First immunoglobulin (Ig)-like domain of carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM); The members here are composed of the immunoglobulin (Ig)-like domain 1 in carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) proteins. 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 1060099030  36 VTIEAEPTKVSEGKDVLLLVHNLPQNLTGYIWYKGQMRDLYHYITSYVVDGEIIIYGPAYSGRETAYSNASLLIQNVTRE 115
Cdd:cd05774     1 LTIELVPPQVAEGENVLLLVHNLPENLLAYAWYKGKTVSPNFLIASYIISTNSSTPGPAYSGRETIYPNGSLLIQNVTQK 80

                          90       100
                  ....*....|....*....|...
gi 1060099030 116 DAGSYTLHIIKGDDGTRGVTGRF 138
Cdd:cd05774    81 DTGFYTLQTITADLQTEQASVHL 103

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1060099030 245 YPSFTYYRSGEVLYLSCSADSNPPAQYSWTINEKFQLPGQKLFIRHITTKHSGLYVCSVRNSATGKESSKSMTVEV 320
Cdd:cd20948     1 SPSDTYYLSGENLNLSCHAASNPPAQYSWTINGTFQTSSQELFLPAITENNEGTYTCSAHNSLTGKNISLVLSVTV 76

First immunoglobulin (Ig)-like domain of carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM); The members here are composed of the immunoglobulin (Ig)-like domain 1 in carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) proteins. 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 1060099030  36 VTIEAEPTKVSEGKDVLLLVHNLPQNLTGYIWYKGQMRDLYHYITSYVVDGEIIIYGPAYSGRETAYSNASLLIQNVTRE 115
Cdd:cd05774     1 LTIELVPPQVAEGENVLLLVHNLPENLLAYAWYKGKTVSPNFLIASYIISTNSSTPGPAYSGRETIYPNGSLLIQNVTQK 80

                          90       100
                  ....*....|....*....|...
gi 1060099030 116 DAGSYTLHIIKGDDGTRGVTGRF 138
Cdd:cd05774    81 DTGFYTLQTITADLQTEQASVHL 103

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1060099030 245 YPSFTYYRSGEVLYLSCSADSNPPAQYSWTINEKFQLPGQKLFIRHITTKHSGLYVCSVRNSATGKESSKSMTVEV 320
Cdd:cd20948     1 SPSDTYYLSGENLNLSCHAASNPPAQYSWTINGTFQTSSQELFLPAITENNEGTYTCSAHNSLTGKNISLVLSVTV 76

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 1060099030  38 IEAEPTKVSEGKDVLLLVHNLPQ---NLTGYIWYKGQMRDLYHY-ITSYVVDGEIIIYGPAYSGRE-TAYSNASLLIQNV 112
Cdd:pfam07686   1 QTPREVTVALGGSVTLPCTYSSSmseASTSVYWYRQPPGKGPTFlIAYYSNGSEEGVKKGRFSGRGdPSNGDGSLTIQNL 80

                          90       100
                  ....*....|....*....|....*..
gi 1060099030 113 TREDAGSYTLHIIKGDDGTRGVTGRFT 139
Cdd:pfam07686  81 TLSDSGTYTCAVIPSGEGVFGKGTRLT 107

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1060099030  163 DVLNFTCEPKSENYTYIWWL--NGQSLPVSPR--VKRPIENRILILPSVTRNETGPYQCEIRDRYGGIRSdPVTLNV 235
Cdd:smart00410  10 ESVTLSCEASGSPPPEVTWYkqGGKLLAESGRfsVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASS-GTTLTV 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 1060099030   41 EPTKVSEGKDVLLLVHnLPQNLTGYI-WYKGqmrdlyhyitsyvvDGEIIIYGPAYSGRETaYSNASLLIQNVTREDAGS 119
Cdd:smart00410   2 PSVTVKEGESVTLSCE-ASGSPPPEVtWYKQ--------------GGKLLAESGRFSVSRS-GSTSTLTISNVTPEDSGT 65

                   ..
gi 1060099030  120 YT 121
Cdd:smart00410  66 YT 67

First immunoglobulin (Ig)-like domain of carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM); The members here are composed of the immunoglobulin (Ig)-like domain 1 in carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) proteins. 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 1060099030  36 VTIEAEPTKVSEGKDVLLLVHNLPQNLTGYIWYKGQMRDLYHYITSYVVDGEIIIYGPAYSGRETAYSNASLLIQNVTRE 115
Cdd:cd05774     1 LTIELVPPQVAEGENVLLLVHNLPENLLAYAWYKGKTVSPNFLIASYIISTNSSTPGPAYSGRETIYPNGSLLIQNVTQK 80

                          90       100
                  ....*....|....*....|...
gi 1060099030 116 DAGSYTLHIIKGDDGTRGVTGRF 138
Cdd:cd05774    81 DTGFYTLQTITADLQTEQASVHL 103

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1060099030 245 YPSFTYYRSGEVLYLSCSADSNPPAQYSWTINEKFQLPGQKLFIRHITTKHSGLYVCSVRNSATGKESSKSMTVEV 320
Cdd:cd20948     1 SPSDTYYLSGENLNLSCHAASNPPAQYSWTINGTFQTSSQELFLPAITENNEGTYTCSAHNSLTGKNISLVLSVTV 76

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1060099030 242 PRIYPSFTYYRSGEVLYLSCSADSNPPAQYSWTINEKFQLPGQKLFIRHITTKHSGLYVCSVRNSATGKeSSKSMTVEV 320
Cdd:pfam13895   2 PVLTPSPTVVTEGEPVTLTCSAPGNPPPSYTWYKDGSAISSSPNFFTLSVSAEDSGTYTCVARNGRGGK-VSNPVELTV 79

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 1060099030 259 LSCSADSNPPAQYSWTINEK-----------FQLPGQKLFIRHITTKHSGLYVCSVRNSATGKESS 313
Cdd:cd00096     3 LTCSASGNPPPTITWYKNGKplppssrdsrrSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASA 68

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060099030  246 PSFTYYRSGEVLYLSCSADSNPPAQYSW--------TINEKFQLPGQK----LFIRHITTKHSGLYVCSVRNSatGKESS 313
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWykqggkllAESGRFSVSRSGststLTISNVTPEDSGTYTCAATNS--SGSAS 78

                   ....*..
gi 1060099030  314 KSMTVEV 320
Cdd:smart00410  79 SGTTLTV 85

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1060099030  163 DVLNFTCEPKSENYTYIWWL--NGQSLPVSPR--VKRPIENRILILPSVTRNETGPYQCEIRDRYGGIRSdPVTLNV 235
Cdd:smart00410  10 ESVTLSCEASGSPPPEVTWYkqGGKLLAESGRfsVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASS-GTTLTV 85

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 1060099030 165 LNFTCEPK-SENYTYIWWLNGQSLPVSPRVKRPIE--NRILILPSVTRNETGPYQCEIRDRYGGIRSDPV 231
Cdd:cd00096     1 VTLTCSASgNPPPTITWYKNGKPLPPSSRDSRRSElgNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1060099030 148 KPYITINNLNP--RENKDVlNFTCEPKSEN-YTYIWWLNGQSLPVSPRVKRPIE--NRILILPSVTRNETGPYQCEIR 220
Cdd:pfam13927   1 KPVITVSPSSVtvREGETV-TLTCEATGSPpPTITWYKNGEPISSGSTRSRSLSgsNSTLTISNVTRSDAGTYTCVAS 77

Immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM); The members here are composed of the immunoglobulin (Ig)-like domain of Down Syndrome Cell Adhesion molecule (DSCAM). DSCAM is a cell adhesion molecule expressed largely in the developing nervous system. The gene encoding DSCAM is located at human chromosome 21q22, the locus associated with the intellectual disability phenotype of Down Syndrome. DSCAM is predicted to be the largest member of the IG superfamily. It has been demonstrated that DSCAM can mediate cation-independent homophilic intercellular adhesion.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060099030 254 GEVLYLSCSADSNPPAQYSW-----TINEKFQ-----------LPGQKLFIRHITTKHSGLYVCSVRNSaTGKESSKSMT 317
Cdd:cd05734    16 GKAVVLNCSADGYPPPTIVWkhskgSGVPQFQhivplngriqlLSNGSLLIKHVLEEDSGYYLCKVSND-VGADISKSMY 94

                  ...
gi 1060099030 318 VEV 320
Cdd:cd05734    95 LTV 97

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060099030 144 PKLPKPYITINNlnprenKDVLNFTCE-PKSENYTYIWWLNGQSLPVSPRvkrpienriLILPSVTRNETGPYQCEIRDR 222
Cdd:pfam13895   2 PVLTPSPTVVTE------GEPVTLTCSaPGNPPPSYTWYKDGSAISSSPN---------FFTLSVSAEDSGTYTCVARNG 66

                          90
                  ....*....|...
gi 1060099030 223 YGGIRSDPVTLNV 235
Cdd:pfam13895  67 RGGKVSNPVELTV 79

N-terminal immunoglobulin (Ig)-like domain of the signaling lymphocyte activation molecule (SLAM) family; The members here are composed of the N-terminal immunoglobulin (Ig)-like domain of the signaling lymphocyte activation molecule (SLAM) family and similar proteins. The SLAM family is a group of immune-cell specific receptors that can regulate both adaptive and innate immune responses. Members of this group include proteins such as CD84, SLAM (CD150), Ly-9 (CD229), NTB-A (ly-108, SLAM6), 19A (CRACC), and SLAMF9. The genes coding for the SLAM family are nested on chromosome 1, in humans at 1q23, and in mice at 1H2. The SLAM family is a subset of the CD2 family, which also includes CD2 and CD58 located on chromosome 1 at 1p13 in humans. In mice, CD2 is located on chromosome 3, and there is no CD58 homolog. The SLAM family proteins are organized as an extracellular domain with either 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060099030  87 EIIIYGPAYSGRETAYSNA-SLLIQNVTREDAGSYTLHIIkgddgTRGVTGRFT--FTLH 143
Cdd:cd16842    46 EIIITDKSYKERLNISQNDySLQISNLTMEDAGSYRARIN-----TKNSRVTITkeFTLH 100

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060099030 243 RIYPSFTYYRSGEVLYLSCSADSNPPAQYSWTINEK-----------FQLPGQKLFIRHITTKHSGLYVCSVRNSATGKE 311
Cdd:cd05736     4 RVYPEFQAKEPGVEASLRCHAEGIPLPRVQWLKNGMdinpklskqltLIANGSELHISNVRYEDTGAYTCIAKNEGGVDE 83

                          90
                  ....*....|
gi 1060099030 312 SSKSMTVEVS 321
Cdd:cd05736    84 DISSLFVEDS 93

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 1060099030 254 GEVLYLSCSADSNPPAQYSWTINE------KFQ-LPGQKLFIRHITTKHSGLYVCSVRNSATGKESSKSMTV 318
Cdd:cd05725    12 DDSAEFQCEVGGDPVPTVRWRKEDgelpkgRYEiLDDHSLKIRKVTAGDMGSYTCVAENMVGKIEASATLTV 83

Immunoglobulin (Ig)-like domain found in Leukocyte Ig-like receptors, Natural killer inhibitory receptors (KIRs) and similar domains; member of Immunoglobulin Constant-2 set of IgSF domains; The members here are composed of the first and second immunoglobulin (Ig)-like domains found in Leukocyte Ig-like receptors (LILRs), Natural killer inhibitory receptors (KIRs, also known as also known as cluster of differentiation (CD) 158), and similar proteins. This group includes LILRB1 (also known as LIR-1), LILRA5 (also known as LIR9), an activating natural cytotoxicity receptor NKp46, the immune-type receptor glycoprotein VI (GPVI), and the IgA-specific receptor Fc-alphaRI (also known as cluster of differentiation (CD) 89). LILRs are a family of immunoreceptors expressed on expressed on T and B cells, on monocytes, dendritic cells, and subgroups of natural killer (NK) cells. The human LILR family contains nine proteins (LILRA1-3, and 5, and LILRB1-5). From functional assays, and as the cytoplasmic domains of various LILRs, for example LILRB1, LILRB2 (also known as LIR-2), and LILRB3 (also known as LIR-3) contain immunoreceptor tyrosine-based inhibitory motifs (ITIMs), it is thought that LIR proteins are inhibitory receptors. Of the eight LIR family proteins, only LILRB1, and LILRB2, show detectable binding to class I MHC molecules; ligands for the other members have yet to be determined. The extracellular portions of the different LIR proteins contain different numbers of Ig-like domains for example, four in the case of LILRB1, and LILRB2, and two in the case of LILRB4 (also known as LIR-5). The activating natural cytotoxicity receptor NKp46 is expressed in natural killer cells, and is organized as an extracellular portion having two Ig-like extracellular domains, a transmembrane domain, and a small cytoplasmic portion. GPVI, which also contains two Ig-like domains, participates in the processes of collagen-mediated platelet activation and arterial thrombus formation. Fc-alphaRI is expressed on monocytes, eosinophils, neutrophils, and macrophages; it mediates IgA-induced immune effector responses such as phagocytosis, antibody-dependent cell-mediated cytotoxicity and respiratory burst. Killer cell immunoglobulin-like receptors (KIRs; also known as CD158 for human KIR) are transmembrane glycoproteins expressed by natural killer cells and subsets of T cells. KIRs are a family of highly polymorphic activating and inhibitory receptors that serve as key regulators of human NK cell function. The KIR proteins are classified by the number of extracellular immunoglobulin domains (2D or 3D) and by whether they have a long (L) or short (S) cytoplasmic domain. KIR proteins with the long cytoplasmic domain transduce inhibitory signals upon ligand binding via an immune tyrosine-based inhibitory motif (ITIM), while KIR proteins with the short cytoplasmic domain lack the ITIM motif and instead associate with the TYRO protein tyrosine kinase binding protein to transduce activating signals. The major ligands for KIR are MHC class I (HLA-A, -B or -C) molecules.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1060099030 168 TCEPKSENYTYIWWLNGQSLPVSPRVKRPIENRI-LILPSVTRNETGPYQCeiRDRYGGIR---SDPVTLNV 235
Cdd:cd16843    21 RCQGPPEAVLFQLYKEGNSLSQGTVREKEPQNKAeFYIPHMDRNHAGRYRC--RYRSGTLWsepSDPLELVV 90

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor (R) and similar proteins; member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor (R) and related proteins. The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. The VEGFR family consists of three members: VEGFR-1 (Flt-1), VEGFR-2 (KDR/Flk-1) and VEGFR-3 (Flt-4). VEGF-A interacts with both VEGFR-1 and VEGFR-2. VEGFR-1 binds strongest to VEGF; VEGF-2 binds more weakly. VEGFR-3 appears not to bind VEGF, but binds other members of the VEGF family (VEGF-C and -D). VEGFRs bind VEGFs with high affinity with the IG-like domains. VEGF-A is important to the growth and maintenance of vascular endothelial cells and to the development of new blood- and lymphatic-vessels in physiological and pathological states. VEGFR-2 is a major mediator of the mitogenic, angiogenic, and microvascular permeability-enhancing effects of VEGF-A. VEGFR-1 may play an inhibitory part in these processes by binding VEGF and interfering with its interaction with VEGFR-2. VEGFR-1 has a signaling role in mediating monocyte chemotaxis. VEGFR-1 and VEGFR-2 may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. VEGFR-3 has been shown to be involved in tumor angiogenesis and growth. This group also contains alpha-type platelet-derived growth factor receptor precursor (PDGFR)-alpha (CD140a), and PDGFR-beta (CD140b). PDGFRs alpha and beta have an extracellular component with five Ig-like domains, a transmembrane segment, and a cytoplasmic portion that has protein tyrosine kinase activity.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060099030 249 TYYRSGEVLYLSCSA--DSNPPAQYSWT---------------INEKFQLPGQK---LFIRHITTKHSGLYVCSVRNSAT 308
Cdd:cd05742    12 TVLPQGETLVLNCTAnvNLNEVVDFQWTypsekegklallkpdIKVDWSEPGEFvstLTIPEATLKDSGTYTCAARSGVM 91

                          90
                  ....*....|
gi 1060099030 309 GKESSKSMTV 318
Cdd:cd05742    92 KKEKQTSVSV 101

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060099030 242 PRI--YPSFTYYRSGEVLYLSCSADSNPPAQYSWTIN-------------EKFQLPGQKLFIRHI-----TTKHSGLYVC 301
Cdd:cd07693     1 PRIveHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNgqpletdkddprsHRIVLPSGSLFFLRVvhgrkGRSDEGVYVC 80

                          90       100
                  ....*....|....*....|
gi 1060099030 302 SVRNSaTGKESSKSMTVEVS 321
Cdd:cd07693    81 VAHNS-LGEAVSRNASLEVA 99

Immunoglobulin I-set domain;

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1060099030 254 GEVLYLSCSADSNPPAQYSWTINEKFQLPGQK-----------LFIRHITTKHSGLYVCSVRNSATGKESSKSMTV 318
Cdd:pfam07679  15 GESARFTCTVTGTPDPEVSWFKDGQPLRSSDRfkvtyeggtytLTISNVQPDDSGKYTCVATNSAGEAEASAELTV 90

Fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 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.

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                  ....*....|....*....|....*....|....*....|....*....|
gi 1060099030 180 WWLNGqsLPVS---PRVKRPIENRILILPSVTRNETGPYQCEIRDRYGGI 226
Cdd:cd05867    33 WSING--APIEgtdPDPRRHVSSGALILTDVQPSDTAVYQCEARNRHGNL 80

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

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1060099030   41 EPTKVSEGKDVLLLVHnLPQNLTGYI-WYKGqmrdlyhyitsyvvDGEIIIYGPAYSGRETaYSNASLLIQNVTREDAGS 119
Cdd:smart00410   2 PSVTVKEGESVTLSCE-ASGSPPPEVtWYKQ--------------GGKLLAESGRFSVSRS-GSTSTLTISNVTPEDSGT 65

                   ..
gi 1060099030  120 YT 121
Cdd:smart00410  66 YT 67