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
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 1297304   92 EGMPRPIYSWNRVENGLLKSTPSQMNQQKgSLIIGNLTDFEEGYYRCTASNNLGNAT 148
Cdd:cd05731  20 EGLPTPDIRWIKLGGELPKGRTKFENFNK-TLKIENVSEADSGEYQCTASNTMGSAR 75

Immunoglobulin V-set domain; This domain is found in antibodies as well as neural protein P0 and CTL4 amongst others.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1297304      1 VFFYQNGQSLSGPsyKNRVTAAMSP--GNATITISNMQSQDTGIYTCEVLNLPESSGQGKILLTVL 64
Cdd:pfam07686  46 IAYYSNGSEEGVK--KGRFSGRGDPsnGDGSLTIQNLTLSDSGTYTCAVIPSGEGVFGKGTRLTVL 109

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
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 1297304   92 EGMPRPIYSWNRVENGLLKSTPSQMNQQKgSLIIGNLTDFEEGYYRCTASNNLGNAT 148
Cdd:cd05731  20 EGLPTPDIRWIKLGGELPKGRTKFENFNK-TLKIENVSEADSGEYQCTASNTMGSAR 75

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1297304      78 VETGHFISLLCYSEeGMPRPIYSWNRVENGLLKSTP---SQMNQQKGSLIIGNLTDFEEGYYRCTASNNLGNATCELNLH 154
Cdd:smart00410   6 VKEGESVTLSCEAS-GSPPPEVTWYKQGGKLLAESGrfsVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGTTLT 84

Immunoglobulin V-set domain; This domain is found in antibodies as well as neural protein P0 and CTL4 amongst others.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1297304      1 VFFYQNGQSLSGPsyKNRVTAAMSP--GNATITISNMQSQDTGIYTCEVLNLPESSGQGKILLTVL 64
Cdd:pfam07686  46 IAYYSNGSEEGVK--KGRFSGRGDPsnGDGSLTIQNLTLSDSGTYTCAVIPSGEGVFGKGTRLTVL 109

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
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 1297304   92 EGMPRPIYSWNRVENGLLKSTPSQMNQQKgSLIIGNLTDFEEGYYRCTASNNLGNAT 148
Cdd:cd05731  20 EGLPTPDIRWIKLGGELPKGRTKFENFNK-TLKIENVSEADSGEYQCTASNTMGSAR 75

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1297304    1 VFFYQNGQSLSGPsYKNRV---TAAMSPGNATITISNMQSQDTGIYTCEVLNLPESSGQGKILLTV 63
Cdd:cd05718  49 VFHPQYGPSVPNP-YAERVeflAARLGLRNATLRIRNLRVEDEGNYICEFATFPQGNRQGTTWLRV 113

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
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 1297304   92 EGMPRPIYSWNRvENGLLKSTPSQMNQQKGSLIIGNLTDFEEGYYRCTASNNLGNA 147
Cdd:cd04969  27 KASPKPTISWSK-GTELLTNSSRICILPDGSLKIKNVTKSDEGKYTCFAVNFFGKA 81

Third immunoglobulin (Ig)-like domain of Neural Cell Adhesion Molecule 1 (NCAM-1); member of the I-set of IgSF domains; The members here are composed of the third 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1297304   66 PPSVP--HCSIRGAVETGHFISLLCySEEGMPRPIYSWNR----VENGLLKSTpsqMNQQKGSLIIGNLTDFEEGYYRCT 139
Cdd:cd05730   1 PPTIRarQSEVNATANLGQSVTLAC-DADGFPEPTMTWTKdgepIESGEEKYS---FNEDGSEMTILDVDKLDEAEYTCI 76

                        90
                ....*....|....
gi 1297304  140 ASNNLGNATCELNL 153
Cdd:cd05730  77 AENKAGEQEAEIHL 90

Immunoglobulin I-set domain;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1297304      4 YQNGQSLSgPSykNRVTAAMSPGNATITISNMQSQDTGIYTCEVLNlpeSSGQ--GKILLTV 63
Cdd:pfam07679  35 FKDGQPLR-SS--DRFKVTYEGGTYTLTISNVQPDDSGKYTCVATN---SAGEaeASAELTV 90

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). 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 1297304   93 GMPRPIYSWNRVENGLLKSTPSQMNQQKG---SLIIGNLTDFEEGYYRCTASNNLGNATCELNL 153
Cdd:cd05744  26 GLPTPDLFWQLNGKPVRPDSAHKMLVRENgrhSLIIEPVTKRDAGIYTCIARNRAGENSFNAEL 89

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
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 1297304    1 VFFYQNGQSLSGPSYKNRVTaamSPGNATITISNMQSQDTGIYTCEVLNLPESSGQGKI 59
Cdd:cd00096  15 ITWYKNGKPLPPSSRDSRRS---ELGNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. 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 telokin Ig domain 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 1297304   92 EGMPRPIYSWNRVENGLLKSTPSQMNQQKG---SLIIGNLTDFEEGYYRCTASNNLGNATCELNL 153
Cdd:cd20973  22 EGYPDPEVKWMKDDNPIVESRRFQIDQDEDglcSLIISDVCGDDSGKYTCKAVNSLGEATCSAEL 86

Immunoglobulin (Ig)-like domain of NrCAM (Ng (neuronglia) CAM-related cell adhesion molecule); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of NrCAM (Ng (neuronglia) CAM-related cell adhesion molecule). NrCAM 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. NrCAM is primarily expressed in the nervous system.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1297304   92 EGMPRPIYSWNRveNG----LLKSTPSQMNQQKGSLII----GNLTDFEEGYYRCTASNNLGNA 147
Cdd:cd05874  26 KGKPPPSFSWTR--NGthfdIDKDPKVTMKPNTGTLVInimnGEKAEAYEGVYQCTARNERGAA 87

Fifth immunoglobulin (Ig) domain of contactin-1; The members here are composed of the fifth immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. 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
                ....*....|....*....|....*....|....*....|....*....|...
gi 1297304   95 PRPIYSWNRVENGLLKSTPSQMnQQKGSLIIGNLTDFEEGYYRCTASNNLGNA 147
Cdd:cd05852  30 PKPKFSWSKGTELLVNNSRISI-WDDGSLEILNITKLDEGSYTCFAENNRGKA 81

Immunoglobulin (Ig)-like domain of human neurofascin (NF); member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first immunoglobulin (Ig)-like domain of human neurofascin (NF). NF 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 a cytoplasmic domain. NF has many alternatively spliced isoforms having different temporal expression patterns during development. NF participates in axon subcellular targeting and synapse formation, however little is known of the functions of the different isoforms. 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 lacks a C" strand.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1297304   92 EGMPRPIYSWNRveNG----LLKSTPSQMNQQKGSLII----GNLTDFEEGYYRCTASNNLGNA 147
Cdd:cd05875  26 KGNPVPTFHWTR--NGkffnVAKDPRVSMRRRSGTLVIdfrgGGRPEDYEGEYQCFARNKFGTA 87

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1297304   86 LLCySEEGMPRPIYSWNRVENGLLKSTPSQMNQQKGSLIIGNLTDFEEGYYRCTASNNLGNAT 148
Cdd:cd20952  19 LNC-QATGEPVPTISWLKDGVPLLGKDERITTLENGSLQIKGAEKSDTGEYTCVALNLSGEAT 80

Immunoglobulin (Ig)-like domain of the aggrecan-like chondroitin sulfate proteoglycan core protein (CSPG); The members here are composed of the immunoglobulin (Ig)-like domain of the aggrecan-like chondroitin sulfate proteoglycan core proteins (CSPGs). Included in this group are the Ig domains of other CSPGs: 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. 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
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1297304    5 QNGQSLSGPSYKNRVTAAMSP---GNATITISNMQSQDTGIYTCEVLNLPESSgQGKILLTV 63
Cdd:cd05878  60 TEGRVRVNSAYQGRVSLPNYPaipSDATLEVQSLRASDSGLYRCEVMHGIEDS-QDTVELVV 120

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 1297304   77 AVETGHFISLLCYSEeGMPRPIYSWNrvengllKSTPSQMNQQK-------------GSLIIGNLTDFEEGYYRCTASNN 143
Cdd:cd20954  12 NVAAGQDVMLHCQAD-GFPTPTVTWK-------KATGSTPGEYKdllydpnvrilpnGTLVFGHVQKENEGHYLCEAKNG 83

                ..
gi 1297304  144 LG 145
Cdd:cd20954  84 IG 85

agrin-responsive second immunoglobulin-like domains (Ig2) of the Muscle-specific kinase (MuSK) ectodomain; a member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin-like (Ig) domains of the Muscle-specific kinase (MuSK) ectodomain. 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
                ....*....|....*....|....*....|....*....|....*....|....*
gi 1297304   93 GMPRPIYSWNRvENGLLKSTPSQMNQQKGSLIIGNLTDFEEGYYRCTASNNLGNA 147
Cdd:cd20968  25 GNPKPSVSWIK-GDDLIKENNRIAVLESGSLRIHNVQKEDAGQYRCVAKNSLGIA 78

Immunoglobulin (Ig)-like domain of myelin oligodendrocyte glycoprotein (MOG); The members here are composed of the immunoglobulin (Ig)-like domain of myelin oligodendrocyte glycoprotein (MOG). MOG, a minor component of the myelin sheath, is an important CNS-specific autoantigen, linked to the pathogenesis of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). It is a transmembrane protein having an extracellular Ig domain. MOG is expressed in the CNS on the outermost lamellae of the myelin sheath, and on the surface of oligodendrocytes, and may participate in the completion, compaction, and/or maintenance of myelin. This group also includes butyrophilin (BTN). BTN is the most abundant protein in bovine milk-fat globule membrane (MFGM).

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 1297304    1 VFFYQNGQSLSG---PSYKNR---VTAAMSPGNATITISNMQSQDTGIYTC 45
Cdd:cd05713  46 VHLYRDGQDQEEeqmPEYRGRtelLKDAIAEGSVALRIHNVRPSDEGQYTC 96

Immunoglobulin (Ig)-like domain of epithelial V-like antigen (EVA) 1; The members here are composed of the immunoglobulin (Ig) domain of epithelial V-like antigen 1 (EVA 1). EVA is also known as myelin protein zero-like 2. EVA is an adhesion molecule and may play a role in the structural organization of the thymus and early lymphocyte development.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1297304    1 VFFYQNG--QSLSGpSYKNRVTAAMSP--GNATITISNMQSQDTGIYTCEVLNLPESSGQ-GKILLTV 63
Cdd:cd05880  50 VFYYHKRpyPPPDG-RFKGRVVWDGNImrRDASILIWQLQPTDNGTYTCQVKNPPDVHGPiGEIRLRV 116

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1297304   93 GMPRPIYSWNRveNGLLKSTPSQMNQQKGSLIIGNLTDFEEGYYRCTASNNLGN--ATCEL 151
Cdd:cd05728  25 GNPRPAYRWLK--NGQPLASENRIEVEAGDLRITKLSLSDSGMYQCVAENKHGTiyASAEL 83

Immunoglobulin Variable (IgV) domain in HERV-H LTR-associating 2 (HHLA2); The members here are composed of the immunoglobulin variable (IgV) region in HERV-H LTR-associating 2 (HHLA2; also known as B7-H7/B7 homolog 7). HHLA2 is a member of the B7 family of immune regulatory proteins. Mature human HHLA2 consists of an extracellular domain (ECD) with three immunoglobulin-like domains, a transmembrane segment, and a cytoplasmic domain. HHLA2 is widely expressed in human cancers including non-small cell lung carcinoma (NSCLS), triple negative breast cancer (TNBC), and melanoma, but has limited expression on normal tissues. Interestingly, unlike other members of B7 family, HHLA2 is not expressed in mice or rats. HHLA2 functions as a T cell coinhibitory molecules as it inhibits the proliferation of activated CD4(+) and CD8(+) T cells and their cytokine production. Furthermore, HHLA2 is constitutively expressed on the surface of human monocytes and is induced on B cells after stimulation, however it is not inducible on T cells.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 1297304    2 FFYQNGQ-SLSGPSYKNRVT---AAMSPGNATITISNMQSQDTGIYTCEV 47
Cdd:cd16091  43 YYYGKDQlESQDQRYRNRTSlfkDQISNGNASLLLRRVQLQDEGRYKCYT 92

Immunoglobulin (Ig)-like domain of human carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) domains 2, 4, and 6, and similar domains; The members here are composed of the second, fourth, and sixth immunoglobulin (Ig)-like domains in human carcinoembryonic antigen (CEA) related cell adhesion molecule (CEACAM) protein subfamily. The CEA family is a group of anchored or secreted glycoproteins expressed by epithelial cells, leukocytes, endothelial cells, and placenta. The CEA family is divided into the CEACAM and pregnancy-specific glycoprotein (PSG) subfamilies. This group represents the CEACAM subfamily. CEACAM1 has many important cellular functions; it is a cell adhesion molecule and a signaling molecule that regulates the growth of tumor cells, an angiogenic factor, and a receptor for bacterial and viral pathogens, including mouse hepatitis virus (MHV). In mice, four isoforms of CEACAM1 generated by alternative splicing have either two [D1, D4] or four [D1-D4] Ig-like domains on the cell surface.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 1297304    6 NGQSLSgpsYKNRVTaaMSPGNATITISNMQSQDTGIYTCEVLNLPESSGQGKILLTVL 64
Cdd:cd05740  36 NGQSLP---VTPRLT--LSNGNRTLTLLNVTREDAGAYQCEISNPVSANRSDPVTLDVI 89

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
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1297304    1 VFFYQNGQSL--SGPSYKNRVTAAMSPG--NATITISNMQSQDTGIYTCEVLNLPESSGQ 56
Cdd:cd05879  50 IFHYGKGQPYidNVGPFKERIEWVGNPSrkDGSIVIHNLDYTDNGTFTCDVKNPPDIVGK 109

Immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain of the human basement membrane heparan sulfate proteoglycan perlecan, also known as HSPG2, and similar proteins. Perlecan consists of five domains: domain I has three putative heparan sulfate attachment sites, domain II has four LDL receptor-like repeats, and one Ig-like repeat, domain III resembles the short arm of laminin chains, domain IV has multiple Ig-like repeats (21 repeats in human perlecan), and domain V resembles the globular G domain of the laminin A chain and internal repeats of EGF. Perlecan may participate in a variety of biological functions including cell binding, LDL-metabolism, basement membrane assembly and selective permeability, calcium binding, and growth- and neurite-promoting activities.

                        10        20        30
                ....*....|....*....|....*....|..
gi 1297304   18 RVTAAMSPGNATITISNMQSQDTGIYTCEVLN 49
Cdd:cd05743  32 RVSITSEGGYGTLTIRDVKESDQGAYTCEAIN 63

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1297304   75 RGAVETGHFISLLCYSEeGMPRPIYSWnRVeNGL---LKSTPSQMNQQKGSLIIGNLTDFEEGYYRCTASNNLGNATCEL 151
Cdd:cd04978   8 SLVLSPGETGELICEAE-GNPQPTITW-RL-NGVpiePAPEDMRRTVDGRTLIFSNLQPNDTAVYQCNASNVHGYLLANA 84

                ...
gi 1297304  152 NLH 154
Cdd:cd04978  85 FLH 87

N-terminal immunoglobulin (Ig)-like domain of T-cell surface antigen CD2, and similar domains; The members here are composed of the N-terminal immunoglobulin (Ig)-like domain (or domain 1) of T-cell surface antigen Clusters of Differentiation (CD) 2 and similar proteins. CD2 is a T-cell specific surface glycoprotein and is critically important for mediating adhesion between T cells and antigen-presenting cells or between cytolytic T cells and target cells. CD2 is located on chromosome 1 at 1p13 in humans and on chromosome 3 in mice. CD2 contains an extracellular domain with two or Ig-like domains, a single transmembrane segment, and a cytoplasmic region rich in proline and basic residues.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 1297304   13 PSYKNRVTaaMSPGNATITISNMQSQDTGIYTCEVLNLPESSGQGKILLTVL 64
Cdd:cd05775  49 GSFKDRVL--LDKESGSLTIKNLTKEDSGTYELEITSTNGKVLSSKFTLEVL 98

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

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                ....*....|....*....|....*....|....*....|....*....|....
gi 1297304   13 PSYKNRV--TAAMSPGNATITISNMQSQDTGIYTCEVLNLP--ESSgqgKILLT 62
Cdd:cd20960  64 PALKGRVafTSNDLSGDASLNISNLKLSDTGTYQCKVKKAPgyAWS---KITLI 114

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1297304      1 VFFYQNGQSLSGPSYKNRVTaamSPGNATITISNMQSQDTGIYTCEVLN 49
Cdd:pfam13927  33 ITWYKNGEPISSGSTRSRSL---SGSNSTLTISNVTRSDAGTYTCVASN 78

First immunoglobulin (Ig) domain of contactin; member of the I-set of (Ig) superfamily domains; The members here are composed of the first 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 1297304   51 PESSGQGKILLTvlvppsvphCSIRGAvetghfisllcyseegmPRPIYSWnRVENGLLKSTPS-QMNQQKGSLIIGNLT 129
Cdd:cd04967  14 PEDSDEKKVALN---------CRARAN-----------------PVPSYRW-LMNGTEIDLESDyRYSLVDGTLVISNPS 66

                        90
                ....*....|....*..
gi 1297304  130 DFEE-GYYRCTASNNLG 145
Cdd:cd04967  67 KAKDaGHYQCLATNTVG 83

Fourth 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 fourth 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 fourth 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 domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, 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 1297304    5 QNGQSLSGPSYKNRVTaamspgNATITISNMQSQDTGIYTCEVLNlpeSSG--QGKILLTV 63
Cdd:cd20978  37 HNGKPLQGPMERATVE------DGTLTIINVQPEDTGYYGCVATN---EIGdiYTETLLHV 88

Immunoglobulin (Ig)-like domain found in Perlecan and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain found in Perlecan. Perlecan is a large multi-domain heparin sulfate proteoglycan, important in tissue development and organogenesis. Perlecan can be represented as 5 major portions; its fourth major portion (domain IV) is a tandem repeat of immunoglobulin-like domains (Ig2-Ig15) which can vary in size due to alternative splicing. Perlecan binds many cellular and extracellular ligands. Its domain IV region has many binding sites. Some of these have been mapped at the level of individual Ig-like domains, including a site restricted to the Ig5 domain for heparin/sulfatide, a site restricted to the Ig3 domain for nidogen-1 and nidogen-2, a site restricted to Ig4-5 for fibronectin, and sites restricted to Ig2 and to Ig13-15 for fibulin-2. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1297304   78 VETGHFISLLCYSEEGMPRPIYSWNRVeNGLLkstPSQMNQQKGSLIIGNLTDFEEGYYRCTASNNL----GNAT 148
Cdd:cd05754  13 VRPGADVSFICRAKSKSPAYTLVWTRV-NGTL---PSRAMDFNGILTIRNVQLSDAGTYVCTGSNMLdtdeATAT 83