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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974672    31 VVIGEVHENVTLHCGNISGLRGQVTWYRNNSEPVFllssnsslrpAEPRFSLV---DATSLHIESLSLGDEGIYTCQ-EI 106
Cdd:smart00410   3 SVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLA----------ESGRFSVSrsgSTSTLTISNVTPEDSGTYTCAaTN 72

                           90
                   ....*....|...
gi 767974672   107 LNVTQWFQVWLQV 119
Cdd:smart00410  73 SSGSASSGTTLTV 85

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974672  324 GGNVTLTCQVSGaYPPAKILWLRNltqpEVIIQPSSRHLITQDGQNSTLTIHNCSQDlDEGYYICRADSPVGVREMEIWL 403
Cdd:pfam07679  15 GESARFTCTVTG-TPDPEVSWFKD----GQPLRSSDRFKVTYEGGTYTLTISNVQPD-DSGKYTCVATNSAGEAEASAEL 88

                  ..
gi 767974672  404 SV 405
Cdd:pfam07679  89 TV 90

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974672    31 VVIGEVHENVTLHCGNISGLRGQVTWYRNNSEPVFllssnsslrpAEPRFSLV---DATSLHIESLSLGDEGIYTCQ-EI 106
Cdd:smart00410   3 SVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLA----------ESGRFSVSrsgSTSTLTISNVTPEDSGTYTCAaTN 72

                           90
                   ....*....|...
gi 767974672   107 LNVTQWFQVWLQV 119
Cdd:smart00410  73 SSGSASSGTTLTV 85

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974672   29 EAVVIGEVHENVTLHC---GNISGLRGQVTWYR----NNSEPVFLLSSNSSLRPA-EPRFSLVDAT-----SLHIESLSL 95
Cdd:pfam07686   3 PREVTVALGGSVTLPCtysSSMSEASTSVYWYRqppgKGPTFLIAYYSNGSEEGVkKGRFSGRGDPsngdgSLTIQNLTL 82

                          90       100
                  ....*....|....*....|....*.
gi 767974672   96 GDEGIYTCQEILNVTQWFQ--VWLQV 119
Cdd:pfam07686  83 SDSGTYTCAVIPSGEGVFGkgTRLTV 108

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767974672  135 TLPNGTLYAARGSQVDFSCNSSSRPPPVVEWWFQALNSSSESFGHNLTVNFFSLLLIS---PNLQGNYTCLALN 205
Cdd:pfam13927   5 TVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISnvtRSDAGTYTCVASN 78

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974672  324 GGNVTLTCQVSGaYPPAKILWLRNltqpEVIIQPSSRHLITQDGQNSTLTIHNCSQDlDEGYYICRADSPVGVREMEIWL 403
Cdd:pfam07679  15 GESARFTCTVTG-TPDPEVSWFKD----GQPLRSSDRFKVTYEGGTYTLTISNVQPD-DSGKYTCVATNSAGEAEASAEL 88

                  ..
gi 767974672  404 SV 405
Cdd:pfam07679  89 TV 90

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767974672 327 VTLTCQVSGaYPPAKILWLRNltqpEVIIQPSSRHLITQDGQNSTLTIHNCSQDlDEGYYICRADSPVGVRE 398
Cdd:cd00096    1 VTLTCSASG-NPPPTITWYKN----GKPLPPSSRDSRRSELGNGTLTISNVTLE-DSGTYTCVASNSAGGSA 66

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974672 311 PSLLSEPMK--TCFTGGNVTLTCQVSGAyPPAKILWLRNltqPEVIIQPSSRHLITQdgqnSTLTIHNCSQDlDEGYYIC 388
Cdd:cd20978    1 PKFIQKPEKnvVVKGGQDVTLPCQVTGV-PQPKITWLHN---GKPLQGPMERATVED----GTLTIINVQPE-DTGYYGC 71

                         90
                 ....*....|....*..
gi 767974672 389 RADSPVGVREMEIWLSV 405
Cdd:cd20978   72 VATNEIGDIYTETLLHV 88

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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767974672  38 ENVTLHCgNISGLRG--QVTWYRN--NSEPVFLLSSNSSLRP----AEPRF--SLVDAT--SLHIESLSLGDEGIYTCQ 104
Cdd:cd00099   14 ESVTLSC-EVSSSFSstYIYWYRQkpGQGPEFLIYLSSSKGKtkggVPGRFsgSRDGTSsfSLTISNLQPEDSGTYYCA 91

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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767974672 324 GGNVTLTCQVSGAYPPAkILWLR----NLTQPEVIIQPSSRHLITQDGQnstLTIHNCsQDLDEGYYICRADSPVG 395
Cdd:cd05726   14 GRTVTFQCETKGNPQPA-IFWQKegsqNLLFPYQPPQPSSRFSVSPTGD---LTITNV-QRSDVGYYICQALNVAG 84

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974672 317 PMK--TCFTGGNVTLTCQVSGaYPPAKILWLRNLTQ-PEviiqpSSRHLITQDGqnsTLTIHNCSQDLDEGYYICRADSP 393
Cdd:cd20958    6 PMGnlTAVAGQTLRLHCPVAG-YPISSITWEKDGRRlPL-----NHRQRVFPNG---TLVIENVQRSSDEGEYTCTARNQ 76

                 ..
gi 767974672 394 VG 395
Cdd:cd20958   77 QG 78

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974672 310 GPSLLSEPMKTCFTGGN----VTLTCQVSGAyPPAKILWLRNLTqpEVIIQPSSRHLITqDGqnsTLTIHNCSQDLDEGY 385
Cdd:cd04967    1 GPVFEEQPDDTIFPEDSdekkVALNCRARAN-PVPSYRWLMNGT--EIDLESDYRYSLV-DG---TLVISNPSKAKDAGH 73

                         90       100
                 ....*....|....*....|
gi 767974672 386 YICRADSPVG-VREMEIWLS 404
Cdd:cd04967   74 YQCLATNTVGsVLSREATLQ 93

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974672 317 PMKTCFT-----GGNVTLTCQVSGAYPPAKILWLRN---LTQPEVIIQPSSRHLITqdgQNSTLTIHnCSQDLDEGYYIC 388
Cdd:cd05761    7 PVITGFTspvveGDEITLTCTTSGSKPAADIRWFKNdkeLKGVKEVQESGAGKTFT---VTSTLRFR-VDRDDDGVAVIC 82

                 ....*
gi 767974672 389 RADSP 393
Cdd:cd05761   83 RVDHE 87

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974672 315 SEPMKTCFTGGNVTLTCQVSGAYPPAKILWLRNL--TQPEVII-----------QPSSRHLITQDGQNS-TLTIHNcSQD 380
Cdd:cd00099    4 SPRSLSVQEGESVTLSCEVSSSFSSTYIYWYRQKpgQGPEFLIylssskgktkgGVPGRFSGSRDGTSSfSLTISN-LQP 82

                 ....*...
gi 767974672 381 LDEGYYIC 388
Cdd:cd00099   83 EDSGTYYC 90

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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 767974672 322 FTGGNVTLTCQVSGAyPPAKILWLRNLTQpeviIQPSSRHLITQDGQNSTLTIHNCSQDL-DEGYYICRADSPVG 395
Cdd:cd05893   13 FEGMPVTFTCRVAGN-PKPKIYWFKDGKQ----ISPKSDHYTIQRDLDGTCSLHTTASTLdDDGNYTIMAANPQG 82

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974672 311 PSLLSEPM-KTCFTGGNVTLTCQVSGaYPPAKILWLRNLTQPE-VIIQPSSRH---LITQDGQnstLTIHNcSQDLDEGY 385
Cdd:cd05765    1 PALVNSPThQTVKVGETASFHCDVTG-RPQPEITWEKQVPGKEnLIMRPNHVRgnvVVTNIGQ---LVIYN-AQPQDAGL 75

                         90       100
                 ....*....|....*....|
gi 767974672 386 YICRADSPVGVREMEIWLSV 405
Cdd:cd05765   76 YTCTARNSGGLLRANFPLSV 95

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767974672  136 LPNGTLYAARGSQVDFSCNSS-SRPPPVVEWWF--QALNSSSESFGHNLTVNFFSLLLISPNLQ--GNYTCLALNQLS 208
Cdd:pfam00047   1 SAPPTVTVLEGDSATLTCSAStGSPGPDVTWSKegGTLIESLKVKHDNGRTTQSSLLISNVTKEdaGTYTCVVNNPGG 78

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 767974672  40 VTLHCGNISGLRGQVTWYRNNSEPvfllssnsSLRPAEPRFSLVDATSLHIESLSLGDEGIYTCQ 104
Cdd:cd00096    1 VTLTCSASGNPPPTITWYKNGKPL--------PPSSRDSRRSELGNGTLTISNVTLEDSGTYTCV 57

Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) Domain C2 of human cardiac Myosin Binding Protein C (MyBP-C) and similar domains. MyBP-C is a thick filament protein involved in the regulation of muscle contraction. Mutations in cardiac MyBP-C gene are the second most frequent cause of hypertrophic cardiomyopathy. MyBP-C binds to myosin with two binding sites, one at its C-terminus and another at its N-terminus. The N-terminal binding site, consisting of immunoglobulin (lg) domains C1 and C2 connected by a flexible linker, interacts with the S2 segment of myosin in a phosphorylation-regulated manner. The C1 and C2 Ig domains can bind to and activate or inhibit the thin filament. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structures of the Ig domains of MyBP-C lack this strand and thus belong to the I-set of Ig superfamily domains. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767974672 324 GGNVTLTCQVSGAYPPAKilWLRNLTQpeviIQPSSRHLITQDGQNSTLTIHNCSQDlDEGYYICRA 390
Cdd:cd20967   12 GHKIRLTVELADPDAEVK--WYKDGQE----LQSSSKVIFESIGAKRTLTVQQASLA-DAGEYQCVA 71

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974672 319 KTCFTGGNVTLTCQVSGAyPPAKILW---LRNLTQPEViiQPSSRHLITQDGQNSTLTIHNCsQDLDEGYYICRADSPVG 395
Cdd:cd05732   11 QTAVELEQITLTCEAEGD-PIPEITWrraTRGISFEEG--DLDGRIVVRGHARVSSLTLKDV-QLTDAGRYDCEASNRIG 86

                         90
                 ....*....|
gi 767974672 396 VREMEIWLSV 405
Cdd:cd05732   87 GDQQSMYLEV 96

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974672 329 LTCQVSGAYPPAKILWLRNLTQPEVIIqpSSRHLItQDGQN----STLTIHncSQDLDEG-YYICRADS---PVGvREME 400
Cdd:cd05759   20 LTCRARGAKPAAEIIWFRDGEQLEGAV--YSKELL-KDGKRettvSTLLIT--PSDLDTGrTFTCRARNeaiPNG-KETS 93

                 ....*
gi 767974672 401 IWLSV 405
Cdd:cd05759   94 ITLDV 98

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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767974672 327 VTLTCQVSGayPPAKILWLRNlTQPeviIQPSSRhlITQDGQNSTLTIHNCSQDlDEGYYICRADSPVGVR 397
Cdd:cd05740   18 VTLTCEPET--QNTSYLWWFN-GQS---LPVTPR--LTLSNGNRTLTLLNVTRE-DAGAYQCEISNPVSAN 79

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974672 311 PSLLSEPMKTCFTGGN-VTLTCQVSGaYPPAKILWLRNL-TQPEVIIQPSSRHLITQDGqNSTLTIHNCSQDlDEGYYIC 388
Cdd:cd20954    2 PRWIVEPVDANVAAGQdVMLHCQADG-FPTPTVTWKKATgSTPGEYKDLLYDPNVRILP-NGTLVFGHVQKE-NEGHYLC 78

                 ....*..
gi 767974672 389 RADSPVG 395
Cdd:cd20954   79 EAKNGIG 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767974672   32 VIGEVHENVTLHCgNISGL-RGQVTWYRNNSEPVFLLSSNSSLRPAEprfslvdaTSLHIESLSLGDEGIYTCQ 104
Cdd:pfam13927  11 VTVREGETVTLTC-EATGSpPPTITWYKNGEPISSGSTRSRSLSGSN--------STLTISNVTRSDAGTYTCV 75

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974672  146 GSQVDFSCNSSSRPPPVVEWWF--QALNSSSEsfgHNLTVNFFSLLLISPNLQ----GNYTCLALNQLSKrhRKVTTELL 219
Cdd:pfam07679  15 GESARFTCTVTGTPDPEVSWFKdgQPLRSSDR---FKVTYEGGTYTLTISNVQpddsGKYTCVATNSAGE--AEASAELT 89

                  .
gi 767974672  220 V 220
Cdd:pfam07679  90 V 90

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974672  323 TGGNVTLTCQVSGAYPPA--KILWLRNLT--QPEVII----------QPSSRHLITQDGQNS--TLTIHNCSQDlDEGYY 386
Cdd:pfam07686  10 LGGSVTLPCTYSSSMSEAstSVYWYRQPPgkGPTFLIayysngseegVKKGRFSGRGDPSNGdgSLTIQNLTLS-DSGTY 88

                          90       100
                  ....*....|....*....|
gi 767974672  387 ICRADSPVGVREM-EIWLSV 405
Cdd:pfam07686  89 TCAVIPSGEGVFGkGTRLTV 108

Immunoglobulin I-set domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 767974672   53 QVTWYRNNSEpvfllssnssLRPaEPRFSLV---DATSLHIESLSLGDEGIYTCQ 104
Cdd:pfam07679  31 EVSWFKDGQP----------LRS-SDRFKVTyegGTYTLTISNVQPDDSGKYTCV 74

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767974672 324 GGNVTLTCQVSGAyPPAKILWLRNLTQpeviiQPSSRHLITQDgqnSTLTIHNCsQDLDEGYYICRADSPVG 395
Cdd:cd05725   12 DDSAEFQCEVGGD-PVPTVRWRKEDGE-----LPKGRYEILDD---HSLKIRKV-TAGDMGSYTCVAENMVG 73

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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767974672 322 FTGGNVTLTCQVSGAyPPAKILWLRNltqPEVIIQPSSRHLITQDGQNS-TLTIHNCSQDlDEGYYICRADSPVGV 396
Cdd:cd05892   13 LEGDPVRLECQISAI-PPPQIFWKKN---NEMLQYNTDRISLYQDNCGRiCLLIQNANKK-DAGWYTVSAVNEAGV 83

First immunoglobulin (Ig)-like domain of carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM); The members here are composed of the immunoglobulin (Ig)-like domain 1 in carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) proteins. The CEA family is a group of anchored or secreted glycoproteins, expressed by epithelial cells, leukocytes, endothelial cells, and placenta. The CEA family is divided into the CEACAM and pregnancy-specific glycoprotein (PSG) subfamilies. This group represents the CEACAM subfamily. CEACAM1 has many important cellular functions: it is a cell adhesion molecule and a signaling molecule that regulates the growth of tumor cells, an angiogenic factor, and a receptor for bacterial and viral pathogens, including mouse hepatitis virus (MHV). In mice, four isoforms of CEACAM1 generated by alternative splicing have either two (D1, D4) or four (D1-D4) Ig-like domains on the cell surface.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974672  30 AVVIGEvheNVTLHCGNISGLRGQVTWYRNNS-EPVFLL-----SSNSSLR-PA-EPRFSLVDATSLHIESLSLGDEGIY 101
Cdd:cd05774    9 QVAEGE---NVLLLVHNLPENLLAYAWYKGKTvSPNFLIasyiiSTNSSTPgPAySGRETIYPNGSLLIQNVTQKDTGFY 85

                         90       100
                 ....*....|....*....|.
gi 767974672 102 TCQeILNV---TQWFQVWLQV 119
Cdd:cd05774   86 TLQ-TITAdlqTEQASVHLQV 105