Immunoglobulin Variable (V) domain of the Coxsackievirus and Adenovirus Receptor (CAR), and similar proteins; The members here are composed of the Variable (V) domain of the Coxsackievirus and Adenovirus Receptor (CAR), and similar proteins. CAR, which is encoded by human CXADR gene, is a cell adhesion molecule of the Immunoglobulin (Ig) superfamily. The CAR acts as a type I membrane receptor for group B1-B6 coxsackie viruses and subgroup C adenoviruses. For instance, adenovirus interacts with the coxsackievirus and adenovirus receptor to enter epithelial airway cells. The CAR is also shown to be involved in physiological processes such as neuronal and heart development, epithelial tight junction integrity, and tumor suppression. The CAR is a component of the epithelial apical junction complex that may function as a homophilic cell adhesion molecule and is essential for tight junction integrity. The CAR is also involved in transepithelial migration of leukocytes through adhesive interactions with JAML a transmembrane protein of the plasma membrane of leukocytes. The interaction between both receptors also mediates the activation of gamma-delta T-cells, a subpopulation of T-cells residing in epithelia and involved in tissue homeostasis and repair. The CAR is composed of one V-set and one C2-set Ig module, a single transmembrane helix, and an intracellular domain. This group belongs to the V-set of IgSF domains, having A, B, E and D strands in one beta-sheet and A', G, F, C, C' and C" in the other

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 23308679  23 LQITStGQTSIEKASGESVKLDCQFTLASDDSGPLDIEWSLQPSDnqKEEKVVIVYSGDRAFEHYYDPLKGRVHFNSPDp 102
Cdd:cd20960   1 LLITS-AQTEIKKVAGENVTLPCHHQLGLEDQGTLDIEWLLLPSD--KVEKVVITYSGDRVYNHYYPALKGRVAFTSND- 76

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 23308679 103 KNGDASMNIMGLKATDTGTYQCKIKKVPGIASRKYLLT 140
Cdd:cd20960  77 LSGDASLNISNLKLSDTGTYQCKVKKAPGYAWSKITLI 114

Immunoglobulin Variable (V) domain of the Coxsackievirus and Adenovirus Receptor (CAR), and similar proteins; The members here are composed of the Variable (V) domain of the Coxsackievirus and Adenovirus Receptor (CAR), and similar proteins. CAR, which is encoded by human CXADR gene, is a cell adhesion molecule of the Immunoglobulin (Ig) superfamily. The CAR acts as a type I membrane receptor for group B1-B6 coxsackie viruses and subgroup C adenoviruses. For instance, adenovirus interacts with the coxsackievirus and adenovirus receptor to enter epithelial airway cells. The CAR is also shown to be involved in physiological processes such as neuronal and heart development, epithelial tight junction integrity, and tumor suppression. The CAR is a component of the epithelial apical junction complex that may function as a homophilic cell adhesion molecule and is essential for tight junction integrity. The CAR is also involved in transepithelial migration of leukocytes through adhesive interactions with JAML a transmembrane protein of the plasma membrane of leukocytes. The interaction between both receptors also mediates the activation of gamma-delta T-cells, a subpopulation of T-cells residing in epithelia and involved in tissue homeostasis and repair. The CAR is composed of one V-set and one C2-set Ig module, a single transmembrane helix, and an intracellular domain. This group belongs to the V-set of IgSF domains, having A, B, E and D strands in one beta-sheet and A', G, F, C, C' and C" in the other

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 23308679  23 LQITStGQTSIEKASGESVKLDCQFTLASDDSGPLDIEWSLQPSDnqKEEKVVIVYSGDRAFEHYYDPLKGRVHFNSPDp 102
Cdd:cd20960   1 LLITS-AQTEIKKVAGENVTLPCHHQLGLEDQGTLDIEWLLLPSD--KVEKVVITYSGDRVYNHYYPALKGRVAFTSND- 76

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 23308679 103 KNGDASMNIMGLKATDTGTYQCKIKKVPGIASRKYLLT 140
Cdd:cd20960  77 LSGDASLNISNLKLSDTGTYQCKVKKAPGYAWSKITLI 114

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 23308679   141 VMVRPSKPKCSAEGQTyvgknMVLKCSsVEGTQPMEYIWerTSGNKLLPPLAIL----DKVTGTMTLKNATGDASGTYRC 216
Cdd:pfam07679   2 KFTQKPKDVEVQEGES-----ARFTCT-VTGTPDPEVSW--FKDGQPLRSSDRFkvtyEGGTYTLTISNVQPDDSGKYTC 73

                          90
                  ....*....|....*..
gi 23308679   217 QAKNRVGTEECVVEVTI 233
Cdd:pfam07679  74 VATNSAGEAEASAELTV 90

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 23308679     40 SVKLDCQFTlaSDDSGPLDIEWSLQPSDNQKEekvVIVYSGDRAfEHYYDP-LKGRVHFnSPDPKNGDASMNIMGLKATD 118
Cdd:smart00406   1 SVTLSCKFS--GSTFSSYYVSWVRQPPGKGLE---WLGYIGSNG-SSYYQEsYKGRFTI-SKDTSKNDVSLTISNLRVED 73

                   ....*...
gi 23308679    119 TGTYQCKI 126
Cdd:smart00406  74 TGTYYCAV 81

Immunoglobulin Variable (V) domain of the Coxsackievirus and Adenovirus Receptor (CAR), and similar proteins; The members here are composed of the Variable (V) domain of the Coxsackievirus and Adenovirus Receptor (CAR), and similar proteins. CAR, which is encoded by human CXADR gene, is a cell adhesion molecule of the Immunoglobulin (Ig) superfamily. The CAR acts as a type I membrane receptor for group B1-B6 coxsackie viruses and subgroup C adenoviruses. For instance, adenovirus interacts with the coxsackievirus and adenovirus receptor to enter epithelial airway cells. The CAR is also shown to be involved in physiological processes such as neuronal and heart development, epithelial tight junction integrity, and tumor suppression. The CAR is a component of the epithelial apical junction complex that may function as a homophilic cell adhesion molecule and is essential for tight junction integrity. The CAR is also involved in transepithelial migration of leukocytes through adhesive interactions with JAML a transmembrane protein of the plasma membrane of leukocytes. The interaction between both receptors also mediates the activation of gamma-delta T-cells, a subpopulation of T-cells residing in epithelia and involved in tissue homeostasis and repair. The CAR is composed of one V-set and one C2-set Ig module, a single transmembrane helix, and an intracellular domain. This group belongs to the V-set of IgSF domains, having A, B, E and D strands in one beta-sheet and A', G, F, C, C' and C" in the other

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 23308679  23 LQITStGQTSIEKASGESVKLDCQFTLASDDSGPLDIEWSLQPSDnqKEEKVVIVYSGDRAFEHYYDPLKGRVHFNSPDp 102
Cdd:cd20960   1 LLITS-AQTEIKKVAGENVTLPCHHQLGLEDQGTLDIEWLLLPSD--KVEKVVITYSGDRVYNHYYPALKGRVAFTSND- 76

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 23308679 103 KNGDASMNIMGLKATDTGTYQCKIKKVPGIASRKYLLT 140
Cdd:cd20960  77 LSGDASLNISNLKLSDTGTYQCKVKKAPGYAWSKITLI 114

Immunoglobulin (Ig)-like domain of protein zero (P0) and similar proteins; The members here are composed of the immunoglobulin (Ig) domain of protein zero (P0), a myelin membrane adhesion molecule. P0 accounts for over 50% of the total protein in peripheral nervous system (PNS) myelin. P0 is a single-pass transmembrane glycoprotein with a highly basic intracellular domain and an extracellular Ig domain. The extracellular domain of P0 (P0-ED) is similar to the Ig variable domain, carrying one acceptor sequence for N-linked glycosylation. P0 plays a role in membrane adhesion in the spiral wraps of the myelin sheath. The intracellular domain is thought to mediate membrane apposition of the cytoplasmic faces and may, through electrostatic interactions, interact directly with lipid headgroups. It is thought that homophilic interactions of the P0 extracellular domain mediate membrane juxtaposition in the extracellular space of PNS myelin. This group also contains the Ig domain of sodium channel subunit beta-2 (SCN2B), and of epithelial V-like antigen 1 (EVA). EVA, also known as myelin protein zero-like 2, is an adhesion molecule, which may play a role in structural organization of the thymus and early lymphocyte development. SCN2B subunits play a role in determining sodium channel density and function in neurons,and in control of electrical excitability in the brain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 23308679  33 IEKASGESVKLDCQFTLASDDSGPLDIEWSLQPSDNQKEEKVVIVYSGDrAFEHYYDPLKGRVHFnSPDPKNGDASMNIM 112
Cdd:cd05715   9 LNVLNGSDVRLTCTFTSCYTVGDAFSVTWTYQPEGGNTTESMFHYSKGK-PYILKVGRFKDRVSW-AGNPSKKDASIVIS 86

                        90       100
                ....*....|....*....|
gi 23308679 113 GLKATDTGTYQCKIKKVPGI 132
Cdd:cd05715  87 NLQFSDNGTYTCDVKNPPDI 106

Immunoglobulin (Ig)-like domain of human cartilage link protein (LP), and similar domains; The members here are composed of the immunoglobulin (Ig)-like domain similar to that found in human cartilage link protein (LP; also called hyaluronan and proteoglycan link protein). In cartilage, chondroitin-keratan sulfate proteoglycan (CSPG), aggrecan, forms cartilage link protein stabilized aggregates with hyaluronan (HA). These aggregates contribute to the tissue's load bearing properties. Aggregates having other CSPGs substituting for aggrecan may contribute to the structural integrity of many different tissues. Members of the vertebrate HPLN (hyaluronan/HA and proteoglycan binding link) protein family are physically linked adjacent to CSPG genes.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 23308679  27 STGQTSIEKASGESVKLDCQFTLASDDSGP--LDIEWSLQPSDNQKEEkVVIVYSGDR--AFEHYydplKGRVHFNSPDP 102
Cdd:cd05877   1 ETVQAKVFSHRGGNVTLPCRYHYEPELSAPrkIRVKWTKLEVDYAKEE-DVLVAIGTRhkSYGSY----QGRVFLRRADD 75

                        90       100
                ....*....|....*....|....
gi 23308679 103 knGDASMNIMGLKATDTGTYQCKI 126
Cdd:cd05877  76 --LDASLVITDLRLEDYGRYRCEV 97

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 23308679    158 VGKNMVLKCSsVEGTQPMEYIWERTSGNKLLPPLAIL---DKVTGTMTLKNATGDASGTYRCQAKNRVGTEECVVEVTI 233
Cdd:smart00410   8 EGESVTLSCE-ASGSPPPEVTWYKQGGKLLAESGRFSvsrSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGTTLTV 85

Immunoglobulin (Ig)-like domain of protein zero (P0); The members here are composed of the immunoglobulin (Ig) domain of protein zero (P0), a myelin membrane adhesion molecule. P0 accounts for over 50% of the total protein in peripheral nervous system (PNS) myelin. P0 is a single-pass transmembrane glycoprotein with a highly basic intracellular domain and an Ig domain. The extracellular domain of P0 (P0-ED) is similar to the Ig variable domain, carrying one acceptor sequence for N-linked glycosylation. P0 plays a role in membrane adhesion in the spiral wraps of the myelin sheath. The intracellular domain is thought to mediate membrane apposition of the cytoplasmic faces and may, through electrostatic interactions, interact directly with lipid headgroups. It is thought that homophilic interactions of the P0 extracellular domain mediate membrane juxtaposition in the extracellular space of PNS myelin.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 23308679  36 ASGESVKLDCQFTLASDDSGPLDIEWSLQPsDNQKEEKVVIVYSGDRAFEHYYDPLKGRVHFNSpDPKNGDASMNIMGLK 115
Cdd:cd05879  12 TVGSDVTLSCSFWSSEWISDDISFTWHYQP-DGSRDAISIFHYGKGQPYIDNVGPFKERIEWVG-NPSRKDGSIVIHNLD 89

                        90       100
                ....*....|....*....|....*...
gi 23308679 116 ATDTGTYQCKIKKVPGIASRKYLLTVMV 143
Cdd:cd05879  90 YTDNGTFTCDVKNPPDIVGKSSQVTLYV 117

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 23308679 159 GKNMVLKCSsVEGTQPMEYIWERtSGNKLLPPLA--ILDKVTGTMTLKNATGDASGTYRCQAKNRVGTEECVVEVTI 233
Cdd:cd20976  16 GQDFVAQCS-ARGKPVPRITWIR-NAQPLQYAADrsTCEAGVGELHIQDVLPEDHGTYTCLAKNAAGQVSCSAWVTV 90

Immunoglobulin (Ig)-like domain of chondroitin sulfate proteoglycans (CSPGs), human cartilage link protein (LP), and similar domains; The members here are composed of the immunoglobulin (Ig)-like domain similar to that found in chondroitin sulfate proteoglycans (CSPGs) and human cartilage link protein (LP). Included in this group are the CSPGs aggrecan, versican, and neurocan. In CSPGs, this Ig-like domain is followed by hyaluronan (HA)-binding tandem repeats, and a C-terminal region with epidermal growth factor-like, lectin-like, and complement regulatory protein-like domains. Separating these N- and C-terminal regions is a nonhomologous glycosaminoglycan attachment region. In cartilage, aggrecan forms cartilage link protein stabilized aggregates with hyaluronan (HA). These aggregates contribute to the tissue's load bearing properties. Aggrecan and versican have a wide distribution in connective tissue and extracellular matrices. Neurocan is localized almost exclusively in nervous tissue. Aggregates having other CSPGs substituting for aggrecan may contribute to the structural integrity of many different tissues. There is considerable evidence that HA-binding CSPGs are involved in developmental processes in the central nervous system. Members of the vertebrate HPLN (hyaluronan/HA and proteoglycan binding link) protein family are physically linked adjacent to CSPG genes.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 23308679  29 GQTSIEKASGESVKLDCQF----TLASDDSGPLDIEWSLQPSDNQKEEKVVIVYSGDRAFEHYYDpLKGRVHFNSPDPKN 104
Cdd:cd05714   3 ESAKVFSHLGGNVTLPCKFyrdpTAFGSGIHKIRIKWTKLTSDSGYLKEVDVLVAMGNVVYHKKT-YGGRVSVPLKPGSD 81

                        90       100
                ....*....|....*....|..
gi 23308679 105 GDASMNIMGLKATDTGTYQCKI 126
Cdd:cd05714  82 SDASLVITDLTASDYGLYRCEV 103

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 23308679 163 VLKCSsVEGTQPMEYIWERtsGNKLLPPLAILDK----VTGTMTLKNATGDASGTYRCQAKNRVGTEE 226
Cdd:cd00096   2 TLTCS-ASGNPPPTITWYK--NGKPLPPSSRDSRrselGNGTLTISNVTLEDSGTYTCVASNSAGGSA 66

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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 23308679  33 IEKASGESVKLDCQFTLASDDSGPLDIEWslqpsdnQKEEKVVI-VYSGDRAFEHYYdplKGRVHFNSPDpkngDASMNI 111
Cdd:cd16086   4 VTKSVKEKALLSCDYNVSVDELAQVRIYW-------QKDDKMVLtIISGDVKVWPEY---KNRTLFDITN----NLSIVI 69

                        90       100       110
                ....*....|....*....|....*....|..
gi 23308679 112 MGLKATDTGTYQCKI-KKVPGIASRKYLLTVM 142
Cdd:cd16086  70 LALRLSDRGTYTCVVqKKERGAYKREHLASVT 101

Immunoglobulin (Ig)-like domain of the chondroitin sulfate proteoglycan core protein (CSPG), versican; The members here are composed of the immunoglobulin (Ig)-like domain of the chondroitin sulfate proteoglycan core protein (CSPG), versican. In CSPGs, the Ig-like domain is followed by hyaluronan (HA)-binding tandem repeats, and a C-terminal region with epidermal growth factor-like, lectin-like, and complement regulatory protein-like domains. Separating these N- and C-terminal regions is a nonhomologous glycosaminoglycan attachment region. In cartilage, the CSPG aggrecan (not included in this group) forms cartilage link protein stabilized aggregates with HA. These aggregates contribute to the tissue's load bearing properties. Like aggrecan, versican has a wide distribution in connective tissue and extracellular matrices. Aggregates having other CSPGs substituting for aggrecan may contribute to the structural integrity of many different tissues. Members of the vertebrate HPLN (hyaluronan/HA and proteoglycan binding link) protein family are physically linked adjacent to CSPG genes.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 23308679  40 SVKLDCQFTL-------ASDDSGPLDIEWS-LQPSDNQKEEK---VVIVYSGDRAFEHYYdplKGRVHFNSPDPKNGDAS 108
Cdd:cd05901  14 SVVLPCRFSTlptlppsYNITSEFLRIKWTkIQVDKNGKDHKettVLVAQNGIIKIGQEY---MGRVSVPSHPEDQGDAS 90

                        90
                ....*....|....*...
gi 23308679 109 MNIMGLKATDTGTYQCKI 126
Cdd:cd05901  91 LTIVKLRASDAGVYRCEV 108

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 23308679   147 KPKCSAEGQTY-VGKNMVLKCSSVeGTQPMEYIWERtsGNKLLPPlaildkvTGTMTLKNATGDASGTYRCQAKNRVGTE 225
Cdd:pfam13895   1 KPVLTPSPTVVtEGEPVTLTCSAP-GNPPPSYTWYK--DGSAISS-------SPNFFTLSVSAEDSGTYTCVARNGRGGK 70

                  ....*....
gi 23308679   226 -ECVVEVTI 233
Cdd:pfam13895  71 vSNPVELTV 79

First immunoglobulin (Ig)-like domain of neural cell adhesion molecule (NCAM-1); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of neural cell adhesion molecule (NCAM-1). NCAM-1 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-nonNCAM), 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 the Ig1, Ig2, and Ig3 domains. 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. 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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 23308679 139 LTVMVRPSkpkcsaEGQTYVGKNMVLKCSSVEGTQPMEYIWERTSGNKLLPP---LAIL--DKVTGTMTLKNATGDASGT 213
Cdd:cd05865   1 LQVDIVPS------QGEISVGESKFFLCQVAGEAKDKDISWFSPNGEKLTPNqqrISVVrnDDYSSTLTIYNANIDDAGI 74

                        90       100
                ....*....|....*....|...
gi 23308679 214 YRCQAKNRVGTE-ECVVEVTITQ 235
Cdd:cd05865  75 YKCVVSNEDEGEsEATVNVKIFQ 97

Second Ig-like domain of Junctional adhesion molecule-1 (JAM1); a member of the I-set of IgSF domains; The members here are composed of the second Ig-like domain of Junctional adhesion molecule-1 (JAM1). JAM1 is an immunoglobulin superfamily (IgSF) protein with two Ig-like domains in its extracellular region; it plays a role in the formation of endothelial and epithelial tight junction and acts as a receptor for mammalian reovirus sigma-1. The IgSF is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. 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 second Ig-like domain of JAM1 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, the A strand of the I-set is discontinuous but lacks 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 23308679 148 PKCSAEGQTYVGKNMVLKCSSVEGTQPMEYIWERTSgnKLLP--PLAI---------LDKVTGTMTLKNATGDASGTYRC 216
Cdd:cd20950   1 PTVNIPSSATIGNRAVLTCSEPDGSPPSEYTWFKDG--VVMPtnPKSTrafsnssysLDPTTGELVFDPLSASDTGEYSC 78

                ....*...
gi 23308679 217 QAKNRVGT 224
Cdd:cd20950  79 EARNGYGT 86

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 23308679 158 VGKNMVLKCSsVEGTQPMEYIWERTSGNKLLPPLAILDKvtGTMTLKNATGDASGTYRCQAKNRVGTEE 226
Cdd:cd05725  11 VDDSAEFQCE-VGGDPVPTVRWRKEDGELPKGRYEILDD--HSLKIRKVTAGDMGSYTCVAENMVGKIE 76

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 23308679 159 GKNMVLKCSsVEGTQPMEYIWE--RTSGNKLLPPLAILDK-----VTGTMTLKNATGDASGTYRCQAKNRVGTE 225
Cdd:cd05734  16 GKAVVLNCS-ADGYPPPTIVWKhsKGSGVPQFQHIVPLNGriqllSNGSLLIKHVLEEDSGYYLCKVSNDVGAD 88

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 23308679  32 SIEKASGESVKLDCQftlASDDSGPLDIEWSLQPSDNQKEEkvviVYSGDRAFEHYYDPLKGRVHFNSPDPKngDASMNI 111
Cdd:cd00099   7 SLSVQEGESVTLSCE---VSSSFSSTYIYWYRQKPGQGPEF----LIYLSSSKGKTKGGVPGRFSGSRDGTS--SFSLTI 77

                        90
                ....*....|...
gi 23308679 112 MGLKATDTGTYQC 124
Cdd:cd00099  78 SNLQPEDSGTYYC 90

First immunoglobulin (Ig) domain of nectin-4, and similar domains; The members here are composed of the first immunoglobulin (Ig) domain of nectin-4 (also known as poliovirus receptor related protein 4 or LNIR receptor). Nectin-4 belongs to the nectin family, which is comprised of four transmembrane glycoproteins (nectins-1 through -4). Nectins are synaptic cell adhesion molecules (CAMs) which participate in adhesion and signaling at various intracellular junctions. Nectins form homophilic cis-dimers, followed by homophilic and heterophilic trans-dimers involved in cell-cell adhesion. For example nectin-4 trans-interacts with nectin-1. Nectin-4 has also been shown to interact with the actin filament-binding protein, afadin. Unlike the other nectins, which are widely expressed in adult tissues, nectin-4 is mainly expressed during embryogenesis, and is not detected in normal adult tissue or in serum. Nectin-4 is re-expressed in breast carcinoma, and patients having metastatic breast cancer have a circulating form of nectin-4 formed from the ectodomain

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 23308679  36 ASGESVKLDCQFTlASDDSGPLDIEWsLQPSDNQKEEKVVIVYS--GDRAFEHYydplKGRVHFNSPDPKnGDASMNIMG 113
Cdd:cd05888   6 VLGQDAKLPCFYR-GDSGEQVGQVAW-ARVDAGEGAQEIALLHSkyGLHVFPAY----EGRVEQPPPPRP-ADGSVLLRN 78

                        90
                ....*....|....*..
gi 23308679 114 LKATDTGTYQCKIKKVP 130
Cdd:cd05888  79 AVQADEGEYECRVSTFP 95

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 23308679 159 GKNMVLKCSSvEGTQPMEYIWERTSGNkLLPPLAILDKVTGTMTLKNATGDASGTYRCQAKNRVGTEECVVEVTI 233
Cdd:cd05731  10 GGVLLLECIA-EGLPTPDIRWIKLGGE-LPKGRTKFENFNKTLKIENVSEADSGEYQCTASNTMGSARHTISVTV 82

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 23308679 158 VGKNMVLKCSSvEGTQPMEYIWE-----RTSGNKLLpplaildkvtgtmtLKNATGDASGTYRCQAKNRVGTEE 226
Cdd:cd20948   9 SGENLNLSCHA-ASNPPAQYSWTingtfQTSSQELF--------------LPAITENNEGTYTCSAHNSLTGKN 67