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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114145511   32 EPLSVPKGKTAELSCSYKTS-VGDNFALEWSFVQPGKPISasVPVLYFTNGhlYPTGSKADRaILLHDPPTGGLATLKLT 110
Cdd:pfam07686   4 REVTVALGGSVTLPCTYSSSmSEASTSVYWYRQPPGKGPT--FLIAYYSNG--SEEGVKKGR-FSGRGDPSNGDGSLTIQ 78

                          90       100       110
                  ....*....|....*....|....*....|...
gi 114145511  111 DLRPSDTGTYLCNVNNPPDFYTNglGLINLTVL 143
Cdd:pfam07686  79 NLTLSDSGTYTCAVIPSGEGVFG--KGTRLTVL 109

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114145511   32 EPLSVPKGKTAELSCSYKTS-VGDNFALEWSFVQPGKPISasVPVLYFTNGhlYPTGSKADRaILLHDPPTGGLATLKLT 110
Cdd:pfam07686   4 REVTVALGGSVTLPCTYSSSmSEASTSVYWYRQPPGKGPT--FLIAYYSNG--SEEGVKKGR-FSGRGDPSNGDGSLTIQ 78

                          90       100       110
                  ....*....|....*....|....*....|...
gi 114145511  111 DLRPSDTGTYLCNVNNPPDFYTNglGLINLTVL 143
Cdd:pfam07686  79 NLTLSDSGTYTCAVIPSGEGVFG--KGTRLTVL 109

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114145511    41 TAELSCSYKTSVGDNFALEWSFVQPGKPISasVPVLYFTNGHLYPTGSKADRAILLHDPpTGGLATLKLTDLRPSDTGTY 120
Cdd:smart00406   1 SVTLSCKFSGSTFSSYYVSWVRQPPGKGLE--WLGYIGSNGSSYYQESYKGRFTISKDT-SKNDVSLTISNLRVEDTGTY 77

                   ..
gi 114145511   121 LC 122
Cdd:smart00406  78 YC 79

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114145511 153 QSGQTSVGGSAALGCRSSeGAPKPVYNWERLGSsPTPPPGSMvqdEVS-GQLILTNLSLTSSGTYRCVASNQMGS--ASC 229
Cdd:cd05728    7 SDTEADIGSSLRWECKAS-GNPRPAYRWLKNGQ-PLASENRI---EVEaGDLRITKLSLSDSGMYQCVAENKHGTiyASA 81

                 ..
gi 114145511 230 EL 231
Cdd:cd05728   82 EL 83

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114145511   32 EPLSVPKGKTAELSCSYKTS-VGDNFALEWSFVQPGKPISasVPVLYFTNGhlYPTGSKADRaILLHDPPTGGLATLKLT 110
Cdd:pfam07686   4 REVTVALGGSVTLPCTYSSSmSEASTSVYWYRQPPGKGPT--FLIAYYSNG--SEEGVKKGR-FSGRGDPSNGDGSLTIQ 78

                          90       100       110
                  ....*....|....*....|....*....|...
gi 114145511  111 DLRPSDTGTYLCNVNNPPDFYTNglGLINLTVL 143
Cdd:pfam07686  79 NLTLSDSGTYTCAVIPSGEGVFG--KGTRLTVL 109

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114145511  25 VEVTVPTEPLSVpKGKTAELSCSYKTS--VGDNFALEWSFvQPGKPISASVPVLYFTNGHLYPTGSKADRAILLHDPpTG 102
Cdd:cd05880    1 IEVYTSKEVEAV-NGTDVRLKCTFSSSapIGDTLVITWNF-RPLDGGREESVFYYHKRPYPPPDGRFKGRVVWDGNI-MR 77

                         90       100
                 ....*....|....*....|....*..
gi 114145511 103 GLATLKLTDLRPSDTGTYLCNVNNPPD 129
Cdd:cd05880   78 RDASILIWQLQPTDNGTYTCQVKNPPD 104

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114145511   152 SQSGQTSVGGSAALGCRSSeGAPKPVYNWERLGSSPTPPPG--SMVQDEVSGQLILTNLSLTSSGTYRCVASNQMGSASC 229
Cdd:smart00410   1 PPSVTVKEGESVTLSCEAS-GSPPPEVTWYKQGGKLLAESGrfSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASS 79

                   ....*.
gi 114145511   230 ELNLSV 235
Cdd:smart00410  80 GTTLTV 85

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114145511  152 SQSGQTSVGGSAALGCRSSeGAPKPVYNWERLGSSPTPPP-GSMVQDEVSGQLILTNLSLTSSGTYRCVASNQMGSASCE 230
Cdd:pfam07679   7 PKDVEVQEGESARFTCTVT-GTPDPEVSWFKDGQPLRSSDrFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSAGEAEAS 85

                  ....*
gi 114145511  231 LNLSV 235
Cdd:pfam07679  86 AELTV 90

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 114145511  159 VGGSAALGCRSsEGAPKPVYNWERLGSSPTPPPGSMV-QDEVSGQLILTNLSLTSSGTYRCVASN 222
Cdd:pfam13927  15 EGETVTLTCEA-TGSPPPTITWYKNGEPISSGSTRSRsLSGSNSTLTISNVTRSDAGTYTCVASN 78

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 114145511 165 LGCRSSeGAPKPVYNWERLGSS-PTPPPGSMVQDEVSGQLILTNLSLTSSGTYRCVASNQMG 225
Cdd:cd00096    3 LTCSAS-GNPPPTITWYKNGKPlPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAG 63

Immunoglobulin domain; Members of the immunoglobulin superfamily are found in hundreds of proteins of different functions. Examples include antibodies, the giant muscle kinase titin and receptor tyrosine kinases. Immunoglobulin-like domains may be involved in protein-protein and protein-ligand interactions.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 114145511  152 SQSGQTSVGGSAALGCRSSEGAPKPVYNWERLGSSPTPPPGSMVQDEVSGQ--LILTNLSLTSSGTYRCVASN 222
Cdd:pfam00047   3 PPTVTVLEGDSATLTCSASTGSPGPDVTWSKEGGTLIESLKVKHDNGRTTQssLLISNVTKEDAGTYTCVVNN 75

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 114145511 149 PLCSQSGQTSVGGSAALGCRSSEGAPKPVYNWERLG-SSPTPPP-------GSMVQDEVSGQLILTNLSLTSSGTYRCVA 220
Cdd:cd20950    1 PTVNIPSSATIGNRAVLTCSEPDGSPPSEYTWFKDGvVMPTNPKstrafsnSSYSLDPTTGELVFDPLSASDTGEYSCEA 80

                 ....*..
gi 114145511 221 SNQMGSA 227
Cdd:cd20950   81 RNGYGTP 87

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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 114145511 159 VGGSAALGCRSsEGAPKPVYNWERLGSSPTPPPGSMVQDEvsGQLILTNLSLTSSGTYRCVASNQMGSASCELNLSV 235
Cdd:cd04969   16 KGGDVIIECKP-KASPKPTISWSKGTELLTNSSRICILPD--GSLKIKNVTKSDEGKYTCFAVNFFGKANSTGSLSV 89

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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 114145511 159 VGGSAALGCrSSEGAPKPVYNWERLGSsPTPPPGSMVQDEVSGQLILTNLSLTSSGTYRCVASNQMGSASCELNLSV 235
Cdd:cd20952   13 VGGTVVLNC-QATGEPVPTISWLKDGV-PLLGKDERITTLENGSLQIKGAEKSDTGEYTCVALNLSGEATWSAVLDV 87

Third immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); 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, 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, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains the chicken neuron-glia cell adhesion molecule, Ng-CAM.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 114145511 160 GGSAALGCrSSEGAPKPVYNWERLgSSPTPPPGSMVQDEvSGQLILTNLSLTSSGTYRCVASNQMGSA 227
Cdd:cd05876   10 GQSLVLEC-IAEGLPTPTVKWLRP-SGPLPPDRVKYQNH-NKTLQLLNVGESDDGEYVCLAENSLGSA 74

Immunoglobulin (Ig)-like domain in the polymeric Ig receptor (pIgR) and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain in the polymeric Ig receptor (pIgR) and similar proteins. pIgR delivers dimeric IgA and pentameric IgM to mucosal secretions. Polymeric immunoglobulin (pIgs) are the first defense against pathogens and toxins. IgA and IgM can form polymers via an 18-residue extension at their C-termini referred to as the tailpiece. pIgR transports pIgs across mucosal epithelia into mucosal secretions. Human pIgR is a glycosylated type I transmembrane protein, comprised of a 620-residue extracellular region, a 23-residue transmembrane region, and a 103-residue cytoplasmic tail. The extracellular region contains five domains that share sequence similarity with Ig variable (v) regions. This group also contains the Ig-like extracellular domains of other receptors such as NK cell receptor Nkp44 and myeloid receptors, among others.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 114145511  86 TGSKADRAILLHDPPTGGLATLKLTDLRPSDTGTYLCNVNNPPDFYT 132
Cdd:cd05716   47 EGVVPGGRISLTDDPDNGVFTVTLNQLRKEDAGWYWCGVGDDGDRGL 93

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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 114145511 160 GGSAALGCRSSeGAPKPVYNWERLGSSPTPPPG-SMVQDEvSGQ--LILTNLSLTSSGTYRCVASNQMGSASCELNLSV 235
Cdd:cd05744   15 GRLCRFDCKVS-GLPTPDLFWQLNGKPVRPDSAhKMLVRE-NGRhsLIIEPVTKRDAGIYTCIARNRAGENSFNAELVV 91

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 114145511  38 KGKTAELSCSYKTSVGDNFAL--EWSFVQPGKpiSASVPVLYFtNGHLYPTGSKADRA-ILLHDPPTGGLATLKLTDLRP 114
Cdd:cd20960   14 AGENVTLPCHHQLGLEDQGTLdiEWLLLPSDK--VEKVVITYS-GDRVYNHYYPALKGrVAFTSNDLSGDASLNISNLKL 90

                         90
                 ....*....|....
gi 114145511 115 SDTGTYLCNVNNPP 128
Cdd:cd20960   91 SDTGTYQCKVKKAP 104

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup 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. 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. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin 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. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114145511 159 VGGSAALGCrSSEGAPKPVYNWERLGSSPTPPPGS-----MVQDEVsgqLILTNLSLTSSGTYRCVASNQMGSASCELNL 233
Cdd:cd05763   13 AGSTARLEC-AATGHPTPQIAWQKDGGTDFPAARErrmhvMPEDDV---FFIVDVKIEDTGVYSCTAQNSAGSISANATL 88

                 ..
gi 114145511 234 SV 235
Cdd:cd05763   89 TV 90

Second 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 second immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. 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 114145511 158 SVGGSAALGCrSSEGAPKPVYNWERLGSSPTPPPGSMVQD---EVSGQLILTNLSLTSSGTYRCVASNQMGSASCELNLS 234
Cdd:cd20953   16 SSASSIALLC-PAQGYPAPSFRWYKFIEGTTRKQAVVLNDrvkQVSGTLIIKDAVVEDSGKYLCVVNNSVGGESVETVLT 94

                 .
gi 114145511 235 V 235
Cdd:cd20953   95 V 95

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 114145511 158 SVGGSAALGCRSsEGAPKPVYNWERLGSSPTPPPGSMVQdEVSGQLILTNLS-LTSSGTYRCVASNQMGSA-SCELNLS 234
Cdd:cd04967   17 SDEKKVALNCRA-RANPVPSYRWLMNGTEIDLESDYRYS-LVDGTLVISNPSkAKDAGHYQCLATNTVGSVlSREATLQ 93

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 114145511 160 GGSAALGCrSSEGAPKPVYNWERLGSSPTPPPGSMVQDevSGQLILTNLSLTSSGTYRCVASNQMGSA 227
Cdd:cd20968   14 GLKAVLPC-TTMGNPKPSVSWIKGDDLIKENNRIAVLE--SGSLRIHNVQKEDAGQYRCVAKNSLGIA 78

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 114145511 160 GGSAALGCrSSEGAPKPVYNWERLGSSPTPPPGSMVQDEVSGQLILTNLSLTSSGTYRCVASNQMGSASCELNLSV 235
Cdd:cd20976   16 GQDFVAQC-SARGKPVPRITWIRNAQPLQYAADRSTCEAGVGELHIQDVLPEDHGTYTCLAKNAAGQVSCSAWVTV 90

Immunoglobulin (Ig) variable (V) domain of T-cell receptor (TCR) gamma chain; The members here are composed of the immunoglobulin (Ig) variable (V) domain of the gamma chain of gamma/delta T-cell receptors (TCRs). TCRs mediate antigen recognition by T lymphocytes, and are heterodimers consisting of alpha and beta chains or gamma and delta chains. Each chain contains a variable (V) and a constant (C) region. The majority of T cells contain alpha/beta TCRs, but a small subset contain gamma/delta TCRs. Alpha/beta TCRs recognize antigens as peptide fragments presented by major histocompatibility complex (MHC) molecules. Gamma/delta TCRs recognize intact protein antigens directly without antigen processing and recognize MHC independently of the bound peptide. Gamma/delta T cells can also be stimulated by non-peptide antigens such as small phosphate- or amine-containing compounds. The variable domain of gamma/delta TCRs is responsible for antigen recognition and is located at the N-terminus of the receptor. Members of this group contain the standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114145511  33 PLSV--PKGKTAELSCSYKTSVGDNFALEWSFVQPGKpisASVPVLYFTNG--HLYPTGSKADRaILLHDPPTGGLATLK 108
Cdd:cd04982    5 QLSItrEESKSVTISCKVSGIDFSTTYIHWYRQKPGQ---ALERLLYVSSTsaVRKDSGKTKNK-FEARKDVGKSTSTLT 80

                         90
                 ....*....|....
gi 114145511 109 LTDLRPSDTGTYLC 122
Cdd:cd04982   81 ITNLEKEDSATYYC 94

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 114145511  25 VEVTVPTEPLSVPkGKTAELSCSYKTSVGDNFA-LEWSFvqPGKPISASVPVLYFTNGHLYPtGSKADRAILLHDPPTGG 103
Cdd:cd05718    1 QRVQVPTEVTGFL-GGSVTLPCSLTSPGTTKITqVTWMK--IGAGSSQNVAVFHPQYGPSVP-NPYAERVEFLAARLGLR 76

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 114145511 104 LATLKLTDLRPSDTGTYLCnvnnppDFYT----NGLGLINLTV 142
Cdd:cd05718   77 NATLRIRNLRVEDEGNYIC------EFATfpqgNRQGTTWLRV 113

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor_like-1(FGFRL1); member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 is comprised of a signal peptide, three extracellular Ig-like modules, a transmembrane segment, and a short intracellular domain. FGFRL1 is expressed preferentially in skeletal tissues. Similar to FGF receptors, the expressed protein interacts specifically with heparin and with FGF2. FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 114145511  62 FVQPGK--------PISASVPVLYFTNGHLYP--TGSKADRAILLHDP--PTGGLATLKLTDLRPSDTGTYLCNVNN 126
Cdd:cd05856    3 FTQPAKmrrrviarPVGSSVRLKCVASGNPRPdiTWLKDNKPLTPPEIgeNKKKKWTLSLKNLKPEDSGKYTCHVSN 79

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 114145511 145 PPSHPLCSQSGQtsVGGSAALGCRSSEGAPKPVYNWERLGSSPTPPPGSMVQ---DEVSGQLILTNLSLTSSGTYRCVAS 221
Cdd:cd05750    1 PKLKEMKSQTVQ--EGSKLVLKCEATSENPSPRYRWFKDGKELNRKRPKNIKirnKKKNSELQINKAKLEDSGEYTCVVE 78

                         90
                 ....*....|....
gi 114145511 222 NQMGSASCELNLSV 235
Cdd:cd05750   79 NILGKDTVTGNVTV 92

Immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM) and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the first 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, or spastic paraplegia type 1, that involves abnormalities of axonal growth. This group also contains NrCAM [Ng(neuronglia)CAM-related cell adhesion molecule], which is primarily expressed in the nervous system, and human neurofascin. 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 114145511 172 GAPKPVYNWERLGSSPTP---PPGSMVQDevSGQLILTNLSLTSS---GTYRCVASNQMGSA 227
Cdd:cd05733   27 GNPQPTFRWTKDGKFFDPakdPRVSMRRR--SGTLVIDNHNGGPEdyqGEYQCYASNELGTA 86

Immunoglobulin (Ig)-like domain of the chondroitin sulfate proteoglycan core protein (CSPG), aggrecan; The members here are composed of the immunoglobulin (Ig)-like domain of the chondroitin sulfate proteoglycan core protein (CSPG), aggrecan. 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, aggrecan forms cartilage link protein stabilized aggregates with HA. These aggregates contribute to the tissue's load bearing properties. Aggrecan has a wide distribution in connective tissue and extracellular matrices. 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 114145511  58 LEWSFVQPGKPISasvpVLYFTNGHLYPTGSKADRAILLHDPPTGGLATLKLTDLRPSDTGTYLCNV 124
Cdd:cd05900   41 IKWSFISKEKESV----LLVATEGKVRVNTEYLDRVSLPNYPAIPSDATLEITELRSNDSGTYRCEV 103

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 114145511  58 LEWSFVQPGKPISASVPVLYFTNGHLYPTGSKADRAILLHDPPTGGLATLKLTDLRPSDTGTYLCNV 124
Cdd:cd05878   39 IKWSKVSVDGKKEKEVVLLVATEGRVRVNSAYQGRVSLPNYPAIPSDATLEVQSLRASDSGLYRCEV 105

Sixth 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 sixth 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 114145511 145 PPS-HPLCSQSGQTSVGGSAALGCRSSEGAPKPVYNWERLGSSPTPPPGSMVQ--DEVSGQLILTNLSLTSSGTYRCVAS 221
Cdd:cd20959    1 PPRiIPFAFGEGAAQVGMRAQLHCGVPGGDLPLNIRWTLDGQPISDDLGITVSrlGRRSSILSIDSLEASHAGNYTCHAR 80

                         90
                 ....*....|....
gi 114145511 222 NQMGSASCELNLSV 235
Cdd:cd20959   81 NSAGSASYTAPLTV 94

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
                 ....*....|....*....|...
gi 114145511 105 ATLKLTDLRPSDTGTYLCNVNNP 127
Cdd:cd00096   39 GTLTISNVTLEDSGTYTCVASNS 61