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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24584160    282 AYLGQDVILECHTEAYPASINYWTTERGDMIISDTSRAGDKYETTSTvsgytkymkLKIRAVGPNDFGTYRCVAKNSLGE 361
Cdd:smart00410   6 VKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSGSTST---------LTISNVTPEDSGTYTCAATNSSGS 76

                   ....*..
gi 24584160    362 TDGNIKL 368
Cdd:smart00410  77 ASSGTTL 83

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24584160   175 PPIIVegLTSNDMVVREGQNISLVCKARGYPEPYVMWRREDGEEM-LIGGEHVNVVDGELLHITKVSRLHMAAYLCVASN 253
Cdd:pfam13927   1 KPVIT--VSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISsGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24584160    282 AYLGQDVILECHTEAYPASINYWTTERGDMIISDTSRAGDKYETTSTvsgytkymkLKIRAVGPNDFGTYRCVAKNSLGE 361
Cdd:smart00410   6 VKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSGSTST---------LTISNVTPEDSGTYTCAATNSSGS 76

                   ....*..
gi 24584160    362 TDGNIKL 368
Cdd:smart00410  77 ASSGTTL 83

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24584160     82 NVTVSVGRDALMACVVENLKGYKVAWVRVDTQtilsihhnVISQNSRISLTYNDHRSwYLHIKEVEETDRGWYMCQVNTD 161
Cdd:smart00410   3 SVTVKEGESVTLSCEASGSPPPEVTWYKQGGK--------LLAESGRFSVSRSGSTS-TLTISNVTPEDSGTYTCAATNS 73

                           90
                   ....*....|...
gi 24584160    162 PMrSRKGYLQVVV 174
Cdd:smart00410  74 SG-SASSGTTLTV 85

First (N-terminal) immunoglobulin (Ig)-like domain of nectin-like molecule-3; member of the V-set of Ig superfamily (IgSF) domains; The members here are composed of the N-terminal immunoglobulin (Ig)-like domain of nectin-like molecule-3, Necl-3 (also known as cell adhesion molecule 2 (CADM2), SynCAM2, IGSF4D). Nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 - Necl-5). They all have an extracellular region containing three Ig-like domains, a transmembrane region, and a 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-3 accumulates in central and peripheral nervous system tissue, and has been shown to selectively interact with oligodendrocytes.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24584160  80 IANVTVSVGRDALMACVVENLKGYKVAWVRVDTQTILSIHHNVISQNsRISLTYNDHRSWYLHIKEVEETDRGWYMCQVN 159
Cdd:cd07701   4 TQNVTVVEGGTANLTCRVDQNDNTSLQWSNPAQQTLYFDDKKALRDN-RIELVRASWHELSISISDVSLSDEGQYTCSLF 82

                        90
                ....*....|....
gi 24584160 160 TDPMRSRKGYLQVV 173
Cdd:cd07701  83 TMPVKTSKAYLTVL 96

BARF1; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24584160  105 VAWVRV---DTQTILS-IHHNVISQNSRISLTYNDHRS---WYLHIKEVEETDRGWYMCQVNTDPMRSRKGYLQVVVPPI 177
Cdd:PHA03376  46 VSWFKLgpgEEQVLIGrMHHDVIFIEWPFRGFFDIHRSantFFLVVTAANISHDGNYLCRMKLGETEVTKQEHLSVVKPL 125

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24584160  178 IVEgLTSNDMVVREGQNISLVCKARGYPEPYVMWRREDGEE---MLIGGEHVNVVDGEL-----LHITKVSRLHMAaylC 249
Cdd:PHA03376 126 TLS-VHSERSQFPDFSVLTVTCTVNAFPHPHVQWLMPEGVEpapTAANGGVMKEKDGSLsvavdLSLPKPWHLPVT---C 201

                 ....
gi 24584160  250 VASN 253
Cdd:PHA03376 202 VGKN 205

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 24584160 186 DMVVREGQNISLVCKARGYPEPYVMWRREDGEEM-----LIGGEHVNVVDGELLHITKVSRLHMAAYLCVASNGVPPSIS 260
Cdd:cd20954  10 DANVAAGQDVMLHCQADGFPTPTVTWKKATGSTPgeykdLLYDPNVRILPNGTLVFGHVQKENEGHYLCEAKNGIGSGLS 89

                ....*..
gi 24584160 261 KRVHLRV 267
Cdd:cd20954  90 KVIFLKV 96

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24584160    184 SNDMVVREGQNISLVCKARGYPEPYVMWRREDGeEMLIGGEHVNVVDGEL---LHITKVSRLHMAAYLCVASNGVpPSIS 260
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKQGG-KLLAESGRFSVSRSGStstLTISNVTPEDSGTYTCAATNSS-GSAS 78

                   ....*..
gi 24584160    261 KRVHLRV 267
Cdd:smart00410  79 SGTTLTV 85

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24584160 186 DMVVREGQNISLVCKARGYPEPYVMWRREDGeEMLIGGEHvnVVDGELLHITKVSRLHMAAYLCVASNGVpPSISKRVHL 265
Cdd:cd05725   6 NQVVLVDDSAEFQCEVGGDPVPTVRWRKEDG-ELPKGRYE--ILDDHSLKIRKVTAGDMGSYTCVAENMV-GKIEASATL 81

                ..
gi 24584160 266 RV 267
Cdd:cd05725  82 TV 83

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24584160   270 PPMLSIPNQLEGAYLGQDVILECHTEAYPASINYWTTErGDMIISDTSRAGDKYETTSTvsgytkymkLKIRAVGPNDFG 349
Cdd:pfam13927   1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKN-GEPISSGSTRSRSLSGSNST---------LTISNVTRSDAG 70

                  ....*...
gi 24584160   350 TYRCVAKN 357
Cdd:pfam13927  71 TYTCVASN 78

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24584160 192 GQNISLVCKARGYPEPYVMWRR-----EDGEEMLIGGEhvnvvDGELLHITKVSRLHMAAYLCVASNGVPPSiSKRVHLR 266
Cdd:cd05730  18 GQSVTLACDADGFPEPTMTWTKdgepiESGEEKYSFNE-----DGSEMTILDVDKLDEAEYTCIAENKAGEQ-EAEIHLK 91

                .
gi 24584160 267 V 267
Cdd:cd05730  92 V 92

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 24584160 195 ISLVCKARGYPEPYVMWRREDGE-EMLIGGEHVNVVDGELLHITKVSRLHMAAYLCVASNGVPPSISKRV 263
Cdd:cd00096   1 VTLTCSASGNPPPTITWYKNGKPlPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24584160 184 SNDMVVREGQNISLVCKARGYPEPYVMWRREDGEemLIGGEHVNVV-DGELLHITKVSRLHMAAYLCVASNGVPPSiSKR 262
Cdd:cd05764   7 THELRVLEGQRATLRCKARGDPEPAIHWISPEGK--LISNSSRTLVyDNGTLDILITTVKDTGAFTCIASNPAGEA-TAR 83

                ....*
gi 24584160 263 VHLRV 267
Cdd:cd05764  84 VELHI 88

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.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 24584160 188 VVREGQNISLVCKARGYPEPYVMWRRedGEEMLIGGEHVNVVDGELLHITKVSRLHMAAYLCVASN 253
Cdd:cd04969  13 LAAKGGDVIIECKPKASPKPTISWSK--GTELLTNSSRICILPDGSLKIKNVTKSDEGKYTCFAVN 76

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24584160 176 PIIVEglTSNDMVVREGQNISLVCKARGYPEPYVMWRReDGEEMLI-----GGEHVNVVDGELLHITKV----SRLHMAA 246
Cdd:cd07693   1 PRIVE--HPSDLIVSKGDPATLNCKAEGRPTPTIQWLK-NGQPLETdkddpRSHRIVLPSGSLFFLRVVhgrkGRSDEGV 77

                        90       100
                ....*....|....*....|.
gi 24584160 247 YLCVASNGVPPSISKRVHLRV 267
Cdd:cd07693  78 YVCVAHNSLGEAVSRNASLEV 98

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24584160 177 IIVEGltSNDMVVREGQNISLVCKARGYPEPYVMWRReDGEEMLIGGEHVNVVDGELLHITKVSRLHMAAYLCVASN 253
Cdd:cd20952   1 IILQG--PQNQTVAVGGTVVLNCQATGEPVPTISWLK-DGVPLLGKDERITTLENGSLQIKGAEKSDTGEYTCVALN 74

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24584160 192 GQNISLVCKARGYPEPYVMWRREDGEE-------MLIGGEHVNVVDGELLhITKVSRLHMAAYLCVASNGVPPSISKRVH 264
Cdd:cd05734  16 GKAVVLNCSADGYPPPTIVWKHSKGSGvpqfqhiVPLNGRIQLLSNGSLL-IKHVLEEDSGYYLCKVSNDVGADISKSMY 94

                ...
gi 24584160 265 LRV 267
Cdd:cd05734  95 LTV 97

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24584160 171 QVVVPPiivegltsNDMVVREGQNISLVCKARGYPEPYVMWRREDGEEMLIGGE------HVNVVDGELLHITKVSRLHM 244
Cdd:cd05726   1 QFVVKP--------RDQVVALGRTVTFQCETKGNPQPAIFWQKEGSQNLLFPYQppqpssRFSVSPTGDLTITNVQRSDV 72

                        90       100
                ....*....|....*....|...
gi 24584160 245 AAYLCVASNgVPPSISKRVHLRV 267
Cdd:cd05726  73 GYYICQALN-VAGSILAKAQLEV 94

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24584160   270 PPMLSIPNQLEGAYlGQDVILECHTEAYPASINYWTTeRGDMIISDtsragDKYETTSTVSGYTkymkLKIRAVGPNDFG 349
Cdd:pfam07679   1 PKFTQKPKDVEVQE-GESARFTCTVTGTPDPEVSWFK-DGQPLRSS-----DRFKVTYEGGTYT----LTISNVQPDDSG 69

                          90
                  ....*....|..
gi 24584160   350 TYRCVAKNSLGE 361
Cdd:pfam07679  70 KYTCVATNSAGE 81

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24584160 185 NDMV-VREGQNISLVCKARGYPEPYVMW--RREDGEEMLIGGEHVNVVDGELlhitKVSRLHM---AAYLCVASNGVPPS 258
Cdd:cd20969   9 AQQVfVDEGHTVQFVCRADGDPPPAILWlsPRKHLVSAKSNGRLTVFPDGTL----EVRYAQVqdnGTYLCIAANAGGND 84

                ....*....
gi 24584160 259 iSKRVHLRV 267
Cdd:cd20969  85 -SMPAHLHV 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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24584160 285 GQDVILECHTEAYPASINYWTTERGDMIISDTSRagDKYETTstvsgytkymkLKIRAVGPNDFGTYRCVAKNSLGETDG 364
Cdd:cd05731  10 GGVLLLECIAEGLPTPDIRWIKLGGELPKGRTKF--ENFNKT-----------LKIENVSEADSGEYQCTASNTMGSARH 76

                ..
gi 24584160 365 NI 366
Cdd:cd05731  77 TI 78

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24584160 191 EGQNISLVCKARGYPEPYVMWRReDGEEMLIGGEHVnVVDGELLHITKVSRLHMAAYLCVASNGVpPSISKRVHLRV 267
Cdd:cd05745   1 EGQTVDFLCEAQGYPQPVIAWTK-GGSQLSVDRRHL-VLSSGTLRISRVALHDQGQYECQAVNIV-GSQRTVAQLTV 74

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24584160   188 VVREGQNISLVCKAR-GYPEPYVMWRREDGEemLIGGEHVNVVDG----ELLHITKVSRLHMAAYLCVASNGVPPSISKR 262
Cdd:pfam00047   7 TVLEGDSATLTCSAStGSPGPDVTWSKEGGT--LIESLKVKHDNGrttqSSLLISNVTKEDAGTYTCVVNNPGGSATLST 84

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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 24584160 186 DMVVREGQNISLVCKARGYPEPYVMWRREDgeEMLIGGEHVNVV-DGE---LLHITKVSRLHMAAYLCVASN 253
Cdd:cd20973   6 DKEVVEGSAARFDCKVEGYPDPEVKWMKDD--NPIVESRRFQIDqDEDglcSLIISDVCGDDSGKYTCKAVN 75

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 24584160 186 DMVVREGQNISLVCKARGYPEPYVMWrredgeemLIGGEHVNV--------VDGELLHITKVSRLHMAAYLCVASN 253
Cdd:cd05868   8 NLVLSPGEDGTLICRANGNPKPSISW--------LTNGVPIEIaptdpsrkVDGDTIIFSKVQERSSAVYQCNASN 75

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24584160 284 LGQDVILECHTEAYPASINYWTTERGDMIISDTSRAGDKyettstvsgytkymKLKIRAVGPNDFGTYRCVAKNSLGETD 363
Cdd:cd05725  11 VDDSAEFQCEVGGDPVPTVRWRKEDGELPKGRYEILDDH--------------SLKIRKVTAGDMGSYTCVAENMVGKIE 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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 24584160 184 SNDMVVREGQNISLVCKARGYPEPYVMWRREDGEEMLIGGEHVNvvDGELLHITKVSRLHMAAYLCVASNG 254
Cdd:cd05876   2 SSSLVALRGQSLVLECIAEGLPTPTVKWLRPSGPLPPDRVKYQN--HNKTLQLLNVGESDDGEYVCLAENS 70

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24584160 182 LTSNDMVVREGQNISLVCKARGYPEPY--VMWRREdgeemligGEHVNVVDGELLHITKVSRLHMAAYLCVASNGVPPSI 259
Cdd:cd20937   7 VTPSDAIVREGDSVTMTCEVSSSNPEYttVSWLKD--------GTSLKKQNTFTLNLREVTKDQSGKYCCQVSNDVGPGR 78

                        90
                ....*....|
gi 24584160 260 SKRVHLRVQF 269
Cdd:cd20937  79 SEEVFLQVQY 88

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24584160 278 QLEGAYLGQDVILECHTEAYPASINYWTteRGDMIISDTSRagdkyeTTSTVSGytkymKLKIRAVGPNDFGTYRCVAKN 357
Cdd:cd04969  10 KKILAAKGGDVIIECKPKASPKPTISWS--KGTELLTNSSR------ICILPDG-----SLKIKNVTKSDEGKYTCFAVN 76

                ...
gi 24584160 358 SLG 360
Cdd:cd04969  77 FFG 79

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 24584160 191 EGQnISLVCKARGYPEPYVMWRREDGEEMLIgGEHVNVVDGELLHITKVSRLHMAAYLCVASN 253
Cdd:cd05849  19 EGK-VSVNCRARANPFPIYKWRKNNLDIDLT-NDRYSMVGGNLVINNPDKYKDAGRYVCIVSN 79

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24584160 175 PPIIVEglTSNDMVVREGQNISLVCKARGYPEPYVMWRReDGEEM-----LIGGEHVNvVDGEL---LHITKVSRLHMAA 246
Cdd:cd20956   1 APVLLE--TFSEQTLQPGPSVSLKCVASGNPLPQITWTL-DGFPIpesprFRVGDYVT-SDGDVvsyVNISSVRVEDGGE 76