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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 292615891  38 DLWSLAEG-ETRLPCRFNVSDSEiTVVQVLWIRENNG-VEEQILTAHFKEGQTEFHSsYSGRVRFETNNPIADSALIIMR 115
Cdd:cd05888    1 DVVTVVLGqDAKLPCFYRGDSGE-QVGQVAWARVDAGeGAQEIALLHSKYGLHVFPA-YEGRVEQPPPPRPADGSVLLRN 78

                         90       100       110
                 ....*....|....*....|....*....|
gi 292615891 116 TLSADEGKYKCKIITFPSGNFEAEIVLTVW 145
Cdd:cd05888   79 AVQADEGEYECRVSTFPAGNFQAELRLRVL 108

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 292615891 157 LIEGQSFRPAASCRA-MAKPVAGLSWDTELPGQSQNQSSDESVSS---IKFSLHPYRSMNGQKLDCLVWHPSQKGPERIS 232
Cdd:cd07704   12 LIDGGNETLAASCTAeTGKPAASVTWETDLGGMESSRTFEHNRTAtvtSEYHLVPTRFANGRPLTCVVSHPALQQDIRIT 91

                 ....*
gi 292615891 233 NKLIV 237
Cdd:cd07704   92 HILDV 96

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 292615891  38 DLWSLAEG-ETRLPCRFNVSDSEiTVVQVLWIRENNG-VEEQILTAHFKEGQTEFHSsYSGRVRFETNNPIADSALIIMR 115
Cdd:cd05888    1 DVVTVVLGqDAKLPCFYRGDSGE-QVGQVAWARVDAGeGAQEIALLHSKYGLHVFPA-YEGRVEQPPPPRPADGSVLLRN 78

                         90       100       110
                 ....*....|....*....|....*....|
gi 292615891 116 TLSADEGKYKCKIITFPSGNFEAEIVLTVW 145
Cdd:cd05888   79 AVQADEGEYECRVSTFPAGNFQAELRLRVL 108

Second immunoglobulin (Ig) domain of nectin-3 and nectin-4 (poliovirus receptor related protein 4), and similar domains; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig) domain of nectin-3 (also known as poliovirus receptor related protein 3 or cluster of differentiation (CD) 113) and nectin-4 (poliovirus receptor related protein 4). Nectin-3 and nectin-4 belong to the nectin family comprised of four transmembrane glycoproteins (nectin-1 through -4). Nectins are synaptic cell adhesion molecules (CAMs) which facilitate adhesion and signaling at various intracellular junctions. Nectins form homophilic cis-dimers, followed by homophilic and heterophilic trans-dimers involved in cell-cell adhesion. Nectin-2 and nectin-3 localize at Sertoli-spermatid junctions where they form heterophilic trans-interactions between the cells that are essential for the formation and maintenance of the junctions and for spermatid development. Nectin-3 has also been shown to form a heterophilic trans-interaction with nectin-1 in ciliary epithelia, establishing the apex-apex adhesion between the pigment and non-pigment cell layers. Nectin-4 has recently been identified in several types of breast carcinoma and can be used as a histological and serological marker for breast cancer.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 292615891 157 LIEGQSFRPAASCRA-MAKPVAGLSWDTELPGQSQNQSSDESVSS---IKFSLHPYRSMNGQKLDCLVWHPSQKGPERIS 232
Cdd:cd07704   12 LIDGGNETLAASCTAeTGKPAASVTWETDLGGMESSRTFEHNRTAtvtSEYHLVPTRFANGRPLTCVVSHPALQQDIRIT 91

                 ....*
gi 292615891 233 NKLIV 237
Cdd:cd07704   92 HILDV 96

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 292615891  257 QGATLQCSGEGNPKPHlFNWTRKDGALPEGVIV-----DGGTLLFSRPLRLADKGHYICTTTNLVGSGKTEIEVKI 327
Cdd:pfam07679  16 ESARFTCTVTGTPDPE-VSWFKDGQPLRSSDRFkvtyeGGTYTLTISNVQPDDSGKYTCVATNSAGEAEASAELTV 90

CD80-like C2-set immunoglobulin domain; These domains belong to the immunoglobulin superfamily.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 292615891  156 TLIEGQSFRPAASCR-AMAKPVAGLSWDTELPG-----QSQNQSSDESVSSIK--FSLHPYRSMNGQKLDCLVWHPSQKG 227
Cdd:pfam08205   8 SLLEGEGPEVVATCSsAGGKPAPRITWYLDGKPleaaeTSSEQDPESGLVTVTseLKLVPSRSDHGQSLTCQVSYGALRG 87

                  .
gi 292615891  228 P 228
Cdd:pfam08205  88 S 88

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 292615891  38 DLWSLAEG-ETRLPCRFNVSDSEiTVVQVLWIRENNG-VEEQILTAHFKEGQTEFHSsYSGRVRFETNNPIADSALIIMR 115
Cdd:cd05888    1 DVVTVVLGqDAKLPCFYRGDSGE-QVGQVAWARVDAGeGAQEIALLHSKYGLHVFPA-YEGRVEQPPPPRPADGSVLLRN 78

                         90       100       110
                 ....*....|....*....|....*....|
gi 292615891 116 TLSADEGKYKCKIITFPSGNFEAEIVLTVW 145
Cdd:cd05888   79 AVQADEGEYECRVSTFPAGNFQAELRLRVL 108

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 292615891  45 GETRLPCRFNVSDSEiTVVQVLWIRENNGVEEQILTAHFKEGQTeFHSSYSGRVRFETNNPIADSALIIMRTLS-ADEGK 123
Cdd:cd05718   15 GSVTLPCSLTSPGTT-KITQVTWMKIGAGSSQNVAVFHPQYGPS-VPNPYAERVEFLAARLGLRNATLRIRNLRvEDEGN 92

                         90       100
                 ....*....|....*....|.
gi 292615891 124 YKCKIITFPSGNFEAEIVLTV 144
Cdd:cd05718   93 YICEFATFPQGNRQGTTWLRV 113

Second immunoglobulin (Ig) domain of poliovirus receptor (PVR, also known as CD155 and Necl-5), and similar domains; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig) domain of poliovirus receptor (PVR, also known as CD155 and nectin-like protein 5 (Necl-5)) and similar proteins. 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), these result from alternate splicing of the CD155 mRNA, and have identical extracellular domains. CD155-beta and CD155-gamma are secreted, while 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" and has a footprint similar to that of the intercellular adhesion molecule-1 receptor on human rhinoviruses. This group also includes the second Ig-like domain of nectin-1, also known as poliovirus receptor related protein(PVRL)1 or CD111.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 292615891 157 LIEGQSFRPAASC-RAMAKPVAGLSWDTELPGQSQNQS---SDESVSSI-KFSLHPYRSMNGQKLDCLVWHPSQKGPERI 231
Cdd:cd05719   11 LLIGGEPTLVATCiSANGKPPASVTWETDLKGEASTTQvrgSNGTVTVTsRYRLVPSREADGQPLTCVVEHPSLEKDQRI 90

                 ....*.
gi 292615891 232 SNKLIV 237
Cdd:cd05719   91 SVTLNV 96

First immunoglobulin variable (IgV) domain of nectin-3 (also known as poliovirus receptor related protein 3), and similar domains; The members here are composed of the first immunoglobulin (Ig) domain of nectin-3 (also known as poliovirus receptor related protein 3 (PVRL3) or cluster of differentiation (CD) 113). Nectin-3 belongs to the nectin family 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, during spermatid development, the nectin-3,-2 trans-interaction is required for the formation of Sertoli cell-spermatid junctions in testis, and during morphogenesis of the ciliary body, the nectin-3,-1 trans-interaction is important for apex-apex adhesion between the pigment and non-pigment layers of the ciliary epithelia. Nectins also heterophilically trans-interact with other CAMs such as nectin-like molecules (Necls); nectin-3 for example, trans-interacts with Necl-5, regulating cell movement and proliferation. Other proteins with which nectin-3 interacts include the actin filament-binding protein, afadin, integrin alpha-beta3, Par-3, and PDGF receptor; its interaction with PDGF receptor regulates the latter's signaling for anti-apoptosis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 292615891  49 LPCRFNVSDseiTVVQVLWIRENnGVEEQILTAHFKEGQTEFHSSYSGRVRFEtnNPIADSALIIMRTLS-ADEGKYKCK 127
Cdd:cd05887   19 LKCLIEVNE---TITQISWEKIH-GKSSQTVAVHHPQYGISIQGEYQGRVSFK--NYSLNDATITLHNVGfSDSGKYICK 92

                         90
                 ....*....|....*..
gi 292615891 128 IITFPSGNFEAEIVLTV 144
Cdd:cd05887   93 AVTFPLGNAQSSTTVTV 109

Second immunoglobulin (Ig) domain of Nectin-2 and Nectin-like protein 5, and similar domains; member of the C1-set of the Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig) domain of nectin-2 (also known as poliovirus receptor related protein 2 or Cluster of Differentiation 112 (CD112)), nectin-like protein 5 (CD155), and similar proteins. Nectins and Nectin-like molecules are a family of Ca(2+)-independent immunoglobulin-like transmembrane glycoproteins belonging to the class of adhesion receptors, consisting of nine members (nectins 1 through 4 and nectin-like proteins 1 through 5). Nectins are synaptic cell adhesion molecules (CAMs) which facilitate adhesion and signaling at various intracellular junctions. Nectins form homophilic cis-dimers, followed by homophilic and heterophilic trans-dimers involved in cell-cell adhesion. Nectin-2 and nectin-3 localize at Sertoli-spermatid junctions where they form heterophilic trans-interactions between the cells that are essential for the formation and maintenance of the junctions and for spermatid development. CD155 is the fifth member in the nectin-like molecule family, and functions as the receptor of poliovirus; therefore, CD155 is also referred to as Necl-5, or PVR. In contrast to all other family members, CD155 lacks self-adhesion capacity, yet it shares with nectins the feature to interact with other nectins. For instance, CD155 heterophilically trans-interacts with nectin-3, thereby contributing significantly to the establishment of adherens junctions between epithelial cells. This group belongs to the Constant 1 (C1)-set of IgSF domains, which has one beta-sheet that is formed by strands A-B-E-D and the other strands by G-F-C-C'.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 292615891 148 PISSLKSYTLIEGQSFRPAASC-RAMAKPVAGLSWDTELPGQ---SQNQSSDESVSSIK--FSLHPYRSMNGQKLDCLVW 221
Cdd:cd07703    1 PKNSAEAQEVQAGGIPVPVARCvSANGRPPARISWSSTLNGNantTQVPGPDSGTVTVTseYSLVPTPEANGKEVTCKVE 80

                         90
                 ....*....|....*.
gi 292615891 222 HPSQKGPERISNKLIV 237
Cdd:cd07703   81 HETLEEPQLLPVTLSV 96

Third immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the third immunoglobulin (Ig)-like domain in peroxidasin. Peroxidasin has a peroxidase domain and interacting extracellular motifs containing four Ig-like domains. It has been suggested that peroxidasin is secreted and has functions related to the stabilization of the extracellular matrix. It may play a part in various other important processes such as removal and destruction of cells which have undergone programmed cell death and protection of the organism against non-self.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 292615891 255 EMQGATLQCSGEGNPKPhLFNWTRKDGALP---EGVIVDGGTLLFSRpLRLADKGHYICTTTNLVGSGKTEIEVKI 327
Cdd:cd05745    1 EGQTVDFLCEAQGYPQP-VIAWTKGGSQLSvdrRHLVLSSGTLRISR-VALHDQGQYECQAVNIVGSQRTVAQLTV 74

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 292615891  42 LAEGET-RLPCRFNVSDSEITVVQVLW-IRENNGVEEQILTAHFKEGQTEFHSSYSGRVRFETNNPIADSALIIMRTLSA 119
Cdd:cd20960   12 KVAGENvTLPCHHQLGLEDQGTLDIEWlLLPSDKVEKVVITYSGDRVYNHYYPALKGRVAFTSNDLSGDASLNISNLKLS 91

                         90
                 ....*....|...
gi 292615891 120 DEGKYKCKIITFP 132
Cdd:cd20960   92 DTGTYQCKVKKAP 104

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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 292615891 261 LQCSGEGNPKPHLfNWTRKDGALPEGVIVDGGtllFSRPLRL-----ADKGHYICTTTNLVGSGKTEIEVKI 327
Cdd:cd05731   15 LECIAEGLPTPDI-RWIKLGGELPKGRTKFEN---FNKTLKIenvseADSGEYQCTASNTMGSARHTISVTV 82

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 292615891    48 RLPCRFnvSDSEITVVQVLWIRENNGVEEQILTAHFKEGQTEFHSSYSGRVRFETNNPIADSALIIMRTLSADEGKYKCK 127
Cdd:smart00406   3 TLSCKF--SGSTFSSYYVSWVRQPPGKGLEWLGYIGSNGSSYYQESYKGRFTISKDTSKNDVSLTISNLRVEDTGTYYCA 80

                   .
gi 292615891   128 I 128
Cdd:smart00406  81 V 81

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 292615891 259 ATLQCSGEGNPKPHLFnWTRKDGALPEGVIVD------GGTLLFsRPLRLADKGHYICTTTNLVG 317
Cdd:cd00096    1 VTLTCSASGNPPPTIT-WYKNGKPLPPSSRDSrrselgNGTLTI-SNVTLEDSGTYTCVASNSAG 63

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. 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 MuSK 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 292615891 259 ATLQCSGEGNPKPHLfNWTRKDGALPEG----VIVDGGTLLFSRPLRLADKGHYICTTTNLVG 317
Cdd:cd20970   20 ATFMCRAEGSPEPEI-SWTRNGNLIIEFntryIVRENGTTLTIRNIRRSDMGIYLCIASNGVP 81

First immunoglobulin variable (IgV) domain of DNAX accessory molecule 1, and similar domains; The members here are composed of the first immunoglobulin (Ig) domain of DNAX accessory molecule 1 (DNAM-1, also known as CD226). DNAM-1 is a transmembrane protein having two Ig-like domains. It is an adhesion molecule which plays a part in tumor-directed cytotoxicity and adhesion in natural killer (NK) cells and T lymphocytes. It has been shown to regulate the NK cell killing of several tumor types, including myeloma cells and ovarian carcinoma cells. DNAM-1 interacts specifically with poliovirus receptor (PVR; CD155) and nectin -2 (CD211), other members of the Ig superfamily. DNAM-1 is expressed in most peripheral T cells, NK cells, monocytes and a subset of B lymphocytes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 292615891  62 VVQVLWIReNNGVEEQILTAHFKEGqTEFHSSYSGRVRFE-TNNPIADSALIIMRTLSADEGKYKCKIITFPSGnfeaei 140
Cdd:cd05889   29 LTQVEWTK-IGGQKDNIAVYHPTHG-MHIRKPYAGRVYFLnSTMASNNMSLSFRNASEDDVGYYSCSLYTYPQG------ 100

                         90
                 ....*....|....
gi 292615891 141 vltVWTKPISSLKS 154
Cdd:cd05889  101 ---SWEKVIQVVQS 111

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 292615891 261 LQCSGEGNPKPhLFNWTRKDGALPEG---VIVDGGTLlFSRPLRLADKGHYICTTTNLVGSGKT 321
Cdd:cd04969   22 IECKPKASPKP-TISWSKGTELLTNSsriCILPDGSL-KIKNVTKSDEGKYTCFAVNFFGKANS 83

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 292615891 249 KDDWFAEMQGATLQCSGEGNPKPHLfNWTR---------KDGALPEGV-IVDGGTLLFSRpLRLADKGHYICTTTNLVGS 318
Cdd:cd20954    9 VDANVAAGQDVMLHCQADGFPTPTV-TWKKatgstpgeyKDLLYDPNVrILPNGTLVFGH-VQKENEGHYLCEAKNGIGS 86

                 .
gi 292615891 319 G 319
Cdd:cd20954   87 G 87

First immunoglobulin (Ig) domain of contactin-5; member of the I-set of Ig superfamily domains; The members here are composed of the first immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-5. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains, anchored to the membrane by glycosylphosphatidylinositol. The different contactins show different expression patterns in the central nervous system. In rats, a lack of contactin-5 (NB-2) results in an impairment of the neuronal activity in the auditory system. Contactin-5 is expressed specifically in the postnatal nervous system, peaking at about 3 weeks postnatal. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala; lower levels of expression have been detected in the corpus callosum, caudate nucleus, and spinal cord. This group belongs to the I-set of IgSF domains.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 292615891 235 LIVHYPPNAVISGYKDDwfaemQGATLQCSGEGNPKPHlFNWTRKdgalpeGVIVD----------GGTLLFSRPLRLAD 304
Cdd:cd05848    3 VFVQEPDDAIFPTDSDE-----KKVILNCEARGNPVPT-YRWLRN------GTEIDtesdyrysliDGNLIISNPSEVKD 70

                         90
                 ....*....|....
gi 292615891 305 KGHYICTTTNLVGS 318
Cdd:cd05848   71 SGRYQCLATNSIGS 84

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 292615891  259 ATLQCSGEGNPKPHlFNWTRKDGALPEG-----VIVDGGTLLFSRPLRLADKGHYICTTTN 314
Cdd:pfam13927  19 VTLTCEATGSPPPT-ITWYKNGEPISSGstrsrSLSGSNSTLTISNVTRSDAGTYTCVASN 78

Fourth immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; Members here are composed the fourth 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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 292615891 249 KDDWFAEMQGATLQCSGEGNPKPHLFnWtRKDGA----LPEGVIVDGGTLLFSRP-------LRLADKGHYICTTTNLVG 317
Cdd:cd05726    7 RDQVVALGRTVTFQCETKGNPQPAIF-W-QKEGSqnllFPYQPPQPSSRFSVSPTgdltitnVQRSDVGYYICQALNVAG 84

                         90
                 ....*....|.
gi 292615891 318 S--GKTEIEVK 326
Cdd:cd05726   85 SilAKAQLEVT 95

First immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. 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 first Ig-like domain of hemolin 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, including vascular (VCAM), intercellular (ICAM), neural (NCAM) and mucosal addressin (MADCAM) cell adhesion molecules, as well as junction adhesion molecules (JAM).

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 292615891 253 FAEMQGATLQCSGEGNPKPHLFNWtRKDG---ALPEGVIV---DGGTLLFSRPlRLADKGHYIC 310
Cdd:cd20979   12 FREGQPTVLECVTEGGDQGVKYSW-LKDGksfNWQEHNVAqrkDEGSLVFLKP-QASDEGQYQC 73

Third immunoglobulin (Ig) domain of contactin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 292615891 234 KLIVHYPpnavisgyKDDWFAEMQGATLQCSGEGNPKPHLfNWTRKDGAL-PEGVIVDGGTLLFSRPLRLADKGHYICTT 312
Cdd:cd04968    2 SIKVRFP--------ADTYALKGQTVTLECFALGNPVPQI-KWRKVDGSPsSQWEITTSEPVLEIPNVQFEDEGTYECEA 72

                 ....*
gi 292615891 313 TNLVG 317
Cdd:cd04968   73 ENSRG 77

Immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins; member of the I-set of IgSF domains; This group contains the immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins. The SALM (for synaptic adhesion-like molecules; also known as Lrfn for leucine-rich repeat and fibronectin type III domain containing) family of adhesion molecules consists of five known members: SALM1/Lrfn2, SALM2/Lrfn1, SALM3/Lrfn4, SALM4/Lrfn3, and SALM5/Lrfn5. SALMs share a similar domain structure, containing leucine-rich repeats (LRRs), an immunoglobulin (Ig) domain, and a fibronectin III (FNIII) domain, followed by a transmembrane domain and a C-terminal PDZ-binding motif. SALM5 is implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons. SALM5 interacts with the Ig domains of LAR (Leukocyte common Antigen-Related) family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPdelta, and PTPsigma). In addition, PTPdelta is implicated in ASDs, ADHD, bipolar disorder, and restless leg syndrome. Studies have shown that LAR-RPTPs are novel and splicing-dependent presynaptic ligands for SALM5, and that they mediate SALM5-dependent presynaptic differentiation. Furthermore, SALM5 maintains AMPA receptor (AMPAR)-mediated excitatory synaptic transmission through mechanisms involving the interaction of SALM5 with LAR-RPTPs. This group belongs to the I-set of immunoglobulin superfamily (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 292615891 252 WFAEMQGATLQCSGEGNPKPHLfNWTRKDGAL----PEGVIVDGGTL--LFSrplRLADKGHYICTTTNLVGSGKTEIEV 325
Cdd:cd05764   11 RVLEGQRATLRCKARGDPEPAI-HWISPEGKLisnsSRTLVYDNGTLdiLIT---TVKDTGAFTCIASNPAGEATARVEL 86

                 ..
gi 292615891 326 KI 327
Cdd:cd05764   87 HI 88

Fourth 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 fourth 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 292615891 260 TLQCSGEGNPKPhLFNWTRKDGALPEG--------VIVDGGTLLF---SRpLRLADKGHYICTTTNLVGS 318
Cdd:cd20956   20 SLKCVASGNPLP-QITWTLDGFPIPESprfrvgdyVTSDGDVVSYvniSS-VRVEDGGEYTCTATNDVGS 87