NCBI Conserved Domain Search

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: 98.62 E-value: 1.56e-24

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341   29 YFISEPLSAVQ-KLGRPVVLHCSAK-PVTARISWLHNGKRLDRNTEQIKIHRGTLTILSLNPSLSGCYQCVANNSVGAVV 106
Cdd:cd20978    2 KFIQKPEKNVVvKGGQDVTLPCQVTgVPQPKITWLHNGKPLQGPMERATVEDGTLTIINVQPEDTGYYGCVATNEIGDIY 81


                 ....*..
gi 81908341  107 SGPATVS 113
Cdd:cd20978   82 TETLLHV 88

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 79.22 E-value: 1.18e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341    405 PVIVTAPANVEVTDGDFVTLSCNATGEPVPVIHWYgrhglitsHPSQVLRSKSRkshlfrpgdldpepvYLIMSQAGSSS 484
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWF--------KDGQPLRSSDR---------------FKVTYEGGTYT 57

                           90       100       110
                   ....*....|....*....|....*....|...
gi 81908341    485 LSIQAVTREHAGKYTCEAVNKHGSTQSEAFLTV 517
Cdd:pfam07679   58 LTISNVQPDDSGKYTCVATNSAGEAEASAELTV 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: 76.03 E-value: 1.22e-16

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 81908341  320 DQKVSLGATVRFTCEVHGNPAPNRTWFHNAQPIRPSSR-HLTEGSVLKITGVIMEDSGLYQCMADNGIGFMQSTGRLQI 397
Cdd:cd20957   10 VQTVDFGRTAVFNCSVTGNPIHTVLWMKDGKPLGHSSRvQILSEDVLVIPSVKREDKGMYQCFVRNDGDSAQATAELKL 88

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

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 74.84 E-value: 3.78e-16

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  718 PEAPDRPTISMASETSVYVTWIPRANGGSPITAFKVEYKRMKSSDWLVAAEDiPPSKLSVEVRSLEPGSIYKFRVIVINH 797
Cdd:cd00063    1 PSPPTNLRVTDVTSTSVTLSWTPPEDDGGPITGYVVEYREKGSGDWKEVEVT-PGSETSYTLTGLKPGTEYEFRVRAVNG 79

                         90
                 ....*....|.
gi 81908341  798 YGESFRSSASR 808
Cdd:cd00063   80 GGESPPSESVT 90

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 74.60 E-value: 3.82e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341    313 SISKGLHDQKVSLGATVRFTCEVHGNPAPNRTWFHNAQPIRPSSRHLT----EGSVLKITGVIMEDSGLYQCMADNGIGF 388
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVtyegGTYTLTISNVQPDDSGKYTCVATNSAGE 81


                   ....*....
gi 81908341    389 MQSTGRLQI 397
Cdd:pfam07679   82 AEASAELTV 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: 72.54 E-value: 2.27e-15

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341     411 PANVEVTDGDFVTLSCNATGEPVPVIHWYgRHGLitshpsQVLRSKSRkshlfrpgdldpepvYLIMSQAGSSSLSIQAV 490
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWY-KQGG------KLLAESGR---------------FSVSRSGSTSTLTISNV 58

                            90       100
                    ....*....|....*....|....*..
gi 81908341     491 TREHAGKYTCEAVNKHGSTQSEAFLTV 517
Cdd:smart00410   59 TPEDSGTYTCAATNSSGSASSGTTLTV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 71.06 E-value: 5.07e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341    404 RPVIVTAPANVEVTDGDFVTLSCNATGEPVPVIHWYgrhglitshpsqvlrsksrkshlFRPGDLDPEPVYLIMSQAGSS 483
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWY-----------------------KNGEPISSGSTRSRSLSGSNS 57

                           90       100
                   ....*....|....*....|.
gi 81908341    484 SLSIQAVTREHAGKYTCEAVN 504
Cdd:pfam13927   58 TLTISNVTRSDAGTYTCVASN 78

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

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 68.57 E-value: 5.86e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  314 ISKGLHDQKVSLGATVRFTCEVHGNPAPNRTWFHNAQPI--RPSSRHLTEGSVLkITGVIMEDSGLYQCMADNGIGFMQS 391
Cdd:cd20978    4 IQKPEKNVVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLqgPMERATVEDGTLT-IINVQPEDTGYYGCVATNEIGDIYT 82


                 ....*.
gi 81908341  392 TGRLQI 397
Cdd:cd20978   83 ETLLHV 88

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

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 66.47 E-value: 2.60e-13

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 81908341  320 DQKVSLGATVRFTCEVHGNPAPNRTWFHNAQPIRPSSRHLTEGSVLKITGVIMEDSGLYQCMADNGIGFMQSTGRLQI 397
Cdd:cd05728    8 DTEADIGSSLRWECKASGNPRPAYRWLKNGQPLASENRIEVEAGDLRITKLSLSDSGMYQCVAENKHGTIYASAELAV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 66.05 E-value: 3.08e-13

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 81908341    313 SISKGLHDQKVSLGATVRFTCEVHGNPAPNRTWFHNAQPIRPSS----RHLTEGSVLKITGVIMEDSGLYQCMADN 384
Cdd:pfam13927    3 VITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGStrsrSLSGSNSTLTISNVTRSDAGTYTCVASN 78

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 65.90 E-value: 4.36e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341    720 APDRPTISMASETSVYVTWIPRANGGSPITAFKVEYKRMKSSDWLVAaEDIPPSKLSVEVRSLEPGSIYKFRVIVINHYG 799
Cdd:pfam00041    2 APSNLTVTDVTSTSLTVSWTPPPDGNGPITGYEVEYRPKNSGEPWNE-ITVPGTTTSVTLTGLKPGTEYEVRVQAVNGGG 80


                   ....*
gi 81908341    800 ESFRS 804
Cdd:pfam00041   81 EGPPS 85

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

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 65.98 E-value: 5.37e-13

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  405 PVIVTAPANVEVTDGDFVTLSCNATGEPVPVIHWygrhglitshpsqvlrskSRKSHLFRPGDLDPepvyLIMSQAGSSS 484
Cdd:cd05744    1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFW------------------QLNGKPVRPDSAHK----MLVRENGRHS 58

                         90       100       110
                 ....*....|....*....|....*....|...
gi 81908341  485 LSIQAVTREHAGKYTCEAVNKHGSTQSEAFLTV 517
Cdd:cd05744   59 LIIEPVTKRDAGIYTCIARNRAGENSFNAELVV 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: 64.44 E-value: 1.91e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  316 KGLHDQKVSLGATVRFTCEVHGNPAPNRTWFHNAQPIRPSSRH---LTEGSV--LKITGVIMEDSGLYQCMADNGIGFMQ 390
Cdd:cd05744    5 QAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHkmlVRENGRhsLIIEPVTKRDAGIYTCIARNRAGENS 84


                 ....*..
gi 81908341  391 STGRLQI 397
Cdd:cd05744   85 FNAELVV 91

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

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 62.73 E-value: 3.96e-12

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 81908341  329 VRFTCEVHGNPAPNRTWFHNAQPIRPSS----RHLTEGSVLKITGVIMEDSGLYQCMADNGIGFMQST 392
Cdd:cd00096    1 VTLTCSASGNPPPTITWYKNGKPLPPSSrdsrRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASA 68

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: 63.31 E-value: 4.54e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  413 NVEVTDGDFVTLSCNATGEPVPVIHWygrhglitshpsqvlrSKSRKSHLFRPGDLDPEPVylIMSQAGSSSLSIQAVTR 492
Cdd:cd05732   10 NQTAVELEQITLTCEAEGDPIPEITW----------------RRATRGISFEEGDLDGRIV--VRGHARVSSLTLKDVQL 71

                         90       100
                 ....*....|....*....|....*
gi 81908341  493 EHAGKYTCEAVNKHGSTQSEAFLTV 517
Cdd:cd05732   72 TDAGRYDCEASNRIGGDQQSMYLEV 96

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: 62.35 E-value: 5.01e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  422 VTLSCNATGEPVPVIHWYgrhglitshpsqvlrsksrkshlFRPGDLDPEPVYLIMSQAGSSSLSIQAVTREHAGKYTCE 501
Cdd:cd00096    1 VTLTCSASGNPPPTITWY-----------------------KNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCV 57

                         90
                 ....*....|...
gi 81908341  502 AVNKHGSTQSEAF 514
Cdd:cd00096   58 ASNSAGGSASASV 70

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

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 62.91 E-value: 5.43e-12

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341     320 DQKVSLGATVRFTCEVHGNPAPNRTWFHNA-QPIRPSSR----HLTEGSVLKITGVIMEDSGLYQCMADNGIGFMQSTGR 394
Cdd:smart00410    3 SVTVKEGESVTLSCEASGSPPPEVTWYKQGgKLLAESGRfsvsRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGTT 82


                    ...
gi 81908341     395 LQI 397
Cdd:smart00410   83 LTV 85

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

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 62.25 E-value: 7.17e-12

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341     718 PEAPDRPTISMASETSVYVTWIP--RANGGSPITAFKVEYKRmKSSDWLVAAEDipPSKLSVEVRSLEPGSIYKFRVIVI 795
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTLSWEPppDDGITGYIVGYRVEYRE-EGSEWKEVNVT--PSSTSYTLTGLKPGTEYEFRVRAV 77


                    ....*.
gi 81908341     796 NHYGES 801
Cdd:smart00060   78 NGAGEG 83

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

Pssm-ID: 143224 [Multi-domain] Cd Length: 92 Bit Score: 61.60 E-value: 1.56e-11

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 81908341  323 VSLGATVRFTCEVHGNPAPNRTWFHNAQPIRPSSRHL---TE-GSVLKITGVIMEDSGLYQCMADNGIG 387
Cdd:cd05747   15 VSEGESARFSCDVDGEPAPTVTWMREGQIIVSSQRHQitsTEyKSTFEISKVQMSDEGNYTVVVENSEG 83

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

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 61.74 E-value: 1.56e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  833 EAVSDTQIMLKWTyiPSSNNNTPIQGFYIYYRPTDSDNDSDYkrDVVEGSKQWHTIGHLQPETSYDIKMQCFNEGGESEF 912
Cdd:cd00063   10 TDVTSTSVTLSWT--PPEDDGGPITGYVVEYREKGSGDWKEV--EVTPGSETSYTLTGLKPGTEYEFRVRAVNGGGESPP 85


                 ....*...
gi 81908341  913 SNVMICET 920
Cdd:cd00063   86 SESVTVTT 93

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: 59.34 E-value: 8.34e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341   33 EPLSAVQKLGRPVVLHCSAkPV---TARISWLHNGKRLDRNTEQIKI-HRGTLTILSLNPSLSGCYQCVANNSVGAVVSG 108
Cdd:cd05724    3 EPSDTQVAVGEMAVLECSP-PRghpEPTVSWRKDGQPLNLDNERVRIvDDGNLLIAEARKSDEGTYKCVATNMVGERESR 81


                 ....*
gi 81908341  109 PATVS 113
Cdd:cd05724   82 AARLS 86

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

Pssm-ID: 409388 Cd Length: 84 Bit Score: 58.36 E-value: 1.89e-10

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  329 VRFTCEVHGNPAPNRTWFHNAQPIRPSSR-HLTEGSVLKITGVIMEDSGLYQCMADNGIGFMQSTGRLQI 397
Cdd:cd05723   15 IVFECEVTGKPTPTVKWVKNGDVVIPSDYfKIVKEHNLQVLGLVKSDEGFYQCIAENDVGNAQASAQLII 84

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: 58.45 E-value: 2.42e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  413 NVEVTDGDFVTLSCNATGEPVPVIHWygrhglitshpsqvlrSKSRKSHLFRPGDLDPEPVYLIMSQAGSSSLSIQAVTR 492
Cdd:cd05870   10 NETTVENGAATLSCKAEGEPIPEITW----------------KRASDGHTFSEGDKSPDGRIEVKGQHGESSLHIKDVKL 73

                         90       100
                 ....*....|....*....|....*
gi 81908341  493 EHAGKYTCEAVNKHGSTQSEAFLTV 517
Cdd:cd05870   74 SDSGRYDCEAASRIGGHQKSMYLDI 98

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

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 57.79 E-value: 2.69e-10

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 81908341  320 DQKVSLGATVRFTCEVHGNPAPNRTWFHNAQPIrPSSR-HLTEGSVLKITGVIMEDSGLYQCMADNGIGFMQSTGRLQI 397
Cdd:cd05725    6 NQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGEL-PKGRyEILDDHSLKIRKVTAGDMGSYTCVAENMVGKIEASATLTV 83

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: 58.25 E-value: 2.84e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  318 LHDQKVSLGATVRFTCEVHGNPAPNRTWFHNAQPIRPSSRHLTEGSV-----LKITGVIMEDSGLYQCMADNGIGFMQST 392
Cdd:cd20975    7 LMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEgglcrLRILAAERGDAGFYTCKAVNEYGARQCE 86


                 ....*
gi 81908341  393 GRLQI 397
Cdd:cd20975   87 ARLEV 91

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

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 57.89 E-value: 3.12e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  406 VIVTAPANVEVTDGDFVTLSCNATGEPVPVIHWygrhglitshpsqvlrskSRKSHLFRPGDLDpepvyliMSQAGSSSL 485
Cdd:cd20952    1 IILQGPQNQTVAVGGTVVLNCQATGEPVPTISW------------------LKDGVPLLGKDER-------ITTLENGSL 55

                         90       100       110
                 ....*....|....*....|....*....|..
gi 81908341  486 SIQAVTREHAGKYTCEAVNKHGSTQSEAFLTV 517
Cdd:cd20952   56 QIKGAEKSDTGEYTCVALNLSGEATWSAVLDV 87

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 57.42 E-value: 4.35e-10

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 81908341    588 PDTYTLVWRTGRDGGMPINAYFVKYRKLDDGsgavGSWHTVRVPGSESELHLTELEPSSLYEVLMVARSAVGEGQP 663
Cdd:pfam00041   13 STSLTVSWTPPPDGNGPITGYEVEYRPKNSG----EPWNEITVPGTTTSVTLTGLKPGTEYEVRVQAVNGGGEGPP 84

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

Pssm-ID: 409474 Cd Length: 92 Bit Score: 57.03 E-value: 6.74e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  318 LHDQKVSLGATVRFTCEVHGNPAPNRTWFHNAQPIRPSSRHLT-----EGSV-LKITGVIMEDSGLYQCMADNGIGFMQS 391
Cdd:cd05893    7 LKHYKIFEGMPVTFTCRVAGNPKPKIYWFKDGKQISPKSDHYTiqrdlDGTCsLHTTASTLDDDGNYTIMAANPQGRISC 86


                 ....*.
gi 81908341  392 TGRLQI 397
Cdd:cd05893   87 TGRLMV 92

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 61.94 E-value: 2.02e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  717 VPEAPDRPTISMASETSVYVTWipRANGGSPITAFKVEYKRMKSSDWLVAAEdipPSKLSVEVRSLEPGSIYKFRVIVIN 796
Cdd:COG3401  232 PPSAPTGLTATADTPGSVTLSW--DPVTESDATGYRVYRSNSGDGPFTKVAT---VTTTSYTDTGLTNGTTYYYRVTAVD 306

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  797 HYGEsfRSSASRPyqVAGFPNRFsnrPITGPHIAYTEAVSDTQIMLKWTyiPSSNNNtpIQGFYIYYRPTDSDNDSDYKR 876
Cdd:COG3401  307 AAGN--ESAPSNV--VSVTTDLT---PPAAPSGLTATAVGSSSITLSWT--ASSDAD--VTGYNVYRSTSGGGTYTKIAE 375

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  877 DVvegSKQWHTIGHLQPETSYDIKMQCFNEGG-ESEFSNVMicetkvkRVPGASEYPMKELSTPPSSSGNGGNVGPATSP 955
Cdd:COG3401  376 TV---TTTSYTDTGLTPGTTYYYKVTAVDAAGnESAPSEEV-------SATTASAASGESLTASVDAVPLTDVAGATAAA 445


                 ....*
gi 81908341  956 ARSSD 960
Cdd:COG3401  446 SAASN 450

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: 54.89 E-value: 3.10e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341    410 APANVEVTDGDFVTLSCNA-TGEPVPVIHWygrhglitSHPSQVLRSKSRKSHLFRpgdldpepvylimsQAGSSSLSIQ 488
Cdd:pfam00047    2 APPTVTVLEGDSATLTCSAsTGSPGPDVTW--------SKEGGTLIESLKVKHDNG--------------RTTQSSLLIS 59

                           90       100
                   ....*....|....*....|....*..
gi 81908341    489 AVTREHAGKYTCEAVNKHGSTQSEAFL 515
Cdd:pfam00047   60 NVTKEDAGTYTCVVNNPGGSATLSTSL 86

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: 54.50 E-value: 4.57e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  315 SKGLHDQKVSLGATVRFTCEVHGNPAPNRTWFHNAQPIRPSSRHLTEGS-----VLKITGVIMEDSGLYQCMADNGIGFM 389
Cdd:cd20973    1 IQTLRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQDedglcSLIISDVCGDDSGKYTCKAVNSLGEA 80


                 ....*...
gi 81908341  390 QSTGRLQI 397
Cdd:cd20973   81 TCSAELTV 88

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

Pssm-ID: 143259 Cd Length: 88 Bit Score: 54.26 E-value: 5.35e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  312 ASISKGLHDQKVSLGATVRFTCEVHGNPAPNRTWFHNAQPIRPSSRHLTEGSVLKITGVIMEDSGLYQCMADNGIGFMQS 391
Cdd:cd05851    2 ADINVKFKDTYALKGQNVTLECFALGNPVPVIRWRKILEPMPATAEISMSGAVLKIFNIQPEDEGTYECEAENIKGKDKH 81


                 ....*..
gi 81908341  392 TGRLQIE 398
Cdd:cd05851   82 QARVYVQ 88

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: 53.79 E-value: 5.43e-09

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 81908341  326 GATVRFTCEVHGNPAPNRTWFHNAQPIRPSSRHLTEGS-VLKITGVIMEDSGLYQCMADNGIGFMQSTGRLQI 397
Cdd:cd05745    2 GQTVDFLCEAQGYPQPVIAWTKGGSQLSVDRRHLVLSSgTLRISRVALHDQGQYECQAVNIVGSQRTVAQLTV 74

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: 54.49 E-value: 6.02e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  321 QKVSLGATVRFTCEVHGNPAPNRTWFHNAQPIRPSSR-----HLTEG----SVLKITGVIMEDSGLYQCMADNGIGFMQS 391
Cdd:cd20956   11 QTLQPGPSVSLKCVASGNPLPQITWTLDGFPIPESPRfrvgdYVTSDgdvvSYVNISSVRVEDGGEYTCTATNDVGSVSH 90


                 ....*.
gi 81908341  392 TGRLQI 397
Cdd:cd20956   91 SARINV 96

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: 53.77 E-value: 8.42e-09

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 81908341     833 EAVSDTQIMLKWTyIPSSNNNTpiqGFYIYYRPTDSDNDSDYKRDVVEGSKQWHTIGHLQPETSYDIKMQCFNEGGES 910
Cdd:smart00060   10 TDVTSTSVTLSWE-PPPDDGIT---GYIVGYRVEYREEGSEWKEVNVTPSSTSYTLTGLKPGTEYEFRVRAVNGAGEG 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: 53.10 E-value: 8.94e-09

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 81908341  238 VTLECVVSGVPASQVYWLKDGQDcLSGSNWRRLYSHLATASI-----DPADSGNYSCVVGNNSSGDVKHVT 303
Cdd:cd00096    1 VTLTCSASGNPPPTITWYKNGKP-LPPSSRDSRRSELGNGTLtisnvTLEDSGTYTCVASNSAGGSASASV 70

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: 53.10 E-value: 9.86e-09

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 81908341   45 VVLHCSAKPV-TARISWLHNGKRLDRNTEQIKIH---RGTLTILSLNPSLSGCYQCVANNSVGAVVS 107
Cdd:cd00096    1 VTLTCSASGNpPPTITWYKNGKPLPPSSRDSRRSelgNGTLTISNVTLEDSGTYTCVASNSAGGSAS 67

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: 53.81 E-value: 1.05e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  408 VTAPANVEVTDGDFVTLSCNATGEPVPVIHWYGRHGLITSHPSQVLRSKSRkshlfrpgdldpepvyLIMSQAGSssLSI 487
Cdd:cd05726    3 VVKPRDQVVALGRTVTFQCETKGNPQPAIFWQKEGSQNLLFPYQPPQPSSR----------------FSVSPTGD--LTI 64

                         90       100       110
                 ....*....|....*....|....*....|
gi 81908341  488 QAVTREHAGKYTCEAVNKHGSTQSEAFLTV 517
Cdd:cd05726   65 TNVQRSDVGYYICQALNVAGSILAKAQLEV 94

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: 53.65 E-value: 1.06e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  574 PDAPNILSPPQTHmPDTYTLVWRTGRDGGMPINAYFVKYRKLDDGSgavgsWHTVRV-PGSESELHLTELEPSSLYEVLM 652
Cdd:cd00063    1 PSPPTNLRVTDVT-STSVTLSWTPPEDDGGPITGYVVEYREKGSGD-----WKEVEVtPGSETSYTLTGLKPGTEYEFRV 74

                         90
                 ....*....|....*....
gi 81908341  653 VARSAVGEGQPAM-LTFRT 670
Cdd:cd00063   75 RAVNGGGESPPSEsVTVTT 93

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

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 53.28 E-value: 1.14e-08

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341     227 SQALAVLPHSPVTLECVVSGVPASQVYWLKDGQDCLSGSN-----WRRLYSHLATASIDPADSGNYSCVVGNNSSGDVKH 301
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGrfsvsRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSG 80


                    ....*
gi 81908341     302 VTYTV 306
Cdd:smart00410   81 TTLTV 85

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: 53.16 E-value: 1.24e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  405 PVIVTAP-ANVEVTDGDFVTLSCNATGEPVPVIHWygrhglitSHPSQVLRSKSRKSHLfrpgdldpepvylimsqaGSS 483
Cdd:cd20978    1 PKFIQKPeKNVVVKGGQDVTLPCQVTGVPQPKITW--------LHNGKPLQGPMERATV------------------EDG 54

                         90       100       110
                 ....*....|....*....|....*....|....
gi 81908341  484 SLSIQAVTREHAGKYTCEAVNKHGSTQSEAFLTV 517
Cdd:cd20978   55 TLTIINVQPEDTGYYGCVATNEIGDIYTETLLHV 88

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: 53.32 E-value: 1.32e-08

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 81908341  326 GATVRFTCEVHGNPAPNRTWFHNAQPIRPSSRHLTEGSVLKITGVIMEDSGLYQCMADNGIGFMQSTGRLQI 397
Cdd:cd04968   16 GQTVTLECFALGNPVPQIKWRKVDGSPSSQWEITTSEPVLEIPNVQFEDEGTYECEAENSRGKDTVQGRIIV 87

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

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 53.19 E-value: 1.48e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  314 ISKGLHDQKVSLGATVRFTCEVHGNPAPNRTWFHNAQPIRPSSR------HLTEG-SVLKITGVIMEDSGLYQCMADNGI 386
Cdd:cd20951    3 FIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDPSSIpgkykiESEYGvHVLHIRRVTVEDSAVYSAVAKNIH 82

                         90
                 ....*....|..
gi 81908341  387 GFMQSTGRLQIE 398
Cdd:cd20951   83 GEASSSASVVVE 94

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: 53.27 E-value: 1.50e-08

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 81908341  314 ISKGLHDQKVSLGATVRFTCEVHGNPAPNRTWFHNAQPIRPSSRHLT--EGSVLKITGVIMEDSGLYQCMADNGIG 387
Cdd:cd20952    2 ILQGPQNQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDERITtlENGSLQIKGAEKSDTGEYTCVALNLSG 77

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

Pssm-ID: 409387 Cd Length: 97 Bit Score: 53.25 E-value: 1.69e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341   29 YFISEPLSAVQKLGRPVVLHCSAKPVTA-RISWLHNGK--RLDRNTEQIKIHRGTLTILSL-----NPSLSGCYQCVANN 100
Cdd:cd05722    3 YFLSEPSDIVAMRGGPVVLNCSAESDPPpKIEWKKDGVllNLVSDERRQQLPNGSLLITSVvhskhNKPDEGFYQCVAQN 82

                         90
                 ....*....|....*
gi 81908341  101 -SVGAVVSGPATVSA 114
Cdd:cd05722   83 eSLGSIVSRTARVTV 97

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 52.18 E-value: 2.15e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 81908341     30 FISEPLSAVQKLGRPVVLHCSAK-PVTARISWLHNGKRLDRNTEQIKIH---RGTLTILSLNPSLSGCYQCVANN 100
Cdd:pfam13927    4 ITVSPSSVTVREGETVTLTCEATgSPPPTITWYKNGEPISSGSTRSRSLsgsNSTLTISNVTRSDAGTYTCVASN 78

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: 2.22e-08

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 81908341  323 VSLGATVRFTCEVHGNPAPNRTWFHNAQPIRPSS---RHLTEGSVLKITGVIMEDSGLYQCMADNGIGF 388
Cdd:cd04978   11 LSPGETGELICEAEGNPQPTITWRLNGVPIEPAPedmRRTVDGRTLIFSNLQPNDTAVYQCNASNVHGY 79

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: 52.62 E-value: 2.73e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  313 SISKGLHDQKVSLGATVRFTCEVHGNPAPNRTWFHNAQPIRPSSRH-----LTEGSVLKITGVIMEDSGLYQCMADNGIG 387
Cdd:cd05763    1 SFTKTPHDITIRAGSTARLECAATGHPTPQIAWQKDGGTDFPAARErrmhvMPEDDVFFIVDVKIEDTGVYSCTAQNSAG 80

                         90
                 ....*....|
gi 81908341  388 FMQSTGRLQI 397
Cdd:cd05763   81 SISANATLTV 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: 52.12 E-value: 3.31e-08

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 81908341      40 KLGRPVVLHCSAK-PVTARISWLHNGKRLDRNTEQIKIHR----GTLTILSLNPSLSGCYQCVANNSVGaVVSGPATVS 113
Cdd:smart00410    7 KEGESVTLSCEASgSPPPEVTWYKQGGKLLAESGRFSVSRsgstSTLTISNVTPEDSGTYTCAATNSSG-SASSGTTLT 84

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: 52.27 E-value: 3.60e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  320 DQKVSLGATVRFTCEVHGNPAPNRTW---------FHNaQPIRPSSRHLTEGS-VLKITGVIMEDSGLYQCMADNGIGFM 389
Cdd:cd05726    8 DQVVALGRTVTFQCETKGNPQPAIFWqkegsqnllFPY-QPPQPSSRFSVSPTgDLTITNVQRSDVGYYICQALNVAGSI 86


                 ....*...
gi 81908341  390 QSTGRLQI 397
Cdd:cd05726   87 LAKAQLEV 94

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: 51.87 E-value: 4.67e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  405 PVIVTAPANVEVTDGDFVTLSCNATGEPVPVIHWygrhgLITSHPSQVLRSKSRkshlfrpgdldpepvylimSQAGSSS 484
Cdd:cd20976    2 PSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITW-----IRNAQPLQYAADRST-------------------CEAGVGE 57

                         90       100       110
                 ....*....|....*....|....*....|...
gi 81908341  485 LSIQAVTREHAGKYTCEAVNKHGSTQSEAFLTV 517
Cdd:cd20976   58 LHIQDVLPEDHGTYTCLAKNAAGQVSCSAWVTV 90

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 51.03 E-value: 5.65e-08

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 81908341    231 AVLPHSPVTLECVVSGVPASQVYWLKDGQDCLSGSNWRRL----YSHLATASIDPADSGNYSCVVGN 293
Cdd:pfam13927   12 TVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSlsgsNSTLTISNVTRSDAGTYTCVASN 78

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: 51.87 E-value: 5.68e-08

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 81908341  320 DQKVSLgatvrfTCEVHGNPAPNRTWFHNAQPIRPSSRH---LTEGSVLKITGVIMEDSGLYQCMADNGIGFMQS 391
Cdd:cd05848   19 EKKVIL------NCEARGNPVPTYRWLRNGTEIDTESDYrysLIDGNLIISNPSEVKDSGRYQCLATNSIGSILS 87

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

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 51.35 E-value: 7.64e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  320 DQKVSLGATVRFTCEVHGNPAPNRTWFHNA-QPIRPSSRHL--TEGSVLKITGVIMEDSGLYQCMADNGI-GFMQSTGRL 395
Cdd:cd20970   11 TVTAREGENATFMCRAEGSPEPEISWTRNGnLIIEFNTRYIvrENGTTLTIRNIRRSDMGIYLCIASNGVpGSVEKRITL 90


                 ..
gi 81908341  396 QI 397
Cdd:cd20970   91 QV 92

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: 51.39 E-value: 8.45e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  316 KGLHdqKVSLGATVRFTCEVHGNPAPNRTWFHNAQPIRPSSR---------HLTegsvLKITGVIMEDSGLYQCMADNGI 386
Cdd:cd05857   11 KKLH--AVPAANTVKFRCPAAGNPTPTMRWLKNGKEFKQEHRiggykvrnqHWS----LIMESVVPSDKGNYTCVVENEY 84

                         90
                 ....*....|.
gi 81908341  387 GFMQSTGRLQI 397
Cdd:cd05857   85 GSINHTYHLDV 95

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

Pssm-ID: 409393 [Multi-domain] Cd Length: 95 Bit Score: 51.07 E-value: 9.12e-08

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 81908341  326 GATVRFTCEVHGNPAPNRTWFHNAQPIRPSS-----RHLTEGSVLKITGVIMEDSGLYQCMADNGIGFMQSTGRLQI 397
Cdd:cd05729   19 ANKVRLECGAGGNPMPNITWLKDGKEFKKEHriggtKVEEKGWSLIIERAIPRDKGKYTCIVENEYGSINHTYDVDV 95

Fibronectin type III domain;

Pssm-ID: 394996 [Multi-domain] Cd Length: 85 Bit Score: 50.49 E-value: 1.18e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341    823 PITGPHIaytEAVSDTQIMLKWTyiPSSNNNTPIQGFYIYYRPTDSDNDSdyKRDVVEGSKQWHTIGHLQPETSYDIKMQ 902
Cdd:pfam00041    2 APSNLTV---TDVTSTSLTVSWT--PPPDGNGPITGYEVEYRPKNSGEPW--NEITVPGTTTSVTLTGLKPGTEYEVRVQ 74

                           90
                   ....*....|.
gi 81908341    903 CFNEGGESEFS 913
Cdd:pfam00041   75 AVNGGGEGPPS 85

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: 50.68 E-value: 1.31e-07

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 81908341  326 GATVRFTCEVHGNPAPNRTWFHNAQPIRPSSRHLT-----EGSVLKITGVIMEDSGLYQCMADNGIG 387
Cdd:cd05891   16 GKTLNLTCTVFGNPDPEVIWFKNDQDIELSEHYSVkleqgKYASLTIKGVTSEDSGKYSINVKNKYG 82

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: 50.11 E-value: 1.71e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  405 PVIVTAPANVEVTDGDFVTLSCNATGEPVPVIHWYGRHGLITSHpsqvlrSKSRKshlfrpgdldpepvYLIMSQAGSSS 484
Cdd:cd20951    1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDPS------SIPGK--------------YKIESEYGVHV 60

                         90       100       110
                 ....*....|....*....|....*....|...
gi 81908341  485 LSIQAVTREHAGKYTCEAVNKHGSTQSEAFLTV 517
Cdd:cd20951   61 LHIRRVTVEDSAVYSAVAKNIHGEASSSASVVV 93

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: 49.70 E-value: 2.65e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  226 LSQALAVLPHSPVTLECVVSGVPASQVYWLKDGQDcLSGSNWRRLY--SHLATASIDPADSGNYSCvVGNNSSGDVkHVT 303
Cdd:cd20978    7 PEKNVVVKGGQDVTLPCQVTGVPQPKITWLHNGKP-LQGPMERATVedGTLTIINVQPEDTGYYGC-VATNEIGDI-YTE 83


                 ....*
gi 81908341  304 YTVNV 308
Cdd:cd20978   84 TLLHV 88

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: 49.77 E-value: 2.83e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  405 PVIVTAPANVEVTDGDFVTLSCNATGEPVPVIHWYGRHGLITshpsqvlrsksrkshlfrpgdLDPEPVYLIMSQAGSSS 484
Cdd:cd05892    1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKKNNEMLQ---------------------YNTDRISLYQDNCGRIC 59

                         90       100       110
                 ....*....|....*....|....*....|...
gi 81908341  485 LSIQAVTREHAGKYTCEAVNKHGSTQSEAFLTV 517
Cdd:cd05892   60 LLIQNANKKDAGWYTVSAVNEAGVVSCNARLDV 92

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

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 49.03 E-value: 3.52e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341   30 FISEPLSAVQKLGRPVVLHCSA--KPVTArISWLHNGKRLDRNTEQIKI-HRGTLTILSLNPSLSGCYQCVANNSvgavv 106
Cdd:cd20952    2 ILQGPQNQTVAVGGTVVLNCQAtgEPVPT-ISWLKDGVPLLGKDERITTlENGSLQIKGAEKSDTGEYTCVALNL----- 75


                 ....*...
gi 81908341  107 SGPATVSA 114
Cdd:cd20952   76 SGEATWSA 83

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: 49.47 E-value: 3.72e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  230 LAVLPHSPVTLECVVSGVPASQVYWLKDGQ-----DCLSGSNWRRLYSHLATASIDPADSGNYSCVVgNNSSGDVKHvTY 304
Cdd:cd05857   14 HAVPAANTVKFRCPAAGNPTPTMRWLKNGKefkqeHRIGGYKVRNQHWSLIMESVVPSDKGNYTCVV-ENEYGSINH-TY 91


                 ....
gi 81908341  305 TVNV 308
Cdd:cd05857   92 HLDV 95

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

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 49.47 E-value: 4.30e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341   31 ISEPLSAVQKLGRPVVLHCSA--KPvTARISWLHNGKRLDRNTEQIKIHR-----GTLTILSLNPSL-----SGCYQCVA 98
Cdd:cd07693    4 VEHPSDLIVSKGDPATLNCKAegRP-TPTIQWLKNGQPLETDKDDPRSHRivlpsGSLFFLRVVHGRkgrsdEGVYVCVA 82

                         90
                 ....*....|....
gi 81908341   99 NNSVGAVVSGPATV 112
Cdd:cd07693   83 HNSLGEAVSRNASL 96

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

Pssm-ID: 409357 [Multi-domain] Cd Length: 88 Bit Score: 49.08 E-value: 4.41e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  406 VIVTAPANVEVTDGDFVTLSCNATGEPVPVIHWYGRHGlitSHPSQVLRSKSrkshlfrpgdldpEPVylimsqagsssL 485
Cdd:cd04968    3 IKVRFPADTYALKGQTVTLECFALGNPVPQIKWRKVDG---SPSSQWEITTS-------------EPV-----------L 55

                         90       100       110
                 ....*....|....*....|....*....|..
gi 81908341  486 SIQAVTREHAGKYTCEAVNKHGSTQSEAFLTV 517
Cdd:cd04968   56 EIPNVQFEDEGTYECEAENSRGKDTVQGRIIV 87

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

Pssm-ID: 409567 Cd Length: 91 Bit Score: 49.01 E-value: 4.63e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  405 PVIVTAPANVEVTDGDFVTLSCNATGEPVPVIHWYGRHglitshpsQVLRSKSRKshlfrpgdldpepvYLIMSQAGSSS 484
Cdd:cd20975    1 PTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNR--------QPVRPDQRR--------------FAEEAEGGLCR 58

                         90       100       110
                 ....*....|....*....|....*....|...
gi 81908341  485 LSIQAVTREHAGKYTCEAVNKHGSTQSEAFLTV 517
Cdd:cd20975   59 LRILAAERGDAGFYTCKAVNEYGARQCEARLEV 91

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 48.41 E-value: 7.04e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 81908341    238 VTLECVVSGVPASQVYWLKDGQDCLSGSNWRRLYSH----LATASIDPADSGNYSCVVGNNSSGDVKHVTYTV 306
Cdd:pfam07679   18 ARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEGgtytLTISNVQPDDSGKYTCVATNSAGEAEASAELTV 90

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: 48.40 E-value: 7.55e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  313 SISKGLHDQKVSLGATVRFTCEVHGNPAPNRTWFHNAQPIRPSSRHLT---EGSVLKITGVIMEDSGLYQCMADNGIGFM 389
Cdd:cd20976    3 SFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQYAADRSTceaGVGELHIQDVLPEDHGTYTCLAKNAAGQV 82


                 ....*...
gi 81908341  390 QSTGRLQI 397
Cdd:cd20976   83 SCSAWVTV 90

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: 48.02 E-value: 9.45e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341   30 FISEP--LSAVQklGRPVVLHCSA--KPVtARISWLHNGKRLDRNTEQIKIHRGT--LTILSLNPSLSGCYQCVANNSVG 103
Cdd:cd20976    4 FSSVPkdLEAVE--GQDFVAQCSArgKPV-PRITWIRNAQPLQYAADRSTCEAGVgeLHIQDVLPEDHGTYTCLAKNAAG 80


                 ..
gi 81908341  104 AV 105
Cdd:cd20976   81 QV 82

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: 48.17 E-value: 1.06e-06

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 81908341  320 DQKVSLGATVRFTCEVHGNPAPNRTWFHNAQPIRPSSRH---LTEGSV--LKITGVIMEDSGLYQCMADNGIG 387
Cdd:cd20990    9 DLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSAHkmlVRENGVhsLIIEPVTSRDAGIYTCIATNRAG 81

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

Pssm-ID: 409453 [Multi-domain] Cd Length: 89 Bit Score: 47.97 E-value: 1.08e-06

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 81908341  326 GATVRFTCEVHGNPAPNRTWFHNAQPIR---PSSRHLTEGSVLKITGVIMEDSGLYQCMADN 384
Cdd:cd05867   14 GETARLDCQVEGIPTPNITWSINGAPIEgtdPDPRRHVSSGALILTDVQPSDTAVYQCEARN 75

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: 47.59 E-value: 1.16e-06

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 81908341   50 SAKPVTArISWLHNGKRLDRNtEQIKIHRGTLTILSLNPSLSGCYQCVANNSVGAV 105
Cdd:cd05728   24 SGNPRPA-YRWLKNGQPLASE-NRIEVEAGDLRITKLSLSDSGMYQCVAENKHGTI 77

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: 47.98 E-value: 1.26e-06

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 81908341  236 SPVTLECVVSGVPASQVYWLKDGQ-----DCLSGSNWRRLYSHLATASIDPADSGNYSCVVgNNSSGDVKHvTYTVNV 308
Cdd:cd05729   20 NKVRLECGAGGNPMPNITWLKDGKefkkeHRIGGTKVEEKGWSLIIERAIPRDKGKYTCIV-ENEYGSINH-TYDVDV 95

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

Pssm-ID: 143224 [Multi-domain] Cd Length: 92 Bit Score: 47.74 E-value: 1.31e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  407 IVTAPANVEVTDGDFVTLSCNATGEPVPVIHWYgRHGlitshpsQVLRSKSRkshlfrpgdldpepvYLIMSQAGSSSLS 486
Cdd:cd05747    6 ILTKPRSLTVSEGESARFSCDVDGEPAPTVTWM-REG-------QIIVSSQR---------------HQITSTEYKSTFE 62

                         90       100       110
                 ....*....|....*....|....*....|
gi 81908341  487 IQAVTREHAGKYTCEAVNKHGSTQSEAFLT 516
Cdd:cd05747   63 ISKVQMSDEGNYTVVVENSEGKQEAQFTLT 92

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: 1.66e-06

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 81908341  138 IGCRvPESNPKAEVRYKiRGKWLMYSTGNYIILPSGNLQILNVSSKDKGSYKCAAYN 194
Cdd:cd04969   22 IECK-PKASPKPTISWS-KGTELLTNSSRICILPDGSLKIKNVTKSDEGKYTCFAVN 76

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: 47.35 E-value: 2.09e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  405 PVIVTAPANVEVTDGDFVTLSCNATGEPVPVIHWYgRHGLITshpsqvlrsksrkshlfrpgDLDPEPVYLIMSQAGSSS 484
Cdd:cd20974    1 PVFTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWF-RDGQVI--------------------STSTLPGVQISFSDGRAK 59

                         90       100       110
                 ....*....|....*....|....*....|...
gi 81908341  485 LSIQAVTREHAGKYTCEAVNKHGSTQSEAFLTV 517
Cdd:cd20974   60 LSIPAVTKANSGRYSLTATNGSGQATSTAELLV 92

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

Pssm-ID: 409399 [Multi-domain] Cd Length: 93 Bit Score: 47.26 E-value: 2.21e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  321 QKVSLGATVRFTCEVHGNPAPNRTWFHNAQPIRPS-SRHLT---EGSVLKITGVIMEDSGLYQCMADNGIGFMQSTGRLQ 396
Cdd:cd05736   10 QAKEPGVEASLRCHAEGIPLPRVQWLKNGMDINPKlSKQLTliaNGSELHISNVRYEDTGAYTCIAKNEGGVDEDISSLF 89


                 ...
gi 81908341  397 IEQ 399
Cdd:cd05736   90 VED 92

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

Pssm-ID: 214495 [Multi-domain] Cd Length: 83 Bit Score: 46.84 E-value: 2.32e-06

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341     574 PDAPNILSPPQTHmPDTYTLVWRTGRDGGmpINAYFVKYRKLDDGSGavGSWHTVRVPGSESELHLTELEPSSLYEVLMV 653
Cdd:smart00060    1 PSPPSNLRVTDVT-STSVTLSWEPPPDDG--ITGYIVGYRVEYREEG--SEWKEVNVTPSSTSYTLTGLKPGTEYEFRVR 75


                    ....*...
gi 81908341     654 ARSAVGEG 661
Cdd:smart00060   76 AVNGAGEG 83

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

Pssm-ID: 143220 Cd Length: 78 Bit Score: 46.33 E-value: 2.65e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  419 GDFVTLSCNATGEPVPVIHWYGRHGLITSHPSqvlrsksrkshlfrpgdldpepvYLIMSQAGSSSLSIQAVTREHAGKY 498
Cdd:cd05743    1 GETVEFTCVATGVPTPIINWRLNWGHVPDSAR-----------------------VSITSEGGYGTLTIRDVKESDQGAY 57

                         90       100
                 ....*....|....*....|.
gi 81908341  499 TCEAVNKHGST--QSEAFLTV 517
Cdd:cd05743   58 TCEAINTRGMVfgIPDGILTV 78

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1(FGFRL1); member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 is comprised of a signal peptide, three extracellular Ig-like modules, a transmembrane segment, and a short intracellular domain. FGFRL1 is expressed preferentially in skeletal tissues. Similar to FGF receptors, the expressed protein interacts specifically with heparin and with FGF2. FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409442 Cd Length: 92 Bit Score: 46.78 E-value: 3.05e-06

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 81908341  236 SPVTLECVVSGVPASQVYWLKDGQDCLS---GSNWRRLYShLATASIDPADSGNYSCVVgNNSSGDVkHVTYTVNV 308
Cdd:cd05856   20 SSVRLKCVASGNPRPDITWLKDNKPLTPpeiGENKKKKWT-LSLKNLKPEDSGKYTCHV-SNRAGEI-NATYKVDV 92

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 46.23 E-value: 3.14e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341    404 RPVIVTAPANVevTDGDFVTLSCNATGEPVPVIHWYGRHGLITSHPsqvlrsksrkshlfrpgdldpepvylimsqagss 483
Cdd:pfam13895    1 KPVLTPSPTVV--TEGEPVTLTCSAPGNPPPSYTWYKDGSAISSSP---------------------------------- 44

                           90       100
                   ....*....|....*....|....*...
gi 81908341    484 SLSIQAVTREHAGKYTCEAVNKHGSTQS 511
Cdd:pfam13895   45 NFFTLSVSAEDSGTYTCVARNGRGGKVS 72

First immunoglobulin-like domains A168 within the A-band segment of human cardiac titin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domain A168 within the A-band segment of human cardiac titin. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the titin-A168169 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409563 Cd Length: 93 Bit Score: 46.69 E-value: 3.40e-06

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 81908341  318 LHDQKVSLGATVRFTCEVHGNPAPNRTWFHNAQPIRPSSRHLT-EGSV----LKITGV-IMEDSGLYQCMADNGIG 387
Cdd:cd20971    8 LRNLNVRYQSNATLVCKVTGHPKPIVKWYRQGKEIIADGLKYRiQEFKggyhQLIIASvTDDDATVYQVRATNQGG 83

Immunoglobulin (Ig)-like domain at the C-terminus of semaphorins; The members here are composed of the immunoglobulin (Ig)-like domain in semaphorins. Semaphorins are transmembrane protein that have important roles in a variety of tissues. Functionally, semaphorins were initially characterized for their importance in the development of the nervous system and in axonal guidance. Later they have been found to be important for the formation and functioning of the cardiovascular, endocrine, gastrointestinal, hepatic, immune, musculoskeletal, renal, reproductive, and respiratory systems. Semaphorins function through binding to their receptors and transmembrane semaphorins also serves as receptors themselves. Although molecular mechanism of semaphorins is poorly understood, the Ig-like domains may be involved in ligand binding or dimerization.

Pssm-ID: 409368 Cd Length: 88 Bit Score: 46.30 E-value: 3.65e-06

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 81908341   40 KLGRPVVLHCSAKPVTARISWLHNGKRLDR-NTEQIKIH-RGTLTILSLNPSLSGCYQCVANNSV 102
Cdd:cd04979    9 KEGDTVILSCSVKSNNAPVTWIHNGKKVPRyRSPRLVLKtERGLLIRSAQEADAGVYECHSGERV 73

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: 46.47 E-value: 4.68e-06

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 81908341  324 SLGATVRFTCEVHGNPAPNRTWFHNAQPIR--PSSRH-LTEGSVLKITGVIMEDSGLYQCMADNGIGFMQST 392
Cdd:cd04967   17 SDEKKVALNCRARANPVPSYRWLMNGTEIDleSDYRYsLVDGTLVISNPSKAKDAGHYQCLATNTVGSVLSR 88

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: 46.39 E-value: 4.87e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  308 VLEHASiskglhDQKVSLGATVRFTCEVHGNPAPNRTWFHNAQPIR-----PSSRH--LTEGSV--LKITG--VIMEDSG 376
Cdd:cd07693    3 IVEHPS------DLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLEtdkddPRSHRivLPSGSLffLRVVHgrKGRSDEG 76

                         90
                 ....*....|.
gi 81908341  377 LYQCMADNGIG 387
Cdd:cd07693   77 VYVCVAHNSLG 87

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: 46.04 E-value: 5.09e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  318 LHDQKVSLGATVRFTCEVHGNPAPNRTWFHNAQPIR--PSSRHLTEGSV--LKITGVIMEDSGLYQCMADNGIGFMQSTG 393
Cdd:cd20972    8 LRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQnsPDIQIHQEGDLhsLIIAEAFEEDTGRYSCLATNSVGSDTTSA 87


                 ....
gi 81908341  394 RLQI 397
Cdd:cd20972   88 EIFV 91

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: 45.69 E-value: 6.94e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  120 FDSSTMHVI----TAEKKNTgfIGCRVpESNPKAEVRYKIRGKWLMYSTGNYIILPSGNLQILN-VSSKDKGSYKCAAYN 194
Cdd:cd05850    5 FEEQPSSTLfpegSAEEKVT--LACRA-RASPPATYRWKMNGTELKMEPDSRYRLVAGNLVISNpVKAKDAGSYQCLASN 81


                 ..
gi 81908341  195 PV 196
Cdd:cd05850   82 RR 83

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 50.39 E-value: 7.20e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  718 PEAPDRPTISMASETSVYVTWIPraNGGSPITAFKVEYKRMKSSDWLVAAEDIppSKLSVEVRSLEPGSIYKFRVIVINH 797
Cdd:COG3401  327 PAAPSGLTATAVGSSSITLSWTA--SSDADVTGYNVYRSTSGGGTYTKIAETV--TTTSYTDTGLTPGTTYYYKVTAVDA 402

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  798 YGESfrSSASRPYQVAGFPNRFSNRPITGPHIAYTEAVSDTQIMLKWTYIPSSNNNTPIQGFYIYYRPTDsDNDSDYKRD 877
Cdd:COG3401  403 AGNE--SAPSEEVSATTASAASGESLTASVDAVPLTDVAGATAAASAASNPGVSAAVLADGGDTGNAVPF-TTTSSTVTA 479

                        170
                 ....*....|
gi 81908341  878 VVEGSKQWHT 887
Cdd:COG3401  480 TTTDTTTANL 489

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: 7.49e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  316 KGLHDQKVSLGATVRFTCE-VHGNPAPNRTWFHN------AQPIRPSSRHLTEGSVLKITGVIMEDSGLYQCMADNGIGF 388
Cdd:cd05750    4 KEMKSQTVQEGSKLVLKCEaTSENPSPRYRWFKDgkelnrKRPKNIKIRNKKKNSELQINKAKLEDSGEYTCVVENILGK 83


                 ....*....
gi 81908341  389 MQSTGRLQI 397
Cdd:cd05750   84 DTVTGNVTV 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: 44.87 E-value: 8.72e-06

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 81908341  329 VRFTCEVHGNPAPNRTWFHNAQPIRPSSR-HLTEGSVLKITGVIMEDSGLYQCMADNGIGFMQSTGRL 395
Cdd:cd05746    1 VQIPCSAQGDPEPTITWNKDGVQVTESGKfHISPEGYLAIRDVGVADQGRYECVARNTIGYASVSMVL 68

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 45.33 E-value: 9.18e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341     29 YFISEPLSAVQKLGRPVVLHCSAK--PvTARISWLHNGKRLdRNTEQIKIH----RGTLTILSLNPSLSGCYQCVANNSV 102
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVTgtP-DPEVSWFKDGQPL-RSSDRFKVTyeggTYTLTISNVQPDDSGKYTCVATNSA 79


                   ...
gi 81908341    103 GAV 105
Cdd:pfam07679   80 GEA 82

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 44.69 E-value: 1.11e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 81908341    318 LHDQKVSLGATVRFTCEVHGNPAPNRTWFHNAQPIRPSSRHLTegsvLKITGvimEDSGLYQCMADNGIGFMQS 391
Cdd:pfam13895    6 PSPTVVTEGEPVTLTCSAPGNPPPSYTWYKDGSAISSSPNFFT----LSVSA---EDSGTYTCVARNGRGGKVS 72

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: 44.76 E-value: 1.17e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 81908341  323 VSLGATVRFTCEVHGNPAPNRTWFHNAQPIRPSSR-HLTEGSVLKITGVIMEDSGLYQCMADNGIGFMQSTGRLQI 397
Cdd:cd04969   14 AAKGGDVIIECKPKASPKPTISWSKGTELLTNSSRiCILPDGSLKIKNVTKSDEGKYTCFAVNFFGKANSTGSLSV 89

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: 44.79 E-value: 1.39e-05

                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 81908341  482 SSSLSIQAVTREHAGKYTCEAVNKHGSTQSEAFLTV 517
Cdd:cd20959   59 SSILSIDSLEASHAGNYTCHARNSAGSASYTAPLTV 94

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: 44.77 E-value: 1.52e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  405 PVIVTAPANVEVTDGDFVTLSCNATGEPVPVIHWYGrhglitshPSQVLRSKSRKSHLFRPGDLDpepvylimsqagsss 484
Cdd:cd05764    1 PLITRHTHELRVLEGQRATLRCKARGDPEPAIHWIS--------PEGKLISNSSRTLVYDNGTLD--------------- 57

                         90       100
                 ....*....|....*....|....*...
gi 81908341  485 lsIQAVTREHAGKYTCEAVNKHG-STQS 511
Cdd:cd05764   58 --ILITTVKDTGAFTCIASNPAGeATAR 83

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: 44.53 E-value: 1.52e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  411 PANVEVTDGDFVTLSCNATGEPVPVIHWYGRHGliTSHPSqvlrSKSRKSHLFRPGDldpepVYLIMSqagssslsiqaV 490
Cdd:cd05763    6 PHDITIRAGSTARLECAATGHPTPQIAWQKDGG--TDFPA----ARERRMHVMPEDD-----VFFIVD-----------V 63

                         90       100
                 ....*....|....*....|....*...
gi 81908341  491 TREHAGKYTCEAVNKHGSTQSEAFLTVV 518
Cdd:cd05763   64 KIEDTGVYSCTAQNSAGSISANATLTVL 91

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: 44.50 E-value: 1.64e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  405 PVIVTAPANVEVTDGDFVTLSCNATGEPVPVIHWYgRHGlitshpsqvlrsksrkshlfrpGDLDPEPVYLIMSQAGSSS 484
Cdd:cd20972    2 PQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWF-CEG----------------------KELQNSPDIQIHQEGDLHS 58

                         90       100       110
                 ....*....|....*....|....*....|...
gi 81908341  485 LSIQAVTREHAGKYTCEAVNKHGSTQSEAFLTV 517
Cdd:cd20972   59 LIIAEAFEEDTGRYSCLATNSVGSDTTSAEIFV 91

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: 44.63 E-value: 1.78e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 81908341  323 VSLGATVRFTCEVHGNPAPNRTWFHNAQPIRPSSRHLTEGSV----LKITGVIMEDSGLYQCMADN 384
Cdd:cd20949   11 VKEGQSATILCEVKGEPQPNVTWHFNGQPISASVADMSKYRIladgLLINKVTQDDTGEYTCRAYQ 76

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

Pssm-ID: 409560 [Multi-domain] Cd Length: 88 Bit Score: 44.54 E-value: 1.81e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 81908341  322 KVSLGATVRFTCEVHGNPAPNRTWFHNAQPIRPSSR-HLTEGSVLKITGVIMEDSGLYQCMADNGIG 387
Cdd:cd20968   10 TIIEGLKAVLPCTTMGNPKPSVSWIKGDDLIKENNRiAVLESGSLRIHNVQKEDAGQYRCVAKNSLG 76

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

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 44.06 E-value: 2.18e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 81908341   34 PLSA-----VQKL--GRPVVLHC--SAKPVTaRISWLHNGKRLDRNTEQIKIHRGTLTILSLNPSLSGCYQCVANNSV 102
Cdd:cd20957    1 PLSAtidppVQTVdfGRTAVFNCsvTGNPIH-TVLWMKDGKPLGHSSRVQILSEDVLVIPSVKREDKGMYQCFVRNDG 77

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: 44.12 E-value: 2.24e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 81908341  326 GATVRFTCEVHGNPAPNRTWFHNAQPIRPSSRH---LTEGSVLKIT--GVIMEDSGLYQCMADNGIG 387
Cdd:cd05737   16 GKTLNLTCNVWGDPPPEVSWLKNDQALAFLDHCnlkVEAGRTVYFTinGVSSEDSGKYGLVVKNKYG 82

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: 43.93 E-value: 2.49e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 81908341  237 PVTLECVVS-GVPASQVYWLKDGQDCLSGSNWRRLYS--HLATASIDPADSGNYSCvVGNNSSG 297
Cdd:cd05724   14 MAVLECSPPrGHPEPTVSWRKDGQPLNLDNERVRIVDdgNLLIAEARKSDEGTYKC-VATNMVG 76

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: 43.98 E-value: 2.71e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341   29 YFISEPLSAVQKLGRPVVLHCSAKPV-TARISWLHNGKRLDRNTEQI--KIHRGTLTILSLNPSLSGCYQCVANNSVGAV 105
Cdd:cd04978    1 YWIIEPPSLVLSPGETGELICEAEGNpQPTITWRLNGVPIEPAPEDMrrTVDGRTLIFSNLQPNDTAVYQCNASNVHGYL 80


                 .
gi 81908341  106 V 106
Cdd:cd04978   81 L 81

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

Pssm-ID: 409394 [Multi-domain] Cd Length: 83 Bit Score: 43.55 E-value: 3.09e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  232 VLPHSPVTLECVVSGVPASQVYWLKDGQDCLSGSNwrRLYSHLATASID---PADSGNYSCvVGNNSSGDVKHvTYTVNV 308
Cdd:cd05731    7 VLRGGVLLLECIAEGLPTPDIRWIKLGGELPKGRT--KFENFNKTLKIEnvsEADSGEYQC-TASNTMGSARH-TISVTV 82

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

Pssm-ID: 409435 Cd Length: 96 Bit Score: 43.78 E-value: 3.12e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341   30 FISEPLSAVQKLG---RPVVLHCSAK--PVTArISWLHNGKRLDRNTE-QIKIHRGTLTILslNPSL---SGCYQCVANN 100
Cdd:cd05848    4 FVQEPDDAIFPTDsdeKKVILNCEARgnPVPT-YRWLRNGTEIDTESDyRYSLIDGNLIIS--NPSEvkdSGRYQCLATN 80

                         90
                 ....*....|..
gi 81908341  101 SVGAVVSGPATV 112
Cdd:cd05848   81 SIGSILSREALL 92

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

Pssm-ID: 409394 [Multi-domain] Cd Length: 83 Bit Score: 43.55 E-value: 3.21e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 81908341  326 GATVRFTCEVHGNPAPNRTWFHNAQPIrPSSRHLTE--GSVLKITGVIMEDSGLYQCMADNGIGFMQST 392
Cdd:cd05731   10 GGVLLLECIAEGLPTPDIRWIKLGGEL-PKGRTKFEnfNKTLKIENVSEADSGEYQCTASNTMGSARHT 77

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: 4.21e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  408 VTAPANVEVTDGDFVTLSCNATGEPVPVIHWygrhgLITSHPsqvlrsksrkshlfrpgdLDPEPVYLIMSQAGsSSLSI 487
Cdd:cd04978    3 IIEPPSLVLSPGETGELICEAEGNPQPTITW-----RLNGVP------------------IEPAPEDMRRTVDG-RTLIF 58

                         90       100       110
                 ....*....|....*....|....*....|.
gi 81908341  488 QAVTREHAGKYTCEAVNKHGSTQSEAFLTVV 518
Cdd:cd04978   59 SNLQPNDTAVYQCNASNVHGYLLANAFLHVL 89

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

Pssm-ID: 409444 Cd Length: 105 Bit Score: 43.80 E-value: 4.87e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  411 PANVEVTDGDFVTLSCNATGEPVPVIHWygrhglitshpsqvLRSKSRKSHLFRPgdlDPEPVYLIMSQAGSSS------ 484
Cdd:cd05858    8 PANTSVVVGTDAEFVCKVYSDAQPHIQW--------------LKHVEKNGSKYGP---DGLPYVEVLKTAGVNTtdkeie 70

                         90       100       110
                 ....*....|....*....|....*....|....
gi 81908341  485 -LSIQAVTREHAGKYTCEAVNKHGSTQSEAFLTV 517
Cdd:cd05858   71 vLYLRNVTFEDAGEYTCLAGNSIGISHHSAWLTV 104

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

Pssm-ID: 409444 Cd Length: 105 Bit Score: 43.80 E-value: 4.92e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  320 DQKVSLGATVRFTCEVHGNPAPNRTWFHNAQpiRPSSRHLTEG----SVLKITGV---------------IMEDSGLYQC 380
Cdd:cd05858   10 NTSVVVGTDAEFVCKVYSDAQPHIQWLKHVE--KNGSKYGPDGlpyvEVLKTAGVnttdkeievlylrnvTFEDAGEYTC 87

                         90
                 ....*....|....*..
gi 81908341  381 MADNGIGFMQSTGRLQI 397
Cdd:cd05858   88 LAGNSIGISHHSAWLTV 104

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: 42.94 E-value: 5.02e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 81908341   34 PLSAVQklGRPVVLHC--SAKPVTaRISWLHNGKRLDRNTEQIKIHRGTLTILSLNPSL-SGCYQCVANNSVG 103
Cdd:cd20958    9 NLTAVA--GQTLRLHCpvAGYPIS-SITWEKDGRRLPLNHRQRVFPNGTLVIENVQRSSdEGEYTCTARNQQG 78

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: 43.22 E-value: 5.18e-05

                         10        20        30
                 ....*....|....*....|....*....|....
gi 81908341  484 SLSIQAVTREHAGKYTCEAVNKHGSTQSEAFLTV 517
Cdd:cd04969   56 SLKIKNVTKSDEGKYTCFAVNFFGKANSTGSLSV 89

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: 43.16 E-value: 5.39e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 81908341  337 GNPAPNRTWFHNAQPIRPSS--RHLTEGSVLKITGVIMEDSGLYQCMADNGIGFMQS-TGRLQI 397
Cdd:cd05724   24 GHPEPTVSWRKDGQPLNLDNerVRIVDDGNLLIAEARKSDEGTYKCVATNMVGERESrAARLSV 87

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

Pssm-ID: 409546 [Multi-domain] Cd Length: 96 Bit Score: 43.07 E-value: 6.00e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  405 PVIVTAPANVEVTDGDFVTLSCNATGEPVPVIHWygrhglitshpsqvlrsksRKSHLFRPG---DLDPEPVYLIMSQAg 481
Cdd:cd20954    2 PRWIVEPVDANVAAGQDVMLHCQADGFPTPTVTW-------------------KKATGSTPGeykDLLYDPNVRILPNG- 61

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 81908341  482 ssSLSIQAVTREHAGKYTCEAVNKHGSTQSEA-FLTV 517
Cdd:cd20954   62 --TLVFGHVQKENEGHYLCEAKNGIGSGLSKViFLKV 96

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

Pssm-ID: 409534 Cd Length: 116 Bit Score: 43.80 E-value: 6.28e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  408 VTAPANVEVTDGDFVTLSCNATGEPVPVIHWYgrhgLITSHPSQVLrsksrkSHLFRPGDLDPEPVYLIMSQAGSSSLSI 487
Cdd:cd20940    4 IKSPLSQQRLVGDSVELHCEAVGSPIPEIQWW----FEGQEPNEIC------SQLWDGARLDRVHINATYHQHATSTISI 73

                         90
                 ....*....|....*..
gi 81908341  488 QAVTREHAGKYTCEAVN 504
Cdd:cd20940   74 DNLTEEDTGTYECRASN 90

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

Pssm-ID: 409397 [Multi-domain] Cd Length: 97 Bit Score: 42.86 E-value: 6.72e-05

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 81908341  320 DQKVSLGATVRFTCEVHGNPAPNRTWFHNAQPIRPSSRH----------LTEGSVLkITGVIMEDSGLYQCMADNGIG 387
Cdd:cd05734   10 DQDGIYGKAVVLNCSADGYPPPTIVWKHSKGSGVPQFQHivplngriqlLSNGSLL-IKHVLEEDSGYYLCKVSNDVG 86

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: 42.92 E-value: 6.90e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  405 PVIVTAPANVEVTDGDFVTLSCNATGEPVPVIHWYgRHGlitsHPSQVLRSKSRKSHLFRPgdldpepvylimsqagSSS 484
Cdd:cd07693    1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWL-KNG----QPLETDKDDPRSHRIVLP----------------SGS 59

                         90       100       110
                 ....*....|....*....|....*....|..
gi 81908341  485 LSIQAV-----TREHAGKYTCEAVNKHGSTQS 511
Cdd:cd07693   60 LFFLRVvhgrkGRSDEGVYVCVAHNSLGEAVS 91

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

Pssm-ID: 143277 [Multi-domain] Cd Length: 97 Bit Score: 42.66 E-value: 7.95e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  420 DFVTLSCNATGEPVPVIHWYGRHGLITSHpsqvlrSKSRKSHLfrpgdldpepvyLIMSQAGSSSLSIQAVTREHAGKYT 499
Cdd:cd05869   18 EQITLTCEASGDPIPSITWRTSTRNISSE------EKTLDGHI------------VVRSHARVSSLTLKYIQYTDAGEYL 79

                         90
                 ....*....|....*...
gi 81908341  500 CEAVNKHGSTQSEAFLTV 517
Cdd:cd05869   80 CTASNTIGQDSQSMYLEV 97

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: 42.16 E-value: 1.14e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 81908341  234 PHSPVTLECVVSGVPASQVYWLKDGQDCLSGSNWR---------RLYSHLATASIDPADSGNYSCVVgNNSSGDVKH 301
Cdd:cd20956   15 PGPSVSLKCVASGNPLPQITWTLDGFPIPESPRFRvgdyvtsdgDVVSYVNISSVRVEDGGEYTCTA-TNDVGSVSH 90

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

Pssm-ID: 409560 [Multi-domain] Cd Length: 88 Bit Score: 42.23 E-value: 1.16e-04

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 81908341  146 NPKAEVRYkIRGKWLMYSTGNYIILPSGNLQILNVSSKDKGSYKCAAYN 194
Cdd:cd20968   26 NPKPSVSW-IKGDDLIKENNRIAVLESGSLRIHNVQKEDAGQYRCVAKN 73

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: 41.89 E-value: 1.30e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  408 VTAPANVEVTDGDFVTLSCNATGEPVPVIHWygrhgLITSHPSQVL-RSKSRKshlfrpgdLDPEPVYLIMSQAGSSSLs 486
Cdd:cd05868    3 ITAPTNLVLSPGEDGTLICRANGNPKPSISW-----LTNGVPIEIApTDPSRK--------VDGDTIIFSKVQERSSAV- 68

                         90       100       110
                 ....*....|....*....|....*....|..
gi 81908341  487 iqavtrehagkYTCEAVNKHGSTQSEAFLTVV 518
Cdd:cd05868   69 -----------YQCNASNEYGYLLANAFVNVL 89

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

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 41.72 E-value: 1.44e-04

                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 81908341     140 CRVPeSNPKAEVR-YKIRGKWLMYStGNYIILPSGN---LQILNVSSKDKGSYKCAAYNPVTSE 199
Cdd:smart00410   16 CEAS-GSPPPEVTwYKQGGKLLAES-GRFSVSRSGStstLTISNVTPEDSGTYTCAATNSSGSA 77

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: 41.77 E-value: 1.44e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 81908341  325 LGATVRFTCEVHGNPAPNRTWFHNAQPI------RPSSRHLTegsvLKITGVIMEDSGLYQCMADNGIGFMQST 392
Cdd:cd05856   18 VGSSVRLKCVASGNPRPDITWLKDNKPLtppeigENKKKKWT----LSLKNLKPEDSGKYTCHVSNRAGEINAT 87

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

Pssm-ID: 409402 [Multi-domain] Cd Length: 89 Bit Score: 41.61 E-value: 1.60e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 81908341  328 TVRFTCEVHGNPApNRTWFHNAQPIRPSSR-HLTEG-SVLKITGVIMEDSGLYQCMADNGIGFMQS 391
Cdd:cd05740   17 AVTLTCEPETQNT-SYLWWFNGQSLPVTPRlTLSNGnRTLTLLNVTREDAGAYQCEISNPVSANRS 81

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

Pssm-ID: 409457 Cd Length: 87 Bit Score: 41.72 E-value: 1.64e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 81908341   33 EPLSAVQKLGRPVVLHCSAKPVTARISWLHNGKRLDRNTEQIKIHRGTLTILSLNPSLSGCYQCVA 98
Cdd:cd05873    2 DPRQRTFKLGGNAELKCSPKSNLARVVWKFQGKVLKAESPKYGLYGDGLLIFNASEADAGRYQCLS 67

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

Pssm-ID: 395002 Cd Length: 86 Bit Score: 41.41 E-value: 1.69e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 81908341    323 VSLGATVRFTCEVH-GNPAPNRTWFHNAQPIRPSSRHLTE-----GSVLKITGVIMEDSGLYQCMADNGIG 387
Cdd:pfam00047    8 VLEGDSATLTCSAStGSPGPDVTWSKEGGTLIESLKVKHDngrttQSSLLISNVTKEDAGTYTCVVNNPGG 78

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

Pssm-ID: 409460 [Multi-domain] Cd Length: 83 Bit Score: 41.44 E-value: 1.82e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  227 SQALAVLPHSPVTLECVVSGVPASQVYWLKDgQDCLSGSNWRRLYSH--LATASIDPADSGNYSCvVGNNSSGDVKHvTY 304
Cdd:cd05876    2 SSSLVALRGQSLVLECIAEGLPTPTVKWLRP-SGPLPPDRVKYQNHNktLQLLNVGESDDGEYVC-LAENSLGSARH-AY 78


                 ....
gi 81908341  305 TVNV 308
Cdd:cd05876   79 YVTV 82

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: 41.43 E-value: 2.12e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  406 VIVTAPANVEVTDGDFVTLSCNATGEPVPVIHWygrhglitshpsqvlrSKSRKshlfrpgDLDPEPVYLI-MSQAGSSS 484
Cdd:cd05891    3 VIGGLPDVVTIMEGKTLNLTCTVFGNPDPEVIW----------------FKNDQ-------DIELSEHYSVkLEQGKYAS 59

                         90       100       110
                 ....*....|....*....|....*....|...
gi 81908341  485 LSIQAVTREHAGKYTCEAVNKHGSTQSEAFLTV 517
Cdd:cd05891   60 LTIKGVTSEDSGKYSINVKNKYGGETVDVTVSV 92

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

Pssm-ID: 409454 Cd Length: 89 Bit Score: 41.51 E-value: 2.26e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 81908341  323 VSLGATVRFTCEVHGNPAPNRTWFHNAQPIR-----PSSRhlTEGSVLKITGVIMEDSGLYQCMADNGIGFM 389
Cdd:cd05868   11 LSPGEDGTLICRANGNPKPSISWLTNGVPIEiaptdPSRK--VDGDTIIFSKVQERSSAVYQCNASNEYGYL 80

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: 41.05 E-value: 2.33e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  411 PANVEVTDGDFVTLSCNATGEPVPVIHWYgRHGlitshpsQVLRSKSRkshlfrpgdldpepvylIMSQAGSssLSIQAV 490
Cdd:cd05728    6 ISDTEADIGSSLRWECKASGNPRPAYRWL-KNG-------QPLASENR-----------------IEVEAGD--LRITKL 58

                         90       100
                 ....*....|....*....|....*..
gi 81908341  491 TREHAGKYTCEAVNKHGSTQSEAFLTV 517
Cdd:cd05728   59 SLSDSGMYQCVAENKHGTIYASAELAV 85

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

Pssm-ID: 409400 [Multi-domain] Cd Length: 91 Bit Score: 41.15 E-value: 2.35e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 81908341  313 SISKGLHDQKVSLGATVRFTCEVHGNPAPNRTWFHNAQPIRPSSRH----LTEGSVLKITGVIMEDSGLYQCMADNGIG 387
Cdd:cd05738    1 IIDMGPQLKVVEKARTATMLCAASGNPDPEISWFKDFLPVDTATSNgrikQLRSGALQIENSEESDQGKYECVATNSAG 79

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: 40.39 E-value: 2.66e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 81908341  140 CRVpESNPKAEVRYKIRGKWLMYST--GNYIILPSGNLQILNVSSKDKGSYKCAAYNPVTSE 199
Cdd:cd00096    5 CSA-SGNPPPTITWYKNGKPLPPSSrdSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGS 65

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

Pssm-ID: 409396 [Multi-domain] Cd Length: 94 Bit Score: 41.24 E-value: 2.93e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  405 PVIVT-APANVEVTDGDFVTLSCNATGEPVPVIHWygrhglitshpsqvlrskSRKSHLFRPGDlDPEpvyLIMSQAgSS 483
Cdd:cd05733    1 PTITEqSPKDYIVDPRDNITIKCEAKGNPQPTFRW------------------TKDGKFFDPAK-DPR---VSMRRR-SG 57

                         90       100       110
                 ....*....|....*....|....*....|.
gi 81908341  484 SLSIQA---VTREHAGKYTCEAVNKHGSTQS 511
Cdd:cd05733   58 TLVIDNhngGPEDYQGEYQCYASNELGTAIS 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: 41.07 E-value: 3.09e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 81908341  240 LECVVSGVPASQVYWLKDGQDCLSGSNWRRLysHLAT-------ASIDPADSGNYSCVVGNNSSGDVKHVTYTV 306
Cdd:cd05763   19 LECAATGHPTPQIAWQKDGGTDFPAARERRM--HVMPeddvffiVDVKIEDTGVYSCTAQNSAGSISANATLTV 90

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

Pssm-ID: 143224 [Multi-domain] Cd Length: 92 Bit Score: 40.80 E-value: 3.24e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  228 QALAVLPHSPVTLECVVSGVPASQVYWLKDGQDCLSGSNWR----RLYSHLATASIDPADSGNYSCVVGNNSSGDVKHVT 303
Cdd:cd05747   11 RSLTVSEGESARFSCDVDGEPAPTVTWMREGQIIVSSQRHQitstEYKSTFEISKVQMSDEGNYTVVVENSEGKQEAQFT 90


                 ..
gi 81908341  304 YT 305
Cdd:cd05747   91 LT 92

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

Pssm-ID: 395002 Cd Length: 86 Bit Score: 40.64 E-value: 3.25e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 81908341     40 KLGRPVVLHCSAKPVT--ARISWLHNGKRLDRNTeQIKIHRG-----TLTILSLNPSLSGCYQCVANNSVG 103
Cdd:pfam00047    9 LEGDSATLTCSASTGSpgPDVTWSKEGGTLIESL-KVKHDNGrttqsSLLISNVTKEDAGTYTCVVNNPGG 78

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: 40.85 E-value: 3.39e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  405 PVIVTAPANVEVTDGDFVTLSCNATGEPVPVIHWygrhglitshpsqvlrsksrkshlfrpgDLDPEPVY------LIMS 478
Cdd:cd20990    1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSW----------------------------QLDGKPIRpdsahkMLVR 52

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 81908341  479 QAGSSSLSIQAVTREHAGKYTCEAVNKHGSTQSEAFLTV 517
Cdd:cd20990   53 ENGVHSLIIEPVTSRDAGIYTCIATNRAGQNSFNLELVV 91

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: 41.07 E-value: 3.48e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 81908341  325 LGATVRFTCEVHGNPAPNRTWFHNAQPIRPSSRHLT---EGSVLKITGVIMEDSGLYQCMADNGIGFMQSTGRLQI 397
Cdd:cd05730   17 LGQSVTLACDADGFPEPTMTWTKDGEPIESGEEKYSfneDGSEMTILDVDKLDEAEYTCIAENKAGEQEAEIHLKV 92

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

Pssm-ID: 409360 Cd Length: 96 Bit Score: 40.85 E-value: 3.66e-04

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 81908341  324 SLGATVRF-TC---EVHGNPAPNRTWFHNAQPIRPSSRHLTE 361
Cdd:cd04971    7 LEEPELRHhWCipfTVRGNPKPTLTWYHNGAVLNESDYIRTE 48

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: 40.64 E-value: 3.85e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 81908341  228 QALAVLPHSPVTLECVVSGVPASQVYWLKDGQDCLSG-----SNWRRLYShLATASIDPADSGNYSCVVGNNSSGD 298
Cdd:cd20972    9 RSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSpdiqiHQEGDLHS-LIIAEAFEEDTGRYSCLATNSVGSD 83

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

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 40.57 E-value: 5.00e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341   31 ISEPLS---AVQKLGRPVVLHCSAKPVTA-RISWLHNGKRL-DRNTEQIKIHRGT-LTILSLNPSLSGCYQCVANNSVGA 104
Cdd:cd20970    3 ISTPQPsftVTAREGENATFMCRAEGSPEpEISWTRNGNLIiEFNTRYIVRENGTtLTIRNIRRSDMGIYLCIASNGVPG 82


                 ....*....
gi 81908341  105 VVSGPATVS 113
Cdd:cd20970   83 SVEKRITLQ 91

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

Pssm-ID: 409402 [Multi-domain] Cd Length: 89 Bit Score: 40.07 E-value: 5.34e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341   44 PVVLHCSAKPVTARISWLHNGKRLdRNTEQIKIHRG--TLTILSLNPSLSGCYQCVANNSVGAVVSGPAT 111
Cdd:cd05740   17 AVTLTCEPETQNTSYLWWFNGQSL-PVTPRLTLSNGnrTLTLLNVTREDAGAYQCEISNPVSANRSDPVT 85

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

Pssm-ID: 409356 [Multi-domain] Cd Length: 96 Bit Score: 40.30 E-value: 5.46e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341   30 FISEPLSAV---QKLGRPVVLHCSAK--PVtARISWLHNGKRLDRNTE-QIKIHRGTLTILslNPSL---SGCYQCVANN 100
Cdd:cd04967    4 FEEQPDDTIfpeDSDEKKVALNCRARanPV-PSYRWLMNGTEIDLESDyRYSLVDGTLVIS--NPSKakdAGHYQCLATN 80

                         90
                 ....*....|...
gi 81908341  101 SVGAVVSGPATVS 113
Cdd:cd04967   81 TVGSVLSREATLQ 93

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: 40.23 E-value: 5.56e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341   39 QKLGRPVVLHC--SAKPvTARISWLHNGKRLDRNTE-QIKIHRGTLTILSLNPSLSGCYQCVANNSVGAV 105
Cdd:cd05856   16 RPVGSSVRLKCvaSGNP-RPDITWLKDNKPLTPPEIgENKKKKWTLSLKNLKPEDSGKYTCHVSNRAGEI 84

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

Pssm-ID: 319300 Cd Length: 92 Bit Score: 40.27 E-value: 6.27e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 81908341  240 LECVVSGVPASQVYWLKDGQDCLSGSNWRRLYSHLATASI-----DPADSGNYSCVVGNNSSGDVKHVTYTV 306
Cdd:cd05737   21 LTCNVWGDPPPEVSWLKNDQALAFLDHCNLKVEAGRTVYFtingvSSEDSGKYGLVVKNKYGSETSDVTVSV 92

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

Pssm-ID: 395002 Cd Length: 86 Bit Score: 39.87 E-value: 6.78e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 81908341    230 LAVLPHSPVTLEC-VVSGVPASQVYWLKDGQDCLSGS----NWRRLYSH-LATASIDPADSGNYSCVVGNNSSGDVK 300
Cdd:pfam00047    6 VTVLEGDSATLTCsASTGSPGPDVTWSKEGGTLIESLkvkhDNGRTTQSsLLISNVTKEDAGTYTCVVNNPGGSATL 82

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

Pssm-ID: 409412 Cd Length: 85 Bit Score: 39.85 E-value: 6.79e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 81908341  321 QKVSLGATVRFTCEVHG-NPAPNRTWFHNAQPIrPSSRHLTEGsVLKITGVIMEDSGLYQCMADNGIGFMQSTGRL 395
Cdd:cd05754   11 QEVRPGADVSFICRAKSkSPAYTLVWTRVNGTL-PSRAMDFNG-ILTIRNVQLSDAGTYVCTGSNMLDTDEATATL 84

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 2 (VEGFR-2); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor receptor 2 (VEGFR-2). The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. VEGFRs bind VEGFs with high affinity at the Ig-like domains. VEGFR-2 (KDR/Flk-1) is a major mediator of the mitogenic, angiogenic and microvascular permeability-enhancing effects of VEGF-A; VEGF-A is important to the growth and maintenance of vascular endothelial cells and to the development of new blood- and lymphatic-vessels in physiological and pathological states. VEGF-A also interacts with VEGFR-1, which it binds more strongly than VEGFR-2. VEGFR-1 and VEGFR-2 may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409450 Cd Length: 89 Bit Score: 39.91 E-value: 6.88e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  322 KVSLGATVRFTCEVHGNPAPNRTWFHNAQPIrpSSRH-LTEGSVLKITGVIMEDSGLYQCMADNGIGFMQ 390
Cdd:cd05864   13 EAKVGERVRIPVKYLGYPPPEIKWYKNGIPI--ESNHtIKAGHVLTIMEVTEKDAGNYTVVLTNPISKEK 80

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: 39.93 E-value: 8.32e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 81908341  224 PALSQA---LAVLPHSPVTLECVVSGVPASQVYWLKDGQD---CLSGSNWRRLYSHLATASIDPADSGNYSCVVGN 293
Cdd:cd20976    2 PSFSSVpkdLEAVEGQDFVAQCSARGKPVPRITWIRNAQPlqyAADRSTCEAGVGELHIQDVLPEDHGTYTCLAKN 77

Fibronectin type 3 domain [General function prediction only];

Pssm-ID: 442628 [Multi-domain] Cd Length: 603 Bit Score: 43.45 E-value: 9.03e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  590 TYTLVWRTGRDGGMPINAYFVKYRKLDDGSGAVGSWHTVRVPGSESELHLTELEPSSLYEVLMVARSAVGEGqPAMLTFR 669
Cdd:COG3401   19 ANTAVNALSKAGGSGKTILVYLAVVLSVTTKESPGTLLVAAGLSSGGGLGTGGRAGTTSGVAAVAVAAAPPT-ATGLTTL 97

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  670 TSKEKMASSKNTQAsfPPVGIPKRPVTSEASNSNFGVVLTDSSRHSGVPEAPDRPTISMASETSVYVTWIPRANGGSPIT 749
Cdd:COG3401   98 TGSGSVGGATNTGL--TSSDEVPSPAVGTATTATAVAGGAATAGTYALGAGLYGVDGANASGTTASSVAGAGVVVSPDTS 175

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  750 AfkveykrmkSSDWLVAAEDIPPSKLSVEVRSLEPGSIYKFRVIVINHYGESFRSSASRPYQVAGFPNRfsnrpitgPHI 829
Cdd:COG3401  176 A---------TAAVATTSLTVTSTTLVDGGGDIEPGTTYYYRVAATDTGGESAPSNEVSVTTPTTPPSA--------PTG 238

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  830 AYTEAVSDTQIMLKWTyipsSNNNTPIQGFYIYYRPTDsdnDSDYKRdVVEGSKQWHTIGHLQPETSYDIKMQCFNEGG- 908
Cdd:COG3401  239 LTATADTPGSVTLSWD----PVTESDATGYRVYRSNSG---DGPFTK-VATVTTTSYTDTGLTNGTTYYYRVTAVDAAGn 310


                 ....*..
gi 81908341  909 ESEFSNV 915
Cdd:COG3401  311 ESAPSNV 317

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: 39.84 E-value: 9.06e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  419 GDFVTLSCNATGEPVPVIHWYGRHGLITSHPSQvlRSKSRKShlfrpgdldpepvylimsqagssSLSIQAVTREHAGKY 498
Cdd:cd05856   19 GSSVRLKCVASGNPRPDITWLKDNKPLTPPEIG--ENKKKKW-----------------------TLSLKNLKPEDSGKY 73


                 ....*....
gi 81908341  499 TCEAVNKHG 507
Cdd:cd05856   74 TCHVSNRAG 82

First immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of fibroblast growth factor receptor (FGFR). Fibroblast growth factors (FGFs) participate in morphogenesis, development, angiogenesis, and wound healing. These FGF-stimulated processes are mediated by four FGFR tyrosine kinases (FGRF1-4). FGFRs are comprised of an extracellular portion consisting of three Ig-like domains, a transmembrane helix, and a cytoplasmic portion having protein tyrosine kinase activity. The highly conserved Ig-like domains 2 and 3, and the linker region between D2 and D3 define a general binding site for all FGFs.

Pssm-ID: 409362 Cd Length: 94 Bit Score: 39.88 E-value: 9.18e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 81908341   28 TYFISEPLSAVQKLGRPVVLHCSAKPVTARISWLHNGKRLDRNTeQIKIHRGTLTILSLNPSLSGCYQCVANNSVGA 104
Cdd:cd04973   10 TYQISEVESYSAHPGDLLQLRCRLRDDVQSINWTKDGVQLGENN-RTRITGEEVQIKDAVPRDSGLYACVTSSPSGS 85

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

Pssm-ID: 409549 [Multi-domain] Cd Length: 88 Bit Score: 39.44 E-value: 9.30e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 81908341  237 PVTLECVVSGVPASQVYWLKDGQDCLSGSNWRRLY-SHLATASIDPADSGNYSCVVGN 293
Cdd:cd20957   18 TAVFNCSVTGNPIHTVLWMKDGKPLGHSSRVQILSeDVLVIPSVKREDKGMYQCFVRN 75

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

Pssm-ID: 409396 [Multi-domain] Cd Length: 94 Bit Score: 39.70 E-value: 9.35e-04

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 81908341  332 TCEVHGNPAPNRTWFHNAQPIRPS-----SRHLTEGS-VLKITGVIMED-SGLYQCMADNGIG 387
Cdd:cd05733   22 KCEAKGNPQPTFRWTKDGKFFDPAkdprvSMRRRSGTlVIDNHNGGPEDyQGEYQCYASNELG 84

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

Pssm-ID: 409397 [Multi-domain] Cd Length: 97 Bit Score: 39.78 E-value: 9.71e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  405 PVIVTAPANVEVTDGDFVTLSCNATGEPVPVIHWygRHglitshpsqvlrSKSRKSHLFRPGDLDPEPVYLImsqaGSSS 484
Cdd:cd05734    2 PRFVVQPNDQDGIYGKAVVLNCSADGYPPPTIVW--KH------------SKGSGVPQFQHIVPLNGRIQLL----SNGS 63

                         90       100       110
                 ....*....|....*....|....*....|....
gi 81908341  485 LSIQAVTREHAGKYTCEAVNKHGSTQSEA-FLTV 517
Cdd:cd05734   64 LLIKHVLEEDSGYYLCKVSNDVGADISKSmYLTV 97

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

Pssm-ID: 409561 Cd Length: 92 Bit Score: 39.68 E-value: 9.81e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 81908341  326 GATVRFTCEVHGNPAPNRTWF----HNAQPIRPSSRHLTEGSVLKITGVIMEDSGLYQCMADNGIGFMQSTGRLQI 397
Cdd:cd20969   17 GHTVQFVCRADGDPPPAILWLsprkHLVSAKSNGRLTVFPDGTLEVRYAQVQDNGTYLCIAANAGGNDSMPAHLHV 92

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: 1.03e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 81908341  326 GATVRFTCEVHGNPAPNRTWFHNAQPIRPSSR-HLTEGSVLKITGVIMEDSGLYQCMADNGIGFMQSTGRLQI 397
Cdd:cd05852   17 GGRVIIECKPKAAPKPKFSWSKGTELLVNNSRiSIWDDGSLEILNITKLDEGSYTCFAENNRGKANSTGVLSV 89

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: 1.04e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 81908341  128 ITAEKKNTGFIGCRvPESNPKAEVRYKiRGKWLMYSTGNYIILPSGNLQILNVSSKDKGSYKCAAYN 194
Cdd:cd05852   12 ILAAKGGRVIIECK-PKAAPKPKFSWS-KGTELLVNNSRISIWDDGSLEILNITKLDEGSYTCFAEN 76

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: 39.12 E-value: 1.12e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 81908341  326 GATVRFTCEVHGNPAPNRTWFHNAQPIRPS-SRHLTEGSVLKITGVIMEDSGLYQCMADNGIGFMQSTGRLQIE 398
Cdd:cd05876   10 GQSLVLECIAEGLPTPTVKWLRPSGPLPPDrVKYQNHNKTLQLLNVGESDDGEYVCLAENSLGSARHAYYVTVE 83

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409422 [Multi-domain] Cd Length: 95 Bit Score: 39.45 E-value: 1.15e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  321 QKVSLGATVRFTCEVHGNPAPNRTW---FHNAQPIRPSSRHLTEGSV------LKITGVIMEDSGLYQCMADNGIGFMQS 391
Cdd:cd05765   10 QTVKVGETASFHCDVTGRPQPEITWekqVPGKENLIMRPNHVRGNVVvtnigqLVIYNAQPQDAGLYTCTARNSGGLLRA 89

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

Pssm-ID: 443767 [Multi-domain] Cd Length: 978 Bit Score: 43.01 E-value: 1.28e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  730 SETSVYVTWIPRANGgspiTAFKVEYKRmKSSDWLVAAEDippSKLSVEVRSLEPGSiYKFRVIVINHYGESFRSSASRP 809
Cdd:COG4733  550 AVTTLTVSWDAPAGA----VAYEVEWRR-DDGNWVSVPRT---SGTSFEVPGIYAGD-YEVRVRAINALGVSSAWAASSE 620

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  810 YQVAGfpnrfsnRPITGPHIAYTEAVS-DTQIMLKWTYIPssnnNTPIQGFYIYYRPTDSDNDSDYKRDVVEGSKqwHTI 888
Cdd:COG4733  621 TTVTG-------KTAPPPAPTGLTATGgLGGITLSWSFPV----DADTLRTEIRYSTTGDWASATVAQALYPGNT--YTL 687


                 ....*....
gi 81908341  889 GHLQPETSY 897
Cdd:COG4733  688 AGLKAGQTY 696

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: 1.29e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  407 IVTAPANVEVTDGDFVTLSCNATGEPVPVIHWYgrhglitsHPSQVLRSKSRKSHLfrpgdldpepvylimsqaGSSSLS 486
Cdd:cd20968    2 ITRPPTNVTIIEGLKAVLPCTTMGNPKPSVSWI--------KGDDLIKENNRIAVL------------------ESGSLR 55

                         90       100       110
                 ....*....|....*....|....*....|..
gi 81908341  487 IQAVTREHAGKYTCEAVNKHGSTQSEAFLTVV 518
Cdd:cd20968   56 IHNVQKEDAGQYRCVAKNSLGIAYSKPVTIEV 87

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

Pssm-ID: 409387 Cd Length: 97 Bit Score: 39.38 E-value: 1.30e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  326 GATVRFTCEVHGNPAPNRTWFHNAQPIRPSSRH----LTEGSVLkITGVIME-----DSGLYQCMADNG-IGFMQS-TGR 394
Cdd:cd05722   16 GGPVVLNCSAESDPPPKIEWKKDGVLLNLVSDErrqqLPNGSLL-ITSVVHSkhnkpDEGFYQCVAQNEsLGSIVSrTAR 94


                 ...
gi 81908341  395 LQI 397
Cdd:cd05722   95 VTV 97

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409422 [Multi-domain] Cd Length: 95 Bit Score: 39.07 E-value: 1.37e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  405 PVIVTAPANVEVTDGDFVTLSCNATGEPVPVIHW----YGRHGLItshpsqvlrsksrkshlfrpgdLDPEPVYLIMSQA 480
Cdd:cd05765    1 PALVNSPTHQTVKVGETASFHCDVTGRPQPEITWekqvPGKENLI----------------------MRPNHVRGNVVVT 58

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 81908341  481 GSSSLSIQAVTREHAGKYTCEAVNKHGSTQSEAFLTV 517
Cdd:cd05765   59 NIGQLVIYNAQPQDAGLYTCTARNSGGLLRANFPLSV 95

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

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 38.94 E-value: 1.63e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 81908341  228 QALAVLPHSPVTLECVVSGVPASQVYWLKDGQDCLSGSN------WRRLYSH-LATASIDPADSGNYSCVVGN 293
Cdd:cd20951    8 QSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDPSSIpgkykiESEYGVHvLHIRRVTVEDSAVYSAVAKN 80

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

Pssm-ID: 464026 [Multi-domain] Cd Length: 79 Bit Score: 38.53 E-value: 1.63e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 81908341    236 SPVTLECVVSGVPASQVYWLKDGQDCLSGSNwrrlyshLATASIDPADSGNYSCVVGNnssGDVKHVTYTVNV 308
Cdd:pfam13895   15 EPVTLTCSAPGNPPPSYTWYKDGSAISSSPN-------FFTLSVSAEDSGTYTCVARN---GRGGKVSNPVEL 77

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: 38.76 E-value: 1.74e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 81908341   41 LGRPVVLHCSA----KPvtaRISWLHNGKRLDRNTEQIKIHRGTLTILSLNPSLSGCYQCVANNSVGAVVSGPATV 112
Cdd:cd20968   13 EGLKAVLPCTTmgnpKP---SVSWIKGDDLIKENNRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLGIAYSKPVTI 85

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

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 38.64 E-value: 1.85e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  221 ILHPALSQALAVLPHSPVTLECVVSGVPASQVYWLKDGQDCLSGSNWRRLYSH---LATASIDPADSGNYSCVVGNNSSG 297
Cdd:cd20970    3 ISTPQPSFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNTRYIVRENgttLTIRNIRRSDMGIYLCIASNGVPG 82

                         90
                 ....*....|.
gi 81908341  298 DVKHvTYTVNV 308
Cdd:cd20970   83 SVEK-RITLQV 92

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

Pssm-ID: 409474 Cd Length: 92 Bit Score: 38.92 E-value: 1.85e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 81908341  237 PVTLECVVSGVPASQVYWLKDGQDCLSGSNWRRLYS--------HLATASIDpaDSGNYSCVVGN 293
Cdd:cd05893   17 PVTFTCRVAGNPKPKIYWFKDGKQISPKSDHYTIQRdldgtcslHTTASTLD--DDGNYTIMAAN 79

Immunoglobulin C1-set domain;

Pssm-ID: 462221 Cd Length: 85 Bit Score: 38.39 E-value: 1.86e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341    232 VLPHSP------VTLECVVSGV--PASQVYWLKDGQDCLSG---------SNWR-RLYSHLATASIDPADSGNYSCVVGN 293
Cdd:pfam07654    3 VFPPSPeelgkpNTLTCLVTGFypPDITVTWLKNGQEVTEGvkttppspnSDWTyQLSSYLTVTPSDWESGDEYTCRVEH 82


                   ...
gi 81908341    294 NSS 296
Cdd:pfam07654   83 EGL 85

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

Pssm-ID: 409534 Cd Length: 116 Bit Score: 39.56 E-value: 1.93e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  321 QKVSLGATVRFTCEVHGNPAPN-RTWFHNAQPIRPSSR----------------HLTEGSVLKITGVIMEDSGLYQCMAD 383
Cdd:cd20940   10 QQRLVGDSVELHCEAVGSPIPEiQWWFEGQEPNEICSQlwdgarldrvhinatyHQHATSTISIDNLTEEDTGTYECRAS 89


                 .
gi 81908341  384 N 384
Cdd:cd20940   90 N 90

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

Pssm-ID: 409419 Cd Length: 99 Bit Score: 38.78 E-value: 1.97e-03

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 81908341  476 IMSQAGSSSLSIQAVTREHAGKYTCEAVNKHGSTQSEAFLTVV 518
Cdd:cd05762   50 IENTENSSKLTITEGQQEHCGCYTLEVENKLGSRQAQVNLTVV 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: 38.32 E-value: 2.55e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 81908341  236 SPVTLECVVSGVPASQVYWLKDGQDCLSGSNWRRLYSH-----LATASIDPADSGNYSCVVGNN 294
Cdd:cd20973   13 SAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQDEdglcsLIISDVCGDDSGKYTCKAVNS 76

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: 37.95 E-value: 2.82e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  429 TGEPVPVIHWYgrhglitshpsqvlrsksrkshlfRPG-DLDPEPVYLIMSQAGSSSLSIQAVTREHAGKYTCEAVNKHG 507
Cdd:cd05748   17 KGRPTPTVTWS------------------------KDGqPLKETGRVQIETTASSTSLVIKNAKRSDSGKYTLTLKNSAG 72

                         90
                 ....*....|
gi 81908341  508 STqsEAFLTV 517
Cdd:cd05748   73 EK--SATINV 80

Immunoglobulin C-Type;

Pssm-ID: 214651 Cd Length: 75 Bit Score: 37.68 E-value: 2.84e-03

                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 81908341     237 PVTLECVVSGV-PAS-QVYWLKDGQDCLSG---------SNWR-RLYSHLATASIDPADSGNYSCVVG 292
Cdd:smart00407    1 KATLVCLVSGFyPPDiTVTWLRNGQEVTEGvsttdplknSDGTyFLSSYLTVPASTWESGDVYTCQVT 68

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: 38.43 E-value: 2.96e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 81908341   45 VVLHCSAK-PVTARISWLHNGKRLDRNTE---QIKIHRGTLTILSLN----PSLSGCYQCVANNSVGAVVS 107
Cdd:cd05874   19 IVIQCEAKgKPPPSFSWTRNGTHFDIDKDpkvTMKPNTGTLVINIMNgekaEAYEGVYQCTARNERGAAVS 89

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

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 37.95 E-value: 3.12e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341   30 FISEPLSAVQKLGRPVVLHCSAKPV-TARISWLHNGKRLdRNTEQIKIHRG----TLTILSLNPSLSGCYQCVANNSVGA 104
Cdd:cd20972    4 FIQKLRSQEVAEGSKVRLECRVTGNpTPVVRWFCEGKEL-QNSPDIQIHQEgdlhSLIIAEAFEEDTGRYSCLATNSVGS 82

                         90
                 ....*....|...
gi 81908341  105 vvsgpATVSADAL 117
Cdd:cd20972   83 -----DTTSAEIF 90

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: 37.96 E-value: 3.31e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 81908341  241 ECVVSGVPASQVYWLKDGQDCLSGSNWRRLYSHLATASIDPADSGNYSCVVGN 293
Cdd:cd05728   20 ECKASGNPRPAYRWLKNGQPLASENRIEVEAGDLRITKLSLSDSGMYQCVAEN 72

First immunoglobulin (Ig)-like domain of neural cell adhesion molecule NCAM-1, 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 of neural cell adhesion molecule NCAM-1. NCAM-1 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-nonNCAM) 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 the Ig1, Ig2, and Ig3 domains. 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). 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: 409366 Cd Length: 95 Bit Score: 38.00 E-value: 3.32e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 81908341   49 CSAKPVTARISWLH-NGKRLDRNTEQIKIH-----RGTLTILSLNPSLSGCYQCVANNSVGAvvSGPATVSAD 115
Cdd:cd04977   22 CKVSGDAKNINWVSpNGEKVLTKHGNLKVVnhgsvLSSLTIYNANINDAGIYKCVATNGKGT--ESEATVKLD 92

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

Pssm-ID: 143220 Cd Length: 78 Bit Score: 37.47 E-value: 3.57e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 81908341  326 GATVRFTCEVHGNPAPNRTWFHNAQPIrPSSRHLTEGS-----VLKITGVIMEDSGLYQCMADNGIG 387
Cdd:cd05743    1 GETVEFTCVATGVPTPIINWRLNWGHV-PDSARVSITSeggygTLTIRDVKESDQGAYTCEAINTRG 66

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

Pssm-ID: 409460 [Multi-domain] Cd Length: 83 Bit Score: 37.58 E-value: 3.76e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 81908341   42 GRPVVLHCSAKPV-TARISWLHNGKRLDRNTEQIKIHRGTLTILSLNPSLSGCYQCVANNSVGAV 105
Cdd:cd05876   10 GQSLVLECIAEGLpTPTVKWLRPSGPLPPDRVKYQNHNKTLQLLNVGESDDGEYVCLAENSLGSA 74

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: 38.23 E-value: 3.80e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  237 PVTLECVVSGVPASQVYWLKDGQDCLSGSNWRR--------LYSHLATASIDPADSGNYSCVVGNNSSGDVKHVTYTVNV 308
Cdd:cd05722   18 PVVLNCSAESDPPPKIEWKKDGVLLNLVSDERRqqlpngslLITSVVHSKHNKPDEGFYQCVAQNESLGSIVSRTARVTV 97

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: 37.72 E-value: 4.25e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  323 VSLGATVRFTCEVHGNPAPNRTWFHNAQPIRPSSR-----HLTEGSV-LKITGVIMEDSGLYQCMADNGIGFMQSTGRLQ 396
Cdd:cd20974   12 VLEGSTATFEAHVSGKPVPEVSWFRDGQVISTSTLpgvqiSFSDGRAkLSIPAVTKANSGRYSLTATNGSGQATSTAELL 91


                 .
gi 81908341  397 I 397
Cdd:cd20974   92 V 92

Third immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the third immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The third Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules, including vascular (VCAM), intercellular (ICAM), neural (NCAM) and mucosal addressin (MADCAM) cell adhesion molecules, as well as junction adhesion molecules (JAM).

Pssm-ID: 409569 Cd Length: 93 Bit Score: 37.76 E-value: 4.38e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 81908341  320 DQKVSLGATVRFTCEVHGNPAPNRTWFHNAQPI------RPSSRHLTEGSVLKITGVIMEDSGLYQCMADNGIGFMQS 391
Cdd:cd20977    9 DMMAKAGDVTMIYCMYGSNPTAHPNYFKNGKDVngnpedRITRHNRTSGKRLLFKTTLPEDEGVYTCEVDNGVGKPQK 86

Immunoglobulin variable domain (IgV); The members here are composed of the immunoglobulin variable domain (IgV). The IgV family contains the standard Ig superfamily V-set AGFCC'C"/DEB domain topology, and are components of immunoglobulin (Ig) and T cell receptors. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. In Ig, each chain is composed of one variable domain (IgV) and one or more constant domains (IgC); these names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. Within the variable domain, there are regions of even more variability called the hypervariable or complementarity-determining regions (CDRs) which are responsible for antigen binding. A predominant feature of most Ig domains is the disulfide bridge connecting 2 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" strands in the other.

Pssm-ID: 409355 [Multi-domain] Cd Length: 111 Bit Score: 38.08 E-value: 4.45e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  411 PANVEVTDGDFVTLSCNATGE-PVPVIHWY-GRHGlitSHPSQVLRSKSRKSHLfrpGDLDPEPVYLIMSQAGSSSLSIQ 488
Cdd:cd00099    5 PRSLSVQEGESVTLSCEVSSSfSSTYIYWYrQKPG---QGPEFLIYLSSSKGKT---KGGVPGRFSGSRDGTSSFSLTIS 78

                         90
                 ....*....|..
gi 81908341  489 AVTREHAGKYTC 500
Cdd:cd00099   79 NLQPEDSGTYYC 90

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: 37.16 E-value: 5.58e-03

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 81908341  326 GATVRFTCEVHGNPAPNRTWFHNAQPIRPSSRHL--TEGSvLKITGV-IMEDSGLYQCMADNGIG-FMQSTGRLQI 397
Cdd:cd20958   15 GQTLRLHCPVAGYPISSITWEKDGRRLPLNHRQRvfPNGT-LVIENVqRSSDEGEYTCTARNQQGqSASRSVFVKV 89

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: 37.82 E-value: 5.61e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341    323 VSLGATVRFTCEVHGNPAPNRTWFH-------------------NAQPIRPSSRHLTEGSV------LKITGVIMEDSGL 377
Cdd:pfam07686    8 VALGGSVTLPCTYSSSMSEASTSVYwyrqppgkgptfliayysnGSEEGVKKGRFSGRGDPsngdgsLTIQNLTLSDSGT 87

                           90       100
                   ....*....|....*....|.
gi 81908341    378 YQC-MADNGIGFMQSTGRLQI 397
Cdd:pfam07686   88 YTCaVIPSGEGVFGKGTRLTV 108

First immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs), and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs). Interactions between IgG and FcgammaR are important to the initiation of cellular and humoral response. IgG binding to FcgammaR leads to a cascade of signals and ultimately to functions such as antibody-dependent-cellular-cytotoxicity (ADCC), endocytosis, phagocytosis, release of inflammatory mediators, etc. FcgammaR has two Ig-like domains. This group also contains FcepsilonRI which binds IgE with high affinity.

Pssm-ID: 409410 [Multi-domain] Cd Length: 79 Bit Score: 36.96 E-value: 5.63e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 81908341  326 GATVRFTCEVHGNPAPNRT-WFHNAQPIRPSSRHLTegsvlkITGVIMEDSGLYQC 380
Cdd:cd05752   15 GEKVTLTCQGFYSPEQNSTqWYHNGTLISSTSSSYR------IVAATVNDSGEYRC 64

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

Pssm-ID: 409363 Cd Length: 102 Bit Score: 37.40 E-value: 6.33e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  321 QKVSLGATVRFTCEVHGNPAPNRTWFH----NAQPI------------RPSSRHLTEGSVLKITGVIMEDSGLYQCMADN 384
Cdd:cd04974   11 QTVVLGSDVEFHCKVYSDAQPHIQWLKhvevNGSKYgpdglpyvtvlkVAGVNTTGEENTLTISNVTFDDAGEYICLAGN 90


                 ...
gi 81908341  385 GIG 387
Cdd:cd04974   91 SIG 93

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

Pssm-ID: 409460 [Multi-domain] Cd Length: 83 Bit Score: 37.20 E-value: 6.38e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 81908341  419 GDFVTLSCNATGEPVPVIHWygrhglitSHPSqvlrsksrkshlfrpgdlDPEPVYLIMSQAGSSSLSIQAVTREHAGKY 498
Cdd:cd05876   10 GQSLVLECIAEGLPTPTVKW--------LRPS------------------GPLPPDRVKYQNHNKTLQLLNVGESDDGEY 63

                         90
                 ....*....|....*....
gi 81908341  499 TCEAVNKHGSTQSEAFLTV 517
Cdd:cd05876   64 VCLAENSLGSARHAYYVTV 82

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: 37.00 E-value: 6.70e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 81908341  140 CRVPESNPKAEVRYKIRGKWLMYSTGNYIILPSGNLQILNVSSKDKGSYKCAAYNPV 196
Cdd:cd05724   19 CSPPRGHPEPTVSWRKDGQPLNLDNERVRIVDDGNLLIAEARKSDEGTYKCVATNMV 75

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

Pssm-ID: 409457 Cd Length: 87 Bit Score: 37.10 E-value: 7.58e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 81908341  134 NTGFIGCRvPESNpKAEVRYKIRGKWLMYSTGNYIILpSGNLQILNVSSKDKGSYKC 190
Cdd:cd05873   12 GNAELKCS-PKSN-LARVVWKFQGKVLKAESPKYGLY-GDGLLIFNASEADAGRYQC 65

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: 36.83 E-value: 9.63e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 81908341  327 ATVRFTCEVHGNPAPNRTWFHNAQPIRPSSRHLTEGS---VLKITGVIMEDSGLYQCMADNGIG 387
Cdd:cd05760   17 SRVTLRCHIDGHPRPTYQWFRDGTPLSDGQGNYSVSSkerTLTLRSAGPDDSGLYYCCAHNAFG 80