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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6806905      30 PRLTIASEGDSVNITCSTRGHlegilmkkiwPQAYNVIYFEDRQEPTvdrtFSGRINFSGSQKNLTITISSLQLADTGDY 109
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGS----------PPPEVTWYKQGGKLLA----ESGRFSVSRSGSTSTLTISNVTPEDSGTY 66

                   ....
gi 6806905     110 TCEA 113
Cdd:smart00410  67 TCAA 70

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6806905      30 PRLTIASEGDSVNITCSTRGHlegilmkkiwPQAYNVIYFEDRQEPTvdrtFSGRINFSGSQKNLTITISSLQLADTGDY 109
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGS----------PPPEVTWYKQGGKLLA----ESGRFSVSRSGSTSTLTISNVTPEDSGTY 66

                   ....
gi 6806905     110 TCEA 113
Cdd:smart00410  67 TCAA 70

Immunoglobulin variable domain (IgV); The members here are composed of the immunoglobulin variable domain (IgV). The IgV family contains the standard Ig superfamily V-set AGFCC'C"/DEB domain topology, and are components of immunoglobulin (Ig) and T cell receptors. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. In Ig, each chain is composed of one variable domain (IgV) and one or more constant domains (IgC); these names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. Within the variable domain, there are regions of even more variability called the hypervariable or complementarity-determining regions (CDRs) which are responsible for antigen binding. A predominant feature of most Ig domains is the disulfide bridge connecting 2 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" strands in the other.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6806905   26 VHQSPRLTIASEGDSVNITCSTRGHLEGILMkkIW-----PQAYNVIYFEDRQEPTVDRTFSGRINFSGSQKNL-TITIS 99
Cdd:cd00099   1 VTQSPRSLSVQEGESVTLSCEVSSSFSSTYI--YWyrqkpGQGPEFLIYLSSSKGKTKGGVPGRFSGSRDGTSSfSLTIS 78

                        90
                ....*....|....*..
gi 6806905  100 SLQLADTGDYTCEAVRK 116
Cdd:cd00099  79 NLQPEDSGTYYCAVSES 95

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6806905      30 PRLTIASEGDSVNITCSTRGHlegilmkkiwPQAYNVIYFEDRQEPTvdrtFSGRINFSGSQKNLTITISSLQLADTGDY 109
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGS----------PPPEVTWYKQGGKLLA----ESGRFSVSRSGSTSTLTISNVTPEDSGTY 66

                   ....
gi 6806905     110 TCEA 113
Cdd:smart00410  67 TCAA 70

Immunoglobulin variable domain (IgV); The members here are composed of the immunoglobulin variable domain (IgV). The IgV family contains the standard Ig superfamily V-set AGFCC'C"/DEB domain topology, and are components of immunoglobulin (Ig) and T cell receptors. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. In Ig, each chain is composed of one variable domain (IgV) and one or more constant domains (IgC); these names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. Within the variable domain, there are regions of even more variability called the hypervariable or complementarity-determining regions (CDRs) which are responsible for antigen binding. A predominant feature of most Ig domains is the disulfide bridge connecting 2 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" strands in the other.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6806905   26 VHQSPRLTIASEGDSVNITCSTRGHLEGILMkkIW-----PQAYNVIYFEDRQEPTVDRTFSGRINFSGSQKNL-TITIS 99
Cdd:cd00099   1 VTQSPRSLSVQEGESVTLSCEVSSSFSSTYI--YWyrqkpGQGPEFLIYLSSSKGKTKGGVPGRFSGSRDGTSSfSLTIS 78

                        90
                ....*....|....*..
gi 6806905  100 SLQLADTGDYTCEAVRK 116
Cdd:cd00099  79 NLQPEDSGTYYCAVSES 95

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6806905     28 QSPRLTIASEGDSVNITCSTRGHLEgilmkkiwPQaynVIYFEDRQEPTVDRtfsgRINFSGSQKNLTITISSLQLADTG 107
Cdd:pfam07679   5 QKPKDVEVQEGESARFTCTVTGTPD--------PE---VSWFKDGQPLRSSD----RFKVTYEGGTYTLTISNVQPDDSG 69

                  ....*..
gi 6806905    108 DYTCEAV 114
Cdd:pfam07679  70 KYTCVAT 76

Immunoglobulin V-Type;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 6806905      66 VIYFEDRQEPTVDRTFSGRINFSG--SQKNLTITISSLQLADTGDYTCE 112
Cdd:smart00406  32 LGYIGSNGSSYYQESYKGRFTISKdtSKNDVSLTISNLRVEDTGTYYCA 80

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6806905   35 ASEGDSVNITCSTRGH-LEGIlmkkIWPQAYNVIYFEDRqeptvdrTFSGRINFSGSQKNLTITISSLQLADTGDYTCEA 113
Cdd:cd05732  13 AVELEQITLTCEAEGDpIPEI----TWRRATRGISFEEG-------DLDGRIVVRGHARVSSLTLKDVQLTDAGRYDCEA 81

First (N-terminal) immunoglobulin (Ig)-like domain of nectin-like molecule-1 (Necl-1); 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-1, Necl-1 (also known as celll adhesion molecule 3 (CADM3), SynCAM2, or IGSF4). 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-1 has 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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 6806905   38 GDSVNITCSTRGHLEGILMkkiWPQ-AYNVIYFEDRQEPTvdrtfSGRINFSGSQKN-LTITISSLQLADTGDYTC 111
Cdd:cd05882  12 GGTVTLKCGVKEHDNSSLQ---WSNtAQQTLYFGEKRALR-----DNRIQLVKSTPTeLIISISNVQLSDEGEYTC 79

First immunoglobulin variable (IgV) domain of poliovirus receptor (PVR, also known as CD155 and necl-5), and similar domains; The members here are composed of the first immunoglobulin (Ig) domain of poliovirus receptor (PVR, also known as CD155 and nectin-like protein 5 (necl-5)). Poliovirus (PV) binds to its cellular receptor (PVR/CD155) to initiate infection. CD155 is a membrane-anchored, single-span glycoprotein; its extracellular region has three Ig-like domains. There are four different isotypes of CD155 (referred to as alpha, beta, gamma, and delta), that result from alternate splicing of the CD155 mRNA, and have identical extracellular domains. CD155-beta and CD155-gamma are secreted; CD155-alpha and CD155-delta are membrane-bound and function as PV receptors. The virus recognition site is contained in the amino-terminal domain, D1. Having the virus attachment site on the receptor distal from the plasma membrane may be important for successful initiation of infection of cells by the virus. CD155 binds in the poliovirus "canyon" with a footprint similar to that of the intercellular adhesion molecule-1 receptor on human rhinoviruses. This group also includes the first Ig-like domain of nectin-1 (also known as poliovirus receptor related protein(PVRL)1; CD111), nectin-3 (also known as PVRL 3), nectin-4 (also known as PVRL4; LNIR receptor)and DNAX accessory molecule 1 (DNAM-1; CD226).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6806905   38 GDSVNITCSTRGHLEGIL-----MKKIWPQAYNVIYFEDRQEPTVDRTFSGRINFSGSQ---KNLTITISSLQLADTGDY 109
Cdd:cd05718  14 GGSVTLPCSLTSPGTTKItqvtwMKIGAGSSQNVAVFHPQYGPSVPNPYAERVEFLAARlglRNATLRIRNLRVEDEGNY 93

                ....*
gi 6806905  110 TCEAV 114
Cdd:cd05718  94 ICEFA 98

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6806905   33 TIASEGDSVNITCSTRGHL-EGILMKKIWPQAYNVIYFEDRQEPTVDRTFSGRINfsgsqknLTITISSLQLADTGDYTC 111
Cdd:cd05742  12 TVLPQGETLVLNCTANVNLnEVVDFQWTYPSEKEGKLALLKPDIKVDWSEPGEFV-------STLTIPEATLKDSGTYTC 84

                        90
                ....*....|....*..
gi 6806905  112 EAVRKVSARGLFTTVVV 128
Cdd:cd05742  85 AARSGVMKKEKQTSVSV 101

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 6806905   41 VNITCSTRGhlegilmkkiwPQAYNVIYFEDRQEPTVDRTFSGRINFSGSqknlTITISSLQLADTGDYTCEA 113
Cdd:cd00096   1 VTLTCSASG-----------NPPPTITWYKNGKPLPPSSRDSRRSELGNG----TLTISNVTLEDSGTYTCVA 58

Immunoglobulin (Ig)-like domain in neuregulins; The members here are composed of the immunoglobulin (Ig)-like domain in neuregulins (NRGs). NRGs are signaling molecules which participate in cell-cell interactions in the nervous system, breast, heart, and other organ systems, and are implicated in the pathology of diseases including schizophrenia, multiple sclerosis, and breast cancer. There are four members of the neuregulin gene family (NRG-1, NRG-2, NRG-3, and NRG-4). The NRG-1 protein, binds to and activates the tyrosine kinases receptors ErbB3 and ErbB4, initiating signaling cascades. The other NRGs proteins bind one or the other or both of these ErbBs. NRG-1 has multiple functions: in the brain it regulates various processes such as radial glia formation and neuronal migration, dendritic development, and expression of neurotransmitters receptors, while in the peripheral nervous system NRG-1 regulates processes such as target cell differentiation, and Schwann cell survival. There are many NRG-1 isoforms which arise from the alternative splicing of mRNA. Less is known of the functions of the other NRGs. NRG-2 and NRG-3 are expressed predominantly in the nervous system. NRG-2 is expressed by motor neurons and terminal Schwann cells, and is concentrated near synaptic sites and may be a signal that regulates synaptic differentiation. NRG-4 has been shown to direct pancreatic islet cell development towards the delta-cell lineage.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 6806905   68 YFEDRQEptVDRTFSGRINFSGSQKNLTITISSLQLADTGDYTCEAVRKV 117
Cdd:cd05750  34 WFKDGKE--LNRKRPKNIKIRNKKKNSELQINKAKLEDSGEYTCVVENIL 81

Immunoglobulin variable domain (IgV) in Cluster of Differentiation (CD) 80; The members here are composed of the immunoglobulin variable region (IgV) in the Cluster of Differentiation (CD) 80). Glycoproteins B7-1 (also known as cluster of differentiation (CD) 80) and B7-2 (also known as CD86) are expressed on antigen-presenting cells and deliver the co-stimulatory signal through CD28 and CTLA-4 (also known as cluster of differentiation 152/CD152) on T cells. signaling through CD28 augments the T-cell response, whereas CTLA-4 signaling attenuates it. CD80 contains two Ig-like domains, an amino-terminal immunoglobulin variable (IgV)-like domain characteristic of adhesion molecules and a membrane proximal immunoglobulin constant (IgC)-like domain similar to the constant domains of antigen receptors. Members of the Ig family are components of immunoglobulin, T-cell receptors, CD1 cell surface glycoproteins, secretory glycoproteins A/C, and Major Histocompatibility Complex (MHC) class I/II molecules. In immunoglobulins, each chain is composed of one variable domain (IgV) and one or more IgC domains. These names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. The IgV domain is responsible for antigen binding, and the IgC domain is involved in oligomerization and molecular interactions.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 6806905   56 MKKIWPQAYNviyfedrqeptvdRTFSGRINfsgsqkNLTITISSLQLADTGDYTCeAVRKvSARGLF 123
Cdd:cd16086  46 DVKVWPEYKN-------------RTLFDITN------NLSIVILALRLSDRGTYTC-VVQK-KERGAY 92