYNSLTEVNSgsLYGLTSLQQLFLS 286
Cdd:cd21340      3 RITHLYLNDKNITKIDNLSL--CKNLKVLYLYDNKITKIEN--LEFLTNLTHLYLQNNQIEKIEN--LENLVNLKKLYLG 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  287 NNSIARINpdGWKFCQKLRELNLSYNnltRLDEGslavlgdlHTLRLGHNSISHInegafrgLKALRILELDHNdisgti 366
Cdd:cd21340     77 GNRISVVE--GLENLTNLEELHIENQ---RLPPG--------EKLTFDPRSLAAL-------SNSLRVLNISGN------ 130

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1779345322  367 edtngafsGLDSLikltlfenkiksvakKAFSGLETLEHLNLGENAIRSIQP--DAFTKMRNLKSLLIQSN 435
Cdd:cd21340    131 --------NIDSL---------------EPLAPLRNLEQLDASNNQISDLEEllDLLSSWPSLRELDLTGN 178

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: 72.87 E-value: 1.63e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  609 IKTPRDSTIRTGHTARLECAAEGHPTPQIAWQKDGGTDFPAARDRRMHVMPDDDVFfiTDVKPVDMGVYSCTAKNTAGTV 688
Cdd:cd04978      3 IIEPPSLVLSPGETGELICEAEGNPQPTITWRLNGVPIEPAPEDMRRTVDGRTLIF--SNLQPNDTAVYQCNASNVHGYL 80


                   ....*....
gi 1779345322  689 SANATLTVL 697
Cdd:cd04978     81 LANAFLHVL 89

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

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 72.54 E-value: 1.88e-15

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322   612 PRDSTIRTGHTARLECAAEGHPTPQIAWQKDGGTdfPAARDRRMHVMPDDDVF--FITDVKPVDMGVYSCTAKNTAGTVS 689
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGK--LLAESGRFSVSRSGSTStlTISNVTPEDSGTYTCAATNSSGSAS 78


                    ....*..
gi 1779345322   690 ANATLTV 696
Cdd:smart00410   79 SGTTLTV 85

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: 72.14 E-value: 3.15e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  700 PHLAQDLEDRSVTVGETVALQCKALGSPPPRITWLHNDQPLRPSDRHHF---TPGNQLLVIGSALLKDAGRYTCLMSNTL 776
Cdd:cd05744      1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMlvrENGRHSLIIEPVTKRDAGIYTCIARNRA 80

                           90
                   ....*....|.
gi 1779345322  777 GTERAHSQLVV 787
Cdd:cd05744     81 GENSFNAELVV 91

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: 71.90 E-value: 3.16e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  606 PSFIKTPRDSTIRTGHTARLECAAEGHPTPQIAWQKDGgTDFPAARDRrMHVMPDDDVFFITDVKPVDMGVYSCTAKNTA 685
Cdd:cd20976      2 PSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNA-QPLQYAADR-STCEAGVGELHIQDVLPEDHGTYTCLAKNAA 79

                           90
                   ....*....|.
gi 1779345322  686 GTVSANATLTV 696
Cdd:cd20976     80 GQVSCSAWVTV 90

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 70.60 E-value: 7.60e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  702 LAQDLEDRSVTVGETVALQCKALGSPPPRITWLHNDQPLRPSDRHHFTPGNQLLVIGSALLKDAGRYTCLMSNTLGTERA 781
Cdd:cd20952      2 ILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDERITTLENGSLQIKGAEKSDTGEYTCVALNLSGEATW 81


                   ....*.
gi 1779345322  782 HSQLVV 787
Cdd:cd20952     82 SAVLDV 87

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 69.90 E-value: 1.24e-14

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1779345322  710 SVTVGETVALQCKALGSPPPRITWLHNDQPLRPSD--RHHFTPGNQLLVIGSALLKDAGRYTCLMSN 774
Cdd:pfam13927   12 TVREGETVTLTCEATGSPPPTITWYKNGEPISSGStrSRSLSGSNSTLTISNVTRSDAGTYTCVASN 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: 69.91 E-value: 1.45e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  609 IKTPRDSTIRTGHTARLECAAEGHPTPQIAWQKDGGtdfPAARDRRMHVMPDDD---VFFITDVKPVDMGVYSCTAKNTA 685
Cdd:cd20973      1 IQTLRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDN---PIVESRRFQIDQDEDglcSLIISDVCGDDSGKYTCKAVNSL 77

                           90
                   ....*....|.
gi 1779345322  686 GTVSANATLTV 696
Cdd:cd20973     78 GEATCSAELTV 88

Leucine rich repeat;

Pssm-ID: 404697 [Multi-domain] Cd Length: 61 Bit Score: 68.71 E-value: 2.01e-14

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1779345322  230 SSLEVLKLQRNSISKLTDGAFFDLSKMKVLHLDYNSLTEVNSGSLYGLTSLQQLFLSNNSI 290
Cdd:pfam13855    1 PNLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

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: 69.46 E-value: 2.05e-14

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322   707 EDRSVTVGETVALQCKALGSPPPRITWLHND-QPLRPSDRHHFTPGNQL--LVIGSALLKDAGRYTCLMSNTLGTERAHS 783
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGgKLLAESGRFSVSRSGSTstLTISNVTPEDSGTYTCAATNSSGSASSGT 81


                    ....
gi 1779345322   784 QLVV 787
Cdd:smart00410   82 TLTV 85

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: 69.45 E-value: 2.10e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  606 PSFIKTPRDSTIRTGHTARLECAAEGHPTPQIAWQKDGGTDFPAARDRRMHVMPDDDVFFITDVKPVDMGVYSCTAKNTA 685
Cdd:cd05744      1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVRENGRHSLIIEPVTKRDAGIYTCIARNRA 80

                           90
                   ....*....|.
gi 1779345322  686 GTVSANATLTV 696
Cdd:cd05744     81 GENSFNAELVV 91

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: 69.51 E-value: 2.72e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  606 PSFIKTPRDSTIRTGHTARLECAAEGHPTPQIAWQKDGgtdFPAARDRRM----HVMPDDDV---FFITDVKPVDMGVYS 678
Cdd:cd20956      2 PVLLETFSEQTLQPGPSVSLKCVASGNPLPQITWTLDG---FPIPESPRFrvgdYVTSDGDVvsyVNISSVRVEDGGEYT 78

                           90
                   ....*....|....*...
gi 1779345322  679 CTAKNTAGTVSANATLTV 696
Cdd:cd20956     79 CTATNDVGSVSHSARINV 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: 68.43 E-value: 5.64e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  700 PHLAQDLEDRSVTVGETVALQCKALGSPPPRITWLHNDQPLR-PSDRHHFTPGNQLLVIGSALLKDAGRYTCLMSNTLGT 778
Cdd:cd20976      2 PSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQyAADRSTCEAGVGELHIQDVLPEDHGTYTCLAKNAAGQ 81


                   ....*....
gi 1779345322  779 ERAHSQLVV 787
Cdd:cd20976     82 VSCSAWVTV 90

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: 67.29 E-value: 1.54e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  608 FIKTPRDSTIRTGHTARLECAAEGHPTPQIAWQKDGGTDF-----PAARDRRMHVMPDDDVfFITDVKPVDMGVYSCTAK 682
Cdd:cd05726      2 FVVKPRDQVVALGRTVTFQCETKGNPQPAIFWQKEGSQNLlfpyqPPQPSSRFSVSPTGDL-TITNVQRSDVGYYICQAL 80

                           90
                   ....*....|....
gi 1779345322  683 NTAGTVSANATLTV 696
Cdd:cd05726     81 NVAGSILAKAQLEV 94

Leucine rich repeat;

Pssm-ID: 404697 [Multi-domain] Cd Length: 61 Bit Score: 66.01 E-value: 1.58e-13

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1779345322  302 QKLRELNLSYNNLTRLDEGSLAVLGDLHTLRLGHNSISHINEGAFRGLKALRILELDHNDI 362
Cdd:pfam13855    1 PNLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

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: 66.66 E-value: 1.80e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  612 PRDSTIRTGHTARLECAA-EGHPTPQIAWQKDGGTdfPAARDRRMHVMpDDDVFFITDVKPVDMGVYSCTAKNTAGT-VS 689
Cdd:cd05724      4 PSDTQVAVGEMAVLECSPpRGHPEPTVSWRKDGQP--LNLDNERVRIV-DDGNLLIAEARKSDEGTYKCVATNMVGErES 80


                   ....*..
gi 1779345322  690 ANATLTV 696
Cdd:cd05724     81 RAARLSV 87

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

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 66.76 E-value: 2.43e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  612 PRDSTIRTGHTARLECAAEGHPTPQIAWQKDGGTdfPAARDRRMHVMPDDDVFFITDVKPVDMGVYSCTAKNTA-GTVSA 690
Cdd:cd20970      9 SFTVTAREGENATFMCRAEGSPEPEISWTRNGNL--IIEFNTRYIVRENGTTLTIRNIRRSDMGIYLCIASNGVpGSVEK 86


                   ....*.
gi 1779345322  691 NATLTV 696
Cdd:cd20970     87 RITLQV 92

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: 6.79e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  608 FIKTPRDSTIRTGHTARLECAAEGHPTPQIAWQKDGGTDfpAARDRRMHVMPdDDVFFITDVKPVDMGVYSCTAKNTAGT 687
Cdd:cd20952      2 ILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPL--LGKDERITTLE-NGSLQIKGAEKSDTGEYTCVALNLSGE 78


                   ....*....
gi 1779345322  688 VSANATLTV 696
Cdd:cd20952     79 ATWSAVLDV 87

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: 65.13 E-value: 7.36e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  606 PSFIKTPRDSTIRTGHTARLECAAEGHPTPQIAWQKDGGTDFPAARDRRMHVMPDDDV--FFITDVKPVDMGVYSCTAKN 683
Cdd:cd20951      1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDPSSIPGKYKIESEYGVhvLHIRRVTVEDSAVYSAVAKN 80

                           90
                   ....*....|...
gi 1779345322  684 TAGTVSANATLTV 696
Cdd:cd20951     81 IHGEASSSASVVV 93

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

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 64.27 E-value: 7.98e-13

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1779345322  717 VALQCKALGSPPPRITWLHNDQPLRPS--DRHHFTPGNQLLVIGSALLKDAGRYTCLMSNTLGTERAHS 783
Cdd:cd00096      1 VTLTCSASGNPPPTITWYKNGKPLPPSsrDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASAS 69

type III secretion system effector E3 ubiquitin transferase SlrP;

Pssm-ID: 185268 [Multi-domain] Cd Length: 754 Bit Score: 72.04 E-value: 1.37e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322   52 LELTATPLDLPVRTVSLNLGHNQLTSIsPEafaNL-PNLRELRLDHNELTSIPdlgqaaskivslylhhnkirsidgrrt 130
Cdd:PRK15370   188 LGLTTIPACIPEQITTLILDNNELKSL-PE---NLqGNIKTLYANSNQLTSIP--------------------------- 236

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  131 gELL--SVETLDLSNNDITELRgQCFPAGLhiRDLYLSNNKISVLElgalDHLGETLQVLRLSRNRISQIPVkafQLPrl 208
Cdd:PRK15370   237 -ATLpdTIQEMELSINRITELP-ERLPSAL--QSLDLFHNKISCLP----ENLPEELRYLSVYDNSIRTLPA---HLP-- 303

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  209 tqlelnrnrirqvegltfqglSSLEVLKLQRNSISKLTDGAFFDLskmKVLHLDYNSLTEVNSgSLygLTSLQQLFLSNN 288
Cdd:PRK15370   304 ---------------------SGITHLNVQSNSLTALPETLPPGL---KTLEAGENALTSLPA-SL--PPELQVLDVSKN 356

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  289 SIArINPDgwKFCQKLRELNLSYNNLTRLDEGSLAVlgdLHTLRLGHNSISHINEG--AFR--GLKALRILeLDHNDISG 364
Cdd:PRK15370   357 QIT-VLPE--TLPPTITTLDVSRNALTNLPENLPAA---LQIMQASRNNLVRLPESlpHFRgeGPQPTRII-VEYNPFSE 429

                          330
                   ....*....|....
gi 1779345322  365 -TIEDTNGAFSGLD 377
Cdd:PRK15370   430 rTIQNMQRLMSSVG 443

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: 64.15 E-value: 1.84e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  608 FIKTPRDSTIRTGHTARLECAAEGHPTPQIAWQKDGGTDFPAARDRRMHVmpDDDVFFITDVKPVDMGVYSCTAKNTAGT 687
Cdd:cd05867      2 WTRRPQSHLYGPGETARLDCQVEGIPTPNITWSINGAPIEGTDPDPRRHV--SSGALILTDVQPSDTAVYQCEARNRHGN 79

                           90
                   ....*....|
gi 1779345322  688 VSANATLTVL 697
Cdd:cd05867     80 LLANAHVHVV 89

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: 63.95 E-value: 2.11e-12

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1779345322  710 SVTVGETVALQCKALGSPPPRITWLHNDQPL-RPSDRHHFTPGNqlLVIGSALLKDAGRYTCLMSNTLGTERAHSQLVV 787
Cdd:cd20978     12 VVKGGQDVTLPCQVTGVPQPKITWLHNGKPLqGPMERATVEDGT--LTIINVQPEDTGYYGCVATNEIGDIYTETLLHV 88

Leucine rich repeat;

Pssm-ID: 404697 [Multi-domain] Cd Length: 61 Bit Score: 62.93 E-value: 2.18e-12

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1779345322  206 PRLTQLELNRNRIRQVEGLTFQGLSSLEVLKLQRNSISKLTDGAFFDLSKMKVLHLDYNSL 266
Cdd:pfam13855    1 PNLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

Leucine rich repeat;

Pssm-ID: 404697 [Multi-domain] Cd Length: 61 Bit Score: 60.62 E-value: 1.48e-11

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1779345322  254 SKMKVLHLDYNSLTEVNSGSLYGLTSLQQLFLSNNSIARINPDGWKFCQKLRELNLSYNNL 314
Cdd:pfam13855    1 PNLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 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: 61.44 E-value: 1.60e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  700 PHLAQDLEDRSVTVGETVALQCKALGSPPPRITWLHNDQPLRPSDRHHFTPGNQL--LVIGSALLKDAGRYTCLMSNTLG 777
Cdd:cd20972      2 PQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSPDIQIHQEGDLhsLIIAEAFEEDTGRYSCLATNSVG 81

                           90
                   ....*....|
gi 1779345322  778 TERAHSQLVV 787
Cdd:cd20972     82 SDTTSAEIFV 91

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: 60.42 E-value: 1.80e-11

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1779345322  623 ARLECAAEGHPTPQIAWQKDGGTDFPAARDRRMHVmPDDDVFFITDVKPVDMGVYSCTAKNTA-GTVSANA 692
Cdd:cd00096      1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSE-LGNGTLTISNVTLEDSGTYTCVASNSAgGSASASV 70

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: 61.06 E-value: 2.53e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  606 PSFIKTPRDSTIRTGHTARLECAAEGHPTPQIAWQKDgGTDFPAARDRRMHVMPDDDVFFITDVKPVDMGVYSCTAKNTA 685
Cdd:cd20972      2 PQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCE-GKELQNSPDIQIHQEGDLHSLIIAEAFEEDTGRYSCLATNSV 80

                           90
                   ....*....|.
gi 1779345322  686 GTVSANATLTV 696
Cdd:cd20972     81 GSDTTSAEIFV 91

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: 60.31 E-value: 2.96e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  608 FIKTPRDSTIRTGHTARLECAAEGHPTPQIAWQKDGGtdfPAARDRRMHVMPDDdvFFITDVKPVDMGVYSCTAKNTAGT 687
Cdd:cd05728      2 WLKVISDTEADIGSSLRWECKASGNPRPAYRWLKNGQ---PLASENRIEVEAGD--LRITKLSLSDSGMYQCVAENKHGT 76


                   ....*....
gi 1779345322  688 VSANATLTV 696
Cdd:cd05728     77 IYASAELAV 85

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: 65.07 E-value: 5.47e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  185 LQVLRLSRN-----RISQIPVKAFQLPRLTQLELNRN------RIRQVEGLTFQGLSSLEVLKLQRNSISKLTDGAFFDL 253
Cdd:cd00116     25 LQVLRLEGNtlgeeAAKALASALRPQPSLKELCLSLNetgripRGLQSLLQGLTKGCGLQELDLSDNALGPDGCGVLESL 104

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  254 SK---MKVLHLDYNSLtEVNSGSLY--GLTSLQ----QLFLSNNSIARINPDGW----KFCQKLRELNLSYNNLTrlDEG 320
Cdd:cd00116    105 LRsssLQELKLNNNGL-GDRGLRLLakGLKDLPpaleKLVLGRNRLEGASCEALakalRANRDLKELNLANNGIG--DAG 181

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  321 ------SLAVLGDLHTLRLGHNSISHIN----EGAFRGLKALRILELDHNDIS--GTIEDTNGAFSGLDSLIKLTLFENK 388
Cdd:cd00116    182 iralaeGLKANCNLEVLDLNNNGLTDEGasalAETLASLKSLEVLNLGDNNLTdaGAAALASALLSPNISLLTLSLSCND 261

                          250       260
                   ....*....|....*....|....*..
gi 1779345322  389 IKSVAKKAFSGL----ETLEHLNLGEN 411
Cdd:cd00116    262 ITDDGAKDLAEVlaekESLLELDLRGN 288

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: 59.78 E-value: 5.55e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  606 PSFIKTPRDSTIRTGHTARLECAAEGHPTPQIAWQKDG-----GTDfpaardrRMHVMPDDD---VFFITDVKPVDMGVY 677
Cdd:cd05892      1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKKNNemlqyNTD-------RISLYQDNCgriCLLIQNANKKDAGWY 73

                           90
                   ....*....|....*....
gi 1779345322  678 SCTAKNTAGTVSANATLTV 696
Cdd:cd05892     74 TVSAVNEAGVVSCNARLDV 92

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: 59.73 E-value: 5.80e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  606 PSFIKTPRDSTIRTGHTARLECAAEGHPTPQIAWQKDGGTDFPAARDRRMHVMPDDDVFFITDVKPVDMGVYSCTAKNTA 685
Cdd:cd20990      1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSAHKMLVRENGVHSLIIEPVTSRDAGIYTCIATNRA 80

                           90
                   ....*....|.
gi 1779345322  686 GTVSANATLTV 696
Cdd:cd20990     81 GQNSFNLELVV 91

Leucine rich repeat;

Pssm-ID: 404697 [Multi-domain] Cd Length: 61 Bit Score: 58.69 E-value: 6.67e-11

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  378 SLIKLTLFENKIKSVAKKAFSGLETLEHLNLGENAIRSIQPDAFTKMRNLKSLLIQSNSL 437
Cdd:pfam13855    2 NLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

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: 59.01 E-value: 1.01e-10

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1779345322  711 VTVGETVALQCKALGSPPPRITWLHNDQPLRPSDRHHFTPgNQLLVIGSALLKDAGRYTCLMSNTLGTERAHSQLVV 787
Cdd:cd04969     14 AAKGGDVIIECKPKASPKPTISWSKGTELLTNSSRICILP-DGSLKIKNVTKSDEGKYTCFAVNFFGKANSTGSLSV 89

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: 58.81 E-value: 1.39e-10

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1779345322  714 GETVALQCKALGSPPPRITWLHNDQPLRP--SDRHHFTPGNQLLVIGSALLKDAGRYTCLMSNTLGTERAHSQLVVTE 789
Cdd:cd05736     15 GVEASLRCHAEGIPLPRVQWLKNGMDINPklSKQLTLIANGSELHISNVRYEDTGAYTCIAKNEGGVDEDISSLFVED 92

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: 1.88e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  606 PSFIKTPRDSTIRTGHTARLECAAEGHPTPQIAWQKDggtdfpaARDRRMHVMPDDDV-----------FFITDVKPVDM 674
Cdd:cd05765      1 PALVNSPTHQTVKVGETASFHCDVTGRPQPEITWEKQ-------VPGKENLIMRPNHVrgnvvvtnigqLVIYNAQPQDA 73

                           90       100
                   ....*....|....*....|..
gi 1779345322  675 GVYSCTAKNTAGTVSANATLTV 696
Cdd:cd05765     74 GLYTCTARNSGGLLRANFPLSV 95

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: 63.14 E-value: 2.26e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322   81 EAFANLPNLRELRLDHNELT--SIPDLGQAA---SKIVSLYLHHNKIRSI--------DGRRTGELLSveTLDLSNNDIT 147
Cdd:cd00116     17 ELLPKLLCLQVLRLEGNTLGeeAAKALASALrpqPSLKELCLSLNETGRIprglqsllQGLTKGCGLQ--ELDLSDNALG 94

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  148 ELRGQCFPAGLHI---RDLYLSNNKISVLEL----GALDHLGETLQVLRLSRNRISQIPV----KAFQ-LPRLTQLELNR 215
Cdd:cd00116     95 PDGCGVLESLLRSsslQELKLNNNGLGDRGLrllaKGLKDLPPALEKLVLGRNRLEGASCealaKALRaNRDLKELNLAN 174

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  216 NRIRqVEGLT--FQGL---SSLEVLKLQRNSI----SKLTDGAFFDLSKMKVLHLDYNSLTEVnsgslyGLTSLQQLFLS 286
Cdd:cd00116    175 NGIG-DAGIRalAEGLkanCNLEVLDLNNNGLtdegASALAETLASLKSLEVLNLGDNNLTDA------GAAALASALLS 247

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*..
gi 1779345322  287 NNsiarinpdgwkfcQKLRELNLSYNNLTRLDEGSLA-VLGDLHTLR 332
Cdd:cd00116    248 PN-------------ISLLTLSLSCNDITDDGAKDLAeVLAEKESLL 281

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: 57.64 E-value: 2.33e-10

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1779345322  620 GHTARLECAAEGHPTPQIAWQKDGGtdfPAARDRRmHVMPDDDVFFITDVKPVDMGVYSCTAKNTAGTVSANATLTV 696
Cdd:cd05745      2 GQTVDFLCEAQGYPQPVIAWTKGGS---QLSVDRR-HLVLSSGTLRISRVALHDQGQYECQAVNIVGSQRTVAQLTV 74

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: 57.93 E-value: 2.39e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  612 PRDSTIRTGHTARLECAAEGHPTPQIAWQKDGGtdfPAARDRRMHVMpDDDVFFITDVKPVDMGVYSCTAKNTAGTVSAN 691
Cdd:cd20957      8 PPVQTVDFGRTAVFNCSVTGNPIHTVLWMKDGK---PLGHSSRVQIL-SEDVLVIPSVKREDKGMYQCFVRNDGDSAQAT 83


                   ...
gi 1779345322  692 ATL 694
Cdd:cd20957     84 AEL 86

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: 57.56 E-value: 3.02e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  703 AQDLEDRSVTVGETVALQCKALGSPPPRITWLHNDQPLRPSDRHHFTPGnqLLVIGSALLKDAGRYTCLMSNTLGTERAH 782
Cdd:cd04968      5 VRFPADTYALKGQTVTLECFALGNPVPQIKWRKVDGSPSSQWEITTSEP--VLEIPNVQFEDEGTYECEAENSRGKDTVQ 82


                   ....*
gi 1779345322  783 SQLVV 787
Cdd:cd04968     83 GRIIV 87

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: 57.42 E-value: 3.05e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  620 GHTARLECAAEGHPTPQIAWQKDGGtDFPAARdrrmhvmPDDDVF----FITDVKPVDMGVYSCTAKNTAGTVSANATLT 695
Cdd:cd05731     10 GGVLLLECIAEGLPTPDIRWIKLGG-ELPKGR-------TKFENFnktlKIENVSEADSGEYQCTASNTMGSARHTISVT 81


                   .
gi 1779345322  696 V 696
Cdd:cd05731     82 V 82

Leucine rich repeat;

Pssm-ID: 404697 [Multi-domain] Cd Length: 61 Bit Score: 56.76 E-value: 3.41e-10

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  184 TLQVLRLSRNRISQIPVKAFQ-LPRLTQLELNRNRIRQVEGLTFQGLSSLEVLKLQRNSI 242
Cdd:pfam13855    2 NLRSLDLSNNRLTSLDDGAFKgLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 57.58 E-value: 3.60e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  704 QDLEDRSVTVGETVALQCKALGSPPPRITWLHNDQPLRPSDRHHFT---PGNQLLVIGSALLKDAGRYTCLMSNTLGTER 780
Cdd:cd20973      2 QTLRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDqdeDGLCSLIISDVCGDDSGKYTCKAVNSLGEAT 81


                   ....*..
gi 1779345322  781 AHSQLVV 787
Cdd:cd20973     82 CSAELTV 88

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: 57.75 E-value: 3.83e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  606 PSFIKTPRDSTIRTGHTARLECAAEGHPTPQIAWQKDG-GTDFPAARDRRMHVMPDDDVFFITDVKPVDMGVYSCTAKNT 684
Cdd:cd20974      1 PVFTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFRDGqVISTSTLPGVQISFSDGRAKLSIPAVTKANSGRYSLTATNG 80

                           90
                   ....*....|...
gi 1779345322  685 AGTVSANATLTVL 697
Cdd:cd20974     81 SGQATSTAELLVL 93

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; depending on isoform composition it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 143224 [Multi-domain] Cd Length: 92 Bit Score: 57.37 E-value: 4.52e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  709 RSVTV--GETVALQCKALGSPPPRITWLHNDQPLRPSDRHHFTPGN--QLLVIGSALLKDAGRYTCLMSNTLGTERAHSQ 784
Cdd:cd05747     11 RSLTVseGESARFSCDVDGEPAPTVTWMREGQIIVSSQRHQITSTEykSTFEISKVQMSDEGNYTVVVENSEGKQEAQFT 90


                   .
gi 1779345322  785 L 785
Cdd:cd05747     91 L 91

Leucine rich repeat C-terminal domain;

Pssm-ID: 214507 [Multi-domain] Cd Length: 51 Bit Score: 55.90 E-value: 4.77e-10

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|..
gi 1779345322   435 NSLLCDCQLHWLPDWLVARG-LQVGINATCAHPESLKGKsVFEVPPSSFVCD 485
Cdd:smart00082    1 NPFICDCELRWLLRWLQANEhLQDPVDLRCASPSSLRGP-LLELLHSEFKCP 51

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

Pssm-ID: 409546 [Multi-domain] Cd Length: 96 Bit Score: 57.32 E-value: 5.15e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  606 PSFIKTPRDSTIRTGHTARLECAAEGHPTPQIAWQKDGGT------DFpaARDRRMHVMPDDDVFFiTDVKPVDMGVYSC 679
Cdd:cd20954      2 PRWIVEPVDANVAAGQDVMLHCQADGFPTPTVTWKKATGStpgeykDL--LYDPNVRILPNGTLVF-GHVQKENEGHYLC 78

                           90
                   ....*....|....*...
gi 1779345322  680 TAKNTAGT-VSANATLTV 696
Cdd:cd20954     79 EAKNGIGSgLSKVIFLKV 96

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: 56.49 E-value: 5.78e-10

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1779345322  714 GETVALQCKALGSPPPRITWLHNDQPLrPSDRHHFTPGNQLLVIGSALLKDAGRYTCLMSNTLGTERAHSQLVV 787
Cdd:cd05745      2 GQTVDFLCEAQGYPQPVIAWTKGGSQL-SVDRRHLVLSSGTLRISRVALHDQGQYECQAVNIVGSQRTVAQLTV 74

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: 56.63 E-value: 5.87e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  708 DRSVTVGETVALQCKALGSPPPRITWLHNDQPLrPSDRHHFTPGNQLLvIGSALLKDAGRYTCLMSNTLGTERAHSQLVV 787
Cdd:cd05725      6 NQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGEL-PKGRYEILDDHSLK-IRKVTAGDMGSYTCVAENMVGKIEASATLTV 83

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: 56.84 E-value: 6.66e-10

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1779345322  710 SVTVGETVALQCKALGSPPPRITWLHNDQPLRPSDR--------HHFTpgnqlLVIGSALLKDAGRYTCLMSNTLGT 778
Cdd:cd05729     15 ALPAANKVRLECGAGGNPMPNITWLKDGKEFKKEHRiggtkveeKGWS-----LIIERAIPRDKGKYTCIVENEYGS 86

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: 56.79 E-value: 7.96e-10

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1779345322  710 SVTVGETVALQCKALGSPPPRITWLHNDQPLRPSDR---HHFTPGNQLLVIGSALLKDAGRYTCLMSNTLGT 778
Cdd:cd05857     15 AVPAANTVKFRCPAAGNPTPTMRWLKNGKEFKQEHRiggYKVRNQHWSLIMESVVPSDKGNYTCVVENEYGS 86

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: 62.11 E-value: 9.26e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322   52 LELTATPLDLPvrTVSLNLGHNQLTSISPEAFANLPNLREL-RLDHNEL-TSIPDLGQAASKIVSLYLHH---------- 119
Cdd:COG5238    105 LAETATAVATP--PPDLRRIMAKTLEDSLILYLALPRRINLiQVLKDPLgGNAVHLLGLAARLGLLAAISmakalqnnsv 182

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  120 -------NKIRSIDGRRTGELL----SVETLDLSNNDITELRGQCFPAGL----HIRDLYLSNNKISVLELGAL-DHL-- 181
Cdd:COG5238    183 etvylgcNQIGDEGIEELAEALtqntTVTTLWLKRNPIGDEGAEILAEALkgnkSLTTLDLSNNQIGDEGVIALaEALkn 262

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  182 GETLQVLRLSRNRISQIPVKAF-----QLPRLTQLELNRNRIRQ------VEGLtfQGLSSLEVLKLQRNSISklTDGAF 250
Cdd:COG5238    263 NTTVETLYLSGNQIGAEGAIALakalqGNTTLTSLDLSVNRIGDegaialAEGL--QGNKTLHTLNLAYNGIG--AQGAI 338

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  251 F------DLSKMKVLHLDYNSLTEVnsgslyGLTSLQQlFLSNNsiarinpdgwkfcQKLRELNLSYNNLTrlDEGSLAV 324
Cdd:COG5238    339 AlakalqENTTLHSLDLSDNQIGDE------GAIALAK-YLEGN-------------TTLRELNLGKNNIG--KQGAEAL 396

                          330
                   ....*....|....*....
gi 1779345322  325 L-----GDLHTLRLGHNSI 338
Cdd:COG5238    397 IdalqtNRLHTLILDGNLI 415

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: 56.31 E-value: 1.00e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  606 PSFIKTP--RDSTIRTGHTARLECAAEGHPTPQIAWQKDGGTdfpAARDRRMHVMPDDDVFfITDVKPVDMGVYSCTAKN 683
Cdd:cd04969      1 PDFELNPvkKKILAAKGGDVIIECKPKASPKPTISWSKGTEL---LTNSSRICILPDGSLK-IKNVTKSDEGKYTCFAVN 76

                           90
                   ....*....|...
gi 1779345322  684 TAGTVSANATLTV 696
Cdd:cd04969     77 FFGKANSTGSLSV 89

Leucine rich repeat;

Pssm-ID: 404697 [Multi-domain] Cd Length: 61 Bit Score: 55.22 E-value: 1.03e-09

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1779345322   67 SLNLGHNQLTSISPEAFANLPNLRELRLDHNELTSI-PDLGQAASKIVSLYLHHNKI 122
Cdd:pfam13855    5 SLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLsPGAFSGLPSLRYLDLSGNRL 61

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

Pssm-ID: 409548 [Multi-domain] Cd Length: 96 Bit Score: 56.03 E-value: 1.26e-09

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1779345322  714 GETVALQCKALGSPPPRITWLHNDQPLRPSDR----HHFTPGNQL---LVIGSALLKDAGRYTCLMSNTLGT 778
Cdd:cd20956     16 GPSVSLKCVASGNPLPQITWTLDGFPIPESPRfrvgDYVTSDGDVvsyVNISSVRVEDGGEYTCTATNDVGS 87

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 55.65 E-value: 1.27e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  489 KPQITVQPEATMTVLGSDVRLTCTaaSSSSSPMTFAWRKDQELLRNAEMENYAHVrahhqaatpdlpgaggggvmEYTTI 568
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVTLTCE--ATGSPPPTITWYKNGEPISSGSTRSRSLS--------------------GSNST 58

                           90       100
                   ....*....|....*....|
gi 1779345322  569 LHLRRVTFAHEGRYQCIITN 588
Cdd:pfam13927   59 LTISNVTRSDAGTYTCVASN 78

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: 55.94 E-value: 1.32e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  700 PHLAQDLEDRSVTVGETVALQCKALGSPPPRITWLHNDQPLRPSDR---HHFTPGNQLLVIGSALLKDAGRYTCLMSNTL 776
Cdd:cd20975      1 PTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRrfaEEAEGGLCRLRILAAERGDAGFYTCKAVNEY 80

                           90
                   ....*....|.
gi 1779345322  777 GTERAHSQLVV 787
Cdd:cd20975     81 GARQCEARLEV 91

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

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 55.87 E-value: 1.33e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  708 DRSVTVGETVALQCKA-LGSPPPRITWLHNDQPLRPSD--RHHFTPGNqlLVIGSALLKDAGRYTCLMSNTLGT-ERAHS 783
Cdd:cd05724      6 DTQVAVGEMAVLECSPpRGHPEPTVSWRKDGQPLNLDNerVRIVDDGN--LLIAEARKSDEGTYKCVATNMVGErESRAA 83


                   ....
gi 1779345322  784 QLVV 787
Cdd:cd05724     84 RLSV 87

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

Pssm-ID: 409391 [Multi-domain] Cd Length: 98 Bit Score: 56.12 E-value: 1.45e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  707 EDRSVTVGETVALQCKALGSPPPRITW--------LHNDQPLRPSDRHHFTPGNQlLVIGSALLKDAGRYTCLMSNTLGT 778
Cdd:cd05726      7 RDQVVALGRTVTFQCETKGNPQPAIFWqkegsqnlLFPYQPPQPSSRFSVSPTGD-LTITNVQRSDVGYYICQALNVAGS 85

                           90
                   ....*....|.
gi 1779345322  779 ERAHSQLVVTE 789
Cdd:cd05726     86 ILAKAQLEVTD 96

Leucine rich repeat;

Pssm-ID: 404697 [Multi-domain] Cd Length: 61 Bit Score: 54.84 E-value: 1.48e-09

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1779345322  135 SVETLDLSNNDITELRGQCFPAGLHIRDLYLSNNKISVLELGALDHLGEtLQVLRLSRNRI 195
Cdd:pfam13855    2 NLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPS-LRYLDLSGNRL 61

Leucine rich repeat;

Pssm-ID: 404697 [Multi-domain] Cd Length: 61 Bit Score: 54.84 E-value: 1.62e-09

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1779345322  328 LHTLRLGHNSISHINEGAFRGLKALRILELDHNDISgTIEdtNGAFSGLDSLIKLTLFENKI 389
Cdd:pfam13855    3 LRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLT-TLS--PGAFSGLPSLRYLDLSGNRL 61

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

Pssm-ID: 143223 Cd Length: 69 Bit Score: 54.88 E-value: 1.62e-09

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1779345322  624 RLECAAEGHPTPQIAWQKDGgtdFPAARDRRMHVMPdDDVFFITDVKPVDMGVYSCTAKNTAGTVSANATLT 695
Cdd:cd05746      2 QIPCSAQGDPEPTITWNKDG---VQVTESGKFHISP-EGYLAIRDVGVADQGRYECVARNTIGYASVSMVLS 69

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: 55.88 E-value: 1.66e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  700 PHLAQDLEDRSVTVGETVALQCKALGSPPPRITWLHNDQPLRPSDRHHF---TPGNQLLVIGSALLKDAGRYTCLMSNTL 776
Cdd:cd20990      1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSAHKMlvrENGVHSLIIEPVTSRDAGIYTCIATNRA 80

                           90
                   ....*....|.
gi 1779345322  777 GTERAHSQLVV 787
Cdd:cd20990     81 GQNSFNLELVV 91

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: 55.55 E-value: 1.80e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  700 PHLAQDLEDRSVTVGETVALQCKALGSPPPRITWLHNDQPLrPSDRHHFTPGNQ-----LLVIGSALLKDAGRYTCLMSN 774
Cdd:cd20971      2 PHFKEELRNLNVRYQSNATLVCKVTGHPKPIVKWYRQGKEI-IADGLKYRIQEFkggyhQLIIASVTDDDATVYQVRATN 80


                   ...
gi 1779345322  775 TLG 777
Cdd:cd20971     81 QGG 83

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

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 55.59 E-value: 2.08e-09

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1779345322  704 QDLEDRSVTVGETVALQCKALGSPPPRITWLHND-QPLRPSDRHHFTPGNQLLVIGSALLKDAGRYTCLMSN 774
Cdd:cd20970      7 QPSFTVTAREGENATFMCRAEGSPEPEISWTRNGnLIIEFNTRYIVRENGTTLTIRNIRRSDMGIYLCIASN 78

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: 55.30 E-value: 2.15e-09

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1779345322  714 GETVALQCKALGSPPPRITWLHNDQPLrPSDRHHFTPGNQLLVIGSALLKDAGRYTCLMSNTLGTERAHSQLVV 787
Cdd:cd05876     10 GQSLVLECIAEGLPTPTVKWLRPSGPL-PPDRVKYQNHNKTLQLLNVGESDDGEYVCLAENSLGSARHAYYVTV 82

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: 55.09 E-value: 2.56e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  606 PSFIKTPRDSTIRT-GHTARLECAAEGHPTPQIAWQKDGGtdfPAARDR-RMHVmpDDDVFFITDVKPVDMGVYSCTAKN 683
Cdd:cd20978      1 PKFIQKPEKNVVVKgGQDVTLPCQVTGVPQPKITWLHNGK---PLQGPMeRATV--EDGTLTIINVQPEDTGYYGCVATN 75

                           90
                   ....*....|...
gi 1779345322  684 TAGTVSANATLTV 696
Cdd:cd20978     76 EIGDIYTETLLHV 88

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: 54.91 E-value: 2.56e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  704 QDLEDRSVTVGETVALQCKALGSPPPRITWLHNDQPLRPSDRHHFTPGNqlLVIGSALLKDAGRYTCLMSNTLGTERAHS 783
Cdd:cd05728      4 KVISDTEADIGSSLRWECKASGNPRPAYRWLKNGQPLASENRIEVEAGD--LRITKLSLSDSGMYQCVAENKHGTIYASA 81


                   ....
gi 1779345322  784 QLVV 787
Cdd:cd05728     82 ELAV 85

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: 54.86 E-value: 2.69e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  609 IKTPRDSTIRTGHTARLECAAEGHPTPQIAWQKDGGTDFPAARDRRmhvmpDDDVFFITDVKPVDMGVYSCTAKNTAGTV 688
Cdd:cd04968      5 VRFPADTYALKGQTVTLECFALGNPVPQIKWRKVDGSPSSQWEITT-----SEPVLEIPNVQFEDEGTYECEAENSRGKD 79


                   ....*...
gi 1779345322  689 SANATLTV 696
Cdd:cd04968     80 TVQGRIIV 87

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: 55.33 E-value: 2.77e-09

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  715 ETVALQCKALGSPPPRITWLHN--DQPLRPSDRHHFTPGNqlLVIGSAL-LKDAGRYTCLMSNTLGTERA 781
Cdd:cd04967     20 KKVALNCRARANPVPSYRWLMNgtEIDLESDYRYSLVDGT--LVISNPSkAKDAGHYQCLATNTVGSVLS 87

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: 54.55 E-value: 4.42e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  699 TPHlaqdleDRSVTVGETVALQCKALGSPPPRITWLHN---DQPLRPSDRHHFTPGNQLLVIGSALLKDAGRYTCLMSNT 775
Cdd:cd05763      5 TPH------DITIRAGSTARLECAATGHPTPQIAWQKDggtDFPAARERRMHVMPEDDVFFIVDVKIEDTGVYSCTAQNS 78

                           90
                   ....*....|..
gi 1779345322  776 LGTERAHSQLVV 787
Cdd:cd05763     79 AGSISANATLTV 90

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: 54.57 E-value: 4.85e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  611 TPRDSTIRTGHTARLECAAEGHPTPQIAWQKDgGTDFPAARDRRMHVMPDDDVFFITDVKPVDMGVYSCTAKNTAGTVSA 690
Cdd:cd05736      6 YPEFQAKEPGVEASLRCHAEGIPLPRVQWLKN-GMDINPKLSKQLTLIANGSELHISNVRYEDTGAYTCIAKNEGGVDED 84


                   ....*....
gi 1779345322  691 NATLTVLET 699
Cdd:cd05736     85 ISSLFVEDS 93

type III secretion system effector E3 ubiquitin transferase SlrP;

Pssm-ID: 185268 [Multi-domain] Cd Length: 754 Bit Score: 60.48 E-value: 5.36e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322   47 VDCSNLELTATPLDLPVRTVSLNLGHNQLTSIsPEafaNLPN-LRELRLDHNELTSIPDlgQAASKIVSLYLHHNKIRSI 125
Cdd:PRK15370   246 MELSINRITELPERLPSALQSLDLFHNKISCL-PE---NLPEeLRYLSVYDNSIRTLPA--HLPSGITHLNVQSNSLTAL 319

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  126 DGRRTgelLSVETLDLSNNDITelrgqCFPAGL--HIRDLYLSNNKISVLElgalDHLGETLQVLRLSRNRISQIPVkaf 203
Cdd:PRK15370   320 PETLP---PGLKTLEAGENALT-----SLPASLppELQVLDVSKNQITVLP----ETLPPTITTLDVSRNALTNLPE--- 384

                          170
                   ....*....|....*.
gi 1779345322  204 QLPRLTQ-LELNRNRI 218
Cdd:PRK15370   385 NLPAALQiMQASRNNL 400

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: 54.15 E-value: 5.69e-09

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1779345322  620 GHTARLECAAEGHPTPQIAWQKDGGTDFPAARDRRMHVMPDDDVFFITDVKPVDMGVYSCTAKNTAGTVSANATLTV 696
Cdd:cd05729     19 ANKVRLECGAGGNPMPNITWLKDGKEFKKEHRIGGTKVEEKGWSLIIERAIPRDKGKYTCIVENEYGSINHTYDVDV 95

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: 54.00 E-value: 5.87e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  700 PHLAQDLEDRSVTVGETVALQCKALGSPPPRITWLHNDQPLRPS-DR---HHFTPGNQLLVIGSALLKDAGRYTCLMSNT 775
Cdd:cd05892      1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKKNNEMLQYNtDRislYQDNCGRICLLIQNANKKDAGWYTVSAVNE 80

                           90
                   ....*....|..
gi 1779345322  776 LGTERAHSQLVV 787
Cdd:cd05892     81 AGVVSCNARLDV 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: 54.28 E-value: 6.11e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  605 LPSFIKT-PRDSTIRTGHTARLECAAEGHPTPQIAWQKDGGtdfPAARDRRMHVMPDD--DVFFITDVKPVDMGVYSCTA 681
Cdd:cd05747      2 LPATILTkPRSLTVSEGESARFSCDVDGEPAPTVTWMREGQ---IIVSSQRHQITSTEykSTFEISKVQMSDEGNYTVVV 78

                           90
                   ....*....|....
gi 1779345322  682 KNTAGTVSANATLT 695
Cdd:cd05747     79 ENSEGKQEAQFTLT 92

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: 53.78 E-value: 6.63e-09

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1779345322  712 TVGETVALQCKALGSPPPRITWLHNDQPLrpSDRHHFTPGnQLLVIGSALLKDAGRYTCLMSNTLGTE--RAHSQLVV 787
Cdd:cd05864     15 KVGERVRIPVKYLGYPPPEIKWYKNGIPI--ESNHTIKAG-HVLTIMEVTEKDAGNYTVVLTNPISKEkqRHTFSLVV 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: 54.02 E-value: 8.51e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  607 SFIKTPRDSTIRTGHTARLECAAEGHPTPQIAWQKDGGTDFPAARDRRmhVMPDDDVFFITDV------KPvDMGVYSCT 680
Cdd:cd05722      3 YFLSEPSDIVAMRGGPVVLNCSAESDPPPKIEWKKDGVLLNLVSDERR--QQLPNGSLLITSVvhskhnKP-DEGFYQCV 79

                           90
                   ....*....|....*...
gi 1779345322  681 AKN-TAGT-VSANATLTV 696
Cdd:cd05722     80 AQNeSLGSiVSRTARVTV 97

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: 53.55 E-value: 1.05e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1779345322  714 GETVALQCKALGSPPPRITWLHNDQPL---RPSDRHHFTPGNQLLViGSALLKDAGRYTCLMSNTLGTERAHSQLVV 787
Cdd:cd20969     17 GHTVQFVCRADGDPPPAILWLSPRKHLvsaKSNGRLTVFPDGTLEV-RYAQVQDNGTYLCIAANAGGNDSMPAHLHV 92

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: 53.71 E-value: 1.09e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  700 PHLAQDLEDRSVTVGETVALQCKALGSPPPRITWLHNDQPLR-----PSDRHHFTPGNQL----LVIGSALLKDAGRYTC 770
Cdd:cd07693      1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLEtdkddPRSHRIVLPSGSLfflrVVHGRKGRSDEGVYVC 80

                           90
                   ....*....|..
gi 1779345322  771 LMSNTLGTERAH 782
Cdd:cd07693     81 VAHNSLGEAVSR 92

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 52.59 E-value: 1.36e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  616 TIRTGHTARLECAAEGHPTPQIAWQKDGgTDFPAARDRRMHVMPDDDVFFITDVKPVDMGVYSCTAKNTAGTVSANATLT 695
Cdd:cd05748      3 VVRAGESLRLDIPIKGRPTPTVTWSKDG-QPLKETGRVQIETTASSTSLVIKNAKRSDSGKYTLTLKNSAGEKSATINVK 81


                   .
gi 1779345322  696 V 696
Cdd:cd05748     82 V 82

Second immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains.

Pssm-ID: 409400 [Multi-domain] Cd Length: 91 Bit Score: 53.09 E-value: 1.41e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  612 PRDSTIRTGHTARLECAAEGHPTPQIAWQKDGGTDFPAARDRRMHvMPDDDVFFITDVKPVDMGVYSCTAKNTAGT-VSA 690
Cdd:cd05738      6 PQLKVVEKARTATMLCAASGNPDPEISWFKDFLPVDTATSNGRIK-QLRSGALQIENSEESDQGKYECVATNSAGTrYSA 84


                   ....*.
gi 1779345322  691 NATLTV 696
Cdd:cd05738     85 PANLYV 90

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: 52.68 E-value: 1.66e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  608 FIKTPRDSTIRTGHTARLECAAEGHPTPQIAWQKDGGTDFPAARDRRMHVmpDDDVFFITDVKPVDMGVYSCTAKNTAGT 687
Cdd:cd05868      2 WITAPTNLVLSPGEDGTLICRANGNPKPSISWLTNGVPIEIAPTDPSRKV--DGDTIIFSKVQERSSAVYQCNASNEYGY 79

                           90
                   ....*....|
gi 1779345322  688 VSANATLTVL 697
Cdd:cd05868     80 LLANAFVNVL 89

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: 57.37 E-value: 1.73e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  260 HLDY--NSLTEVNSGSLYGLT---SLQQLFLSNNSIA----RINPDGWKFCQ-KLRELNLSYNNLTRLDEGSLA----VL 325
Cdd:cd00116     85 ELDLsdNALGPDGCGVLESLLrssSLQELKLNNNGLGdrglRLLAKGLKDLPpALEKLVLGRNRLEGASCEALAkalrAN 164

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  326 GDLHTLRLGHNSISHinEGA---FRGLKA---LRILELDHNdisgTIEDTNG-AFSGldslikltlfenkiksvakkAFS 398
Cdd:cd00116    165 RDLKELNLANNGIGD--AGIralAEGLKAncnLEVLDLNNN----GLTDEGAsALAE--------------------TLA 218

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*..
gi 1779345322  399 GLETLEHLNLGENAIRS-----IQPDAFTKMRNLKSLLIQSNSLLCD 440
Cdd:cd00116    219 SLKSLEVLNLGDNNLTDagaaaLASALLSPNISLLTLSLSCNDITDD 265

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: 52.94 E-value: 1.98e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  700 PHLAQDLEDRSVTVGETVALQCKALGSPPPRITW-LHNDQPLRPSDRHHFTPGNQL------LVIGSALLKDAGRYTCLM 772
Cdd:cd05765      1 PALVNSPTHQTVKVGETASFHCDVTGRPQPEITWeKQVPGKENLIMRPNHVRGNVVvtnigqLVIYNAQPQDAGLYTCTA 80

                           90
                   ....*....|....*
gi 1779345322  773 SNTLGTERAHSQLVV 787
Cdd:cd05765     81 RNSGGLLRANFPLSV 95

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: 52.55 E-value: 2.50e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1779345322  620 GHTARLECAAEGHPTPQIAWQKDGG--TDFPAARDRRMHVmpdddVFFITDVKPVDMGVYSCTAKNTAGTVsaNATLTV 696
Cdd:cd05856     19 GSSVRLKCVASGNPRPDITWLKDNKplTPPEIGENKKKKW-----TLSLKNLKPEDSGKYTCHVSNRAGEI--NATYKV 90

Leucine rich repeat;

Pssm-ID: 404697 [Multi-domain] Cd Length: 61 Bit Score: 50.99 E-value: 2.93e-08

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1779345322  352 LRILELDHNDISGtIEDtnGAFSGLDSLIKLTLFENKIKSVAKKAFSGLETLEHLNLGENAI 413
Cdd:pfam13855    3 LRSLDLSNNRLTS-LDD--GAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

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: 52.09 E-value: 3.27e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1779345322  714 GETVALQCKALGSPPPRITWLHNDQPLRPSDRHHFTPGNQLLVIGSALLKDAGRYTCLMSNTLGTERAHSQLVV 787
Cdd:cd05764     15 GQRATLRCKARGDPEPAIHWISPEGKLISNSSRTLVYDNGTLDILITTVKDTGAFTCIASNPAGEATARVELHI 88

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: 51.78 E-value: 4.15e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  713 VGETVALQCKALGSPPPRITWLHNDQPLRP-----SDRHHFTpgnqlLVIGSALLKDAGRYTCLMSNTLG 777
Cdd:cd05856     18 VGSSVRLKCVASGNPRPDITWLKDNKPLTPpeigeNKKKKWT-----LSLKNLKPEDSGKYTCHVSNRAG 82

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: 56.21 E-value: 4.39e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322   35 PCAQNCTCSGDSVDCSNLELTATPLDLPVRTVSLNLGHNQLTSIS------PEAFANLPNLRELRLDHNELTsiPDLG-- 106
Cdd:cd00116     23 LCLQVLRLEGNTLGEEAAKALASALRPQPSLKELCLSLNETGRIPrglqslLQGLTKGCGLQELDLSDNALG--PDGCgv 100

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  107 -QAASKIVSL---YLHHNKIrsidGRRTGELLSVETLDLSnnditelrgqcfpagLHIRDLYLSNNKisvLELGALDHLG 182
Cdd:cd00116    101 lESLLRSSSLqelKLNNNGL----GDRGLRLLAKGLKDLP---------------PALEKLVLGRNR---LEGASCEALA 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  183 ETLQVLRlsrnrisqipvkafqlpRLTQLELNRNRIRqVEGLT--FQGL---SSLEVLKLQRNSI----SKLTDGAFFDL 253
Cdd:cd00116    159 KALRANR-----------------DLKELNLANNGIG-DAGIRalAEGLkanCNLEVLDLNNNGLtdegASALAETLASL 220

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  254 SKMKVLHLDYNSLT-----EVNSGSLYGLTSLQQLFLSNNSIARInpDGWKFCQ------KLRELNLSYNNLTRLDEGSL 322
Cdd:cd00116    221 KSLEVLNLGDNNLTdagaaALASALLSPNISLLTLSLSCNDITDD--GAKDLAEvlaekeSLLELDLRGNKFGEEGAQLL 298


                   .
gi 1779345322  323 A 323
Cdd:cd00116    299 A 299

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

Pssm-ID: 188093 [Multi-domain] Cd Length: 2740 Bit Score: 57.01 E-value: 6.98e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  407 NLGENAIRSIQPDAFTKMRNLKSLLIQSNSLLCDCQLHWLPDWLVARGLQV--GINATCAHPESLKGKSVFEVPPSSFVC 484
Cdd:TIGR00864    1 DISNNKISTIEEGICANLCNLSEIDLSGNPFECDCGLARLPRWAEEKGVKVrqPEAALCAGPGALAGQPLLGIPLLDSGC 80


                   .
gi 1779345322  485 D 485
Cdd:TIGR00864   81 D 81

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: 50.63 E-value: 8.13e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  609 IKTPRDSTIRTGHTARLECAAEGH-PTPQIAWQKDGGTDFPAARDRrmhvmpdDDVFFITDVKPVDMGVYSCTAKNTAGT 687
Cdd:cd05754      5 VEEPRSQEVRPGADVSFICRAKSKsPAYTLVWTRVNGTLPSRAMDF-------NGILTIRNVQLSDAGTYVCTGSNMLDT 77


                   ....*..
gi 1779345322  688 VSANATL 694
Cdd:cd05754     78 DEATATL 84

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: 51.11 E-value: 8.90e-08

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1779345322  717 VALQCKALGSPPPRITWLHNDQPLRPSDRHHFTPGNQLLVIGSALLKDAGRYTCLMSNTLGTERA 781
Cdd:cd05849     22 VSVNCRARANPFPIYKWRKNNLDIDLTNDRYSMVGGNLVINNPDKYKDAGRYVCIVSNIYGKVRS 86

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: 50.95 E-value: 9.92e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  700 PHLAQDLEDRSVTVGETVALQCKALGSPPPRITWLHNDQPLRPSDRHHFTPGN--QLLVIGSALLK-----DAGRYTCLM 772
Cdd:cd05734      2 PRFVVQPNDQDGIYGKAVVLNCSADGYPPPTIVWKHSKGSGVPQFQHIVPLNGriQLLSNGSLLIKhvleeDSGYYLCKV 81

                           90
                   ....*....|.
gi 1779345322  773 SNTLGTERAHS 783
Cdd:cd05734     82 SNDVGADISKS 92

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

Pssm-ID: 409550 [Multi-domain] Cd Length: 89 Bit Score: 50.64 E-value: 1.01e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  606 PSFIKTPRDSTIRTGHTARLECAAEGHPTPQIAWQKDGGTdFPAarDRRMHVMPdDDVFFITDV-KPVDMGVYSCTAKNT 684
Cdd:cd20958      1 PPFIRPMGNLTAVAGQTLRLHCPVAGYPISSITWEKDGRR-LPL--NHRQRVFP-NGTLVIENVqRSSDEGEYTCTARNQ 76

                           90
                   ....*....|..
gi 1779345322  685 AGTvSANATLTV 696
Cdd:cd20958     77 QGQ-SASRSVFV 87

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 50.09 E-value: 1.09e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  611 TPRDSTIRTGHTARLECAAEGHPTPQIAWQKDGgtdfpaardrrmHVMPDDDVFFITDVKPVDMGVYSCTAKNTAG-TVS 689
Cdd:pfam13895    5 TPSPTVVTEGEPVTLTCSAPGNPPPSYTWYKDG------------SAISSSPNFFTLSVSAEDSGTYTCVARNGRGgKVS 72


                   ....*..
gi 1779345322  690 ANATLTV 696
Cdd:pfam13895   73 NPVELTV 79

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: 49.80 E-value: 1.36e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  620 GHTARLECAAEGHPTPQIAWQKDGGtdfPAARDRRMHVMPDDD--VFFITDVKPVDMGVYSCTAKNTAGTVSAN--ATLT 695
Cdd:cd05743      1 GETVEFTCVATGVPTPIINWRLNWG---HVPDSARVSITSEGGygTLTIRDVKESDQGAYTCEAINTRGMVFGIpdGILT 77


                   .
gi 1779345322  696 V 696
Cdd:cd05743     78 V 78

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 50.22 E-value: 1.42e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1779345322  707 EDRSVTVGETVALQCKALGSPPPRITWLHNDQPLRPSDRHHFTPGNQlLVIGSALLKDAGRYTCLMSNTLGTERAHSQL 785
Cdd:cd20957      9 PVQTVDFGRTAVFNCSVTGNPIHTVLWMKDGKPLGHSSRVQILSEDV-LVIPSVKREDKGMYQCFVRNDGDSAQATAEL 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: 50.20 E-value: 1.43e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  700 PHLaQDLEDRSVTVGETVALQCKALG-SPPPRITWLHNDQPLRPSDRHHF----TPGNQLLVIGSALLKDAGRYTCLMSN 774
Cdd:cd05750      1 PKL-KEMKSQTVQEGSKLVLKCEATSeNPSPRYRWFKDGKELNRKRPKNIkirnKKKNSELQINKAKLEDSGEYTCVVEN 79

                           90
                   ....*....|...
gi 1779345322  775 TLGTERAHSQLVV 787
Cdd:cd05750     80 ILGKDTVTGNVTV 92

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: 49.86 E-value: 1.88e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  704 QDLEDRSVTVGETVALQCKALG-SPPPRITWLHNDQPLrPSDRHHFtpgNQLLVIGSALLKDAGRYTCLMSNTLGTERAH 782
Cdd:cd05754      6 EEPRSQEVRPGADVSFICRAKSkSPAYTLVWTRVNGTL-PSRAMDF---NGILTIRNVQLSDAGTYVCTGSNMLDTDEAT 81


                   ...
gi 1779345322  783 SQL 785
Cdd:cd05754     82 ATL 84

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: 49.90 E-value: 2.00e-07

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1779345322  714 GETVALQCKALGSPPPRITWLHNDQPLRPSDRHH--FTPGNQL-LVIGSALLKDAGRYTCLMSNTLGTE 779
Cdd:cd05737     16 GKTLNLTCNVWGDPPPEVSWLKNDQALAFLDHCNlkVEAGRTVyFTINGVSSEDSGKYGLVVKNKYGSE 84

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.

Pssm-ID: 143207 [Multi-domain] Cd Length: 95 Bit Score: 49.93 E-value: 2.19e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  614 DSTIRTGHTARLECAAEGHPTPQIAWQKDGGtdfPAARDRRMHVMPDDDV-FFITDVKPVDMGVYSCTAKNTAGTVSANA 692
Cdd:cd05730     12 NATANLGQSVTLACDADGFPEPTMTWTKDGE---PIESGEEKYSFNEDGSeMTILDVDKLDEAEYTCIAENKAGEQEAEI 88


                   ....
gi 1779345322  693 TLTV 696
Cdd:cd05730     89 HLKV 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: 49.86 E-value: 2.20e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  711 VTVGETVALQCKALGSPPPRIT--WLHNDQPLRPS-DRHHF-------TPGNqlLVIGSALLKDAGRYTCLMSNTLGTER 780
Cdd:cd04970     14 ITVGENATLQCHASHDPTLDLTftWSFNGVPIDLEkIEGHYrrrygkdSNGD--LEIVNAQLKHAGRYTCTAQTVVDSDS 91


                   ....*..
gi 1779345322  781 AHSQLVV 787
Cdd:cd04970     92 ASATLVV 98

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: 49.25 E-value: 3.08e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  607 SFIKTPRDSTIRTGHTARLECAAEGHPTPQIAWQKDGG-TDFPAARDRRMHVMpdDDVFFITDVKPVDMGVYSCTAKNTA 685
Cdd:cd20949      1 TFTENAYVTTVKEGQSATILCEVKGEPQPNVTWHFNGQpISASVADMSKYRIL--ADGLLINKVTQDDTGEYTCRAYQVN 78

                           90
                   ....*....|.
gi 1779345322  686 GTVSANATLTV 696
Cdd:cd20949     79 SIASDMQERTV 89

Leucine rich repeat N-terminal domain;

Pssm-ID: 214470 [Multi-domain] Cd Length: 33 Bit Score: 46.93 E-value: 4.66e-07

                            10        20        30
                    ....*....|....*....|....*....|.
gi 1779345322    35 PCAQNCTCSGDSVDCSNLELTATPLDLPVRT 65
Cdd:smart00013    1 ACPAPCNCSGTAVDCSGRGLTEVPLDLPPDT 31

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: 48.35 E-value: 4.94e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1779345322  717 VALQCKALGSPPPRITWLHNDQPLRPSDRHHFTPGNQLLVIGsaLLK-DAGRYTCLMSNTLGTERAHSQLVV 787
Cdd:cd05723     15 IVFECEVTGKPTPTVKWVKNGDVVIPSDYFKIVKEHNLQVLG--LVKsDEGFYQCIAENDVGNAQASAQLII 84

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

Pssm-ID: 409394 [Multi-domain] Cd Length: 83 Bit Score: 48.17 E-value: 6.93e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  710 SVTV--GETVALQCKALGSPPPRITWLHNDQPLrPSDRHHFTPGNQLLVIGSALLKDAGRYTCLMSNTLGTERaHSQLVV 787
Cdd:cd05731      4 STMVlrGGVLLLECIAEGLPTPDIRWIKLGGEL-PKGRTKFENFNKTLKIENVSEADSGEYQCTASNTMGSAR-HTISVT 81


                   ..
gi 1779345322  788 TE 789
Cdd:cd05731     82 VE 83

Leucine rich repeat;

Pssm-ID: 404697 [Multi-domain] Cd Length: 61 Bit Score: 47.13 E-value: 8.04e-07

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1779345322   87 PNLRELRLDHNELTSI-PDLGQAASKIVSLYLHHNKIRSIDGRRTGELLSVETLDLSNNDI 146
Cdd:pfam13855    1 PNLRSLDLSNNRLTSLdDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

type III secretion system effector E3 ubiquitin transferase SspH2;

Pssm-ID: 185285 [Multi-domain] Cd Length: 788 Bit Score: 52.86 E-value: 1.02e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322   26 QSYGLSSDTPCAQNCTCSGDSV-DCSNLELTATPLDLPVRTVSLNLGHNQLTSISpeafANLPNLRELRLDHNELTSIP- 103
Cdd:PRK15387   184 ESRGRAAVVQKMRACLNNGNAVlNVGESGLTTLPDCLPAHITTLVIPDNNLTSLP----ALPPELRTLEVSGNQLTSLPv 259

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  104 ----------------DLGQAASKIVSLYLHHNKIRSIDGRRTG-ELLSVETLDLS---------------NNDITELrg 151
Cdd:PRK15387   260 lppgllelsifsnpltHLPALPSGLCKLWIFGNQLTSLPVLPPGlQELSVSDNQLAslpalpselcklwayNNQLTSL-- 337

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  152 QCFPAGLhiRDLYLSNNKISVL---------------ELGALDHLGETLQVLRLSRNRISQIPVkafqLP-RLTQLELNR 215
Cdd:PRK15387   338 PTLPSGL--QELSVSDNQLASLptlpselyklwaynnRLTSLPALPSGLKELIVSGNRLTSLPV----LPsELKELMVSG 411

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1779345322  216 NRIRQVEGLTfQGLSSLEVLklqRNSISKLTDgAFFDLSKMKVLHLDYNSLTEVNSGSLYGLTS 279
Cdd:PRK15387   412 NRLTSLPMLP-SGLLSLSVY---RNQLTRLPE-SLIHLSSETTVNLEGNPLSERTLQALREITS 470

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: 46.79 E-value: 1.41e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1779345322  717 VALQCKALGSPPPRITWLHNDQPLRPSDRHHFTPGNQlLVIGSALLKDAGRYTCLMSNTLG 777
Cdd:cd05746      1 VQIPCSAQGDPEPTITWNKDGVQVTESGKFHISPEGY-LAIRDVGVADQGRYECVARNTIG 60

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: 47.21 E-value: 1.46e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  612 PRDSTIR-TGHTARLECAAEGHPTPQIAWQKDGGTDFPaardRRMHVMPDDDVFFITDVKPVDMGVYSCTAKNTAGTVSA 690
Cdd:cd05876      1 SSSSLVAlRGQSLVLECIAEGLPTPTVKWLRPSGPLPP----DRVKYQNHNKTLQLLNVGESDDGEYVCLAENSLGSARH 76


                   ....*.
gi 1779345322  691 NATLTV 696
Cdd:cd05876     77 AYYVTV 82

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: 47.18 E-value: 1.47e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  706 LEDRSVTVGETVALQCKALGSPPPRITWLHNDQPLRPSDRHHFTPGNQLLVIGSALLKDAGRYTCLMSNTLGtERAHSQL 785
Cdd:cd20958      7 MGNLTAVAGQTLRLHCPVAGYPISSITWEKDGRRLPLNHRQRVFPNGTLVIENVQRSSDEGEYTCTARNQQG-QSASRSV 85


                   ...
gi 1779345322  786 VVT 788
Cdd:cd20958     86 FVK 88

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: 47.49 E-value: 1.49e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  606 PSFIKTPRDSTIRTGHTARLECAAEGHPTPQIAWQKDGGTDFP-----AARDRRMHVMPDDDVfFITDVKPVDMGVYSCT 680
Cdd:cd05734      2 PRFVVQPNDQDGIYGKAVVLNCSADGYPPPTIVWKHSKGSGVPqfqhiVPLNGRIQLLSNGSL-LIKHVLEEDSGYYLCK 80

                           90
                   ....*....|....*..
gi 1779345322  681 AKNTAGT-VSANATLTV 696
Cdd:cd05734     81 VSNDVGAdISKSMYLTV 97

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: 46.81 E-value: 1.62e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1779345322  725 GSPPPRITWLHNDQPLRPSDRHHF--TPGNQLLVIGSALLKDAGRYTCLMSNTLGTERAHSQLVV 787
Cdd:cd05748     18 GRPTPTVTWSKDGQPLKETGRVQIetTASSTSLVIKNAKRSDSGKYTLTLKNSAGEKSATINVKV 82

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: 47.63 E-value: 1.63e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  608 FIKTPRDSTIRT----GHTARLECA-AEGHPTPQIAWQKDGGTDFPAAR---DRRMHVMPDDDVFFiTDVKPVDMGV--- 676
Cdd:cd20965      1 YLLDPQVKTKEKkpveGKPFKLDCNvPPGYPKPTIEWKKQLVSDSSKADtilDRRITISPNGDLYF-TNVTKEDVSTdyk 79


                   ....*....
gi 1779345322  677 YSCTAKNTA 685
Cdd:cd20965     80 YVCVAKTPA 88

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: 51.71 E-value: 1.65e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322   43 SGDSVDCSNLELTATPLDLPVRTVSLNLGHNQLTSISPEAFANL----PNLRELRLDHNELT-----SIPDLGQAASKIV 113
Cdd:COG5238    244 SNNQIGDEGVIALAEALKNNTTVETLYLSGNQIGAEGAIALAKAlqgnTTLTSLDLSVNRIGdegaiALAEGLQGNKTLH 323

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  114 SLYLHHNKIRSIDGRRTGELL----SVETLDLSNNDIT----ELRGQCFPAGLHIRDLYLSNNKISvlELGALDhLGETL 185
Cdd:COG5238    324 TLNLAYNGIGAQGAIALAKALqentTLHSLDLSDNQIGdegaIALAKYLEGNTTLRELNLGKNNIG--KQGAEA-LIDAL 400

                          170       180       190
                   ....*....|....*....|....*....|....*.
gi 1779345322  186 QVLRLSRNRISQIPVKAFQLPRLTQLelnRNRIRQV 221
Cdd:COG5238    401 QTNRLHTLILDGNLIGAEAQQRLEQL---LERIKSV 433

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: 47.26 E-value: 1.71e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  700 PHLAQDLEDRSVTVGETVALQCKALGSPPPRITWLHNDQPLRPSDRHHF--TPGNQLLVIGSALLKDAGRYTCLMSNTLG 777
Cdd:cd05762      2 PQIIQFPEDMKVRAGESVELFCKVTGTQPITCTWMKFRKQIQEGEGIKIenTENSSKLTITEGQQEHCGCYTLEVENKLG 81

                           90
                   ....*....|...
gi 1779345322  778 TERAHSQLVVTER 790
Cdd:cd05762     82 SRQAQVNLTVVDK 94

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: 46.83 E-value: 2.15e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1779345322  711 VTV--GETVALQCKALGSPPPRITWLHNDQPLRPSDrHHFTPGNQ----LLVIGSALLKDAGRYTCLMSNTLGTER 780
Cdd:cd05891     11 VTImeGKTLNLTCTVFGNPDPEVIWFKNDQDIELSE-HYSVKLEQgkyaSLTIKGVTSEDSGKYSINVKNKYGGET 85

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 46.87 E-value: 2.33e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  490 PQITVQPEATMTVLGSDVRLTCTAASSSssPMTFAWRKDQELLRNAEmenyaHVRAHhqaatpdlpgaggggVMEYTTIL 569
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTP--DPEVSWFKDGQPLRSSD-----RFKVT---------------YEGGTYTL 58

                           90       100       110
                   ....*....|....*....|....*....|...
gi 1779345322  570 HLRRVTFAHEGRYQCIITNHFGStYSSKARLIV 602
Cdd:pfam07679   59 TISNVQPDDSGKYTCVATNSAGE-AEASAELTV 90

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: 46.84 E-value: 2.39e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1779345322  715 ETVALQCKALGSPPPRITWLHN--DQPLRPSDRHHFTPGNqlLVIGSAL-LKDAGRYTCLMSNTLGT 778
Cdd:cd05850     21 EKVTLACRARASPPATYRWKMNgtELKMEPDSRYRLVAGN--LVISNPVkAKDAGSYQCLASNRRGT 85

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 46.23 E-value: 2.68e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1779345322  711 VTVGETVALQCKALGSPPPRITWLHNDQPLRPSDRHHFTpgnqllvigSALLKDAGRYTCLMSNTLGTERAHS 783
Cdd:pfam13895   11 VTEGEPVTLTCSAPGNPPPSYTWYKDGSAISSSPNFFTL---------SVSAEDSGTYTCVARNGRGGKVSNP 74

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: 2.75e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1779345322  710 SVTVGETVALQCKALGSPPPRITWLHNDQPLRPS--DRHHFTPGNQLLVIGSALLKDAGRYTCLMSNTLGT 778
Cdd:cd20949     10 TVKEGQSATILCEVKGEPQPNVTWHFNGQPISASvaDMSKYRILADGLLINKVTQDDTGEYTCRAYQVNSI 80

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: 47.54 E-value: 3.14e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  336 NSISHINEGAFRGLKALRILELDHNdISgTIEDtnGAFSGLdSLIKLTlFENKIKSVAKKAFSGLETLEHLNLGENaIRS 415
Cdd:pfam13306   20 SSLTSIGEYAFSNCTSLKSITLPSS-LT-SIGS--YAFYNC-SLTSIT-IPSSLTSIGEYAFSNCSNLKSITLPSN-LTS 92

                           90       100
                   ....*....|....*....|
gi 1779345322  416 IQPDAFTKMrNLKSLLIQSN 435
Cdd:pfam13306   93 IGSYAFSNC-SLKSITIPSS 111

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: 46.15 E-value: 3.86e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  606 PSFIKTPRDSTIRTGHTAR--LECAAEGHPTPQIAWQKdgGTDFpAARDRRMHVMpDDDVFFITDVKPVDMGVYSCTAKN 683
Cdd:cd05852      1 PTFEFNPMKKKILAAKGGRviIECKPKAAPKPKFSWSK--GTEL-LVNNSRISIW-DDGSLEILNITKLDEGSYTCFAEN 76

                           90
                   ....*....|...
gi 1779345322  684 TAGTVSANATLTV 696
Cdd:cd05852     77 NRGKANSTGVLSV 89

Leucine rich repeat N-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 N-terminus of tandem leucine rich repeats.

Pssm-ID: 396168 [Multi-domain] Cd Length: 28 Bit Score: 44.16 E-value: 3.90e-06

                           10        20
                   ....*....|....*....|....*...
gi 1779345322   35 PCAQNCTCSGDSVDCSNLELTATPLDLP 62
Cdd:pfam01462    1 ACPVPCHCSATVVNCSDRGLTAVPRDLP 28

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: 46.23 E-value: 4.02e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  707 EDRSVTVGETVALQCKALGSPPPRITWLHNDQPL--RPSD---RHHFTPGNQLLVIgSALLKDAGRYTCLMSNTLGTERA 781
Cdd:cd20977      8 KDMMAKAGDVTMIYCMYGSNPTAHPNYFKNGKDVngNPEDritRHNRTSGKRLLFK-TTLPEDEGVYTCEVDNGVGKPQK 86


                   ....*..
gi 1779345322  782 HS-QLVV 787
Cdd:cd20977     87 HSlKLTV 93

Leucine rich repeat;

Pssm-ID: 404697 [Multi-domain] Cd Length: 61 Bit Score: 45.21 E-value: 4.06e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1779345322  110 SKIVSLYLHHNKIRSIDGRRTGELLSVETLDLSNNDITELRGQCFpAGLH-IRDLYLSNNKI 170
Cdd:pfam13855    1 PNLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAF-SGLPsLRYLDLSGNRL 61

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: 46.03 E-value: 4.18e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1779345322  711 VTVGETVALQCKA-LGSPPPRITWLHNDQPLRPSDRHHFTPGNQ---LLVIGSALLKDAGRYTCLMSNTLG 777
Cdd:pfam00047    8 VLEGDSATLTCSAsTGSPGPDVTWSKEGGTLIESLKVKHDNGRTtqsSLLISNVTKEDAGTYTCVVNNPGG 78

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions) through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain.

Pssm-ID: 143207 [Multi-domain] Cd Length: 95 Bit Score: 46.08 E-value: 4.56e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1779345322  713 VGETVALQCKALGSPPPRITWLHNDQPLRPSD-RHHFTPGNQLLVIGSALLKDAGRYTCLMSNTLGTERAHSQLVV 787
Cdd:cd05730     17 LGQSVTLACDADGFPEPTMTWTKDGEPIESGEeKYSFNEDGSEMTILDVDKLDEAEYTCIAENKAGEQEAEIHLKV 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: 45.59 E-value: 6.33e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  700 PHLAQdLEDRSVTVGETVALQCKALGSPPPRITWlhndqpLRPSDRHHFTPGN-------------QLLVIGSALLKDAG 766
Cdd:cd05732      3 PKITY-LENQTAVELEQITLTCEAEGDPIPEITW------RRATRGISFEEGDldgrivvrgharvSSLTLKDVQLTDAG 75

                           90
                   ....*....|.
gi 1779345322  767 RYTCLMSNTLG 777
Cdd:cd05732     76 RYDCEASNRIG 86

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: 45.70 E-value: 6.72e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1779345322  717 VALQCKALGSPPPRITWLHNDQPLR-PSD-RHHFTPGNqLLVIGSALLKDAGRYTCLMSNTLGT 778
Cdd:cd05848     22 VILNCEARGNPVPTYRWLRNGTEIDtESDyRYSLIDGN-LIISNPSEVKDSGRYQCLATNSIGS 84

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: 45.38 E-value: 7.77e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1779345322  707 EDRSVTVGETVALQCKALGSPPPRITW--LHNDQP-----LRPSDRHHFTPgNQLLVIGSALLKDAGRYTCLMSNTLGT 778
Cdd:cd20954      9 VDANVAAGQDVMLHCQADGFPTPTVTWkkATGSTPgeykdLLYDPNVRILP-NGTLVFGHVQKENEGHYLCEAKNGIGS 86

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: 45.09 E-value: 9.02e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  607 SFIKTPRDSTIrtghtarLECAAEGHPTPQIAWQKDgGTDFPAARDRRMHVMPDDDVFFIT--DVKPVDM-GVYSCTAKN 683
Cdd:cd05733     10 DYIVDPRDNIT-------IKCEAKGNPQPTFRWTKD-GKFFDPAKDPRVSMRRRSGTLVIDnhNGGPEDYqGEYQCYASN 81


                   ....*...
gi 1779345322  684 TAGTVSAN 691
Cdd:cd05733     82 ELGTAISN 89

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: 44.88 E-value: 9.76e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1779345322  625 LECAAEGHPTPQIAWQKDGGTDFPAardRRMHVMPDDDVFFITDVKPvDMGVYSCTAKNTAGTVSANATLTV 696
Cdd:cd05723     17 FECEVTGKPTPTVKWVKNGDVVIPS---DYFKIVKEHNLQVLGLVKS-DEGFYQCIAENDVGNAQASAQLII 84

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: 44.97 E-value: 1.09e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  610 KTPRDSTIRTGHTARLECAAEGHPTPQIAWQKDgGTDFPAARDRRMHVMPDDDVFFITDVKPVDM----GVYSCTAKNTA 685
Cdd:cd05874      6 QSPKDYIVDPRENIVIQCEAKGKPPPSFSWTRN-GTHFDIDKDPKVTMKPNTGTLVINIMNGEKAeayeGVYQCTARNER 84


                   ....*.
gi 1779345322  686 GTVSAN 691
Cdd:cd05874     85 GAAVSN 90

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: 44.93 E-value: 1.11e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  714 GETVALQCKALGSPPPRITWLHNDQPLRPSDRhhftpgnqLLVIGSALLK-------DAGRYTCLMSNTLGTerAHSQLV 786
Cdd:cd20968     14 GLKAVLPCTTMGNPKPSVSWIKGDDLIKENNR--------IAVLESGSLRihnvqkeDAGQYRCVAKNSLGI--AYSKPV 83


                   ...
gi 1779345322  787 VTE 789
Cdd:cd20968     84 TIE 86

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: 1.12e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  709 RSVTVGETVALQCKALGSPPPRITWL-HND--------------QPLRPSDRHHFTPGNQLLVIGsALLKDAGRYTCLMS 773
Cdd:cd04974     11 QTVVLGSDVEFHCKVYSDAQPHIQWLkHVEvngskygpdglpyvTVLKVAGVNTTGEENTLTISN-VTFDDAGEYICLAG 89


                   ....
gi 1779345322  774 NTLG 777
Cdd:cd04974     90 NSIG 93

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: 44.93 E-value: 1.13e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  610 KTPRDSTIRTGHTARLECAAEGHPTPQIAWQKDggtDFPAARDRRMHVMpDDDVFFITDVKPVDMGVYSCTAKNTAGTV- 688
Cdd:cd20968      4 RPPTNVTIIEGLKAVLPCTTMGNPKPSVSWIKG---DDLIKENNRIAVL-ESGSLRIHNVQKEDAGQYRCVAKNSLGIAy 79


                   ....*...
gi 1779345322  689 SANATLTV 696
Cdd:cd20968     80 SKPVTIEV 87

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: 44.02 E-value: 1.39e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1779345322  714 GETVALQCKALGSPPPRITWLHNDQPLRPSDRHHFTP--GNQLLVIGSALLKDAGRYTCLMSNTLGTERAHSQLVVT 788
Cdd:cd05743      1 GETVEFTCVATGVPTPIINWRLNWGHVPDSARVSITSegGYGTLTIRDVKESDQGAYTCEAINTRGMVFGIPDGILT 77

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: 44.37 E-value: 1.51e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1779345322  706 LEDRSVTVGETVALQCkALGSPPPRITWLHN--DQPLRPSDRHHFTpGNQLLVIGSALLKDAGRYTCLMSN-TLGT 778
Cdd:cd04979      3 FKQISVKEGDTVILSC-SVKSNNAPVTWIHNgkKVPRYRSPRLVLK-TERGLLIRSAQEADAGVYECHSGErVLGS 76

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: 44.55 E-value: 1.52e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  606 PSFIKTPRDSTIRTGHTAR---LECAAEGHPTPQIAWQKDgGTDFPAARDRRMHVMpdDDVFFITDVKPV-DMGVYSCTA 681
Cdd:cd05848      2 PVFVQEPDDAIFPTDSDEKkviLNCEARGNPVPTYRWLRN-GTEIDTESDYRYSLI--DGNLIISNPSEVkDSGRYQCLA 78

                           90
                   ....*....|....
gi 1779345322  682 KNTAGTV-SANATL 694
Cdd:cd05848     79 TNSIGSIlSREALL 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: 44.54 E-value: 1.55e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  606 PSFIKTPRDSTIRTGHTAR---LECAAEGHPTPQIAWQKDGgTDFPAARDRRmHVMPDDDVFFITDVKPVDMGVYSCTAK 682
Cdd:cd04967      2 PVFEEQPDDTIFPEDSDEKkvaLNCRARANPVPSYRWLMNG-TEIDLESDYR-YSLVDGTLVISNPSKAKDAGHYQCLAT 79

                           90
                   ....*....|...
gi 1779345322  683 NTAGTV-SANATL 694
Cdd:cd04967     80 NTVGSVlSREATL 92

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: 44.30 E-value: 1.60e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  616 TIRTGHTARLECAAEGHPTPQIAWQKDGGTDFPAARDRRMHVMPDDDVFFiTDVKPVDMGVYSCTAKNTAGTVSANATLT 695
Cdd:cd20969     13 FVDEGHTVQFVCRADGDPPPAILWLSPRKHLVSAKSNGRLTVFPDGTLEV-RYAQVQDNGTYLCIAANAGGNDSMPAHLH 91


                   .
gi 1779345322  696 V 696
Cdd:cd20969     92 V 92

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

Pssm-ID: 409475 Cd Length: 86 Bit Score: 43.68 E-value: 2.30e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  616 TIRTGHTARLECAAEGHPTPQIAWQKdGGTDFPAARDR-RMHVMPDDDVFFITDVKPVDMGVYSCTAKNTAGTVSANATL 694
Cdd:cd05894      6 VVVAGNKLRLDVPISGEPAPTVTWSR-GDKAFTATEGRvRVESYKDLSSFVIEGAEREDEGVYTITVTNPVGEDHASLFV 84


                   ..
gi 1779345322  695 TV 696
Cdd:cd05894     85 KV 86

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: 43.74 E-value: 2.35e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  707 EDRSVTVGETVALQCKALGSPPPRITWLHNDQPLRPSDRhhftpgnqlLVIGSALL-----KDAGRYTCLMSNTLGTERA 781
Cdd:cd05739      5 SNHEVMPGGSVNLTCVAVGAPMPYVKWMKGGEELTKEDE---------MPVGRNVLeltniYESANYTCVAISSLGMIEA 75


                   ....*.
gi 1779345322  782 HSQLVV 787
Cdd:cd05739     76 TAQVTV 81

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: 43.86 E-value: 2.42e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  699 TPHLAQDLEDRSVTVGETVALQCKALGSPPPRITWLHNDQPLrPSDRHHFTPGnQLLVIGSALLKDAGRYTCLMSNTLGT 778
Cdd:cd05851      1 PADINVKFKDTYALKGQNVTLECFALGNPVPVIRWRKILEPM-PATAEISMSG-AVLKIFNIQPEDEGTYECEAENIKGK 78


                   ....*....
gi 1779345322  779 ERAHSQLVV 787
Cdd:cd05851     79 DKHQARVYV 87

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: 44.05 E-value: 2.68e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1779345322  613 RDSTIRTGHTARLECAAEGHPTPQIAWQK--DGGTDFPAARDRRMHVMPDDDVFFIT--DVKPVDMGVYSCTAKNTAG 686
Cdd:cd05732      9 ENQTAVELEQITLTCEAEGDPIPEITWRRatRGISFEEGDLDGRIVVRGHARVSSLTlkDVQLTDAGRYDCEASNRIG 86

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: 44.57 E-value: 2.84e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  608 FIKTPRDSTIRTGHTARLECAAEGHPTPQIAWQKDGGTD-------FPAARDRRMHV-----MPDDDVFFITDVKPVDMG 675
Cdd:cd20940      3 FIKSPLSQQRLVGDSVELHCEAVGSPIPEIQWWFEGQEPneicsqlWDGARLDRVHInatyhQHATSTISIDNLTEEDTG 82


                   ....*...
gi 1779345322  676 VYSCTAKN 683
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: 43.46 E-value: 3.04e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1779345322  716 TVALQCKALGSPPPRITWLHNDQPLRPS---DRHHFTPGNqLLVIGSALLKDAGRYTCLMSNTLGTE-RAHSQLVV 787
Cdd:cd05738     16 TATMLCAASGNPDPEISWFKDFLPVDTAtsnGRIKQLRSG-ALQIENSEESDQGKYECVATNSAGTRySAPANLYV 90

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: 43.47 E-value: 3.12e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1779345322  613 RDSTIRTGHTARLECAAEGHPTPQIAWQKDgGTDFPAARDRRMhvmpDDDVFFITDVKPVDMGVYSCTAKNTAG 686
Cdd:cd05851      9 KDTYALKGQNVTLECFALGNPVPVIRWRKI-LEPMPATAEISM----SGAVLKIFNIQPEDEGTYECEAENIKG 77

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: 43.36 E-value: 3.73e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  712 TVGE-TVALQCKALGSPPPRITWLHNDQPLRPSDRHHfTPgnQLLVIGSALLKDAGRYTCLMSNTLGTER 780
Cdd:cd04976     15 TAGKrSVRLPMKVKAYPPPEVVWYKDGLPLTEKARYL-TR--HSLIIKEVTEEDTGNYTILLSNKQSNVF 81

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: 3.81e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  620 GHTARLECAAEGHPTPQIAWQKDGGtdfPAARDRRM---HVMPDDDVFFITDVKPVDMGVYSCTAKNTAGTVSANATLTV 696
Cdd:cd05857     19 ANTVKFRCPAAGNPTPTMRWLKNGK---EFKQEHRIggyKVRNQHWSLIMESVVPSDKGNYTCVVENEYGSINHTYHLDV 95

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: 43.15 E-value: 4.03e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1779345322  710 SVTVGETVALQCKAlGSPPPRITWLHNDQPLRPSDRHHFTPGNQLLVIGSALLKDAGRYTCLMSN 774
Cdd:cd05740     11 PVEDKDAVTLTCEP-ETQNTSYLWWFNGQSLPVTPRLTLSNGNRTLTLLNVTREDAGAYQCEISN 74

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: 41.46 E-value: 4.51e-05

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 1779345322   67 SLNLGHNQLTSISPeaFANLPNLRELRLDHN-ELTSIPDL 105
Cdd:pfam12799    5 VLDLSNNQITDIPP--LAKLPNLETLDLSGNnKITDLSDL 42

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: 42.90 E-value: 4.56e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1779345322  711 VTVGETVALQCKALGSPPPRITWLHNDQPLR-PSDRHHF--TPGNQLLVIGSALLKDAGRYTCLMSNTLGTERA 781
Cdd:cd05894      7 VVAGNKLRLDVPISGEPAPTVTWSRGDKAFTaTEGRVRVesYKDLSSFVIEGAEREDEGVYTITVTNPVGEDHA 80

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: 43.18 E-value: 4.83e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  709 RSVTVGE--TVALQCKALGSPPPRITWLHNDQPLRPsdrhHFTPGN---------QLLVIGSALLKDAGRYTCLMSNTLG 777
Cdd:cd20951      8 QSHTVWEksDAKLRVEVQGKPDPEVKWYKNGVPIDP----SSIPGKykieseygvHVLHIRRVTVEDSAVYSAVAKNIHG 83

                           90
                   ....*....|
gi 1779345322  778 TERAHSQLVV 787
Cdd:cd20951     84 EASSSASVVV 93

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

Pssm-ID: 409440 Cd Length: 102 Bit Score: 43.11 E-value: 5.23e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  711 VTVGETVALQCKALGSPPPRIT--WLHNDQPL---RPSDRHHFTPGNQL---LVIGSALLKDAGRYTCLMSNTLGTERAH 782
Cdd:cd05854     14 INQGENLTLQCHASHDPTMDLTftWSLDDFPIdldKPNGHYRRMEVKETigdLVIVNAQLSHAGTYTCTAQTVVDSASAS 93


                   ....*
gi 1779345322  783 SQLVV 787
Cdd:cd05854     94 ATLVV 98

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: 43.69 E-value: 5.85e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  341 INEGAFRGLKaLRILELDHNDISgtIEdtNGAFSGLDSLIKLTlFENKIKSVAKKAFSGLEtLEHLNLGENaIRSIQPDA 420
Cdd:pfam13306    3 IGSYAFYNCS-LTSITIPSSLTS--IG--EYAFSNCTSLKSIT-LPSSLTSIGSYAFYNCS-LTSITIPSS-LTSIGEYA 74

                           90
                   ....*....|....*
gi 1779345322  421 FTKMRNLKSLLIQSN 435
Cdd:pfam13306   75 FSNCSNLKSITLPSN 89

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: 43.04 E-value: 5.94e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  700 PHLAQdLEDRSVTVGETVALQCKALGSPPPRITWlhndqpLRPSDRHHFTPGNQ---------------LLVIGSALLKD 764
Cdd:cd05870      3 PHIIQ-LKNETTVENGAATLSCKAEGEPIPEITW------KRASDGHTFSEGDKspdgrievkgqhgesSLHIKDVKLSD 75

                           90
                   ....*....|...
gi 1779345322  765 AGRYTCLMSNTLG 777
Cdd:cd05870     76 SGRYDCEAASRIG 88

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

Pssm-ID: 279765 Cd Length: 26 Bit Score: 40.88 E-value: 6.30e-05

                           10        20
                   ....*....|....*....|....*.
gi 1779345322  460 NATCAHPESLKGKSVFEVPPSSFVCD 485
Cdd:pfam01463    1 NARCASPPRLRGQPLLDLLPSDFSCS 26

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: 43.04 E-value: 6.42e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  604 VLPSFIKTPRDSTIRTGhTARLECAAEGHPTPQIAWQK--DGGT--DFPAARDRRMHVMPD--DDVFFITDVKPVDMGVY 677
Cdd:cd05870      1 VQPHIIQLKNETTVENG-AATLSCKAEGEPIPEITWKRasDGHTfsEGDKSPDGRIEVKGQhgESSLHIKDVKLSDSGRY 79


                   ....*....
gi 1779345322  678 SCTAKNTAG 686
Cdd:cd05870     80 DCEAASRIG 88

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: 42.99 E-value: 6.43e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  615 STIRTGHTARLECAAEGHPTPQIAWQKDGGtdfPAARDRRMH-VMPDDDVFFITDVKPVDMGVYSCTAKNTAGTV--SAN 691
Cdd:cd05760     11 AEIQPSSRVTLRCHIDGHPRPTYQWFRDGT---PLSDGQGNYsVSSKERTLTLRSAGPDDSGLYYCCAHNAFGSVcsSQN 87


                   ....*..
gi 1779345322  692 ATLTVLE 698
Cdd:cd05760     88 FTLSIID 94

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: 42.78 E-value: 6.77e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  606 PSFIKTPRDSTIRTGHT-ARLECAAEGHPTPQIAWQKDGGT---DFPAAR----DRRMHVMPdddvFFITDVK-PVDMGV 676
Cdd:cd20955      2 PVFLKEPTNRIDFSNSTgAEIECKASGNPMPEIIWIRSDGTavgDVPGLRqissDGKLVFPP----FRAEDYRqEVHAQV 77

                           90
                   ....*....|..
gi 1779345322  677 YSCTAKNTAGTV 688
Cdd:cd20955     78 YACLARNQFGSI 89

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: 42.67 E-value: 7.41e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  700 PHLaQDLEDRSVTVGETVALQCKALGSPPP-RITWLHNDQPLRPSDRHHFT-----PGNQLLVIGSALLKDAGRYTCLMS 773
Cdd:cd05895      1 PKL-KEMKSQEVAAGSKLVLRCETSSEYPSlRFKWFKNGKEINRKNKPENIkiqkkKKKSELRINKASLADSGEYMCKVS 79

                           90
                   ....*....|....
gi 1779345322  774 NTLGTERAHSQLVV 787
Cdd:cd05895     80 SKLGNDSASANVTI 93

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: 42.34 E-value: 9.12e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  700 PHLAQDLEDRSVTVGETVALQCKALGSPPPRITWLHNDQPLR----PSDRHHFTPGNQLLVIGSALLKDAGRYTCLMSNT 775
Cdd:cd20974      1 PVFTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFRDGQVIStstlPGVQISFSDGRAKLSIPAVTKANSGRYSLTATNG 80

                           90
                   ....*....|...
gi 1779345322  776 LGTERAHSQLVVT 788
Cdd:cd20974     81 SGQATSTAELLVL 93

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: 42.34 E-value: 9.85e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  612 PRDSTIRTGHTARLECAAEGHPTPQIA--WQKDG---GTDFPAARDRRMHVMPDDDVFFITDVKPVDMGVYSCTAKNTAG 686
Cdd:cd05854      9 PSSADINQGENLTLQCHASHDPTMDLTftWSLDDfpiDLDKPNGHYRRMEVKETIGDLVIVNAQLSHAGTYTCTAQTVVD 88

                           90
                   ....*....|....
gi 1779345322  687 TVSANATLTVLETP 700
Cdd:cd05854     89 SASASATLVVRGPP 102

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.

Pssm-ID: 395002 Cd Length: 86 Bit Score: 41.80 E-value: 1.31e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  610 KTPRDSTIRTGHTARLEC-AAEGHPTPQIAWQKDGGTdfpaaRDRRMHVMPDDD-----VFFITDVKPVDMGVYSCTAKN 683
Cdd:pfam00047    1 SAPPTVTVLEGDSATLTCsASTGSPGPDVTWSKEGGT-----LIESLKVKHDNGrttqsSLLISNVTKEDAGTYTCVVNN 75

                           90
                   ....*....|.
gi 1779345322  684 TAGTVSANATL 694
Cdd:pfam00047   76 PGGSATLSTSL 86

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: 41.81 E-value: 1.49e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  612 PRDSTIRTGHTARLECAAEGHPTPQIAWQKDggtDFPAAR-DR-RMHVMPDDDVFF-ITDVKPVDMGVYSCTAKNTAGTV 688
Cdd:cd05737      8 PDVVTIMEGKTLNLTCNVWGDPPPEVSWLKN---DQALAFlDHcNLKVEAGRTVYFtINGVSSEDSGKYGLVVKNKYGSE 84


                   ....*...
gi 1779345322  689 SANATLTV 696
Cdd:cd05737     85 TSDVTVSV 92

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 40.89 E-value: 2.64e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1779345322  714 GETVALQCKALGSPPPRITWLHNDQPLRPsdrHHFTPGNqlLVIGSALL------KDAGRYTCLMSNTLGT 778
Cdd:cd04978     14 GETGELICEAEGNPQPTITWRLNGVPIEP---APEDMRR--TVDGRTLIfsnlqpNDTAVYQCNASNVHGY 79

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: 40.85 E-value: 2.91e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  700 PHLAQDLEDRSVTVGETVALQCKALGSPPPRITWLHNDQPLRPSDRHHFTP----GNQLLVIGSALLKDAGRYTCLMSNT 775
Cdd:cd05893      1 PFFEMKLKHYKIFEGMPVTFTCRVAGNPKPKIYWFKDGKQISPKSDHYTIQrdldGTCSLHTTASTLDDDGNYTIMAANP 80

                           90
                   ....*....|..
gi 1779345322  776 LGTERAHSQLVV 787
Cdd:cd05893     81 QGRISCTGRLMV 92

Immunoglobulin (Ig)-like domain of human neurofascin (NF); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of human neurofascin (NF). NF 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 a cytoplasmic domain. NF has many alternatively spliced isoforms having different temporal expression patterns during development. NF participates in axon subcellular targeting and synapse formation, however little is known of the functions of the different isoforms. 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: 409459 Cd Length: 95 Bit Score: 40.73 E-value: 3.82e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  605 LPSFIKTPRDSTIrtghtarLECAAEGHPTPQIAWQKDGGTdFPAARDRRMHVMPDDDVFFI---TDVKPVDM-GVYSCT 680
Cdd:cd05875      8 AKDYIVDPRDNIL-------IECEAKGNPVPTFHWTRNGKF-FNVAKDPRVSMRRRSGTLVIdfrGGGRPEDYeGEYQCF 79

                           90
                   ....*....|.
gi 1779345322  681 AKNTAGTVSAN 691
Cdd:cd05875     80 ARNKFGTALSN 90

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: 40.35 E-value: 4.56e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1779345322  714 GETVALQCKALGSPPPRITWLHNDQP--LRPSDRHHFTPGNQllVIGSALLKDAGR-YTCLMSNTLG 777
Cdd:cd05868     14 GEDGTLICRANGNPKPSISWLTNGVPieIAPTDPSRKVDGDT--IIFSKVQERSSAvYQCNASNEYG 78

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: 40.22 E-value: 4.78e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  711 VTVGETVALQCKALGSPPPRITWLH------NDQPLRPSDRHHFTPGNqlLVIGSALLKDAGRYTCLMSNTLGTERAHSQ 784
Cdd:cd20953     15 VSSASSIALLCPAQGYPAPSFRWYKfiegttRKQAVVLNDRVKQVSGT--LIIKDAVVEDSGKYLCVVNNSVGGESVETV 92


                   ...
gi 1779345322  785 LVV 787
Cdd:cd20953     93 LTV 95

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: 39.40 E-value: 5.65e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1779345322  713 VGETVALQCKALGSPPPRITWLHNDQPLRPSdrhhftpgnQLLVIGSALLKDAGRYTCLMSNTLGTERAHSQLVVT 788
Cdd:cd20948      9 SGENLNLSCHAASNPPAQYSWTINGTFQTSS---------QELFLPAITENNEGTYTCSAHNSLTGKNISLVLSVT 75

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: 39.70 E-value: 6.81e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  703 AQDLEDRSVTVGETVALQCKALGSPPPRITWLHNDQPLRPSDRHHFT----PGNQLLVIGSALLKD-AGRYTCLMSNTLG 777
Cdd:cd05733      5 EQSPKDYIVDPRDNITIKCEAKGNPQPTFRWTKDGKFFDPAKDPRVSmrrrSGTLVIDNHNGGPEDyQGEYQCYASNELG 84

                           90
                   ....*....|
gi 1779345322  778 TERAHSQLVV 787
Cdd:cd05733     85 TAISNEIRLV 94

Immunoglobulin (Ig) constant domain of the complement receptor of the immunoglobulin superfamily (CRIg); The members here are composed of the Immunoglobulin (Ig) constant domain of the complement receptor of the immunoglobulin superfamily (CRIg). The N-terminal domain of CRIg (also referred to as Z39Ig and V-set and Ig domain-containing 4 (VSIG4)) belongs to the IgV family of immunoglobulin-like domains while the C-terminal domain of CRIg belongs to the IgC family of immunoglobulin-like domains. CRIg plays a role in the complement system, an inhibitor of the alternative pathway convertases, and a negative regulator of T cell activation. 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 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.

Pssm-ID: 409504 Cd Length: 86 Bit Score: 39.74 E-value: 7.05e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  710 SVTVGETVALQCKALGSPPPRITWL----HNDQPLRPSDRhhftpgnQLLVIGSALLKDAGRYTCLMSNTLGTERaHSQL 785
Cdd:cd16082      9 TVPQGMRISLQCQAWGSPPISYVWYkeqtNNQEPIKVAAL-------STLLFKPAVVADSGSYFCTAKGRVGSEQ-RSDI 80


                   .
gi 1779345322  786 V 786
Cdd:cd16082     81 V 81

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

Pssm-ID: 463713 [Multi-domain] Cd Length: 44 Bit Score: 38.38 E-value: 7.15e-04

                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 1779345322  278 TSLQQLFLSNNSIARInpDGWKFCQKLRELNLSYNNL 314
Cdd:pfam12799    1 PNLEVLDLSNNQITDI--PPLAKLPNLETLDLSGNNK 35

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: 39.83 E-value: 7.79e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  621 HTARLECAAEGHPTPQIAWQKdggtdFPAARDRRMHVMPDDDV------FFITDVKPVDMGVYSCTAKNTAGTVSANATL 694
Cdd:cd20953     19 SSIALLCPAQGYPAPSFRWYK-----FIEGTTRKQAVVLNDRVkqvsgtLIIKDAVVEDSGKYLCVVNNSVGGESVETVL 93


                   ..
gi 1779345322  695 TV 696
Cdd:cd20953     94 TV 95

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

Pssm-ID: 409360 Cd Length: 96 Bit Score: 39.69 E-value: 8.11e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1779345322  725 GSPPPRITWLHNDQPLRPSDRH----HFTPGNQLLVIGSALLK-----DAGRYTCLMSNTLGTERA 781
Cdd:cd04971     24 GNPKPTLTWYHNGAVLNESDYIrteiHYEAATPTEYHGCLKFDnpthvNNGNYTLVASNEYGQDSK 89

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: 38.73 E-value: 1.12e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  612 PRDSTIRTGHTARLECAAEGHPTPQIAWQKdGGTDFPaardrRMHVMP-DDDVFFITDVKpvDMGVYSCTAKNTAGTVSA 690
Cdd:cd05739      4 PSNHEVMPGGSVNLTCVAVGAPMPYVKWMK-GGEELT-----KEDEMPvGRNVLELTNIY--ESANYTCVAISSLGMIEA 75


                   ....*.
gi 1779345322  691 NATLTV 696
Cdd:cd05739     76 TAQVTV 81

Leucine-rich repeat;

Pssm-ID: 405295 [Multi-domain] Cd Length: 175 Bit Score: 40.90 E-value: 1.29e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  137 ETLDLSNNDITELRGqcFPAGLHIRDLYLSNNKISvlelgaldHLGETLQVLrlsrnrisqipvkafqLPRLTQLELNRN 216
Cdd:pfam14580   45 DTIDFSDNEIRKLDG--FPLLRRLKTLLLNNNRIC--------RIGEGLGEA----------------LPNLTELILTNN 98

                           90       100
                   ....*....|....*....|....*....
gi 1779345322  217 RIRQ-VEGLTFQGLSSLEVLKLQRNSISK 244
Cdd:pfam14580   99 NLQElGDLDPLASLKKLTFLSLLRNPVTN 127

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: 39.00 E-value: 1.48e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  493 TVQPEATMTVLGSDVRLTCTAASSSssPMTFAWRKDQELLRNAEMENYAHVrahhqaatPDlpgagggGVMEYTTILHlR 572
Cdd:cd05722      5 LSEPSDIVAMRGGPVVLNCSAESDP--PPKIEWKKDGVLLNLVSDERRQQL--------PN-------GSLLITSVVH-S 66

                           90       100       110
                   ....*....|....*....|....*....|.
gi 1779345322  573 RVTFAHEGRYQCIITN-HFGSTYSSKARLIV 602
Cdd:cd05722     67 KHNKPDEGFYQCVAQNeSLGSIVSRTARVTV 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: 38.22 E-value: 1.79e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 1779345322  701 HLAQDLEDRSVTVGETVALQCKALGSPPP-RITWLHNDQPL 740
Cdd:cd05749      1 HFTVEPEDLAVTANTPFNLTCQAVGPPEPvEILWWQGGSPL 41

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: 38.26 E-value: 1.92e-03

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322   496 PEATMTVLGSDVRLTCTAASSSSSPMTfaWRKDQellrnaemenyahvrahhqaatPDLPGAGGGGVMEY---TTILHLR 572
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVT--WYKQG----------------------GKLLAESGRFSVSRsgsTSTLTIS 56

                            90       100       110
                    ....*....|....*....|....*....|
gi 1779345322   573 RVTFAHEGRYQCIITNHFGStYSSKARLIV 602
Cdd:smart00410   57 NVTPEDSGTYTCAATNSSGS-ASSGTTLTV 85

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

Pssm-ID: 409453 [Multi-domain] Cd Length: 89 Bit Score: 38.34 E-value: 2.04e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1779345322  714 GETVALQCKALGSPPPRITWLHNDQPLR---PSDRHHFTPGNqlLVIGSALLKDAGRYTCLMSNTLGTERAHSQLVV 787
Cdd:cd05867     14 GETARLDCQVEGIPTPNITWSINGAPIEgtdPDPRRHVSSGA--LILTDVQPSDTAVYQCEARNRHGNLLANAHVHV 88

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: 38.69 E-value: 2.16e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  612 PRDSTIRTGHTARLECAAEGHPTPQIA--WQKDG-GTDF--PAARDRRMHVMPDDDVFFITDVKPVDMGVYSCTAKNTAG 686
Cdd:cd04970      9 PSNADITVGENATLQCHASHDPTLDLTftWSFNGvPIDLekIEGHYRRRYGKDSNGDLEIVNAQLKHAGRYTCTAQTVVD 88

                           90
                   ....*....|....
gi 1779345322  687 TVSANATLTVLETP 700
Cdd:cd04970     89 SDSASATLVVRGPP 102

Leucine-rich repeat;

Pssm-ID: 405295 [Multi-domain] Cd Length: 175 Bit Score: 40.13 E-value: 2.33e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  277 LTSLQQLFLSNNSIARINPDGWKFCQKLRELNLSYNNLTRL-DEGSLAVLGDLHTLRLGHNSIS---HINEGAFRGLKAL 352
Cdd:pfam14580   63 LRRLKTLLLNNNRICRIGEGLGEALPNLTELILTNNNLQELgDLDPLASLKKLTFLSLLRNPVTnkpHYRLYVIYKVPQL 142


                   ....
gi 1779345322  353 RILE 356
Cdd:pfam14580  143 RLLD 146

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: 38.21 E-value: 2.49e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1779345322  729 PRITWLHNDQPLrPSDRHHFTPGNQLLVIGSALLKDAGRYTCLMSNT 775
Cdd:cd20994     31 PKVQWYKDCKPL-LLDDKRFAGLESDLLIFNVTVQDQGNYTCHTSYT 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: 38.16 E-value: 2.97e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  490 PQITVQPEATMTVLGSD-VRLTCtaASSSSSPMTFAWRKDQELLrnaEMENYAHVRAHHQAATpdLPGAGGGGVMEytti 568
Cdd:cd05733      1 PTITEQSPKDYIVDPRDnITIKC--EAKGNPQPTFRWTKDGKFF---DPAKDPRVSMRRRSGT--LVIDNHNGGPE---- 69

                           90       100       110
                   ....*....|....*....|....*....|...
gi 1779345322  569 lhlrrvtfAHEGRYQCIITNHFGSTYSSKARLI 601
Cdd:cd05733     70 --------DYQGEYQCYASNELGTAISNEIRLV 94

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: 38.40 E-value: 3.01e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  612 PRDSTIRTGHTARLECAAEGHPTPQIAW----QKDG---GTD-FPAAR----------DRRMhvmpddDVFFITDVKPVD 673
Cdd:cd05858      8 PANTSVVVGTDAEFVCKVYSDAQPHIQWlkhvEKNGskyGPDgLPYVEvlktagvnttDKEI------EVLYLRNVTFED 81

                           90       100
                   ....*....|....*....|....
gi 1779345322  674 MGVYSCTAKNTAGTVSANATLTVL 697
Cdd:cd05858     82 AGEYTCLAGNSIGISHHSAWLTVL 105

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: 41.31 E-value: 3.06e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  278 TSLQQLFLSNNSIArinPDGWKF-------CQKLRELNLSYNNLTrlDEGsLAVLGD-------LHTLRLGHNSISHinE 343
Cdd:COG5238    208 TTVTTLWLKRNPIG---DEGAEIlaealkgNKSLTTLDLSNNQIG--DEG-VIALAEalknnttVETLYLSGNQIGA--E 279

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  344 GA------FRGLKALRILELDHNDIS--GTIEDTNGaFSGLDSLIKLTLFENKI-----KSVAkKAFSGLETLEHLNLGE 410
Cdd:COG5238    280 GAialakaLQGNTTLTSLDLSVNRIGdeGAIALAEG-LQGNKTLHTLNLAYNGIgaqgaIALA-KALQENTTLHSLDLSD 357


                   ...
gi 1779345322  411 NAI 413
Cdd:COG5238    358 NQI 360

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: 38.07 E-value: 3.06e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1779345322  729 PRITWLHNDQPLRpsDRHHFTPGNQLLVIGSALLKDAGRYTCLMSNT 775
Cdd:cd05757     30 PPIQWYKDCKPLQ--GDKRFIPKGSKLLIQNVTEEDAGNYTCKFTYT 74

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

Pssm-ID: 409398 Cd Length: 101 Bit Score: 38.24 E-value: 3.18e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  712 TVGETVALQCKALGSPPPRITWLHNDQPLRPSD--RHHFTP---GNQL---LVIGSALLKDAGRYTCLMSNTLGTERAHS 783
Cdd:cd05735     16 TKGQKKEMSCTAHGEKPIIVRWEKEDTIINPSEmsRYLVTTkevGDEVistLQILPTVREDSGFFSCHAINSYGEDRGII 95


                   ....*.
gi 1779345322  784 QLVVTE 789
Cdd:cd05735     96 QLTVQE 101

Immunoglobulin (Ig)-like domain of semaphorin 4D (Sema4D) and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain of semaphorin 4D (Sema4D) and similar proteins. Sema4D is a Class IV semaphorin. Semaphorins are classified based on structural features additional to the Sema domain. Sema4D has extracellular Sema and Ig domains, a transmembrane domain, and a short cytoplasmic domain. Sema4D plays a part in the development of GABAergic synapses. Sema4D in addition is an immune semaphorin. It is abundant on resting T cells; its expression is weak on resting B cells and antigen presenting cells (APCs), but is upregulated by various stimuli. The receptor used by Sema4D in the immune system is CD72. Sem4D enhances the activation of B cells and DCs through binding CD72, perhaps by reducing CD72s inhibitory signals. The receptor used by Sema4D in the non-lymphatic tissues is plexin-B1. Sem4D is anchored to the cell surface but its extracellular domain can be released from the cell surface by a metalloprotease-dependent process. Sem4D may mediate its effects in its membrane-bound form and/or its cleaved form.

Pssm-ID: 409457 Cd Length: 87 Bit Score: 37.87 E-value: 3.19e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1779345322  705 DLEDRSVTVGETVALQCKALgSPPPRITWLHNDQPLRPSDRHHFTPGNQLLvIGSALLKDAGRYTCL 771
Cdd:cd05873      2 DPRQRTFKLGGNAELKCSPK-SNLARVVWKFQGKVLKAESPKYGLYGDGLL-IFNASEADAGRYQCL 66

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: 37.86 E-value: 3.21e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  705 DLEDRSVTVGETVALQCKAL-GSPPPRITWLHNDQPLrpSDRHHFT-----PGNQLLVIGSALLKDAGRYTCLMSNTLGT 778
Cdd:cd20959      8 AFGEGAAQVGMRAQLHCGVPgGDLPLNIRWTLDGQPI--SDDLGITvsrlgRRSSILSIDSLEASHAGNYTCHARNSAGS 85


                   ....*....
gi 1779345322  779 ERAHSQLVV 787
Cdd:cd20959     86 ASYTAPLTV 94

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: 37.86 E-value: 3.68e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  619 TGHTARLECAAEGHPTP-QIAWQKDGG--TDFPAARDRRmhVMPDDDVFFITDVKPVDMGVYSCTAKNTAGTVSANATLT 695
Cdd:cd20959     16 VGMRAQLHCGVPGGDLPlNIRWTLDGQpiSDDLGITVSR--LGRRSSILSIDSLEASHAGNYTCHARNSAGSASYTAPLT 93


                   .
gi 1779345322  696 V 696
Cdd:cd20959     94 V 94

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: 36.07 E-value: 3.74e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 1779345322  185 LQVLRLSRNRISQIPVKAfQLPRLTQLELNRN-RIRQVEGL 224
Cdd:pfam12799    3 LEVLDLSNNQITDIPPLA-KLPNLETLDLSGNnKITDLSDL 42

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: 37.92 E-value: 3.80e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  490 PQITVQPEATMTVLGSDVRLTCTAASSSSSpmTFAWRKDQELLRNAEMEnyahVRAHHQAatpdLPGagggGVMEYTTIL 569
Cdd:cd07693      1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTP--TIQWLKNGQPLETDKDD----PRSHRIV----LPS----GSLFFLRVV 66

                           90       100       110
                   ....*....|....*....|....*....|...
gi 1779345322  570 HLRRVTfAHEGRYQCIITNHFGSTYSSKARLIV 602
Cdd:cd07693     67 HGRKGR-SDEGVYVCVAHNSLGEAVSRNASLEV 98

Fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell adhesion molecule 5 (CEACAM5) and similar domains; member of the C2-set IgSF domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell adhesion molecule 5 (CEACAM5) and similar domains. The CEA family is a group of anchored or secreted glycoproteins, expressed by epithelial cells, leukocytes, endothelial cells and placenta. The CEA family is divided into the CEACAM and pregnancy-specific glycoprotein (PSG) subfamilies. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), also known as CD66e (Cluster of Differentiation 66e), is a cell surface glycoprotein that plays a role in cell adhesion, intracellular signaling and tumor progression. Diseases associated with CEACAM5 include lung cancer and rectum cancer. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409540 Cd Length: 76 Bit Score: 37.09 E-value: 3.83e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  611 TPRDSTIRTGHTARLECAAEGHPTPQIAWQKDGGtdfpaardRRMHvmpdDDVFFITDVKPVDMGVYSCTAKNTAGTVSA 690
Cdd:cd20948      1 SPSDTYYLSGENLNLSCHAASNPPAQYSWTINGT--------FQTS----SQELFLPAITENNEGTYTCSAHNSLTGKNI 68


                   ....*.
gi 1779345322  691 NATLTV 696
Cdd:cd20948     69 SLVLSV 74

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: 38.29 E-value: 4.19e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  198 IPVKAFQLPRLTQLELNRNrIRQVEGLTFQGLSSLEVLKLQrNSISKLTDGAFFDlSKMKVLHLDyNSLTEVNSGSLYGL 277
Cdd:pfam13306    3 IGSYAFYNCSLTSITIPSS-LTSIGEYAFSNCTSLKSITLP-SSLTSIGSYAFYN-CSLTSITIP-SSLTSIGEYAFSNC 78

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1779345322  278 TSLQQLFLSNNsIARINPDGWKFCqKLRELNLSyNNLTRLDEGS 321
Cdd:pfam13306   79 SNLKSITLPSN-LTSIGSYAFSNC-SLKSITIP-SSVTTIGSYA 119

Immunoglobulin (Ig)-like domain of the class IV semaphorin Sema4B; The members here are composed of the immunoglobulin (Ig)-like domain of Sema4B and similar proteins. Sema4B is a Class IV semaphorin. Semaphorins are classified based on structural features additional to the Sema domain. Sema4B has extracellular Sema and Ig domains, a transmembrane domain, and a short cytoplasmic domain. Sema4B has been shown to preferentially regulate the development of the postsynaptic specialization at the glutamatergic synapses. This cytoplasmic domain includes a PDZ-binding motif upon which the synaptic localization of Sem4B is dependent. Sema4B is a ligand of CLCP1. CLCP1 was identified in an expression profiling analysis, which compared a highly metastic lung cancer subline with its low metastic parental line. Sema4B was shown to promote CLCP1 endocytosis and their interaction is a potential target for therapeutic intervention of metastasis.

Pssm-ID: 409456 Cd Length: 86 Bit Score: 37.42 E-value: 4.55e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1779345322  709 RSVTVGETVALQCKaLGSPPPRITWLHNDQPLRPSDRHHFTPGNQLLVIGsALLKDAGRYTC 770
Cdd:cd05872      6 RTVVAGADVVLPCQ-LRSNLASPVWLFNGTPLNAQFSYLRLGTDGLLILV-TSPEHSGTYRC 65

hypothetical protein; Provisional

Pssm-ID: 178695 [Multi-domain] Cd Length: 623 Bit Score: 40.95 E-value: 4.97e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  283 LFLSNNSIARINPDGWKFCQKLRELNLSYNNLTRLDEGSLAVLGDLHTLRLGHNSISHINEGAFRGLKALRILELDHNDI 362
Cdd:PLN03150   423 LGLDNQGLRGFIPNDISKLRHLQSINLSGNSIRGNIPPSLGSITSLEVLDLSYNSFNGSIPESLGQLTSLRILNLNGNSL 502

                           90
                   ....*....|
gi 1779345322  363 SGTIEDTNGA 372
Cdd:PLN03150   503 SGRVPAALGG 512

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: 37.60 E-value: 5.07e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322  718 ALQCKALGSPPPRITWLHNDQPLRPSD----RHHFTPG----NQLLVIGSALLKDAGRYTCLMSNTLGTERAHSQLVVTE 789
Cdd:cd05773     27 NLVCQAQGVPRVQFRWAKNGVPLDLGNpryeETTEHTGtvhtSILTIINVSAALDYALFTCTAHNSLGEDSLDIQLVSTS 106


                   .
gi 1779345322  790 R 790
Cdd:cd05773    107 R 107

Immunoglobulin Variable (IgV) domain of B7-H4; The members here are composed of the immunoglobulin variable (IgV) domain of B7-H4 (also known as B7-S1, B7x, or Vtcn1). B7-H4 is one of the B7 family of immune-regulatory ligands that act as negative regulators of T cell function; it contains one IgV domain and one IgC domain. The B7-family consists of structurally related cell-surface protein ligands, which bind to receptors on lymphocytes that regulate immune responses. The binding of B7-H4 to unidentified receptors results in the inhibition of TCR-mediated T cell proliferation, cell-cycle progression and IL-2 production. As a co-inhibitory molecule, B7-H4 is widely expressed in tumor tissues and its expression is significantly associated with poor prognosis in human cancers such as glioma, pancreatic cancer, oral squamous cell carcinoma, renal cell carcinoma, and lung cancer.

Pssm-ID: 409576 Cd Length: 110 Bit Score: 37.58 E-value: 5.85e-03

                           10        20        30
                   ....*....|....*....|....*....|.
gi 1779345322  751 GNQLLVIGSALLKDAGRYTCLMSNTLGTERA 781
Cdd:cd20984     74 GNASLRLKNVQLTDAGTYLCIISNSKGTGNA 104

Leucine-rich repeats, outliers;

Pssm-ID: 197688 [Multi-domain] Cd Length: 24 Bit Score: 35.02 E-value: 6.37e-03

                            10
                    ....*....|....*....
gi 1779345322    86 LPNLRELRLDHNELTSIPD 104
Cdd:smart00370    1 LPNLRELDLSNNQLSSLPP 19

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

Pssm-ID: 197687 [Multi-domain] Cd Length: 24 Bit Score: 35.02 E-value: 6.37e-03

                            10
                    ....*....|....*....
gi 1779345322    86 LPNLRELRLDHNELTSIPD 104
Cdd:smart00369    1 LPNLRELDLSNNQLSSLPP 19

Leucine-rich repeat;

Pssm-ID: 405295 [Multi-domain] Cd Length: 175 Bit Score: 38.59 E-value: 8.21e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779345322   90 RELRLDHNELTSIPDLGQAASKIVSLYLHHNKIRSIDG----RRTGELLsvetldLSNNDIT---ELRGQCFPaglHIRD 162
Cdd:pfam14580   22 RELDLRGYKIPIIENLGATLDQFDTIDFSDNEIRKLDGfpllRRLKTLL------LNNNRICrigEGLGEALP---NLTE 92

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1779345322  163 LYLSNNKISvlELGALDHLGE--TLQVLRLSRNRISQIP-VKAFQLPRLTQLE-LNRNRIRQVE 222
Cdd:pfam14580   93 LILTNNNLQ--ELGDLDPLASlkKLTFLSLLRNPVTNKPhYRLYVIYKVPQLRlLDFRKVKQKE 154

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: 8.65e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1779345322   87 PNLRELRLDHNELTSIPDLGQaASKIVSLYLHHN-KIRSIDG 127
Cdd:pfam12799    1 PNLEVLDLSNNQITDIPPLAK-LPNLETLDLSGNnKITDLSD 41