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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 217273053    24 QNITARIGEPLVLSCKgAPKKPPQQLEWKLNTGRteawKVLSPQGGPWDSVARilpNGSLLLPATGIVDEGTFRCRATNR 103
Cdd:smart00410   2 PSVTVKEGESVTLSCE-ASGSPPPEVTWYKQGGK----LLAESGRFSVSRSGS---TSTLTISNVTPEDSGTYTCAATNS 73

                           90
                   ....*....|...
gi 217273053   104 RGkEVKSNYRVRV 116
Cdd:smart00410  74 SG-SASSGTTLTV 85

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 217273053    24 QNITARIGEPLVLSCKgAPKKPPQQLEWKLNTGRteawKVLSPQGGPWDSVARilpNGSLLLPATGIVDEGTFRCRATNR 103
Cdd:smart00410   2 PSVTVKEGESVTLSCE-ASGSPPPEVTWYKQGGK----LLAESGRFSVSRSGS---TSTLTISNVTPEDSGTYTCAATNS 73

                           90
                   ....*....|...
gi 217273053   104 RGkEVKSNYRVRV 116
Cdd:smart00410  74 SG-SASSGTTLTV 85

Fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell adhesion molecule 5 (CEACAM5) and similar domains; member of the C2-set IgSF domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell adhesion molecule 5 (CEACAM5) and similar 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. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), also known as CD66e (Cluster of Differentiation 66e), is a cell surface glycoprotein that plays a role in cell adhesion, intracellular signaling and tumor progression. Diseases associated with CEACAM5 include lung cancer and rectum cancer. 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 217273053  22 GGQNITARIGEPLVLSCKGApKKPPQQLEWKLN-TGRTeawkvlSPQggpwdsvarilpngSLLLPATGIVDEGTFRCRA 100
Cdd:cd20948    1 SPSDTYYLSGENLNLSCHAA-SNPPAQYSWTINgTFQT------SSQ--------------ELFLPAITENNEGTYTCSA 59

                         90
                 ....*....|....*..
gi 217273053 101 TNR-RGKEVKSNYRVRV 116
Cdd:cd20948   60 HNSlTGKNISLVLSVTV 76

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 217273053    24 QNITARIGEPLVLSCKgAPKKPPQQLEWKLNTGRteawKVLSPQGGPWDSVARilpNGSLLLPATGIVDEGTFRCRATNR 103
Cdd:smart00410   2 PSVTVKEGESVTLSCE-ASGSPPPEVTWYKQGGK----LLAESGRFSVSRSGS---TSTLTISNVTPEDSGTYTCAATNS 73

                           90
                   ....*....|...
gi 217273053   104 RGkEVKSNYRVRV 116
Cdd:smart00410  74 SG-SASSGTTLTV 85

Fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell adhesion molecule 5 (CEACAM5) and similar domains; member of the C2-set IgSF domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain of the carcinoembryonic antigen (CEA) related cell adhesion molecule 5 (CEACAM5) and similar 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. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), also known as CD66e (Cluster of Differentiation 66e), is a cell surface glycoprotein that plays a role in cell adhesion, intracellular signaling and tumor progression. Diseases associated with CEACAM5 include lung cancer and rectum cancer. 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 217273053  22 GGQNITARIGEPLVLSCKGApKKPPQQLEWKLN-TGRTeawkvlSPQggpwdsvarilpngSLLLPATGIVDEGTFRCRA 100
Cdd:cd20948    1 SPSDTYYLSGENLNLSCHAA-SNPPAQYSWTINgTFQT------SSQ--------------ELFLPAITENNEGTYTCSA 59

                         90
                 ....*....|....*..
gi 217273053 101 TNR-RGKEVKSNYRVRV 116
Cdd:cd20948   60 HNSlTGKNISLVLSVTV 76

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 217273053  34 LVLSCKgAPKKPPQQLEWKLNTGrteawkvlSPQGGPWDSVARILPNGSLLLPATGIVDEGTFRCRATNRRGKEVKSN 111
Cdd:cd00096    1 VTLTCS-ASGNPPPTITWYKNGK--------PLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASAS 69

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 217273053  20 VAGGQNITARIGEPLVLSCKgAPKKPPQQLEWkLNTGRTEAWKvlspqggpwDSVARILPNGSLLLPATGIVDEGTFRCR 99
Cdd:cd20952    3 LQGPQNQTVAVGGTVVLNCQ-ATGEPVPTISW-LKDGVPLLGK---------DERITTLENGSLQIKGAEKSDTGEYTCV 71

                 ....*..
gi 217273053 100 ATNRRGK 106
Cdd:cd20952   72 ALNLSGE 78

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 217273053  31 GEPLVLSCKgAPKKPPQQLEWKLNTGRTEA-WKVLSpqggpWDSVARILPNGSLLLPATGIVDEGTFRCRATN 102
Cdd:cd20954   16 GQDVMLHCQ-ADGFPTPTVTWKKATGSTPGeYKDLL-----YDPNVRILPNGTLVFGHVQKENEGHYLCEAKN 82

Immunoglobulin I-set domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1); The members here are composed of the immunoglobulin I-set (IgI) domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1). Human Lingo-1 is a central nervous system-specific transmembrane glycoprotein also known as LERN-1, which functions as a negative regulator of neuronal survival, axonal regeneration, and oligodendrocyte differentiation and myelination. Lingo-1 is a key component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors. The ligand-binding ectodomain of human Lingo-1 contains a bimodular, kinked structure composed of leucine-rich repeat (LRR) and immunoglobulin (Ig)-like modules. Diseases associated with Lingo-1 include mental retardation, autosomal recessive 64 and essential tremor. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the Lingo-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 217273053  24 QNITARIGEPLVLSCKgAPKKPPQQLEWkLNTGRteawkvlSPQGGPWDSVARILPNGSLLLPATGIVDEGTFRCRATNr 103
Cdd:cd20969   10 QQVFVDEGHTVQFVCR-ADGDPPPAILW-LSPRK-------HLVSAKSNGRLTVFPDGTLEVRYAQVQDNGTYLCIAAN- 79

                         90
                 ....*....|...
gi 217273053 104 RGKEVKSNYRVRV 116
Cdd:cd20969   80 AGGNDSMPAHLHV 92