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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665401054  443 LYPPSPPLLTGYNDGdiLISGSILKLQCSSAGGNPPPTLQWYKNDKIINAPSKLVDS------KITSELSLLVNASDNNA 516
Cdd:cd05761     1 LGVPEKPVITGFTSP--VVEGDEITLTCTTSGSKPAADIRWFKNDKELKGVKEVQESgagktfTVTSTLRFRVDRDDDGV 78

                          90
                  ....*....|.
gi 665401054  517 IYKCKVQNAAI 527
Cdd:cd05761    79 AVICRVDHESL 89

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 665401054  162 NLTlhCIAENANPAAEIVWFQGEVPVSTAPIVTVNQTAPKRFTTSSTLHLQPRAEDDYKEFSCEARHKALP 232
Cdd:cd05759    19 NLT--CRARGAKPAAEIIWFRDGEQLEGAVYSKELLKDGKRETTVSTLLITPSDLDTGRTFTCRARNEAIP 87

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665401054   833 PEIDHSPgfTRYAARLGVRAQLICRSLASPQPSFIWRRHGKDLKmqrrnkfKSVERQVDALNFESALLIENTSPDDYGQY 912
Cdd:pfam13927    2 PVITVSP--SSVTVREGETVTLTCEATGSPPPTITWYKNGEPIS-------SGSTRSRSLSGSNSTLTISNVTRSDAGTY 72

                   ....*.
gi 665401054   913 ECVVRN 918
Cdd:pfam13927   73 TCVASN 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 665401054     45 PHDLQILEGTDTLLRCEVS-NRAGKVQWTKDGFALgfsavIPGFPRYSVLVDAKQnaYNLQIKNATLEDDAEYQCQVGPA 123
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASgSPPPEVTWYKQGGKL-----LAESGRFSVSRSGST--STLTISNVTPEDSGTYTCAATNS 73

                            90
                    ....*....|....
gi 665401054    124 AGNpaIRANAKLSI 137
Cdd:smart00410   74 SGS--ASSGTTLTV 85

Fibronectin type 3 domain [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665401054  932 PSRPDAPLQLRVGNVSDTGVDLNWTPGFDGGMQTYFRLRlKQHGEDKYKYVDAKPGHQNISLDGLKPGATYYFSVMAANE 1011
Cdd:COG3401   324 LTPPAAPSGLTATAVGSSSITLSWTASSDADVTGYNVYR-STSGGGTYTKIAETVTTTSYTDTGLTPGTTYYYKVTAVDA 402

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665401054 1012 AGGSKFMPDIKLTLSKGSQPHSAEYTEKDELPNVMIIGIT-SAAMVLLVLNAALVAWFVIRRQNKSQSEAEPSNDDVYSK 1090
Cdd:COG3401   403 AGNESAPSEEVSATTASAASGESLTASVDAVPLTDVAGATaAASAASNPGVSAAVLADGGDTGNAVPFTTTSSTVTATTT 482

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 665401054 1091 DDSQSVYKLPITALQADVQKKAAASTYLVENVDIIQSTAYPPKYQESSMCTPPYPLCNPDF 1151
Cdd:COG3401   483 DTTTANLSVTTGSLVGGSGASSVTNSVSVIGASAAAAVGGAPDGTPNVTGASPVTVGASTG 543

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 665401054  443 LYPPSPPLLTGYNDGdiLISGSILKLQCSSAGGNPPPTLQWYKNDKIINAPSKLVDS------KITSELSLLVNASDNNA 516
Cdd:cd05761     1 LGVPEKPVITGFTSP--VVEGDEITLTCTTSGSKPAADIRWFKNDKELKGVKEVQESgagktfTVTSTLRFRVDRDDDGV 78

                          90
                  ....*....|.
gi 665401054  517 IYKCKVQNAAI 527
Cdd:cd05761    79 AVICRVDHESL 89

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.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665401054    935 PDAPLQLRVGNVSDTGVDLNWTPGFDGGMQTY---FRLRlKQHGEDKYKYVDAKPGHQNISLDGLKPGATYYFSVMAANE 1011
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTLSWEPPPDDGITGYivgYRVE-YREEGSEWKEVNVTPSSTSYTLTGLKPGTEYEFRVRAVNG 79

                    ....
gi 665401054   1012 AGGS 1015
Cdd:smart00060   80 AGEG 83

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 665401054  246 LYPPGAPFFEGYSQgeTLHRGQEVQIACRSRGGNPPAQLTWYRNGVAISSPQRTSGRLSENVY------KFTAAAEDNGA 319
Cdd:cd05761     1 LGVPEKPVITGFTS--PVVEGDEITLTCTTSGSKPAADIRWFKNDKELKGVKEVQESGAGKTFtvtstlRFRVDRDDDGV 78

                          90       100
                  ....*....|....*....|....
gi 665401054  320 NLVCEAKN-LLATTPLRAELNLTV 342
Cdd:cd05761    79 AVICRVDHeSLTSTPKQTQQVLEV 102

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665401054   833 PEIDHSPgfTRYAARLGVRAQLICRSLASPQPSFIWRRHGKDLKmqrrnkfKSVERQVDALNFESALLIENTSPDDYGQY 912
Cdd:pfam13927    2 PVITVSP--SSVTVREGETVTLTCEATGSPPPTITWYKNGEPIS-------SGSTRSRSLSGSNSTLTISNVTRSDAGTY 72

                   ....*.
gi 665401054   913 ECVVRN 918
Cdd:pfam13927   73 TCVASN 78

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665401054  748 RSFVAGEPAVLACHIQARPLEAahVRWSRDGYDLAT-RTISSFENGTalLQIASVER-SDIGNFTCIVDNQRGAPAAQNV 825
Cdd:cd20958    10 LTAVAGQTLRLHCPVAGYPISS--ITWEKDGRRLPLnHRQRVFPNGT--LVIENVQRsSDEGEYTCTARNQQGQSASRSV 85

                  ....
gi 665401054  826 LLVV 829
Cdd:cd20958    86 FVKV 89

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 665401054  852 AQLICRSLASPQPSFIWRRHGKDLKMQRRNKFKSVERQvdalnfeSALLIENTSPDDYGQYECVVRNSLGQASTT 926
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSELGN-------GTLTISNVTLEDSGTYTCVASNSAGGSASA 68

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 665401054   266 GQEVQIACRSRGGNPPAQLTWYRNG---------VAISSPQRTSGRLSEnvYKFTAAAEDNGANLVCEAKN 327
Cdd:pfam08205   14 GPEVVATCSSAGGKPAPRITWYLDGkpleaaetsSEQDPESGLVTVTSE--LKLVPSRSDHGQSLTCQVSY 82

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 665401054   470 CSSAGGNPPPTLQWYKNDKIINAPSKLVDSK-------ITSELSLLVNASDNNAIYKCKVQNAA 526
Cdd:pfam08205   21 CSSAGGKPAPRITWYLDGKPLEAAETSSEQDpesglvtVTSELKLVPSRSDHGQSLTCQVSYGA 84

Immunoglobulin I-set domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665401054    40 KFHLTPHDLQILEGTDTLLRCEVS-NRAGKVQWTKDGfalgfsAVIPGFPRYSVlvDAKQNAYNLQIKNATLEDDAEYQC 118
Cdd:pfam07679    2 KFTQKPKDVEVQEGESARFTCTVTgTPDPEVSWFKDG------QPLRSSDRFKV--TYEGGTYTLTISNVQPDDSGKYTC 73

                   ..
gi 665401054   119 QV 120
Cdd:pfam07679   74 VA 75

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

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665401054    668 ASGNPMViTYTWTKDG--LPISSNSLSGQRLISDGpRLNISRLSRNDAGVYICEALNSQGTALLEIQVAV 735
Cdd:smart00410   18 ASGSPPP-EVTWYKQGgkLLAESGRFSVSRSGSTS-TLTISNVTPEDSGTYTCAATNSSGSASSGTTLTV 85

Immunoglobulin (Ig)-like domain found in neuregulin (NRG)-1; The members here are composed of the immunoglobulin (Ig)-like domain found in neuregulin (NRG)-1. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. NRG-1 belongs to the neuregulin gene family which is comprised of four genes. This group represents NRG-1. NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, and heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. The NRG-1 protein binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. NRG-1 has multiple functions, for example, in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665401054   49 QILEGTDTLLRCEVSNR--AGKVQWTKDGFALGF-----SAVIPGFPRYSvlvdakqnayNLQIKNATLEDDAEYQCQVG 121
Cdd:cd05895    10 EVAAGSKLVLRCETSSEypSLRFKWFKNGKEINRknkpeNIKIQKKKKKS----------ELRINKASLADSGEYMCKVS 79

                          90
                  ....*....|.
gi 665401054  122 PAAGNPAIRAN 132
Cdd:cd05895    80 SKLGNDSASAN 90

Fibronectin type 3 domain [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665401054  932 PSRPDAPLQLRVGNVSDTGVDLNWTPGFDGGMQTYFRLRlKQHGEDKYKYVDAKPGHQNISLDGLKPGATYYFSVMAANE 1011
Cdd:COG3401   324 LTPPAAPSGLTATAVGSSSITLSWTASSDADVTGYNVYR-STSGGGTYTKIAETVTTTSYTDTGLTPGTTYYYKVTAVDA 402

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665401054 1012 AGGSKFMPDIKLTLSKGSQPHSAEYTEKDELPNVMIIGIT-SAAMVLLVLNAALVAWFVIRRQNKSQSEAEPSNDDVYSK 1090
Cdd:COG3401   403 AGNESAPSEEVSATTASAASGESLTASVDAVPLTDVAGATaAASAASNPGVSAAVLADGGDTGNAVPFTTTSSTVTATTT 482

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 665401054 1091 DDSQSVYKLPITALQADVQKKAAASTYLVENVDIIQSTAYPPKYQESSMCTPPYPLCNPDF 1151
Cdd:COG3401   483 DTTTANLSVTTGSLVGGSGASSVTNSVSVIGASAAAAVGGAPDGTPNVTGASPVTVGASTG 543

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

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665401054    258 SQGETLHRGQEVQIACRSRGgNPPAQLTWYRNG-VAISSPQRTSGRLSENVYKFT---AAAEDNGaNLVCEAKNllATTP 333
Cdd:smart00410    1 PPSVTVKEGESVTLSCEASG-SPPPEVTWYKQGgKLLAESGRFSVSRSGSTSTLTisnVTPEDSG-TYTCAATN--SSGS 76

                    ....*....
gi 665401054    334 LRAELNLTV 342
Cdd:smart00410   77 ASSGTTLTV 85

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 665401054  343 LYAPKDVYLSGANQAKV-GDSVQLSCVTAPSNPQARISWSINGRPLDNSTYKTTSSSDGGWVSSSNISLTIDSQSRTFIA 421
Cdd:cd05761     1 LGVPEKPVITGFTSPVVeGDEITLTCTTSGSKPAADIRWFKNDKELKGVKEVQESGAGKTFTVTSTLRFRVDRDDDGVAV 80

                          90
                  ....*....|
gi 665401054  422 VCHALNTELT 431
Cdd:cd05761    81 ICRVDHESLT 90

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 665401054   365 LSCVTAPSNPQARISWSINGRPLDNSTYKTTSSSDGGWVSSS 406
Cdd:pfam08205   19 ATCSSAGGKPAPRITWYLDGKPLEAAETSSEQDPESGLVTVT 60

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 665401054  443 LYPPSPPLLTGYNDGdiLISGSILKLQCSSAGGNPPPTLQWYKNDKIINAPSKLVDS------KITSELSLLVNASDNNA 516
Cdd:cd05761     1 LGVPEKPVITGFTSP--VVEGDEITLTCTTSGSKPAADIRWFKNDKELKGVKEVQESgagktfTVTSTLRFRVDRDDDGV 78

                          90
                  ....*....|.
gi 665401054  517 IYKCKVQNAAI 527
Cdd:cd05761    79 AVICRVDHESL 89

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.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665401054    935 PDAPLQLRVGNVSDTGVDLNWTPGFDGGMQTY---FRLRlKQHGEDKYKYVDAKPGHQNISLDGLKPGATYYFSVMAANE 1011
Cdd:smart00060    1 PSPPSNLRVTDVTSTSVTLSWEPPPDDGITGYivgYRVE-YREEGSEWKEVNVTPSSTSYTLTGLKPGTEYEFRVRAVNG 79

                    ....
gi 665401054   1012 AGGS 1015
Cdd:smart00060   80 AGEG 83

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 665401054  246 LYPPGAPFFEGYSQgeTLHRGQEVQIACRSRGGNPPAQLTWYRNGVAISSPQRTSGRLSENVY------KFTAAAEDNGA 319
Cdd:cd05761     1 LGVPEKPVITGFTS--PVVEGDEITLTCTTSGSKPAADIRWFKNDKELKGVKEVQESGAGKTFtvtstlRFRVDRDDDGV 78

                          90       100
                  ....*....|....*....|....
gi 665401054  320 NLVCEAKN-LLATTPLRAELNLTV 342
Cdd:cd05761    79 AVICRVDHeSLTSTPKQTQQVLEV 102

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 665401054  140 APSSIVIEGYaRNARVEVEErqnLTLHCIAENANPAAEIVWFQGEVPVSTAPIVtVNQTAPKRFTTSSTLHLQPRAEDDY 219
Cdd:cd05761     3 VPEKPVITGF-TSPVVEGDE---ITLTCTTSGSKPAADIRWFKNDKELKGVKEV-QESGAGKTFTVTSTLRFRVDRDDDG 77

                          90       100
                  ....*....|....*....|....*.
gi 665401054  220 KEFSCEARHKALpPDVPMRAQVQLSV 245
Cdd:cd05761    78 VAVICRVDHESL-TSTPKQTQQVLEV 102

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
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 665401054  668 ASGNPMViTYTWTKDGLPISSNSLSGQRLISDGPRLNISRLSRNDAGVYICEALNSQGT 726
Cdd:cd00096     7 ASGNPPP-TITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGG 64

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 665401054   739 PTITAVSEGRSFVAGEPAVLACHIQARPleAAHVRWSRDGYDLATRTIS--SFENGTALLQIASVERSDIGNFTCIVDN 815
Cdd:pfam13927    2 PVITVSPSSVTVREGETVTLTCEATGSP--PPTITWYKNGEPISSGSTRsrSLSGSNSTLTISNVTRSDAGTYTCVASN 78

Immunoglobulin I-set domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665401054   845 AARLGVRAQLICRSLASPQPSFIWRRHGKDLKMQRRnkfksveRQVDALNFESALLIENTSPDDYGQYECVVRNSLGQAS 924
Cdd:pfam07679   11 EVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDR-------FKVTYEGGTYTLTISNVQPDDSGKYTCVATNSAGEAE 83

                   ....
gi 665401054   925 TTLE 928
Cdd:pfam07679   84 ASAE 87

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 665401054   266 GQEVQIACRSRGGNPPAQLTWYRNG---------VAISSPQRTSGRLSEnvYKFTAAAEDNGANLVCEAKN 327
Cdd:pfam08205   14 GPEVVATCSSAGGKPAPRITWYLDGkpleaaetsSEQDPESGLVTVTSE--LKLVPSRSDHGQSLTCQVSY 82

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

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665401054    846 ARLGVRAQLICRSLASPQPSFIWRRHGKDLKMQRRNKfksverQVDALNFESALLIENTSPDDYGQYECVVRNSLGQAST 925
Cdd:smart00410    6 VKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRF------SVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASS 79

                    ...
gi 665401054    926 TLE 928
Cdd:smart00410   80 GTT 82

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 665401054   448 PPLLTGYNDGDILISGSILKLQCSsAGGNPPPTLQWYKNDKIINAPSKLVDSKITSELSLLVNA--SDNNAIYKCKVQN 524
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVTLTCE-ATGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNvtRSDAGTYTCVASN 78

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665401054  751 VAGEPAVLACHIQARPLEAahVRWSRDGYDLATRT--ISSFENGTalLQIASVERSDIGNFTCIVDNQRGAPAAQNVLLV 828
Cdd:cd20952    12 AVGGTVVLNCQATGEPVPT--ISWLKDGVPLLGKDerITTLENGS--LQIKGAEKSDTGEYTCVALNLSGEATWSAVLDV 87