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 1622898096  19 KKIPVEEGLCTTIPCAFEFPKELPSNSMIMGYWL----NKNVSSLVATNKPNATVGDNTKDRFSMTGNLDEEDCTLLIHD 94
Cdd:cd05712     7 KSVTVQEGLCVLIPCSFSYPADYWVSNPVHGYWYrggpYPKYRPPVATNNRTREVHESTQGRFRLLGDPGKKNCSLSISD 86

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1622898096  95 ILKGNSATYLFYADLGeqksaflGENIKLFVSDLT 129
Cdd:cd05712    87 ARPEDSGKYFFRVERG-------DSNKYSYLSNQL 114

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622898096 580 PPTIT-DVTSARTALGRAALLRCEAMAVPPADFQWYKDDRLLSSGTAegLKVQTERTRSMLLFANVSARHYGNYTCRAAN 658
Cdd:pfam13927   1 KPVITvSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGST--RSRSLSGSNSTLTISNVTRSDAGTYTCVASN 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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622898096 132 PELHIPEILLAEKPVTLNCTLKGTCKEIKALFrSWKNPAISSSSSSVP--------------HFILRPEDHGNTLGCHLN 197
Cdd:cd20987     1 PNIHVPEELEAGQEVTLTCSVPDNCPALSPEF-SWLGAALTPLPPVLGrleeegttthssvlTFTPRPEDHGTNLTCQVK 79

                          90
                  ....*....|....
gi 1622898096 198 FSLANVTRSSLVKL 211
Cdd:cd20987    80 FPGATVTTERTIQL 93

Immunoglobulin Variable (IgV) domain at the N-terminus of CD33 and related Siglecs (sialic acid-binding Ig-like lectins); The members here are composed of the immunoglobulin (Ig) domain at the N-terminus of Cluster of Differentiation (CD) 33 and related Siglecs (sialic acid-binding Ig-like lectins). Siglec refers to a structurally related protein family that specifically recognizes sialic acid in oligosaccharide chains of glycoproteins and glycolipids. Siglecs are type I transmembrane proteins, organized as an extracellular module composed of Ig-like domains, an N-terminal variable set of Ig-like carbohydrate recognition domains, and 1 to 16 constant Ig-like domains, followed by transmembrane and short cytoplasmic domains. Human Siglecs are classified into two subgroups, one subgroup is comprised of sialoadhesin (Siglec-1), CD22 (Siglec-2), and MAG, the other subgroup is comprised of CD33-related Siglecs which include CD33 (Siglec-3) and human Siglecs 5-11.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622898096  19 KKIPVEEGLCTTIPCAFEFPKELPSNSMIMGYWL----NKNVSSLVATNKPNATVGDNTKDRFSMTGNLDEEDCTLLIHD 94
Cdd:cd05712     7 KSVTVQEGLCVLIPCSFSYPADYWVSNPVHGYWYrggpYPKYRPPVATNNRTREVHESTQGRFRLLGDPGKKNCSLSISD 86

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1622898096  95 ILKGNSATYLFYADLGeqksaflGENIKLFVSDLT 129
Cdd:cd05712    87 ARPEDSGKYFFRVERG-------DSNKYSYLSNQL 114

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622898096 580 PPTIT-DVTSARTALGRAALLRCEAMAVPPADFQWYKDDRLLSSGTAegLKVQTERTRSMLLFANVSARHYGNYTCRAAN 658
Cdd:pfam13927   1 KPVITvSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGST--RSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

Second immunoglobulin domain of Cluster of Differentiation (CD) 33 and related Siglecs; member of the C2-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig) domain of Cluster of Differentiation (CD) 33 (also known as sialic-acid binding immunoglobulin type-lectin 3 (Siglec-3)) and related Siglecs. CD33, a Siglec family member, is a well-known immunotherapeutic target in acute myeloid leukemia (AML). It is an inhibitory sialoadhesin expressed in human leukocytes of the myeloid lineage and some lymphoid subsets, including natural killer (NK) cells. Siglecs are primarily expressed on immune cells and recognize sialic acid-containing glycan ligands. Siglecs are organized as an extracellular module composed of Ig-like domains (an N-terminal variable set of Ig-like carbohydrate recognition domains, and 1 to 16 constant Ig-like domains), followed by transmembrane and short cytoplasmic domains. Human Siglecs are classified into two subgroups, one subgroup is comprised of sialoadhesin (Siglec-1), CD22 (Siglec-2), and MAG (Siglec-4, myelin-associated glycoprotein), the other subgroup is comprised of CD33-related Siglecs which include CD33 (Siglec-3) and human Siglecs 5-11. CD33 (Siglec-3) is the smallest Siglec member. It preferentially binds to alpha2-6- and alpha2-3-sialylated glycans and strongly binds to sialylated ligands on leukemic cell lines. 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. This group includes CD33-related Siglecs which belong to the C2-set of IgSF domains. Unlike the C1-set, the C2-set structures do not have a D strand.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622898096 132 PELHIPEILLAEKPVTLNCTLKGTCKEIKALFrSWKNPAISSSSSSVP--------------HFILRPEDHGNTLGCHLN 197
Cdd:cd20987     1 PNIHVPEELEAGQEVTLTCSVPDNCPALSPEF-SWLGAALTPLPPVLGrleeegttthssvlTFTPRPEDHGTNLTCQVK 79

                          90
                  ....*....|....
gi 1622898096 198 FSLANVTRSSLVKL 211
Cdd:cd20987    80 FPGATVTTERTIQL 93

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 1622898096 581 PTITDVTSARTALGRAALLRCEAMAVPPA-DFQWYKDDRLLSSGTAEGLKVQTERTRSMLLFANVSARHYGNYTCRAANR 659
Cdd:cd05750     1 PKLKEMKSQTVQEGSKLVLKCEATSENPSpRYRWFKDGKELNRKRPKNIKIRNKKKNSELQINKAKLEDSGEYTCVVENI 80

                          90
                  ....*....|
gi 1622898096 660 LGASSASMRL 669
Cdd:cd05750    81 LGKDTVTGNV 90

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1622898096  593 LGRAALLRCEAMAVPPADFQWYKDD-RLLSSGtaEGLKVQTERTRSMLLFANVSARHYGNYTCRAANRLGASSASMRL 669
Cdd:smart00410   8 EGESVTLSCEASGSPPPEVTWYKQGgKLLAES--GRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGTTL 83

Fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM); The members here are composed of the fourth immunoglobulin (Ig)-like domain of the L1 cell adhesion molecule (CAM). L1 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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1622898096 228 KTVLCSCSFHGIPTPSVQWWMGGVPVDVNSMDNIPRVTSSTRVpwansTINLigEPEIVMRLRCEGKNQYG 298
Cdd:cd05867    15 ETARLDCQVEGIPTPNITWSINGAPIEGTDPDPRRHVSSGALI-----LTDV--QPSDTAVYQCEARNRHG 78

Immunoglobulin Variable (IgV) domain at the N-terminus of CD33 and related Siglecs (sialic acid-binding Ig-like lectins); The members here are composed of the immunoglobulin (Ig) domain at the N-terminus of Cluster of Differentiation (CD) 33 and related Siglecs (sialic acid-binding Ig-like lectins). Siglec refers to a structurally related protein family that specifically recognizes sialic acid in oligosaccharide chains of glycoproteins and glycolipids. Siglecs are type I transmembrane proteins, organized as an extracellular module composed of Ig-like domains, an N-terminal variable set of Ig-like carbohydrate recognition domains, and 1 to 16 constant Ig-like domains, followed by transmembrane and short cytoplasmic domains. Human Siglecs are classified into two subgroups, one subgroup is comprised of sialoadhesin (Siglec-1), CD22 (Siglec-2), and MAG, the other subgroup is comprised of CD33-related Siglecs which include CD33 (Siglec-3) and human Siglecs 5-11.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622898096  19 KKIPVEEGLCTTIPCAFEFPKELPSNSMIMGYWL----NKNVSSLVATNKPNATVGDNTKDRFSMTGNLDEEDCTLLIHD 94
Cdd:cd05712     7 KSVTVQEGLCVLIPCSFSYPADYWVSNPVHGYWYrggpYPKYRPPVATNNRTREVHESTQGRFRLLGDPGKKNCSLSISD 86

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1622898096  95 ILKGNSATYLFYADLGeqksaflGENIKLFVSDLT 129
Cdd:cd05712    87 ARPEDSGKYFFRVERG-------DSNKYSYLSNQL 114

Immunoglobulin domain; This family contains immunoglobulin-like domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622898096 580 PPTIT-DVTSARTALGRAALLRCEAMAVPPADFQWYKDDRLLSSGTAegLKVQTERTRSMLLFANVSARHYGNYTCRAAN 658
Cdd:pfam13927   1 KPVITvSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGST--RSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

First (N-terminal) immunoglobulin (Ig)-like domain of nectin-like molecule-3; member of the V-set of Ig superfamily (IgSF) domains; The members here are composed of the N-terminal immunoglobulin (Ig)-like domain of nectin-like molecule-3, Necl-3 (also known as cell adhesion molecule 2 (CADM2), SynCAM2, IGSF4D). Nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 - Necl-5). They all have an extracellular region containing three Ig-like domains, a transmembrane region, and a cytoplasmic region. The N-terminal Ig-like domain of the extracellular region, belongs to the V-type subfamily of Ig domains, is essential to cell-cell adhesion, and plays a part in the interaction with the envelope glycoprotein D of various viruses. Necl-3 accumulates in central and peripheral nervous system tissue, and has been shown to selectively interact with oligodendrocytes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622898096 404 NYTVCEGDNATLSCFIDEH-VTRVAWLNRSN-ILYAGNDRWTSDPRVRLLINTPEEFSILITEVGLGDEGLYTCSFQTrh 481
Cdd:cd07701     6 NVTVVEGGTANLTCRVDQNdNTSLQWSNPAQqTLYFDDKKALRDNRIELVRASWHELSISISDVSLSDEGQYTCSLFT-- 83

                          90
                  ....*....|..
gi 1622898096 482 QPY-TTQVYLIV 492
Cdd:cd07701    84 MPVkTSKAYLTV 95

First (N-terminal) immunoglobulin (Ig)-like domain of nectin-like molecule-1 (Necl-1); member of the V-set of Ig superfamily (IgSF) domains; The members here are composed of the N-terminal immunoglobulin (Ig)-like domain of nectin-like molecule-1, Necl-1 (also known as celll adhesion molecule 3 (CADM3), SynCAM2, or IGSF4). Nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 - Necl-5). They all have an extracellular region containing three Ig-like domains, a transmembrane region, and a cytoplasmic region. The N-terminal Ig-like domain of the extracellular region belongs to the V-type subfamily of Ig domains, is essential to cell-cell adhesion, and plays a part in the interaction with the envelope glycoprotein D of various viruses. Necl-1 has Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is specifically expressed in neural tissue and is important to the formation of synapses, axon bundles, and myelinated axons.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1622898096 406 TVCEGDNATLSCFIDEHV-TRVAWLNRSN-ILYAGNDRWTSDPRVRLLINTPEEFSILITEVGLGDEGLYTCSFQT 479
Cdd:cd05882     8 TVAVGGTVTLKCGVKEHDnSSLQWSNTAQqTLYFGEKRALRDNRIQLVKSTPTELIISISNVQLSDEGEYTCSIFT 83

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622898096  502 SSPVTVNEGGSVNLLCLAVGRPEPTVTWRQ-------LRDGFTSEGE----ILEISDIQRGQAGEYECVTHNGVNSApdS 570
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYKqggkllaESGRFSVSRSgstsTLTISNVTPEDSGTYTCAATNSSGSA--S 78

                   ....*..
gi 1622898096  571 RRVLVTV 577
Cdd:smart00410  79 SGTTLTV 85

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622898096 506 TVNEGGSVNLLCLAVGRPEPTVTWrqLRDGF--------------TSEGEI---LEISDIQRGQAGEYECVTHNGVNSAP 568
Cdd:cd20956    12 TLQPGPSVSLKCVASGNPLPQITW--TLDGFpipesprfrvgdyvTSDGDVvsyVNISSVRVEDGGEYTCTATNDVGSVS 89

                  ....*..
gi 1622898096 569 DSRRVLV 575
Cdd:cd20956    90 HSARINV 96

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 1622898096 597 ALLRCEAMAVPPADFQWYKDDRLLSSGTAEglKVQTERTRSMLLFANVSARHYGNYTCRAANRLGASSAS 666
Cdd:cd00096     1 VTLTCSASGNPPPTITWYKNGKPLPPSSRD--SRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASA 68

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1622898096 495 PARIVNISSPVTVNEGGSVNLLCLAVGRPEPTVTWRQLrDG-------FTSEGEILEISDIQRGQAGEYECVTHN 562
Cdd:cd04968     1 PSIKVRFPADTYALKGQTVTLECFALGNPVPQIKWRKV-DGspssqweITTSEPVLEIPNVQFEDEGTYECEAEN 74

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622898096 505 VTVNEGGSVNLLCLAVGRPEPTVTWrqLRDGFTSEGE----------ILEISDIQRGQAGEYECVTHNGVNSApdSRRVL 574
Cdd:cd20952     9 QTVAVGGTVVLNCQATGEPVPTISW--LKDGVPLLGKderittlengSLQIKGAEKSDTGEYTCVALNLSGEA--TWSAV 84

                  ...
gi 1622898096 575 VTV 577
Cdd:cd20952    85 LDV 87

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1622898096  593 LGRAALLRCEAMAVPPADFQWYKDD-RLLSSGtaEGLKVQTERTRSMLLFANVSARHYGNYTCRAANRLGASSASMRL 669
Cdd:smart00410   8 EGESVTLSCEASGSPPPEVTWYKQGgKLLAES--GRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGTTL 83

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 1622898096 593 LGRAALLRCEA-MAVPPADFQWYKDDRLLSSGTaEGLKVQTERTRSMLLFANVSARHYGNYTCRAANRLGASSASMRL 669
Cdd:pfam00047  10 EGDSATLTCSAsTGSPGPDVTWSKEGGTLIESL-KVKHDNGRTTQSSLLISNVTKEDAGTYTCVVNNPGGSATLSTSL 86

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622898096 502 SSPVTVNEGGSVNLLCLAVGRPEPTVTWRQL-------RDGFTSEGEILEISDIQRGQAGEYECVTHNGVNSAPDSRRVL 574
Cdd:cd05876     2 SSSLVALRGQSLVLECIAEGLPTPTVKWLRPsgplppdRVKYQNHNKTLQLLNVGESDDGEYVCLAENSLGSARHAYYVT 81

                  .
gi 1622898096 575 V 575
Cdd:cd05876    82 V 82

Immunoglobulin domain; This domain contains immunoglobulin-like domains.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622898096 497 RIVNISSPVTVNEGGSVNLLCLAVGRPEPTVTWRqlRDG-FTSEGEILEISDIQRGQAGEYECVTHNGVNSaPDSRRVLV 575
Cdd:pfam13895   1 KPVLTPSPTVVTEGEPVTLTCSAPGNPPPSYTWY--KDGsAISSSPNFFTLSVSAEDSGTYTCVARNGRGG-KVSNPVEL 77

                  ..
gi 1622898096 576 TV 577
Cdd:pfam13895  78 TV 79

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; 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 and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622898096 494 VPARIVNISSPVTVNEGGSVNLLCLAVGRPEPTVTWrqLRDG------------FTSEGEILEISDIQRGQAGEYECVTH 561
Cdd:cd05747     2 LPATILTKPRSLTVSEGESARFSCDVDGEPAPTVTW--MREGqiivssqrhqitSTEYKSTFEISKVQMSDEGNYTVVVE 79

                  .
gi 1622898096 562 N 562
Cdd:cd05747    80 N 80

Third immunoglobulin (Ig)-like domain of the receptor protein tyrosine phosphatase (RPTP)-F (also known as LAR), type IIa; member of the I-set of IgSF domains; The members here are composed of the third 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. Included in this group is Drosophila LAR (DLAR).

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1622898096 502 SSPVTVNE---GGSVNLLCLAVGRPEPTVTWRQLRDGFTSEGE------ILEISDIQrgQAGEYECV 559
Cdd:cd05739     1 SIPPSNHEvmpGGSVNLTCVAVGAPMPYVKWMKGGEELTKEDEmpvgrnVLELTNIY--ESANYTCV 65

First (N-terminal) immunoglobulin (Ig)-like domain of nectin-like molecule 2; member of the V-set of Ig superfamily (IgSF) domains; The members here are composed of the N-terminal immunoglobulin (Ig)-like domain of nectin-like molecule-2, Necl-2 (also known as cell adhesion molecule 1 (CADM1), SynCAM1, IGSF4A, Tslc1, sgIGSF, and RA175). Nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 - Necl-5). They all have an extracellular region containing three Ig-like domains, a transmembrane region, and a cytoplasmic region. The N-terminal Ig-like domain of the extracellular region, belongs to the V-type subfamily of Ig domains, is essential to cell-cell adhesion, and plays a part in the interaction with the envelope glycoprotein D of various viruses. Necl-2 has Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-2 is expressed in a wide variety of tissues and is a putative tumour suppressor gene, which is downregulated in aggressive neuroblastoma.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622898096 403 DNYTVCEGDNATLSCFI---DEHVTRVAWLNRSNIlYAGNDRWTSDPRVRLLINTPEEFSILITEVGLGDEGLYTCSFQT 479
Cdd:cd05881     4 EDVTVVEGEVATISCRVknsDDSVIQLLNPNRQTI-YFRDFRPLKDSRFQLVNFSSSELRVSLTNVSISDEGRYFCQLYT 82

                  ....*....
gi 1622898096 480 R--HQPYTT 486
Cdd:cd05881    83 DppQEAYTT 91

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1622898096 513 VNLLCLAVGRPEPTVTWR----------QLRDGFTSEGEILEISDIQRGQAGEYECVTHNGV 564
Cdd:cd00096     1 VTLTCSASGNPPPTITWYkngkplppssRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSA 62

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 2 (NCAM-2); The members here are composed of the fourth Ig domain of Neural Cell Adhesion Molecule NCAM-2 (also known as OCAM/mamFas II and RNCAM). NCAM-2 is organized similarly to NCAM, including five N-terminal Ig-like domains and two fibronectin type III domains. NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE), and may function like NCAM, as an adhesion molecule. One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1622898096 505 VTVNEGGSVNLLCLAVGRPEPTVTWRQLRDGFT-SEGE----------------ILEISDIQRGQAGEYEC 558
Cdd:cd05870    11 ETTVENGAATLSCKAEGEPIPEITWKRASDGHTfSEGDkspdgrievkgqhgesSLHIKDVKLSDSGRYDC 81

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622898096 581 PTITDVTSartalGRAALLRCEAMAVPPADFQWYKDDRLLSSGTAEGLKVQTerTRSMLLFANVSARHYGNYTCRAANRL 660
Cdd:cd20949     6 AYVTTVKE-----GQSATILCEVKGEPQPNVTWHFNGQPISASVADMSKYRI--LADGLLINKVTQDDTGEYTCRAYQVN 78

                  ....
gi 1622898096 661 GASS 664
Cdd:cd20949    79 SIAS 82

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622898096 505 VTVNEGGSVNLLCLAVGRPEPTVTWRQlrdgftSEGEI------------LEISDIQRGQAGEYECVTHNGVNSAPDSRR 572
Cdd:cd05725     7 QVVLVDDSAEFQCEVGGDPVPTVRWRK------EDGELpkgryeilddhsLKIRKVTAGDMGSYTCVAENMVGKIEASAT 80

                  ...
gi 1622898096 573 VLV 575
Cdd:cd05725    81 LTV 83

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 1622898096 593 LGRAALLRCEAMAVPPADFQWYKDDRLLSSGTAEglkvQTERTRSMLLFANVSARHYGNYTCRAANRLGASSAS 666
Cdd:cd05856    18 VGSSVRLKCVASGNPRPDITWLKDNKPLTPPEIG----ENKKKKWTLSLKNLKPEDSGKYTCHVSNRAGEINAT 87

Immunoglobulin (Ig)-like I-set domain of Neural Cell Adhesion Molecule 1 (NCAM-1) and similar proteins; The members here are composed of the fourth 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. Also included in this group is NCAM-2 (also known as OCAM/mamFas II and RNCAM) NCAM-2 is differentially expressed in the developing and mature olfactory epithelium (OE). One of the unique features of I-set domains is the lack of a C" strand. The structures of this group show that the Ig domain lacks this strand and thus is a member of the I-set of Ig domains.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622898096 581 PTITDVTSARTALGRAALLRCEAMAVPPADFQWYKDDRLLSS--GTAEGLKVQTERTR-SMLLFANVSARHYGNYTCRAA 657
Cdd:cd05732     3 PKITYLENQTAVELEQITLTCEAEGDPIPEITWRRATRGISFeeGDLDGRIVVRGHARvSSLTLKDVQLTDAGRYDCEAS 82

                          90
                  ....*....|..
gi 1622898096 658 NRLGASSASMRL 669
Cdd:cd05732    83 NRIGGDQQSMYL 94

Fourth immunoglobulin (Ig)-like domain of peroxidasin; The members here are composed of the fourth 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1622898096 513 VNLLCLAVGRPEPTVTWRqlRDGF---------TSEGEILEISDIQRGQAGEYECVTHNGVNSAPDS 570
Cdd:cd05746     1 VQIPCSAQGDPEPTITWN--KDGVqvtesgkfhISPEGYLAIRDVGVADQGRYECVARNTIGYASVS 65

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 1622898096 594 GRAALLRCEAMAVPPADFQWYKDDRLLSSGTAEGLKVQTERTRSmLLFANVSARHYGNYTCRAANRLGASSASMRLL 670
Cdd:cd20990    15 GKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSAHKMLVRENGVHS-LIIEPVTSRDAGIYTCIATNRAGQNSFNLELV 90