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 1773401384  19 FPLTQNVTVVEGGTAILTCRVDQNDNTSLQWSNPAQQTLYFDDKKALRDNRIELVRASWHELSISVSDVSLSDEGQYTCS 98
Cdd:cd07701     1 FPLTQNVTVVEGGTANLTCRVDQNDNTSLQWSNPAQQTLYFDDKKALRDNRIELVRASWHELSISISDVSLSDEGQYTCS 80

                          90
                  ....*....|....*.
gi 1773401384  99 LFTMPVKTSKAYLTVL 114
Cdd:cd07701    81 LFTMPVKTSKAYLTVL 96

putative band 4.1 homologues' binding motif;

                           10
                   ....*....|....*....
gi 1773401384  341 LGRYLARHKGTYLTNEAKG 359
Cdd:smart00294   1 MYRYKHRDEGSYHTHEPKG 19

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 1773401384  19 FPLTQNVTVVEGGTAILTCRVDQNDNTSLQWSNPAQQTLYFDDKKALRDNRIELVRASWHELSISVSDVSLSDEGQYTCS 98
Cdd:cd07701     1 FPLTQNVTVVEGGTANLTCRVDQNDNTSLQWSNPAQQTLYFDDKKALRDNRIELVRASWHELSISISDVSLSDEGQYTCS 80

                          90
                  ....*....|....*.
gi 1773401384  99 LFTMPVKTSKAYLTVL 114
Cdd:cd07701    81 LFTMPVKTSKAYLTVL 96

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1773401384 220 PSVKIIPSTPFPQEGQPLILTCESKGKPLPEpVLWTKDGGELPD----PDRMVVSGRELNILFLNKTDNGTYRCEATN 293
Cdd:pfam13927   2 PVITVSPSSVTVREGETVTLTCEATGSPPPT-ITWYKNGEPISSgstrSRSLSGSNSTLTISNVTRSDAGTYTCVASN 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 1773401384  232 QEGQPLILTCESKGKPLPEpVLWTKDGGE-LPDPDRMVVSGRELN-ILFLNKT---DNGTYRCEATNTIGQSSAEYVLIV 306
Cdd:smart00410   7 KEGESVTLSCEASGSPPPE-VTWYKQGGKlLAESGRFSVSRSGSTsTLTISNVtpeDSGTYTCAATNSSGSASSGTTLTV 85

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1773401384  23 QNVTVVEGGTAILTCRVDQNDNTSLQWsnpaqqtlYFDDKKaLRDNRIELVRASWHELSISVSDVSLSDEGQYTC 97
Cdd:pfam13927   9 SSVTVREGETVTLTCEATGSPPPTITW--------YKNGEP-ISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTC 74

Immunoglobulin C-Type;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1773401384  136 QLTCKTSGSKPA-ADIRWFKN-DKEIKDVKY---LKEEDAnrkTFTVSSTLDFRVDRSDDGVAVICRVDHESL 203
Cdd:smart00407   3 TLVCLVSGFYPPdITVTWLRNgQEVTEGVSTtdpLKNSDG---TYFLSSYLTVPASTWESGDVYTCQVTHEGL 72

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 1773401384  19 FPLTQNVTVVEGGTAILTCRVDQNDNTSLQWSNPAQQTLYFDDKKALRDNRIELVRASWHELSISVSDVSLSDEGQYTCS 98
Cdd:cd07701     1 FPLTQNVTVVEGGTANLTCRVDQNDNTSLQWSNPAQQTLYFDDKKALRDNRIELVRASWHELSISISDVSLSDEGQYTCS 80

                          90
                  ....*....|....*.
gi 1773401384  99 LFTMPVKTSKAYLTVL 114
Cdd:cd07701    81 LFTMPVKTSKAYLTVL 96

First (N-terminal) immunoglobulin (Ig)-like domain of the nectin-like molecules; member of the V-set of Ig superfamily (IgSF) domains; The members here are composed of the N-terminal immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 (also known as cell adhesion molecule 3 (CADM3)), Necl-2 (CADM1), Necl-3 (CADM2), and similar proteins. At least five nectin-like molecules have been identified (Necl-1 to 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-1, Necl-2, and Necl-3 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 accumulates in central and peripheral nervous system tissue and has been shown to selectively interact with oligodendrocytes. This group also contains Class-I MHC-restricted T-cell-associated molecule (CRTAM), whose expression pattern is consistent with its expression in Class-I MHC-restricted T-cells.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1773401384  20 PLTQNVTVVEGGTAILTCRVDQNDNTSLQWSNPAQQTLYFDDKKALRDNRIELVRASWHELSISVSDVSLSDEGQYTCSL 99
Cdd:cd05717     1 PHTQDVTVVEGETLTLKCQVSLRDDSSLQWLNPNGQTIYFNDKRALRDSRYQLLNHSASELSISVSNVTLSDEGVYTCLH 80

                          90
                  ....*....|....
gi 1773401384 100 FTMPVKTSKAYLTV 113
Cdd:cd05717    81 YTDPVSTKKVTVTV 94

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1773401384 114 LGVPEKPQISGFSSPVMEGDLMQLTCKTSGSKPAADIRWFKNDKEIKDVKYLKEEDANRKTFTVSSTLDFRVDRSDDGVA 193
Cdd:cd07705     1 LGIPQKPQITGYESAFKEKDKAKLRCTSSGSKPAANIKWRKGDQELEGAPTSVQEDGNGKTFTVSSSVEFQVTREDDGAE 80

                          90       100
                  ....*....|....*....|...
gi 1773401384 194 VICRVDHESLNATPQVAMQVLEI 216
Cdd:cd07705    81 ITCSVGHESLHDSDRSTSQRIEV 103

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1773401384 117 PEKPQISgFSSPVMEGDLMQLTCKTSGSKPAADIRWFKNDKEIKDVKYLKEedaNRKTFTVSSTLDFRVDRSDDGVAVIC 196
Cdd:cd05885     4 PENPVVE-VREQAVEGGEVELSCLVPRSRPAATLRWYRDRKELKGVSSGQE---NGKVWSVASTVRFRVDRKDDGGIVIC 79

                  ....*..
gi 1773401384 197 RVDHESL 203
Cdd:cd05885    80 EAQNQAL 86

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1773401384 137 LTCKTSGSKPAADIRWFKNDKEIKDVKYLKEEDANRKTFTVSSTLDFRVDRSDDGVAVICRVDHESL 203
Cdd:pfam08205  19 ATCSSAGGKPAPRITWYLDGKPLEAAETSSEQDPESGLVTVTSELKLVPSRSDHGQSLTCQVSYGAL 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1773401384 234 GQPLILTCESKGKPLPEpVLWTKDGGELPDPDRMVVSGRELNILFLNKTDNGTYRCEATNTIGQSSAEYVLIV 306
Cdd:cd05725    12 DDSAEFQCEVGGDPVPT-VRWRKEDGELPKGRYEILDDHSLKIRKVTAGDMGSYTCVAENMVGKIEASATLTV 83

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1773401384 232 QEGQPLILTCESKGKPLPEpVLWTKDGGELPDPDRMVVSGRE----LNILFLNKTDNGTYRCEATNTIGQSSAEYVLIV 306
Cdd:pfam07679  13 QEGESARFTCTVTGTPDPE-VSWFKDGQPLRSSDRFKVTYEGgtytLTISNVQPDDSGKYTCVATNSAGEAEASAELTV 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 1773401384 237 LILTCESKGKPLPEpVLWTKDGGELP----DPDRMVVSGRELNILFLNKTDNGTYRCEATNTIGQSSAEYV 303
Cdd:cd00096     1 VTLTCSASGNPPPT-ITWYKNGKPLPpssrDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1773401384 234 GQPLILTCESKGKPLPEpVLWTKDGGELPdPDRMVVS--GRELNILFLNKTDNGTYRCEATNTIGQSSAEYVLIV 306
Cdd:cd05731    10 GGVLLLECIAEGLPTPD-IRWIKLGGELP-KGRTKFEnfNKTLKIENVSEADSGEYQCTASNTMGSARHTISVTV 82

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1773401384 232 QEGQPLILTCESKGKPLPEpVLWTKDGGELPDPDRM-----------VVSgrELNILFLNKTDNGTYRCEATNTIGQSS 299
Cdd:cd20956    14 QPGPSVSLKCVASGNPLPQ-ITWTLDGFPIPESPRFrvgdyvtsdgdVVS--YVNISSVRVEDGGEYTCTATNDVGSVS 89

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1773401384 232 QEGQPLILTCESKGKPLPEpVLWTKDGGEL--PDPDRMVVSGReLNILFLNKTDNGTYRCEATNTIGQSSAEYVLIV 306
Cdd:cd20978    14 KGGQDVTLPCQVTGVPQPK-ITWLHNGKPLqgPMERATVEDGT-LTIINVQPEDTGYYGCVATNEIGDIYTETLLHV 88

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1773401384 224 IIPSTPFPQEGQPLILTCESKGKPLPEPVLWTKDGGELPDPDRMVVSGR-----ELNILFLNKTDNGTYRCEATNTIGQS 298
Cdd:pfam00047   1 SAPPTVTVLEGDSATLTCSASTGSPGPDVTWSKEGGTLIESLKVKHDNGrttqsSLLISNVTKEDAGTYTCVVNNPGGSA 80

                  ....*.
gi 1773401384 299 SAEYVL 304
Cdd:pfam00047  81 TLSTSL 86

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1773401384 220 PSVKIIPSTPFpQEGQPLILTCESKGkpLPEPVLWTKDGGELPDPDRMVVSG--RELNILFLNKTDNGTYRCEATNTIGQ 297
Cdd:cd05740     2 PFISSNNSNPV-EDKDAVTLTCEPET--QNTSYLWWFNGQSLPVTPRLTLSNgnRTLTLLNVTREDAGAYQCEISNPVSA 78

                  ....*.
gi 1773401384 298 SSAEYV 303
Cdd:cd05740    79 NRSDPV 84

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 1773401384  25 VTVVEGGTAILTCRV---DQNDNTSLQWS------NPAQQTLYF--DDKKALRDNRIELVRA-SWHELSISVSDVSLSDE 92
Cdd:pfam07686   6 VTVALGGSVTLPCTYsssMSEASTSVYWYrqppgkGPTFLIAYYsnGSEEGVKKGRFSGRGDpSNGDGSLTIQNLTLSDS 85

                          90       100
                  ....*....|....*....|....
gi 1773401384  93 GQYTCSLFTMP--VKTSKAYLTVL 114
Cdd:pfam07686  86 GTYTCAVIPSGegVFGKGTRLTVL 109

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1773401384 220 PSVKIIPSTPFPQEGQPLILTCESKGKPLPEpVLWTKDGGELP-DPDRMVVSGR--ELNILFLNKTDNGTYRCEATNTIG 296
Cdd:cd20976     2 PSFSSVPKDLEAVEGQDFVAQCSARGKPVPR-ITWIRNAQPLQyAADRSTCEAGvgELHIQDVLPEDHGTYTCLAKNAAG 80

                  ....
gi 1773401384 297 QSSA 300
Cdd:cd20976    81 QVSC 84

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1773401384 233 EGQPLILTCESKGKPLPEpVLWTK--DG--GELPDPD-RMVVSGR----ELNILFLNKTDNGTYRCEATNTIGQSS 299
Cdd:cd05732    15 ELEQITLTCEAEGDPIPE-ITWRRatRGisFEEGDLDgRIVVRGHarvsSLTLKDVQLTDAGRYDCEASNRIGGDQ 89

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1773401384 239 LTCESKGKPLPEpVLWTKDGGELPDPDRMVVSGR-ELNILFLNKTDNGTYRCEATNTIGQSSAEYVL 304
Cdd:cd05746     3 IPCSAQGDPEPT-ITWNKDGVQVTESGKFHISPEgYLAIRDVGVADQGRYECVARNTIGYASVSMVL 68

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1773401384 119 KPQISGFSSP--VMEGDLMQLTCKTSGSkPAADIRWFKNDKEIKDVKYLK-EEDANRKTFTVSStldfrVDRSDDGV 192
Cdd:pfam13927   1 KPVITVSPSSvtVREGETVTLTCEATGS-PPPTITWYKNGEPISSGSTRSrSLSGSNSTLTISN-----VTRSDAGT 71

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1773401384 120 PQISGFSSP--VMEGDLMQLTCKTSGSkPAADIRWFKNDKEIK-DVKYLKEEDANRKTFTVSstldfRVDRSDDGV 192
Cdd:pfam07679   1 PKFTQKPKDveVQEGESARFTCTVTGT-PDPEVSWFKDGQPLRsSDRFKVTYEGGTYTLTIS-----NVQPDDSGK 70

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1773401384 234 GQPLILTCESKGKPLPEpVLWTKDGGELPDPDRMVV---SGRELNILFLNKTDNGTYRCEATNTIGQSSAEYVLIV 306
Cdd:cd05730    18 GQSVTLACDADGFPEPT-MTWTKDGEPIESGEEKYSfneDGSEMTILDVDKLDEAEYTCIAENKAGEQEAEIHLKV 92

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1773401384 234 GQPLILTCESKGKPLpEPVLWTKDGGELPDPDR-MVVSGRELNILFLNK-TDNGTYRCEATNTIGQSS 299
Cdd:cd20958    15 GQTLRLHCPVAGYPI-SSITWEKDGRRLPLNHRqRVFPNGTLVIENVQRsSDEGEYTCTARNQQGQSA 81

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 1773401384 220 PSVKIIPStpfpQEGQPLILTCESKGKPLPEpVLWTKDGGELPDPDRM-VVSGRELNILFLNKTDNGTYRCEATNTIGQS 298
Cdd:cd04969     7 PVKKKILA----AKGGDVIIECKPKASPKPT-ISWSKGTELLTNSSRIcILPDGSLKIKNVTKSDEGKYTCFAVNFFGKA 81

                  ....*...
gi 1773401384 299 SAEYVLIV 306
Cdd:cd04969    82 NSTGSLSV 89

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1773401384 220 PSVKII-PSTPFPQEGQPLILTCESKGKPLPEpVLWTKDGGELPDPDRMVVSGRELNILFLNKTDNGTYRCEATNTIGQS 298
Cdd:cd04968     1 PSIKVRfPADTYALKGQTVTLECFALGNPVPQ-IKWRKVDGSPSSQWEITTSEPVLEIPNVQFEDEGTYECEAENSRGKD 79

                  ....*....
gi 1773401384 299 SAEYVLIVH 307
Cdd:cd04968    80 TVQGRIIVQ 88

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1773401384 233 EGQPLILTCESKGKPLPEpVLWTKDGGELPD-PDRMVVSGRELNILFLNKT---DNGTYRCEATNTIGQ--SSAE 301
Cdd:cd20972    15 EGSKVRLECRVTGNPTPV-VRWFCEGKELQNsPDIQIHQEGDLHSLIIAEAfeeDTGRYSCLATNSVGSdtTSAE 88

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1773401384 221 SVKIIPSTPFPQEGQPLILTCESKGKPLPEpVLWTKDGGELPDPDRMVVSGRE-LNILFLNKTDNGTYRCEATNTI--GQ 297
Cdd:cd20957     3 SATIDPPVQTVDFGRTAVFNCSVTGNPIHT-VLWMKDGKPLGHSSRVQILSEDvLVIPSVKREDKGMYQCFVRNDGdsAQ 81

                  ....
gi 1773401384 298 SSAE 301
Cdd:cd20957    82 ATAE 85

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1773401384 219 TPSVKIIPSTPFPQEGQPLILTCESKGKPLPEpVLWTKDGGELPDPDRMVVSGRELNILFLNKTDNGTYRCEATNTIGQ 297
Cdd:cd05851     1 PADINVKFKDTYALKGQNVTLECFALGNPVPV-IRWRKILEPMPATAEISMSGAVLKIFNIQPEDEGTYECEAENIKGK 78

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 1773401384 222 VKIIPSTPFPQEGQPLILTCE-SKGKPLPEPVLWTKDGGELPDPDRMVvsgreLNILFLNKTDNGTYRCEATNTIG-QSS 299
Cdd:cd20937     5 IKVTPSDAIVREGDSVTMTCEvSSSNPEYTTVSWLKDGTSLKKQNTFT-----LNLREVTKDQSGKYCCQVSNDVGpGRS 79