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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 58037299 140 NPGISANTSALVEGMDSVVAKCL--TNSSNISWYVNFVPTSGSNRMTISPDGKTLIIHRVSRYD 201
Cdd:cd05740   1 KPFISSNNSNPVEDKDAVTLTCEpeTQNTSYLWWFNGQSLPVTPRLTLSNGNRTLTLLNVTRED 64

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 58037299 140 NPGISANTSALVEGMDSVVAKCL--TNSSNISWYVNFVPTSGSNRMTISPDGKTLIIHRVSRYD 201
Cdd:cd05740   1 KPFISSNNSNPVEDKDAVTLTCEpeTQNTSYLWWFNGQSLPVTPRLTLSNGNRTLTLLNVTRED 64

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 58037299   246 TADIGSSVQLECNCFSKPEPRYHWIHNGS----------FLSIPENNMTLPSLSWEQMGSYRCVVEN 302
Cdd:pfam13927  12 TVREGETVTLTCEATGSPPPTITWYKNGEpissgstrsrSLSGSNSTLTISNVTRSDAGTYTCVASN 78

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 58037299    34 ISPDSLLGVEKYRTILT---LENVPEDVLEYSWYRGK-DNSTENMIFSYKPP-NTRHPGPSYSGRENVTRA-GSLVVRMS 107
Cdd:pfam07686   1 QTPREVTVALGGSVTLPctySSSMSEASTSVYWYRQPpGKGPTFLIAYYSNGsEEGVKKGRFSGRGDPSNGdGSLTIQNL 80

                          90
                  ....*....|....*..
gi 58037299   108 AVNDTGYYTVEVDTSNE 124
Cdd:pfam07686  81 TLSDSGTYTCAVIPSGE 97

Immunoglobulin (Ig)-like domain of carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain in carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) and related domains. 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. This family corresponds to the D1 Ig-like domain. Also belonging to this group is the N-terminal immunoglobulin (Ig)-like domain of the signaling lymphocyte activation molecule (SLAM) family, CD84-like family. The SLAM family is a group of immune-cell specific receptors that can regulate both adaptive and innate immune responses. SLAM family proteins are organized as an extracellular domain with having two or four Ig-like domains, a single transmembrane segment, and a cytoplasmic region having Tyr-based motifs. The extracellular domain is organized as a membrane-distal Ig variable (IgV) domain that is responsible for ligand recognition and a membrane-proximal truncated Ig constant-2 (IgC2) domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 58037299  35 SPDSLLGVEKYRTILTLENVPEDVLEYSWYRGKDNSTENMIFSYKP-PNTRHPGPSYSGRENVTRAGSLVVRMSAVNDTG 113
Cdd:cd05741   1 SSEQFYGAEGKNVLLLVPNLQTPLKSVSWYKGKQVSRNDEIAEYENsSDEFRAGSAFSGREYIYTNGSLLIQNITLSDTG 80

                        90       100
                ....*....|....*....|..
gi 58037299 114 YYTVEV-DTSNETQRATGWLQI 134
Cdd:cd05741  81 FYTLEStNIGGKTESATFQLHV 102

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 58037299 247 ADIGSSVQLECNCFSKPEPRYHWIHNGSFLS------IPENNMTLPSLSWEQMGSYRCVVEN 302
Cdd:cd05728  11 ADIGSSLRWECKASGNPRPAYRWLKNGQPLAsenrieVEAGDLRITKLSLSDSGMYQCVAEN 72

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 58037299    243 GVLTADIGSSVQLECNCFSKPEPRYHWIHNG-SFLSIPEN----------NMTLPSLSWEQMGSYRCVVENPETQLTFYR 311
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGgKLLAESGRfsvsrsgstsTLTISNVTPEDSGTYTCAATNSSGSASSGT 81

                   ....
gi 58037299    312 DVTI 315
Cdd:smart00410  82 TLTV 85

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 58037299   246 TADIGSSVQLECNCFSKPEPRYHWIHNGSFLSiPENNMTLPSLSWEQMGSYRCVVENPETQLTfYRDVTIQ 316
Cdd:pfam13895  10 VVTEGEPVTLTCSAPGNPPPSYTWYKDGSAIS-SSPNFFTLSVSAEDSGTYTCVARNGRGGKV-SNPVELT 78

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 58037299 244 VLTADIGSSVQLECNCFSKPEPRYHWIHNGSFLS-------IPENNMTLPSLSWEQMGSYRCVVENP 303
Cdd:cd20957  10 VQTVDFGRTAVFNCSVTGNPIHTVLWMKDGKPLGhssrvqiLSEDVLVIPSVKREDKGMYQCFVRND 76

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 58037299 240 FFAGVLTAdIGSSVQLECNCFSKPEPRYHWIH-NGS-----FLSIPENNMTLPSLSWEQMGSYRCVVEN 302
Cdd:cd04968   7 FPADTYAL-KGQTVTLECFALGNPVPQIKWRKvDGSpssqwEITTSEPVLEIPNVQFEDEGTYECEAEN 74

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 58037299    34 ISPDSLLGVEKYRTILT---LENVPEDVLEYSWYRGK-DNSTENMIFSYKPP-NTRHPGPSYSGRENVTRA-GSLVVRMS 107
Cdd:pfam07686   1 QTPREVTVALGGSVTLPctySSSMSEASTSVYWYRQPpGKGPTFLIAYYSNGsEEGVKKGRFSGRGDPSNGdGSLTIQNL 80

                          90
                  ....*....|....*..
gi 58037299   108 AVNDTGYYTVEVDTSNE 124
Cdd:pfam07686  81 TLSDSGTYTCAVIPSGE 97

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 58037299 246 TADIGSSVQLECNCFSKPEPRYHWIHNGSFLSIPENNMT--------LPSLSWEQMGSYRCVVENPE 304
Cdd:cd20952  10 TVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDERITtlengslqIKGAEKSDTGEYTCVALNLS 76