NCBI Conserved Domain Search

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 71.90 E-value: 4.73e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623   881 GERGRLPCRAQGSPKPQFIWRQDKKDLPINRTYKYEVEErkidsltYESTLIVDKVAPADYGAYECVARNELGEAVETVR 960
Cdd:pfam07679   15 GESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEG-------GTYTLTISNVQPDDSGKYTCVATNSAGEAEASAE 87


                   ...
gi 665399623   961 LEI 963
Cdd:pfam07679   88 LTV 90

Second immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 - Necl-4; member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 (also known as cell adhesion molecule 3 or CADM3), Necl-2 (also known as CADM1), Necl-3 (also known as CADM2) and Necl-4 (also known as CADM4). These nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. The N-terminal Ig-like domain of the extracellular region belongs to the V-type subfamily of Ig domains, is essential to cell-cell adhesion, and plays a part in the interaction with the envelope glycoprotein D of various viruses. Necl-1 and Necl-2 have Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is specifically expressed in neural tissue and is important to the formation of synapses, axon bundles, and myelinated axons. Necl-2 is expressed in a wide variety of tissues, and is a putative tumour suppressor gene, which is downregulated in aggressive neuroblastoma. Necl-3 has been shown to accumulate in tissues of the central and peripheral nervous system, where it is expressed in ependymal cells and myelinated axons. It is observed at the interface between the axon shaft and the myelin sheath. Necl-4 is expressed on Schwann cells, and plays a key part in initiating peripheral nervous system (PNS) myelination. Necl-4 participates in cell-cell adhesion and is proposed to play a role in tumor suppression.

Pssm-ID: 409418 Cd Length: 102 Bit Score: 68.99 E-value: 6.39e-14

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  173 PPASIEIKGYshnsKVEVRENQDLQLKCIVANAKPAAQIVWYRGNVEYKpeKREDTVEESTAKRFTTTSSLKLKPGPDDD 252
Cdd:cd05761     3 VPEKPVITGF----TSPVVEGDEITLTCTTSGSKPAADIRWFKNDKELK--GVKEVQESGAGKTFTVTSTLRFRVDRDDD 76

                          90       100
                  ....*....|....*....|....*..
gi 665399623  253 YTEYTCQARHKALsPDMPMRATVQLSV 279
Cdd:cd05761    77 GVAVICRVDHESL-TSTPKQTQQVLEV 102

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 68.44 E-value: 7.89e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623   678 PKFVPPPSSTAVGvEGESLQVSLQTRANPTPvTYKWTKDGTTIPQDGDHRIFADGG--SLNFTRLHRDDAGIYSCSASNS 755
Cdd:pfam07679    1 PKFTQKPKDVEVQ-EGESARFTCTVTGTPDP-EVSWFKDGQPLRSSDRFKVTYEGGtyTLTISNVQPDDSGKYTCVATNS 78

                           90
                   ....*....|..
gi 665399623   756 QGGATLNITVVV 767
Cdd:pfam07679   79 AGEAEASAELTV 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: 63.67 E-value: 4.19e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  967 PDPPLSLNILNVTHDTVTLAWT-PGFDGGLKASYRVRYRMADREQYKYID-GLPNSHKLTIGGLRMNTLYLFSVMSWNEL 1044
Cdd:cd00063     1 PSPPTNLRVTDVTSTSVTLSWTpPEDDGGPITGYVVEYREKGSGDWKEVEvTPGSETSYTLTGLKPGTEYEFRVRAVNGG 80


                  ....*..
gi 665399623 1045 GQSSYLP 1051
Cdd:cd00063    81 GESPPSE 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: 62.63 E-value: 6.44e-12

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623    967 PDPPLSLNILNVTHDTVTLAWTPGFDGGLKaSYRVRYRMADRE---QYKYIDGLPNSHKLTIGGLRMNTLYLFSVMSWNE 1043
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTLSWEPPPDDGIT-GYIVGYRVEYREegsEWKEVNVTPSSTSYTLTGLKPGTEYEFRVRAVNG 79


                    ....
gi 665399623   1044 LGQS 1047
Cdd:smart00060   80 AGEG 83

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 61.81 E-value: 1.24e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623   677 RPKFVPPPSSTAVgVEGESLQVSLQTRANPTPvTYKWTKDGTTIP--QDGDHRIFADGGSLNFTRLHRDDAGIYSCSASN 754
Cdd:pfam13927    1 KPVITVSPSSVTV-REGETVTLTCEATGSPPP-TITWYKNGEPISsgSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

Second immunoglobulin (Ig)-like domain of nectin-like molcule-1 (Necl-1); member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of nectin-like molcule-1 (Necl-1; also known as cell adhesion molecule3 (CADM3)). These nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. The N-terminal Ig-like domain of the extracellular region belongs to the V-type subfamily of Ig domains is essential to cell-cell adhesion and plays a part in the interaction with the envelope glycoprotein D of various viruses. Necl-1 and Necl-2 have Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is specifically expressed in neural tissue and is important to the formation of synapses, axon bundles, and myelinated axons. Necl-2 is expressed in a wide variety of tissues and is a putative tumour suppressor gene which is downregulated in aggressive neuroblastoma. Ig domains are likely to participate in ligand binding and recognition.

Pssm-ID: 409502 Cd Length: 103 Bit Score: 61.14 E-value: 4.43e-11

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  174 PASIEIKGYshnsKVEVRENQDLQLKCIVANAKPAAQIVWYRGNVEYKPEKREdTVEESTAKRFTTTSSLKLKPGPDDDY 253
Cdd:cd07705     4 PQKPQITGY----ESAFKEKDKAKLRCTSSGSKPAANIKWRKGDQELEGAPTS-VQEDGNGKTFTVSSSVEFQVTREDDG 78

                          90
                  ....*....|..
gi 665399623  254 TEYTCQARHKAL 265
Cdd:cd07705    79 AEITCSVGHESL 90

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 60.27 E-value: 4.83e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623   865 PEIAKTPTLLRAASGtgERGRLPCRAQGSPKPQFIWRQDKKDLPINRTykyeveeRKIDSLTYESTLIVDKVAPADYGAY 944
Cdd:pfam13927    2 PVITVSPSSVTVREG--ETVTLTCEATGSPPPTITWYKNGEPISSGST-------RSRSLSGSNSTLTISNVTRSDAGTY 72


                   ....*.
gi 665399623   945 ECVARN 950
Cdd:pfam13927   73 TCVASN 78

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: 59.65 E-value: 5.59e-11

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 665399623  885 RLPCRAQGSPKPQFIWRQDKKDLPINRTYKYEVEerkidslTYESTLIVDKVAPADYGAYECVARNELGEAVET 958
Cdd:cd00096     2 TLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSE-------LGNGTLTISNVTLEDSGTYTCVASNSAGGSASA 68

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: 59.44 E-value: 1.14e-10

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623    881 GERGRLPCRAQGSPKPQFIWRQDKKDLPINRTYKyeveerKIDSLTYESTLIVDKVAPADYGAYECVARNELGEAVETVR 960
Cdd:smart00410    9 GESVTLSCEASGSPPPEVTWYKQGGKLLAESGRF------SVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGTT 82


                    ...
gi 665399623    961 LEI 963
Cdd:smart00410   83 LTV 85

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

Pssm-ID: 400489 Cd Length: 89 Bit Score: 58.58 E-value: 1.98e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623   584 IEPEELR---PGMEATIICDSSSSNPPAKLSWWKDGIPIEGINNTSKPGLWGGTVSTL-EFRVNVTQEMNGQVYTCQSAN 659
Cdd:pfam08205    3 IEPPASLlegEGPEVVATCSSAGGKPAPRITWYLDGKPLEAAETSSEQDPESGLVTVTsELKLVPSRSDHGQSLTCQVSY 82


                   ....*..
gi 665399623   660 EALQRSA 666
Cdd:pfam08205   83 GALRGSI 89

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

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 57.61 E-value: 4.44e-10

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 665399623  693 GESLQVSLQTRANPTPvTYKWTKDGTTIPQDGdhRIFADGGSLNFTRLHRDDAGIYSCSASNSQG 757
Cdd:cd05728    14 GSSLRWECKASGNPRP-AYRWLKNGQPLASEN--RIEVEAGDLRITKLSLSDSGMYQCVAENKHG 75

Second immunoglobulin (Ig)-like domain of nectin-like molecule-3 (Necl-3); member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of nectin-like molecule-3 (Necl-3; also known as cell adhesion molecule 2 (CADM2)). Nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. Necl-3 has been shown to accumulate in tissues of the central and peripheral nervous system where it is expressed in ependymal cells and myelinated axons. It is observed at the interface between the axon shaft and the myelin sheath. Ig domains are likely to participate in ligand binding and recognition.

Pssm-ID: 409467 Cd Length: 104 Bit Score: 58.02 E-value: 5.28e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  170 VISPPASIEIKGYSHnskvEVRENQDLQLKCIVANAKPAAQIVWYRGNVEYKPEKrEDTVEESTAKRFTTTSSLKLKPGP 249
Cdd:cd05884     1 VLGVPEKPQISGFTS----PVMEGDHIQLTCKTSGSKPAADIRWFKNDKEVKDVK-YLKAEDANRKTFTVSSSLDFHVDR 75

                          90
                  ....*....|....*..
gi 665399623  250 DDDYTEYTCQARHKALS 266
Cdd:cd05884    76 DDDGVAITCRVDHESLT 92

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

Pssm-ID: 143223 Cd Length: 69 Bit Score: 55.65 E-value: 1.35e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 665399623  885 RLPCRAQGSPKPQFIWRQDkkDLPINRTYKYEVEErkidsltyESTLIVDKVAPADYGAYECVARNELGEA 955
Cdd:cd05746     2 QIPCSAQGDPEPTITWNKD--GVQVTESGKFHISP--------EGYLAIRDVGVADQGRYECVARNTIGYA 62

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: 55.97 E-value: 1.57e-09

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623    685 SSTAVGVEGESLQVSLQTRANPTPvTYKWTKDG-TTIPQDGDHRIFADGG--SLNFTRLHRDDAGIYSCSASNSQGGATL 761
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPP-EVTWYKQGgKLLAESGRFSVSRSGStsTLTISNVTPEDSGTYTCAATNSSGSASS 79


                    ....*.
gi 665399623    762 NITVVV 767
Cdd:smart00410   80 GTTLTV 85

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

Pssm-ID: 409393 [Multi-domain] Cd Length: 95 Bit Score: 56.46 E-value: 1.66e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  885 RLPCRAQGSPKPQFIWRQDKKDL-PINRTYKYEVEERKIdsltyesTLIVDKVAPADYGAYECVARNELGEAVETVRLEI 963
Cdd:cd05729    23 RLECGAGGNPMPNITWLKDGKEFkKEHRIGGTKVEEKGW-------SLIIERAIPRDKGKYTCIVENEYGSINHTYDVDV 95

Second immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 - Necl-4; member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 (also known as cell adhesion molecule 3 or CADM3), Necl-2 (also known as CADM1), Necl-3 (also known as CADM2) and Necl-4 (also known as CADM4). These nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. The N-terminal Ig-like domain of the extracellular region belongs to the V-type subfamily of Ig domains, is essential to cell-cell adhesion, and plays a part in the interaction with the envelope glycoprotein D of various viruses. Necl-1 and Necl-2 have Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is specifically expressed in neural tissue and is important to the formation of synapses, axon bundles, and myelinated axons. Necl-2 is expressed in a wide variety of tissues, and is a putative tumour suppressor gene, which is downregulated in aggressive neuroblastoma. Necl-3 has been shown to accumulate in tissues of the central and peripheral nervous system, where it is expressed in ependymal cells and myelinated axons. It is observed at the interface between the axon shaft and the myelin sheath. Necl-4 is expressed on Schwann cells, and plays a key part in initiating peripheral nervous system (PNS) myelination. Necl-4 participates in cell-cell adhesion and is proposed to play a role in tumor suppression.

Pssm-ID: 409418 Cd Length: 102 Bit Score: 56.28 E-value: 1.86e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  477 LYPPAPPLISGYmEGQIIPAGSVQkLLCVSSGGNPLATLTWYKNDKRINSV--IRAADK----SVSAEITILANVSDNQA 550
Cdd:cd05761     1 LGVPEKPVITGF-TSPVVEGDEIT-LTCTTSGSKPAADIRWFKNDKELKGVkeVQESGAgktfTVTSTLRFRVDRDDDGV 78

                          90
                  ....*....|
gi 665399623  551 QYRCEASNSA 560
Cdd:cd05761    79 AVICRVDHES 88

Second immunoglobulin (Ig)-like domain of nectin-like molecule 2 (Necl-2); member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of nectin-like molecule 2 (Necl-2; also known as cell adhesion molecule 1 (CADM1)). Nectin-like molecules (Necls) have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. Necl-2 has Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is expressed in a wide variety of tissues and is a putative tumour suppressor gene which is downregulated in aggressive neuroblastoma. Ig domains are likely to participate in ligand binding and recognition.

Pssm-ID: 409466 Cd Length: 99 Bit Score: 56.08 E-value: 1.97e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  184 HNSKVEVR-----ENQDLQLKCIVANAKPAAQIVWYRGNVEYKPEKredTVEESTAKRFTTTSSLKLKPGPDDDYTEYTC 258
Cdd:cd05883     5 RNLVIDIQkdtavEGEEIELNCTAMASKPAATIRWFKGNKELTGKS---EVEEWYSRMFTVTSQLMLKVTKEDDGVPVIC 81


                  ....*.
gi 665399623  259 QARHKA 264
Cdd:cd05883    82 LVDHPA 87

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 55.26 E-value: 2.20e-09

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 665399623   772 TIKSVSENIVVNPGEDAMLSCTVEGKPltEEHVKWERVGYDM--TVKTSTTFANGTSYLHIKDAKREDVGNFRCVADN 847
Cdd:pfam13927    3 VITVSPSSVTVREGETVTLTCEATGSP--PPTITWYKNGEPIssGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 55.73 E-value: 2.29e-09

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 665399623   776 VSENIVVNPGEDAMLSCTVEGKPltEEHVKWERVGYDMTV--KTSTTFANGTSYLHIKDAKREDVGNFRCVADNRV 849
Cdd:pfam07679    6 KPKDVEVQEGESARFTCTVTGTP--DPEVSWFKDGQPLRSsdRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSA 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: 55.66 E-value: 2.60e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  870 TPTLLRAASGTGERGRLPCRAQGSPKPQFIWRQDKKDLPINRTYKYEVEErkidslTYESTLIVDKVAPADYGAYECVAR 949
Cdd:cd20973     1 IQTLRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQDE------DGLCSLIISDVCGDDSGKYTCKAV 74

                          90
                  ....*....|....
gi 665399623  950 NELGEAVETVRLEI 963
Cdd:cd20973    75 NSLGEATCSAELTV 88

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: 55.32 E-value: 2.95e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  869 KTPTLLRAASGTgeRGRLPCRAQGSPKPQFIWRQD-KKDLPINRtykyeveERKIDSLTYESTLIVDKVAPADYGAYECV 947
Cdd:cd05763     4 KTPHDITIRAGS--TARLECAATGHPTPQIAWQKDgGTDFPAAR-------ERRMHVMPEDDVFFIVDVKIEDTGVYSCT 74

                          90
                  ....*....|....*.
gi 665399623  948 ARNELGEAVETVRLEI 963
Cdd:cd05763    75 AQNSAGSISANATLTV 90

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

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 55.20 E-value: 3.51e-09

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 665399623    777 SENIVVNPGEDAMLSCTVEGKPltEEHVKWERVGYDM---TVKTSTTFANGTSYLHIKDAKREDVGNFRCVADN 847
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSP--PPEVTWYKQGGKLlaeSGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATN 72

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: 54.95 E-value: 4.96e-09

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 665399623  773 IKSVSENIVVNPGEDAMLSCTVEGKPLTEehVKWERVGYDMTVKTSTTFAN-GTSYLHIKDAKREDVGNFRCVADNRV 849
Cdd:cd20976     4 FSSVPKDLEAVEGQDFVAQCSARGKPVPR--ITWIRNAQPLQYAADRSTCEaGVGELHIQDVLPEDHGTYTCLAKNAA 79

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 54.19 E-value: 6.70e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623    73 KFRTTPHDLQVLEGAEAMMRCEVAnvaGA----VQWTKDGfalgfsAVIPGFPRYSVlgDRKQGIYNLRISNASINDDAD 148
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVT---GTpdpeVSWFKDG------QPLRSSDRFKV--TYEGGTYTLTISNVQPDDSGK 70

                           90       100
                   ....*....|....*....|....
gi 665399623   149 YQCQVgparLNSA--IRANAKLTV 170
Cdd:pfam07679   71 YTCVA----TNSAgeAEASAELTV 90

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: 53.49 E-value: 8.93e-09

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 665399623  701 QTRANPTPvTYKWTKDGTTIPQDGDHRIF--ADGGSLNFTRLHRDDAGIYSCSASNSQGGAT 760
Cdd:cd00096     6 SASGNPPP-TITWYKNGKPLPPSSRDSRRseLGNGTLTISNVTLEDSGTYTCVASNSAGGSA 66

Immunoglobulin Constant-1 (C1)-set domain; The members here are composed of C1-set domains, classical Ig-like domains resembling the antibody constant domain. Members of the IgC1 family are components of immunoglobulin, T-cell receptors, CD1 cell surface glycoproteins, secretory glycoproteins A/C, and major histocompatibility complex (MHC) class I/II molecules. In immunoglobulins, each chain is composed of one variable domain (IgV) and one or more IgC domains. These names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. The IgV domain is responsible for antigen binding, while the IgC domain is involved in oligomerization and molecular interactions. 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 strands by G, F, C, and C'.

Pssm-ID: 409354 Cd Length: 95 Bit Score: 54.00 E-value: 1.21e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  186 SKVEVRENQDLQLKCIVANAKPA-AQIVWYRGNVEYKPEKREDTVEESTAKRFTTTSSLKLKPGPDDDYTEYTCQARHKA 264
Cdd:cd00098     7 PSPEEKGGGKVTLVCLVSGFYPKdITVTWLKNGVPLTSGVSTSSPVEPNDGTYSVTSSLTVPPSDWDEGATYTCVVTHES 86


                  ...
gi 665399623  265 LSP 267
Cdd:cd00098    87 LKS 89

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

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 53.71 E-value: 1.34e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  678 PKFVPPPSSTAVGVeGESLQVSLQTRANPTPvTYKWTKDGTTIPQDGD----HRIFADGGSLNF-----TRLHRDDAGIY 748
Cdd:cd07693     1 PRIVEHPSDLIVSK-GDPATLNCKAEGRPTP-TIQWLKNGQPLETDKDdprsHRIVLPSGSLFFlrvvhGRKGRSDEGVY 78

                          90
                  ....*....|..
gi 665399623  749 SCSASNSQGGAT 760
Cdd:cd07693    79 VCVAHNSLGEAV 90

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 53.19 E-value: 1.42e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 665399623   968 DPPLSLNILNVTHDTVTLAWTPGFDGGLK-ASYRVRYRMADREQY-KYIDGLPNSHKLTIGGLRMNTLYLFSV 1038
Cdd:pfam00041    1 SAPSNLTVTDVTSTSLTVSWTPPPDGNGPiTGYEVEYRPKNSGEPwNEITVPGTTTSVTLTGLKPGTEYEVRV 73

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: 54.17 E-value: 1.43e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  861 VKFAPEIAKTPTLLR-AASGTGER-GRLPCRAQGSPKPQFIWRqdKKDLPINRTYKYEVEERKIDSLTYESTLIVDKVAP 938
Cdd:cd05773     1 VRFAPDLQKGPQLRKvASRGDGSSdANLVCQAQGVPRVQFRWA--KNGVPLDLGNPRYEETTEHTGTVHTSILTIINVSA 78

                          90       100       110
                  ....*....|....*....|....*....|.
gi 665399623  939 A-DYGAYECVARNELGEAVETVRLEITSQPD 968
Cdd:cd05773    79 AlDYALFTCTAHNSLGEDSLDIQLVSTSRPD 109

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

Pssm-ID: 400489 Cd Length: 89 Bit Score: 53.19 E-value: 1.71e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623   188 VEVRENQDLQ--LKCIVANAKPAAQIVWYRGNVEYKPEkrEDTVEESTA-KRFTTTSSLKLKPGPDDDYTEYTCQARHKA 264
Cdd:pfam08205    7 ASLLEGEGPEvvATCSSAGGKPAPRITWYLDGKPLEAA--ETSSEQDPEsGLVTVTSELKLVPSRSDHGQSLTCQVSYGA 84


                   ..
gi 665399623   265 LS 266
Cdd:pfam08205   85 LR 86

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

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 52.78 E-value: 2.02e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  865 PEIAKTPTLLRAASGtGERGRLPCRAQGSPKPQFIWRQDKKdlpinrtykyEVEERKIDSLTYESTLIVDKVAPADYGAY 944
Cdd:cd20978     1 PKFIQKPEKNVVVKG-GQDVTLPCQVTGVPQPKITWLHNGK----------PLQGPMERATVEDGTLTIINVQPEDTGYY 69

                          90
                  ....*....|....*....
gi 665399623  945 ECVARNELGEAVETVRLEI 963
Cdd:cd20978    70 GCVATNEIGDIYTETLLHV 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: 52.97 E-value: 2.07e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  678 PKFVPPPSSTAVGvEGESLQVSLQTRANPTPVTyKWTKDGTTIPQDGDHRIFADGG--SLNFTRLHRDDAGIYSCSASNS 755
Cdd:cd20972     2 PQFIQKLRSQEVA-EGSKVRLECRVTGNPTPVV-RWFCEGKELQNSPDIQIHQEGDlhSLIIAEAFEEDTGRYSCLATNS 79

                          90
                  ....*....|..
gi 665399623  756 QGGATLNITVVV 767
Cdd:cd20972    80 VGSDTTSAEIFV 91

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

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 52.84 E-value: 2.57e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  875 RAASGTGERGRLPCRAQGSPKPQFIWRQDKKDLPINRTYKYEVEERKidsltyesTLIVDKVAPADYGAYECVARNELGE 954
Cdd:cd04978     8 SLVLSPGETGELICEAEGNPQPTITWRLNGVPIEPAPEDMRRTVDGR--------TLIFSNLQPNDTAVYQCNASNVHGY 79


                  ..
gi 665399623  955 AV 956
Cdd:cd04978    80 LL 81

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: 52.12 E-value: 3.65e-08

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623     78 PHDLQVLEGAEAMMRCEVANVAGA-VQWTKDGFALgfsavIPGFPRYSVlgDRKQGIYNLRISNASINDDADYQCQVGPA 156
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPeVTWYKQGGKL-----LAESGRFSV--SRSGSTSTLTISNVTPEDSGTYTCAATNS 73

                            90
                    ....*....|....
gi 665399623    157 RLNsaIRANAKLTV 170
Cdd:smart00410   74 SGS--ASSGTTLTV 85

Second immunoglobulin (Ig)-like domain of nectin-like molecule-3 (Necl-3); member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of nectin-like molecule-3 (Necl-3; also known as cell adhesion molecule 2 (CADM2)). Nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. Necl-3 has been shown to accumulate in tissues of the central and peripheral nervous system where it is expressed in ependymal cells and myelinated axons. It is observed at the interface between the axon shaft and the myelin sheath. Ig domains are likely to participate in ligand binding and recognition.

Pssm-ID: 409467 Cd Length: 104 Bit Score: 52.62 E-value: 4.10e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  476 VLYPPAPPLISGY----MEGQIIpagsvqKLLCVSSGGNPLATLTWYKNDKRINSV--IRAADK-----SVSAEITILAN 544
Cdd:cd05884     1 VLGVPEKPQISGFtspvMEGDHI------QLTCKTSGSKPAADIRWFKNDKEVKDVkyLKAEDAnrktfTVSSSLDFHVD 74

                          90       100
                  ....*....|....*....|...
gi 665399623  545 VSDNQAQYRC----EASNSATEI 563
Cdd:cd05884    75 RDDDGVAITCrvdhESLTATPQI 97

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: 51.63 E-value: 4.68e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  881 GERGRLPCRAQGSPKPQFIWRQDKKDLPINRtykYEVEERKidsltyesTLIVDKVAPADYGAYECVARNELGEAVETVR 960
Cdd:cd05725    12 DDSAEFQCEVGGDPVPTVRWRKEDGELPKGR---YEILDDH--------SLKIRKVTAGDMGSYTCVAENMVGKIEASAT 80


                  .
gi 665399623  961 L 961
Cdd:cd05725    81 L 81

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: 51.74 E-value: 5.49e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  681 VPPPSSTAVGVEGESLQVSLQTRANPTPvTYKWTKDGTTIPQ-DGDHRIFADGGSLNFTRLHRDDAGIYSCSASNSQGGA 759
Cdd:cd20970     5 TPQPSFTVTAREGENATFMCRAEGSPEP-EISWTRNGNLIIEfNTRYIVRENGTTLTIRNIRRSDMGIYLCIASNGVPGS 83

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: 51.68 E-value: 6.95e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  196 LQLKCIVANAKPAAQIVWYRgnveyKPEKREDTVEEST----AKRFTTTSSLKLKPGPDDDYTEYTCQARHKALspdmPM 271
Cdd:cd05759    18 YNLTCRARGAKPAAEIIWFR-----DGEQLEGAVYSKEllkdGKRETTVSTLLITPSDLDTGRTFTCRARNEAI----PN 88

                          90
                  ....*....|
gi 665399623  272 --RATVQLSV 279
Cdd:cd05759    89 gkETSITLDV 98

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

Pssm-ID: 409394 [Multi-domain] Cd Length: 83 Bit Score: 50.87 E-value: 8.75e-08

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 665399623  886 LPCRAQGSPKPQFIWRQDKKDLPINRTYKYEveerkidsltYESTLIVDKVAPADYGAYECVARNELGEAVET--VRLE 962
Cdd:cd05731    15 LECIAEGLPTPDIRWIKLGGELPKGRTKFEN----------FNKTLKIENVSEADSGEYQCTASNTMGSARHTisVTVE 83

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: 51.30 E-value: 1.05e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  589 LRPGMEATIICDSSSSNPPAKLSWWKDGIPIEGINNTS---KPGLWGGTVSTLEfrVNVTQEMNGQVYTCQSANEALQRS 665
Cdd:cd05759    12 LQAGVPYNLTCRARGAKPAAEIIWFRDGEQLEGAVYSKellKDGKRETTVSTLL--ITPSDLDTGRTFTCRARNEAIPNG 89


                  ....*....
gi 665399623  666 AHEAVSLDV 674
Cdd:cd05759    90 KETSITLDV 98

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

Pssm-ID: 143207 [Multi-domain] Cd Length: 95 Bit Score: 51.09 E-value: 1.05e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  865 PEIAKTPTLLRAASGTGERGRLPCRAQGSPKPQFIWRQDKKdlPInrtykyEVEERKIdSLTYE-STLIVDKVAPADYGA 943
Cdd:cd05730     2 PTIRARQSEVNATANLGQSVTLACDADGFPEPTMTWTKDGE--PI------ESGEEKY-SFNEDgSEMTILDVDKLDEAE 72

                          90       100
                  ....*....|....*....|...
gi 665399623  944 YECVARNELGEAVETVRLEITSQ 966
Cdd:cd05730    73 YTCIAENKAGEQEAEIHLKVFAK 95

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: 50.57 E-value: 1.24e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  684 PSSTAVGVEGESLqVSLQTRANPTPvTYKWTKDGTTIPQDGDHRIFADGGSLNFTRLHRDDAGIYSCSASNSQGGATLNI 763
Cdd:cd20952     6 PQNQTVAVGGTVV-LNCQATGEPVP-TISWLKDGVPLLGKDERITTLENGSLQIKGAEKSDTGEYTCVALNLSGEATWSA 83


                  ....
gi 665399623  764 TVVV 767
Cdd:cd20952    84 VLDV 87

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: 50.71 E-value: 1.28e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  864 APEIAKTPTLLRAASGTGerGRLPCRAQGSPKPQFIWRQDKKDLpinrtyKYEVEERKIDSLTYEstLIVDKVAPADYGA 943
Cdd:cd20976     1 APSFSSVPKDLEAVEGQD--FVAQCSARGKPVPRITWIRNAQPL------QYAADRSTCEAGVGE--LHIQDVLPEDHGT 70

                          90       100
                  ....*....|....*....|
gi 665399623  944 YECVARNELGEAVETVRLEI 963
Cdd:cd20976    71 YTCLAKNAAGQVSCSAWVTV 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: 50.48 E-value: 1.50e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 665399623  684 PSSTAVGVeGESLQVSLQT-RANPTPvTYKWTKDGTTIPQDGDHRIFADGGSLNFTRLHRDDAGIYSCSASNSQG 757
Cdd:cd05724     4 PSDTQVAV-GEMAVLECSPpRGHPEP-TVSWRKDGQPLNLDNERVRIVDDGNLLIAEARKSDEGTYKCVATNMVG 76

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: 50.19 E-value: 1.85e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  678 PKFVPPPSSTAVgVEGESLQVSLQTRANPTPVTYkWTKDGTTIPQDGDHRIFADGG---SLNFTRLHRDDAGIYSCSASN 754
Cdd:cd05744     1 PHFLQAPGDLEV-QEGRLCRFDCKVSGLPTPDLF-WQLNGKPVRPDSAHKMLVRENgrhSLIIEPVTKRDAGIYTCIARN 78

                          90
                  ....*....|...
gi 665399623  755 SQGGATLNITVVV 767
Cdd:cd05744    79 RAGENSFNAELVV 91

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

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 50.19 E-value: 2.29e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  881 GERGRLPCRAQGSPKPQFIWRQDKKDLPINRTYKYEVEErkidslTYESTLIVDKVAPADYGAYECVARNELGEAVETVR 960
Cdd:cd05744    15 GRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVRE------NGRHSLIIEPVTKRDAGIYTCIARNRAGENSFNAE 88


                  ...
gi 665399623  961 LEI 963
Cdd:cd05744    89 LVV 91

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

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 49.57 E-value: 3.21e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 665399623  784 PGEDAMLSCTVEGKPLTEehVKWERVGYDMTVKTS---TTFANGTSyLHIKDAKREDVGNFRCVADNRVDnpTNRDI 857
Cdd:cd05736    14 PGVEASLRCHAEGIPLPR--VQWLKNGMDINPKLSkqlTLIANGSE-LHISNVRYEDTGAYTCIAKNEGG--VDEDI 85

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

Pssm-ID: 409387 Cd Length: 97 Bit Score: 49.78 E-value: 3.45e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  680 FVPPPSStAVGVEGESLQVSLQTRANPTPVTyKWTKDGTTIPQDGDHR--IFADGGSL--NF--TRLHRDDAGIYSCSAS 753
Cdd:cd05722     4 FLSEPSD-IVAMRGGPVVLNCSAESDPPPKI-EWKKDGVLLNLVSDERrqQLPNGSLLitSVvhSKHNKPDEGFYQCVAQ 81

                          90
                  ....*....|.
gi 665399623  754 NSQGGATLNIT 764
Cdd:cd05722    82 NESLGSIVSRT 92

Second immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 - Necl-4; member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 (also known as cell adhesion molecule 3 or CADM3), Necl-2 (also known as CADM1), Necl-3 (also known as CADM2) and Necl-4 (also known as CADM4). These nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. The N-terminal Ig-like domain of the extracellular region belongs to the V-type subfamily of Ig domains, is essential to cell-cell adhesion, and plays a part in the interaction with the envelope glycoprotein D of various viruses. Necl-1 and Necl-2 have Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is specifically expressed in neural tissue and is important to the formation of synapses, axon bundles, and myelinated axons. Necl-2 is expressed in a wide variety of tissues, and is a putative tumour suppressor gene, which is downregulated in aggressive neuroblastoma. Necl-3 has been shown to accumulate in tissues of the central and peripheral nervous system, where it is expressed in ependymal cells and myelinated axons. It is observed at the interface between the axon shaft and the myelin sheath. Necl-4 is expressed on Schwann cells, and plays a key part in initiating peripheral nervous system (PNS) myelination. Necl-4 participates in cell-cell adhesion and is proposed to play a role in tumor suppression.

Pssm-ID: 409418 Cd Length: 102 Bit Score: 49.73 E-value: 3.75e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  576 APETVKIRIEPEELRPGMEATIICDSSSSNPPAKLSWWKDGIPIEG---INNTSKPGLWggTV-STLEFRVNvtQEMNGQ 651
Cdd:cd05761     3 VPEKPVITGFTSPVVEGDEITLTCTTSGSKPAADIRWFKNDKELKGvkeVQESGAGKTF--TVtSTLRFRVD--RDDDGV 78

                          90
                  ....*....|.
gi 665399623  652 VYTCQSANEAL 662
Cdd:cd05761    79 AVICRVDHESL 89

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: 49.43 E-value: 3.98e-07

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 665399623  881 GERGRLPCRAQGSPKPQFIWRQDKKdLPINRTYKYEVEERKidsltyeSTLIVDKVAPADYGAYECVARNELGEAVE 957
Cdd:cd20970    17 GENATFMCRAEGSPEPEISWTRNGN-LIIEFNTRYIVRENG-------TTLTIRNIRRSDMGIYLCIASNGVPGSVE 85

Second immunoglobulin (Ig) domain of Nectin-2 and Nectin-like protein 5, and similar domains; member of the C1-set of the Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig) domain of nectin-2 (also known as poliovirus receptor related protein 2 or Cluster of Differentiation 112 (CD112)), nectin-like protein 5 (CD155), and similar proteins. Nectins and Nectin-like molecules are a family of Ca(2+)-independent immunoglobulin-like transmembrane glycoproteins belonging to the class of adhesion receptors, consisting of nine members (nectins 1 through 4 and nectin-like proteins 1 through 5). Nectins are synaptic cell adhesion molecules (CAMs) which facilitate adhesion and signaling at various intracellular junctions. Nectins form homophilic cis-dimers, followed by homophilic and heterophilic trans-dimers involved in cell-cell adhesion. Nectin-2 and nectin-3 localize at Sertoli-spermatid junctions where they form heterophilic trans-interactions between the cells that are essential for the formation and maintenance of the junctions and for spermatid development. CD155 is the fifth member in the nectin-like molecule family, and functions as the receptor of poliovirus; therefore, CD155 is also referred to as Necl-5, or PVR. In contrast to all other family members, CD155 lacks self-adhesion capacity, yet it shares with nectins the feature to interact with other nectins. For instance, CD155 heterophilically trans-interacts with nectin-3, thereby contributing significantly to the establishment of adherens junctions between epithelial cells. This group belongs to the Constant 1 (C1)-set of IgSF domains, which has one beta-sheet that is formed by strands A-B-E-D and the other strands by G-F-C-C'.

Pssm-ID: 409500 Cd Length: 97 Bit Score: 48.94 E-value: 7.27e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  183 SHNSKVEVRENQDLQL--KCIVANAKPAAQIVWyRGNVEYKPekREDTVEESTAKRFTTTSSLKLKPGPDDDYTEYTCQA 260
Cdd:cd07703     3 NSAEAQEVQAGGIPVPvaRCVSANGRPPARISW-SSTLNGNA--NTTQVPGPDSGTVTVTSEYSLVPTPEANGKEVTCKV 79

                          90
                  ....*....|....*...
gi 665399623  261 RHKALS-PDM-PMRATVQ 276
Cdd:cd07703    80 EHETLEePQLlPVTLSVR 97

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: 48.19 E-value: 9.82e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  865 PEIAKTPTLLRAasGTGERGRLPCRAQGSPKPQFIWRqdKKDLPINRTY---KYEVEERKidsltYESTLIVDKVAPADY 941
Cdd:cd20951     1 PEFIIRLQSHTV--WEKSDAKLRVEVQGKPDPEVKWY--KNGVPIDPSSipgKYKIESEY-----GVHVLHIRRVTVEDS 71

                          90
                  ....*....|....
gi 665399623  942 GAYECVARNELGEA 955
Cdd:cd20951    72 AVYSAVAKNIHGEA 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 47.95 E-value: 1.01e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623   285 PPYIEGYSAGETLRRGQTVELMCRSRgGNPPAQLIWYKNGSQIRMAYRTSGRLSENIYTFT---AEAGDNkARFRCEASN 361
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVTLTCEAT-GSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTisnVTRSDA-GTYTCVASN 78

Second immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 - Necl-4; member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 (also known as cell adhesion molecule 3 or CADM3), Necl-2 (also known as CADM1), Necl-3 (also known as CADM2) and Necl-4 (also known as CADM4). These nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. The N-terminal Ig-like domain of the extracellular region belongs to the V-type subfamily of Ig domains, is essential to cell-cell adhesion, and plays a part in the interaction with the envelope glycoprotein D of various viruses. Necl-1 and Necl-2 have Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is specifically expressed in neural tissue and is important to the formation of synapses, axon bundles, and myelinated axons. Necl-2 is expressed in a wide variety of tissues, and is a putative tumour suppressor gene, which is downregulated in aggressive neuroblastoma. Necl-3 has been shown to accumulate in tissues of the central and peripheral nervous system, where it is expressed in ependymal cells and myelinated axons. It is observed at the interface between the axon shaft and the myelin sheath. Necl-4 is expressed on Schwann cells, and plays a key part in initiating peripheral nervous system (PNS) myelination. Necl-4 participates in cell-cell adhesion and is proposed to play a role in tumor suppression.

Pssm-ID: 409418 Cd Length: 102 Bit Score: 48.58 E-value: 1.07e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  280 LYPPGPPYIEGYSagETLRRGQTVELMCRSRGGNPPAQLIWYKNGSQIRMAYRTSGRLSENIYT------FTAEAGDNKA 353
Cdd:cd05761     1 LGVPEKPVITGFT--SPVVEGDEITLTCTTSGSKPAADIRWFKNDKELKGVKEVQESGAGKTFTvtstlrFRVDRDDDGV 78


                  ....*....
gi 665399623  354 RFRCEASNV 362
Cdd:cd05761    79 AVICRVDHE 87

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: 48.03 E-value: 1.43e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  865 PEIAKTPTLlrAASGTGERGRLPCRAQGSPKPQFIWRQDKKDLPINRTYKYeveerkiDSLTYESTLIVDKVAPADYGAY 944
Cdd:cd05736     1 PVIRVYPEF--QAKEPGVEASLRCHAEGIPLPRVQWLKNGMDINPKLSKQL-------TLIANGSELHISNVRYEDTGAY 71


                  ....*....
gi 665399623  945 ECVARNELG 953
Cdd:cd05736    72 TCIAKNEGG 80

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

Pssm-ID: 409356 [Multi-domain] Cd Length: 96 Bit Score: 48.01 E-value: 1.61e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  678 PKFVPPPSSTAVGVEGESLQVSL--QTRANPTPvTYKWTKDGTTIPQDGDHRIFADGGSLNFTR-LHRDDAGIYSCSASN 754
Cdd:cd04967     2 PVFEEQPDDTIFPEDSDEKKVALncRARANPVP-SYRWLMNGTEIDLESDYRYSLVDGTLVISNpSKAKDAGHYQCLATN 80


                  ...
gi 665399623  755 SQG 757
Cdd:cd04967    81 TVG 83

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: 46.94 E-value: 1.72e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 665399623  788 AMLSCTVEGKPLTEehVKWERVGYDM--TVKTSTTFANGTSYLHIKDAKREDVGNFRCVADNRV 849
Cdd:cd00096     1 VTLTCSASGNPPPT--ITWYKNGKPLppSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSA 62

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: 47.42 E-value: 1.82e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  678 PKFVPPPSSTAVGvEGESLQVSLQTRANPTPVTyKWTKDGTTI---PQDGDHRIFADGG--SLNFTRLHRDDAGIYSCSA 752
Cdd:cd20951     1 PEFIIRLQSHTVW-EKSDAKLRVEVQGKPDPEV-KWYKNGVPIdpsSIPGKYKIESEYGvhVLHIRRVTVEDSAVYSAVA 78

                          90
                  ....*....|....*.
gi 665399623  753 SNSQGGATLNITVVVE 768
Cdd:cd20951    79 KNIHGEASSSASVVVE 94

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

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 47.45 E-value: 2.10e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 665399623  886 LPCRAQGSPKPQFIWRQDKKDLpinrtykyeVEERKIdSLTYESTLIVDKVAPADYGAYECVARNELGEAVETVRLEI 963
Cdd:cd04969    22 IECKPKASPKPTISWSKGTELL---------TNSSRI-CILPDGSLKIKNVTKSDEGKYTCFAVNFFGKANSTGSLSV 89

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: 47.24 E-value: 2.36e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  678 PKFVPPPSSTAVGVEGESLQVSL--QTRANPTPvTYKWTKDGTTIPQDGDHRIFADGGSLNFTRLHR-DDAGIYSCSASN 754
Cdd:cd05848     2 PVFVQEPDDAIFPTDSDEKKVILncEARGNPVP-TYRWLRNGTEIDTESDYRYSLIDGNLIISNPSEvKDSGRYQCLATN 80


                  ...
gi 665399623  755 SQG 757
Cdd:cd05848    81 SIG 83

Second immunoglobulin (Ig)-like domain of nectin-like molecule-4 (Necl-4); member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of nectin-like molecule-4 (Necl-4; also known as cell adhesion molecule 4 (CADM4)). Nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1-Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. Ig domains are likely to participate in ligand binding and recognition. Necl-4 is expressed on Schwann cells, and plays a key part in initiating peripheral nervous system (PNS) myelination. In injured peripheral nerve cells, the mRNA signal for both Necl-4 and Necl-5 was observed to be elevated. Necl-4 participates in cell-cell adhesion and is proposed to play a role in tumor suppression.

Pssm-ID: 409468 Cd Length: 100 Bit Score: 47.26 E-value: 2.63e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  185 NSKVEVRENQ----DLQLKCIVANAKPAAQIVWYRGNVEYKPEkredTVEESTAKRFTTTSSLKLKPGPDDDYTEYTCQA 260
Cdd:cd05885     6 NPVVEVREQAveggEVELSCLVPRSRPAATLRWYRDRKELKGV----SSGQENGKVWSVASTVRFRVDRKDDGGIVICEA 81


                  ....*
gi 665399623  261 RHKAL 265
Cdd:cd05885    82 QNQAL 86

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: 47.28 E-value: 2.76e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  888 CRAQGSPKPQFIWRQDKKDLPINRTYKYEVEERkidsltyESTLIVD---KVAPADY-GAYECVARNELGEAVET-VRLE 962
Cdd:cd05875    23 CEAKGNPVPTFHWTRNGKFFNVAKDPRVSMRRR-------SGTLVIDfrgGGRPEDYeGEYQCFARNKFGTALSNkIRLQ 95

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: 46.42 E-value: 4.40e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623   683 PPSSTAVGVEGESLQVSLQTRANPTPVTYKWTKDGTTIPQ-------DGDHRIFadggSLNFTRLHRDDAGIYSCSASNS 755
Cdd:pfam00047    1 SAPPTVTVLEGDSATLTCSASTGSPGPDVTWSKEGGTLIEslkvkhdNGRTTQS----SLLISNVTKEDAGTYTCVVNNP 76

                           90
                   ....*....|
gi 665399623   756 QGGATLNITV 765
Cdd:pfam00047   77 GGSATLSTSL 86

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: 46.25 E-value: 4.54e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  684 PSSTAVGVEGESLQVSLQTRANPTPVTyKWTKDGTTIPQDgdhRIFAD--GGSLNFTRLHRDDAGIYSCSASNSQGGATL 761
Cdd:cd05731     1 SESSTMVLRGGVLLLECIAEGLPTPDI-RWIKLGGELPKG---RTKFEnfNKTLKIENVSEADSGEYQCTASNTMGSARH 76


                  ....*..
gi 665399623  762 NITVVVE 768
Cdd:cd05731    77 TISVTVE 83

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 46.02 E-value: 4.66e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 665399623   482 PPLISGYMEGQIIPAGSVQKLLCVSSGgNPLATLTWYKNDKRINSVIRAADKSVSAEIT-ILANVSDNQA-QYRCEASN 558
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVTLTCEATG-SPPPTITWYKNGEPISSGSTRSRSLSGSNSTlTISNVTRSDAgTYTCVASN 78

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 45.63 E-value: 5.19e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623   581 KIRIEPEE--LRPGMEATIICdSSSSNPPAKLSWWKDGIPIegINNTSKPGLWGGTVSTLEFRvNVTQEMNGqVYTCQSA 658
Cdd:pfam13927    3 VITVSPSSvtVREGETVTLTC-EATGSPPPTITWYKNGEPI--SSGSTRSRSLSGSNSTLTIS-NVTRSDAG-TYTCVAS 77


                   .
gi 665399623   659 N 659
Cdd:pfam13927   78 N 78

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

Pssm-ID: 400489 Cd Length: 89 Bit Score: 45.87 E-value: 5.92e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623   286 PYIEGySAGETLRRGQTVELMCRSRGGNPPAQLIWYKNGSQIRMAYRTSGRLSEN-------IYTFTAEAGDNKARFRCE 358
Cdd:pfam08205    1 PTIEP-PASLLEGEGPEVVATCSSAGGKPAPRITWYLDGKPLEAAETSSEQDPESglvtvtsELKLVPSRSDHGQSLTCQ 79


                   ...
gi 665399623   359 ASN 361
Cdd:pfam08205   80 VSY 82

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: 45.86 E-value: 6.03e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 665399623  777 SENIVVNPGEDAMLSCTVEGKPltEEHVKWERVGYDmTVKTSTTFANGTSYLHIKDAKREDVGNFRCVADNRV 849
Cdd:cd05731     2 ESSTMVLRGGVLLLECIAEGLP--TPDIRWIKLGGE-LPKGRTKFENFNKTLKIENVSEADSGEYQCTASNTM 71

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

Pssm-ID: 409460 [Multi-domain] Cd Length: 83 Bit Score: 45.67 E-value: 6.54e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  886 LPCRAQGSPKPQFIWRQDKKDLPINRTYKyeveerkidsLTYESTLIVDKVAPADYGAYECVARNELGEA 955
Cdd:cd05876    15 LECIAEGLPTPTVKWLRPSGPLPPDRVKY----------QNHNKTLQLLNVGESDDGEYVCLAENSLGSA 74

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 45.46 E-value: 7.09e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623   677 RPKFVPPPSSTAvgvEGESLQVSLQTRANPTPvTYKWTKDGTTIPQDGDHRIfadggslnfTRLHRDDAGIYSCSASNSQ 756
Cdd:pfam13895    1 KPVLTPSPTVVT---EGEPVTLTCSAPGNPPP-SYTWYKDGSAISSSPNFFT---------LSVSAEDSGTYTCVARNGR 67

                           90
                   ....*....|..
gi 665399623   757 GG---ATLNITV 765
Cdd:pfam13895   68 GGkvsNPVELTV 79

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: 45.57 E-value: 7.29e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 665399623  773 IKSVSENIVVNPGEDAMLSCTVEGKPLTEehVKWERVGYDMTVKTS--TTFANGTsyLHIKDAKREDVGNFRCVADN 847
Cdd:cd20952     2 ILQGPQNQTVAVGGTVVLNCQATGEPVPT--ISWLKDGVPLLGKDEriTTLENGS--LQIKGAEKSDTGEYTCVALN 74

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 50.39 E-value: 7.94e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  967 PDPPLSLNILNVTHDTVTLAWTPGFDGGLkASYRVrYRMADRE-QYKYIDGLPNSHKLTIGGLRMNTLYLFSVMSWNELG 1045
Cdd:COG3401   327 PAAPSGLTATAVGSSSITLSWTASSDADV-TGYNV-YRSTSGGgTYTKIAETVTTTSYTDTGLTPGTTYYYKVTAVDAAG 404

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 665399623 1046 QSSYLPDLARAETKEAPPPSHPASSLGGGPPTTSQTPLGGTSG 1088
Cdd:COG3401   405 NESAPSEEVSATTASAASGESLTASVDAVPLTDVAGATAAASA 447

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: 45.58 E-value: 9.03e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  871 PTLLRAASGTGERGR---LPCRAQG-SPKPQFIWRQDKKDLPINRTykyevEERKIDSLTYESTLIVDKVAPADYGAYEC 946
Cdd:cd05750     1 PKLKEMKSQTVQEGSklvLKCEATSeNPSPRYRWFKDGKELNRKRP-----KNIKIRNKKKNSELQINKAKLEDSGEYTC 75

                          90
                  ....*....|....*..
gi 665399623  947 VARNELGEAVETVRLEI 963
Cdd:cd05750    76 VVENILGKDTVTGNVTV 92

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: 45.31 E-value: 9.09e-06

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 665399623   82 QVLEGAEAMMRCEVANVAGAVQWTKDGFALGFSAVIpgfpRYSVLGDRKQgiynLRISNASINDDADYQCQVGPARL 158
Cdd:cd20967     8 QVSKGHKIRLTVELADPDAEVKWYKDGQELQSSSKV----IFESIGAKRT----LTVQQASLADAGEYQCVAGGEKC 76

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

Pssm-ID: 409541 [Multi-domain] Cd Length: 89 Bit Score: 45.40 E-value: 9.36e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  679 KFVPPPSSTAVGvEGESLQVSLQTRANPTPVTyKWTKDGTTIPQD----GDHRIFADGGSLNftRLHRDDAGIYSCSASN 754
Cdd:cd20949     1 TFTENAYVTTVK-EGQSATILCEVKGEPQPNV-TWHFNGQPISASvadmSKYRILADGLLIN--KVTQDDTGEYTCRAYQ 76


                  ....*.
gi 665399623  755 SQGGAT 760
Cdd:cd20949    77 VNSIAS 82

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

Pssm-ID: 395002 Cd Length: 86 Bit Score: 45.26 E-value: 9.92e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623   775 SVSENIVVNPGEDAMLSCTVEGKPlTEEHVKWERvgYDMTVKTSTTFANGTSY-----LHIKDAKREDVGNFRCVADNRV 849
Cdd:pfam00047    1 SAPPTVTVLEGDSATLTCSASTGS-PGPDVTWSK--EGGTLIESLKVKHDNGRttqssLLISNVTKEDAGTYTCVVNNPG 77


                   ....
gi 665399623   850 DNPT 853
Cdd:pfam00047   78 GSAT 81

Second immunoglobulin (Ig)-like domain of nectin-like molecule-4 (Necl-4); member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of nectin-like molecule-4 (Necl-4; also known as cell adhesion molecule 4 (CADM4)). Nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1-Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. Ig domains are likely to participate in ligand binding and recognition. Necl-4 is expressed on Schwann cells, and plays a key part in initiating peripheral nervous system (PNS) myelination. In injured peripheral nerve cells, the mRNA signal for both Necl-4 and Necl-5 was observed to be elevated. Necl-4 participates in cell-cell adhesion and is proposed to play a role in tumor suppression.

Pssm-ID: 409468 Cd Length: 100 Bit Score: 45.33 E-value: 1.21e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  576 APETVKIRIEpEELRPGMEATIICDSSSSNPPAKLSWWKDGIPIEGINNTSKPGLWGGTVSTLEFRVNvtQEMNGQVYTC 655
Cdd:cd05885     3 APENPVVEVR-EQAVEGGEVELSCLVPRSRPAATLRWYRDRKELKGVSSGQENGKVWSVASTVRFRVD--RKDDGGIVIC 79

                          90       100
                  ....*....|....*....|..
gi 665399623  656 QSANEALqRSAHEAV---SLDV 674
Cdd:cd05885    80 EAQNQAL-PSGHSKQtqyVLDV 100

Second immunoglobulin (Ig)-like domain of nectin-like molecule-4 (Necl-4); member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of nectin-like molecule-4 (Necl-4; also known as cell adhesion molecule 4 (CADM4)). Nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1-Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. Ig domains are likely to participate in ligand binding and recognition. Necl-4 is expressed on Schwann cells, and plays a key part in initiating peripheral nervous system (PNS) myelination. In injured peripheral nerve cells, the mRNA signal for both Necl-4 and Necl-5 was observed to be elevated. Necl-4 participates in cell-cell adhesion and is proposed to play a role in tumor suppression.

Pssm-ID: 409468 Cd Length: 100 Bit Score: 45.33 E-value: 1.41e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  477 LYPPAPPLISgyMEGQIIPAGSVQkLLCVSSGGNPLATLTWYKNDKRINSVIRAAD--KSVSAEITILANV--SDNQAQY 552
Cdd:cd05885     1 LVAPENPVVE--VREQAVEGGEVE-LSCLVPRSRPAATLRWYRDRKELKGVSSGQEngKVWSVASTVRFRVdrKDDGGIV 77


                  ....*...
gi 665399623  553 RCEASNSA 560
Cdd:cd05885    78 ICEAQNQA 85

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: 45.23 E-value: 1.46e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  885 RLPCRAQGSPKPQFIWRQDKKDL-PINRTYKYEVEERkidsltyESTLIVDKVAPADYGAYECVARNELGEAVETVRLEI 963
Cdd:cd05857    23 KFRCPAAGNPTPTMRWLKNGKEFkQEHRIGGYKVRNQ-------HWSLIMESVVPSDKGNYTCVVENEYGSINHTYHLDV 95

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: 44.88 E-value: 1.50e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623   881 GERGRLPCRA-QGSPKPQFIWRQDKKDLPINRTYKyeveerKIDSLTYESTLIVDKVAPADYGAYECVARNELGEAVETV 959
Cdd:pfam00047   11 GDSATLTCSAsTGSPGPDVTWSKEGGTLIESLKVK------HDNGRTTQSSLLISNVTKEDAGTYTCVVNNPGGSATLST 84


                   ..
gi 665399623   960 RL 961
Cdd:pfam00047   85 SL 86

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 44.48 E-value: 1.67e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 665399623   183 SHNSKVEVRENQDLQLKCIVAnAKPAAQIVWYRGNveykpeKREDTVEESTAKRFTTTSSLKLKPGPDDDYTEYTCQAR 261
Cdd:pfam13927    6 VSPSSVTVREGETVTLTCEAT-GSPPPTITWYKNG------EPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVAS 77

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: 44.86 E-value: 1.72e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  697 QVSLQTRA--NPTP-VTykWTKDGTTIPQD-----GDHRIfADG---GSLNFTRLHRDDAGIYSCSASNSQGGAT----L 761
Cdd:cd20956    18 SVSLKCVAsgNPLPqIT--WTLDGFPIPESprfrvGDYVT-SDGdvvSYVNISSVRVEDGGEYTCTATNDVGSVShsarI 94


                  ..
gi 665399623  762 NI 763
Cdd:cd20956    95 NV 96

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: 44.86 E-value: 1.79e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  881 GERGRLPCRAQGSPKPQFIWRQDkkDLPINRTYKYEVEerkiDSLTYESTLI----VDKVAPADYGAYECVARNELGEAV 956
Cdd:cd20956    16 GPSVSLKCVASGNPLPQITWTLD--GFPIPESPRFRVG----DYVTSDGDVVsyvnISSVRVEDGGEYTCTATNDVGSVS 89


                  ....*..
gi 665399623  957 ETVRLEI 963
Cdd:cd20956    90 HSARINV 96

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: 44.92 E-value: 1.81e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  676 YRPKFVPPPSSTAVGVEGESLQVSL--QTRANPtPVTYKWTKDGTTIPQDGDHRIFADGGSLNFTR-LHRDDAGIYSCSA 752
Cdd:cd05850     1 YGPVFEEQPSSTLFPEGSAEEKVTLacRARASP-PATYRWKMNGTELKMEPDSRYRLVAGNLVISNpVKAKDAGSYQCLA 79


                  ....*
gi 665399623  753 SNSQG 757
Cdd:cd05850    80 SNRRG 84

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: 44.50 E-value: 1.86e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 665399623  879 GTGERGRLPCRAQGSPKPQFIWRQDkkDLPINRTYKYevEERKIDSltyeSTLIVDKVAPADYGAYECVARNELG 953
Cdd:cd05867    12 GPGETARLDCQVEGIPTPNITWSIN--GAPIEGTDPD--PRRHVSS----GALILTDVQPSDTAVYQCEARNRHG 78

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

Pssm-ID: 409550 [Multi-domain] Cd Length: 89 Bit Score: 44.48 E-value: 1.89e-05

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 665399623  713 WTKDGTTIPQDGDHRIFADGgSLNFTRLHRD-DAGIYSCSASNSQG---GATLNITV 765
Cdd:cd20958    34 WEKDGRRLPLNHRQRVFPNG-TLVIENVQRSsDEGEYTCTARNQQGqsaSRSVFVKV 89

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: 43.86 E-value: 2.17e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 665399623  502 LLCVSSGgNPLATLTWYKNDKRI--NSVIRAADKSVSAEITILANVSDNQAQYRCEASNSATE 562
Cdd:cd00096     3 LTCSASG-NPPPTITWYKNGKPLppSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGG 64

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: 43.86 E-value: 2.28e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 665399623  595 ATIICdSSSSNPPAKLSWWKDGIPIEgiNNTSKPGLWGGTVSTLEFRvNVTQEMNGqVYTCQSANEALQRSAHEA 669
Cdd:cd00096     1 VTLTC-SASGNPPPTITWYKNGKPLP--PSSRDSRRSELGNGTLTIS-NVTLEDSG-TYTCVASNSAGGSASASV 70

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: 43.92 E-value: 2.33e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  683 PPSSTAVGVeGESLQVSLQTRANPTPvTYKWTKDGTTIPqDGDHRIFADGgSLNFTRLHRDDAGIYSCSASNSQGGATLN 762
Cdd:cd05725     3 RPQNQVVLV-DDSAEFQCEVGGDPVP-TVRWRKEDGELP-KGRYEILDDH-SLKIRKVTAGDMGSYTCVAENMVGKIEAS 78


                  ....*
gi 665399623  763 ITVVV 767
Cdd:cd05725    79 ATLTV 83

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: 2.51e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  881 GERGRLPCRAQGSPKPQFIWRQDKKDLPINrtykyevEERKIDSLTYESTLIVDKVAPADYGAYECVARNELGEAVETVR 960
Cdd:cd05748     7 GESLRLDIPIKGRPTPTVTWSKDGQPLKET-------GRVQIETTASSTSLVIKNAKRSDSGKYTLTLKNSAGEKSATIN 79


                  .
gi 665399623  961 L 961
Cdd:cd05748    80 V 80

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: 44.23 E-value: 2.78e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  880 TGERGRLPCRAQ-GSPKPQFIWRQDKKDLPIN--RTYKYEVEERKIDSLTYEstLIVDKVAPADYGAYECVARNELGEAV 956
Cdd:cd20950    11 IGNRAVLTCSEPdGSPPSEYTWFKDGVVMPTNpkSTRAFSNSSYSLDPTTGE--LVFDPLSASDTGEYSCEARNGYGTPM 88


                  ....*....
gi 665399623  957 --ETVRLEI 963
Cdd:cd20950    89 rsNAVRMEA 97

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: 44.16 E-value: 2.97e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  678 PKFVPPPSSTAVgVEGESLQVSLQTRANPTPvTYKWTKDGTTIPQDGDH-RIFADGGSLNFTRLHRDDAGIYSCSASNSQ 756
Cdd:cd20976     2 PSFSSVPKDLEA-VEGQDFVAQCSARGKPVP-RITWIRNAQPLQYAADRsTCEAGVGELHIQDVLPEDHGTYTCLAKNAA 79

                          90
                  ....*....|.
gi 665399623  757 GGATLNITVVV 767
Cdd:cd20976    80 GQVSCSAWVTV 90

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: 43.47 E-value: 3.19e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 665399623  303 VELMCRSRGgNPPAQLIWYKNGSQIRMAYRTSGRLSENIYTFT---AEAGDNkARFRCEASN 361
Cdd:cd00096     1 VTLTCSASG-NPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTisnVTLEDS-GTYTCVASN 60

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

Pssm-ID: 409582 Cd Length: 91 Bit Score: 43.94 E-value: 3.29e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 665399623  881 GERGRLPCRAQGSPKPQFIWRQDKKDLPINRTYKYEVEERKIDSltyestLIVDKVAPADYGAYECVARNELGE 954
Cdd:cd20990    15 GKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSAHKMLVRENGVHS------LIIEPVTSRDAGIYTCIATNRAGQ 82

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: 43.65 E-value: 4.66e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 665399623  489 MEGQIIPAGSVQKLLCVSSGGNPLATLTWYKNDKRINSV----IRAADKSVSAEITI-LANVSDNqAQYRCEASN 558
Cdd:cd05750     6 MKSQTVQEGSKLVLKCEATSENPSPRYRWFKDGKELNRKrpknIKIRNKKKNSELQInKAKLEDS-GEYTCVVEN 79

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

Pssm-ID: 409454 Cd Length: 89 Bit Score: 43.43 E-value: 4.74e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 665399623  881 GERGRLPCRAQGSPKPQFIWRQDKKDLPInrtyKYEVEERKIDSltyeSTLIVDKVAPADYGAYECVARNELG 953
Cdd:cd05868    14 GEDGTLICRANGNPKPSISWLTNGVPIEI----APTDPSRKVDG----DTIIFSKVQERSSAVYQCNASNEYG 78

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

Pssm-ID: 409396 [Multi-domain] Cd Length: 94 Bit Score: 43.55 E-value: 4.91e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 665399623  886 LPCRAQGSPKPQFIWRQDKKDLPINRTYKYEVEERkidsltyESTLIVD--KVAPADY-GAYECVARNELGEAV 956
Cdd:cd05733    21 IKCEAKGNPQPTFRWTKDGKFFDPAKDPRVSMRRR-------SGTLVIDnhNGGPEDYqGEYQCYASNELGTAI 87

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

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 43.21 E-value: 5.28e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  682 PPPSstAVGVEGESLQVSLQTRANPTPvTYKWTKDGTTI-PQDGDHRIFADGGSLNFTRLHRDDAGIYSCSASNSQGGAT 760
Cdd:cd04978     5 EPPS--LVLSPGETGELICEAEGNPQP-TITWRLNGVPIePAPEDMRRTVDGRTLIFSNLQPNDTAVYQCNASNVHGYLL 81


                  ....*..
gi 665399623  761 LNITVVV 767
Cdd:cd04978    82 ANAFLHV 88

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: 42.77 E-value: 6.69e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  871 PTLLRAASGtgERGRLPCRA-QGSPKPQFIWRQDKKDLPINRTYKYEVEERKidsltyestLIVDKVAPADYGAYECVAR 949
Cdd:cd05724     4 PSDTQVAVG--EMAVLECSPpRGHPEPTVSWRKDGQPLNLDNERVRIVDDGN---------LLIAEARKSDEGTYKCVAT 72

                          90
                  ....*....|....*
gi 665399623  950 NELGEAV-ETVRLEI 963
Cdd:cd05724    73 NMVGEREsRAARLSV 87

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: 42.95 E-value: 6.87e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 665399623   188 VEVRENQDLQLKCIVANAKPAAQIVWYRGNvEYKPEKREDTveesTAKRFTTTSSLKLKPGPDDDYTEYTCQARH 262
Cdd:pfam00047    6 VTVLEGDSATLTCSASTGSPGPDVTWSKEG-GTLIESLKVK----HDNGRTTQSSLLISNVTKEDAGTYTCVVNN 75

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: 43.07 E-value: 6.89e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 665399623  881 GERGRLPCRAQGSPKPQFIWRQDKKDLPinRTYKyEVEERKIDSLTYESTLIVDKVAPADYGAYECVARNELGEAVETV 959
Cdd:cd20954    16 GQDVMLHCQADGFPTPTVTWKKATGSTP--GEYK-DLLYDPNVRILPNGTLVFGHVQKENEGHYLCEAKNGIGSGLSKV 91

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

Pssm-ID: 143222 [Multi-domain] Cd Length: 74 Bit Score: 42.62 E-value: 6.95e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 665399623  692 EGESLQVSLQTRANPTPVTyKWTKDGTTIPQDGDHRIFADGgSLNFTRLHRDDAGIYSCSASNSQG 757
Cdd:cd05745     1 EGQTVDFLCEAQGYPQPVI-AWTKGGSQLSVDRRHLVLSSG-TLRISRVALHDQGQYECQAVNIVG 64

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: 43.00 E-value: 7.42e-05

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 665399623  886 LPCRAQGSPKPQFIWRQDKKDLPINRTYKYeveerkidSLTYESTLIVDKVAPADYGAYECVARNELGEAVET 958
Cdd:cd04967    24 LNCRARANPVPSYRWLMNGTEIDLESDYRY--------SLVDGTLVISNPSKAKDAGHYQCLATNTVGSVLSR 88

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

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 42.49 E-value: 8.26e-05

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623    296 TLRRGQTVELMCRSRgGNPPAQLIWYKNGSQ-IRMAYRTSGRLSENIYTFT---AEAGDNkARFRCEASNvmSQNPLKAE 371
Cdd:smart00410    5 TVKEGESVTLSCEAS-GSPPPEVTWYKQGGKlLAESGRFSVSRSGSTSTLTisnVTPEDS-GTYTCAATN--SSGSASSG 80


                    ....*
gi 665399623    372 VELSV 376
Cdd:smart00410   81 TTLTV 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: 42.88 E-value: 9.13e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  687 TAVGVEGESLQVSLQTRA-NPTPvTYKWTKDGTTIPQDGDHRIFADGG----SLNFTRLHRDDAGIYSCSASNSQGGATL 761
Cdd:cd05750     8 SQTVQEGSKLVLKCEATSeNPSP-RYRWFKDGKELNRKRPKNIKIRNKkknsELQINKAKLEDSGEYTCVVENILGKDTV 86


                  ....*.
gi 665399623  762 NITVVV 767
Cdd:cd05750    87 TGNVTV 92

Immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins; member of the I-set of IgSF domains; This group contains the immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins. The SALM (for synaptic adhesion-like molecules; also known as Lrfn for leucine-rich repeat and fibronectin type III domain containing) family of adhesion molecules consists of five known members: SALM1/Lrfn2, SALM2/Lrfn1, SALM3/Lrfn4, SALM4/Lrfn3, and SALM5/Lrfn5. SALMs share a similar domain structure, containing leucine-rich repeats (LRRs), an immunoglobulin (Ig) domain, and a fibronectin III (FNIII) domain, followed by a transmembrane domain and a C-terminal PDZ-binding motif. SALM5 is implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons. SALM5 interacts with the Ig domains of LAR (Leukocyte common Antigen-Related) family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPdelta, and PTPsigma). In addition, PTPdelta is implicated in ASDs, ADHD, bipolar disorder, and restless leg syndrome. Studies have shown that LAR-RPTPs are novel and splicing-dependent presynaptic ligands for SALM5, and that they mediate SALM5-dependent presynaptic differentiation. Furthermore, SALM5 maintains AMPA receptor (AMPAR)-mediated excitatory synaptic transmission through mechanisms involving the interaction of SALM5 with LAR-RPTPs. This group belongs to the I-set of immunoglobulin superfamily (IgSF) domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409421 [Multi-domain] Cd Length: 88 Bit Score: 42.46 E-value: 9.63e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  881 GERGRLPCRAQGSPKPQFIWRQDKKDLPIN--RTYKYEveerkidsltyESTLIVDKVAPADYGAYECVARNELGEAVET 958
Cdd:cd05764    15 GQRATLRCKARGDPEPAIHWISPEGKLISNssRTLVYD-----------NGTLDILITTVKDTGAFTCIASNPAGEATAR 83


                  ....*
gi 665399623  959 VRLEI 963
Cdd:cd05764    84 VELHI 88

Second immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 - Necl-4; member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 (also known as cell adhesion molecule 3 or CADM3), Necl-2 (also known as CADM1), Necl-3 (also known as CADM2) and Necl-4 (also known as CADM4). These nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. The N-terminal Ig-like domain of the extracellular region belongs to the V-type subfamily of Ig domains, is essential to cell-cell adhesion, and plays a part in the interaction with the envelope glycoprotein D of various viruses. Necl-1 and Necl-2 have Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is specifically expressed in neural tissue and is important to the formation of synapses, axon bundles, and myelinated axons. Necl-2 is expressed in a wide variety of tissues, and is a putative tumour suppressor gene, which is downregulated in aggressive neuroblastoma. Necl-3 has been shown to accumulate in tissues of the central and peripheral nervous system, where it is expressed in ependymal cells and myelinated axons. It is observed at the interface between the axon shaft and the myelin sheath. Necl-4 is expressed on Schwann cells, and plays a key part in initiating peripheral nervous system (PNS) myelination. Necl-4 participates in cell-cell adhesion and is proposed to play a role in tumor suppression.

Pssm-ID: 409418 Cd Length: 102 Bit Score: 42.80 E-value: 1.03e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  377 LFAPTHVTVMGPTEARV-GDIVPLTCTTAPSNPPAEIKWMVGGRQVRNATSKTIVSPEGGWTTTSNITAVVEPNKRSLVV 455
Cdd:cd05761     1 LGVPEKPVITGFTSPVVeGDEITLTCTTSGSKPAADIRWFKNDKELKGVKEVQESGAGKTFTVTSTLRFRVDRDDDGVAV 80


                  ..
gi 665399623  456 IC 457
Cdd:cd05761    81 IC 82

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

Pssm-ID: 143278 [Multi-domain] Cd Length: 98 Bit Score: 42.66 E-value: 1.23e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  778 ENIVVNPGEDAMLSCTVEGKPLTEehVKWERVGYDMTV---------KTSTTFANGTSYLHIKDAKREDVGNFRCVADNR 848
Cdd:cd05870     9 KNETTVENGAATLSCKAEGEPIPE--ITWKRASDGHTFsegdkspdgRIEVKGQHGESSLHIKDVKLSDSGRYDCEAASR 86


                  .
gi 665399623  849 V 849
Cdd:cd05870    87 I 87

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 42.24 E-value: 1.24e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623   300 GQTVELMCRSRGgNPPAQLIWYKNGSQIRMAYRTSGRLSENIYTFT---AEAGDnKARFRCEASNVMSQNplKAEVELSV 376
Cdd:pfam07679   15 GESARFTCTVTG-TPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTisnVQPDD-SGKYTCVATNSAGEA--EASAELTV 90

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

Pssm-ID: 462230 Cd Length: 109 Bit Score: 42.83 E-value: 1.32e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623    76 TTPHDLQVLEGAEAMMRCEV----ANVAGAVQWTKDGFALGFSAVIPGF----------PRYSVLGDRKQGIYNLRISNA 141
Cdd:pfam07686    1 QTPREVTVALGGSVTLPCTYsssmSEASTSVYWYRQPPGKGPTFLIAYYsngseegvkkGRFSGRGDPSNGDGSLTIQNL 80

                           90
                   ....*....|....
gi 665399623   142 SINDDADYQCQVGP 155
Cdd:pfam07686   81 TLSDSGTYTCAVIP 94

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

Pssm-ID: 409561 Cd Length: 92 Bit Score: 41.99 E-value: 1.48e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  690 GVEGESLQVSLQTRANPTPvTYKWTKDGT---TIPQDGDHRIFADGgSLNFTRLHRDDAGIYSCSASNSQGGATLNITVV 766
Cdd:cd20969    14 VDEGHTVQFVCRADGDPPP-AILWLSPRKhlvSAKSNGRLTVFPDG-TLEVRYAQVQDNGTYLCIAANAGGNDSMPAHLH 91


                  .
gi 665399623  767 V 767
Cdd:cd20969    92 V 92

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: 42.18 E-value: 1.51e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  688 AVGVEGESLQVSLQTRANPTPvTYKWTKDGTTIPQDGDHRIFADGG---SLNFTRLHRDDAGIYSCSASNSQGGATLNIT 764
Cdd:cd20973     7 KEVVEGSAARFDCKVEGYPDP-EVKWMKDDNPIVESRRFQIDQDEDglcSLIISDVCGDDSGKYTCKAVNSLGEATCSAE 85


                  ...
gi 665399623  765 VVV 767
Cdd:cd20973    86 LTV 88

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

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 41.72 E-value: 1.59e-04

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623    585 EPEELRPGMEATIICdSSSSNPPAKLSWWKDG-IPIEGINNTSkpGLWGGTVSTLEFRvNVTQEMNGqVYTCQSANEALQ 663
Cdd:smart00410    2 PSVTVKEGESVTLSC-EASGSPPPEVTWYKQGgKLLAESGRFS--VSRSGSTSTLTIS-NVTPEDSG-TYTCAATNSSGS 76


                    ...
gi 665399623    664 RSA 666
Cdd:smart00410   77 ASS 79

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: 41.46 E-value: 1.84e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  881 GERGRLPCRAQGSPKPQFIWRQDKKDLPINRTYKyeveerkidsLTYESTLIVDKVAPADYGAYECVARNELGEAVETVR 960
Cdd:cd05745     2 GQTVDFLCEAQGYPQPVIAWTKGGSQLSVDRRHL----------VLSSGTLRISRVALHDQGQYECQAVNIVGSQRTVAQ 71


                  ...
gi 665399623  961 LEI 963
Cdd:cd05745    72 LTV 74

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: 42.05 E-value: 1.88e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  286 PYIEGySAGETLRRGQTVELMCRSRGGNPPAQLIWYKNGSQIRMAYRTSGRLSE-------NIYTFTAEAGDNKARFRCE 358
Cdd:cd05759     2 PVIEG-GPVISLQAGVPYNLTCRARGAKPAAEIIWFRDGEQLEGAVYSKELLKDgkrettvSTLLITPSDLDTGRTFTCR 80

                          90
                  ....*....|....*...
gi 665399623  359 ASNVMSQNPLKAEVELSV 376
Cdd:cd05759    81 ARNEAIPNGKETSITLDV 98

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: 41.75 E-value: 1.91e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 665399623  782 VNPGEDAMLSCTVEGKPLTEehVKWERVGYDMTvKTSTTFANGTSYLHIKDAKREDVGNFRCVADNRVD 850
Cdd:cd20957    13 VDFGRTAVFNCSVTGNPIHT--VLWMKDGKPLG-HSSRVQILSEDVLVIPSVKREDKGMYQCFVRNDGD 78

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

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 41.77 E-value: 2.04e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  881 GERGRLPCRAQGSPKPQFIWRQDKKDLpinRTYKYEVEERKIdsLTYESTLIVDKVAP-----ADYGAYECVARNELGEA 955
Cdd:cd07693    15 GDPATLNCKAEGRPTPTIQWLKNGQPL---ETDKDDPRSHRI--VLPSGSLFFLRVVHgrkgrSDEGVYVCVAHNSLGEA 89


                  .
gi 665399623  956 V 956
Cdd:cd07693    90 V 90

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

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 41.75 E-value: 2.11e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  881 GERGRLPCRAQGSPKPQFIWRQDKKDLPINrtykyeveERKidSLTYESTLIVDKVAPADYGAYECVARNELGEAVETVR 960
Cdd:cd20957    16 GRTAVFNCSVTGNPIHTVLWMKDGKPLGHS--------SRV--QILSEDVLVIPSVKREDKGMYQCFVRNDGDSAQATAE 85


                  ...
gi 665399623  961 LEI 963
Cdd:cd20957    86 LKL 88

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: 41.55 E-value: 2.22e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  879 GTGERGRLPCRAQGSPKPQFIWRQDkkDLPINRTYKYEVEERKIDsltyeSTLIVDKVAPADYGAYECVARNELGEAVET 958
Cdd:cd20949    12 KEGQSATILCEVKGEPQPNVTWHFN--GQPISASVADMSKYRILA-----DGLLINKVTQDDTGEYTCRAYQVNSIASDM 84


                  ....*
gi 665399623  959 VRLEI 963
Cdd:cd20949    85 QERTV 89

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

Pssm-ID: 409454 Cd Length: 89 Bit Score: 41.51 E-value: 2.24e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 665399623  589 LRPGMEATIICdSSSSNPPAKLSWWKDGIPIEGINNTSKPGLWGGTVStlefrVNVTQEMNGQVYTCQSANE 660
Cdd:cd05868    11 LSPGEDGTLIC-RANGNPKPSISWLTNGVPIEIAPTDPSRKVDGDTII-----FSKVQERSSAVYQCNASNE 76

Immunoglobulin Constant-1 (C1)-set domain; The members here are composed of C1-set domains, classical Ig-like domains resembling the antibody constant domain. Members of the IgC1 family are components of immunoglobulin, T-cell receptors, CD1 cell surface glycoproteins, secretory glycoproteins A/C, and major histocompatibility complex (MHC) class I/II molecules. In immunoglobulins, each chain is composed of one variable domain (IgV) and one or more IgC domains. These names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. The IgV domain is responsible for antigen binding, while the IgC domain is involved in oligomerization and molecular interactions. 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 strands by G, F, C, and C'.

Pssm-ID: 409354 Cd Length: 95 Bit Score: 41.68 E-value: 2.29e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  579 TVKIRIEPEELRPGMEATIICDSSSSNPP-AKLSWWKDGIPIEGINNTS---KPGLWGGTV-STLefRVNVTQEMNGQVY 653
Cdd:cd00098     1 TVTLLPPSPEEKGGGKVTLVCLVSGFYPKdITVTWLKNGVPLTSGVSTSspvEPNDGTYSVtSSL--TVPPSDWDEGATY 78

                          90
                  ....*....|..
gi 665399623  654 TCQSANEALQRS 665
Cdd:cd00098    79 TCVVTHESLKSP 90

Fifth 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 fifth 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 (also known as Neph1), Kirrel2 (also known as Neph3), and Drosophila RST (also known as 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: 319310 Cd Length: 98 Bit Score: 41.75 E-value: 2.29e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  881 GERGRLPCRAQGSPKPQFI-WRQDKKDLPINRTYKYEVEERKIDSLTYeSTLIVDKVAPADYG-AYECVARNELGEAVET 958
Cdd:cd05758    16 GEKARLECLVFSSPPPDRIvWSWDEGFLESGSSGRFSVETFPTEPGVI-SVLHISGTQRSDFQtSFNCSAWNRFGEGTAI 94


                  ....
gi 665399623  959 VRLE 962
Cdd:cd05758    95 VSLG 98

Second immunoglobulin (Ig) domain of Nectin-2 and Nectin-like protein 5, and similar domains; member of the C1-set of the Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig) domain of nectin-2 (also known as poliovirus receptor related protein 2 or Cluster of Differentiation 112 (CD112)), nectin-like protein 5 (CD155), and similar proteins. Nectins and Nectin-like molecules are a family of Ca(2+)-independent immunoglobulin-like transmembrane glycoproteins belonging to the class of adhesion receptors, consisting of nine members (nectins 1 through 4 and nectin-like proteins 1 through 5). Nectins are synaptic cell adhesion molecules (CAMs) which facilitate adhesion and signaling at various intracellular junctions. Nectins form homophilic cis-dimers, followed by homophilic and heterophilic trans-dimers involved in cell-cell adhesion. Nectin-2 and nectin-3 localize at Sertoli-spermatid junctions where they form heterophilic trans-interactions between the cells that are essential for the formation and maintenance of the junctions and for spermatid development. CD155 is the fifth member in the nectin-like molecule family, and functions as the receptor of poliovirus; therefore, CD155 is also referred to as Necl-5, or PVR. In contrast to all other family members, CD155 lacks self-adhesion capacity, yet it shares with nectins the feature to interact with other nectins. For instance, CD155 heterophilically trans-interacts with nectin-3, thereby contributing significantly to the establishment of adherens junctions between epithelial cells. This group belongs to the Constant 1 (C1)-set of IgSF domains, which has one beta-sheet that is formed by strands A-B-E-D and the other strands by G-F-C-C'.

Pssm-ID: 409500 Cd Length: 97 Bit Score: 41.62 E-value: 2.31e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  585 EPEELRPGMEATII--CDSSSSNPPAKLSWWKDgipIEG-INNTSKPGLWGGTVS-TLEFRVNVTQEMNGQVYTCQSANE 660
Cdd:cd07703     6 EAQEVQAGGIPVPVarCVSANGRPPARISWSST---LNGnANTTQVPGPDSGTVTvTSEYSLVPTPEANGKEVTCKVEHE 82

                          90
                  ....*....|....
gi 665399623  661 ALQRSAHEAVSLDV 674
Cdd:cd07703    83 TLEEPQLLPVTLSV 96

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: 41.43 E-value: 2.43e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 665399623  885 RLPCRAQGSPKPQFIWRQDKKdlPINRTYKYEVEErkidsltyeSTLIVDKVAPADYGAYECVARNELG 953
Cdd:cd05728    18 RWECKASGNPRPAYRWLKNGQ--PLASENRIEVEA---------GDLRITKLSLSDSGMYQCVAENKHG 75

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

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 40.95 E-value: 2.83e-04

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623    186 SKVEVRENQDLQLKCIVaNAKPAAQIVWYRGNVEYKPEKREDTVEEStakrfTTTSSLKLKP-GPDDDYTeYTCQARhka 264
Cdd:smart00410    2 PSVTVKEGESVTLSCEA-SGSPPPEVTWYKQGGKLLAESGRFSVSRS-----GSTSTLTISNvTPEDSGT-YTCAAT--- 71

                            90
                    ....*....|....*
gi 665399623    265 lSPDMPMRATVQLSV 279
Cdd:smart00410   72 -NSSGSASSGTTLTV 85

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

Pssm-ID: 409540 Cd Length: 76 Bit Score: 40.94 E-value: 2.93e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  684 PSSTAVgVEGESLQVSLQTRANPtPVTYKWTKDGTtiPQDGDHrifadggSLNFTRLHRDDAGIYSCSASNSQGGATLNI 763
Cdd:cd20948     2 PSDTYY-LSGENLNLSCHAASNP-PAQYSWTINGT--FQTSSQ-------ELFLPAITENNEGTYTCSAHNSLTGKNISL 70


                  ....*.
gi 665399623  764 TVVVEY 769
Cdd:cd20948    71 VLSVTV 76

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 40.84 E-value: 2.96e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623   864 APEIAKTPTLLRaasgTGERGRLPCRAQGSPKPQFIWRqdKKDLPINRTYKYeveerkidsltyestlIVDKVAPADYGA 943
Cdd:pfam13895    1 KPVLTPSPTVVT----EGEPVTLTCSAPGNPPPSYTWY--KDGSAISSSPNF----------------FTLSVSAEDSGT 58

                           90
                   ....*....|
gi 665399623   944 YECVARNELG 953
Cdd:pfam13895   59 YTCVARNGRG 68

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: 41.38 E-value: 3.07e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  871 PTLLRA---ASGTGERGRLPCRAQGSPKPQFIWRQDKKDLpinrTYKYEVEERKidsltYESTLIVDKVAPADYGAYECV 947
Cdd:cd05856     6 PAKMRRrviARPVGSSVRLKCVASGNPRPDITWLKDNKPL----TPPEIGENKK-----KKWTLSLKNLKPEDSGKYTCH 76

                          90
                  ....*....|....*.
gi 665399623  948 ARNELGEAVETVRLEI 963
Cdd:cd05856    77 VSNRAGEINATYKVDV 92

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

Pssm-ID: 409395 [Multi-domain] Cd Length: 96 Bit Score: 41.36 E-value: 3.28e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 665399623  778 ENIVVNPGEDAMLSCTVEGKPLTEehVKWERVGYDMTVKTSTTFAN-------GTSYLHIKDAKREDVGNFRCVADNRV 849
Cdd:cd05732     9 ENQTAVELEQITLTCEAEGDPIPE--ITWRRATRGISFEEGDLDGRivvrghaRVSSLTLKDVQLTDAGRYDCEASNRI 85

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

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 40.94 E-value: 3.43e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 665399623  886 LPCRAQGSPKPQFIWRQDKKDLPinrtykyeVEERKIDSLTyESTLIVDKVAPADYGAYECVARNELGEAVETVRLEI 963
Cdd:cd20952    19 LNCQATGEPVPTISWLKDGVPLL--------GKDERITTLE-NGSLQIKGAEKSDTGEYTCVALNLSGEATWSAVLDV 87

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

Pssm-ID: 143299 Cd Length: 92 Bit Score: 41.05 E-value: 3.50e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 665399623  886 LPCRAQGSPKPQFIWRQDKKDLPINRTYKYEVEERKIDSLTyestliVDKVAPADYGAYECVARNELG 953
Cdd:cd05891    21 LTCTVFGNPDPEVIWFKNDQDIELSEHYSVKLEQGKYASLT------IKGVTSEDSGKYSINVKNKYG 82

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: 40.69 E-value: 3.91e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  679 KFVPPPSSTAVgVEGESLQVSLQTRANPTPvTYKWTKDGTTIPQDGDHRIFaDGGSLNFTRLHRDDAGIYSCSASNSQGG 758
Cdd:cd20968     1 KITRPPTNVTI-IEGLKAVLPCTTMGNPKP-SVSWIKGDDLIKENNRIAVL-ESGSLRIHNVQKEDAGQYRCVAKNSLGI 77

                          90
                  ....*....|.
gi 665399623  759 A-TLNITVVVE 768
Cdd:cd20968    78 AySKPVTIEVE 88

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

Pssm-ID: 400489 Cd Length: 89 Bit Score: 40.86 E-value: 4.16e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 665399623   380 PTHVTVMGPTEArvgdivpLTCTTAPSNPPAEIKWMVGGRQVRNA-TSKTIVSPEGGWTTTSNITAVV--EPNKRSLV 454
Cdd:pfam08205    7 ASLLEGEGPEVV-------ATCSSAGGKPAPRITWYLDGKPLEAAeTSSEQDPESGLVTVTSELKLVPsrSDHGQSLT 77

Second immunoglobulin (Ig)-like domain of nectin-like molcule-1 (Necl-1); member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of nectin-like molcule-1 (Necl-1; also known as cell adhesion molecule3 (CADM3)). These nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. The N-terminal Ig-like domain of the extracellular region belongs to the V-type subfamily of Ig domains is essential to cell-cell adhesion and plays a part in the interaction with the envelope glycoprotein D of various viruses. Necl-1 and Necl-2 have Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is specifically expressed in neural tissue and is important to the formation of synapses, axon bundles, and myelinated axons. Necl-2 is expressed in a wide variety of tissues and is a putative tumour suppressor gene which is downregulated in aggressive neuroblastoma. Ig domains are likely to participate in ligand binding and recognition.

Pssm-ID: 409502 Cd Length: 103 Bit Score: 41.11 E-value: 4.26e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  480 PAPPLISGYMEGqiIPAGSVQKLLCVSSGGNPLATLTWYKNDKRIN----SVIRAADK---SVSAEITILANVSDNQAQY 552
Cdd:cd07705     4 PQKPQITGYESA--FKEKDKAKLRCTSSGSKPAANIKWRKGDQELEgaptSVQEDGNGktfTVSSSVEFQVTREDDGAEI 81


                  ..
gi 665399623  553 RC 554
Cdd:cd07705    82 TC 83

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: 40.01 E-value: 4.30e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 665399623  196 LQLKCiVANAKPAAQIVWYRGNVEYKPEKREDTVEEstakrfTTTSSLKLKPGPDDDYTEYTCQARHKA 264
Cdd:cd00096     1 VTLTC-SASGNPPPTITWYKNGKPLPPSSRDSRRSE------LGNGTLTISNVTLEDSGTYTCVASNSA 62

Fifth immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3 protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3 protein (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). These proteins contain multiple Ig domains, have properties of cell adhesion molecules, and are important in organ development. Neph1 and 2 may mediate axonal guidance and synapse formation in certain areas of the CNS. In the kidney they participate in the formation of the slit diaphragm.

Pssm-ID: 409479 Cd Length: 98 Bit Score: 41.09 E-value: 4.58e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  881 GERGRLPCRAQGSPKPQFI-WRQDKKDLPINRTYKYEVEERKIDSLTYeSTLIVDKVAPADYGA-YECVARNELGEAVET 958
Cdd:cd05898    16 GERGKVKCFIGSTPPPDRIaWAWKENVLESGTLERYTVERTSTGSGVL-STLTINNIMEADFQThYNCTAWNSFGSGTAI 94


                  ....
gi 665399623  959 VRLE 962
Cdd:cd05898    95 IQLE 98

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: 40.62 E-value: 4.74e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  481 APPLISGYMEGQIIPAGSVQkLLCVSSGgNPLATLTWYKNDKRI--NSVIRAADK-SVSAEITILANVSDNQAQ----YR 553
Cdd:cd20956     1 APVLLETFSEQTLQPGPSVS-LKCVASG-NPLPQITWTLDGFPIpeSPRFRVGDYvTSDGDVVSYVNISSVRVEdggeYT 78


                  ....*..
gi 665399623  554 CEASNSA 560
Cdd:cd20956    79 CTATNDV 85

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

Pssm-ID: 409387 Cd Length: 97 Bit Score: 40.92 E-value: 5.02e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623   74 FRTTPHDLQVLEGAEAMMRCEVANVAGAV-QWTKDGFALGFSAVipgfPRYSVLGDRKQGIYNLRISNASINDDADYQCQ 152
Cdd:cd05722     4 FLSEPSDIVAMRGGPVVLNCSAESDPPPKiEWKKDGVLLNLVSD----ERRQQLPNGSLLITSVVHSKHNKPDEGFYQCV 79

                          90
                  ....*....|....*...
gi 665399623  153 VGPARLNSAIRANAKLTV 170
Cdd:cd05722    80 AQNESLGSIVSRTARVTV 97

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

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 40.51 E-value: 5.10e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 665399623  497 GSVQKLLCvSSGGNPLATLTWYKNDKRINSVIRAADKSVSAEITILANVSDNQAQ-YRCEASN 558
Cdd:cd04978    14 GETGELIC-EAEGNPQPTITWRLNGVPIEPAPEDMRRTVDGRTLIFSNLQPNDTAvYQCNASN 75

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: 40.26 E-value: 5.42e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 665399623   586 PEELRPGMEATIICDSSSSNPPAKLSWWKDG-IPIEGinNTSKPGLWGGTVSTLEFrVNVTQEmNGQVYTCQSAN 659
Cdd:pfam00047    5 TVTVLEGDSATLTCSASTGSPGPDVTWSKEGgTLIES--LKVKHDNGRTTQSSLLI-SNVTKE-DAGTYTCVVNN 75

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: 40.45 E-value: 5.42e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  880 TGERGR---LPCRAQGSPKPQFIWRQDKKDLpinrtykyeVEERKIDSLTYES--TLIVDKVAPADYGAYECVARNELGE 954
Cdd:cd20969    13 FVDEGHtvqFVCRADGDPPPAILWLSPRKHL---------VSAKSNGRLTVFPdgTLEVRYAQVQDNGTYLCIAANAGGN 83


                  ....*....
gi 665399623  955 AVETVRLEI 963
Cdd:cd20969    84 DSMPAHLHV 92

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

Pssm-ID: 409551 Cd Length: 94 Bit Score: 40.55 E-value: 5.47e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  693 GESLQVSLQTRANPTPVTYKWTKDGTTIPQD---GDHRIFADGGSLNFTRLHRDDAGIYSCSASNSQGGA 759
Cdd:cd20959    17 GMRAQLHCGVPGGDLPLNIRWTLDGQPISDDlgiTVSRLGRRSSILSIDSLEASHAGNYTCHARNSAGSA 86

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

Pssm-ID: 409436 [Multi-domain] Cd Length: 95 Bit Score: 40.32 E-value: 6.67e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  678 PKFVPPPSSTAVGVEGESLQVSL--QTRANPTPVtYKWTKDGTTIPQDGDHRIFAdGGSLNFTRLHRD-DAGIYSCSASN 754
Cdd:cd05849     2 PVFEEQPIDTIYPEESTEGKVSVncRARANPFPI-YKWRKNNLDIDLTNDRYSMV-GGNLVINNPDKYkDAGRYVCIVSN 79

                          90
                  ....*....|...
gi 665399623  755 SQGG-----ATLN 762
Cdd:cd05849    80 IYGKvrsreATLS 92

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409473 Cd Length: 92 Bit Score: 40.14 E-value: 6.73e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  881 GERGRLPCRAQGSPKPQFIWRQDKKDLPIN--RTYKYEVEERKIdsltyesTLIVDKVAPADYGAYECVARNELGEAVET 958
Cdd:cd05892    15 GDPVRLECQISAIPPPQIFWKKNNEMLQYNtdRISLYQDNCGRI-------CLLIQNANKKDAGWYTVSAVNEAGVVSCN 87


                  ....*
gi 665399623  959 VRLEI 963
Cdd:cd05892    88 ARLDV 92

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

Pssm-ID: 409582 Cd Length: 91 Bit Score: 40.08 E-value: 6.80e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  678 PKFVPPPSSTAVGvEGESLQVSLQTRANPTPvTYKWTKDGTTIPQDGDHRIFA-DGG--SLNFTRLHRDDAGIYSCSASN 754
Cdd:cd20990     1 PHFLQAPGDLTVQ-EGKLCRMDCKVSGLPTP-DLSWQLDGKPIRPDSAHKMLVrENGvhSLIIEPVTSRDAGIYTCIATN 78

                          90
                  ....*....|...
gi 665399623  755 SQGGATLNITVVV 767
Cdd:cd20990    79 RAGQNSFNLELVV 91

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

Pssm-ID: 409435 Cd Length: 96 Bit Score: 40.31 E-value: 6.82e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 665399623  886 LPCRAQGSPKPQFIWRQDKKDLPINRTYKYEVeerkidsltYESTLIVDKVAPA-DYGAYECVARNELG 953
Cdd:cd05848    24 LNCEARGNPVPTYRWLRNGTEIDTESDYRYSL---------IDGNLIISNPSEVkDSGRYQCLATNSIG 83

Second immunoglobulin (Ig)-like domain of nectin-like molecule-3 (Necl-3); member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of nectin-like molecule-3 (Necl-3; also known as cell adhesion molecule 2 (CADM2)). Nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. Necl-3 has been shown to accumulate in tissues of the central and peripheral nervous system where it is expressed in ependymal cells and myelinated axons. It is observed at the interface between the axon shaft and the myelin sheath. Ig domains are likely to participate in ligand binding and recognition.

Pssm-ID: 409467 Cd Length: 104 Bit Score: 40.68 E-value: 6.95e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  590 RPGMEA---TIICDSSSSNPPAKLSWWKDGIPIEGINNTSKPGLWGGTV---STLEFRVNvtQEMNGQVYTCQSANEALQ 663
Cdd:cd05884    15 SPVMEGdhiQLTCKTSGSKPAADIRWFKNDKEVKDVKYLKAEDANRKTFtvsSSLDFHVD--RDDDGVAITCRVDHESLT 92


                  ....*.
gi 665399623  664 RSAHEA 669
Cdd:cd05884    93 ATPQIA 98

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 43.84 E-value: 7.67e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  963 ITSQPDPPLSLNILNVTHDTVTLAWTPGFDGGLkASYRVRYRMADREQYKYIDGLPNSHkLTIGGLRMNTLYLFSVMSWN 1042
Cdd:COG3401   229 PTTPPSAPTGLTATADTPGSVTLSWDPVTESDA-TGYRVYRSNSGDGPFTKVATVTTTS-YTDTGLTNGTTYYYRVTAVD 306

                          90       100
                  ....*....|....*....|...
gi 665399623 1043 ELGQSSYLPDLARAETKEAPPPS 1065
Cdd:COG3401   307 AAGNESAPSNVVSVTTDLTPPAA 329

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: 8.49e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 665399623  689 VGVEGESLQVSLQTRANPTPvTYKWTKDGTTIPQDGDHRIFADGgSLNFTRLHRDDAGIYSCSASNSQGGATLNITVVV 767
Cdd:cd04969    13 LAAKGGDVIIECKPKASPKP-TISWSKGTELLTNSSRICILPDG-SLKIKNVTKSDEGKYTCFAVNFFGKANSTGSLSV 89

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: 39.96 E-value: 9.38e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  875 RAASGTGERGRLPCRAQGSPKPQFIWRQDKKDLpinrtykyEVEERKID------SLTYESTLIVDKVAPADYGAYECVA 948
Cdd:cd05869    11 QTAMELEEQITLTCEASGDPIPSITWRTSTRNI--------SSEEKTLDghivvrSHARVSSLTLKYIQYTDAGEYLCTA 82

                          90
                  ....*....|....*
gi 665399623  949 RNELGEAVETVRLEI 963
Cdd:cd05869    83 SNTIGQDSQSMYLEV 97

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: 39.71 E-value: 1.02e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  483 PLISGYMEGQIIPAGSVQKLlCVSSGGNPLATLTWYKNDKRINSVIRAADKSVSAE----ITILANVS-DNQAQYRCEAS 557
Cdd:cd20951     1 PEFIIRLQSHTVWEKSDAKL-RVEVQGKPDPEVKWYKNGVPIDPSSIPGKYKIESEygvhVLHIRRVTvEDSAVYSAVAK 79


                  ....*.
gi 665399623  558 NSATEI 563
Cdd:cd20951    80 NIHGEA 85

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409566 [Multi-domain] Cd Length: 93 Bit Score: 39.64 E-value: 1.05e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  678 PKFVPPPSSTAVgVEGESLQVSLQTRANPTPvTYKWTKDGTTIPQDGDHRI---FADGGS-LNFTRLHRDDAGIYSCSAS 753
Cdd:cd20974     1 PVFTQPLQSVVV-LEGSTATFEAHVSGKPVP-EVSWFRDGQVISTSTLPGVqisFSDGRAkLSIPAVTKANSGRYSLTAT 78

                          90
                  ....*....|....
gi 665399623  754 NSQGGATLNITVVV 767
Cdd:cd20974    79 NGSGQATSTAELLV 92

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: 1.07e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 665399623  773 IKSVSENIVVNPGEDAMLSCTVEGKPltEEHVKWERVGYDMTVKT-STTFANGTsyLHIKDAKREDVGNFRCVADN 847
Cdd:cd20978     4 IQKPEKNVVVKGGQDVTLPCQVTGVP--QPKITWLHNGKPLQGPMeRATVEDGT--LTIINVQPEDTGYYGCVATN 75

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 39.30 E-value: 1.09e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 665399623   296 TLRRGQTVELMCrSRGGNPPAQLIWYKNGSQIrmayRTSGrlseNIYTFTAEAgDNKARFRCEASN 361
Cdd:pfam13895   10 VVTEGEPVTLTC-SAPGNPPPSYTWYKDGSAI----SSSP----NFFTLSVSA-EDSGTYTCVARN 65

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

Pssm-ID: 400489 Cd Length: 89 Bit Score: 39.71 E-value: 1.13e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 665399623   504 CVSSGGNPLATLTWYKNDKRIN-----SVIRAADK--SVSAEITILANVSDNQAQYRCEASNSA 560
Cdd:pfam08205   21 CSSAGGKPAPRITWYLDGKPLEaaetsSEQDPESGlvTVTSELKLVPSRSDHGQSLTCQVSYGA 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: 39.30 E-value: 1.18e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  678 PKFVPPPSSTAVGVEGESLQVSLQTRANPTPvTYKWTKDGTTIPQDGDHRIFADGGsLNFTRLHRDDAGIYSCSASNSQG 757
Cdd:cd20978     1 PKFIQKPEKNVVVKGGQDVTLPCQVTGVPQP-KITWLHNGKPLQGPMERATVEDGT-LTIINVQPEDTGYYGCVATNEIG 78

                          90
                  ....*....|
gi 665399623  758 GATLNITVVV 767
Cdd:cd20978    79 DIYTETLLHV 88

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 39.55 E-value: 1.18e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 665399623   492 QIIPAGSVQKLLCVSSGgNPLATLTWYKNDKRINSV--IRAADKSVSAEITILANVSDNQAQYRCEASNSATE 562
Cdd:pfam07679   10 VEVQEGESARFTCTVTG-TPDPEVSWFKDGQPLRSSdrFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSAGE 81

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: 39.71 E-value: 1.18e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 665399623  782 VNPGEDAMLSCTVEGKPltEEHVKWERVGYDMTVktSTTFAN-------GTSYLHIKDAKREDVGNFRCVADNR 848
Cdd:cd20951    12 VWEKSDAKLRVEVQGKP--DPEVKWYKNGVPIDP--SSIPGKykieseyGVHVLHIRRVTVEDSAVYSAVAKNI 81

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 39.09 E-value: 1.20e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623    73 KFRTTPHDLQVLEGAEAMMRCEV-ANVAGAVQWTKDGfalgfsavIPGFPRYSVLGDRKQGIYNLRISNASINDDADYQC 151
Cdd:pfam13927    3 VITVSPSSVTVREGETVTLTCEAtGSPPPTITWYKNG--------EPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTC 74


                   ..
gi 665399623   152 QV 153
Cdd:pfam13927   75 VA 76

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: 39.60 E-value: 1.25e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  678 PKF-VPPPSSTAVGVEGESLQVSLQTRANPTPvTYKWTKdGTTIPQDGDHRIFADGGSLNFTRLHRDDAGIYSCSASNSQ 756
Cdd:cd05852     1 PTFeFNPMKKKILAAKGGRVIIECKPKAAPKP-KFSWSK-GTELLVNNSRISIWDDGSLEILNITKLDEGSYTCFAENNR 78

                          90
                  ....*....|.
gi 665399623  757 GGATLNITVVV 767
Cdd:cd05852    79 GKANSTGVLSV 89

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

Pssm-ID: 409458 Cd Length: 95 Bit Score: 39.58 E-value: 1.27e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 665399623  888 CRAQGSPKPQFIWRQDKKDLPINRtykyeveERKIDSLTYESTLIVDKV----APADYGAYECVARNELGEAV 956
Cdd:cd05874    23 CEAKGKPPPSFSWTRNGTHFDIDK-------DPKVTMKPNTGTLVINIMngekAEAYEGVYQCTARNERGAAV 88

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 38.92 E-value: 1.29e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623   492 QIIPAGSVQKLLCvSSGGNPLATLTWYKNDKRINSviraadksvSAEITILANVSDNQAQYRCEASNSATEIPlFQSTTL 571
Cdd:pfam13895    9 TVVTEGEPVTLTC-SAPGNPPPSYTWYKDGSAISS---------SPNFFTLSVSAEDSGTYTCVARNGRGGKV-SNPVEL 77


                   ..
gi 665399623   572 SV 573
Cdd:pfam13895   78 TV 79

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: 39.41 E-value: 1.30e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  777 SENIVVNPGEDAMLSCTVEGKPltEEHVKWERVGydMTVKTSTT----FANGTSyLHIKDAKREDVGNFRCVADNRVDNP 852
Cdd:cd20970     9 SFTVTAREGENATFMCRAEGSP--EPEISWTRNG--NLIIEFNTryivRENGTT-LTIRNIRRSDMGIYLCIASNGVPGS 83


                  ....*....
gi 665399623  853 TNRDILLIV 861
Cdd:cd20970    84 VEKRITLQV 92

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: 39.45 E-value: 1.38e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 665399623  697 QVSLQTRA--NPTPvTYKWTK-DGTTIPQDGDHRifaDGGSLNFTRLHRDDAGIYSCSASNSQG 757
Cdd:cd04968    18 TVTLECFAlgNPVP-QIKWRKvDGSPSSQWEITT---SEPVLEIPNVQFEDEGTYECEAENSRG 77

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: 39.38 E-value: 1.41e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 665399623  692 EGESLQVSLQTRANPTPVTyKWTKDGTtiPQDGDHRIFADGGSLNFTRL-----HRDDAGIYSCSASNSQGG 758
Cdd:cd20975    14 EGQDVIMSIRVQGEPKPVV-SWLRNRQ--PVRPDQRRFAEEAEGGLCRLrilaaERGDAGFYTCKAVNEYGA 82

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: 39.11 E-value: 1.44e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 665399623  692 EGESLQVSLQTRANPTPvTYKWTKDGTTIPQDGDHRI--FADGGSLNFTRLHRDDAGIYSCSASNSQGGATLNITVVV 767
Cdd:cd05748     6 AGESLRLDIPIKGRPTP-TVTWSKDGQPLKETGRVQIetTASSTSLVIKNAKRSDSGKYTLTLKNSAGEKSATINVKV 82

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

Pssm-ID: 409560 [Multi-domain] Cd Length: 88 Bit Score: 39.15 E-value: 1.49e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 665399623  881 GERGRLPCRAQGSPKPQFIWRqdKKDLPINRTYKYEVEErkidsltyESTLIVDKVAPADYGAYECVARNELGEA 955
Cdd:cd20968    14 GLKAVLPCTTMGNPKPSVSWI--KGDDLIKENNRIAVLE--------SGSLRIHNVQKEDAGQYRCVAKNSLGIA 78

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: 1.60e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 665399623  705 NPTPvTYKWTKDGTTIPQD-GDHRIFADGGSLNFTRLHRDDAGIYSCSASNSQGGA------TLNI 763
Cdd:cd05760    28 HPRP-TYQWFRDGTPLSDGqGNYSVSSKERTLTLRSAGPDDSGLYYCCAHNAFGSVcssqnfTLSI 92

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: 39.36 E-value: 1.69e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  496 AGSVQKLLCVSSGGNPLATLTWYKNDKRINSVIRAAD-----KSVSAEITILANVS--DNQAQYRCEASNSATEIPLFQS 568
Cdd:cd05759    14 AGVPYNLTCRARGAKPAAEIIWFRDGEQLEGAVYSKEllkdgKRETTVSTLLITPSdlDTGRTFTCRARNEAIPNGKETS 93


                  ....*
gi 665399623  569 TTLSV 573
Cdd:cd05759    94 ITLDV 98

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: 39.07 E-value: 1.81e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  867 IAKTPTLLRAAsgTGERGRLPCRAQGSPKPQFIWRQ-DKKDLPinrtykyeveeRKIDSlTYESTLIVDKVAPADYGAYE 945
Cdd:cd04968     4 KVRFPADTYAL--KGQTVTLECFALGNPVPQIKWRKvDGSPSS-----------QWEIT-TSEPVLEIPNVQFEDEGTYE 69

                          90       100
                  ....*....|....*....|.
gi 665399623  946 CVARNELGEavETVRLEITSQ 966
Cdd:cd04968    70 CEAENSRGK--DTVQGRIIVQ 88

Third immunoglobulin domain in Cluster of Differentiation (CD) 22; member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third immunoglobulin domain in Cluster of Differentiation (CD) 22 (also known as Siglec-2). CD22, a sialic-acid binding immunoglobulin type-lectin (Siglec) family member, is an inhibitory co-receptor of the B-cell receptor (BCR). The inhibitory function of CD22 and its restricted expression on B cells makes CD22 an attractive target against dysregulated B cells that cause autoimmune diseases and B-cell-derived cancers. CD22 plays a vital role in establishing a baseline level of B-cell inhibition, and thus is an important determinant of homeostasis in humoral immunity. Siglecs are primarily expressed on immune cells and recognize sialic acid-containing glycan ligands. Siglecs are organized as an extracellular module composed of Ig-like domains (an N-terminal variable set of Ig-like carbohydrate recognition domains, and 1 to 16 constant Ig-like domains), followed by transmembrane and short cytoplasmic domains. Human Siglecs are classified into two subgroups, one subgroup is comprised of sialoadhesin (Siglec-1), CD22 (Siglec-2), and MAG (Siglec-4, myelin-associated glycoprotein), the other subgroup is comprised of CD33-related Siglecs which include CD33 (Siglec-3) and human Siglecs 5-11. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. This group belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

Pssm-ID: 409531 Cd Length: 88 Bit Score: 39.01 E-value: 2.05e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  686 STAVGVEGESLQVSLQ-TRANPTPVTYKWTKDGTTIPQDgdhrifaDGGSLNFTRLHRDDAGIYSCSASNSQG-GATLNI 763
Cdd:cd20937    10 SDAIVREGDSVTMTCEvSSSNPEYTTVSWLKDGTSLKKQ-------NTFTLNLREVTKDQSGKYCCQVSNDVGpGRSEEV 82


                  ....*.
gi 665399623  764 TVVVEY 769
Cdd:cd20937    83 FLQVQY 88

Fourth immunoglobulin (Ig)-like domain of stem cell factor receptor (SCFR), and similar domains; member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of stem cell factor receptor (SCFR). In addition to SCFR, this group also includes the fourth Ig domain of macrophage colony stimulating factor receptor (M-CSF-R). SCFR, also called receptor tyrosine kinase KIT or proto-oncogene c-Kit, contains an extracellular component having five Ig-like domains, a transmembrane segment, and a cytoplasmic portion having protein tyrosine kinase activity. SCFR and its ligand SCF are critical for normal hematopoiesis, mast cell development, melanocytes, and gametogenesis. SCF binds to the second and third Ig-like domains of SCFR, this fourth Ig-like domain participates in SCFR dimerization, which follows ligand binding. Deletion of this fourth SCFR Ig-like domain abolishes the ligand-induced dimerization of SCFR and completely inhibits signal transduction. M-CSF-R, also called proto-oncogene c-Fms, acts as cell-surface receptor for CSF1 and IL34 and plays an essential role in the regulation of survival, proliferation and differentiation of hematopoietic precursor cells, such as macrophages and monocytes. 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: 409364 Cd Length: 101 Bit Score: 39.13 E-value: 2.15e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  693 GESLQVSLQTRANPTPVTYKWTKDGTT-------IPQDGDHRIFADGGSLNFTRLHRDDAGIYSCSASNSQGGATLNITV 765
Cdd:cd04975    18 GENLDLIVEVEAYPKPEHQNWTYMGPFftdkwedLPNSENESTYRYVSTLHLTRLKGSEAGTYTFLASNSDVNAALAFEV 97


                  ....
gi 665399623  766 VVEY 769
Cdd:cd04975    98 YLNY 101

CH2 domain (second constant Ig domain of the heavy chain) in immunoglobulin mu chain; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin constant domain (IgC) of mu heavy chains. This domain is found on the Fc fragment. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. There are two types of light chains: kappa and lambda; each is composed of a constant domain and a variable domain. There are five types of heavy chains: alpha, delta, epsilon, gamma, and mu, all consisting of a variable domain (VH) with three (alpha, delta and gamma) or four (epsilon and mu) constant domains (CH1 to CH4). Ig molecules are modular proteins, in which the variable and constant domains have clear, conserved sequence patterns.

Pssm-ID: 409513 Cd Length: 99 Bit Score: 38.91 E-value: 2.18e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  186 SKVEVRENQDLQLKCIVANAKPAA-QIVWYRGNVEYKPEKREDTVE--ESTAKRFTTTSSLKLKPGPDDDYTEYTCQARH 262
Cdd:cd16093    10 SREEFLGNRTATFVCLATGFSPKTiSFKWLRNGKEVTSSTGAVVEEpkEDGKTLYSATSFLTITESEWKSQTEFTCEFKH 89


                  ...
gi 665399623  263 KAL 265
Cdd:cd16093    90 KGE 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: 38.83 E-value: 2.28e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  678 PKFVPPPSSTAVgVEGESLQVSLQTRANPTPvTYKWTKDGTTIPqdGDHRIFA--------DGGSLNFTRLHRDDAGIYS 749
Cdd:cd20954     2 PRWIVEPVDANV-AAGQDVMLHCQADGFPTP-TVTWKKATGSTP--GEYKDLLydpnvrilPNGTLVFGHVQKENEGHYL 77


                  ....*...
gi 665399623  750 CSASNSQG 757
Cdd:cd20954    78 CEAKNGIG 85

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

Pssm-ID: 143220 Cd Length: 78 Bit Score: 38.24 E-value: 2.71e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 665399623  881 GERGRLPCRAQGSPKPQFIWRQDKKDLPinrtykyevEERKIDSLTY--ESTLIVDKVAPADYGAYECVARNELG 953
Cdd:cd05743     1 GETVEFTCVATGVPTPIINWRLNWGHVP---------DSARVSITSEggYGTLTIRDVKESDQGAYTCEAINTRG 66

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

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 38.26 E-value: 2.97e-03

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623    490 EGQIIPAGSVQKLLCVSSGgNPLATLTWYKNDKRI---NSVIRAADKSVSAEITIlANVS-DNQAQYRCEASNSATEIpl 565
Cdd:smart00410    2 PSVTVKEGESVTLSCEASG-SPPPEVTWYKQGGKLlaeSGRFSVSRSGSTSTLTI-SNVTpEDSGTYTCAATNSSGSA-- 77


                    ....*...
gi 665399623    566 FQSTTLSV 573
Cdd:smart00410   78 SSGTTLTV 85

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

Pssm-ID: 409545 Cd Length: 95 Bit Score: 38.68 E-value: 3.01e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  862 KFAPEIAKTPTLLRAASGTGergrLPCRAQGSPKPQFIWrqdkkdlpinrtYKY-EVEERKI-----DSLTYES-TLIVD 934
Cdd:cd20953     3 KIPGLSKSQPLTVSSASSIA----LLCPAQGYPAPSFRW------------YKFiEGTTRKQavvlnDRVKQVSgTLIIK 66

                          90       100
                  ....*....|....*....|....*.
gi 665399623  935 KVAPADYGAYECVARNEL-GEAVETV 959
Cdd:cd20953    67 DAVVEDSGKYLCVVNNSVgGESVETV 92

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

Pssm-ID: 409391 [Multi-domain] Cd Length: 98 Bit Score: 38.40 E-value: 3.17e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  679 KFVPPPSSTAVGvEGESLQVSLQTRANPTPVTYkWTKDGTTI-------PQDGDHRIFADGGSLNFTRLHRDDAGIYSCS 751
Cdd:cd05726     1 QFVVKPRDQVVA-LGRTVTFQCETKGNPQPAIF-WQKEGSQNllfpyqpPQPSSRFSVSPTGDLTITNVQRSDVGYYICQ 78

                          90       100
                  ....*....|....*....|
gi 665399623  752 ASNSQGG----ATLNITVVV 767
Cdd:cd05726    79 ALNVAGSilakAQLEVTDVL 98

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

Pssm-ID: 143207 [Multi-domain] Cd Length: 95 Bit Score: 38.37 E-value: 3.36e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 665399623  693 GESLQVSLQTRANPTPvTYKWTKDGTTIPQDGDHRIFADGGS-LNFTRLHRDDAGIYSCSASNSQG--GATLNITVVVE 768
Cdd:cd05730    18 GQSVTLACDADGFPEP-TMTWTKDGEPIESGEEKYSFNEDGSeMTILDVDKLDEAEYTCIAENKAGeqEAEIHLKVFAK 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: 38.37 E-value: 3.39e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 665399623  706 PTPvTYKWTKDG-TTIPQDGDHRI--FADGGSLNFTRLHRDDAGIYSCSASNSQGGATLNITVVV 767
Cdd:cd05763    27 PTP-QIAWQKDGgTDFPAARERRMhvMPEDDVFFIVDVKIEDTGVYSCTAQNSAGSISANATLTV 90

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

Pssm-ID: 319300 Cd Length: 92 Bit Score: 38.34 E-value: 3.40e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 665399623  886 LPCRAQGSPKPQFIWRQDKKDLPINRTYKYEVEERKidsltyESTLIVDKVAPADYGAYECVARNELG 953
Cdd:cd05737    21 LTCNVWGDPPPEVSWLKNDQALAFLDHCNLKVEAGR------TVYFTINGVSSEDSGKYGLVVKNKYG 82

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 37.76 E-value: 4.02e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623   777 SENIVVNPGEDAMLSCTVEGKPLTEehVKWERVGydMTVKTSTTFangtsylHIKDAKREDVGNFRCVADNRVDNPTNRD 856
Cdd:pfam13895    6 PSPTVVTEGEPVTLTCSAPGNPPPS--YTWYKDG--SAISSSPNF-------FTLSVSAEDSGTYTCVARNGRGGKVSNP 74


                   ....*
gi 665399623   857 ILLIV 861
Cdd:pfam13895   75 VELTV 79

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: 38.06 E-value: 4.24e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  865 PEIAKTPTLLRAASGTGERGRLPCRAQGSPKPQFIWRQDKKDLpinrtykyeVEERKIdSLTYESTLIVDKVAPADYGAY 944
Cdd:cd05852     1 PTFEFNPMKKKILAAKGGRVIIECKPKAAPKPKFSWSKGTELL---------VNNSRI-SIWDDGSLEILNITKLDEGSY 70

                          90
                  ....*....|....*....
gi 665399623  945 ECVARNELGEAVETVRLEI 963
Cdd:cd05852    71 TCFAENNRGKANSTGVLSV 89

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: 37.92 E-value: 4.25e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 665399623  489 MEGQII--PAGSVQKLLCVSSGgNPLATLTWYKNDKRINSVIRAADKSVSAEITILANVSDNQAQYRCEASNSATEI 563
Cdd:cd05856     9 MRRRVIarPVGSSVRLKCVASG-NPRPDITWLKDNKPLTPPEIGENKKKKWTLSLKNLKPEDSGKYTCHVSNRAGEI 84

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: 37.76 E-value: 4.39e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 665399623  779 NIVVNPGEDAMLSCTVEGKPLTEehVKWERVGYDMTVKTSTTFANGTsyLHIKDAKREDVGNFRCVADNRV 849
Cdd:cd05725     6 NQVVLVDDSAEFQCEVGGDPVPT--VRWRKEDGELPKGRYEILDDHS--LKIRKVTAGDMGSYTCVAENMV 72

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: 37.89 E-value: 4.56e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  881 GERGRLPCRAQGSPKPQFIWRQDKKDLPINRTY---KYEVEERkidslTYESTLIVDKVAPADYGAYECVARNELGEAVE 957
Cdd:cd05732    16 LEQITLTCEAEGDPIPEITWRRATRGISFEEGDldgRIVVRGH-----ARVSSLTLKDVQLTDAGRYDCEASNRIGGDQQ 90


                  ....*.
gi 665399623  958 TVRLEI 963
Cdd:cd05732    91 SMYLEV 96

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: 37.95 E-value: 4.66e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  295 ETLRRGQTVELMCRSRGgNPPAQLIWYKNGSQIRMAYRTSGRLSENIYTF-TAEA-GDNKARFRCEASNVMSQNPLKAEV 372
Cdd:cd20972    11 QEVAEGSKVRLECRVTG-NPTPVVRWFCEGKELQNSPDIQIHQEGDLHSLiIAEAfEEDTGRYSCLATNSVGSDTTSAEI 89

Second immunoglobulin (Ig) domain of poliovirus receptor (PVR, also known as CD155 and Necl-5), and similar domains; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig) domain of poliovirus receptor (PVR, also known as CD155 and nectin-like protein 5 (Necl-5)) and similar proteins. Poliovirus (PV) binds to its cellular receptor (PVR/CD155) to initiate infection. CD155 is a membrane-anchored, single-span glycoprotein; its extracellular region has three Ig-like domains. There are four different isotypes of CD155 (referred to as alpha, beta, gamma, and delta), these result from alternate splicing of the CD155 mRNA, and have identical extracellular domains. CD155-beta and CD155-gamma are secreted, while CD155-alpha and CD155-delta are membrane-bound and function as PV receptors. The virus recognition site is contained in the amino-terminal domain, D1. Having the virus attachment site on the receptor distal from the plasma membrane may be important for successful initiation of infection of cells by the virus. CD155 binds in the poliovirus "canyon" and has a footprint similar to that of the intercellular adhesion molecule-1 receptor on human rhinoviruses. This group also includes the second Ig-like domain of nectin-1, also known as poliovirus receptor related protein(PVRL)1 or CD111.

Pssm-ID: 409384 Cd Length: 96 Bit Score: 37.86 E-value: 4.99e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  579 TVKIRIEPEELRPGMEATI-ICDSSSSNPPAKLSWWKDgipIEGINNTSKPGLWGGTVS-TLEFRVNVTQEMNGQVYTCQ 656
Cdd:cd05719     2 TNSLEGGPALLIGGEPTLVaTCISANGKPPASVTWETD---LKGEASTTQVRGSNGTVTvTSRYRLVPSREADGQPLTCV 78

                          90
                  ....*....|....*...
gi 665399623  657 SANEALQRSAHEAVSLDV 674
Cdd:cd05719    79 VEHPSLEKDQRISVTLNV 96

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: 5.43e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  773 IKSVSENIVVNPGEDAMLSCTVEGKPLTEehVKWerVGYDMTVKTSTTFANGTS-YLHIKDAKREDVGNFRCVADNRVDN 851
Cdd:cd20968     2 ITRPPTNVTIIEGLKAVLPCTTMGNPKPS--VSW--IKGDDLIKENNRIAVLESgSLRIHNVQKEDAGQYRCVAKNSLGI 77

                          90
                  ....*....|.
gi 665399623  852 PTNRDILLIVK 862
Cdd:cd20968    78 AYSKPVTIEVE 88

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

Pssm-ID: 409551 Cd Length: 94 Bit Score: 37.86 E-value: 5.47e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  877 ASGTGERGRLPCR-AQGSPKPQFIWRQDKKDLPINrtykYEVEERKIDSltYESTLIVDKVAPADYGAYECVARNELGEA 955
Cdd:cd20959    13 AAQVGMRAQLHCGvPGGDLPLNIRWTLDGQPISDD----LGITVSRLGR--RSSILSIDSLEASHAGNYTCHARNSAGSA 86


                  ....*...
gi 665399623  956 VETVRLEI 963
Cdd:cd20959    87 SYTAPLTV 94

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: 37.17 E-value: 7.32e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623   292 SAGETLRRGQTVELMCRSRGGNPPAQLIWYKNGS------QIRMAYRTSGRLSENIYTFTAE-AGDnkarFRCEASNVMS 364
Cdd:pfam00047    3 PPTVTVLEGDSATLTCSASTGSPGPDVTWSKEGGtlieslKVKHDNGRTTQSSLLISNVTKEdAGT----YTCVVNNPGG 78


                   ....*.
gi 665399623   365 QNPLKA 370
Cdd:pfam00047   79 SATLST 84

Fourth immunoglobulin (Ig)-like domain of stem cell factor receptor (SCFR); member of the I-set of IgSF domains; The members here are composed of the fourth Immunoglobulin (Ig)-like domain in stem cell factor receptor (SCFR). SCFR is organized as an extracellular component having five IG-like domains, a transmembrane segment, and a cytoplasmic portion having protein tyrosine kinase activity. SCFR and its ligand SCF are critical for normal hematopoiesis, mast cell development, melanocytes, and gametogenesis. SCF binds to the second and third Ig-like domains of SCFR. This fourth Ig-like domain participates in SCFR dimerization, which follows ligand binding. Deletion of this fourth domain abolishes the ligand-induced dimerization of SCFR and completely inhibits signal transduction. 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: 409446 Cd Length: 101 Bit Score: 37.15 E-value: 8.98e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665399623  693 GESLQVSLQTRANPTPVTYKWTKDGTTIPQDGDHRIFADGGS-------LNFTRLHRDDAGIYSCSASNSQGGATLNITV 765
Cdd:cd05860    18 GENLDLRVEYEAYPKPEHQVWIYMNETLTNTSDHYVKSKTEGnnryvseLHLTRLKGTEGGIYTFLVSNSDASASVTFNV 97


                  ..
gi 665399623  766 VV 767
Cdd:cd05860    98 YV 99

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: 36.15 E-value: 9.99e-03

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 665399623   89 AMMRCEVANVAGA-VQWTKDGFALGFSAVIPGFprysvlgdRKQGIYNLRISNASINDDADYQCQV 153
Cdd:cd00096     1 VTLTCSASGNPPPtITWYKNGKPLPPSSRDSRR--------SELGNGTLTISNVTLEDSGTYTCVA 58