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 328927055 142 PVCRVPKAVPVGKMATLHCQESEGHPRPHYSWYRNDVPLPTDSRANPRFRNSSFHLNSETGTLVFTAVHKDDSGQYYCIA 221
Cdd:cd20950    1 PTVNIPSSATIGNRAVLTCSEPDGSPPSEYTWFKDGVVMPTNPKSTRAFSNSSYSLDPTTGELVFDPLSASDTGEYSCEA 80

                         90
                 ....*....|....*..
gi 328927055 222 SNDAGSA-RCEEQEMEV 237
Cdd:cd20950   81 RNGYGTPmRSNAVRMEA 97

Second Ig-like domain of Junctional adhesion molecule-1 (JAM1); a member of the I-set of IgSF domains; The members here are composed of the second Ig-like domain of Junctional adhesion molecule-1 (JAM1). JAM1 is an immunoglobulin superfamily (IgSF) protein with two Ig-like domains in its extracellular region; it plays a role in the formation of endothelial and epithelial tight junction and acts as a receptor for mammalian reovirus sigma-1. The IgSF is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The second Ig-like domain of JAM1 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, the A strand of the I-set is discontinuous but lacks a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 328927055 142 PVCRVPKAVPVGKMATLHCQESEGHPRPHYSWYRNDVPLPTDSRANPRFRNSSFHLNSETGTLVFTAVHKDDSGQYYCIA 221
Cdd:cd20950    1 PTVNIPSSATIGNRAVLTCSEPDGSPPSEYTWFKDGVVMPTNPKSTRAFSNSSYSLDPTTGELVFDPLSASDTGEYSCEA 80

                         90
                 ....*....|....*..
gi 328927055 222 SNDAGSA-RCEEQEMEV 237
Cdd:cd20950   81 RNGYGTPmRSNAVRMEA 97

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 328927055   150 VPVGKMATLHCqESEGHPRPHYSWYRND-VPLPTDSRANPRFRNSSFhlnsetgTLVFTAVHKDDSGQYYCIASNDAGSA 228
Cdd:smart00410   6 VKEGESVTLSC-EASGSPPPEVTWYKQGgKLLAESGRFSVSRSGSTS-------TLTISNVTPEDSGTYTCAATNSSGSA 77

                   ...
gi 328927055   229 RCE 231
Cdd:smart00410  78 SSG 80

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 328927055   37 SNRTPVVQEFESVELSCIITDSQTSD-PRIEW-KKIQDEQTTYVFF-------DNKIQGDLAGRAEI-LGKTSLKIWNVT 106
Cdd:pfam07686   2 TPREVTVALGGSVTLPCTYSSSMSEAsTSVYWyRQPPGKGPTFLIAyysngseEGVKKGRFSGRGDPsNGDGSLTIQNLT 81

                          90       100
                  ....*....|....*....|....*....
gi 328927055  107 RRDSALYRCEVVARNDRKEIDEivIELTV 135
Cdd:pfam07686  82 LSDSGTYTCAVIPSGEGVFGKG--TRLTV 108

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 328927055 142 PVCRVPKAVPVGKMATLHCQESEGHPRPHYSWYRNDVPLPTDSRANPRFRNSSFHLNSETGTLVFTAVHKDDSGQYYCIA 221
Cdd:cd20950    1 PTVNIPSSATIGNRAVLTCSEPDGSPPSEYTWFKDGVVMPTNPKSTRAFSNSSYSLDPTTGELVFDPLSASDTGEYSCEA 80

                         90
                 ....*....|....*..
gi 328927055 222 SNDAGSA-RCEEQEMEV 237
Cdd:cd20950   81 RNGYGTPmRSNAVRMEA 97

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 328927055 156 ATLHCqESEGHPRPHYSWYRNDVPLPTDSRANPRFRNSSfhlnsetGTLVFTAVHKDDSGQYYCIASNDAGSAR 229
Cdd:cd00096    1 VTLTC-SASGNPPPTITWYKNGKPLPPSSRDSRRSELGN-------GTLTISNVTLEDSGTYTCVASNSAGGSA 66

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 328927055   150 VPVGKMATLHCqESEGHPRPHYSWYRND-VPLPTDSRANPRFRNSSFhlnsetgTLVFTAVHKDDSGQYYCIASNDAGSA 228
Cdd:smart00410   6 VKEGESVTLSC-EASGSPPPEVTWYKQGgKLLAESGRFSVSRSGSTS-------TLTISNVTPEDSGTYTCAATNSSGSA 77

                   ...
gi 328927055   229 RCE 231
Cdd:smart00410  78 SSG 80

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (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 Ig I1 domain of the titin I-band 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, 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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 328927055 147 PKAVPVGKMATLHCqESEGHPRPHYSWYRNDVPLptDSRANPRfrNSSFHLNSETGTLVFTAVHKDDSGQYYCIASNDAG 226
Cdd:cd20951    9 SHTVWEKSDAKLRV-EVQGKPDPEVKWYKNGVPI--DPSSIPG--KYKIESEYGVHVLHIRRVTVEDSAVYSAVAKNIHG 83

                 ....
gi 328927055 227 SARC 230
Cdd:cd20951   84 EASS 87

Second immunoglobulin (Ig)-like domain of protein tyrosine kinase (PTK) 7; The members here are composed of the second immunoglobulin (Ig)-like domain in protein tyrosine kinase (PTK) 7, also known as CCK4. PTK7 is a subfamily of the receptor protein tyrosine kinase family, and is referred to as an RPTK-like molecule. RPTKs transduce extracellular signals across the cell membrane and play important roles in regulating cell proliferation, migration, and differentiation. PTK7 is organized as an extracellular portion having seven Ig-like domains, a single transmembrane region, and a cytoplasmic tyrosine kinase-like domain. PTK7 is considered a pseudokinase as it has several unusual residues in some of the highly conserved tyrosine kinase (TK) motifs; it is predicted to lack TK activity. PTK7 may function as a cell-adhesion molecule. PTK7 mRNA is expressed at high levels in placenta, melanocytes, liver, lung, pancreas, and kidney. PTK7 is overexpressed in several cancers, including melanoma and colon cancer lines.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 328927055 157 TLHCQeSEGHPRPHYSWYRNDVPLPtDSRANprfrnssFHLNSETGTLVFTAVHKDDSGQYYCIASNDAGSArCEEQ 233
Cdd:cd05760   20 TLRCH-IDGHPRPTYQWFRDGTPLS-DGQGN-------YSVSSKERTLTLRSAGPDDSGLYYCCAHNAFGSV-CSSQ 86

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 328927055 150 VPVGKMATLHCQeSEGHPRPHYSWYRNDVPLPTDsraNPRFRNSsfhlnsETGTLVFTAVHKDDSGQYYCIASNDAGSA 228
Cdd:cd20952   11 VAVGGTVVLNCQ-ATGEPVPTISWLKDGVPLLGK---DERITTL------ENGSLQIKGAEKSDTGEYTCVALNLSGEA 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 328927055 160 CQESeGHPRPHYSWYRNDVPLPTDSRanprfrnssfhLNSETGTLVFTAVHKDDSGQYYCIASNDAGS 227
Cdd:cd05728   21 CKAS-GNPRPAYRWLKNGQPLASENR-----------IEVEAGDLRITKLSLSDSGMYQCVAENKHGT 76

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 328927055 146 VPKAVPVGKMATLHCQeSEGHPRPHYSWYRNDVPLP---TDSRANPRFRnssFHLNsetGTLVFTAVHKDDSGQYYCIAS 222
Cdd:cd20954    9 VDANVAAGQDVMLHCQ-ADGFPTPTVTWKKATGSTPgeyKDLLYDPNVR---ILPN---GTLVFGHVQKENEGHYLCEAK 81

                 ....*
gi 328927055 223 NDAGS 227
Cdd:cd20954   82 NGIGS 86

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 328927055    42 VVQEFESVELSCIItdSQTSDPRIEWKKiqdEQTTYVFFDNKIQGDLAGraeilGKTSLKIWNVTRRDSALYRCevVARN 121
Cdd:smart00410   5 TVKEGESVTLSCEA--SGSPPPEVTWYK---QGGKLLAESGRFSVSRSG-----STSTLTISNVTPEDSGTYTC--AATN 72

                           90
                   ....*....|....
gi 328927055   122 DRKEIDEIViELTV 135
Cdd:smart00410  73 SSGSASSGT-TLTV 85

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 328927055 153 GKMATLHCqESEGHPRPHYSWYRNDVPLPTDSRanprfrnssfHLNSETGTLVFTAVHKDDSGQYYCIASNDAGSARCEE 232
Cdd:cd05745    2 GQTVDFLC-EAQGYPQPVIAWTKGGSQLSVDRR----------HLVLSSGTLRISRVALHDQGQYECQAVNIVGSQRTVA 70

                 .
gi 328927055 233 Q 233
Cdd:cd05745   71 Q 71

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 328927055  150 VPVGKMATLHCQESEGHPRPHYSWYRNDVPLPTDSRANPRFRNSSfhlnseTGTLVFTAVHKDDSGQYYCIASN 223
Cdd:pfam00047   8 VLEGDSATLTCSASTGSPGPDVTWSKEGGTLIESLKVKHDNGRTT------QSSLLISNVTKEDAGTYTCVVNN 75

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 328927055 152 VGKMATLHCQESEGHPRPHYSWYRNDVPLPTDSRANPRfrnssfHLNSETGTLVFTAVHKDDSGQYYCIASNDAGSA 228
Cdd:cd20959   16 VGMRAQLHCGVPGGDLPLNIRWTLDGQPISDDLGITVS------RLGRRSSILSIDSLEASHAGNYTCHARNSAGSA 86

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 328927055 163 SEGHPRPHYSWYRNDVPLPTDsranpRFRNSSFHlnsetGTLVFTAVHKDDSGQYYCIASNDAGSAR 229
Cdd:cd05731   19 AEGLPTPDIRWIKLGGELPKG-----RTKFENFN-----KTLKIENVSEADSGEYQCTASNTMGSAR 75

Second immunoglobulin (Ig)-like domain of a Follistatin-related protein 5, and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in human Follistatin-related protein 5 (FSTL5) and a follistatin-like molecule encoded by the CNS-related Mahya gene. Mahya genes have been retained in certain Bilaterian branches during evolution. They are conserved in Hymenoptera and Deuterostomes, but are absent from other metazoan species such as fruit fly and nematode. Mahya proteins are secretory, with a follistatin-like domain (Kazal-type serine/threonine protease inhibitor domain and EF-hand calcium-binding domain), two Ig-like domains, and a novel C-terminal domain. Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Follistatin is a secreted, multidomain protein that binds activins with high affinity and antagonizes their signaling.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 328927055 142 PVCRV---PKAVPVGKMATLHCQeSEGHPRPHYSWYRNDVPLPTDsranprfRNSSFHLNSETGTLVFTAVHKDDSGQYY 218
Cdd:cd05736    1 PVIRVypeFQAKEPGVEASLRCH-AEGIPLPRVQWLKNGMDINPK-------LSKQLTLIANGSELHISNVRYEDTGAYT 72

                 ....*...
gi 328927055 219 CIASNDAG 226
Cdd:cd05736   73 CIAKNEGG 80

Immunoglobulin variable domain (IgV); The members here are composed of the immunoglobulin variable domain (IgV). The IgV family contains the standard Ig superfamily V-set AGFCC'C"/DEB domain topology, and are components of immunoglobulin (Ig) and T cell receptors. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. In Ig, each chain is composed of one variable domain (IgV) and one or more constant domains (IgC); these names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. Within the variable domain, there are regions of even more variability called the hypervariable or complementarity-determining regions (CDRs) which are responsible for antigen binding. A predominant feature of most Ig domains is the disulfide bridge connecting 2 beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E and, D strands in one sheet and A', G, F, C, C', and C" strands in the other.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 328927055 150 VPVGKMATLHCQESEGHPRPHYSWYR-------------NDVPLPTDSRANPRFRnSSFHLNSeTGTLVFTAVHKDDSGQ 216
Cdd:cd00099   10 VQEGESVTLSCEVSSSFSSTYIYWYRqkpgqgpefliylSSSKGKTKGGVPGRFS-GSRDGTS-SFSLTISNLQPEDSGT 87

                 ....*.
gi 328927055 217 YYCIAS 222
Cdd:cd00099   88 YYCAVS 93

Second immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain found in the receptor protein tyrosine phosphatase (RPTP)-F, also known as LAR. LAR belongs to the RPTP type IIa subfamily. Members of this subfamily are cell adhesion molecule-like proteins involved in central nervous system (CNS) development. They have large extracellular portions comprised of multiple Ig-like domains and two to nine fibronectin type III (FNIII) domains and a cytoplasmic portion having two tandem phosphatase domains.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 328927055 148 KAVPVGKMATLHCQESeGHPRPHYSWYRNDVPLPTDSrANPRFRNSsfhlnsETGTLVFTAVHKDDSGQYYCIASNDAGS 227
Cdd:cd05738    9 KVVEKARTATMLCAAS-GNPDPEISWFKDFLPVDTAT-SNGRIKQL------RSGALQIENSEESDQGKYECVATNSAGT 80

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 328927055 153 GKMATLHCqESEGHPRPHYSWYRNDVPL---PTDSRanprfrnssfhLNSETGTLVFTAVHKDDSGQYYCIASNDAG 226
Cdd:cd04978   14 GETGELIC-EAEGNPQPTITWRLNGVPIepaPEDMR-----------RTVDGRTLIFSNLQPNDTAVYQCNASNVHG 78

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 328927055 152 VGKMATLHCqESEGHPRPHYSWYRNDVPLPTDsranprfrNSSFHLNSETGTLVFTAVHKDDSGQYYCIASNDAGsarce 231
Cdd:cd05730   17 LGQSVTLAC-DADGFPEPTMTWTKDGEPIESG--------EEKYSFNEDGSEMTILDVDKLDEAEYTCIAENKAG----- 82

                 ....*.
gi 328927055 232 EQEMEV 237
Cdd:cd05730   83 EQEAEI 88

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. 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. The Ig-like domain of the Twitchin is a member of the I-set 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. 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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 328927055 150 VPVGKMATLHCqESEGHPRPHYSWYRNDVPLPTDSRANPRFRNSSFhlnsetgTLVFTAVHKDDSGQYYCIASNDAGSAR 229
Cdd:cd20949   11 VKEGQSATILC-EVKGEPQPNVTWHFNGQPISASVADMSKYRILAD-------GLLINKVTQDDTGEYTCRAYQVNSIAS 82

                 ....*...
gi 328927055 230 cEEQEMEV 237
Cdd:cd20949   83 -DMQERTV 89

Immunoglobulin-like domain of human nephrin and similar proteins; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin-like domain in human nephrin and similar proteins. Nephrin is an integral component of the slit diaphragm and is a central component of the glomerular ultrafilter. Nephrin plays a structural role and has a role in signaling. Nephrin is a transmembrane protein having a short intracellular portion, an extracellular portion comprised of eight Ig-like domains, and one fibronectin type III-like domain. The extracellular portions of nephrin from neighboring foot processes of separate podocyte cells may interact with each other, and in association with other components of the slit diaphragm form a porous molecular sieve within the slit pore. The intracellular portion of nephrin is associated with linker proteins, which connect nephrin to the actin cytoskeleton. The intracellular portion is tyrosine phosphorylated, and mediates signaling from the slit diaphragm into the podocytes.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 328927055 136 QVKPVTPVCRVPKAVPVGKMATLHCQeSEGHPRPHYSWYRNDVPLptdSRANPRFRNSSFH-LNSETGTLVFTAVHK-DD 213
Cdd:cd05773    6 DLQKGPQLRKVASRGDGSSDANLVCQ-AQGVPRVQFRWAKNGVPL---DLGNPRYEETTEHtGTVHTSILTIINVSAaLD 81

                         90
                 ....*....|....
gi 328927055 214 SGQYYCIASNDAGS 227
Cdd:cd05773   82 YALFTCTAHNSLGE 95

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 328927055 150 VPVGKMATLHCQESEGHPRPHYSWYRNDVPLPTDSRANPRFRNSSfhLNSEtgtLVFTAVHKDDSGQYYCIASNDAGSA 228
Cdd:cd05750   11 VQEGSKLVLKCEATSENPSPRYRWFKDGKELNRKRPKNIKIRNKK--KNSE---LQINKAKLEDSGEYTCVVENILGKD 84

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        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 328927055  47 ESVELSciITDSQTSDPRIEWKKIQDEQTTYVFFDN-KIQGDLAGRAEILGKT-SLKIWNVTRRDSALYRCEVVarNDRK 124
Cdd:cd05775   11 GNVTLT--ISSLQDDIDEIKWKKTKDKIVEWENNIGpTYFGSFKDRVLLDKESgSLTIKNLTKEDSGTYELEIT--STNG 86

                         90
                 ....*....|..
gi 328927055 125 EIDEIVIELTVQ 136
Cdd:cd05775   87 KVLSSKFTLEVL 98

Fifth 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 fifth 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 328927055 153 GKMATLHCQESeGHPRPHYSWYRNDVPLPTDSRanprfrnssfHLNSETGTLVFTAVHKD-DSGQYYCIASNDAG-SAR 229
Cdd:cd20958   15 GQTLRLHCPVA-GYPISSITWEKDGRRLPLNHR----------QRVFPNGTLVIENVQRSsDEGEYTCTARNQQGqSAS 82

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 328927055 165 GHPRPHYSWYRNDVPLPTDSRANprfrnssFHLNSETGTLVFTAVHKDDSGQYYCIASNDAGSA 228
Cdd:cd05748   18 GRPTPTVTWSKDGQPLKETGRVQ-------IETTASSTSLVIKNAKRSDSGKYTLTLKNSAGEK 74

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. 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 328927055 150 VPVGKMATLHCQESeGHPRPHYSWYRNDVPLPTDSRANPRFRNSSFHlnsetgTLVFTAVHKDDSGQYYCIASNDAG 226
Cdd:cd20990   12 VQEGKLCRMDCKVS-GLPTPDLSWQLDGKPIRPDSAHKMLVRENGVH------SLIIEPVTSRDAGIYTCIATNRAG 81

Fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-related cell adhesion molecule); The members here are composed of the fourth immunoglobulin (Ig)-like domain of NrCAM (NgCAM-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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 328927055 153 GKMATLHCQESeGHPRPHYSWYRNDVPL---PTD-SRanprfrnssfhlNSETGTLVFTAVHKDDSGQYYCIASNDAG 226
Cdd:cd05868   14 GEDGTLICRAN-GNPKPSISWLTNGVPIeiaPTDpSR------------KVDGDTIIFSKVQERSSAVYQCNASNEYG 78