NCBI Conserved Domain Search

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 89.29 E-value: 1.21e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534 1446 SRPSLTQYELDNLNKHRRYEIRMSVYNAVGEGPSSPPQEVFVGEAVPtAAPRNVVVHGATATQLDVTWEPPPldsqNGDI 1525
Cdd:COG3401   187 VTSTTLVDGGGDIEPGTTYYYRVAATDTGGESAPSNEVSVTTPTTPP-SAPTGLTATADTPGSVTLSWDPVT----ESDA 261

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534 1526 QGYKIYFWEAQRGNLTeRVKTlfLAENSVKLKNLTGYTAYMVSVAAFNAAGD-GPRSTPTQGQTQQAAPSAPSSVKFSEL 1604
Cdd:COG3401   262 TGYRVYRSNSGDGPFT-KVAT--VTTTSYTDTGLTNGTTYYYRVTAVDAAGNeSAPSNVVSVTTDLTPPAAPSGLTATAV 338

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534 1605 TTTSVNVSWEAPqfPNGILEGYRlVYEPCSPVDGVSKIVTVdVKGNSplwLKVKDLAEGVTYRFRIRAKTfTYGPE---- 1680
Cdd:COG3401   339 GSSSITLSWTAS--SDADVTGYN-VYRSTSGGGTYTKIAET-VTTTS---YTDTGLTPGTTYYYKVTAVD-AAGNEsaps 410

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534 1681 ----IEANVTTGPGEGAPGPPGVPIIVRYSSAIAIHWSSGDPGKGPITRYVIEARPSDEGLWDILIKDIPKEVSSYTFSm 1756
Cdd:COG3401   411 eevsATTASAASGESLTASVDAVPLTDVAGATAAASAASNPGVSAAVLADGGDTGNAVPFTTTSSTVTATTTDTTTANL- 489

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*
gi 119609534 1757 diLKPGVSYDFRVIAVNDYGFGTPSSPSQSVPAQKANPFYEEWWF 1801
Cdd:COG3401   490 --SVTTGSLVGGSGASSVTNSVSVIGASAAAAVGGAPDGTPNVTG 532

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: 77.05 E-value: 8.50e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  177 PQFVKEPERHITAEMEKVVDIPCQAKGVPPPSITWYKDAAVVEVEKLTrfRQRNDGGLQISGLVPDDTGMFQCFARNAAG 256
Cdd:cd20978     1 PKFIQKPEKNVVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMER--ATVEDGTLTIINVQPEDTGYYGCVATNEIG 78

                          90
                  ....*....|
gi 119609534  257 EVQTSTYLAV 266
Cdd:cd20978    79 DIYTETLLHV 88

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 76.00 E-value: 2.39e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534 1495 APRNVVVHGATATQLDVTWEPPPLDsqNGDIQGYKIYFWEAQRGNlTERVKTLFLAENSVKLKNLTGYTAYMVSVAAFNA 1574
Cdd:cd00063     3 PPTNLRVTDVTSTSVTLSWTPPEDD--GGPITGYVVEYREKGSGD-WKEVEVTPGSETSYTLTGLKPGTEYEFRVRAVNG 79

                          90
                  ....*....|....
gi 119609534 1575 AGDGPRSTPTQGQT 1588
Cdd:cd00063    80 GGESPPSESVTVTT 93

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: 75.23 E-value: 3.98e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  273 ITRGPLDSTVIDGMSVVLACETSGAPRPAITWQKGERILAsgsVQLPRFTPLESGSLLISPTHISDAGTYTCLATNSRGV 352
Cdd:cd20952     2 ILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLL---GKDERITTLENGSLQIKGAEKSDTGEYTCVALNLSGE 78


                  ....*....
gi 119609534  353 DEASADLVV 361
Cdd:cd20952    79 ATWSAVLDV 87

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 82.74 E-value: 1.07e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  471 TVERRAINLTWTKPFDGNSPLIRYILEMSENNAPWTVLLASVDPKATSVTVKGLVPARSYQFRLCAVNDVGKGQFSkDTE 550
Cdd:COG3401   146 GLYGVDGANASGTTASSVAGAGVVVSPDTSATAAVATTSLTVTSTTLVDGGGDIEPGTTYYYRVAATDTGGESAPS-NEV 224

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  551 RVSLPEEPPtAPPQNVIASGRTNQSIMIQWQPPPESHqngiLKGYIIRYCLAGLPvgyQFKNITDADVNNLLLEDLIIWT 630
Cdd:COG3401   225 SVTTPTTPP-SAPTGLTATADTPGSVTLSWDPVTESD----ATGYRVYRSNSGDG---PFTKVATVTTTSYTDTGLTNGT 296

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  631 NYEIEVAAYNSAGL-GVYSSKVTEWTLQGVPTvPPGNVHAEATNSTTIRFTWNAPSPQFInginQGYKL--IAWEPEQEE 707
Cdd:COG3401   297 TYYYRVTAVDAAGNeSAPSNVVSVTTDLTPPA-APSGLTATAVGSSSITLSWTASSDADV----TGYNVyrSTSGGGTYT 371

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  708 EVTMVTARPNFQDsihvgfvSGLKKFTEYFTSVLCFTTPGDGPRSTPQlVRTHEDVPGPVGHLSFSEILDTSlkVSWQEP 787
Cdd:COG3401   372 KIAETVTTTSYTD-------TGLTPGTTYYYKVTAVDAAGNESAPSEE-VSATTASAASGESLTASVDAVPL--TDVAGA 441

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  788 GEKNGILTGYRISWEEYNRTNTRVTHYLPNVTLEYRVTGLTALTTYTIEVAAMTSKGQGQVSASTISSGVPPELPGPPTN 867
Cdd:COG3401   442 TAAASAASNPGVSAAVLADGGDTGNAVPFTTTSSTVTATTTDTTTANLSVTTGSLVGGSGASSVTNSVSVIGASAAAAVG 521

                         410       420       430
                  ....*....|....*....|....*....|
gi 119609534  868 LGISNIGPRSVTLQFRPGYDGKTSISRWLV 897
Cdd:COG3401   522 GAPDGTPNVTGASPVTVGASTGDVLITDLV 551

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 72.68 E-value: 2.93e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534   271 PNITRGPLDSTVIDGMSVVLACETSGAPRPAITWQKGERILASGSvqlpRFTPLESG---SLLISPTHISDAGTYTCLAT 347
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSD----RFKVTYEGgtyTLTISNVQPDDSGKYTCVAT 76

                           90
                   ....*....|....
gi 119609534   348 NSRGVDEASADLVV 361
Cdd:pfam07679   77 NSAGEAEASAELTV 90

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 81.20 E-value: 3.28e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534 1057 QTVVGRTRESVPSSGPTNVSALATTSSSMLVRWSEVPEADRNGLVLGYKVMYKEKDSDTQPRFWLVEGNSSRSAQLTGLG 1136
Cdd:COG3401   116 EVPSPAVGTATTATAVAGGAATAGTYALGAGLYGVDGANASGTTASSVAGAGVVVSPDTSATAAVATTSLTVTSTTLVDG 195

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534 1137 KYVL-----YEVQVLAFTRIGDGSPShPPILERTLDDVPGPPMGILFPEVRTTSVRLIWQPPAAPNgiILAYQItHRlnT 1211
Cdd:COG3401   196 GGDIepgttYYYRVAATDTGGESAPS-NEVSVTTPTTPPSAPTGLTATADTPGSVTLSWDPVTESD--ATGYRV-YR--S 269

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534 1212 TTANTATVEVLAPSARQYTATGLKPESVYLFRITAQTRKGWGEAAEALVVTTEKRDRPQPPSrpMVQQEDVRARSVLLSW 1291
Cdd:COG3401   270 NSGDGPFTKVATVTTTSYTDTGLTNGTTYYYRVTAVDAAGNESAPSNVVSVTTDLTPPAAPS--GLTATAVGSSSITLSW 347

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534 1292 EPGSDglSPVRYYTIQTRELPSGRWALHSASVshNASSFIVDRLKPFTSYKFRVKATNDIGDSEFSEESESLTTLQAAPD 1371
Cdd:COG3401   348 TASSD--ADVTGYNVYRSTSGGGTYTKIAETV--TTTSYTDTGLTPGTTYYYKVTAVDAAGNESAPSEEVSATTASAASG 423

                         330       340
                  ....*....|....*....|
gi 119609534 1372 EAPTILSVTPHTTTSVLIRW 1391
Cdd:COG3401   424 ESLTASVDAVPLTDVAGATA 443

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: 72.49 E-value: 3.69e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  271 PNITRGPLD--STVIDGMSVVLACETSGAPRPAITWQKGERILasgsVQLPRFTPLESGSLLISPTHISDAGTYTCLATN 348
Cdd:cd04969     1 PDFELNPVKkkILAAKGGDVIIECKPKASPKPTISWSKGTELL----TNSSRICILPDGSLKIKNVTKSDEGKYTCFAVN 76

                          90
                  ....*....|...
gi 119609534  349 SRGVDEASADLVV 361
Cdd:cd04969    77 FFGKANSTGSLSV 89

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 81.20 E-value: 3.73e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  829 ALTTYTIEVAAMTSKGQGQVSASTISSGVPPELPGPPTNLGISNIGPRSVtlqfrpGYDGKTSISRWLVEAQVGVVGEGE 908
Cdd:COG3401   104 GGATNTGLTSSDEVPSPAVGTATTATAVAGGAATAGTYALGAGLYGVDGA------NASGTTASSVAGAGVVVSPDTSAT 177

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  909 EWLLIHQLSNEPDARSMEVPDLNPFTCYSFRMRQVNIVGTSPPSQPSRKIQTLQAPpdMAPANVSLRTASETSLWLRWMP 988
Cdd:COG3401   178 AAVATTSLTVTSTTLVDGGGDIEPGTTYYYRVAATDTGGESAPSNEVSVTTPTTPP--SAPTGLTATADTPGSVTLSWDP 255

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  989 lpemeyNGNPESVGYKIKYSRSDGHGKTlshVVQDRVERDYTIEDLEEWTEYRVQVQAFNAIG-SGPWSQTVVGRTRESV 1067
Cdd:COG3401   256 ------VTESDATGYRVYRSNSGDGPFT---KVATVTTTSYTDTGLTNGTTYYYRVTAVDAAGnESAPSNVVSVTTDLTP 326

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534 1068 PSSgPTNVSALATTSSSMLVRWSEVPEADrnglVLGYKVmYKEKDSDTQPRfWLVEGNSSRSAQLTGLGKYVLYEVQVLA 1147
Cdd:COG3401   327 PAA-PSGLTATAVGSSSITLSWTASSDAD----VTGYNV-YRSTSGGGTYT-KIAETVTTTSYTDTGLTPGTTYYYKVTA 399

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 119609534 1148 FTRIGDGSPSHPPILERTLDDVPGPPMGILFPEVRTTSVRLIWQPPAAPNGIILAYQIT 1206
Cdd:COG3401   400 VDAAGNESAPSEEVSATTASAASGESLTASVDAVPLTDVAGATAAASAASNPGVSAAVL 458

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 72.53 E-value: 4.90e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534 1170 PGPPMGILFPEVRTTSVRLIWQPPAAPNGIILAYQITHRlNTTTANTATVEVLAPSARQYTATGLKPESVYLFRITAQTR 1249
Cdd:cd00063     1 PSPPTNLRVTDVTSTSVTLSWTPPEDDGGPITGYVVEYR-EKGSGDWKEVEVTPGSETSYTLTGLKPGTEYEFRVRAVNG 79

                          90
                  ....*....|....
gi 119609534 1250 KGWGEAAEALVVTT 1263
Cdd:cd00063    80 GGESPPSESVTVTT 93

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 80.82 E-value: 5.09e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534 1332 VDRLKPFTSYKFRVKATNDIGDSEFSEESEsLTTLQAAPdEAPTILSVTPHTTTSVLIRWQPPAEdkingillgfriryr 1411
Cdd:COG3401   196 GGDIEPGTTYYYRVAATDTGGESAPSNEVS-VTTPTTPP-SAPTGLTATADTPGSVTLSWDPVTE--------------- 258

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534 1412 ellyEGLRGFTLRGINNPGATWAELTSmysmrnlsrPSLTQYELDNLNKHRRYEIRMSVYNAVG-EGPSSPPQEVFVGEA 1490
Cdd:COG3401   259 ----SDATGYRVYRSNSGDGPFTKVAT---------VTTTSYTDTGLTNGTTYYYRVTAVDAAGnESAPSNVVSVTTDLT 325

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534 1491 VPtAAPRNVVVHGATATQLDVTWEPppldSQNGDIQGYKIYFWEAQRGNLTERVKTlfLAENSVKLKNLTGYTAYMVSVA 1570
Cdd:COG3401   326 PP-AAPSGLTATAVGSSSITLSWTA----SSDADVTGYNVYRSTSGGGTYTKIAET--VTTTSYTDTGLTPGTTYYYKVT 398

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534 1571 AFNAAGD-GPRSTPTQGQTQQAAPSAPssvkfselTTTSVNVSWEAPQFPNGILEGYRLVYEPCSPVDGVSKIVTVDVKG 1649
Cdd:COG3401   399 AVDAAGNeSAPSEEVSATTASAASGES--------LTASVDAVPLTDVAGATAAASAASNPGVSAAVLADGGDTGNAVPF 470

                         330       340       350
                  ....*....|....*....|....*....|....*...
gi 119609534 1650 NSPLWLKVKDLAEGVTYRFRIRAKTFTYGPEIEANVTT 1687
Cdd:COG3401   471 TTTSSTVTATTTDTTTANLSVTTGSLVGGSGASSVTNS 508

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 72.14 E-value: 6.19e-15

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  459 PHAPEHPvaTLSTVERRAINLTWTKPFDGNSPLIRYILEMSENNAPWTVLLASVDPKATSVTVKGLVPARSYQFRLCAVN 538
Cdd:cd00063     1 PSPPTNL--RVTDVTSTSVTLSWTPPEDDGGPITGYVVEYREKGSGDWKEVEVTPGSETSYTLTGLKPGTEYEFRVRAVN 78

                          90
                  ....*....|..
gi 119609534  539 DVGKGQFSKDTE 550
Cdd:cd00063    79 GGGESPPSESVT 90

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 70.91 E-value: 1.22e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  1495 APRNVVVHGATATQLDVTWEPPPldSQNGDIQGYKIYFWEaQRGNLTERVKTLFLAENSVKLKNLTGYTAYMVSVAAFNA 1574
Cdd:pfam00041    2 APSNLTVTDVTSTSLTVSWTPPP--DGNGPITGYEVEYRP-KNSGEPWNEITVPGTTTSVTLTGLKPGTEYEVRVQAVNG 78


                   ....*..
gi 119609534  1575 AGDGPRS 1581
Cdd:pfam00041   79 GGEGPPS 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 70.67 E-value: 1.38e-14

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 119609534   271 PNITRGPLDSTVIDGMSVVLACETSGAPRPAITWQKGERILASGSVQlPRFTPLESGSLLISPTHISDAGTYTCLATN 348
Cdd:pfam13927    2 PVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTR-SRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

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

Pssm-ID: 409560 [Multi-domain] Cd Length: 88 Bit Score: 70.35 E-value: 2.49e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  273 ITRGPLDSTVIDGMSVVLACETSGAPRPAITWQKGERILASGSvqlpRFTPLESGSLLISPTHISDAGTYTCLATNSRGV 352
Cdd:cd20968     2 ITRPPTNVTIIEGLKAVLPCTTMGNPKPSVSWIKGDDLIKENN----RIAVLESGSLRIHNVQKEDAGQYRCVAKNSLGI 77

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 69.83 E-value: 3.79e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  968 APANVSLRTASETSLWLRWMPLPEmeynGNPESVGYKIKYsRSDGHGKTLSHVVQDRVERDYTIEDLEEWTEYRVQVQAF 1047
Cdd:cd00063     3 PPTNLRVTDVTSTSVTLSWTPPED----DGGPITGYVVEY-REKGSGDWKEVEVTPGSETSYTLTGLKPGTEYEFRVRAV 77

                          90
                  ....*....|....*.
gi 119609534 1048 NAIGSGPWSQTVVGRT 1063
Cdd:cd00063    78 NGGGESPPSESVTVTT 93

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

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 68.96 E-value: 5.93e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  275 RGPLDSTVIDGMSVVLACETSGAPRPAITWQKGErilasGSVQLPRFTPLESGSLLISPTHISDAGTYTCLATNSRGVDE 354
Cdd:cd05725     2 KRPQNQVVLVDDSAEFQCEVGGDPVPTVRWRKED-----GELPKGRYEILDDHSLKIRKVTAGDMGSYTCVAENMVGKIE 76


                  ....*..
gi 119609534  355 ASADLVV 361
Cdd:cd05725    77 ASATLTV 83

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 68.82 E-value: 7.58e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534   177 PQFVKEPeRHITAEMEKVVDIPCQAKGVPPPSITWYKDAAVVEVEKltRFRQRNDGG---LQISGLVPDDTGMFQCFARN 253
Cdd:pfam07679    1 PKFTQKP-KDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSD--RFKVTYEGGtytLTISNVQPDDSGKYTCVATN 77

                           90
                   ....*....|...
gi 119609534   254 AAGEVQTSTYLAV 266
Cdd:pfam07679   78 SAGEAEASAELTV 90

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 68.68 E-value: 9.19e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534 1269 PQPPSRPMVqqEDVRARSVLLSWEPGSDGLSPVRYYTIQTRELPSGRWALHSaSVSHNASSFIVDRLKPFTSYKFRVKAT 1348
Cdd:cd00063     1 PSPPTNLRV--TDVTSTSVTLSWTPPEDDGGPITGYVVEYREKGSGDWKEVE-VTPGSETSYTLTGLKPGTEYEFRVRAV 77


                  ....*
gi 119609534 1349 NDIGD 1353
Cdd:cd00063    78 NGGGE 82

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 67.83 E-value: 1.63e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534   968 APANVSLRTASETSLWLRWMPLPEmeynGNPESVGYKIKYsRSDGHGKTLSHVVQDRVERDYTIEDLEEWTEYRVQVQAF 1047
Cdd:pfam00041    2 APSNLTVTDVTSTSLTVSWTPPPD----GNGPITGYEVEY-RPKNSGEPWNEITVPGTTTSVTLTGLKPGTEYEVRVQAV 76


                   ....*....
gi 119609534  1048 NAIGSGPWS 1056
Cdd:pfam00041   77 NGGGEGPPS 85

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 67.91 E-value: 1.66e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  764 PGPVGHLSFSEILDTSLKVSWQEPGEKNGILTGYRISWEEYNRTNTRVTHYLPNVTLEYRVTGLTALTTYTIEVAAMTSK 843
Cdd:cd00063     1 PSPPTNLRVTDVTSTSVTLSWTPPEDDGGPITGYVVEYREKGSGDWKEVEVTPGSETSYTLTGLKPGTEYEFRVRAVNGG 80


                  ....*....
gi 119609534  844 GQGQVSAST 852
Cdd:cd00063    81 GESPPSESV 89

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 67.52 E-value: 2.79e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534 1593 PSAPSSVKFSELTTTSVNVSWEAPQFPNGILEGYRLVYEPcspvDGVSKIVTVDVKGNSPLWLKVKDLAEGVTYRFRIRA 1672
Cdd:cd00063     1 PSPPTNLRVTDVTSTSVTLSWTPPEDDGGPITGYVVEYRE----KGSGDWKEVEVTPGSETSYTLTGLKPGTEYEFRVRA 76


                  ..
gi 119609534 1673 KT 1674
Cdd:cd00063    77 VN 78

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 66.67 E-value: 3.38e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534   765 GPVGHLSFSEILDTSLKVSWQEPGEKNGILTGYRISWEEYNrTNTRVTHY-LPNVTLEYRVTGLTALTTYTIEVAAMTSK 843
Cdd:pfam00041    1 SAPSNLTVTDVTSTSLTVSWTPPPDGNGPITGYEVEYRPKN-SGEPWNEItVPGTTTSVTLTGLKPGTEYEVRVQAVNGG 79


                   ....*.
gi 119609534   844 GQGQVS 849
Cdd:pfam00041   80 GEGPPS 85

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 73.50 E-value: 8.23e-13

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  602 AGLPVGYQFKNITDADVNNLLLEDLIIWTNYEIEVAAYNSAGLGVYSSKVTEWTLQGVPTVPPGNVHAEATNSTTIRFTW 681
Cdd:COG3401    63 SGGGLGTGGRAGTTSGVAAVAVAAAPPTATGLTTLTGSGSVGGATNTGLTSSDEVPSPAVGTATTATAVAGGAATAGTYA 142

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  682 NAPSPQFINGINQGYKLIAWEPEQEEEVTMVTARPNFQDSIHVGFVS--------GLKKFTEYFTSVLCFTTPGDGPRST 753
Cdd:COG3401   143 LGAGLYGVDGANASGTTASSVAGAGVVVSPDTSATAAVATTSLTVTSttlvdgggDIEPGTTYYYRVAATDTGGESAPSN 222

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  754 PQLVRTHEDVPGPVGHLSFSEILDTSLKVSWQEPGEKNgiLTGYRI--------SWEEYNRTNTrvthylpnvtLEYRVT 825
Cdd:COG3401   223 EVSVTTPTTPPSAPTGLTATADTPGSVTLSWDPVTESD--ATGYRVyrsnsgdgPFTKVATVTT----------TSYTDT 290

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  826 GLTALTTYTIEVAAMTSKGQGQVSASTISSGVPPELPGPPTNLGISNIGPRSVTLQFRPGYDGKtsISRWLVEaqVGVVG 905
Cdd:COG3401   291 GLTNGTTYYYRVTAVDAAGNESAPSNVVSVTTDLTPPAAPSGLTATAVGSSSITLSWTASSDAD--VTGYNVY--RSTSG 366

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  906 EGeEWLLIHQLSNEPdarSMEVPDLNPFTCYSFRMRQVNIVGTSPPSQPSRKIQTLQAPPDMAPANVSLRTASETSLWLR 985
Cdd:COG3401   367 GG-TYTKIAETVTTT---SYTDTGLTPGTTYYYKVTAVDAAGNESAPSEEVSATTASAASGESLTASVDAVPLTDVAGAT 442

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  986 WMPLPEMEYNGNPESVGYKIKYSRSDGHGKTLSHVVQDRVERDYTIEDLEEWteyrvQVQAFNAIGSGPWSQTVVGRTRE 1065
Cdd:COG3401   443 AAASAASNPGVSAAVLADGGDTGNAVPFTTTSSTVTATTTDTTTANLSVTTG-----SLVGGSGASSVTNSVSVIGASAA 517

                         490
                  ....*....|....*....
gi 119609534 1066 SVPSSGPTNVSALATTSSS 1084
Cdd:COG3401   518 AAVGGAPDGTPNVTGASPV 536

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: 65.04 E-value: 9.75e-13

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 119609534  195 VDIPCQAKGVPPPSITWYKDAAVVEVEKLTRFRQRNDGG-LQISGLVPDDTGMFQCFARNAAGEVQTST 262
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSELGNGtLTISNVTLEDSGTYTCVASNSAGGSASAS 69

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

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 64.66 E-value: 1.22e-12

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 119609534  288 VVLACETSGAPRPAITWQKGERILASgSVQLPRFTPLESGSLLISPTHISDAGTYTCLATNS-RGVDEASA 357
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPP-SSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSaGGSASASV 70

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 65.21 E-value: 1.29e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  271 PNITRGPLDSTVIDGMSVVLACETSGAPRPAITWQKGERILASGS-----VQlprftplESG--SLLISPTHISDAGTYT 343
Cdd:cd05744     1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSahkmlVR-------ENGrhSLIIEPVTKRDAGIYT 73

                          90
                  ....*....|....*...
gi 119609534  344 CLATNSRGVDEASADLVV 361
Cdd:cd05744    74 CIARNRAGENSFNAELVV 91

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 64.36 E-value: 2.44e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  1594 SAPSSVKFSELTTTSVNVSWEAPQFPNGILEGYRLVYEPCspvDGVSKIVTVDVKGNSPLwLKVKDLAEGVTYRFRIRAK 1673
Cdd:pfam00041    1 SAPSNLTVTDVTSTSLTVSWTPPPDGNGPITGYEVEYRPK---NSGEPWNEITVPGTTTS-VTLTGLKPGTEYEVRVQAV 76


                   .
gi 119609534  1674 T 1674
Cdd:pfam00041   77 N 77

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 64.17 E-value: 2.78e-12

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534   1495 APRNVVVHGATATQLDVTWEPPPLDSQNGDIQGYKIYFWEAQRGNLTERVKTlflAENSVKLKNLTGYTAYMVSVAAFNA 1574
Cdd:smart00060    3 PPSNLRVTDVTSTSVTLSWEPPPDDGITGYIVGYRVEYREEGSEWKEVNVTP---SSTSYTLTGLKPGTEYEFRVRAVNG 79


                    ....
gi 119609534   1575 AGDG 1578
Cdd:smart00060   80 AGEG 83

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

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 64.06 E-value: 2.82e-12

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534    277 PLDSTVIDGMSVVLACETSGAPRPAITWQKGERILASGSvqlPRFTPLESG---SLLISPTHISDAGTYTCLATNSRGVD 353
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAES---GRFSVSRSGstsTLTISNVTPEDSGTYTCAATNSSGSA 77


                    ....*...
gi 119609534    354 EASADLVV 361
Cdd:smart00410   78 SSGTTLTV 85

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: 63.57 E-value: 4.83e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  277 PLDSTVIDGMSVVLACETS-GAPRPAITWQKGERILASGSvqlPRFTPLESGSLLISPTHISDAGTYTCLATNSRGVDEA 355
Cdd:cd05724     4 PSDTQVAVGEMAVLECSPPrGHPEPTVSWRKDGQPLNLDN---ERVRIVDDGNLLIAEARKSDEGTYKCVATNMVGERES 80


                  ..
gi 119609534  356 SA 357
Cdd:cd05724    81 RA 82

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: 63.67 E-value: 5.18e-12

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 119609534  199 CQAKGVPPPSITWYKDAAVVEVeKLTRFRQRNDGGLQISGLVPDDTGMFQCFARNAAGEVQTSTYLAV 266
Cdd:cd20952    21 CQATGEPVPTISWLKDGVPLLG-KDERITTLENGSLQIKGAEKSDTGEYTCVALNLSGEATWSAVLDV 87

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 63.67 E-value: 5.94e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534 1070 SGPTNVSALATTSSSMLVRWSevPEADRNGLVLGYKVMYKEKDSDtQPRFWLVEGNSSRSAQLTGLGKYVLYEVQVLAFT 1149
Cdd:cd00063     2 SPPTNLRVTDVTSTSVTLSWT--PPEDDGGPITGYVVEYREKGSG-DWKEVEVTPGSETSYTLTGLKPGTEYEFRVRAVN 78

                          90
                  ....*....|
gi 119609534 1150 RIGDGSPSHP 1159
Cdd:cd00063    79 GGGESPPSES 88

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 62.63 E-value: 8.36e-12

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534    459 PHAPEHPvaTLSTVERRAINLTWTKPFDGN--SPLIRYILEMSENNAPWTVLlaSVDPKATSVTVKGLVPARSYQFRLCA 536
Cdd:smart00060    1 PSPPSNL--RVTDVTSTSVTLSWEPPPDDGitGYIVGYRVEYREEGSEWKEV--NVTPSSTSYTLTGLKPGTEYEFRVRA 76


                    ....*..
gi 119609534    537 VNDVGKG 543
Cdd:smart00060   77 VNGAGEG 83

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

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 62.91 E-value: 8.57e-12

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 119609534    195 VDIPCQAKGVPPPSITWYKDAA--VVEVEKLTRFRQRNDGGLQISGLVPDDTGMFQCFARNAAGEVQTSTYLAV 266
Cdd:smart00410   12 VTLSCEASGSPPPEVTWYKQGGklLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGTTLTV 85

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 62.82 E-value: 9.21e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  1072 PTNVSALATTSSSMLVRWSevPEADRNGLVLGYKVMYKEKDsDTQPRFWLVEGNSSRSAQLTGLGKYVLYEVQVLAFTRI 1151
Cdd:pfam00041    3 PSNLTVTDVTSTSLTVSWT--PPPDGNGPITGYEVEYRPKN-SGEPWNEITVPGTTTSVTLTGLKPGTEYEVRVQAVNGG 79


                   ....*.
gi 119609534  1152 GDGSPS 1157
Cdd:pfam00041   80 GEGPPS 85

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 62.82 E-value: 9.30e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534   461 APEHPvaTLSTVERRAINLTWTKPFDGNSPLIRYILEMSENNAPWTVLLASVDPKATSVTVKGLVPARSYQFRLCAVNDV 540
Cdd:pfam00041    2 APSNL--TVTDVTSTSLTVSWTPPPDGNGPITGYEVEYRPKNSGEPWNEITVPGTTTSVTLTGLKPGTEYEVRVQAVNGG 79


                   ....*.
gi 119609534   541 GKGQFS 546
Cdd:pfam00041   80 GEGPPS 85

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 62.51 E-value: 1.43e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534 1372 EAPTILSVTPHTTTSVLIRWQPPAEDkiNGILLGFRIRYRELlyeglrgftlrginnPGATWAELTSmysmrnlSRPSLT 1451
Cdd:cd00063     2 SPPTNLRVTDVTSTSVTLSWTPPEDD--GGPITGYVVEYREK---------------GSGDWKEVEV-------TPGSET 57

                          90       100       110
                  ....*....|....*....|....*....|....
gi 119609534 1452 QYELDNLNKHRRYEIRMSVYNAVGEGPSSPPQEV 1485
Cdd:cd00063    58 SYTLTGLKPGTEYEFRVRAVNGGGESPPSESVTV 91

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 61.74 E-value: 2.51e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  562 PPQNVIASGRTNQSIMIQWQPPPEShqNGILKGYIIRYCLAGLPVGYQFkNITDADVNNLLLEDLIIWTNYEIEVAAYNS 641
Cdd:cd00063     3 PPTNLRVTDVTSTSVTLSWTPPEDD--GGPITGYVVEYREKGSGDWKEV-EVTPGSETSYTLTGLKPGTEYEFRVRAVNG 79

                          90
                  ....*....|....
gi 119609534  642 AGLGVYSSKVTEWT 655
Cdd:cd00063    80 GGESPPSESVTVTT 93

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 61.28 E-value: 2.83e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  1701 IIVRYSSAIAIHWSSGDPGKGPITRYVIEARPSDEGLWDILIkDIPKEVSSYTFSMdiLKPGVSYDFRVIAVNDYGFGTP 1780
Cdd:pfam00041    8 VTDVTSTSLTVSWTPPPDGNGPITGYEVEYRPKNSGEPWNEI-TVPGTTTSVTLTG--LKPGTEYEVRVQAVNGGGEGPP 84


                   .
gi 119609534  1781 S 1781
Cdd:pfam00041   85 S 85

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 61.09 E-value: 3.91e-11

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534    764 PGPVGHLSFSEILDTSLKVSWQEPGEKNGI--LTGYRISWEEYNRTNTRVTHylPNVTLEYRVTGLTALTTYTIEVAAMT 841
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTLSWEPPPDDGITgyIVGYRVEYREEGSEWKEVNV--TPSSTSYTLTGLKPGTEYEFRVRAVN 78


                    ....*
gi 119609534    842 SKGQG 846
Cdd:smart00060   79 GAGEG 83

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 60.71 E-value: 4.39e-11

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534    968 APANVSLRTASETSLWLRWMPlPEMEYNGNPEsVGYKIKYSRSDGHGKTLSHVVQDRVerdYTIEDLEEWTEYRVQVQAF 1047
Cdd:smart00060    3 PPSNLRVTDVTSTSVTLSWEP-PPDDGITGYI-VGYRVEYREEGSEWKEVNVTPSSTS---YTLTGLKPGTEYEFRVRAV 77


                    ....*.
gi 119609534   1048 NAIGSG 1053
Cdd:smart00060   78 NGAGEG 83

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 60.97 E-value: 5.43e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534 1706 SSAIAIHWSSGDPGKGPITRYVIEARPSDEGLWDILIKdipKEVSSYTFSMDILKPGVSYDFRVIAVNDYGFGTPSSPSQ 1785
Cdd:cd00063    14 STSVTLSWTPPEDDGGPITGYVVEYREKGSGDWKEVEV---TPGSETSYTLTGLKPGTEYEFRVRAVNGGGESPPSESVT 90

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 60.27 E-value: 6.45e-11

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 119609534   176 PPQFVKEPERHITAEMEKVVdIPCQAKGVPPPSITWYKDAAVVEVEKLTRFRQRNDGG-LQISGLVPDDTGMFQCFARN 253
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVT-LTCEATGSPPPTITWYKNGEPISSGSTRSRSLSGSNStLTISNVTRSDAGTYTCVASN 78

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 59.94 E-value: 9.31e-11

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534   1593 PSAPSSVKFSELTTTSVNVSWEAPQFPNGilEGYRLVYEPC-SPVDGVSKIVTVDVKGNSplwLKVKDLAEGVTYRFRIR 1671
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTLSWEPPPDDGI--TGYIVGYRVEyREEGSEWKEVNVTPSSTS---YTLTGLKPGTEYEFRVR 75


                    ...
gi 119609534   1672 AKT 1674
Cdd:smart00060   76 AVN 78

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: 59.71 E-value: 1.06e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  271 PNITRGPLDSTVIDGMS-VVLACETSGAPRPAITW-QKGERIlasgSVQLPRFTpLESGSLLISPTHISDAGTYTCLATN 348
Cdd:cd20978     1 PKFIQKPEKNVVVKGGQdVTLPCQVTGVPQPKITWlHNGKPL----QGPMERAT-VEDGTLTIINVQPEDTGYYGCVATN 75

                          90
                  ....*....|...
gi 119609534  349 SRGVDEASADLVV 361
Cdd:cd20978    76 EIGDIYTETLLHV 88

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: 59.52 E-value: 1.33e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  176 PPQFVKEPERHITAEMEKVVdIPCQAKGVPPPSITWYKDAAvvEVEKLTRFRQRNDGGLQ---ISGLVPDDTGMFQCFAR 252
Cdd:cd20972     1 PPQFIQKLRSQEVAEGSKVR-LECRVTGNPTPVVRWFCEGK--ELQNSPDIQIHQEGDLHsliIAEAFEEDTGRYSCLAT 77

                          90
                  ....*....|....
gi 119609534  253 NAAGEVQTSTYLAV 266
Cdd:cd20972    78 NSVGSDTTSAEIFV 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: 58.73 E-value: 1.49e-10

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 119609534  195 VDIPCQAKGVPPPSITWYKDAavVEVEKLTRFRQRNDGGLQISGLVPDDTGMFQCFARNAAGEVQTSTYLA 265
Cdd:cd05746     1 VQIPCSAQGDPEPTITWNKDG--VQVTESGKFHISPEGYLAIRDVGVADQGRYECVARNTIGYASVSMVLS 69

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: 1.81e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  270 APNITRGPLDSTVIDGMSVVLACETSGAPRPAITW-QKGERILASGSVQLPRFTPLESgsLLISPTHISDAGTYTCLATN 348
Cdd:cd20972     1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWfCEGKELQNSPDIQIHQEGDLHS--LIIAEAFEEDTGRYSCLATN 78

                          90
                  ....*....|...
gi 119609534  349 SRGVDEASADLVV 361
Cdd:cd20972    79 SVGSDTTSAEIFV 91

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 58.78 E-value: 1.99e-10

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534   1269 PQPPSRPMVqqEDVRARSVLLSWEPGSD--GLSPVRYYTIQTRElPSGRWalHSASVSHNASSFIVDRLKPFTSYKFRVK 1346
Cdd:smart00060    1 PSPPSNLRV--TDVTSTSVTLSWEPPPDdgITGYIVGYRVEYRE-EGSEW--KEVNVTPSSTSYTLTGLKPGTEYEFRVR 75


                    ....*..
gi 119609534   1347 ATNDIGD 1353
Cdd:smart00060   76 AVNGAGE 82

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 58.78 E-value: 2.24e-10

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534   1070 SGPTNVSALATTSSSMLVRWSEVPEADRNGLVLGYKVMYKEKDSDTQPrfwLVEGNSSRSAQLTGLGKYVLYEVQVLAFT 1149
Cdd:smart00060    2 SPPSNLRVTDVTSTSVTLSWEPPPDDGITGYIVGYRVEYREEGSEWKE---VNVTPSSTSYTLTGLKPGTEYEFRVRAVN 78


                    ....*
gi 119609534   1150 RIGDG 1154
Cdd:smart00060   79 GAGEG 83

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 58.58 E-value: 2.54e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534   562 PPQNVIASGRTNQSIMIQWQPPPesHQNGILKGYIIRYCLAGLPvGYQFKNITDADVNNLLLEDLIIWTNYEIEVAAYNS 641
Cdd:pfam00041    2 APSNLTVTDVTSTSLTVSWTPPP--DGNGPITGYEVEYRPKNSG-EPWNEITVPGTTTSVTLTGLKPGTEYEVRVQAVNG 78


                   ....*..
gi 119609534   642 AGLGVYS 648
Cdd:pfam00041   79 GGEGPPS 85

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: 58.38 E-value: 2.85e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  277 PLDSTVIDGMSVVLACETSGAPRPAITWQK-GERILASGSVQLprftplESGSLLISPTHISDAGTYTCLATNSRGVDEA 355
Cdd:cd05728     6 ISDTEADIGSSLRWECKASGNPRPAYRWLKnGQPLASENRIEV------EAGDLRITKLSLSDSGMYQCVAENKHGTIYA 79


                  ....*.
gi 119609534  356 SADLVV 361
Cdd:cd05728    80 SAELAV 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: 58.42 E-value: 3.13e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  270 APNITRGPLDSTVIDGMSVVLACETSGAPRPAITWQKGERILasgSVQLPRFT-PLESGSLLISPTHISDAGTYTCLATN 348
Cdd:cd20976     1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPL---QYAADRSTcEAGVGELHIQDVLPEDHGTYTCLAKN 77

                          90
                  ....*....|...
gi 119609534  349 SRGVDEASADLVV 361
Cdd:cd20976    78 AAGQVSCSAWVTV 90

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 58.39 E-value: 3.35e-10

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534    562 PPQNVIASGRTNQSIMIQWQPPPESHQNgilkGYIIRYCLAGLPVGYQFKNI-TDADVNNLLLEDLIIWTNYEIEVAAYN 640
Cdd:smart00060    3 PPSNLRVTDVTSTSVTLSWEPPPDDGIT----GYIVGYRVEYREEGSEWKEVnVTPSSTSYTLTGLKPGTEYEFRVRAVN 78


                    ....*
gi 119609534    641 SAGLG 645
Cdd:smart00060   79 GAGEG 83

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 58.20 E-value: 3.98e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  1271 PPSRpmVQQEDVRARSVLLSWEPGSDGLSPVRYYTIQTRELPSGRWALHSaSVSHNASSFIVDRLKPFTSYKFRVKATND 1350
Cdd:pfam00041    2 APSN--LTVTDVTSTSLTVSWTPPPDGNGPITGYEVEYRPKNSGEPWNEI-TVPGTTTSVTLTGLKPGTEYEVRVQAVNG 78


                   ..
gi 119609534  1351 IG 1352
Cdd:pfam00041   79 GG 80

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

Pssm-ID: 409391 [Multi-domain] Cd Length: 98 Bit Score: 58.04 E-value: 5.22e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  277 PLDSTVIDGMSVVLACETSGAPRPAITWQK--GERILASGSVQLP--RFTPLESGSLLISPTHISDAGTYTCLATNSRGV 352
Cdd:cd05726     6 PRDQVVALGRTVTFQCETKGNPQPAIFWQKegSQNLLFPYQPPQPssRFSVSPTGDLTITNVQRSDVGYYICQALNVAGS 85


                  ....*....
gi 119609534  353 DEASADLVV 361
Cdd:cd05726    86 ILAKAQLEV 94

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 57.82 E-value: 6.22e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  271 PNITRGPLDSTVIDGMSVVLACETSGAPRPAITWQK-GERILASGSVQLPRFTPlESG--SLLISPTHISDAGTYTCLAT 347
Cdd:cd20951     1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKnGVPIDPSSIPGKYKIES-EYGvhVLHIRRVTVEDSAVYSAVAK 79

                          90
                  ....*....|....
gi 119609534  348 NSRGVDEASADLVV 361
Cdd:cd20951    80 NIHGEASSSASVVV 93

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 57.42 E-value: 6.94e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534   863 GPPTNLGISNIGPRSVTLQFRPGYDGKTSISRWLVEAQVgvVGEGEEWlliHQLSNEPDARSMEVPDLNPFTCYSFRMRQ 942
Cdd:pfam00041    1 SAPSNLTVTDVTSTSLTVSWTPPPDGNGPITGYEVEYRP--KNSGEPW---NEITVPGTTTSVTLTGLKPGTEYEVRVQA 75

                           90
                   ....*....|
gi 119609534   943 VNIVGTSPPS 952
Cdd:pfam00041   76 VNGGGEGPPS 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 56.80 E-value: 9.37e-10

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 119609534   366 RITKPPQDQSVIKGTQASMVCGVTHDPRVTIRyiWEKDGATLGTESHPRIRLD-RNGSLHISQTWSGDIGTYTCRV 440
Cdd:pfam13927    3 VITVSPSSVTVREGETVTLTCEATGSPPPTIT--WYKNGEPISSGSTRSRSLSgSNSTLTISNVTRSDAGTYTCVA 76

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409582 Cd Length: 91 Bit Score: 57.42 E-value: 9.39e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  271 PNITRGPLDSTVIDGMSVVLACETSGAPRPAITWQKGERILASGSVQlpRFTPLESG--SLLISPTHISDAGTYTCLATN 348
Cdd:cd20990     1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSAH--KMLVRENGvhSLIIEPVTSRDAGIYTCIATN 78

                          90
                  ....*....|...
gi 119609534  349 SRGVDEASADLVV 361
Cdd:cd20990    79 RAGQNSFNLELVV 91

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 57.04 E-value: 1.02e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  1373 APTILSVTPHTTTSVLIRWQPPaeDKINGILLGFRIRYRELlyeglrgftlrginNPGATWAELTSmysmrnlsRPSLTQ 1452
Cdd:pfam00041    2 APSNLTVTDVTSTSLTVSWTPP--PDGNGPITGYEVEYRPK--------------NSGEPWNEITV--------PGTTTS 57

                           90       100
                   ....*....|....*....|....*...
gi 119609534  1453 YELDNLNKHRRYEIRMSVYNAVGEGPSS 1480
Cdd:pfam00041   58 VTLTGLKPGTEYEVRVQAVNGGGEGPPS 85

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: 57.10 E-value: 1.07e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  271 PNITRGPLDSTVIDGMSVVLACETSGAPRPAITWQKGERILASGSvqlPRFTPLESGSLLISPTHISDAGTYTCLATNSR 350
Cdd:cd05764     1 PLITRHTHELRVLEGQRATLRCKARGDPEPAIHWISPEGKLISNS---SRTLVYDNGTLDILITTVKDTGAFTCIASNPA 77

                          90
                  ....*....|.
gi 119609534  351 GVDEASADLVV 361
Cdd:cd05764    78 GEATARVELHI 88

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 56.65 E-value: 1.18e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  1171 GPPMGILFPEVRTTSVRLIWQPPAAPNGIILAYQITHRLNTTTANTATVEVlAPSARQYTATGLKPESVYLFRITAQTRK 1250
Cdd:pfam00041    1 SAPSNLTVTDVTSTSLTVSWTPPPDGNGPITGYEVEYRPKNSGEPWNEITV-PGTTTSVTLTGLKPGTEYEVRVQAVNGG 79


                   ....
gi 119609534  1251 GWGE 1254
Cdd:pfam00041   80 GEGP 83

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: 56.40 E-value: 2.23e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  365 TRITKPPQDQSVIKGTQASMVCGVTHDPRVTIRYIWEKDGATL-----GTESHPRIRLDRNGSLHISQTWSGDIGTYTCR 439
Cdd:cd04970     3 TRITLAPSNADITVGENATLQCHASHDPTLDLTFTWSFNGVPIdlekiEGHYRRRYGKDSNGDLEIVNAQLKHAGRYTCT 82

                          90       100
                  ....*....|....*....|
gi 119609534  440 VISAGGNDSRSAHLRVRQLP 459
Cdd:cd04970    83 AQTVVDSDSASATLVVRGPP 102

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 56.08 E-value: 2.27e-09

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534   1170 PGPPMGILFPEVRTTSVRLIWQPPAAPNGIilAYQITHRLNTTTANTATVEVLA-PSARQYTATGLKPESVYLFRITAQT 1248
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTLSWEPPPDDGIT--GYIVGYRVEYREEGSEWKEVNVtPSSTSYTLTGLKPGTEYEFRVRAVN 78


                    ....*
gi 119609534   1249 RKGWG 1253
Cdd:smart00060   79 GAGEG 83

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 55.70 E-value: 2.34e-09

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534   1373 APTILSVTPHTTTSVLIRWQPPAEDKINGILLGFRIRYREllyeglrgftlrginnPGATWAELTsmysmrnlSRPSLTQ 1452
Cdd:smart00060    3 PPSNLRVTDVTSTSVTLSWEPPPDDGITGYIVGYRVEYRE----------------EGSEWKEVN--------VTPSSTS 58

                            90       100
                    ....*....|....*....|....*
gi 119609534   1453 YELDNLNKHRRYEIRMSVYNAVGEG 1477
Cdd:smart00060   59 YTLTGLKPGTEYEFRVRAVNGAGEG 83

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: 2.95e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  268 SIAPNITRGPLDSTVIDGMSVVLACETSGAPRPAITWQKGERILASGSVQLPRFTPLESgSLLISPTHISDAGTYTCLAT 347
Cdd:cd05747     1 TLPATILTKPRSLTVSEGESARFSCDVDGEPAPTVTWMREGQIIVSSQRHQITSTEYKS-TFEISKVQMSDEGNYTVVVE 79

                          90
                  ....*....|..
gi 119609534  348 NSRGVDEASADL 359
Cdd:cd05747    80 NSEGKQEAQFTL 91

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: 55.39 E-value: 3.60e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  271 PNITRGPLDSTVI--DGMSVVLACETSGAPRPAITWQKGERILASGSvqlpRFTPLESGSLLISPTHISDAGTYTCLATN 348
Cdd:cd05852     1 PTFEFNPMKKKILaaKGGRVIIECKPKAAPKPKFSWSKGTELLVNNS----RISIWDDGSLEILNITKLDEGSYTCFAEN 76

                          90
                  ....*....|...
gi 119609534  349 SRGVDEASADLVV 361
Cdd:cd05852    77 NRGKANSTGVLSV 89

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 55.20 E-value: 5.16e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  862 PGPPTNLGISNIGPRSVTLQFRPGYDGKTSISRWLVEAQVGVVGEGEEWLlihqlSNEPDARSMEVPDLNPFTCYSFRMR 941
Cdd:cd00063     1 PSPPTNLRVTDVTSTSVTLSWTPPEDDGGPITGYVVEYREKGSGDWKEVE-----VTPGSETSYTLTGLKPGTEYEFRVR 75

                          90
                  ....*....|....*
gi 119609534  942 QVNIVGTSPPSQPSR 956
Cdd:cd00063    76 AVNGGGESPPSESVT 90

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

Pssm-ID: 143222 [Multi-domain] Cd Length: 74 Bit Score: 54.56 E-value: 6.13e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 119609534  193 KVVDIPCQAKGVPPPSITWYKDAAVVEVEKltRFRQRNDGGLQISGLVPDDTGMFQCFARNAAGEVQTSTYLAV 266
Cdd:cd05745     3 QTVDFLCEAQGYPQPVIAWTKGGSQLSVDR--RHLVLSSGTLRISRVALHDQGQYECQAVNIVGSQRTVAQLTV 74

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

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 54.32 E-value: 7.51e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  369 KPPQDQSVIKGTQASMVCGVTHDPRVTIRyiWEKDGATLgTESHPRIRLDRngSLHISQTWSGDIGTYTCRVISAGGNDS 448
Cdd:cd05725     2 KRPQNQVVLVDDSAEFQCEVGGDPVPTVR--WRKEDGEL-PKGRYEILDDH--SLKIRKVTAGDMGSYTCVAENMVGKIE 76


                  ....*..
gi 119609534  449 RSAHLRV 455
Cdd:cd05725    77 ASATLTV 83

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: 54.42 E-value: 8.77e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  367 ITKPPQDQSVIKGTQASMVCGVTHDPRVTIRyiWEKDGATLGTEShPRIRLDRNGSLHISQTWSGDIGTYTCRVISAGGN 446
Cdd:cd20952     2 ILQGPQNQTVAVGGTVVLNCQATGEPVPTIS--WLKDGVPLLGKD-ERITTLENGSLQIKGAEKSDTGEYTCVALNLSGE 78


                  ....*....
gi 119609534  447 DSRSAHLRV 455
Cdd:cd20952    79 ATWSAVLDV 87

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 54.55 E-value: 9.42e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  179 FVKEPeRHITAEMEKVVDIPCQAKGVPPPSITWYKDAAvveveklTRF---RQR------NDGGLQISGLVPDDTGMFQC 249
Cdd:cd05763     2 FTKTP-HDITIRAGSTARLECAATGHPTPQIAWQKDGG-------TDFpaaRERrmhvmpEDDVFFIVDVKIEDTGVYSC 73

                          90
                  ....*....|....*..
gi 119609534  250 FARNAAGEVQTSTYLAV 266
Cdd:cd05763    74 TAQNSAGSISANATLTV 90

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: 54.26 E-value: 9.47e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  274 TRGPLDSTVIDGMSVVLACETSGAPRPAITWQKGERILASGSVQLPRFTPLESGsLLISPTHISDAGTYTCLATNSRGVD 353
Cdd:cd20949     3 TENAYVTTVKEGQSATILCEVKGEPQPNVTWHFNGQPISASVADMSKYRILADG-LLINKVTQDDTGEYTCRAYQVNSIA 81


                  ....*...
gi 119609534  354 EASADLVV 361
Cdd:cd20949    82 SDMQERTV 89

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

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 53.66 E-value: 1.27e-08

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534    371 PQDQSVIKGTQASMVCGVTHDPRVTIRyiWEKDGATLGTEShPRIRLDRNG---SLHISQTWSGDIGTYTCRVISAGGND 447
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVT--WYKQGGKLLAES-GRFSVSRSGstsTLTISNVTPEDSGTYTCAATNSSGSA 77


                    ....*...
gi 119609534    448 SRSAHLRV 455
Cdd:smart00410   78 SSGTTLTV 85

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 53.62 E-value: 1.44e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  177 PQFVKEP-ERHITAEMEKVVDIPCQAKGVPPPSITWYKDAAVVEVEKltRFRQRNDGGLQISGLVPDDTGMFQCFARNAA 255
Cdd:cd04969     1 PDFELNPvKKKILAAKGGDVIIECKPKASPKPTISWSKGTELLTNSS--RICILPDGSLKIKNVTKSDEGKYTCFAVNFF 78

                          90
                  ....*....|.
gi 119609534  256 GEVQTSTYLAV 266
Cdd:cd04969    79 GKANSTGSLSV 89

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

Pssm-ID: 409387 Cd Length: 97 Bit Score: 54.02 E-value: 1.51e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 119609534  277 PLDSTVIDGMSVVLACETSGAPRPAITWQKGERILASGSVQlpRFTPLESGSLLI-----SPTHISDAGTYTCLATN 348
Cdd:cd05722     8 PSDIVAMRGGPVVLNCSAESDPPPKIEWKKDGVLLNLVSDE--RRQQLPNGSLLItsvvhSKHNKPDEGFYQCVAQN 82

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: 53.78 E-value: 1.59e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  274 TRGPLDSTVIDGMSVVLACETSGAPRPAITWQKgerilaSGSVQLP-------RFTPlESGSLLISPTHISDAGTYTCLA 346
Cdd:cd05763     3 TKTPHDITIRAGSTARLECAATGHPTPQIAWQK------DGGTDFPaarerrmHVMP-EDDVFFIVDVKIEDTGVYSCTA 75

                          90
                  ....*....|....*
gi 119609534  347 TNSRGVDEASADLVV 361
Cdd:cd05763    76 QNSAGSISANATLTV 90

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

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 53.17 E-value: 2.09e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  371 PQDQSVIKGTQASMVCG--VTH-DPRVTiryiWEKDGATLgTESHPRIRLDRNGSLHISQTWSGDIGTYTCRVI-SAGGN 446
Cdd:cd05724     4 PSDTQVAVGEMAVLECSppRGHpEPTVS----WRKDGQPL-NLDNERVRIVDDGNLLIAEARKSDEGTYKCVATnMVGER 78


                  ....*....
gi 119609534  447 DSRSAHLRV 455
Cdd:cd05724    79 ESRAARLSV 87

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 53.27 E-value: 2.11e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  177 PQFVKEPERHITAEmEKVVDIPCQAKGVPPPSITWYKDAAVVEVEKLTRFRQRNDG--GLQISGLVPDDTGMFQCFARNA 254
Cdd:cd05744     1 PHFLQAPGDLEVQE-GRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVRENGrhSLIIEPVTKRDAGIYTCIARNR 79

                          90
                  ....*....|..
gi 119609534  255 AGEVQTSTYLAV 266
Cdd:cd05744    80 AGENSFNAELVV 91

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 53.42 E-value: 2.27e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534   366 RITKPPQDQSVIKGTQASMVCGVTHDPRVTIRyiWEKDGATLGTESHPRIRLDRN-GSLHISQTWSGDIGTYTCRVISAG 444
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVTGTPDPEVS--WFKDGQPLRSSDRFKVTYEGGtYTLTISNVQPDDSGKYTCVATNSA 79

                           90
                   ....*....|.
gi 119609534   445 GNDSRSAHLRV 455
Cdd:pfam07679   80 GEAEASAELTV 90

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: 52.98 E-value: 2.97e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  179 FVKEPERHITAEMEkVVDIPCQAKGVPPPSITWYKDAAVVEVEKLTRFRQRNDGGLQISGLVPDDTGMFQCFARNAAGEV 258
Cdd:cd05867     2 WTRRPQSHLYGPGE-TARLDCQVEGIPTPNITWSINGAPIEGTDPDPRRHVSSGALILTDVQPSDTAVYQCEARNRHGNL 80


                  ....*...
gi 119609534  259 QTSTYLAV 266
Cdd:cd05867    81 LANAHVHV 88

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 52.88 E-value: 2.98e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  663 PPGNVHAEATNSTTIRFTWNAPSPqfINGINQGYKlIAWEPEQEEEVTMVTARPNFQDSIHvgfVSGLKKFTEYFTSVLC 742
Cdd:cd00063     3 PPTNLRVTDVTSTSVTLSWTPPED--DGGPITGYV-VEYREKGSGDWKEVEVTPGSETSYT---LTGLKPGTEYEFRVRA 76

                          90
                  ....*....|....*..
gi 119609534  743 FTTPGDGPRSTPQLVRT 759
Cdd:cd00063    77 VNGGGESPPSESVTVTT 93

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

Pssm-ID: 409387 Cd Length: 97 Bit Score: 52.87 E-value: 4.33e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  179 FVKEPERHITAEMEKVVdIPCQAKGVPPPSITWYKDAAVVEVEKLTRFRQRNDGGLQISGLV------PDDtGMFQCFAR 252
Cdd:cd05722     4 FLSEPSDIVAMRGGPVV-LNCSAESDPPPKIEWKKDGVLLNLVSDERRQQLPNGSLLITSVVhskhnkPDE-GFYQCVAQ 81


                  .
gi 119609534  253 N 253
Cdd:cd05722    82 N 82

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: 52.25 E-value: 5.36e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  176 PPQFVKEPERHITAEMEKVVdIPCQAKGVPPPSITWYKDAAVVEVEKLTRFRQRNDGGLQISGLVPDDTGMFQCFARNAA 255
Cdd:cd20976     1 APSFSSVPKDLEAVEGQDFV-AQCSARGKPVPRITWIRNAQPLQYAADRSTCEAGVGELHIQDVLPEDHGTYTCLAKNAA 79

                          90
                  ....*....|.
gi 119609534  256 GEVQTSTYLAV 266
Cdd:cd20976    80 GQVSCSAWVTV 90

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: 52.02 E-value: 6.52e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 119609534  183 PERHITAEMEKVVdIPCQAKGVPPPSITWYKDAAVVEVEKLTRFRQRNDGG---LQISGLVPDD-TGMFQCFARNAAG 256
Cdd:cd05733     8 PKDYIVDPRDNIT-IKCEAKGNPQPTFRWTKDGKFFDPAKDPRVSMRRRSGtlvIDNHNGGPEDyQGEYQCYASNELG 84

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

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 51.88 E-value: 6.73e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 119609534  285 GMSVVLACETSGAPRPAITWQK-GERILASGSVQLprfTPLESGS-LLISPTHISDAGTYTCLATNSRGVDEASADLVV 361
Cdd:cd05736    15 GVEASLRCHAEGIPLPRVQWLKnGMDINPKLSKQL---TLIANGSeLHISNVRYEDTGAYTCIAKNEGGVDEDISSLFV 90

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: 51.81 E-value: 7.07e-08

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 119609534  199 CQAKGVPPPSITWYKDAAVVEVEKLtrFRQRNDGGLQISGLVPDDTGMFQCFARNAAGEVQTSTYLAV 266
Cdd:cd05723    19 CEVTGKPTPTVKWVKNGDVVIPSDY--FKIVKEHNLQVLGLVKSDEGFYQCIAENDVGNAQASAQLII 84

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: 51.18 E-value: 7.43e-08

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  102 VTLECVANARPliKLHIIWKKDGVLL------SGGISDHNRRLTIPNPTGSDAGYYECEA 155
Cdd:cd00096     1 VTLTCSASGNP--PPTITWYKNGKPLppssrdSRRSELGNGTLTISNVTLEDSGTYTCVA 58

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: 51.80 E-value: 7.50e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 119609534  281 TVIDGMSVVLACETSGAPRPAITWQKGERILASGSVQlprfTPLESGSLLISPTH-ISDAGTYTCLATNSRG 351
Cdd:cd20958    11 TAVAGQTLRLHCPVAGYPISSITWEKDGRRLPLNHRQ----RVFPNGTLVIENVQrSSDEGEYTCTARNQQG 78

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: 51.88 E-value: 7.65e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  178 QFVKEPERHITAeMEKVVDIPCQAKGVPPPSITWYKDAAVV------EVEKLTRFRQRNDGGLQISGLVPDDTGMFQCFA 251
Cdd:cd05726     1 QFVVKPRDQVVA-LGRTVTFQCETKGNPQPAIFWQKEGSQNllfpyqPPQPSSRFSVSPTGDLTITNVQRSDVGYYICQA 79

                          90
                  ....*....|....*...
gi 119609534  252 RNAAGEVQTSTYLAVTSI 269
Cdd:cd05726    80 LNVAGSILAKAQLEVTDV 97

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 51.41 E-value: 8.82e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 119609534    91 KNTSVVAGtSEVTLECVANARPliKLHIIWKKDGVLLSGG------ISDHNRRLTIPNPTGSDAGYYECEA 155
Cdd:pfam13927    9 SSVTVREG-ETVTLTCEATGSP--PPTITWYKNGEPISSGstrsrsLSGSNSTLTISNVTRSDAGTYTCVA 76

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: 50.79 E-value: 9.03e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 119609534  382 ASMVCGVTHDPRVTIRyiWEKDGATLGTESHPRIRL-DRNGSLHISQTWSGDIGTYTCRVI-SAGGNDSRSA 451
Cdd:cd00096     1 VTLTCSASGNPPPTIT--WYKNGKPLPPSSRDSRRSeLGNGTLTISNVTLEDSGTYTCVASnSAGGSASASV 70

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: 51.09 E-value: 9.12e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  284 DGMSVVLACETSGAPRPAITWQKGerilasGSvQLP---RFTPLESGSLLISPTHISDAGTYTCLATNSRGVDEASADLV 360
Cdd:cd05745     1 EGQTVDFLCEAQGYPQPVIAWTKG------GS-QLSvdrRHLVLSSGTLRISRVALHDQGQYECQAVNIVGSQRTVAQLT 73


                  .
gi 119609534  361 V 361
Cdd:cd05745    74 V 74

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: 51.17 E-value: 1.27e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 119609534  183 PERHITAEMEKVVDIPCQAKGVPPPSITWYKDAAVVEVEKLT-RFRQRNDGGLQISGLVPDDTGMFQCFARNAAG 256
Cdd:cd05738     5 GPQLKVVEKARTATMLCAASGNPDPEISWFKDFLPVDTATSNgRIKQLRSGALQIENSEESDQGKYECVATNSAG 79

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: 51.01 E-value: 1.53e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  271 PNITRGPLDSTVIDGMSVVLACETSGAPRPAITWQKG----ERILASGSVQLPRFTPLESGSLLISPTHISDAGTYTCLA 346
Cdd:cd05765     1 PALVNSPTHQTVKVGETASFHCDVTGRPQPEITWEKQvpgkENLIMRPNHVRGNVVVTNIGQLVIYNAQPQDAGLYTCTA 80

                          90
                  ....*....|....*
gi 119609534  347 TNSRGVDEASADLVV 361
Cdd:cd05765    81 RNSGGLLRANFPLSV 95

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

Pssm-ID: 143277 [Multi-domain] Cd Length: 97 Bit Score: 50.75 E-value: 2.29e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 119609534  288 VVLACETSGAPRPAITWQKGERILASGSVQLPRFTPLES----GSLLISPTHISDAGTYTCLATNSRGVDEASADLVV 361
Cdd:cd05869    20 ITLTCEASGDPIPSITWRTSTRNISSEEKTLDGHIVVRSharvSSLTLKYIQYTDAGEYLCTASNTIGQDSQSMYLEV 97

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: 49.49 E-value: 2.72e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 119609534  288 VVLACETSGAPRPAITWQK-GERILASGsvqlpRFTPLESGSLLISPTHISDAGTYTCLATNSRGVdeASADLVV 361
Cdd:cd05746     1 VQIPCSAQGDPEPTITWNKdGVQVTESG-----KFHISPEGYLAIRDVGVADQGRYECVARNTIGY--ASVSMVL 68

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

Pssm-ID: 143207 [Multi-domain] Cd Length: 95 Bit Score: 50.32 E-value: 2.85e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  285 GMSVVLACETSGAPRPAITWQKGERILASGSvqlPRFTPLESGS-LLISPTHISDAGTYTCLATNSRGVDEASADLVVWA 363
Cdd:cd05730    18 GQSVTLACDADGFPEPTMTWTKDGEPIESGE---EKYSFNEDGSeMTILDVDKLDEAEYTCIAENKAGEQEAEIHLKVFA 94


                  .
gi 119609534  364 R 364
Cdd:cd05730    95 K 95

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: 49.91 E-value: 3.13e-07

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 119609534  199 CQAKGVPPPSITWYKDAAVVEVEKLTrfrQRNDGGLQISGLVPDDTGMFQCFARNAAGEVQTSTYLAV 266
Cdd:cd05728    21 CKASGNPRPAYRWLKNGQPLASENRI---EVEAGDLRITKLSLSDSGMYQCVAENKHGTIYASAELAV 85

Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409357 [Multi-domain] Cd Length: 88 Bit Score: 49.85 E-value: 3.42e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  273 ITRGPLDSTVIDGMSVVLACETSGAPRPAITWQKgerilASGSvQLPRFTPLESGSLL-ISPTHISDAGTYTCLATNSRG 351
Cdd:cd04968     4 KVRFPADTYALKGQTVTLECFALGNPVPQIKWRK-----VDGS-PSSQWEITTSEPVLeIPNVQFEDEGTYECEAENSRG 77

                          90
                  ....*....|
gi 119609534  352 VDEASADLVV 361
Cdd:cd04968    78 KDTVQGRIIV 87

First immunoglobulin (Ig) domain of contactin-5; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-5. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains, anchored to the membrane by glycosylphosphatidylinositol. The different contactins show different expression patterns in the central nervous system. In rats, a lack of contactin-5 (NB-2) results in an impairment of the neuronal activity in the auditory system. Contactin-5 is expressed specifically in the postnatal nervous system, peaking at about 3 weeks postnatal. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala; lower levels of expression have been detected in the corpus callosum, caudate nucleus, and spinal cord. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409435 Cd Length: 96 Bit Score: 49.94 E-value: 3.56e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  177 PQFVKEPERHI--TAEMEKVVDIPCQAKGVPPPSITWYKDAAVVEVEKLTRFrQRNDGGLQISGlvPD---DTGMFQCFA 251
Cdd:cd05848     2 PVFVQEPDDAIfpTDSDEKKVILNCEARGNPVPTYRWLRNGTEIDTESDYRY-SLIDGNLIISN--PSevkDSGRYQCLA 78


                  ....*..
gi 119609534  252 RNAAGEV 258
Cdd:cd05848    79 TNSIGSI 85

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: 49.86 E-value: 4.49e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  271 PNITRGPLDSTVIDGMSVVLACETSGAPRPAITWQK-GERILASGSVQLPRFTPLESGSLLI-----SPTHISDAGTYTC 344
Cdd:cd07693     1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKnGQPLETDKDDPRSHRIVLPSGSLFFlrvvhGRKGRSDEGVYVC 80


                  ....*...
gi 119609534  345 LATNSRGV 352
Cdd:cd07693    81 VAHNSLGE 88

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: 49.62 E-value: 4.95e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  277 PLDSTVIDGMSVVLACETSGAPRPAITWQK------GE-RILASGsvqlPRFTPLESGSLLISPTHISDAGTYTCLATNS 349
Cdd:cd20954     8 PVDANVAAGQDVMLHCQADGFPTPTVTWKKatgstpGEyKDLLYD----PNVRILPNGTLVFGHVQKENEGHYLCEAKNG 83


                  ..
gi 119609534  350 RG 351
Cdd:cd20954    84 IG 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: 49.55 E-value: 5.18e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  177 PQFVKEPERHI--TAEMEKVVDIPCQAKGVPPPSITWYKDAAVVEVEKLTRFRQRnDGGLQISGlvPD---DTGMFQCFA 251
Cdd:cd04967     2 PVFEEQPDDTIfpEDSDEKKVALNCRARANPVPSYRWLMNGTEIDLESDYRYSLV-DGTLVISN--PSkakDAGHYQCLA 78


                  ....*..
gi 119609534  252 RNAAGEV 258
Cdd:cd04967    79 TNTVGSV 85

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: 49.22 E-value: 7.01e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  369 KPPQDQSVIKGTQASMVCGVTHDpRVTIRYIWEKDGATLGTESHP---RIRLDRNGS-LHISQTWSGDIGTYTCRVISAG 444
Cdd:cd05895     4 KEMKSQEVAAGSKLVLRCETSSE-YPSLRFKWFKNGKEINRKNKPeniKIQKKKKKSeLRINKASLADSGEYMCKVSSKL 82

                          90
                  ....*....|.
gi 119609534  445 GNDSRSAHLRV 455
Cdd:cd05895    83 GNDSASANVTI 93

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: 48.96 E-value: 7.69e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  177 PQFVKEPERHITAEMEKVVdIPCQAKGVPPPSITWYKDAAVVEVE----KLTRFRQRNDGGLQISGLVPDDTGMFQCFAR 252
Cdd:cd20951     1 PEFIIRLQSHTVWEKSDAK-LRVEVQGKPDPEVKWYKNGVPIDPSsipgKYKIESEYGVHVLHIRRVTVEDSAVYSAVAK 79

                          90
                  ....*....|....
gi 119609534  253 NAAGEVQTSTYLAV 266
Cdd:cd20951    80 NIHGEASSSASVVV 93

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 48.57 E-value: 8.10e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534   663 PPGNVHAEATNSTTIRFTWNAPSPQfiNGINQGYKLIAWEPEQEEEVTMVTARPNfQDSIHvgfVSGLKKFTEYFTSVLC 742
Cdd:pfam00041    2 APSNLTVTDVTSTSLTVSWTPPPDG--NGPITGYEVEYRPKNSGEPWNEITVPGT-TTSVT---LTGLKPGTEYEVRVQA 75

                           90
                   ....*....|
gi 119609534   743 FTTPGDGPRS 752
Cdd:pfam00041   76 VNGGGEGPPS 85

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: 48.66 E-value: 9.10e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  369 KPPQDQSVIKGTQASMVCGVT-HDPrvTIRYIWEKDGATLGTESHPRIRL---DRNGSLHISQTWSGDIGTYTCRVISAG 444
Cdd:cd05750     4 KEMKSQTVQEGSKLVLKCEATsENP--SPRYRWFKDGKELNRKRPKNIKIrnkKKNSELQINKAKLEDSGEYTCVVENIL 81

                          90
                  ....*....|.
gi 119609534  445 GNDSRSAHLRV 455
Cdd:cd05750    82 GKDTVTGNVTV 92

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: 48.66 E-value: 9.21e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  271 PNIT--RGPLDSTVIDGMSVVLACETSGAPRPAITWQKGERILASGSvqlPRFTPLESGSLLISPTHI-SDAGTYTCLAT 347
Cdd:cd20970     1 PVIStpQPSFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFN---TRYIVRENGTTLTIRNIRrSDMGIYLCIAS 77

                          90
                  ....*....|....*
gi 119609534  348 N-SRGVDEASADLVV 361
Cdd:cd20970    78 NgVPGSVEKRITLQV 92

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

Pssm-ID: 143207 [Multi-domain] Cd Length: 95 Bit Score: 48.77 E-value: 1.04e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  176 PPQF-VKEPERHITAEMEKVVDIPCQAKGVPPPSITWYKDAAVVEVEKlTRFRQRNDGG-LQISGLVPDDTGMFQCFARN 253
Cdd:cd05730     1 PPTIrARQSEVNATANLGQSVTLACDADGFPEPTMTWTKDGEPIESGE-EKYSFNEDGSeMTILDVDKLDEAEYTCIAEN 79

                          90
                  ....*....|...
gi 119609534  254 AAGEVQTSTYLAV 266
Cdd:cd05730    80 KAGEQEAEIHLKV 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: 47.97 E-value: 1.27e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  274 TRGPLDSTVIDGMSVVLACETSGAPRPAITWQKgerilasGSVQLPRFTPLESGSLLISPTHISDAGTYTCLATNSRGVD 353
Cdd:cd05739     1 SIPPSNHEVMPGGSVNLTCVAVGAPMPYVKWMK-------GGEELTKEDEMPVGRNVLELTNIYESANYTCVAISSLGMI 73


                  ....*...
gi 119609534  354 EASADLVV 361
Cdd:cd05739    74 EATAQVTV 81

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: 48.16 E-value: 1.33e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  180 VKEPERHITAeMEKVVDIPCQAKGVPPPSITWYKDAAVVEVeklTRFRQRNDGGLQISGLVPDDTGMFQCFARNAAGEVQ 259
Cdd:cd05725     1 VKRPQNQVVL-VDDSAEFQCEVGGDPVPTVRWRKEDGELPK---GRYEILDDHSLKIRKVTAGDMGSYTCVAENMVGKIE 76


                  ....*..
gi 119609534  260 TSTYLAV 266
Cdd:cd05725    77 ASATLTV 83

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: 48.26 E-value: 1.76e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  277 PLDSTVIDGMSVVLACETSGAPRPAITW---------QKGERILASGSVQLprftpLESGSLLISPTHISDAGTYTCLAT 347
Cdd:cd05734     8 PNDQDGIYGKAVVLNCSADGYPPPTIVWkhskgsgvpQFQHIVPLNGRIQL-----LSNGSLLIKHVLEEDSGYYLCKVS 82


                  ....*.
gi 119609534  348 NSRGVD 353
Cdd:cd05734    83 NDVGAD 88

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

Pssm-ID: 395002 Cd Length: 86 Bit Score: 47.57 E-value: 2.05e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 119609534   281 TVIDGMSVVLACETS-GAPRPAITWQKGERILASGSVQLPRFTPLESGSLLISPTHISDAGTYTCLATNSRGVDEASA 357
Cdd:pfam00047    7 TVLEGDSATLTCSAStGSPGPDVTWSKEGGTLIESLKVKHDNGRTTQSSLLISNVTKEDAGTYTCVVNNPGGSATLST 84

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: 47.50 E-value: 2.27e-06

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534     91 KNTSVVAGtSEVTLECVANARPliKLHIIWKKDG---VLLSGGIS----DHNRRLTIPNPTGSDAGYYECEAvlrSSSVP 163
Cdd:smart00410    2 PSVTVKEG-ESVTLSCEASGSP--PPEVTWYKQGgklLAESGRFSvsrsGSTSTLTISNVTPEDSGTYTCAA---TNSSG 75

                            90
                    ....*....|
gi 119609534    164 SVVRGAYLSV 173
Cdd:smart00410   76 SASSGTTLTV 85

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

Pssm-ID: 409388 Cd Length: 84 Bit Score: 47.19 E-value: 2.39e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  277 PLDSTVIDGMSVVLACETSGAPRPAITWQKgerilaSGSVQLPR--FTPLESGSLLISPTHISDAGTYTCLATNSRGVDE 354
Cdd:cd05723     4 PSNIYAHESMDIVFECEVTGKPTPTVKWVK------NGDVVIPSdyFKIVKEHNLQVLGLVKSDEGFYQCIAENDVGNAQ 77


                  ....*..
gi 119609534  355 ASADLVV 361
Cdd:cd05723    78 ASAQLII 84

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: 47.66 E-value: 2.48e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  177 PQFVKEPERHITAEMEKVVDIPCQAKGVPPPSITWYKDAAVVEVEKLTRFRQRN-DGGLQI---SGLVPDD-TGMFQCFA 251
Cdd:cd05875     1 PTITKQSAKDYIVDPRDNILIECEAKGNPVPTFHWTRNGKFFNVAKDPRVSMRRrSGTLVIdfrGGGRPEDyEGEYQCFA 80


                  ....*
gi 119609534  252 RNAAG 256
Cdd:cd05875    81 RNKFG 85

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: 47.06 E-value: 3.35e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  175 EPPQFVKEPERhiTAEMEkvvdipCQAKGVPPPSITWYKDAAVVEVEKLTRFRQRNDGGLQISGLVPDDTGMFQCFARNA 254
Cdd:cd04978     5 EPPSLVLSPGE--TGELI------CEAEGNPQPTITWRLNGVPIEPAPEDMRRTVDGRTLIFSNLQPNDTAVYQCNASNV 76

                          90
                  ....*....|..
gi 119609534  255 AGEVQTSTYLAV 266
Cdd:cd04978    77 HGYLLANAFLHV 88

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: 47.31 E-value: 3.42e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  273 ITRGPLDSTVIDGMSVVLACETSGAPRPAITWQKG----ERILASGsvqlpRFTPLESGSLLISPTHISDAGTYTCLATN 348
Cdd:cd05738     2 IDMGPQLKVVEKARTATMLCAASGNPDPEISWFKDflpvDTATSNG-----RIKQLRSGALQIENSEESDQGKYECVATN 76

                          90
                  ....*....|....
gi 119609534  349 SRGVD-EASADLVV 361
Cdd:cd05738    77 SAGTRySAPANLYV 90

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

Pssm-ID: 409546 [Multi-domain] Cd Length: 96 Bit Score: 47.31 E-value: 3.77e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  176 PPQFVKEPERHITAEMEKVVdIPCQAKGVPPPSITW----------YKDaavveVEKLTRFRQRNDGGLQISGLVPDDTG 245
Cdd:cd20954     1 PPRWIVEPVDANVAAGQDVM-LHCQADGFPTPTVTWkkatgstpgeYKD-----LLYDPNVRILPNGTLVFGHVQKENEG 74

                          90
                  ....*....|.
gi 119609534  246 MFQCFARNAAG 256
Cdd:cd20954    75 HYLCEAKNGIG 85

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: 46.63 E-value: 4.04e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  199 CQA-KGVPPPSITWYKDAAVVeVEKLTRFRQRNDGGLQISGLVPDDTGMFQCFARNAAGEVQTST-YLAV 266
Cdd:cd05724    19 CSPpRGHPEPTVSWRKDGQPL-NLDNERVRIVDDGNLLIAEARKSDEGTYKCVATNMVGERESRAaRLSV 87

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 46.45 E-value: 4.68e-06

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534    663 PPGNVHAEATNSTTIRFTWNAPSPQFINGINQGYKLIAWEP-EQEEEVTMVTARPNFQdsihvgfVSGLKKFTEYFTSVL 741
Cdd:smart00060    3 PPSNLRVTDVTSTSVTLSWEPPPDDGITGYIVGYRVEYREEgSEWKEVNVTPSSTSYT-------LTGLKPGTEYEFRVR 75


                    ....*...
gi 119609534    742 CFTTPGDG 749
Cdd:smart00060   76 AVNGAGEG 83

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: 46.75 E-value: 4.71e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  281 TVIDGMSVVLACETSGAPRPAITWQKGERILASGSVQLPRFTPLES----GSLLISPTHISDAGTYTCLATNSRGVDEAS 356
Cdd:cd05732    12 TAVELEQITLTCEAEGDPIPEITWRRATRGISFEEGDLDGRIVVRGharvSSLTLKDVQLTDAGRYDCEASNRIGGDQQS 91

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: 46.31 E-value: 5.27e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  367 ITKPPQDQSVIKGTQASMVCGVTHDPRVTIRYIwEKDGATLGTEShpRIRLDRNGSLHISQTWSGDIGTYTCRVISAGGN 446
Cdd:cd05764     3 ITRHTHELRVLEGQRATLRCKARGDPEPAIHWI-SPEGKLISNSS--RTLVYDNGTLDILITTVKDTGAFTCIASNPAGE 79


                  ....*....
gi 119609534  447 DSRSAHLRV 455
Cdd:cd05764    80 ATARVELHI 88

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 46.07 E-value: 5.81e-06

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534    862 PGPPTNLGISNIGPRSVTLQFRPGYDGktSISRWLVEAQVGVVGEGEEWlliHQLSNEPDARSMEVPDLNPFTCYSFRMR 941
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTLSWEPPPDD--GITGYIVGYRVEYREEGSEW---KEVNVTPSSTSYTLTGLKPGTEYEFRVR 75


                    ....*...
gi 119609534    942 QVNIVGTS 949
Cdd:smart00060   76 AVNGAGEG 83

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: 46.41 E-value: 6.35e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  199 CQAKGVPPPSITWYKDAAVVEVEKLTRFRQRNDG--GLQISGLVPDDTGMFQCFARNAAGEVQTSTYLAV 266
Cdd:cd20973    19 CKVEGYPDPEVKWMKDDNPIVESRRFQIDQDEDGlcSLIISDVCGDDSGKYTCKAVNSLGEATCSAELTV 88

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 45.85 E-value: 6.52e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534   270 APNITRGPldSTVIDGMSVVLACETSGAPRPAITWQKGERILASgsvqlprftpleSGSLLISPTHISDAGTYTCLATNS 349
Cdd:pfam13895    1 KPVLTPSP--TVVTEGEPVTLTCSAPGNPPPSYTWYKDGSAISS------------SPNFFTLSVSAEDSGTYTCVARNG 66

                           90
                   ....*....|...
gi 119609534   350 RGV-DEASADLVV 361
Cdd:pfam13895   67 RGGkVSNPVELTV 79

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

Pssm-ID: 395002 Cd Length: 86 Bit Score: 46.03 E-value: 8.21e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534   369 KPPQDQSVIKGTQASMVCGVTHDPRVTIrYIWEKDGATL--GTESHPRIRLDRNGSLHISQTWSGDIGTYTCRVISAGGN 446
Cdd:pfam00047    1 SAPPTVTVLEGDSATLTCSASTGSPGPD-VTWSKEGGTLieSLKVKHDNGRTTQSSLLISNVTKEDAGTYTCVVNNPGGS 79


                   ....*
gi 119609534   447 DSRSA 451
Cdd:pfam00047   80 ATLST 84

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

Pssm-ID: 409541 [Multi-domain] Cd Length: 89 Bit Score: 46.17 E-value: 8.23e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 119609534  197 IPCQAKGVPPPSITWYKDAAVVE--VEKLTRFRQrNDGGLQISGLVPDDTGMFQCFARNAAG 256
Cdd:cd20949    19 ILCEVKGEPQPNVTWHFNGQPISasVADMSKYRI-LADGLLINKVTQDDTGEYTCRAYQVNS 79

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: 46.03 E-value: 9.02e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  278 LDSTVIDGMSVVLACETSGAPRPAITWQKGER-ILASGSVQlprFTPLESG--SLLISPTHISDAGTYTCLATNSRGVDE 354
Cdd:cd20973     5 RDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNpIVESRRFQ---IDQDEDGlcSLIISDVCGDDSGKYTCKAVNSLGEAT 81


                  ....*..
gi 119609534  355 ASADLVV 361
Cdd:cd20973    82 CSAELTV 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: 46.01 E-value: 9.03e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 119609534  285 GMSVVLACETSGAPRPAITWQKGERILASGSVQLPRftpLESGSLLISPTHISDAGTYTCLATNSRG 351
Cdd:cd05856    19 GSSVRLKCVASGNPRPDITWLKDNKPLTPPEIGENK---KKKWTLSLKNLKPEDSGKYTCHVSNRAG 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: 45.96 E-value: 9.22e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  188 TAEMEKVVDIPCQAKGVPPPSITWYKDAAVVEvEKLTRFRQRNDGG-LQISGLVPDDTGMFQCFARN-AAGEVQTSTYLA 265
Cdd:cd20970    13 TAREGENATFMCRAEGSPEPEISWTRNGNLII-EFNTRYIVRENGTtLTIRNIRRSDMGIYLCIASNgVPGSVEKRITLQ 91


                  .
gi 119609534  266 V 266
Cdd:cd20970    92 V 92

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 45.68 E-value: 9.47e-06

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 119609534   1706 SSAIAIHWS--SGDPGKGPITRYVIEARPSDEGlWdiliKDIPKEVSSYTFSMDILKPGVSYDFRVIAVNDYGFG 1778
Cdd:smart00060   14 STSVTLSWEppPDDGITGYIVGYRVEYREEGSE-W----KEVNVTPSSTSYTLTGLKPGTEYEFRVRAVNGAGEG 83

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: 45.93 E-value: 1.06e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  102 VTLECVANARPLIKlhIIWKKDGVLLSGGiSDHNRRLTipnPTGS--------------DAGYYECEAVLRSSSvpSVV- 166
Cdd:cd05722    19 VVLNCSAESDPPPK--IEWKKDGVLLNLV-SDERRQQL---PNGSllitsvvhskhnkpDEGFYQCVAQNESLG--SIVs 90


                  ....*..
gi 119609534  167 RGAYLSV 173
Cdd:cd05722    91 RTARVTV 97

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

Pssm-ID: 409561 Cd Length: 92 Bit Score: 45.84 E-value: 1.14e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  187 ITAEMEKVVDIPCQAKGVPPPSITW-YKDAAVVEVEKLTRFRQRNDGGLQISGLVPDDTGMFQCFARNAAGEVQTSTYLA 265
Cdd:cd20969    12 VFVDEGHTVQFVCRADGDPPPAILWlSPRKHLVSAKSNGRLTVFPDGTLEVRYAQVQDNGTYLCIAANAGGNDSMPAHLH 91


                  .
gi 119609534  266 V 266
Cdd:cd20969    92 V 92

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

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 45.62 E-value: 1.36e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 119609534  199 CQAKGVPPPSITWYKDAAVVEVEKLTRFRQR---NDGGLQISGLVPD-----DTGMFQCFARNAAGE 257
Cdd:cd07693    22 CKAEGRPTPTIQWLKNGQPLETDKDDPRSHRivlPSGSLFFLRVVHGrkgrsDEGVYVCVAHNSLGE 88

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: 45.36 E-value: 1.50e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  181 KEPERHITAEMEKVVdIPCQAKGVPPPSITWYKDAAVVEVEKLTRFRQRNDGG---LQISGLVPDDT--GMFQCFARNAA 255
Cdd:cd05874     6 QSPKDYIVDPRENIV-IQCEAKGKPPPSFSWTRNGTHFDIDKDPKVTMKPNTGtlvINIMNGEKAEAyeGVYQCTARNER 84


                  .
gi 119609534  256 G 256
Cdd:cd05874    85 G 85

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409582 Cd Length: 91 Bit Score: 45.09 E-value: 1.83e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  177 PQFVKEPErHITAEMEKVVDIPCQAKGVPPPSITWYKDAAVVEVEKLTRFRQRNDG--GLQISGLVPDDTGMFQCFARNA 254
Cdd:cd20990     1 PHFLQAPG-DLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSAHKMLVRENGvhSLIIEPVTSRDAGIYTCIATNR 79

                          90
                  ....*....|..
gi 119609534  255 AGEVQTSTYLAV 266
Cdd:cd20990    80 AGQNSFNLELVV 91

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: 45.24 E-value: 1.88e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 119609534  195 VDIPCQAKGVPPPSITWYKDAAVVEVEKLTRFRqRNDGGLQISGLVPDDTGMFQCFARNAAGEVQtSTY 263
Cdd:cd05856    22 VRLKCVASGNPRPDITWLKDNKPLTPPEIGENK-KKKWTLSLKNLKPEDSGKYTCHVSNRAGEIN-ATY 88

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: 44.83 E-value: 2.05e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  186 HITAEMEKVVDIPCQAKGVPPPSITWYKDAavvevEKLT---RFRQRNDGGLQISGLVPDDTGMFQCFARNAAGEVQTST 262
Cdd:cd20957    10 VQTVDFGRTAVFNCSVTGNPIHTVLWMKDG-----KPLGhssRVQILSEDVLVIPSVKREDKGMYQCFVRNDGDSAQATA 84


                  ..
gi 119609534  263 YL 264
Cdd:cd20957    85 EL 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: 44.79 E-value: 2.37e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  176 PPQFVKEPERHiTAEMEKVVDIPCQAKGVPPPSITW--YKDAAVVEVEKLT----RFRQRNDGGLQISGLVPDDTGMFQC 249
Cdd:cd05734     1 PPRFVVQPNDQ-DGIYGKAVVLNCSADGYPPPTIVWkhSKGSGVPQFQHIVplngRIQLLSNGSLLIKHVLEEDSGYYLC 79

                          90
                  ....*....|....*...
gi 119609534  250 FARNAAG-EVQTSTYLAV 266
Cdd:cd05734    80 KVSNDVGaDISKSMYLTV 97

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

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 44.12 E-value: 2.87e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  288 VVLACET-------SGAPRPAITWQKGERILA-SGSVQLPrfTPLESGSLLISPTHISDAGTYTCLATNSRGVDEASADL 359
Cdd:cd05748     3 VVRAGESlrldipiKGRPTPTVTWSKDGQPLKeTGRVQIE--TTASSTSLVIKNAKRSDSGKYTLTLKNSAGEKSATINV 80


                  ..
gi 119609534  360 VV 361
Cdd:cd05748    81 KV 82

First immunoglobulin (Ig) domain of contactin-5; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-5. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains, anchored to the membrane by glycosylphosphatidylinositol. The different contactins show different expression patterns in the central nervous system. In rats, a lack of contactin-5 (NB-2) results in an impairment of the neuronal activity in the auditory system. Contactin-5 is expressed specifically in the postnatal nervous system, peaking at about 3 weeks postnatal. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala; lower levels of expression have been detected in the corpus callosum, caudate nucleus, and spinal cord. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409435 Cd Length: 96 Bit Score: 44.55 E-value: 3.10e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 119609534  277 PLDStviDGMSVVLACETSGAPRPAITW-QKGERILASGSVqlpRFTPLEsGSLLIS-PTHISDAGTYTCLATNSRGV 352
Cdd:cd05848    14 PTDS---DEKKVILNCEARGNPVPTYRWlRNGTEIDTESDY---RYSLID-GNLIISnPSEVKDSGRYQCLATNSIGS 84

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: 44.37 E-value: 3.19e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  277 PLDSTVIDGMSVVLACETSGAPRPAITWQKGERILASGSvqlPRFTPLESGS----LLISPTHISDAGTYTCLATNSRGV 352
Cdd:cd05892     7 PQNKKVLEGDPVRLECQISAIPPPQIFWKKNNEMLQYNT---DRISLYQDNCgricLLIQNANKKDAGWYTVSAVNEAGV 83


                  ....*....
gi 119609534  353 DEASADLVV 361
Cdd:cd05892    84 VSCNARLDV 92

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

Pssm-ID: 143259 Cd Length: 88 Bit Score: 44.24 E-value: 3.45e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  279 DSTVIDGMSVVLACETSGAPRPAITWQK-GERILASGSVQLprftpleSGSLL-ISPTHISDAGTYTCLATNSRGVDEAS 356
Cdd:cd05851    10 DTYALKGQNVTLECFALGNPVPVIRWRKiLEPMPATAEISM-------SGAVLkIFNIQPEDEGTYECEAENIKGKDKHQ 82


                  ....*
gi 119609534  357 ADLVV 361
Cdd:cd05851    83 ARVYV 87

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

Pssm-ID: 409394 [Multi-domain] Cd Length: 83 Bit Score: 43.94 E-value: 3.78e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 119609534  281 TVIDGMSVVLACETSGAPRPAITWQKGERILASGSVQLPRFtpleSGSLLISPTHISDAGTYTCLATNSRG 351
Cdd:cd05731     6 MVLRGGVLLLECIAEGLPTPDIRWIKLGGELPKGRTKFENF----NKTLKIENVSEADSGEYQCTASNTMG 72

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: 43.38 E-value: 5.85e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 119609534  180 VKEPERHITAEMEKVVDIPCQAKGVPPPSITWYKDAAVVEVEklTRFRQRNDGGLQISGLVPDDTGMFQCFARNAAG 256
Cdd:cd20968     2 ITRPPTNVTIIEGLKAVLPCTTMGNPKPSVSWIKGDDLIKEN--NRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLG 76

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: 43.73 E-value: 5.99e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  274 TRGPLDSTVIDGMSVVLACETSGAPRPAITWQ-KGERILASGSVQLPRftpLESGSLLISPTHISDAGTYTCLATNSRGV 352
Cdd:cd05867     3 TRRPQSHLYGPGETARLDCQVEGIPTPNITWSiNGAPIEGTDPDPRRH---VSSGALILTDVQPSDTAVYQCEARNRHGN 79


                  ....*....
gi 119609534  353 DEASADLVV 361
Cdd:cd05867    80 LLANAHVHV 88

Third immunoglobulin (Ig)-like domain of fibroblast growth factor receptor 2 (FGFR2); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain of human fibroblast growth factor receptor 2 (FGFR2). Fibroblast growth factors (FGFs) participate in morphogenesis, development, angiogenesis, and wound healing. These FGF-stimulated processes are mediated by four FGFR tyrosine kinases (FGRF1-4). FGFRs are comprised of an extracellular portion consisting of three Ig-like domains, a transmembrane helix, and a cytoplasmic portion having protein tyrosine kinase activity. The highly conserved Ig-like domains 2 and 3, and the linker region between D2 and D3 define a general binding site for FGFs. FGFR2 is required for male sex determination. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409444 Cd Length: 105 Bit Score: 43.80 E-value: 6.37e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  277 PLDSTVIDGMSVVLACETSGAPRPAITWQKGERILAS--GSVQLPRFTPLESGS----------LLISPTHISDAGTYTC 344
Cdd:cd05858     8 PANTSVVVGTDAEFVCKVYSDAQPHIQWLKHVEKNGSkyGPDGLPYVEVLKTAGvnttdkeievLYLRNVTFEDAGEYTC 87

                          90
                  ....*....|....*..
gi 119609534  345 LATNSRGVDEASADLVV 361
Cdd:cd05858    88 LAGNSIGISHHSAWLTV 104

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: 43.53 E-value: 6.44e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  281 TVIDGMSVVLACETSGAPRPAITW-QKGERILASGSVQlpRFTPLESGSLLISPTHISDAGTYTCLATNSRGVDEASADL 359
Cdd:cd20969    13 FVDEGHTVQFVCRADGDPPPAILWlSPRKHLVSAKSNG--RLTVFPDGTLEVRYAQVQDNGTYLCIAANAGGNDSMPAHL 90


                  ..
gi 119609534  360 VV 361
Cdd:cd20969    91 HV 92

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: 42.86 E-value: 7.30e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  285 GMSVVLACETSGAPRPAITWQkgeriLASGSVQLPRFTPLES----GSLLISPTHISDAGTYTCLATNSRGVDEASADLV 360
Cdd:cd05743     1 GETVEFTCVATGVPTPIINWR-----LNWGHVPDSARVSITSeggyGTLTIRDVKESDQGAYTCEAINTRGMVFGIPDGI 75


                  .
gi 119609534  361 V 361
Cdd:cd05743    76 L 76

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

Pssm-ID: 409440 Cd Length: 102 Bit Score: 43.49 E-value: 7.96e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  365 TRITKPPQDQSVIKGTQASMVCGVTHDPRVTIRYIWEKDGATLG---TESHPRiRLDRN---GSLHISQTWSGDIGTYTC 438
Cdd:cd05854     3 TKITLAPSSADINQGENLTLQCHASHDPTMDLTFTWSLDDFPIDldkPNGHYR-RMEVKetiGDLVIVNAQLSHAGTYTC 81

                          90       100
                  ....*....|....*....|.
gi 119609534  439 RVISAGGNDSRSAHLRVRQLP 459
Cdd:cd05854    82 TAQTVVDSASASATLVVRGPP 102

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

Pssm-ID: 409412 Cd Length: 85 Bit Score: 42.93 E-value: 9.02e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  277 PLDSTVIDGMSVVLACET-SGAPRPAITWQKGERILASGSVQLprftpleSGSLLISPTHISDAGTYTCLATNSRGVDEA 355
Cdd:cd05754     8 PRSQEVRPGADVSFICRAkSKSPAYTLVWTRVNGTLPSRAMDF-------NGILTIRNVQLSDAGTYVCTGSNMLDTDEA 80


                  ....
gi 119609534  356 SADL 359
Cdd:cd05754    81 TATL 84

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

Pssm-ID: 409475 Cd Length: 86 Bit Score: 42.90 E-value: 1.09e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 119609534  281 TVIDGMSVVLACETSGAPRPAITWQKGERILASGSVQLPRFTPLESGSLLISPTHISDAGTYTCLATNSRGVDEAS 356
Cdd:cd05894     6 VVVAGNKLRLDVPISGEPAPTVTWSRGDKAFTATEGRVRVESYKDLSSFVIEGAEREDEGVYTITVTNPVGEDHAS 81

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. 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 Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. 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: 409559 Cd Length: 82 Bit Score: 42.61 E-value: 1.17e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  376 VIKGTQASMVCGVT-HDPRVTiryiWEKDGATLGTEShpRIRLDRNGS---LHISQTWSGDIGTYTCRVisagGNDSRSA 451
Cdd:cd20967     9 VSKGHKIRLTVELAdPDAEVK----WYKDGQELQSSS--KVIFESIGAkrtLTVQQASLADAGEYQCVA----GGEKCSF 78


                  ....
gi 119609534  452 HLRV 455
Cdd:cd20967    79 ELFV 82

Phage-related protein, tail protein J [Mobilome: prophages, transposons];

Pssm-ID: 443767 [Multi-domain] Cd Length: 978 Bit Score: 47.25 E-value: 1.20e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534 1463 RYEIRM-----SVYNAV--GEGPSSPPQEVFVGeaVPTAAPRNVVVHGATATQLDVTWEPPPLDSqngdiqGYKIYfWEA 1535
Cdd:COG4733   503 TYTITAvqhapEKYAAIdaGAFDDVPPQWPPVN--VTTSESLSVVAQGTAVTTLTVSWDAPAGAV------AYEVE-WRR 573

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534 1536 QRGNLTervktlFLAENSVKLKNLTGYTA--YMVSVAAFNAAGD-GPRSTPTQGQTQQ--AAPSAPSSvkfseLTTTS-- 1608
Cdd:COG4733   574 DDGNWV------SVPRTSGTSFEVPGIYAgdYEVRVRAINALGVsSAWAASSETTVTGktAPPPAPTG-----LTATGgl 642

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 119609534 1609 --VNVSWEAPQFPNgiLEGYRLVYEPcSPVDGVSKIVTVDVKGNSPLWlkvKDLAEGVTYRFRIRA 1672
Cdd:COG4733   643 ggITLSWSFPVDAD--TLRTEIRYST-TGDWASATVAQALYPGNTYTL---AGLKAGQTYYYRARA 702

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: 42.69 E-value: 1.23e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  367 ITKPPQDQSVIKGTQASMVCGVTHDPRVTIryIWEKDGATLGTE-SHPRIRLDRNGSLHISQTWSGDIGTYTCRVI-SAG 444
Cdd:cd05738     2 IDMGPQLKVVEKARTATMLCAASGNPDPEI--SWFKDFLPVDTAtSNGRIKQLRSGALQIENSEESDQGKYECVATnSAG 79

                          90
                  ....*....|..
gi 119609534  445 GNDSRSAHLRVR 456
Cdd:cd05738    80 TRYSAPANLYVR 91

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

Pssm-ID: 409387 Cd Length: 97 Bit Score: 42.85 E-value: 1.33e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  368 TKPPQDQSVIKGTQASMVCGVTHDPRVTIRyiWEKDGATLGTESHPRIRLDRNGSLHI-----SQTWSGDIGTYTC--RV 440
Cdd:cd05722     5 LSEPSDIVAMRGGPVVLNCSAESDPPPKIE--WKKDGVLLNLVSDERRQQLPNGSLLItsvvhSKHNKPDEGFYQCvaQN 82

                          90
                  ....*....|....*
gi 119609534  441 ISAGGNDSRSAHLRV 455
Cdd:cd05722    83 ESLGSIVSRTARVTV 97

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

Pssm-ID: 409402 [Multi-domain] Cd Length: 89 Bit Score: 42.38 E-value: 1.67e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534   92 NTSVVAGTSEVTLECVANArplIKLHIIWKKDGVLLSGG----ISDHNRRLTIPNPTGSDAGYYECEA-----VLRSSSV 162
Cdd:cd05740     8 NSNPVEDKDAVTLTCEPET---QNTSYLWWFNGQSLPVTprltLSNGNRTLTLLNVTREDAGAYQCEIsnpvsANRSDPV 84

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: 41.99 E-value: 1.98e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 119609534   91 KNTSVVaGTSEVTLECVANARPliKLHIIWKKDGVLLSGGISD---HNRRLTIPNPTGSDAGYYECEAV 156
Cdd:cd20978     9 KNVVVK-GGQDVTLPCQVTGVP--QPKITWLHNGKPLQGPMERatvEDGTLTIINVQPEDTGYYGCVAT 74

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: 42.21 E-value: 2.03e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  181 KEPERHITAEMEKVVDIPCQAKGVPPPSITWYKDAAVVEVEKLTR-FRQRNDG-GLQISGLVPDDTGMFQCFARNAAGEV 258
Cdd:cd05729     8 KMEEREHALPAANKVRLECGAGGNPMPNITWLKDGKEFKKEHRIGgTKVEEKGwSLIIERAIPRDKGKYTCIVENEYGSI 87


                  ....*...
gi 119609534  259 QTSTYLAV 266
Cdd:cd05729    88 NHTYDVDV 95

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: 42.15 E-value: 2.20e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 119609534  193 KVVDIPCQAKGVPPPSITWYKDAAVVEVEKLT---RFRQRNdGGLQISGLVPDDTGMFQCFARNAAGEVQTSTYLAV 266
Cdd:cd05857    20 NTVKFRCPAAGNPTPTMRWLKNGKEFKQEHRIggyKVRNQH-WSLIMESVVPSDKGNYTCVVENEYGSINHTYHLDV 95

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: 41.84 E-value: 2.30e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  368 TKPPQDQSVIKGTQASMVCGVTHDPRVTIryIWEKDGATlgteSHPRIRLDR------NGSLHISQTWSGDIGTYTCRVI 441
Cdd:cd05763     3 TKTPHDITIRAGSTARLECAATGHPTPQI--AWQKDGGT----DFPAARERRmhvmpeDDVFFIVDVKIEDTGVYSCTAQ 76

                          90
                  ....*....|....
gi 119609534  442 SAGGNDSRSAHLRV 455
Cdd:cd05763    77 NSAGSISANATLTV 90

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

Pssm-ID: 409391 [Multi-domain] Cd Length: 98 Bit Score: 42.25 E-value: 2.35e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  371 PQDQSVIKGTQASMVCGVTHDPRVTIryIWEKDGA------TLGTESHPRIRLDRNGSLHISQTWSGDIGTYTCRVISAG 444
Cdd:cd05726     6 PRDQVVALGRTVTFQCETKGNPQPAI--FWQKEGSqnllfpYQPPQPSSRFSVSPTGDLTITNVQRSDVGYYICQALNVA 83

                          90
                  ....*....|.
gi 119609534  445 GNDSRSAHLRV 455
Cdd:cd05726    84 GSILAKAQLEV 94

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: 41.86 E-value: 2.62e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  371 PQDQSVIKGTQASMVCGVTH--DPRVTiryiWEKDGATLGTESHPRIRLDRNGS-LHISQTWSGDIGTYTCRVISAGGND 447
Cdd:cd05736     7 PEFQAKEPGVEASLRCHAEGipLPRVQ----WLKNGMDINPKLSKQLTLIANGSeLHISNVRYEDTGAYTCIAKNEGGVD 82

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

Pssm-ID: 409438 Cd Length: 89 Bit Score: 41.52 E-value: 2.74e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  177 PQFVKEP-ERHITAEMEKVVDIPCQAKGVPPPSITWYKDAAVVEveKLTRFRQRNDGGLQISGLVPDDTGMFQCFARNAA 255
Cdd:cd05852     1 PTFEFNPmKKKILAAKGGRVIIECKPKAAPKPKFSWSKGTELLV--NNSRISIWDDGSLEILNITKLDEGSYTCFAENNR 78

                          90
                  ....*....|.
gi 119609534  256 GEVQTSTYLAV 266
Cdd:cd05852    79 GKANSTGVLSV 89

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: 41.78 E-value: 3.00e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 119609534  199 CQAKGVPPPSITWYKD-AAVVEVEkltRFRQ------RND--GGLQISGLVPDDTGMFQCFARNAAGEVQTSTYLAV 266
Cdd:cd20956    23 CVASGNPLPQITWTLDgFPIPESP---RFRVgdyvtsDGDvvSYVNISSVRVEDGGEYTCTATNDVGSVSHSARINV 96

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: 41.36 E-value: 3.05e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  277 PLDSTVIDGMSVVLACETSGAPRPAITWQK-GERILASGSVQLprftpLESGSLLISPTHISDAGTYTCLATNSRGVDEA 355
Cdd:cd20957     8 PPVQTVDFGRTAVFNCSVTGNPIHTVLWMKdGKPLGHSSRVQI-----LSEDVLVIPSVKREDKGMYQCFVRNDGDSAQA 82


                  ....
gi 119609534  356 SADL 359
Cdd:cd20957    83 TAEL 86

First immunoglobulin (Ig) domain of contactin; member of the I-set of (Ig) superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 409356 [Multi-domain] Cd Length: 96 Bit Score: 41.85 E-value: 3.05e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 119609534  288 VVLACETSGAPRPAITWQK--GERILASGSvqlpRFTpLESGSLLIS-PTHISDAGTYTCLATNSRG 351
Cdd:cd04967    22 VALNCRARANPVPSYRWLMngTEIDLESDY----RYS-LVDGTLVISnPSKAKDAGHYQCLATNTVG 83

IL-beta-binding protein; Provisional

Pssm-ID: 165149 [Multi-domain] Cd Length: 326 Bit Score: 45.01 E-value: 3.12e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  320 RFTPLESGS--LLISPTHiSDAGTYTCLATNSRGVDEASADLVVWARTR-----ITKPpqdQSVIKGTQASMVCgvthdP 392
Cdd:PHA02785   74 RIIPIDNGSnmLILNPTQ-SDSGIYICITKNETYCDMMSLNLTIVSVSEsnidlISYP---QIVNERSTGEMVC-----P 144

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  393 RVTIrYIWEKDGATLGTESHPRIRLDR-----NGSLHISQTWSGDIGTYTCRVISAGG----NDSRSAHLRVRQ--LPHA 461
Cdd:PHA02785  145 NINA-FIASNVNADIIWSGHRRLRNKRlkqrtPGIITIEDVRKNDAGYYTCVLKYIYGdktyNVTRIVKLEVRDriIPPT 223

                         170
                  ....*....|....*....
gi 119609534  462 PEHPVATLSTVerrAINLT 480
Cdd:PHA02785  224 MQLPEGVVTSI---GSNLT 239

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: 41.69 E-value: 3.22e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  184 ERHIT---AEMEKVVDIPCQAKGVPPPSITWYKDAAVV--EVEKLTRFRQRNDGGLQISGL-VPDDTGMFQCFARNAAGE 257
Cdd:cd20971     5 KEELRnlnVRYQSNATLVCKVTGHPKPIVKWYRQGKEIiaDGLKYRIQEFKGGYHQLIIASvTDDDATVYQVRATNQGGS 84


                  ...
gi 119609534  258 VQT 260
Cdd:cd20971    85 VSG 87

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

Pssm-ID: 409393 [Multi-domain] Cd Length: 95 Bit Score: 41.82 E-value: 3.24e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 119609534  285 GMSVVLACETSGAPRPAITWQKGERILASGSVQLPRFTPLESGSLLISPTHISDAGTYTCLATNSRGVDEASADLVV 361
Cdd:cd05729    19 ANKVRLECGAGGNPMPNITWLKDGKEFKKEHRIGGTKVEEKGWSLIIERAIPRDKGKYTCIVENEYGSINHTYDVDV 95

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

Pssm-ID: 409397 [Multi-domain] Cd Length: 97 Bit Score: 41.71 E-value: 3.30e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  371 PQDQSVIKGTQASMVCGVTHDPRVTIryIWE-KDGATLGTESHP-----RIRLDRNGSLHISQTWSGDIGTYTCRVISAG 444
Cdd:cd05734     8 PNDQDGIYGKAVVLNCSADGYPPPTI--VWKhSKGSGVPQFQHIvplngRIQLLSNGSLLIKHVLEEDSGYYLCKVSNDV 85

                          90
                  ....*....|..
gi 119609534  445 GND-SRSAHLRV 455
Cdd:cd05734    86 GADiSKSMYLTV 97

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: 41.38 E-value: 3.36e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  100 SEVTLECVA--NARPLIKlhiiWKK-DGVLLS-GGISDHNRRLTIPNPTGSDAGYYECEA 155
Cdd:cd04968    17 QTVTLECFAlgNPVPQIK----WRKvDGSPSSqWEITTSEPVLEIPNVQFEDEGTYECEA 72

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: 40.94 E-value: 5.07e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  368 TKPPQDQSVIKGTQASMVCGVTHDPrvTIRYIWEKDGATLGTESHPRIRLDRNG--SLHISQTWSGDIGTYTCRVISAGG 445
Cdd:cd05744     4 LQAPGDLEVQEGRLCRFDCKVSGLP--TPDLFWQLNGKPVRPDSAHKMLVRENGrhSLIIEPVTKRDAGIYTCIARNRAG 81

                          90
                  ....*....|
gi 119609534  446 NDSRSAHLRV 455
Cdd:cd05744    82 ENSFNAELVV 91

Sixth immunoglobulin (Ig) domain of contactin; The members here are composed of the sixth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409359 Cd Length: 102 Bit Score: 41.00 E-value: 6.39e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  270 APNITRGPLDSTVIDGMSVVLACETSGAPRPAIT--WQ-KGERI-LASGSVQLPRFTPLES-GSLLISPTHISDAGTYTC 344
Cdd:cd04970     2 ATRITLAPSNADITVGENATLQCHASHDPTLDLTftWSfNGVPIdLEKIEGHYRRRYGKDSnGDLEIVNAQLKHAGRYTC 81

                          90
                  ....*....|....*..
gi 119609534  345 LATNSRGVDEASADLVV 361
Cdd:cd04970    82 TAQTVVDSDSASATLVV 98

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 44.61 E-value: 6.44e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  458 LPHAPEHPVATLSTveRRAINLTWTKPFDGNspLIRYILEMSENNA-PWTVLLASVdpKATSVTVKGLVPARSYQFRLCA 536
Cdd:COG3401   326 PPAAPSGLTATAVG--SSSITLSWTASSDAD--VTGYNVYRSTSGGgTYTKIAETV--TTTSYTDTGLTPGTTYYYKVTA 399

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  537 VNDVGKGqfSKDTERVSLPEEPPTAPPQNVIASGRTNQSIMIQWQPPPESHQNGILKGYIIRyclAGLPVGYQFKNITDA 616
Cdd:COG3401   400 VDAAGNE--SAPSEEVSATTASAASGESLTASVDAVPLTDVAGATAAASAASNPGVSAAVLA---DGGDTGNAVPFTTTS 474

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  617 DVNNLLLEDLiiwTNYEIEVAAYNSAGLGVYSSKVTEWTLQGVPTVPPGnvhaeATNSTTIRFTWNAPSPQFINGINQGY 696
Cdd:COG3401   475 STVTATTTDT---TTANLSVTTGSLVGGSGASSVTNSVSVIGASAAAAV-----GGAPDGTPNVTGASPVTVGASTGDVL 546


                  ..
gi 119609534  697 KL 698
Cdd:COG3401   547 IT 548

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: 40.47 E-value: 7.04e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  282 VIDGMSVVLACETSGAPRPAITWQKGERILASGSVQLPRFTPLE-SGSLLISPTHISDAGTYTCLATNSRGVDEASADLV 360
Cdd:cd05893    12 IFEGMPVTFTCRVAGNPKPKIYWFKDGKQISPKSDHYTIQRDLDgTCSLHTTASTLDDDGNYTIMAANPQGRISCTGRLM 91


                  .
gi 119609534  361 V 361
Cdd:cd05893    92 V 92

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

Pssm-ID: 409419 Cd Length: 99 Bit Score: 40.71 E-value: 8.40e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  271 PNITRGPLDSTVIDGMSVVLACETSGAPRPAITWQKGERILASGsvQLPRFTPLESGS-LLISPTHISDAGTYTCLATNS 349
Cdd:cd05762     2 PQIIQFPEDMKVRAGESVELFCKVTGTQPITCTWMKFRKQIQEG--EGIKIENTENSSkLTITEGQQEHCGCYTLEVENK 79

                          90
                  ....*....|..
gi 119609534  350 RGVDEASADLVV 361
Cdd:cd05762    80 LGSRQAQVNLTV 91

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: 40.19 E-value: 8.45e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  281 TVIDGMSVVLACE-TSGAPRPAITWQKGERilasgsvQLPRFTPLE--------SGSLLISPTHISDAGTYTCLATNSRG 351
Cdd:cd05750    10 TVQEGSKLVLKCEaTSENPSPRYRWFKDGK-------ELNRKRPKNikirnkkkNSELQINKAKLEDSGEYTCVVENILG 82

                          90
                  ....*....|
gi 119609534  352 VDEASADLVV 361
Cdd:cd05750    83 KDTVTGNVTV 92

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 40.07 E-value: 8.75e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 119609534   195 VDIPCQAKGVPPPSITWYKDAAVVevekltrfrqRNDGGLQISGLVPDDTGMFQCFARNAAGeVQTSTYLAVT 267
Cdd:pfam13895   17 VTLTCSAPGNPPPSYTWYKDGSAI----------SSSPNFFTLSVSAEDSGTYTCVARNGRG-GKVSNPVELT 78

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: 40.32 E-value: 9.22e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 119609534  197 IPCQAKGVPPPSITWYKDAAVVEVEKLTRFR-QRNDGGLQISGLVPDDTGMFQCFARNAAG 256
Cdd:cd05736    20 LRCHAEGIPLPRVQWLKNGMDINPKLSKQLTlIANGSELHISNVRYEDTGAYTCIAKNEGG 80

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: 40.15 E-value: 9.33e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  271 PNITRGPLDSTVIDGMSVVLACETSGAPRPAITWQKGERILASGSVQLPRFTPLESGSLLISPTHISDAGTYTCLATNSR 350
Cdd:cd20975     1 PTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGGLCRLRILAAERGDAGFYTCKAVNEY 80

                          90
                  ....*....|.
gi 119609534  351 GVDEASADLVV 361
Cdd:cd20975    81 GARQCEARLEV 91

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

Pssm-ID: 143277 [Multi-domain] Cd Length: 97 Bit Score: 40.35 E-value: 9.76e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  184 ERHITAEMEKVVDIPCQAKGVPPPSITWYKDAAVVEVEKLT---RFRQRND---GGLQISGLVPDDTGMFQCFARNAAGE 257
Cdd:cd05869     9 ENQTAMELEEQITLTCEASGDPIPSITWRTSTRNISSEEKTldgHIVVRSHarvSSLTLKYIQYTDAGEYLCTASNTIGQ 88


                  ....*....
gi 119609534  258 VQTSTYLAV 266
Cdd:cd05869    89 DSQSMYLEV 97

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: 39.75 E-value: 1.19e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534   91 KNTSVVAGTSEVTLECVANARPliKLHIIWKKDGVLLSGG----ISDhNRRLTIPNPTGSDAGYYECEAV 156
Cdd:cd04969     9 KKKILAAKGGDVIIECKPKASP--KPTISWSKGTELLTNSsricILP-DGSLKIKNVTKSDEGKYTCFAV 75

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: 39.68 E-value: 1.21e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  367 ITKPPQDQSVIKGTQASMVCGVTHDPRVTIryIWEKDGATLgTESHPRIRLDRNGsLHISQTWSGDIGTYTCRVISAGGN 446
Cdd:cd20978     4 IQKPEKNVVVKGGQDVTLPCQVTGVPQPKI--TWLHNGKPL-QGPMERATVEDGT-LTIINVQPEDTGYYGCVATNEIGD 79


                  ....*....
gi 119609534  447 DSRSAHLRV 455
Cdd:cd20978    80 IYTETLLHV 88

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: 39.84 E-value: 1.41e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  177 PQFVKEPErHITAEMEKVVDIPCQAKGVPPPSITWYKDAAVVEVEKLTRFRQR------NDGGLQISGLVPDDTGMFQCF 250
Cdd:cd05765     1 PALVNSPT-HQTVKVGETASFHCDVTGRPQPEITWEKQVPGKENLIMRPNHVRgnvvvtNIGQLVIYNAQPQDAGLYTCT 79

                          90
                  ....*....|....*.
gi 119609534  251 ARNAAGEVQTSTYLAV 266
Cdd:cd05765    80 ARNSGGLLRANFPLSV 95

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

Pssm-ID: 409412 Cd Length: 85 Bit Score: 39.46 E-value: 1.54e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  370 PPQDQSVIKGTQASMVC-GVTHDPRVTIRyiWEKDGATLGTESHprirlDRNGSLHISQTWSGDIGTYTC 438
Cdd:cd05754     7 EPRSQEVRPGADVSFICrAKSKSPAYTLV--WTRVNGTLPSRAM-----DFNGILTIRNVQLSDAGTYVC 69

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: 39.49 E-value: 1.57e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534    91 KNTSVVAGTSeVTLEC-VANARPLIklHIIWKKDG--VLLSGGISDHNRR-----LTIPNPTGSDAGYYECEAVLRSSSV 162
Cdd:pfam00047    4 PTVTVLEGDS-ATLTCsASTGSPGP--DVTWSKEGgtLIESLKVKHDNGRttqssLLISNVTKEDAGTYTCVVNNPGGSA 80


                   ....
gi 119609534   163 PSVV 166
Cdd:pfam00047   81 TLST 84

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: 39.44 E-value: 1.88e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  371 PQDQSVIKGTQASMVCGVTHDPRVTIryIWEKDGATLGTEShpRIRLDRNGSLHISQTWSGDIGTYTCRVisagGNDSRS 450
Cdd:cd20957     8 PPVQTVDFGRTAVFNCSVTGNPIHTV--LWMKDGKPLGHSS--RVQILSEDVLVIPSVKREDKGMYQCFV----RNDGDS 79


                  .
gi 119609534  451 A 451
Cdd:cd20957    80 A 80

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: 39.09 E-value: 2.01e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  368 TKPPQDQSVIKGTQASMVCGVTHDPRVTIRyiWEKDGATLGTESHPRIRLDRNG--SLHISQTWSGDIGTYTCRVISAGG 445
Cdd:cd20973     1 IQTLRDKEVVEGSAARFDCKVEGYPDPEVK--WMKDDNPIVESRRFQIDQDEDGlcSLIISDVCGDDSGKYTCKAVNSLG 78

                          90
                  ....*....|
gi 119609534  446 NDSRSAHLRV 455
Cdd:cd20973    79 EATCSAELTV 88

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: 39.56 E-value: 2.46e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  371 PQDQSVIKGTQASMVCGVTHDPRVTIRYI--WEKDGATLGTESHPRIRLDRNGS----------LHISQTWSGDIGTYTC 438
Cdd:cd05858     8 PANTSVVVGTDAEFVCKVYSDAQPHIQWLkhVEKNGSKYGPDGLPYVEVLKTAGvnttdkeievLYLRNVTFEDAGEYTC 87

                          90
                  ....*....|....*..
gi 119609534  439 RVISAGGNDSRSAHLRV 455
Cdd:cd05858    88 LAGNSIGISHHSAWLTV 104

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: 39.14 E-value: 2.53e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 119609534  288 VVLACETSGAPRPAITWQKG--ERILASGSvqlpRFTpLESGSLLIS-PTHISDAGTYTCLATNSRG 351
Cdd:cd05850    23 VTLACRARASPPATYRWKMNgtELKMEPDS----RYR-LVAGNLVISnPVKAKDAGSYQCLASNRRG 84

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 38.53 E-value: 2.84e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 119609534    92 NTSVVAGTSEVTLECVANARPLIKlhIIWKKDGVLLSGgisdhNRRLTIPNPTGSDAGYYECEAVLRSSSVPS 164
Cdd:pfam13895    7 SPTVVTEGEPVTLTCSAPGNPPPS--YTWYKDGSAISS-----SPNFFTLSVSAEDSGTYTCVARNGRGGKVS 72

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: 39.14 E-value: 2.85e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  177 PQFVKEPERHITAEMEKVVDIPCQAKGVPPPSITWYKDAAVVEVEKLTRFRQRNDGGLQISGLVPDDTGMFQCFARNAAG 256
Cdd:cd05760     1 PVVLKHPASAAEIQPSSRVTLRCHIDGHPRPTYQWFRDGTPLSDGQGNYSVSSKERTLTLRSAGPDDSGLYYCCAHNAFG 80


                  ....*
gi 119609534  257 EVQTS 261
Cdd:cd05760    81 SVCSS 85

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: 38.58 E-value: 2.96e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  274 TRGPLDSTVIDGMSVVLACETSGAPRPAITWQKGERILASGSVQLPRFtpLESGSLLISPTHISDAGTYTCLATNSRGVD 353
Cdd:cd04978     3 IIEPPSLVLSPGETGELICEAEGNPQPTITWRLNGVPIEPAPEDMRRT--VDGRTLIFSNLQPNDTAVYQCNASNVHGYL 80


                  ....*...
gi 119609534  354 EASADLVV 361
Cdd:cd04978    81 LANAFLHV 88

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: 39.14 E-value: 3.08e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  270 APNITRGPLDSTVI---DGMSVV-LACETSGAPRPAITWQKGERILasgSVQLPRFTP-------LESGSLLISP-THIS 337
Cdd:cd05773     4 APDLQKGPQLRKVAsrgDGSSDAnLVCQAQGVPRVQFRWAKNGVPL---DLGNPRYEEttehtgtVHTSILTIINvSAAL 80

                          90       100
                  ....*....|....*....|....*..
gi 119609534  338 DAGTYTCLATNSRGVDEASADLVVWAR 364
Cdd:cd05773    81 DYALFTCTAHNSLGEDSLDIQLVSTSR 107

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: 38.60 E-value: 3.34e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  177 PQFVKEPERHITAEMEKVvDIPCQAKGVPPPSITWYKDAAVVEVE-KLTRFRQRNDG--GLQISGLVPDDTGMFQCFARN 253
Cdd:cd05892     1 PMFIQKPQNKKVLEGDPV-RLECQISAIPPPQIFWKKNNEMLQYNtDRISLYQDNCGriCLLIQNANKKDAGWYTVSAVN 79

                          90
                  ....*....|...
gi 119609534  254 AAGEVQTSTYLAV 266
Cdd:cd05892    80 EAGVVSCNARLDV 92

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

Pssm-ID: 409546 [Multi-domain] Cd Length: 96 Bit Score: 38.45 E-value: 3.79e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 119609534  371 PQDQSVIKGTQASMVCGVTHDPRVTIryIWEKD-GATLGT----ESHPRIRLDRNGSLHISQTWSGDIGTYTC 438
Cdd:cd20954     8 PVDANVAAGQDVMLHCQADGFPTPTV--TWKKAtGSTPGEykdlLYDPNVRILPNGTLVFGHVQKENEGHYLC 78

Purple acid Phosphatase, N-terminal domain; This domain is found at the N-terminus of Purple acid phosphatase proteins.

Pssm-ID: 465220 [Multi-domain] Cd Length: 93 Bit Score: 38.54 E-value: 4.18e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534   462 PEHPVATLSTVERrAINLTWTKPFDGNSPLIRYILEMSENNAPWTVLLASVDPKA------TSVTVKGLVPARSYQFRLC 535
Cdd:pfam16656    1 PEQVHLSLTGDST-SMTVSWVTPSAVTSPVVQYGTSSSALTSTATATSSTYTTGDggtgyiHRATLTGLEPGTTYYYRVG 79


                   ....*
gi 119609534   536 AVNDV 540
Cdd:pfam16656   80 DDNGG 84

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: 38.37 E-value: 4.73e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  177 PQFVKEPERHITAE--MEKVVDIPCQAKGVPPPSITWYKDAAVVEVEKLTRFRQRNdGGLQISGLV-PDDTGMFQCFARN 253
Cdd:cd05850     3 PVFEEQPSSTLFPEgsAEEKVTLACRARASPPATYRWKMNGTELKMEPDSRYRLVA-GNLVISNPVkAKDAGSYQCLASN 81


                  ....*
gi 119609534  254 AAGEV 258
Cdd:cd05850    82 RRGTV 86

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: 38.23 E-value: 4.76e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 119609534  199 CQAKGVPPPSITWYKDAAVVeVEKLTRFRQRNDGGLQISGLVPDDTGMFQCFARNAAGEVQTSTYLAV 266
Cdd:cd05764    22 CKARGDPEPAIHWISPEGKL-ISNSSRTLVYDNGTLDILITTVKDTGAFTCIASNPAGEATARVELHI 88

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

Pssm-ID: 409547 Cd Length: 99 Bit Score: 38.54 E-value: 4.78e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  177 PQFVKEPERHITAEMEKVVDIPCQAKGVPPPSITWYKD--AAVVEVEKLTRFrqRNDGGLQISGLVPDD------TGMFQ 248
Cdd:cd20955     2 PVFLKEPTNRIDFSNSTGAEIECKASGNPMPEIIWIRSdgTAVGDVPGLRQI--SSDGKLVFPPFRAEDyrqevhAQVYA 79

                          90
                  ....*....|
gi 119609534  249 CFARNAAGEV 258
Cdd:cd20955    80 CLARNQFGSI 89

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: 38.27 E-value: 5.03e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  184 ERHITAEMEKVVdIPCQAKGVPPPSITWYKDAAVVEVEKLT---RFRQRNDGG---LQISGLVPDDTGMFQCFARNAAGE 257
Cdd:cd05732     9 ENQTAVELEQIT-LTCEAEGDPIPEITWRRATRGISFEEGDldgRIVVRGHARvssLTLKDVQLTDAGRYDCEASNRIGG 87


                  ....*....
gi 119609534  258 VQTSTYLAV 266
Cdd:cd05732    88 DQQSMYLEV 96

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: 37.97 E-value: 5.38e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  183 PERHITAEMEKVVDIPCQAKGVPPPSITWYKDAAVVEVEKLTRfrQRNDGGLQISGLVPDDTGMFQCFARNAAGEVQTST 262
Cdd:cd05876     1 SSSSLVALRGQSLVLECIAEGLPTPTVKWLRPSGPLPPDRVKY--QNHNKTLQLLNVGESDDGEYVCLAENSLGSARHAY 78


                  ....
gi 119609534  263 YLAV 266
Cdd:cd05876    79 YVTV 82

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 38.01 E-value: 5.42e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 119609534    91 KNTSVVAGTSeVTLECVANARPliKLHIIWKKDGVLLSGG------ISDHNRRLTIPNPTGSDAGYYECEAV 156
Cdd:pfam07679    8 KDVEVQEGES-ARFTCTVTGTP--DPEVSWFKDGQPLRSSdrfkvtYEGGTYTLTISNVQPDDSGKYTCVAT 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: 37.75 E-value: 6.46e-03

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  364 RTRITKPPQDQ-SVIKGTQASMVCGVTHDPRVTIRYIWEKDgATLGTESHPRIRLDRNGSLHISQTWSGDIGTYTCRVIS 442
Cdd:cd20969     1 RAAIRDRKAQQvFVDEGHTVQFVCRADGDPPPAILWLSPRK-HLVSAKSNGRLTVFPDGTLEVRYAQVQDNGTYLCIAAN 79

                          90
                  ....*....|...
gi 119609534  443 AGGNDSRSAHLRV 455
Cdd:cd20969    80 AGGNDSMPAHLHV 92

First immunoglobulin (Ig)-like domain of carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM); The members here are composed of the immunoglobulin (Ig)-like domain 1 in carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) proteins. 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: 409430 Cd Length: 105 Bit Score: 38.02 E-value: 7.62e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 119609534  387 GVTHDPRVTI-RYIWEKDGATLGTESHPRIRLDRNGSLHISQTWSGDIGTYTCRVISAGGNDSR-SAHLRV 455
Cdd:cd05774    35 GKTVSPNFLIaSYIISTNSSTPGPAYSGRETIYPNGSLLIQNVTQKDTGFYTLQTITADLQTEQaSVHLQV 105

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: 37.61 E-value: 8.57e-03

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 119609534  366 RITKPPQDQSVIKGTQASMVCGVTHDPRVTIRYIWEKDGatlgTESHPRIRLDRNGSLHISQTWSGDIGTYTC 438
Cdd:cd20968     1 KITRPPTNVTIIEGLKAVLPCTTMGNPKPSVSWIKGDDL----IKENNRIAVLESGSLRIHNVQKEDAGQYRC 69

Second Ig-like domain of Junctional adhesion molecule-1 (JAM1); a member of the I-set of IgSF domains; The members here are composed of the second Ig-like domain of Junctional adhesion molecule-1 (JAM1). JAM1 is an immunoglobulin superfamily (IgSF) protein with two Ig-like domains in its extracellular region; it plays a role in the formation of endothelial and epithelial tight junction and acts as a receptor for mammalian reovirus sigma-1. The IgSF is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The second Ig-like domain of JAM1 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, the A strand of the I-set is discontinuous but lacks a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.

Pssm-ID: 409542 Cd Length: 97 Bit Score: 37.68 E-value: 9.63e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 119609534  203 GVPPPSITWYKDAAVVEVE-KLTRFRQRND-------GGLQISGLVPDDTGMFQCFARNAAGEVQTS 261
Cdd:cd20950    24 GSPPSEYTWFKDGVVMPTNpKSTRAFSNSSysldpttGELVFDPLSASDTGEYSCEARNGYGTPMRS 90

Second immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3, 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 of Kirrel (kin of irregular chiasm-like) 3 (also known as Neph2). This protein has five Ig-like domains, one transmembrane domain, and a cytoplasmic tail. Included in this group is mammalian Kirrel (Neph1), Kirrel2 (Neph3), and Drosophila RST (irregular chiasm C-roughest) protein. These proteins contain multiple Ig domains, have properties of cell adhesion molecules, and are important in organ development.

Pssm-ID: 409416 Cd Length: 98 Bit Score: 37.43 E-value: 9.84e-03

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  281 TVIDGMSVV---------LACETSGA-PRPAITWQKGERIL--ASGSVQLPRFTPLES--GSLLISPTHISDAGTYTCLA 346
Cdd:cd05759     2 PVIEGGPVIslqagvpynLTCRARGAkPAAEIIWFRDGEQLegAVYSKELLKDGKRETtvSTLLITPSDLDTGRTFTCRA 81


                  ..
gi 119609534  347 TN 348
Cdd:cd05759    82 RN 83

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: 37.20 E-value: 9.88e-03

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119609534  282 VIDGMSVVLACETSGAPRPAITWQKGERILASGSVQLPRFtpleSGSLLISPTHISDAGTYTCLATNSRG 351
Cdd:cd05876     7 ALRGQSLVLECIAEGLPTPTVKWLRPSGPLPPDRVKYQNH----NKTLQLLNVGESDDGEYVCLAENSLG 72