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: 203.62 E-value: 1.98e-61

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  607 SFIKTPRDSTIRTGHTARLECAAEGHPAPQIAWQKDGGTDFPAARDRRMHVMPDDDVFFITDVKPVDMGVYSCTAKNTAG 686
Cdd:cd05763     1 SFTKTPHDITIRAGSTARLECAATGHPTPQIAWQKDGGTDFPAARERRMHVMPEDDVFFIVDVKIEDTGVYSCTAQNSAG 80

                          90
                  ....*....|.
gi 583978668  687 TVSANATLTVL 697
Cdd:cd05763    81 SISANATLTVL 91

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

Pssm-ID: 443914 [Multi-domain] Cd Length: 414 Bit Score: 133.52 E-value: 3.24e-33

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668   39 NCTCSGDSVDCSNLELTATPLDLPVRTVSLNLGYNKLTSISPEAFANLPNLRELRLDHNELTSIPDLGQAASTIVSLYLH 118
Cdd:COG4886     1 LLLLLLSLTLKLLLLLLLELLTTLILLLLLLLLLLALLLLSLLSLLLLLTLLLSLLLRDLLLSSLLLLLSLLLLLLLSLL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  119 HNKIRSIDGRRTGELLSVETLDLSNND-ITELRgqcfpaglHIRDLYLSNNKISVL--ELGVLDHlgetLQVLRLSRNRI 195
Cdd:COG4886    81 LLSLLLLGLTDLGDLTNLTELDLSGNEeLSNLT--------NLESLDLSGNQLTDLpeELANLTN----LKELDLSNNQL 148

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  196 SQIPVKAFQLPRLTQLELNRNRIRQVeGLTFQGLSSLEVLKLQRNSISKLTDgAFFDLAKMKVLHLDYNSLTEVnSGSLY 275
Cdd:COG4886   149 TDLPEPLGNLTNLKSLDLSNNQLTDL-PEELGNLTNLKELDLSNNQITDLPE-PLGNLTNLEELDLSGNQLTDL-PEPLA 225

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  276 GLTSLQQLFLSNNSIARInpDGWKFCQKLRELNLSYNNLTRLDEgsLAVLGDLHTLRLGHNSISHINEGAFRGLKALRIL 355
Cdd:COG4886   226 NLTNLETLDLSNNQLTDL--PELGNLTNLEELDLSNNQLTDLPP--LANLTNLKTLDLSNNQLTDLKLKELELLLGLNSL 301

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  356 ELDHNDISGTIEDTNGAFSGLDSLIKLTLFGNKIKSVAKKAFSGLDTLEHLNLGENAIRSIQPDAFTKMRNLKSLLIQSN 435
Cdd:COG4886   302 LLLLLLLNLLELLILLLLLTTLLLLLLLLKGLLVTLTTLALSLSLLALLTLLLLLNLLSLLLTLLLTLGLLGLLEATLLT 381

                         410       420
                  ....*....|....*....|....*..
gi 583978668  436 SLLCDCQLHWLPDWLVARGLQVGINAT 462
Cdd:COG4886   382 LALLLLTLLLLLLTTTAGVLLLTLALL 408

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

Pssm-ID: 443914 [Multi-domain] Cd Length: 414 Bit Score: 121.58 E-value: 3.43e-29

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  110 STIVSLYLHHNKIRSIDGRRTGELLSVETLDLSNNDITELRGQCFPAGLHIRDLYLSNNKISVLELGVLDHLGETLQVLR 189
Cdd:COG4886     9 TLKLLLLLLLELLTTLILLLLLLLLLLALLLLSLLSLLLLLTLLLSLLLRDLLLSSLLLLLSLLLLLLLSLLLLSLLLLG 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  190 LSrnrisqipvKAFQLPRLTQLELNRNRirqveglTFQGLSSLEVLKLQRNSISKLTDgAFFDLAKMKVLHLDYNSLTEV 269
Cdd:COG4886    89 LT---------DLGDLTNLTELDLSGNE-------ELSNLTNLESLDLSGNQLTDLPE-ELANLTNLKELDLSNNQLTDL 151

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  270 NSgSLYGLTSLQQLFLSNNSIARInPDGWKFCQKLRELNLSYNNLTRLDEgSLAVLGDLHTLRLGHNSISHINEgAFRGL 349
Cdd:COG4886   152 PE-PLGNLTNLKSLDLSNNQLTDL-PEELGNLTNLKELDLSNNQITDLPE-PLGNLTNLEELDLSGNQLTDLPE-PLANL 227

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  350 KALRILELDHNDISgTIEDtngaFSGLDSLIKLTLFGNKIKSVAKkaFSGLDTLEHLNLGENAIRSIQPDAFTKMRNLKS 429
Cdd:COG4886   228 TNLETLDLSNNQLT-DLPE----LGNLTNLEELDLSNNQLTDLPP--LANLTNLKTLDLSNNQLTDLKLKELELLLGLNS 300

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 583978668  430 LLIQSNSLLCDCQLHWLPDWLVARGLQVGINATCAHPESLKGKSVFEVPPSSFVCDDLP 488
Cdd:COG4886   301 LLLLLLLLNLLELLILLLLLTTLLLLLLLLKGLLVTLTTLALSLSLLALLTLLLLLNLL 359

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 102.34 E-value: 5.67e-26

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668   606 PSFIKTPRDSTIRTGHTARLECAAEGHPAPQIAWQKDGgTDFPAARDRRMHVMPDDDVFFITDVKPVDMGVYSCTAKNTA 685
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDG-QPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSA 79

                           90
                   ....*....|.
gi 583978668   686 GTVSANATLTV 696
Cdd:pfam07679   80 GEAEASAELTV 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: 94.47 E-value: 1.34e-21

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  207 RLTQLELNRNRIRQVEGLTFqgLSSLEVLKLQRNSISKLTDgaFFDLAKMKVLHLDYNSLTEVNSgsLYGLTSLQQLFLS 286
Cdd:cd21340     3 RITHLYLNDKNITKIDNLSL--CKNLKVLYLYDNKITKIEN--LEFLTNLTHLYLQNNQIEKIEN--LENLVNLKKLYLG 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  287 NNSIARINpdGWKFCQKLRELNLSYNNLTR-----LDEGSLAVLGD-LHTLRLGHNSISHINEgaFRGLKALRILELDHN 360
Cdd:cd21340    77 GNRISVVE--GLENLTNLEELHIENQRLPPgekltFDPRSLAALSNsLRVLNISGNNIDSLEP--LAPLRNLEQLDASNN 152

                         170       180       190
                  ....*....|....*....|....*....|....
gi 583978668  361 DISGtIEDTNGAFSGLDSLIKLTLFGNKIKSVAK 394
Cdd:cd21340   153 QISD-LEELLDLLSSWPSLRELDLTGNPVCKKPK 185

leucine-rich repeat receptor-like protein kinase; Provisional

Pssm-ID: 215061 [Multi-domain] Cd Length: 968 Bit Score: 99.15 E-value: 6.43e-21

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668   30 LSSDTPCAQNCTCSGdsVDCSNLEltatpldlpvRTVSLNL-GYNKLTSISPEAFaNLPNLRELRLDHNELT-SIP-DLG 106
Cdd:PLN00113   48 LSNWNSSADVCLWQG--ITCNNSS----------RVVSIDLsGKNISGKISSAIF-RLPYIQTINLSNNQLSgPIPdDIF 114

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  107 QAASTIVSLYLHHNKIR-SIDGrrtGELLSVETLDLSNNDITELRGQCFPAGLHIRDLYLSNNkisVLELGVLDHLGE-- 183
Cdd:PLN00113  115 TTSSSLRYLNLSNNNFTgSIPR---GSIPNLETLDLSNNMLSGEIPNDIGSFSSLKVLDLGGN---VLVGKIPNSLTNlt 188

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  184 TLQVLRLSRNR-ISQIPVKAFQLPRLTQLELNRNRIRQVEGLTFQGLSSLEVLKLQRNSISKLTDGAFFDLAKMKVLHLD 262
Cdd:PLN00113  189 SLEFLTLASNQlVGQIPRELGQMKSLKWIYLGYNNLSGEIPYEIGGLTSLNHLDLVYNNLTGPIPSSLGNLKNLQYLFLY 268

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  263 YNSLTEVNSGSLYGLTSLQQLFLSNNSIARINPDGWKFCQKLRELNLSYNNLTRLDEGSLAVLGDLHTLRLGHNSISHIN 342
Cdd:PLN00113  269 QNKLSGPIPPSIFSLQKLISLDLSDNSLSGEIPELVIQLQNLEILHLFSNNFTGKIPVALTSLPRLQVLQLWSNKFSGEI 348

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  343 EGAFRGLKALRILELDHNDISGTIEDTNGAfSGldSLIKLTLFGNKIKSVAKKAFSGLDTLEHLNLGENAIRSIQPDAFT 422
Cdd:PLN00113  349 PKNLGKHNNLTVLDLSTNNLTGEIPEGLCS-SG--NLFKLILFSNSLEGEIPKSLGACRSLRRVRLQDNSFSGELPSEFT 425

                         410
                  ....*....|....*.
gi 583978668  423 KMRNLKSLLIQSNSLL 438
Cdd:PLN00113  426 KLPLVYFLDISNNNLQ 441

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 86.93 E-value: 1.55e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668   700 PHLAQDLEDRSVTVGETVALQCKALGSPPPRITWLHNDQPLRPSDRH--HFTPGNQLLVIGSALLKDAGRYTCLMSNTLG 777
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFkvTYEGGTYTLTISNVQPDDSGKYTCVATNSAG 80

                           90
                   ....*....|
gi 583978668   778 TERAHSQLVV 787
Cdd:pfam07679   81 EAEASAELTV 90

leucine-rich repeat receptor-like protein kinase; Provisional

Pssm-ID: 215061 [Multi-domain] Cd Length: 968 Bit Score: 96.46 E-value: 4.51e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668   68 LNLGYNKLTSISPEAFANLPNLRELRLDHNELT-SIP-DLGQAAStIVSLYLHHNKIRSIDGRRTGELLSVETLDLSNND 145
Cdd:PLN00113  169 LDLGGNVLVGKIPNSLTNLTSLEFLTLASNQLVgQIPrELGQMKS-LKWIYLGYNNLSGEIPYEIGGLTSLNHLDLVYNN 247

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  146 ITelrGQCFPAGLHIRDL---YLSNNKI------SVLELGVLDHL--------GE---------TLQVLRL-SRNRISQI 198
Cdd:PLN00113  248 LT---GPIPSSLGNLKNLqylFLYQNKLsgpippSIFSLQKLISLdlsdnslsGEipelviqlqNLEILHLfSNNFTGKI 324

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  199 PVKAFQLPRLTQLELNRNRIRQVEGLTFQGLSSLEVLKLQRNSIS-KLTDGaFFDLAKMKVLHLDYNSLTEVNSGSLYGL 277
Cdd:PLN00113  325 PVALTSLPRLQVLQLWSNKFSGEIPKNLGKHNNLTVLDLSTNNLTgEIPEG-LCSSGNLFKLILFSNSLEGEIPKSLGAC 403

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  278 TSLQQLFLSNNSIARINPDGWKFCQKLRELNLSYNNLTRLDEGSLAVLGDLHTLRLGHNSISHINEGAFRGlKALRILEL 357
Cdd:PLN00113  404 RSLRRVRLQDNSFSGELPSEFTKLPLVYFLDISNNNLQGRINSRKWDMPSLQMLSLARNKFFGGLPDSFGS-KRLENLDL 482

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  358 DHNDISGTIEDTNGAFSgldSLIKLTLFGNKIKSVAKKAFSGLDTLEHLNLGENAIRSIQPDAFTKMRNLKSLLIQSNSL 437
Cdd:PLN00113  483 SRNQFSGAVPRKLGSLS---ELMQLKLSENKLSGEIPDELSSCKKLVSLDLSHNQLSGQIPASFSEMPVLSQLDLSQNQL 559

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: 82.44 E-value: 6.03e-19

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  609 IKTPRDSTIRTGHTARLECAAEGHPAPQIAWQKDGGtDFPaarDRRMHVMpDDDVFFITDVKPVDMGVYSCTAKNTAGTV 688
Cdd:cd05725     1 VKRPQNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDG-ELP---KGRYEIL-DDHSLKIRKVTAGDMGSYTCVAENMVGKI 75


                  ....*...
gi 583978668  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: 84.84 E-value: 2.42e-18

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668   74 KLTSIspEAFANLPNLRELRLDHNELTSIPDLGQAaSTIVSLYLHHNKIRSIDGrrTGELLSVETLDLSNNDITELrgqc 153
Cdd:cd21340    13 NITKI--DNLSLCKNLKVLYLYDNKITKIENLEFL-TNLTHLYLQNNQIEKIEN--LENLVNLKKLYLGGNRISVV---- 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  154 fpAGLH----IRDLYLSNNKisvLELGV--------LDHLGETLQVLRLSRNRISQI-PVKAfqLPRLTQLELNRNRIRQ 220
Cdd:cd21340    84 --EGLEnltnLEELHIENQR---LPPGEkltfdprsLAALSNSLRVLNISGNNIDSLePLAP--LRNLEQLDASNNQISD 156

                         170       180
                  ....*....|....*....|....*.
gi 583978668  221 VEGL--TFQGLSSLEVLKLQRNSISK 244
Cdd:cd21340   157 LEELldLLSSWPSLRELDLTGNPVCK 182

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: 82.14 E-value: 2.21e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  115 LYLHHNKIRSIDGRRTGELLSVetLDLSNNDITELRG-QCFPaglHIRDLYLSNNKISVLElgVLDHLgetlqvlrlsrn 193
Cdd:cd21340     7 LYLNDKNITKIDNLSLCKNLKV--LYLYDNKITKIENlEFLT---NLTHLYLQNNQIEKIE--NLENL------------ 67

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  194 risqipvkafqlPRLTQLELNRNRIRQVEGLtfQGLSSLEVLKLQRNSI---SKLTdgafFDLAKM-------KVLHLDY 263
Cdd:cd21340    68 ------------VNLKKLYLGGNRISVVEGL--ENLTNLEELHIENQRLppgEKLT----FDPRSLaalsnslRVLNISG 129

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 583978668  264 NSLTEVNsgSLYGLTSLQQLFLSNNSIARINPDGWKF--CQKLRELNLSYNNLTR 316
Cdd:cd21340   130 NNIDSLE--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: 76.05 E-value: 1.49e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  606 PSFIKTPRDSTIRTGHTARLECAAEGHPAPQIAWQKDG---GTDFPAARDRRMhVMPDDDVFFITDV-----KPvDMGVY 677
Cdd:cd07693     1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGqplETDKDDPRSHRI-VLPSGSLFFLRVVhgrkgRS-DEGVY 78

                          90       100
                  ....*....|....*....|
gi 583978668  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: 84.51 E-value: 2.03e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668   66 VSLNLGYNKLTSISPEAFANLPNLRELRLDHNELT-SIPDLGQAASTIVSLYLHHNKIRSIDGRRTGELLSVETLDLSNN 144
Cdd:PLN00113  287 ISLDLSDNSLSGEIPELVIQLQNLEILHLFSNNFTgKIPVALTSLPRLQVLQLWSNKFSGEIPKNLGKHNNLTVLDLSTN 366

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  145 DITelrGQcFPAGL----HIRDLYLSNNKisvLELGVLDHLG--ETLQVLRLSRNRIS-QIPVKAFQLPRLTQLELNRNR 217
Cdd:PLN00113  367 NLT---GE-IPEGLcssgNLFKLILFSNS---LEGEIPKSLGacRSLRRVRLQDNSFSgELPSEFTKLPLVYFLDISNNN 439

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  218 IRQVEGLTFQGLSSLEVLKLQRNSIS-KLTDgaFFDLAKMKVLHLDYNSLTEVNSGSLYGLTSLQQLFLSNNSIARINPD 296
Cdd:PLN00113  440 LQGRINSRKWDMPSLQMLSLARNKFFgGLPD--SFGSKRLENLDLSRNQFSGAVPRKLGSLSELMQLKLSENKLSGEIPD 517

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  297 GWKFCQKLRELNLSYNNLTRLDEGSLAVLGDLHTLRLGHNSISHINEGAFRGLKALRILELDHNDISGTIEDTnGAFSGL 376
Cdd:PLN00113  518 ELSSCKKLVSLDLSHNQLSGQIPASFSEMPVLSQLDLSQNQLSGEIPKNLGNVESLVQVNISHNHLHGSLPST-GAFLAI 596


                  ..
gi 583978668  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: 72.60 E-value: 1.24e-15

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 583978668   606 PSFIKTPRDSTIRTGHTARLECAAEGHPAPQIAWQKDGGTDFPaARDRRMHVMPDDDVFFITDVKPVDMGVYSCTAKN 683
Cdd:pfam13927    2 PVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISS-GSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

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 583978668  700 PHLAQDLEDRSVTVGETVALQCKALGSPPPRITWLHNDQPLRPSDRHHF---TPGNQLLVIGSALLKDAGRYTCLMSNTL 776
Cdd:cd05744     1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMlvrENGRHSLIIEPVTKRDAGIYTCIARNRA 80

                          90
                  ....*....|.
gi 583978668  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: 3.32e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  606 PSFIKTPRDSTIRTGHTARLECAAEGHPAPQIAWQKDGgTDFPAARDRrMHVMPDDDVFFITDVKPVDMGVYSCTAKNTA 685
Cdd:cd20976     2 PSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNA-QPLQYAADR-STCEAGVGELHIQDVLPEDHGTYTCLAKNAA 79

                          90
                  ....*....|.
gi 583978668  686 GTVSANATLTV 696
Cdd:cd20976    80 GQVSCSAWVTV 90

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: 71.38 E-value: 4.48e-15

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668    612 PRDSTIRTGHTARLECAAEGHPAPQIAWQKDGGTdfPAARDRRMHVMPDDDVF--FITDVKPVDMGVYSCTAKNTAGTVS 689
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGK--LLAESGRFSVSRSGSTStlTISNVTPEDSGTYTCAATNSSGSAS 78


                    ....*..
gi 583978668    690 ANATLTV 696
Cdd:smart00410   79 SGTTLTV 85

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: 7.61e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  702 LAQDLEDRSVTVGETVALQCKALGSPPPRITWLHNDQPLRPSDRHHFTPGNQLLVIGSALLKDAGRYTCLMSNTLGTERA 781
Cdd:cd20952     2 ILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDERITTLENGSLQIKGAEKSDTGEYTCVALNLSGEATW 81


                  ....*.
gi 583978668  782 HSQLVV 787
Cdd:cd20952    82 SAVLDV 87

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: 70.56 E-value: 8.56e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  609 IKTPRDSTIRTGHTARLECAAEGHPAPQIAWQKDGGTDFPAARDRRMHVMPDDDVFfiTDVKPVDMGVYSCTAKNTAGTV 688
Cdd:cd04978     3 IIEPPSLVLSPGETGELICEAEGNPQPTITWRLNGVPIEPAPEDMRRTVDGRTLIF--SNLQPNDTAVYQCNASNVHGYL 80


                  ....*....
gi 583978668  689 SANATLTVL 697
Cdd:cd04978    81 LANAFLHVL 89

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 69.52 E-value: 1.44e-14

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 583978668   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: 1.68e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  609 IKTPRDSTIRTGHTARLECAAEGHPAPQIAWQKDGGtdfPAARDRRMHVMPDDD---VFFITDVKPVDMGVYSCTAKNTA 685
Cdd:cd20973     1 IQTLRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDN---PIVESRRFQIDQDEDglcSLIISDVCGDDSGKYTCKAVNSL 77

                          90
                  ....*....|.
gi 583978668  686 GTVSANATLTV 696
Cdd:cd20973    78 GEATCSAELTV 88

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: 2.30e-14

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668    707 EDRSVTVGETVALQCKALGSPPPRITWLHND-QPLRPSDRHHFTPGNQL--LVIGSALLKDAGRYTCLMSNTLGTERAHS 783
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGgKLLAESGRFSVSRSGSTstLTISNVTPEDSGTYTCAATNSSGSASSGT 81


                    ....
gi 583978668    784 QLVV 787
Cdd:smart00410   82 TLTV 85

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

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 68.43 E-value: 5.65e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  700 PHLAQDLEDRSVTVGETVALQCKALGSPPPRITWLHNDQPLR-PSDRHHFTPGNQLLVIGSALLKDAGRYTCLMSNTLGT 778
Cdd:cd20976     2 PSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQyAADRSTCEAGVGELHIQDVLPEDHGTYTCLAKNAAGQ 81


                  ....*....
gi 583978668  779 ERAHSQLVV 787
Cdd:cd20976    82 VSCSAWVTV 90

Leucine rich repeat;

Pssm-ID: 404697 [Multi-domain] Cd Length: 61 Bit Score: 67.16 E-value: 6.19e-14

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 583978668   230 SSLEVLKLQRNSISKLTDGAFFDLAKMKVLHLDYNSLTEVNSGSLYGLTSLQQLFLSNNSI 290
Cdd:pfam13855    1 PNLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

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: 68.29 E-value: 6.78e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  606 PSFIKTPRDSTIRTGHTARLECAAEGHPAPQIAWQKDGGTDFPAARDRRMHVMPDDDVFFITDVKPVDMGVYSCTAKNTA 685
Cdd:cd05744     1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVRENGRHSLIIEPVTKRDAGIYTCIARNRA 80

                          90
                  ....*....|.
gi 583978668  686 GTVSANATLTV 696
Cdd:cd05744    81 GENSFNAELVV 91

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

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 67.92 E-value: 8.16e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  612 PRDSTIRTGHTARLECAAEGHPAPQIAWQKDGGTdfPAARDRRMHVMPDDDVFFITDVKPVDMGVYSCTAKNTA-GTVSA 690
Cdd:cd20970     9 SFTVTAREGENATFMCRAEGSPEPEISWTRNGNL--IIEFNTRYIVRENGTTLTIRNIRRSDMGIYLCIASNGVpGSVEK 86


                  ....*.
gi 583978668  691 NATLTV 696
Cdd:cd20970    87 RITLQV 92

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: 67.59 E-value: 1.23e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  606 PSFIKTPRDSTIRTGHTARLECAAEGHPAPQIAWQKDGgtdFPAARDRRM----HVMPDDDV---FFITDVKPVDMGVYS 678
Cdd:cd20956     2 PVLLETFSEQTLQPGPSVSLKCVASGNPLPQITWTLDG---FPIPESPRFrvgdYVTSDGDVvsyVNISSVRVEDGGEYT 78

                          90
                  ....*....|....*...
gi 583978668  679 CTAKNTAGTVSANATLTV 696
Cdd:cd20956    79 CTATNDVGSVSHSARINV 96

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: 67.67 E-value: 1.39e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  608 FIKTPRDSTIRTGHTARLECAAEGHPAPQIAWQKDGGTDF-----PAARDRRMHVMPDDDVfFITDVKPVDMGVYSCTAK 682
Cdd:cd05726     2 FVVKPRDQVVALGRTVTFQCETKGNPQPAIFWQKEGSQNLlfpyqPPQPSSRFSVSPTGDL-TITNVQRSDVGYYICQAL 80

                          90
                  ....*....|....
gi 583978668  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: 1.59e-13

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 583978668   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: 65.50 E-value: 5.70e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  612 PRDSTIRTGHTARLECAA-EGHPAPQIAWQKDGGTdfPAARDRRMHVMpDDDVFFITDVKPVDMGVYSCTAKNTAGT-VS 689
Cdd:cd05724     4 PSDTQVAVGEMAVLECSPpRGHPEPTVSWRKDGQP--LNLDNERVRIV-DDGNLLIAEARKSDEGTYKCVATNMVGErES 80


                  ....*..
gi 583978668  690 ANATLTV 696
Cdd:cd05724    81 RAARLSV 87

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

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 65.21 E-value: 7.14e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  608 FIKTPRDSTIRTGHTARLECAAEGHPAPQIAWQKDGGTDfpAARDRRMHVMPdDDVFFITDVKPVDMGVYSCTAKNTAGT 687
Cdd:cd20952     2 ILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPL--LGKDERITTLE-NGSLQIKGAEKSDTGEYTCVALNLSGE 78


                  ....*....
gi 583978668  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: 8.53e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  606 PSFIKTPRDSTIRTGHTARLECAAEGHPAPQIAWQKDGGTDFPAARDRRMHVMPDDDV--FFITDVKPVDMGVYSCTAKN 683
Cdd:cd20951     1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDPSSIPGKYKIESEYGVhvLHIRRVTVEDSAVYSAVAKN 80

                          90
                  ....*....|...
gi 583978668  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: 8.90e-13

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 583978668  717 VALQCKALGSPPPRITWLHNDQPLRPS--DRHHFTPGNQLLVIGSALLKDAGRYTCLMSNTLGTERAHS 783
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSsrDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASAS 69

Leucine rich repeat;

Pssm-ID: 404697 [Multi-domain] Cd Length: 61 Bit Score: 62.93 E-value: 1.85e-12

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 583978668   206 PRLTQLELNRNRIRQVEGLTFQGLSSLEVLKLQRNSISKLTDGAFFDLAKMKVLHLDYNSL 266
Cdd:pfam13855    1 PNLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 63.95 E-value: 2.11e-12

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 583978668  710 SVTVGETVALQCKALGSPPPRITWLHNDQPL-RPSDRHHFTPGNqlLVIGSALLKDAGRYTCLMSNTLGTERAHSQLVV 787
Cdd:cd20978    12 VVKGGQDVTLPCQVTGVPQPKITWLHNGKPLqGPMERATVEDGT--LTIINVQPEDTGYYGCVATNEIGDIYTETLLHV 88

type III secretion system effector E3 ubiquitin transferase SlrP;

Pssm-ID: 185268 [Multi-domain] Cd Length: 754 Bit Score: 71.27 E-value: 2.47e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668   52 LELTATPLDLPVRTVSLNLGYNKLTSIsPEafaNL-PNLRELRLDHNELTSIPdlgqaaSTIVSlylhhnkirsidgrrt 130
Cdd:PRK15370  188 LGLTTIPACIPEQITTLILDNNELKSL-PE---NLqGNIKTLYANSNQLTSIP------ATLPD---------------- 241

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  131 gellSVETLDLSNNDITELRgQCFPAGLhiRDLYLSNNKISVLElgvlDHLGETLQVLRLSRNRISQIPVkafQLPrltq 210
Cdd:PRK15370  242 ----TIQEMELSINRITELP-ERLPSAL--QSLDLFHNKISCLP----ENLPEELRYLSVYDNSIRTLPA---HLP---- 303

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  211 lelnrnrirqvegltfqglSSLEVLKLQRNSISKLTDGAFFDLakmKVLHLDYNSLTEVNSgSLygLTSLQQLFLSNNSI 290
Cdd:PRK15370  304 -------------------SGITHLNVQSNSLTALPETLPPGL---KTLEAGENALTSLPA-SL--PPELQVLDVSKNQI 358

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  291 ArINPDgwKFCQKLRELNLSYNNLTRLDEGSLAVlgdLHTLRLGHNSISHINEG--AFR--GLKALRILeLDHNDISG-T 365
Cdd:PRK15370  359 T-VLPE--TLPPTITTLDVSRNALTNLPENLPAA---LQIMQASRNNLVRLPESlpHFRgeGPQPTRII-VEYNPFSErT 431

                         330
                  ....*....|..
gi 583978668  366 IEDTNGAFSGLD 377
Cdd:PRK15370  432 IQNMQRLMSSVG 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: 62.61 E-value: 6.35e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  608 FIKTPRDSTIRTGHTARLECAAEGHPAPQIAWQKDGGTDFPAARDRRMHVmpDDDVFFITDVKPVDMGVYSCTAKNTAGT 687
Cdd:cd05867     2 WTRRPQSHLYGPGETARLDCQVEGIPTPNITWSINGAPIEGTDPDPRRHV--SSGALILTDVQPSDTAVYQCEARNRHGN 79

                          90
                  ....*....|
gi 583978668  688 VSANATLTVL 697
Cdd:cd05867    80 LLANAHVHVV 89

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: 1.44e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  700 PHLAQDLEDRSVTVGETVALQCKALGSPPPRITWLHNDQPLRPSDRHHFTPGNQL--LVIGSALLKDAGRYTCLMSNTLG 777
Cdd:cd20972     2 PQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSPDIQIHQEGDLhsLIIAEAFEEDTGRYSCLATNSVG 81

                          90
                  ....*....|
gi 583978668  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: 2.25e-11

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 583978668  623 ARLECAAEGHPAPQIAWQKDGGTDFPAARDRRMHVmPDDDVFFITDVKPVDMGVYSCTAKNTA-GTVSANA 692
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSE-LGNGTLTISNVTLEDSGTYTCVASNSAgGSASASV 70

Leucine rich repeat;

Pssm-ID: 404697 [Multi-domain] Cd Length: 61 Bit Score: 59.85 E-value: 2.46e-11

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668   255 KMKVLHLDYNSLTEVNSGSLYGLTSLQQLFLSNNSIARINPDGWKFCQKLRELNLSYNNL 314
Cdd:pfam13855    2 NLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

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: 3.75e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  608 FIKTPRDSTIRTGHTARLECAAEGHPAPQIAWQKDGGtdfPAARDRRMHVMPDDdvFFITDVKPVDMGVYSCTAKNTAGT 687
Cdd:cd05728     2 WLKVISDTEADIGSSLRWECKASGNPRPAYRWLKNGQ---PLASENRIEVEAGD--LRITKLSLSDSGMYQCVAENKHGT 76


                  ....*....
gi 583978668  688 VSANATLTV 696
Cdd:cd05728    77 IYASAELAV 85

Leucine rich repeat;

Pssm-ID: 404697 [Multi-domain] Cd Length: 61 Bit Score: 58.69 E-value: 5.55e-11

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668   378 SLIKLTLFGNKIKSVAKKAFSGLDTLEHLNLGENAIRSIQPDAFTKMRNLKSLLIQSNSL 437
Cdd:pfam13855    2 NLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

Leucine rich repeat;

Pssm-ID: 404697 [Multi-domain] Cd Length: 61 Bit Score: 58.30 E-value: 8.44e-11

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 583978668   328 LHTLRLGHNSISHINEGAFRGLKALRILELDHNDISgTIEdtNGAFSGLDSLIKLTLFGNKI 389
Cdd:pfam13855    3 LRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLT-TLS--PGAFSGLPSLRYLDLSGNRL 61

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

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 59.08 E-value: 9.67e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  612 PRDSTIRTGHTARLECAAEGHPAPQIAWQKDGGtdfPAARDRRMHVMpDDDVFFITDVKPVDMGVYSCTAKNTAGTVSAN 691
Cdd:cd20957     8 PPVQTVDFGRTAVFNCSVTGNPIHTVLWMKDGK---PLGHSSRVQIL-SEDVLVIPSVKREDKGMYQCFVRNDGDSAQAT 83


                  ...
gi 583978668  692 ATL 694
Cdd:cd20957    84 AEL 86

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 583978668  711 VTVGETVALQCKALGSPPPRITWLHNDQPLRPSDRHHFTPgNQLLVIGSALLKDAGRYTCLMSNTLGTERAHSQLVV 787
Cdd:cd04969    14 AAKGGDVIIECKPKASPKPTISWSKGTELLTNSSRICILP-DGSLKIKNVTKSDEGKYTCFAVNFFGKANSTGSLSV 89

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: 59.13 E-value: 1.14e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  606 PSFIKTPRDSTIRTGHTARLECAAEGHPAPQIAWQKDgGTDFPAARDRRMHVMPDDDVFFITDVKPVDMGVYSCTAKNTA 685
Cdd:cd20972     2 PQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCE-GKELQNSPDIQIHQEGDLHSLIIAEAFEEDTGRYSCLATNSV 80

                          90
                  ....*....|.
gi 583978668  686 GTVSANATLTV 696
Cdd:cd20972    81 GSDTTSAEIFV 91

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

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 58.81 E-value: 1.40e-10

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 583978668  714 GETVALQCKALGSPPPRITWLHNDQPLRP--SDRHHFTPGNQLLVIGSALLKDAGRYTCLMSNTLGTERAHSQLVVTE 789
Cdd:cd05736    15 GVEASLRCHAEGIPLPRVQWLKNGMDINPklSKQLTLIANGSELHISNVRYEDTGAYTCIAKNEGGVDEDISSLFVED 92

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: 63.53 E-value: 1.55e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668   81 EAFANLPNLRELRLDHNELT--SIPDLGQAA---STIVSLYLHHNKIRSI--------DGRRTGELLSveTLDLSNNDIT 147
Cdd:cd00116    17 ELLPKLLCLQVLRLEGNTLGeeAAKALASALrpqPSLKELCLSLNETGRIprglqsllQGLTKGCGLQ--ELDLSDNALG 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  148 ELRGQCFPAGLHI---RDLYLSNNKISVLEL----GVLDHLGETLQVLRLSRNRISQIPV----KAFQ-LPRLTQLELNR 215
Cdd:cd00116    95 PDGCGVLESLLRSsslQELKLNNNGLGDRGLrllaKGLKDLPPALEKLVLGRNRLEGASCealaKALRaNRDLKELNLAN 174

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  216 NRIRqVEGLT--FQGL---SSLEVLKLQRNSI----SKLTDGAFFDLAKMKVLHLDYNSLTEVnsgslyGLTSLQQLFLS 286
Cdd:cd00116   175 NGIG-DAGIRalAEGLkanCNLEVLDLNNNGLtdegASALAETLASLKSLEVLNLGDNNLTDA------GAAALASALLS 247

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*..
gi 583978668  287 NNsiarinpdgwkfcQKLRELNLSYNNLTRLDEGSLA-VLGDLHTLR 332
Cdd:cd00116   248 PN-------------ISLLTLSLSCNDITDDGAKDLAeVLAEKESLL 281

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: 58.33 E-value: 1.91e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  606 PSFIKTPRDSTIRTGHTARLECAAEGHPAPQIAWQKDggtdfpaARDRRMHVMPDDDV-----------FFITDVKPVDM 674
Cdd:cd05765     1 PALVNSPTHQTVKVGETASFHCDVTGRPQPEITWEKQ-------VPGKENLIMRPNHVrgnvvvtnigqLVIYNAQPQDA 73

                          90       100
                  ....*....|....*....|..
gi 583978668  675 GVYSCTAKNTAGTVSANATLTV 696
Cdd:cd05765    74 GLYTCTARNSGGLLRANFPLSV 95

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: 2.01e-10

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 583978668  620 GHTARLECAAEGHPAPQIAWQKDGGtdfPAARDRRmHVMPDDDVFFITDVKPVDMGVYSCTAKNTAGTVSANATLTV 696
Cdd:cd05745     2 GQTVDFLCEAQGYPQPVIAWTKGGS---QLSVDRR-HLVLSSGTLRISRVALHDQGQYECQAVNIVGSQRTVAQLTV 74

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: 58.24 E-value: 2.13e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  606 PSFIKTPRDSTIRTGHTARLECAAEGHPAPQIAWQKDG-----GTDfpaardrRMHVMPDDD---VFFITDVKPVDMGVY 677
Cdd:cd05892     1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKKNNemlqyNTD-------RISLYQDNCgriCLLIQNANKKDAGWY 73

                          90
                  ....*....|....*....
gi 583978668  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: 58.19 E-value: 2.61e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  606 PSFIKTPRDSTIRTGHTARLECAAEGHPAPQIAWQKDGGTDFPAARDRRMHVMPDDDVFFITDVKPVDMGVYSCTAKNTA 685
Cdd:cd20990     1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSAHKMLVRENGVHSLIIEPVTSRDAGIYTCIATNRA 80

                          90
                  ....*....|.
gi 583978668  686 GTVSANATLTV 696
Cdd:cd20990    81 GQNSFNLELVV 91

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 583978668  703 AQDLEDRSVTVGETVALQCKALGSPPPRITWLHNDQPLRPSDRHHFTPGnqLLVIGSALLKDAGRYTCLMSNTLGTERAH 782
Cdd:cd04968     5 VRFPADTYALKGQTVTLECFALGNPVPQIKWRKVDGSPSSQWEITTSEP--VLEIPNVQFEDEGTYECEAENSRGKDTVQ 82


                  ....*
gi 583978668  783 SQLVV 787
Cdd:cd04968    83 GRIIV 87

Leucine rich repeat;

Pssm-ID: 404697 [Multi-domain] Cd Length: 61 Bit Score: 56.76 E-value: 3.49e-10

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668   184 TLQVLRLSRNRISQIPVKAFQ-LPRLTQLELNRNRIRQVEGLTFQGLSSLEVLKLQRNSI 242
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: 57.47 E-value: 3.57e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  606 PSFIKTP--RDSTIRTGHTARLECAAEGHPAPQIAWQKDGGTdfpAARDRRMHVMPDDDVFfITDVKPVDMGVYSCTAKN 683
Cdd:cd04969     1 PDFELNPvkKKILAAKGGDVIIECKPKASPKPTISWSKGTEL---LTNSSRICILPDGSLK-IKNVTKSDEGKYTCFAVN 76

                          90
                  ....*....|...
gi 583978668  684 TAGTVSANATLTV 696
Cdd:cd04969    77 FFGKANSTGSLSV 89

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: 3.68e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  704 QDLEDRSVTVGETVALQCKALGSPPPRITWLHNDQPLRPSDRHHFT---PGNQLLVIGSALLKDAGRYTCLMSNTLGTER 780
Cdd:cd20973     2 QTLRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDqdeDGLCSLIISDVCGDDSGKYTCKAVNSLGEAT 81


                  ....*..
gi 583978668  781 AHSQLVV 787
Cdd:cd20973    82 CSAELTV 88

Leucine rich repeat C-terminal domain;

Pssm-ID: 214507 [Multi-domain] Cd Length: 51 Bit Score: 55.90 E-value: 4.20e-10

                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|..
gi 583978668    435 NSLLCDCQLHWLPDWLVARG-LQVGINATCAHPESLKGKsVFEVPPSSFVCD 485
Cdd:smart00082    1 NPFICDCELRWLLRWLQANEhLQDPVDLRCASPSSLRGP-LLELLHSEFKCP 51

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: 57.36 E-value: 4.30e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  606 PSFIKTPRDSTIRTGHTARLECAAEGHPAPQIAWQKDG-GTDFPAARDRRMHVMPDDDVFFITDVKPVDMGVYSCTAKNT 684
Cdd:cd20974     1 PVFTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFRDGqVISTSTLPGVQISFSDGRAKLSIPAVTKANSGRYSLTATNG 80

                          90
                  ....*....|...
gi 583978668  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 583978668  709 RSVTV--GETVALQCKALGSPPPRITWLHNDQPLRPSDRHHFTPGN--QLLVIGSALLKDAGRYTCLMSNTLGTERAHSQ 784
Cdd:cd05747    11 RSLTVseGESARFSCDVDGEPAPTVTWMREGQIIVSSQRHQITSTEykSTFEISKVQMSDEGNYTVVVENSEGKQEAQFT 90


                  .
gi 583978668  785 L 785
Cdd:cd05747    91 L 91

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: 5.04e-10

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 583978668  714 GETVALQCKALGSPPPRITWLHNDQPLrPSDRHHFTPGNQLLVIGSALLKDAGRYTCLMSNTLGTERAHSQLVV 787
Cdd:cd05745     2 GQTVDFLCEAQGYPQPVIAWTKGGSQL-SVDRRHLVLSSGTLRISRVALHDQGQYECQAVNIVGSQRTVAQLTV 74

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: 61.99 E-value: 5.29e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  185 LQVLRLSRN-----RISQIPVKAFQLPRLTQLELNRN------RIRQVEGLTFQGLSSLEVLKLQRNSISKLTDGAFFDL 253
Cdd:cd00116    25 LQVLRLEGNtlgeeAAKALASALRPQPSLKELCLSLNetgripRGLQSLLQGLTKGCGLQELDLSDNALGPDGCGVLESL 104

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  254 AK---MKVLHLDYNSLtEVNSGSLY--GLTSLQ----QLFLSNNSIARINPDGW----KFCQKLRELNLSYNNLTrlDEG 320
Cdd:cd00116   105 LRsssLQELKLNNNGL-GDRGLRLLakGLKDLPpaleKLVLGRNRLEGASCEALakalRANRDLKELNLANNGIG--DAG 181

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  321 ------SLAVLGDLHTLRLGHNSISHIN----EGAFRGLKALRILELDHNDIS--GTIEDTNGAFSGLDSLIKLTLFGNK 388
Cdd:cd00116   182 iralaeGLKANCNLEVLDLNNNGLTDEGasalAETLASLKSLEVLNLGDNNLTdaGAAALASALLSPNISLLTLSLSCND 261

                         250       260
                  ....*....|....*....|....*..
gi 583978668  389 IKSVAKKAFS-GLD---TLEHLNLGEN 411
Cdd:cd00116   262 ITDDGAKDLAeVLAekeSLLELDLRGN 288

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 56.80 E-value: 5.33e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668   489 KPQITVQPETTMTVLGSDVRLTCTaaSSSSSPMTFAWRKDQELLRNAEMENYAHVrahhqaatpdlpgaggggvmEYTTI 568
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVTLTCE--ATGSPPPTITWYKNGEPISSGSTRSRSLS--------------------GSNST 58

                           90       100
                   ....*....|....*....|
gi 583978668   569 LHLRRVTFAHEGRYQCIITN 588
Cdd:pfam13927   59 LTISNVTRSDAGTYTCVASN 78

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 583978668  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: 6.67e-10

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 583978668  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 583978668  710 SVTVGETVALQCKALGSPPPRITWLHNDQPLRPSDR---HHFTPGNQLLVIGSALLKDAGRYTCLMSNTLGT 778
Cdd:cd05857    15 AVPAANTVKFRCPAAGNPTPTMRWLKNGKEFKQEHRiggYKVRNQHWSLIMESVVPSDKGNYTCVVENEYGS 86

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: 56.25 E-value: 9.48e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  606 PSFIKTPRDSTIRT-GHTARLECAAEGHPAPQIAWQKDGGtdfPAARDR-RMHVmpDDDVFFITDVKPVDMGVYSCTAKN 683
Cdd:cd20978     1 PKFIQKPEKNVVVKgGQDVTLPCQVTGVPQPKITWLHNGK---PLQGPMeRATV--EDGTLTIINVQPEDTGYYGCVATN 75

                          90
                  ....*....|...
gi 583978668  684 TAGTVSANATLTV 696
Cdd:cd20978    76 EIGDIYTETLLHV 88

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: 1.25e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 583978668  714 GETVALQCKALGSPPPRITWLHNDQPLRPSDR----HHFTPGNQL---LVIGSALLKDAGRYTCLMSNTLGT 778
Cdd:cd20956    16 GPSVSLKCVASGNPLPQITWTLDGFPIPESPRfrvgDYVTSDGDVvsyVNISSVRVEDGGEYTCTATNDVGS 87

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 583978668  700 PHLAQDLEDRSVTVGETVALQCKALGSPPPRITWLHNDQPLRPSDR---HHFTPGNQLLVIGSALLKDAGRYTCLMSNTL 776
Cdd:cd20975     1 PTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRrfaEEAEGGLCRLRILAAERGDAGFYTCKAVNEY 80

                          90
                  ....*....|.
gi 583978668  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 583978668  708 DRSVTVGETVALQCKA-LGSPPPRITWLHNDQPLRPSD--RHHFTPGNqlLVIGSALLKDAGRYTCLMSNTLGT-ERAHS 783
Cdd:cd05724     6 DTQVAVGEMAVLECSPpRGHPEPTVSWRKDGQPLNLDNerVRIVDDGN--LLIAEARKSDEGTYKCVATNMVGErESRAA 83


                  ....
gi 583978668  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: 1.36e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  707 EDRSVTVGETVALQCKALGSPPPRITW--------LHNDQPLRPSDRHHFTPGNQlLVIGSALLKDAGRYTCLMSNTLGT 778
Cdd:cd05726     7 RDQVVALGRTVTFQCETKGNPQPAIFWqkegsqnlLFPYQPPQPSSRFSVSPTGD-LTITNVQRSDVGYYICQALNVAGS 85

                          90
                  ....*....|.
gi 583978668  779 ERAHSQLVVTE 789
Cdd:cd05726    86 ILAKAQLEVTD 96

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

Pssm-ID: 143224 [Multi-domain] Cd Length: 92 Bit Score: 55.82 E-value: 1.47e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  605 LPSFIKT-PRDSTIRTGHTARLECAAEGHPAPQIAWQKDGGtdfPAARDRRMHVMPDD--DVFFITDVKPVDMGVYSCTA 681
Cdd:cd05747     2 LPATILTkPRSLTVSEGESARFSCDVDGEPAPTVTWMREGQ---IIVSSQRHQITSTEykSTFEISKVQMSDEGNYTVVV 78

                          90
                  ....*....|....
gi 583978668  682 KNTAGTVSANATLT 695
Cdd:cd05747    79 ENSEGKQEAQFTLT 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: 55.88 E-value: 1.55e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  700 PHLAQDLEDRSVTVGETVALQCKALGSPPPRITWLHNDQPLRPSDRHHF---TPGNQLLVIGSALLKDAGRYTCLMSNTL 776
Cdd:cd20990     1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSAHKMlvrENGVHSLIIEPVTSRDAGIYTCIATNRA 80

                          90
                  ....*....|.
gi 583978668  777 GTERAHSQLVV 787
Cdd:cd20990    81 GQNSFNLELVV 91

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: 1.69e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 583978668  624 RLECAAEGHPAPQIAWQKDGgtdFPAARDRRMHVMPdDDVFFITDVKPVDMGVYSCTAKNTAGTVSANATLT 695
Cdd:cd05746     2 QIPCSAQGDPEPTITWNKDG---VQVTESGKFHISP-EGYLAIRDVGVADQGRYECVARNTIGYASVSMVLS 69

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: 1.87e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  700 PHLAQDLEDRSVTVGETVALQCKALGSPPPRITWLHNDQPLrPSDRHHFTPGNQ-----LLVIGSALLKDAGRYTCLMSN 774
Cdd:cd20971     2 PHFKEELRNLNVRYQSNATLVCKVTGHPKPIVKWYRQGKEI-IADGLKYRIQEFkggyhQLIIASVTDDDATVYQVRATN 80


                  ...
gi 583978668  775 TLG 777
Cdd:cd20971    81 QGG 83

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

Pssm-ID: 409394 [Multi-domain] Cd Length: 83 Bit Score: 55.11 E-value: 1.88e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  620 GHTARLECAAEGHPAPQIAWQKDGGtDFPAARdrrmhvmPDDDVF----FITDVKPVDMGVYSCTAKNTAGTVSANATLT 695
Cdd:cd05731    10 GGVLLLECIAEGLPTPDIRWIKLGG-ELPKGR-------TKFENFnktlKIENVSEADSGEYQCTASNTMGSARHTISVT 81


                  .
gi 583978668  696 V 696
Cdd:cd05731    82 V 82

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 583978668  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: 2.11e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 583978668  714 GETVALQCKALGSPPPRITWLHNDQPLrPSDRHHFTPGNQLLVIGSALLKDAGRYTCLMSNTLGTERAHSQLVV 787
Cdd:cd05876    10 GQSLVLECIAEGLPTPTVKWLRPSGPL-PPDRVKYQNHNKTLQLLNVGESDDGEYVCLAENSLGSARHAYYVTV 82

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 583978668  704 QDLEDRSVTVGETVALQCKALGSPPPRITWLHNDQPLRPSDRHHFTPGNqlLVIGSALLKDAGRYTCLMSNTLGTERAHS 783
Cdd:cd05728     4 KVISDTEADIGSSLRWECKASGNPRPAYRWLKNGQPLASENRIEVEAGD--LRITKLSLSDSGMYQCVAENKHGTIYASA 81


                  ....
gi 583978668  784 QLVV 787
Cdd:cd05728    82 ELAV 85

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 583978668  715 ETVALQCKALGSPPPRITWLHN--DQPLRPSDRHHFTPGNqlLVIGSAL-LKDAGRYTCLMSNTLGTERA 781
Cdd:cd04967    20 KKVALNCRARANPVPSYRWLMNgtEIDLESDYRYSLVDGT--LVISNPSkAKDAGHYQCLATNTVGSVLS 87

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: 2.80e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  609 IKTPRDSTIRTGHTARLECAAEGHPAPQIAWQKDGGTDFPAARDRRmhvmpDDDVFFITDVKPVDMGVYSCTAKNTAGTV 688
Cdd:cd04968     5 VRFPADTYALKGQTVTLECFALGNPVPQIKWRKVDGSPSSQWEITT-----SEPVLEIPNVQFEDEGTYECEAENSRGKD 79


                  ....*...
gi 583978668  689 SANATLTV 696
Cdd:cd04968    80 TVQGRIIV 87

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: 55.01 E-value: 3.62e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  606 PSFIKTPRDSTIRTGHTARLECAAEGHPAPQIAWQKDGGT------DFpaARDRRMHVMPDDDVFFiTDVKPVDMGVYSC 679
Cdd:cd20954     2 PRWIVEPVDANVAAGQDVMLHCQADGFPTPTVTWKKATGStpgeykDL--LYDPNVRILPNGTLVF-GHVQKENEGHYLC 78

                          90
                  ....*....|....*...
gi 583978668  680 TAKNTAGT-VSANATLTV 696
Cdd:cd20954    79 EAKNGIGSgLSKVIFLKV 96

Leucine rich repeat;

Pssm-ID: 404697 [Multi-domain] Cd Length: 61 Bit Score: 53.68 E-value: 3.72e-09

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 583978668   135 SVETLDLSNNDITELRGQCFPAGLHIRDLYLSNNKISVLELGVLDHLGEtLQVLRLSRNRI 195
Cdd:pfam13855    2 NLRSLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPS-LRYLDLSGNRL 61

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: 4.43e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  699 TPHlaqdleDRSVTVGETVALQCKALGSPPPRITWLHN---DQPLRPSDRHHFTPGNQLLVIGSALLKDAGRYTCLMSNT 775
Cdd:cd05763     5 TPH------DITIRAGSTARLECAATGHPTPQIAWQKDggtDFPAARERRMHVMPEDDVFFIVDVKIEDTGVYSCTAQNS 78

                          90
                  ....*....|..
gi 583978668  776 LGTERAHSQLVV 787
Cdd:cd05763    79 AGSISANATLTV 90

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: 59.42 E-value: 5.79e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  118 HHNKIRSIDGRRTGELLSVETLDLSNNDITELRG-QCFPAGLHIRDLYLSNNKISVLELGVL----DHLGETLQVLRLSR 192
Cdd:COG5238   110 TAVATPPPDLRRIMAKTLEDSLILYLALPRRINLiQVLKDPLGGNAVHLLGLAARLGLLAAIsmakALQNNSVETVYLGC 189

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  193 NRISQIPVKAF-----QLPRLTQLELNRNRI--RQVEGL--TFQGLSSLEVLKLQRNsisKLTDGAFFDLAKmkvlHLDY 263
Cdd:COG5238   190 NQIGDEGIEELaealtQNTTVTTLWLKRNPIgdEGAEILaeALKGNKSLTTLDLSNN---QIGDEGVIALAE----ALKN 262

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  264 NsltevnsgslyglTSLQQLFLSNNSI----ARINPDGWKFCQKLRELNLSYNNLTrlDEG------SLAVLGDLHTLRL 333
Cdd:COG5238   263 N-------------TTVETLYLSGNQIgaegAIALAKALQGNTTLTSLDLSVNRIG--DEGaialaeGLQGNKTLHTLNL 327

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  334 GHNSIShiNEGAFRGLKALR------ILELDHNDIS--GTIEDTNgAFSGLDSLIKLTLFGNKIKSVAKKAFSGL---DT 402
Cdd:COG5238   328 AYNGIG--AQGAIALAKALQenttlhSLDLSDNQIGdeGAIALAK-YLEGNTTLRELNLGKNNIGKQGAEALIDAlqtNR 404

                         330       340
                  ....*....|....*....|
gi 583978668  403 LEHLNLGENAIRSIQPDAFT 422
Cdd:COG5238   405 LHTLILDGNLIGAEAQQRLE 424

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: 59.42 E-value: 5.94e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668   52 LELTATPLDLPvrTVSLNLGYNKLTSISPEAFANLPNLREL-RLDHNEL-TSIPDLGQAASTIVSLYLHH---------- 119
Cdd:COG5238   105 LAETATAVATP--PPDLRRIMAKTLEDSLILYLALPRRINLiQVLKDPLgGNAVHLLGLAARLGLLAAISmakalqnnsv 182

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  120 -------NKIRSIDGRRTGELL----SVETLDLSNNDITELRGQCFPAGL----HIRDLYLSNNKIS---VLELGVLDHL 181
Cdd:COG5238   183 etvylgcNQIGDEGIEELAEALtqntTVTTLWLKRNPIGDEGAEILAEALkgnkSLTTLDLSNNQIGdegVIALAEALKN 262

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  182 GETLQVLRLSRNRISQIPVKAF-----QLPRLTQLELNRNRIRQ------VEGLtfQGLSSLEVLKLQRNSISklTDGAF 250
Cdd:COG5238   263 NTTVETLYLSGNQIGAEGAIALakalqGNTTLTSLDLSVNRIGDegaialAEGL--QGNKTLHTLNLAYNGIG--AQGAI 338

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  251 FdLAKmkvlHLDYNsltevnsgslyglTSLQQLFLSNNSIARINPDGW----KFCQKLRELNLSYNNLTrlDEGSLAVL- 325
Cdd:COG5238   339 A-LAK----ALQEN-------------TTLHSLDLSDNQIGDEGAIALakylEGNTTLRELNLGKNNIG--KQGAEALId 398

                         330
                  ....*....|....*..
gi 583978668  326 ----GDLHTLRLGHNSI 338
Cdd:COG5238   399 alqtNRLHTLILDGNLI 415

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: 5.99e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  700 PHLAQDLEDRSVTVGETVALQCKALGSPPPRITWLHNDQPLRPS-DR---HHFTPGNQLLVIGSALLKDAGRYTCLMSNT 775
Cdd:cd05892     1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKKNNEMLQYNtDRislYQDNCGRICLLIQNANKKDAGWYTVSAVNE 80

                          90
                  ....*....|..
gi 583978668  776 LGTERAHSQLVV 787
Cdd:cd05892    81 AGVVSCNARLDV 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: 6.64e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 583978668  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: 53.64 E-value: 9.67e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  607 SFIKTPRDSTIRTGHTARLECAAEGHPAPQIAWQKDGGTDFPAARDRRmhVMPDDDVFFITDV------KPvDMGVYSCT 680
Cdd:cd05722     3 YFLSEPSDIVAMRGGPVVLNCSAESDPPPKIEWKKDGVLLNLVSDERR--QQLPNGSLLITSVvhskhnKP-DEGFYQCV 79

                          90
                  ....*....|....*...
gi 583978668  681 AKN-TAGT-VSANATLTV 696
Cdd:cd05722    80 AQNeSLGSiVSRTARVTV 97

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 53.71 E-value: 1.05e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  700 PHLAQDLEDRSVTVGETVALQCKALGSPPPRITWLHNDQPLR-----PSDRHHFTPGNQL----LVIGSALLKDAGRYTC 770
Cdd:cd07693     1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLEtdkddPRSHRIVLPSGSLfflrVVHGRKGRSDEGVYVC 80

                          90
                  ....*....|..
gi 583978668  771 LMSNTLGTERAH 782
Cdd:cd07693    81 VAHNSLGEAVSR 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: 53.55 E-value: 1.05e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 583978668  714 GETVALQCKALGSPPPRITWLHNDQPL---RPSDRHHFTPGNQLLViGSALLKDAGRYTCLMSNTLGTERAHSQLVV 787
Cdd:cd20969    17 GHTVQFVCRADGDPPPAILWLSPRKHLvsaKSNGRLTVFPDGTLEV-RYAQVQDNGTYLCIAANAGGNDSMPAHLHV 92

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: 53.03 E-value: 1.34e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  611 TPRDSTIRTGHTARLECAAEGHPAPQIAWQKDgGTDFPAARDRRMHVMPDDDVFFITDVKPVDMGVYSCTAKNTAGTVSA 690
Cdd:cd05736     6 YPEFQAKEPGVEASLRCHAEGIPLPRVQWLKN-GMDINPKLSKQLTLIANGSELHISNVRYEDTGAYTCIAKNEGGVDED 84


                  ....*....
gi 583978668  691 NATLTVLET 699
Cdd:cd05736    85 ISSLFVEDS 93

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: 52.94 E-value: 1.53e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  609 IKTPRDSTIRTGHTARLECAAEGH-PAPQIAWQKDGGTDFPAARDRrmhvmpdDDVFFITDVKPVDMGVYSCTAKNTAGT 687
Cdd:cd05754     5 VEEPRSQEVRPGADVSFICRAKSKsPAYTLVWTRVNGTLPSRAMDF-------NGILTIRNVQLSDAGTYVCTGSNMLDT 77


                  ....*..
gi 583978668  688 VSANATL 694
Cdd:cd05754    78 DEATATL 84

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: 1.64e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  612 PRDSTIRTGHTARLECAAEGHPAPQIAWQKDGGTDFPAARDRRMHvMPDDDVFFITDVKPVDMGVYSCTAKNTAGT-VSA 690
Cdd:cd05738     6 PQLKVVEKARTATMLCAASGNPDPEISWFKDFLPVDTATSNGRIK-QLRSGALQIENSEESDQGKYECVATNSAGTrYSA 84


                  ....*.
gi 583978668  691 NATLTV 696
Cdd:cd05738    85 PANLYV 90

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: 1.69e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  260 HLDY--NSLTEVNSGSLYGLT---SLQQLFLSNNSIA----RINPDGWKFCQ-KLRELNLSYNNLTRLDEGSLA----VL 325
Cdd:cd00116    85 ELDLsdNALGPDGCGVLESLLrssSLQELKLNNNGLGdrglRLLAKGLKDLPpALEKLVLGRNRLEGASCEALAkalrAN 164

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  326 GDLHTLRLGHNSISHinEGA---FRGLKA---LRILELDHNdisgTIEDTNG-AFSGldslikltlfgnkiksvakkAFS 398
Cdd:cd00116   165 RDLKELNLANNGIGD--AGIralAEGLKAncnLEVLDLNNN----GLTDEGAsALAE--------------------TLA 218

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 583978668  399 GLDTLEHLNLGENAIRS-----IQPDAFTKMRNLKSLLIQSNSLLCD 440
Cdd:cd00116   219 SLKSLEVLNLGDNNLTDagaaaLASALLSPNISLLTLSLSCNDITDD 265

Leucine rich repeat;

Pssm-ID: 404697 [Multi-domain] Cd Length: 61 Bit Score: 51.76 E-value: 1.76e-08

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 583978668    67 SLNLGYNKLTSISPEAFANLPNLRELRLDHNELTSI-PDLGQAASTIVSLYLHHNKI 122
Cdd:pfam13855    5 SLDLSNNRLTSLDDGAFKGLSNLKVLDLSNNLLTTLsPGAFSGLPSLRYLDLSGNRL 61

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: 2.02e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  700 PHLAQDLEDRSVTVGETVALQCKALGSPPPRITW-LHNDQPLRPSDRHHFTPGNQL------LVIGSALLKDAGRYTCLM 772
Cdd:cd05765     1 PALVNSPTHQTVKVGETASFHCDVTGRPQPEITWeKQVPGKENLIMRPNHVRGNVVvtnigqLVIYNAQPQDAGLYTCTA 80

                          90
                  ....*....|....*
gi 583978668  773 SNTLGTERAHSQLVV 787
Cdd:cd05765    81 RNSGGLLRANFPLSV 95

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409393 [Multi-domain] Cd Length: 95 Bit Score: 52.61 E-value: 2.41e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 583978668  620 GHTARLECAAEGHPAPQIAWQKDGGTDFPAARDRRMHVMPDDDVFFITDVKPVDMGVYSCTAKNTAGTVSANATLTV 696
Cdd:cd05729    19 ANKVRLECGAGGNPMPNITWLKDGKEFKKEHRIGGTKVEEKGWSLIIERAIPRDKGKYTCIVENEYGSINHTYDVDV 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: 56.98 E-value: 2.41e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668   35 PCAQNCTCSGDSVDCSNLELTATPLDLPVRTVSLNLGYNKLTSIS------PEAFANLPNLRELRLDHNELT-----SIP 103
Cdd:cd00116    23 LCLQVLRLEGNTLGEEAAKALASALRPQPSLKELCLSLNETGRIPrglqslLQGLTKGCGLQELDLSDNALGpdgcgVLE 102

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  104 DLGQaASTIVSLYLHHNKIrsidGRRTGELLSVETLDLSnnditelrgqcfpagLHIRDLYLSNNKisvLELGVLDHLGE 183
Cdd:cd00116   103 SLLR-SSSLQELKLNNNGL----GDRGLRLLAKGLKDLP---------------PALEKLVLGRNR---LEGASCEALAK 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  184 TLQVLRlsrnrisqipvkafqlpRLTQLELNRNRIRqVEGLT--FQGL---SSLEVLKLQRNSI----SKLTDGAFFDLA 254
Cdd:cd00116   160 ALRANR-----------------DLKELNLANNGIG-DAGIRalAEGLkanCNLEVLDLNNNGLtdegASALAETLASLK 221

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  255 KMKVLHLDYNSLT-----EVNSGSLYGLTSLQQLFLSNNSIARInpDGWKFCQ------KLRELNLSYNNLTRLDEGSLA 323
Cdd:cd00116   222 SLEVLNLGDNNLTdagaaALASALLSPNISLLTLSLSCNDITDD--GAKDLAEvlaekeSLLELDLRGNKFGEEGAQLLA 299

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: 51.82 E-value: 2.67e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  616 TIRTGHTARLECAAEGHPAPQIAWQKDGgTDFPAARDRRMHVMPDDDVFFITDVKPVDMGVYSCTAKNTAGTVSANATLT 695
Cdd:cd05748     3 VVRAGESLRLDIPIKGRPTPTVTWSKDG-QPLKETGRVQIETTASSTSLVIKNAKRSDSGKYTLTLKNSAGEKSATINVK 81


                  .
gi 583978668  696 V 696
Cdd:cd05748    82 V 82

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: 51.71 E-value: 3.44e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 583978668  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 583978668  713 VGETVALQCKALGSPPPRITWLHNDQPLRP-----SDRHHFTpgnqlLVIGSALLKDAGRYTCLMSNTLG 777
Cdd:cd05856    18 VGSSVRLKCVASGNPRPDITWLKDNKPLTPpeigeNKKKKWT-----LSLKNLKPEDSGKYTCHVSNRAG 82

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: 51.52 E-value: 5.43e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  608 FIKTPRDSTIRTGHTARLECAAEGHPAPQIAWQKDGGTDFPAARDRRMHVmpDDDVFFITDVKPVDMGVYSCTAKNTAGT 687
Cdd:cd05868     2 WITAPTNLVLSPGEDGTLICRANGNPKPSISWLTNGVPIEIAPTDPSRKV--DGDTIIFSKVQERSSAVYQCNASNEYGY 79

                          90
                  ....*....|
gi 583978668  688 VSANATLTVL 697
Cdd:cd05868    80 LLANAFVNVL 89

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: 6.58e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668   407 NLGENAIRSIQPDAFTKMRNLKSLLIQSNSLLCDCQLHWLPDWLVARGLQV--GINATCAHPESLKGKSVFEVPPSSFVC 484
Cdd:TIGR00864    1 DISNNKISTIEEGICANLCNLSEIDLSGNPFECDCGLARLPRWAEEKGVKVrqPEAALCAGPGALAGQPLLGIPLLDSGC 80


                   .
gi 583978668   485 D 485
Cdd:TIGR00864   81 D 81

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: 51.01 E-value: 8.06e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 583978668  620 GHTARLECAAEGHPAPQIAWQKDGG--TDFPAARDRRMHVmpdddVFFITDVKPVDMGVYSCTAKNTAGTVsaNATLTV 696
Cdd:cd05856    19 GSSVRLKCVASGNPRPDITWLKDNKplTPPEIGENKKKKW-----TLSLKNLKPEDSGKYTCHVSNRAGEI--NATYKV 90

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 583978668  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: 1.05e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  700 PHLAQDLEDRSVTVGETVALQCKALGSPPPRITWLHNDQPLRPSDRHHFTPGN--QLLVIGSALLK-----DAGRYTCLM 772
Cdd:cd05734     2 PRFVVQPNDQDGIYGKAVVLNCSADGYPPPTIVWKHSKGSGVPQFQHIVPLNGriQLLSNGSLLIKhvleeDSGYYLCKV 81

                          90
                  ....*....|.
gi 583978668  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: 50.26 E-value: 1.22e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  606 PSFIKTPRDSTIRTGHTARLECAAEGHPAPQIAWQKDGGTdFPAarDRRMHVMPdDDVFFITDV-KPVDMGVYSCTAKNT 684
Cdd:cd20958     1 PPFIRPMGNLTAVAGQTLRLHCPVAGYPISSITWEKDGRR-LPL--NHRQRVFP-NGTLVIENVqRSSDEGEYTCTARNQ 76

                          90
                  ....*....|..
gi 583978668  685 AGTvSANATLTV 696
Cdd:cd20958    77 QGQ-SASRSVFV 87

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 583978668  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 583978668  700 PHLaQDLEDRSVTVGETVALQCKALG-SPPPRITWLHNDQPLRPSDRHHF----TPGNQLLVIGSALLKDAGRYTCLMSN 774
Cdd:cd05750     1 PKL-KEMKSQTVQEGSKLVLKCEATSeNPSPRYRWFKDGKELNRKRPKNIkirnKKKNSELQINKAKLEDSGEYTCVVEN 79

                          90
                  ....*....|...
gi 583978668  775 TLGTERAHSQLVV 787
Cdd:cd05750    80 ILGKDTVTGNVTV 92

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 583978668  714 GETVALQCKALGSPPPRITWLHNDQPLRPSDRHH--FTPGNQL-LVIGSALLKDAGRYTCLMSNTLGTE 779
Cdd:cd05737    16 GKTLNLTCNVWGDPPPEVSWLKNDQALAFLDHCNlkVEAGRTVyFTINGVSSEDSGKYGLVVKNKYGSE 84

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: 49.48 E-value: 2.04e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  704 QDLEDRSVTVGETVALQCKALG-SPPPRITWLHNDQPLrPSDRHHFtpgNQLLVIGSALLKDAGRYTCLMSNTLGTERAH 782
Cdd:cd05754     6 EEPRSQEVRPGADVSFICRAKSkSPAYTLVWTRVNGTL-PSRAMDF---NGILTIRNVQLSDAGTYVCTGSNMLDTDEAT 81


                  ...
gi 583978668  783 SQL 785
Cdd:cd05754    82 ATL 84

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: 2.25e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  711 VTVGETVALQCKALGSPPPRIT--WLHNDQPLRPS-DRHHF-------TPGNqlLVIGSALLKDAGRYTCLMSNTLGTER 780
Cdd:cd04970    14 ITVGENATLQCHASHDPTLDLTftWSFNGVPIDLEkIEGHYrrrygkdSNGD--LEIVNAQLKHAGRYTCTAQTVVDSDS 91


                  ....*..
gi 583978668  781 AHSQLVV 787
Cdd:cd04970    92 ASATLVV 98

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: 2.33e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  614 DSTIRTGHTARLECAAEGHPAPQIAWQKDGGtdfPAARDRRMHVMPDDDV-FFITDVKPVDMGVYSCTAKNTAGTVSANA 692
Cdd:cd05730    12 NATANLGQSVTLACDADGFPEPTMTWTKDGE---PIESGEEKYSFNEDGSeMTILDVDKLDEAEYTCIAENKAGEQEAEI 88


                  ....
gi 583978668  693 TLTV 696
Cdd:cd05730    89 HLKV 92

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 49.32 E-value: 2.40e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668   611 TPRDSTIRTGHTARLECAAEGHPAPQIAWQKDGgtdfpaardrrmHVMPDDDVFFITDVKPVDMGVYSCTAKNTAG-TVS 689
Cdd:pfam13895    5 TPSPTVVTEGEPVTLTCSAPGNPPPSYTWYKDG------------SAISSSPNFFTLSVSAEDSGTYTCVARNGRGgKVS 72


                   ....*..
gi 583978668   690 ANATLTV 696
Cdd:pfam13895   73 NPVELTV 79

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: 3.03e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  607 SFIKTPRDSTIRTGHTARLECAAEGHPAPQIAWQKDGG-TDFPAARDRRMHVMpdDDVFFITDVKPVDMGVYSCTAKNTA 685
Cdd:cd20949     1 TFTENAYVTTVKEGQSATILCEVKGEPQPNVTWHFNGQpISASVADMSKYRIL--ADGLLINKVTQDDTGEYTCRAYQVN 78

                          90
                  ....*....|.
gi 583978668  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 583978668     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: 4.95e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 583978668  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: 47.79 E-value: 7.07e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  710 SVTV--GETVALQCKALGSPPPRITWLHNDQPLrPSDRHHFTPGNQLLVIGSALLKDAGRYTCLMSNTLGTERaHSQLVV 787
Cdd:cd05731     4 STMVlrGGVLLLECIAEGLPTPDIRWIKLGGEL-PKGRTKFENFNKTLKIENVSEADSGEYQCTASNTMGSAR-HTISVT 81


                  ..
gi 583978668  788 TE 789
Cdd:cd05731    82 VE 83

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

Pssm-ID: 143220 Cd Length: 78 Bit Score: 47.48 E-value: 1.06e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  620 GHTARLECAAEGHPAPQIAWQKDGGtdfPAARDRRMHVMPDDD--VFFITDVKPVDMGVYSCTAKNTAGTVSAN--ATLT 695
Cdd:cd05743     1 GETVEFTCVATGVPTPIINWRLNWG---HVPDSARVSITSEGGygTLTIRDVKESDQGAYTCEAINTRGMVFGIpdGILT 77


                  .
gi 583978668  696 V 696
Cdd:cd05743    78 V 78

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 583978668  717 VALQCKALGSPPPRITWLHNDQPLRPSDRHHFTPGNQlLVIGSALLKDAGRYTCLMSNTLG 777
Cdd:cd05746     1 VQIPCSAQGDPEPTITWNKDGVQVTESGKFHISPEGY-LAIRDVGVADQGRYECVARNTIG 60

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: 1.50e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  706 LEDRSVTVGETVALQCKALGSPPPRITWLHNDQPLRPSDRHHFTPGNQLLVIGSALLKDAGRYTCLMSNTLGtERAHSQL 785
Cdd:cd20958     7 MGNLTAVAGQTLRLHCPVAGYPISSITWEKDGRRLPLNHRQRVFPNGTLVIENVQRSSDEGEYTCTARNQQG-QSASRSV 85


                  ...
gi 583978668  786 VVT 788
Cdd:cd20958    86 FVK 88

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 583978668  725 GSPPPRITWLHNDQPLRPSDRHHF--TPGNQLLVIGSALLKDAGRYTCLMSNTLGTERAHSQLVV 787
Cdd:cd05748    18 GRPTPTVTWSKDGQPLKETGRVQIetTASSTSLVIKNAKRSDSGKYTLTLKNSAGEKSATINVKV 82

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: 1.65e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  606 PSFIKTPRDSTIRTGHTARLECAAEGHPAPQIAWQKDGGTDFP-----AARDRRMHVMPDDDVfFITDVKPVDMGVYSCT 680
Cdd:cd05734     2 PRFVVQPNDQDGIYGKAVVLNCSADGYPPPTIVWKHSKGSGVPqfqhiVPLNGRIQLLSNGSL-LIKHVLEEDSGYYLCK 80

                          90
                  ....*....|....*..
gi 583978668  681 AKNTAGT-VSANATLTV 696
Cdd:cd05734    81 VSNDVGAdISKSMYLTV 97

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: 47.64 E-value: 1.65e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  700 PHLAQDLEDRSVTVGETVALQCKALGSPPPRITWLHNDQPLRPSDRHHF--TPGNQLLVIGSALLKDAGRYTCLMSNTLG 777
Cdd:cd05762     2 PQIIQFPEDMKVRAGESVELFCKVTGTQPITCTWMKFRKQIQEGEGIKIenTENSSKLTITEGQQEHCGCYTLEVENKLG 81

                          90
                  ....*....|...
gi 583978668  778 TERAHSQLVVTER 790
Cdd:cd05762    82 SRQAQVNLTVVDK 94

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: 1.66e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  608 FIKTPRDSTIRT----GHTARLECA-AEGHPAPQIAWQKDGGTDFPAAR---DRRMHVMPDDDVFFiTDVKPVDMGV--- 676
Cdd:cd20965     1 YLLDPQVKTKEKkpveGKPFKLDCNvPPGYPKPTIEWKKQLVSDSSKADtilDRRITISPNGDLYF-TNVTKEDVSTdyk 79


                  ....*....
gi 583978668  677 YSCTAKNTA 685
Cdd:cd20965    80 YVCVAKTPA 88

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 46.87 E-value: 1.88e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668   490 PQITVQPETTMTVLGSDVRLTCTAASSSssPMTFAWRKDQELLRNAEmenyaHVRAHhqaatpdlpgaggggVMEYTTIL 569
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTP--DPEVSWFKDGQPLRSSD-----RFKVT---------------YEGGTYTL 58

                           90       100       110
                   ....*....|....*....|....*....|...
gi 583978668   570 HLRRVTFAHEGRYQCIITNHFGStYSSKARLIV 602
Cdd:pfam07679   59 TISNVQPDDSGKYTCVATNSAGE-AEASAELTV 90

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

Pssm-ID: 143299 Cd Length: 92 Bit Score: 46.83 E-value: 2.15e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 583978668  711 VTV--GETVALQCKALGSPPPRITWLHNDQPLRPSDrHHFTPGNQ----LLVIGSALLKDAGRYTCLMSNTLGTER 780
Cdd:cd05891    11 VTImeGKTLNLTCTVFGNPDPEVIWFKNDQDIELSE-HYSVKLEQgkyaSLTIKGVTSEDSGKYSINVKNKYGGET 85

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 583978668  715 ETVALQCKALGSPPPRITWLHN--DQPLRPSDRHHFTPGNqlLVIGSAL-LKDAGRYTCLMSNTLGT 778
Cdd:cd05850    21 EKVTLACRARASPPATYRWKMNgtELKMEPDSRYRLVAGN--LVISNPVkAKDAGSYQCLASNRRGT 85

Leucine rich repeat;

Pssm-ID: 404697 [Multi-domain] Cd Length: 61 Bit Score: 45.59 E-value: 2.54e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 583978668    87 PNLRELRLDHNELTSI-PDLGQAASTIVSLYLHHNKIRSIDGRRTGELLSVETLDLSNNDI 146
Cdd:pfam13855    1 PNLRSLDLSNNRLTSLdDGAFKGLSNLKVLDLSNNLLTTLSPGAFSGLPSLRYLDLSGNRL 61

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.

Pssm-ID: 409541 [Multi-domain] Cd Length: 89 Bit Score: 46.56 E-value: 2.75e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 583978668  710 SVTVGETVALQCKALGSPPPRITWLHNDQPLRPS--DRHHFTPGNQLLVIGSALLKDAGRYTCLMSNTLGT 778
Cdd:cd20949    10 TVKEGQSATILCEVKGEPQPNVTWHFNGQPISASvaDMSKYRILADGLLINKVTQDDTGEYTCRAYQVNSI 80

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 45.85 E-value: 3.11e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 583978668   711 VTVGETVALQCKALGSPPPRITWLHNDQPLRPSDRHHFTpgnqllvigSALLKDAGRYTCLMSNTLGTERAHS 783
Cdd:pfam13895   11 VTEGEPVTLTCSAPGNPPPSYTWYKDGSAISSSPNFFTL---------SVSAEDSGTYTCVARNGRGGKVSNP 74

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: 3.94e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  606 PSFIKTPRDSTIRTGHTAR--LECAAEGHPAPQIAWQKdgGTDFpAARDRRMHVMpDDDVFFITDVKPVDMGVYSCTAKN 683
Cdd:cd05852     1 PTFEFNPMKKKILAAKGGRviIECKPKAAPKPKFSWSK--GTEL-LVNNSRISIW-DDGSLEILNITKLDEGSYTCFAEN 76

                          90
                  ....*....|...
gi 583978668  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: 3.95e-06

                           10        20
                   ....*....|....*....|....*...
gi 583978668    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: 4.19e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  707 EDRSVTVGETVALQCKALGSPPPRITWLHNDQPL--RPSD---RHHFTPGNQLLVIgSALLKDAGRYTCLMSNTLGTERA 781
Cdd:cd20977     8 KDMMAKAGDVTMIYCMYGSNPTAHPNYFKNGKDVngNPEDritRHNRTSGKRLLFK-TTLPEDEGVYTCEVDNGVGKPQK 86


                  ....*..
gi 583978668  782 HS-QLVV 787
Cdd:cd20977    87 HSlKLTV 93

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: 46.25 E-value: 4.30e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  607 SFIKTPRDSTIrtghtarLECAAEGHPAPQIAWQKDgGTDFPAARDRRMHVMPDDDVFFIT--DVKPVDM-GVYSCTAKN 683
Cdd:cd05733    10 DYIVDPRDNIT-------IKCEAKGNPQPTFRWTKD-GKFFDPAKDPRVSMRRRSGTLVIDnhNGGPEDYqGEYQCYASN 81


                  ....*...
gi 583978668  684 TAGTVSAN 691
Cdd:cd05733    82 ELGTAISN 89

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: 45.60 E-value: 4.54e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  616 TIRTGHTARLECAAEGHPAPQIAWQKdGGTDFPAARDR-RMHVMPDDDVFFITDVKPVDMGVYSCTAKNTAGTVSANATL 694
Cdd:cd05894     6 VVVAGNKLRLDVPISGEPAPTVTWSR-GDKAFTATEGRvRVESYKDLSSFVIEGAEREDEGVYTITVTNPVGEDHASLFV 84


                  ..
gi 583978668  695 TV 696
Cdd:cd05894    85 KV 86

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 583978668  713 VGETVALQCKALGSPPPRITWLHNDQPLRPSD-RHHFTPGNQLLVIGSALLKDAGRYTCLMSNTLGTERAHSQLVV 787
Cdd:cd05730    17 LGQSVTLACDADGFPEPTMTWTKDGEPIESGEeKYSFNEDGSEMTILDVDKLDEAEYTCIAENKAGEQEAEIHLKV 92

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: 45.65 E-value: 4.57e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 583978668   711 VTVGETVALQCKA-LGSPPPRITWLHNDQPLRPSDRHHFTPGNQ---LLVIGSALLKDAGRYTCLMSNTLG 777
Cdd:pfam00047    8 VLEGDSATLTCSAsTGSPGPDVTWSKEGGTLIESLKVKHDNGRTtqsSLLISNVTKEDAGTYTCVVNNPGG 78

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: 46.77 E-value: 5.45e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668   336 NSISHINEGAFRGLKALRILELDHNdISgTIEDtnGAFSGLdSLIKLTlFGNKIKSVAKKAFSGLDTLEHLNLGENaIRS 415
Cdd:pfam13306   20 SSLTSIGEYAFSNCTSLKSITLPSS-LT-SIGS--YAFYNC-SLTSIT-IPSSLTSIGEYAFSNCSNLKSITLPSN-LTS 92

                           90       100
                   ....*....|....*....|
gi 583978668   416 IQPDAFTKMrNLKSLLIQSN 435
Cdd:pfam13306   93 IGSYAFSNC-SLKSITIPSS 111

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: 6.34e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  700 PHLAQdLEDRSVTVGETVALQCKALGSPPPRITWlhndqpLRPSDRHHFTPGN-------------QLLVIGSALLKDAG 766
Cdd:cd05732     3 PKITY-LENQTAVELEQITLTCEAEGDPIPEITW------RRATRGISFEEGDldgrivvrgharvSSLTLKDVQLTDAG 75

                          90
                  ....*....|.
gi 583978668  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: 6.73e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 583978668  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: 7.78e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 583978668  707 EDRSVTVGETVALQCKALGSPPPRITW--LHNDQP-----LRPSDRHHFTPgNQLLVIGSALLKDAGRYTCLMSNTLGT 778
Cdd:cd20954     9 VDANVAAGQDVMLHCQADGFPTPTVTWkkATGSTPgeykdLLYDPNVRILP-NGTLVFGHVQKENEGHYLCEAKNGIGS 86

Immunoglobulin (Ig)-like domain of NrCAM (Ng (neuronglia) CAM-related cell adhesion molecule); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of NrCAM (Ng (neuronglia) CAM-related cell adhesion molecule). NrCAM belongs to the L1 subfamily of cell adhesion molecules (CAMs) and is comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region, and an intracellular domain. NrCAM is primarily expressed in the nervous system.

Pssm-ID: 409458 Cd Length: 95 Bit Score: 44.97 E-value: 1.01e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  610 KTPRDSTIRTGHTARLECAAEGHPAPQIAWQKDgGTDFPAARDRRMHVMPDDDVFFITDVKPVDM----GVYSCTAKNTA 685
Cdd:cd05874     6 QSPKDYIVDPRENIVIQCEAKGKPPPSFSWTRN-GTHFDIDKDPKVTMKPNTGTLVINIMNGEKAeayeGVYQCTARNER 84


                  ....*.
gi 583978668  686 GTVSAN 691
Cdd:cd05874    85 GAAVSN 90

type III secretion system effector E3 ubiquitin transferase SspH2;

Pssm-ID: 185285 [Multi-domain] Cd Length: 788 Bit Score: 49.78 E-value: 1.03e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668   40 CTCSGDSV-DCSNLELTATPLDLPVRTVSLNLGYNKLTSISpeafANLPNLRELRLDHNELTSIP--------------- 103
Cdd:PRK15387  198 CLNNGNAVlNVGESGLTTLPDCLPAHITTLVIPDNNLTSLP----ALPPELRTLEVSGNQLTSLPvlppgllelsifsnp 273

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  104 --DLGQAASTIVSLYLHHNKIRSIDGRRTG-ELLSVETLDLS---------------NNDITELrgQCFPAGLhiRDLYL 165
Cdd:PRK15387  274 ltHLPALPSGLCKLWIFGNQLTSLPVLPPGlQELSVSDNQLAslpalpselcklwayNNQLTSL--PTLPSGL--QELSV 349

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  166 SNNKISVL---------------ELGVLDHLGETLQVLRLSRNRISQIPVkafqLP-RLTQLELNRNRIRQVEGLTfQGL 229
Cdd:PRK15387  350 SDNQLASLptlpselyklwaynnRLTSLPALPSGLKELIVSGNRLTSLPV----LPsELKELMVSGNRLTSLPMLP-SGL 424

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|
gi 583978668  230 SSLEVLklqRNSISKLTDgAFFDLAKMKVLHLDYNSLTEVNSGSLYGLTS 279
Cdd:PRK15387  425 LSLSVY---RNQLTRLPE-SLIHLSSETTVNLEGNPLSERTLQALREITS 470

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 583978668  714 GETVALQCKALGSPPPRITWLHNDQPLRPSDRhhftpgnqLLVIGSALLK-------DAGRYTCLMSNTLGTerAHSQLV 786
Cdd:cd20968    14 GLKAVLPCTTMGNPKPSVSWIKGDDLIKENNR--------IAVLESGSLRihnvqkeDAGQYRCVAKNSLGI--AYSKPV 83


                  ...
gi 583978668  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: 1.15e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  709 RSVTVGETVALQCKALGSPPPRITWL-HND--------------QPLRPSDRHHFTPGNQLLVIGsALLKDAGRYTCLMS 773
Cdd:cd04974    11 QTVVLGSDVEFHCKVYSDAQPHIQWLkHVEvngskygpdglpyvTVLKVAGVNTTGEENTLTISN-VTFDDAGEYICLAG 89


                  ....
gi 583978668  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: 44.54 E-value: 1.15e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  610 KTPRDSTIRTGHTARLECAAEGHPAPQIAWQKDggtDFPAARDRRMHVMpDDDVFFITDVKPVDMGVYSCTAKNTAGTV- 688
Cdd:cd20968     4 RPPTNVTIIEGLKAVLPCTTMGNPKPSVSWIKG---DDLIKENNRIAVL-ESGSLRIHNVQKEDAGQYRCVAKNSLGIAy 79


                  ....*...
gi 583978668  689 SANATLTV 696
Cdd:cd20968    80 SKPVTIEV 87

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: 44.52 E-value: 1.20e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  612 PRDSTIR-TGHTARLECAAEGHPAPQIAWQKDGGTDFPaardRRMHVMPDDDVFFITDVKPVDMGVYSCTAKNTAGTVSA 690
Cdd:cd05876     1 SSSSLVAlRGQSLVLECIAEGLPTPTVKWLRPSGPLPP----DRVKYQNHNKTLQLLNVGESDDGEYVCLAENSLGSARH 76


                  ....*.
gi 583978668  691 NATLTV 696
Cdd:cd05876    77 AYYVTV 82

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: 1.43e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 583978668  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: 1.46e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 583978668  706 LEDRSVTVGETVALQCkALGSPPPRITWLHN--DQPLRPSDRHHFTpGNQLLVIGSALLKDAGRYTCLMSN-TLGT 778
Cdd:cd04979     3 FKQISVKEGDTVILSC-SVKSNNAPVTWIHNgkKVPRYRSPRLVLK-TERGLLIRSAQEADAGVYECHSGErVLGS 76

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: 44.69 E-value: 1.47e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  616 TIRTGHTARLECAAEGHPAPQIAWQKDGGTDFPAARDRRMHVMPDDDVFFiTDVKPVDMGVYSCTAKNTAGTVSANATLT 695
Cdd:cd20969    13 FVDEGHTVQFVCRADGDPPPAILWLSPRKHLVSAKSNGRLTVFPDGTLEV-RYAQVQDNGTYLCIAANAGGNDSMPAHLH 91


                  .
gi 583978668  696 V 696
Cdd:cd20969    92 V 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 583978668  606 PSFIKTPRDSTIRTGHTAR---LECAAEGHPAPQIAWQKDGgTDFPAARDRRmHVMPDDDVFFITDVKPVDMGVYSCTAK 682
Cdd:cd04967     2 PVFEEQPDDTIFPEDSDEKkvaLNCRARANPVPSYRWLMNG-TEIDLESDYR-YSLVDGTLVISNPSKAKDAGHYQCLAT 79

                          90
                  ....*....|...
gi 583978668  683 NTAGTV-SANATL 694
Cdd:cd04967    80 NTVGSVlSREATL 92

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: 2.36e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  707 EDRSVTVGETVALQCKALGSPPPRITWLHNDQPLRPSDRhhftpgnqlLVIGSALL-----KDAGRYTCLMSNTLGTERA 781
Cdd:cd05739     5 SNHEVMPGGSVNLTCVAVGAPMPYVKWMKGGEELTKEDE---------MPVGRNVLeltniYESANYTCVAISSLGMIEA 75


                  ....*.
gi 583978668  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 583978668  699 TPHLAQDLEDRSVTVGETVALQCKALGSPPPRITWLHNDQPLrPSDRHHFTPGnQLLVIGSALLKDAGRYTCLMSNTLGT 778
Cdd:cd05851     1 PADINVKFKDTYALKGQNVTLECFALGNPVPVIRWRKILEPM-PATAEISMSG-AVLKIFNIQPEDEGTYECEAENIKGK 78


                  ....*....
gi 583978668  779 ERAHSQLVV 787
Cdd:cd05851    79 DKHQARVYV 87

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 583978668  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: 3.28e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 583978668  613 RDSTIRTGHTARLECAAEGHPAPQIAWQKDgGTDFPAARDRRMhvmpDDDVFFITDVKPVDMGVYSCTAKNTAG 686
Cdd:cd05851     9 KDTYALKGQNVTLECFALGNPVPVIRWRKI-LEPMPATAEISM----SGAVLKIFNIQPEDEGTYECEAENIKG 77

Immunoglobulin-like Ig0 domain of basigin-1 (BSG1) and similar proteins; The members here are composed of the immunoglobulin (Ig) domain of the collagenase stimulatory factor, basigin-1 (BSG1; also known as Cluster of Differentiation 147 (CD147) and Extracellular Matrix Metalloproteinase Inducer (EMMPRIN)) and similar proteins. CD147 is a transmembrane glycoprotein that belongs to the immunoglobulin superfamily. It is expressed in nearly all cells including platelets and fibroblasts and is involved in inflammatory diseases, and cancer progression. CD147 is highly expressed in several cancers and used as a prognostic marker. The two primary isoforms of CD147 that are related to cancer progression have been identified: CD147 Ig1-Ig2 (also called Basigin-2) that is ubiquitously expressed in most tissues and CD147 Ig0-Ig1-Ig2 (also called Basigin-1) that is retinal specific and implicated in retinoblastoma. Studies showed that CD147 Ig0 domain is a potent stimulator of interleukin-6 and suggest that the CD147 Ig0 dimer is the functional unit required for activity.

Pssm-ID: 409534 Cd Length: 116 Bit Score: 44.18 E-value: 3.29e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  608 FIKTPRDSTIRTGHTARLECAAEGHPAPQIAWQKDGGTD-------FPAARDRRMHV-----MPDDDVFFITDVKPVDMG 675
Cdd:cd20940     3 FIKSPLSQQRLVGDSVELHCEAVGSPIPEIQWWFEGQEPneicsqlWDGARLDRVHInatyhQHATSTISIDNLTEEDTG 82


                  ....*...
gi 583978668  676 VYSCTAKN 683
Cdd:cd20940    83 TYECRASN 90

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: 43.34 E-value: 3.42e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668   610 KTPRDSTIRTGHTARLEC-AAEGHPAPQIAWQKDGGTdfpaaRDRRMHVMPDDD-----VFFITDVKPVDMGVYSCTAKN 683
Cdd:pfam00047    1 SAPPTVTVLEGDSATLTCsASTGSPGPDVTWSKEGGT-----LIESLKVKHDNGrttqsSLLISNVTKEDAGTYTCVVNN 75

                           90
                   ....*....|.
gi 583978668   684 TAGTVSANATL 694
Cdd:pfam00047   76 PGGSATLSTSL 86

Fourth immunoglobulin (Ig)-like domain in neogenin, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain in neogenin and related proteins. Neogenin is a cell surface protein which is expressed in the developing nervous system of vertebrate embryos in the growing nerve cells. It is also expressed in other embryonic tissues, and may play a general role in developmental processes such as cell migration, cell-cell recognition, and tissue growth regulation. Included in this group is the tumor suppressor protein DCC which is deleted in colorectal carcinoma. DCC and neogenin each have four Ig-like domains followed by six fibronectin type III domains, a transmembrane domain, and an intracellular domain. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409388 Cd Length: 84 Bit Score: 43.34 E-value: 3.52e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 583978668  625 LECAAEGHPAPQIAWQKDGGTDFPAardRRMHVMPDDDVFFITDVKPvDMGVYSCTAKNTAGTVSANATLTV 696
Cdd:cd05723    17 FECEVTGKPTPTVKWVKNGDVVIPS---DYFKIVKEHNLQVLGLVKS-DEGFYQCIAENDVGNAQASAQLII 84

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 583978668  712 TVGE-TVALQCKALGSPPPRITWLHNDQPLRPSDRHHfTPgnQLLVIGSALLKDAGRYTCLMSNTLGTER 780
Cdd:cd04976    15 TAGKrSVRLPMKVKAYPPPEVVWYKDGLPLTEKARYL-TR--HSLIIKEVTEEDTGNYTILLSNKQSNVF 81

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: 3.96e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 583978668  710 SVTVGETVALQCKAlGSPPPRITWLHNDQPLRPSDRHHFTPGNQLLVIGSALLKDAGRYTCLMSN 774
Cdd:cd05740    11 PVEDKDAVTLTCEP-ETQNTSYLWWFNGQSLPVTPRLTLSNGNRTLTLLNVTREDAGAYQCEISN 74

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 583978668  711 VTVGETVALQCKALGSPPPRITWLHNDQPLR-PSDRHHF--TPGNQLLVIGSALLKDAGRYTCLMSNTLGTERA 781
Cdd:cd05894     7 VVAGNKLRLDVPISGEPAPTVTWSRGDKAFTaTEGRVRVesYKDLSSFVIEGAEREDEGVYTITVTNPVGEDHA 80

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: 43.39 E-value: 4.64e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  606 PSFIKTPRDSTIRTGHTAR---LECAAEGHPAPQIAWQKDgGTDFPAARDRRMHVMpdDDVFFITDVKPV-DMGVYSCTA 681
Cdd:cd05848     2 PVFVQEPDDAIFPTDSDEKkviLNCEARGNPVPTYRWLRN-GTEIDTESDYRYSLI--DGNLIISNPSEVkDSGRYQCLA 78

                          90
                  ....*....|....
gi 583978668  682 KNTAGTV-SANATL 694
Cdd:cd05848    79 TNSIGSIlSREALL 92

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: 4.84e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  709 RSVTVGE--TVALQCKALGSPPPRITWLHNDQPLRPsdrhHFTPGN---------QLLVIGSALLKDAGRYTCLMSNTLG 777
Cdd:cd20951     8 QSHTVWEksDAKLRVEVQGKPDPEVKWYKNGVPIDP----SSIPGKykieseygvHVLHIRRVTVEDSAVYSAVAKNIHG 83

                          90
                  ....*....|
gi 583978668  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: 5.66e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  711 VTVGETVALQCKALGSPPPRIT--WLHNDQPL---RPSDRHHFTPGNQL---LVIGSALLKDAGRYTCLMSNTLGTERAH 782
Cdd:cd05854    14 INQGENLTLQCHASHDPTMDLTftWSLDDFPIdldKPNGHYRRMEVKETigdLVIVNAQLSHAGTYTCTAQTVVDSASAS 93


                  ....*
gi 583978668  783 SQLVV 787
Cdd:cd05854    94 ATLVV 98

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 2 (NCAM-2); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule NCAM-2 (also known as OCAM/mamFas II and RNCAM). NCAM-2 is organized similarly to NCAM, including five N-terminal Ig-like domains and two fibronectin type III domains. NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE), and may function like NCAM, as an adhesion molecule. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 143278 [Multi-domain] Cd Length: 98 Bit Score: 43.04 E-value: 5.72e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  700 PHLAQdLEDRSVTVGETVALQCKALGSPPPRITWlhndqpLRPSDRHHFTPGNQ---------------LLVIGSALLKD 764
Cdd:cd05870     3 PHIIQ-LKNETTVENGAATLSCKAEGEPIPEITW------KRASDGHTFSEGDKspdgrievkgqhgesSLHIKDVKLSD 75

                          90
                  ....*....|...
gi 583978668  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: 5.83e-05

                           10        20
                   ....*....|....*....|....*.
gi 583978668   460 NATCAHPESLKGKSVFEVPPSSFVCD 485
Cdd:pfam01463    1 NARCASPPRLRGQPLLDLLPSDFSCS 26

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: 42.61 E-value: 6.63e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  615 STIRTGHTARLECAAEGHPAPQIAWQKDGGtdfPAARDRRMH-VMPDDDVFFITDVKPVDMGVYSCTAKNTAGTV--SAN 691
Cdd:cd05760    11 AEIQPSSRVTLRCHIDGHPRPTYQWFRDGT---PLSDGQGNYsVSSKERTLTLRSAGPDDSGLYYCCAHNAFGSVcsSQN 87


                  ....*..
gi 583978668  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: 7.40e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  606 PSFIKTPRDSTIRTGHT-ARLECAAEGHPAPQIAWQKDGGT---DFPAAR----DRRMHVMPdddvFFITDVK-PVDMGV 676
Cdd:cd20955     2 PVFLKEPTNRIDFSNSTgAEIECKASGNPMPEIIWIRSDGTavgDVPGLRqissDGKLVFPP----FRAEDYRqEVHAQV 77

                          90
                  ....*....|..
gi 583978668  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: 7.42e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  700 PHLaQDLEDRSVTVGETVALQCKALGSPPP-RITWLHNDQPLRPSDRHHFT-----PGNQLLVIGSALLKDAGRYTCLMS 773
Cdd:cd05895     1 PKL-KEMKSQEVAAGSKLVLRCETSSEYPSlRFKWFKNGKEINRKNKPENIkiqkkKKKSELRINKASLADSGEYMCKVS 79

                          90
                  ....*....|....
gi 583978668  774 NTLGTERAHSQLVV 787
Cdd:cd05895    80 SKLGNDSASANVTI 93

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: 42.66 E-value: 7.51e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  604 VLPSFIKTPRDSTIRTGhTARLECAAEGHPAPQIAWQK--DGGT--DFPAARDRRMHVMPD--DDVFFITDVKPVDMGVY 677
Cdd:cd05870     1 VQPHIIQLKNETTVENG-AATLSCKAEGEPIPEITWKRasDGHTfsEGDKSPDGRIEVKGQhgESSLHIKDVKLSDSGRY 79


                  ....*....
gi 583978668  678 SCTAKNTAG 686
Cdd:cd05870    80 DCEAASRIG 88

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1) and similar proteins; The members here are composed of the fourth immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule (NCAM-1). NCAM plays important roles in the development and regeneration of the central nervous system, in synaptogenesis and neural migration. NCAM mediates cell-cell and cell-substratum recognition and adhesion via homophilic (NCAM-NCAM), and heterophilic (NCAM-non-NCAM), interactions. NCAM is expressed as three major isoforms having different intracellular extensions. The extracellular portion of NCAM has five N-terminal Ig-like domains and two fibronectin type III domains. The double zipper adhesion complex model for NCAM homophilic binding involves Ig1, Ig2, and Ig3. By this model, Ig1 and Ig2 mediate dimerization of NCAM molecules situated on the same cell surface (cis interactions), and Ig3 domains mediate interactions between NCAM molecules expressed on the surface of opposing cells (trans interactions), through binding to the Ig1 and Ig2 domains. The adhesive ability of NCAM is modulated by the addition of polysialic acid chains to the fifth Ig-like domain. Also included in this group is NCAM-2 (also known as OCAM/mamFas II and RNCAM) NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE). One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

Pssm-ID: 409395 [Multi-domain] Cd Length: 96 Bit Score: 42.51 E-value: 8.32e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 583978668  613 RDSTIRTGHTARLECAAEGHPAPQIAWQK--DGGTDFPAARDRRMHVMPDDDVFFIT--DVKPVDMGVYSCTAKNTAG 686
Cdd:cd05732     9 ENQTAVELEQITLTCEAEGDPIPEITWRRatRGISFEEGDLDGRIVVRGHARVSSLTlkDVQLTDAGRYDCEASNRIG 86

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: 9.58e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  700 PHLAQDLEDRSVTVGETVALQCKALGSPPPRITWLHNDQPLR----PSDRHHFTPGNQLLVIGSALLKDAGRYTCLMSNT 775
Cdd:cd20974     1 PVFTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFRDGQVIStstlPGVQISFSDGRAKLSIPAVTKANSGRYSLTATNG 80

                          90
                  ....*....|...
gi 583978668  776 LGTERAHSQLVVT 788
Cdd:cd20974    81 SGQATSTAELLVL 93

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

Pssm-ID: 463839 [Multi-domain] Cd Length: 127 Bit Score: 42.92 E-value: 1.31e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668   341 INEGAFRGLKaLRILELDHNDISgtIEdtNGAFSGLDSLIKLTlFGNKIKSVAKKAFSGLdTLEHLNLGENaIRSIQPDA 420
Cdd:pfam13306    3 IGSYAFYNCS-LTSITIPSSLTS--IG--EYAFSNCTSLKSIT-LPSSLTSIGSYAFYNC-SLTSITIPSS-LTSIGEYA 74

                           90
                   ....*....|....*
gi 583978668   421 FTKMRNLKSLLIQSN 435
Cdd:pfam13306   75 FSNCSNLKSITLPSN 89

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: 41.76 E-value: 1.33e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  620 GHTARLECAAEGHPAPQIAWQKDGGtdfPAARDRRM---HVMPDDDVFFITDVKPVDMGVYSCTAKNTAGTVSANATLTV 696
Cdd:cd05857    19 ANTVKFRCPAAGNPTPTMRWLKNGK---EFKQEHRIggyKVRNQHWSLIMESVVPSDKGNYTCVVENEYGSINHTYHLDV 95

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: 41.50 E-value: 1.60e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  605 LPSFIKTPRDSTIrtghtarLECAAEGHPAPQIAWQKDGGTdFPAARDRRMHVMPDDDVFFI---TDVKPVDM-GVYSCT 680
Cdd:cd05875     8 AKDYIVDPRDNIL-------IECEAKGNPVPTFHWTRNGKF-FNVAKDPRVSMRRRSGTLVIdfrGGGRPEDYeGEYQCF 79

                          90
                  ....*....|.
gi 583978668  681 AKNTAGTVSAN 691
Cdd:cd05875    80 ARNKFGTALSN 90

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

Pssm-ID: 463713 [Multi-domain] Cd Length: 44 Bit Score: 39.92 E-value: 1.84e-04

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 583978668    67 SLNLGYNKLTSISPeaFANLPNLRELRLDHN-ELTSIPDL 105
Cdd:pfam12799    5 VLDLSNNQITDIPP--LAKLPNLETLDLSGNnKITDLSDL 42

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 583978668  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: 3.15e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  700 PHLAQDLEDRSVTVGETVALQCKALGSPPPRITWLHNDQPLRPSDRHHFTP----GNQLLVIGSALLKDAGRYTCLMSNT 775
Cdd:cd05893     1 PFFEMKLKHYKIFEGMPVTFTCRVAGNPKPKIYWFKDGKQISPKSDHYTIQrdldGTCSLHTTASTLDDDGNYTIMAANP 80

                          90
                  ....*....|..
gi 583978668  776 LGTERAHSQLVV 787
Cdd:cd05893    81 QGRISCTGRLMV 92

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 583978668  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 583978668  711 VTVGETVALQCKALGSPPPRITWLH------NDQPLRPSDRHHFTPGNqlLVIGSALLKDAGRYTCLMSNTLGTERAHSQ 784
Cdd:cd20953    15 VSSASSIALLCPAQGYPAPSFRWYKfiegttRKQAVVLNDRVKQVSGT--LIIKDAVVEDSGKYLCVVNNSVGGESVETV 92


                  ...
gi 583978668  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: 5.60e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 583978668  713 VGETVALQCKALGSPPPRITWLHNDQPLRPSdrhhftpgnQLLVIGSALLKDAGRYTCLMSNTLGTERAHSQLVVT 788
Cdd:cd20948     9 SGENLNLSCHAASNPPAQYSWTINGTFQTSS---------QELFLPAITENNEGTYTCSAHNSLTGKNISLVLSVT 75

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: 39.80 E-value: 5.61e-04

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668    496 PETTMTVLGSDVRLTCTAASSSSSPMTfaWRKDQellrnaemenyahvrahhqaatPDLPGAGGGGVMEY---TTILHLR 572
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVT--WYKQG----------------------GKLLAESGRFSVSRsgsTSTLTIS 56

                            90       100       110
                    ....*....|....*....|....*....|
gi 583978668    573 RVTFAHEGRYQCIITNHFGStYSSKARLIV 602
Cdd:smart00410   57 NVTPEDSGTYTCAATNSSGS-ASSGTTLTV 85

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

Pssm-ID: 319300 Cd Length: 92 Bit Score: 39.88 E-value: 5.78e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  612 PRDSTIRTGHTARLECAAEGHPAPQIAWQKDggtDFPAAR-DR-RMHVMPDDDVFF-ITDVKPVDMGVYSCTAKNTAGTV 688
Cdd:cd05737     8 PDVVTIMEGKTLNLTCNVWGDPPPEVSWLKN---DQALAFlDHcNLKVEAGRTVYFtINGVSSEDSGKYGLVVKNKYGSE 84


                  ....*...
gi 583978668  689 SANATLTV 696
Cdd:cd05737    85 TSDVTVSV 92

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

Pssm-ID: 409545 Cd Length: 95 Bit Score: 39.83 E-value: 6.80e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  621 HTARLECAAEGHPAPQIAWQKdggtdFPAARDRRMHVMPDDDV------FFITDVKPVDMGVYSCTAKNTAGTVSANATL 694
Cdd:cd20953    19 SSIALLCPAQGYPAPSFRWYK-----FIEGTTRKQAVVLNDRVkqvsgtLIIKDAVVEDSGKYLCVVNNSVGGESVETVL 93


                  ..
gi 583978668  695 TV 696
Cdd:cd20953    94 TV 95

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

Pssm-ID: 409396 [Multi-domain] Cd Length: 94 Bit Score: 39.70 E-value: 6.81e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  703 AQDLEDRSVTVGETVALQCKALGSPPPRITWLHNDQPLRPSDRHHFT----PGNQLLVIGSALLKD-AGRYTCLMSNTLG 777
Cdd:cd05733     5 EQSPKDYIVDPRDNITIKCEAKGNPQPTFRWTKDGKFFDPAKDPRVSmrrrSGTLVIDNHNGGPEDyQGEYQCYASNELG 84

                          90
                  ....*....|
gi 583978668  778 TERAHSQLVV 787
Cdd:cd05733    85 TAISNEIRLV 94

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: 40.03 E-value: 6.97e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  612 PRDSTIRTGHTARLECAAEGHPAPQIA--WQKDG---GTDFPAARDRRMHVMPDDDVFFITDVKPVDMGVYSCTAKNTAG 686
Cdd:cd05854     9 PSSADINQGENLTLQCHASHDPTMDLTftWSLDDfpiDLDKPNGHYRRMEVKETIGDLVIVNAQLSHAGTYTCTAQTVVD 88

                          90
                  ....*....|....
gi 583978668  687 TVSANATLTVLETP 700
Cdd:cd05854    89 SASASATLVVRGPP 102

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: 7.06e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  710 SVTVGETVALQCKALGSPPPRITWL----HNDQPLRPSDRhhftpgnQLLVIGSALLKDAGRYTCLMSNTLGTERaHSQL 785
Cdd:cd16082     9 TVPQGMRISLQCQAWGSPPISYVWYkeqtNNQEPIKVAAL-------STLLFKPAVVADSGSYFCTAKGRVGSEQ-RSDI 80


                  .
gi 583978668  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: 7.30e-04

                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 583978668   278 TSLQQLFLSNNSIARInpDGWKFCQKLRELNLSYNNL 314
Cdd:pfam12799    1 PNLEVLDLSNNQITDI--PPLAKLPNLETLDLSGNNK 35

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: 8.44e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 583978668  725 GSPPPRITWLHNDQPLRPSDRH----HFTPGNQLLVIGSALLK-----DAGRYTCLMSNTLGTERA 781
Cdd:cd04971    24 GNPKPTLTWYHNGAVLNESDYIrteiHYEAATPTEYHGCLKFDnpthvNNGNYTLVASNEYGQDSK 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: 39.38 E-value: 1.18e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  493 TVQPETTMTVLGSDVRLTCTAASSSssPMTFAWRKDQELLRNAEMENYAHVrahhqaatPDlpgagggGVMEYTTILHlR 572
Cdd:cd05722     5 LSEPSDIVAMRGGPVVLNCSAESDP--PPKIEWKKDGVLLNLVSDERRQQL--------PN-------GSLLITSVVH-S 66

                          90       100       110
                  ....*....|....*....|....*....|.
gi 583978668  573 RVTFAHEGRYQCIITN-HFGSTYSSKARLIV 602
Cdd:cd05722    67 KHNKPDEGFYQCVAQNeSLGSIVSRTARVTV 97

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: 1.23e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  612 PRDSTIRTGHTARLECAAEGHPAPQIAWQKdGGTDFPaardrRMHVMP-DDDVFFITDVKpvDMGVYSCTAKNTAGTVSA 690
Cdd:cd05739     4 PSNHEVMPGGSVNLTCVAVGAPMPYVKWMK-GGEELT-----KEDEMPvGRNVLELTNIY--ESANYTCVAISSLGMIEA 75


                  ....*.
gi 583978668  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: 1.27e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668   137 ETLDLSNNDITELRGqcFPAGLHIRDLYLSNNKISvlelgvldHLGETLQVLrlsrnrisqipvkafqLPRLTQLELNRN 216
Cdd:pfam14580   45 DTIDFSDNEIRKLDG--FPLLRRLKTLLLNNNRIC--------RIGEGLGEA----------------LPNLTELILTNN 98

                           90       100
                   ....*....|....*....|....*....
gi 583978668   217 RIRQ-VEGLTFQGLSSLEVLKLQRNSISK 244
Cdd:pfam14580   99 NLQElGDLDPLASLKKLTFLSLLRNPVTN 127

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: 1.74e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 583978668  701 HLAQDLEDRSVTVGETVALQCKALGSPPP-RITWLHNDQPL 740
Cdd:cd05749     1 HFTVEPEDLAVTANTPFNLTCQAVGPPEPvEILWWQGGSPL 41

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: 1.83e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 583978668  714 GETVALQCKALGSPPPRITWLHNDQPLR---PSDRHHFTPGNqlLVIGSALLKDAGRYTCLMSNTLGTERAHSQLVV 787
Cdd:cd05867    14 GETARLDCQVEGIPTPNITWSINGAPIEgtdPDPRRHVSSGA--LILTDVQPSDTAVYQCEARNRHGNLLANAHVHV 88

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

Pssm-ID: 411060 [Multi-domain] Cd Length: 220 Bit Score: 40.92 E-value: 1.98e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 583978668   68 LNLGYNKLTSISPeaFANLPNLRELRLDHNELTSIPDLGQAASTIVSL 115
Cdd:cd21340   125 LNISGNNIDSLEP--LAPLRNLEQLDASNNQISDLEELLDLLSSWPSL 170

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 583978668   277 LTSLQQLFLSNNSIARINPDGWKFCQKLRELNLSYNNLTRL-DEGSLAVLGDLHTLRLGHNSIS---HINEGAFRGLKAL 352
Cdd:pfam14580   63 LRRLKTLLLNNNRICRIGEGLGEALPNLTELILTNNNLQELgDLDPLASLKKLTFLSLLRNPVTnkpHYRLYVIYKVPQL 142


                   ....
gi 583978668   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 583978668  729 PRITWLHNDQPLrPSDRHHFTPGNQLLVIGSALLKDAGRYTCLMSNT 775
Cdd:cd20994    31 PKVQWYKDCKPL-LLDDKRFAGLESDLLIFNVTVQDQGNYTCHTSYT 76

leucine-rich repeat receptor-like protein kinase; Provisional

Pssm-ID: 215061 [Multi-domain] Cd Length: 968 Bit Score: 41.76 E-value: 2.66e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668   66 VSLNLGYNKLTSISPEAFANLPNLRELRLDHNELT-SIP-DLGQAAStIVSLYLHHNKIR-SIDGrrTGELLSVETLDLS 142
Cdd:PLN00113  526 VSLDLSHNQLSGQIPASFSEMPVLSQLDLSQNQLSgEIPkNLGNVES-LVQVNISHNHLHgSLPS--TGAFLAINASAVA 602


                  ...
gi 583978668  143 NND 145
Cdd:PLN00113  603 GNI 605

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: 2.67e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  490 PQITVQPETTMTVLGSD-VRLTCtaASSSSSPMTFAWRKDQELLrnaEMENYAHVRAHHQAATpdLPGAGGGGVMEytti 568
Cdd:cd05733     1 PTITEQSPKDYIVDPRDnITIKC--EAKGNPQPTFRWTKDGKFF---DPAKDPRVSMRRRSGT--LVIDNHNGGPE---- 69

                          90       100       110
                  ....*....|....*....|....*....|...
gi 583978668  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: 3.13e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  612 PRDSTIRTGHTARLECAAEGHPAPQIAW----QKDG---GTD-FPAAR----------DRRMhvmpddDVFFITDVKPVD 673
Cdd:cd05858     8 PANTSVVVGTDAEFVCKVYSDAQPHIQWlkhvEKNGskyGPDgLPYVEvlktagvnttDKEI------EVLYLRNVTFED 81

                          90       100
                  ....*....|....*....|....
gi 583978668  674 MGVYSCTAKNTAGTVSANATLTVL 697
Cdd:cd05858    82 AGEYTCLAGNSIGISHHSAWLTVL 105

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: 3.15e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  705 DLEDRSVTVGETVALQCKAL-GSPPPRITWLHNDQPLrpSDRHHFT-----PGNQLLVIGSALLKDAGRYTCLMSNTLGT 778
Cdd:cd20959     8 AFGEGAAQVGMRAQLHCGVPgGDLPLNIRWTLDGQPI--SDDLGITvsrlgRRSSILSIDSLEASHAGNYTCHARNSAGS 85


                  ....*....
gi 583978668  779 ERAHSQLVV 787
Cdd:cd20959    86 ASYTAPLTV 94

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: 3.19e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  712 TVGETVALQCKALGSPPPRITWLHNDQPLRPSD--RHHFTP---GNQL---LVIGSALLKDAGRYTCLMSNTLGTERAHS 783
Cdd:cd05735    16 TKGQKKEMSCTAHGEKPIIVRWEKEDTIINPSEmsRYLVTTkevGDEVistLQILPTVREDSGFFSCHAINSYGEDRGII 95


                  ....*.
gi 583978668  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: 3.20e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 583978668  705 DLEDRSVTVGETVALQCKALgSPPPRITWLHNDQPLRPSDRHHFTPGNQLLvIGSALLKDAGRYTCL 771
Cdd:cd05873     2 DPRQRTFKLGGNAELKCSPK-SNLARVVWKFQGKVLKAESPKYGLYGDGLL-IFNASEADAGRYQCL 66

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: 3.22e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  490 PQITVQPETTMTVLGSDVRLTCTAASSSSSpmTFAWRKDQELLRNAEMEnyahVRAHHQAatpdLPGagggGVMEYTTIL 569
Cdd:cd07693     1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTP--TIQWLKNGQPLETDKDD----PRSHRIV----LPS----GSLFFLRVV 66

                          90       100       110
                  ....*....|....*....|....*....|...
gi 583978668  570 HLRRVTfAHEGRYQCIITNHFGSTYSSKARLIV 602
Cdd:cd07693    67 HGRKGR-SDEGVYVCVAHNSLGEAVSRNASLEV 98

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: 37.69 E-value: 3.22e-03

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 583978668  729 PRITWLHNDQPLRpsDRHHFTPGNQLLVIGSALLKDAGRYTCLMSNT 775
Cdd:cd05757    30 PPIQWYKDCKPLQ--GDKRFIPKGSKLLIQNVTEEDAGNYTCKFTYT 74

hypothetical protein; Provisional

Pssm-ID: 178695 [Multi-domain] Cd Length: 623 Bit Score: 41.34 E-value: 3.25e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  177 VLDHLGETLQVLRlsrnriSQIPVKAFQLPRLTQLELNRNRIRQVEGLTFQGLSSLEVLKLQRNSISKLTDGAFFDLAKM 256
Cdd:PLN03150  419 FIDGLGLDNQGLR------GFIPNDISKLRHLQSINLSGNSIRGNIPPSLGSITSLEVLDLSYNSFNGSIPESLGQLTSL 492

                          90       100
                  ....*....|....*....|.
gi 583978668  257 KVLHLDYNSLTEVNSGSLYGL 277
Cdd:PLN03150  493 RILNLNGNSLSGRVPAALGGR 513

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: 3.76e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  619 TGHTARLECAAEGHPAP-QIAWQKDGG--TDFPAARDRRmhVMPDDDVFFITDVKPVDMGVYSCTAKNTAGTVSANATLT 695
Cdd:cd20959    16 VGMRAQLHCGVPGGDLPlNIRWTLDGQpiSDDLGITVSR--LGRRSSILSIDSLEASHAGNYTCHARNSAGSASYTAPLT 93


                  .
gi 583978668  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: 3.82e-03

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 583978668   185 LQVLRLSRNRISQIPVKAfQLPRLTQLELNRN-RIRQVEGL 224
Cdd:pfam12799    3 LEVLDLSNNQITDIPPLA-KLPNLETLDLSGNnKITDLSDL 42

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: 3.84e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  611 TPRDSTIRTGHTARLECAAEGHPAPQIAWQKDGGtdfpaardRRMHvmpdDDVFFITDVKPVDMGVYSCTAKNTAGTVSA 690
Cdd:cd20948     1 SPSDTYYLSGENLNLSCHAASNPPAQYSWTINGT--------FQTS----SQELFLPAITENNEGTYTCSAHNSLTGKNI 68


                  ....*.
gi 583978668  691 NATLTV 696
Cdd:cd20948    69 SLVLSV 74

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: 37.91 E-value: 3.98e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  612 PRDSTIRTGHTARLECAAEGHPAPQIA--WQKDG-GTDF--PAARDRRMHVMPDDDVFFITDVKPVDMGVYSCTAKNTAG 686
Cdd:cd04970     9 PSNADITVGENATLQCHASHDPTLDLTftWSFNGvPIDLekIEGHYRRRYGKDSNGDLEIVNAQLKHAGRYTCTAQTVVD 88

                          90
                  ....*....|....
gi 583978668  687 TVSANATLTVLETP 700
Cdd:cd04970    89 SDSASATLVVRGPP 102

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: 4.38e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 583978668  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: 4.98e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  283 LFLSNNSIARINPDGWKFCQKLRELNLSYNNLTRLDEGSLAVLGDLHTLRLGHNSISHINEGAFRGLKALRILELDHNDI 362
Cdd:PLN03150  423 LGLDNQGLRGFIPNDISKLRHLQSINLSGNSIRGNIPPSLGSITSLEVLDLSYNSFNGSIPESLGQLTSLRILNLNGNSL 502

                          90
                  ....*....|
gi 583978668  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: 5.17e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 583978668  718 ALQCKALGSPPPRITWLHNDQPLRPSD----RHHFTPG----NQLLVIGSALLKDAGRYTCLMSNTLGTERAHSQLVVTE 789
Cdd:cd05773    27 NLVCQAQGVPRVQFRWAKNGVPLDLGNpryeETTEHTGtvhtSILTIINVSAALDYALFTCTAHNSLGEDSLDIQLVSTS 106


                  .
gi 583978668  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: 5.86e-03

                          10        20        30
                  ....*....|....*....|....*....|.
gi 583978668  751 GNQLLVIGSALLKDAGRYTCLMSNTLGTERA 781
Cdd:cd20984    74 GNASLRLKNVQLTDAGTYLCIISNSKGTGNA 104

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

Pssm-ID: 197687 [Multi-domain] Cd Length: 24 Bit Score: 35.02 E-value: 6.08e-03

                            10
                    ....*....|....*....
gi 583978668     86 LPNLRELRLDHNELTSIPD 104
Cdd:smart00369    1 LPNLRELDLSNNQLSSLPP 19

Leucine-rich repeats, outliers;

Pssm-ID: 197688 [Multi-domain] Cd Length: 24 Bit Score: 35.02 E-value: 6.08e-03

                            10
                    ....*....|....*....
gi 583978668     86 LPNLRELRLDHNELTSIPD 104
Cdd:smart00370    1 LPNLRELDLSNNQLSSLPP 19

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: 36.68 E-value: 8.63e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 583978668  620 GHTARLECAAEGHPAPQIAWQKDGGTDFPAArdRRMHVMPDDDV-FFITDVKpvDMGVYSCTAKNTAGTVSANATLTV 696
Cdd:cd05764    15 GQRATLRCKARGDPEPAIHWISPEGKLISNS--SRTLVYDNGTLdILITTVK--DTGAFTCIASNPAGEATARVELHI 88