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 2319158864 138 LGIPQKPIITGYKSSLREKETATLNCQSSGSKPAAQLTWRKGDQELHGDQTRIQEDPNGKTFTVSSSVSFQVTREDDGAN 217
Cdd:cd07705     1 LGIPQKPQITGYESAFKEKDKAKLRCTSSGSKPAANIKWRKGDQELEGAPTSVQEDGNGKTFTVSSSVEFQVTREDDGAE 80

                          90       100
                  ....*....|....*....|...
gi 2319158864 218 IVCSVNHESLKGADRSTSQRIEV 240
Cdd:cd07705    81 ITCSVGHESLHDSDRSTSQRIEV 103

putative band 4.1 homologues' binding motif;

                           10
                   ....*....|....*.
gi 2319158864  365 YLIRHKGTYLTHEAKG 380
Cdd:smart00294   4 YKHRDEGSYHTHEPKG 19

Second immunoglobulin (Ig)-like domain of nectin-like molcule-1 (Necl-1); member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of nectin-like molcule-1 (Necl-1; also known as cell adhesion molecule3 (CADM3)). These nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one 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 and Necl-2 have 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. Necl-2 is expressed in a wide variety of tissues and is a putative tumour suppressor gene which is downregulated in aggressive neuroblastoma. Ig domains are likely to participate in ligand binding and recognition.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2319158864 138 LGIPQKPIITGYKSSLREKETATLNCQSSGSKPAAQLTWRKGDQELHGDQTRIQEDPNGKTFTVSSSVSFQVTREDDGAN 217
Cdd:cd07705     1 LGIPQKPQITGYESAFKEKDKAKLRCTSSGSKPAANIKWRKGDQELEGAPTSVQEDGNGKTFTVSSSVEFQVTREDDGAE 80

                          90       100
                  ....*....|....*....|...
gi 2319158864 218 IVCSVNHESLKGADRSTSQRIEV 240
Cdd:cd07705    81 ITCSVGHESLHDSDRSTSQRIEV 103

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2319158864   47 SDETVVAGGTVVLKCQVKDHEDSSLQWSNPAQQTLYFgekralrDNRIQlVSSTPHELSISISNVALADEGEYTC 121
Cdd:smart00410   2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAE-------SGRFS-VSRSGSTSTLTISNVTPEDSGTYTC 68

Immunoglobulin (Ig) constant domain of the complement receptor of the immunoglobulin superfamily (CRIg); The members here are composed of the Immunoglobulin (Ig) constant domain of the complement receptor of the immunoglobulin superfamily (CRIg). The N-terminal domain of CRIg (also referred to as Z39Ig and V-set and Ig domain-containing 4 (VSIG4)) belongs to the IgV family of immunoglobulin-like domains while the C-terminal domain of CRIg belongs to the IgC family of immunoglobulin-like domains. CRIg plays a role in the complement system, an inhibitor of the alternative pathway convertases, and a negative regulator of T cell activation. 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 such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins such as 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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2319158864 257 EGQKLLLHCEGRGNPvPQQYVWVKE--GSEPPLKMTQESALIFPFLNKSDSGTYGCTATSNMGS 318
Cdd:cd16082    12 QGMRISLQCQAWGSP-PISYVWYKEqtNNQEPIKVAALSTLLFKPAVVADSGSYFCTAKGRVGS 74

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2319158864  154 REKETATLNCQSSGSkPAAQLTWRKGDQELHGDQTRIQEDPNGKTF--TVSSsvsfqVTREDDGaNIVCSVN 223
Cdd:smart00410   7 KEGESVTLSCEASGS-PPPEVTWYKQGGKLLAESGRFSVSRSGSTStlTISN-----VTPEDSG-TYTCAAT 71

putative band 4.1 homologues' binding motif;

                           10
                   ....*....|....*.
gi 2319158864  365 YLIRHKGTYLTHEAKG 380
Cdd:smart00294   4 YKHRDEGSYHTHEPKG 19

Second immunoglobulin (Ig)-like domain of nectin-like molcule-1 (Necl-1); member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of nectin-like molcule-1 (Necl-1; also known as cell adhesion molecule3 (CADM3)). These nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one 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 and Necl-2 have 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. Necl-2 is expressed in a wide variety of tissues and is a putative tumour suppressor gene which is downregulated in aggressive neuroblastoma. Ig domains are likely to participate in ligand binding and recognition.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2319158864 138 LGIPQKPIITGYKSSLREKETATLNCQSSGSKPAAQLTWRKGDQELHGDQTRIQEDPNGKTFTVSSSVSFQVTREDDGAN 217
Cdd:cd07705     1 LGIPQKPQITGYESAFKEKDKAKLRCTSSGSKPAANIKWRKGDQELEGAPTSVQEDGNGKTFTVSSSVEFQVTREDDGAE 80

                          90       100
                  ....*....|....*....|...
gi 2319158864 218 IVCSVNHESLKGADRSTSQRIEV 240
Cdd:cd07705    81 ITCSVGHESLHDSDRSTSQRIEV 103

Second immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 - Necl-4; member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the nectin-like molecules Necl-1 (also known as cell adhesion molecule 3 or CADM3), Necl-2 (also known as CADM1), Necl-3 (also known as CADM2) and Necl-4 (also known as CADM4). These nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one 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 and Necl-2 have 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. Necl-2 is expressed in a wide variety of tissues, and is a putative tumour suppressor gene, which is downregulated in aggressive neuroblastoma. Necl-3 has been shown to accumulate in tissues of the central and peripheral nervous system, where it is expressed in ependymal cells and myelinated axons. It is observed at the interface between the axon shaft and the myelin sheath. Necl-4 is expressed on Schwann cells, and plays a key part in initiating peripheral nervous system (PNS) myelination. Necl-4 participates in cell-cell adhesion and is proposed to play a role in tumor suppression.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2319158864 138 LGIPQKPIITGYKSSLREKETATLNCQSSGSKPAAQLTWRKGDQELHGdQTRIQEDPNGKTFTVSSSVSFQVTREDDGAN 217
Cdd:cd05761     1 LGVPEKPVITGFTSPVVEGDEITLTCTTSGSKPAADIRWFKNDKELKG-VKEVQESGAGKTFTVTSTLRFRVDRDDDGVA 79

                          90       100
                  ....*....|....*....|...
gi 2319158864 218 IVCSVNHESLKGADRSTSQRIEV 240
Cdd:cd05761    80 VICRVDHESLTSTPKQTQQVLEV 102

Second immunoglobulin (Ig)-like domain of nectin-like molecule-3 (Necl-3); member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of nectin-like molecule-3 (Necl-3; also known as cell adhesion molecule 2 (CADM2)). Nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. Necl-3 has been shown to accumulate in tissues of the central and peripheral nervous system where it is expressed in ependymal cells and myelinated axons. It is observed at the interface between the axon shaft and the myelin sheath. Ig domains are likely to participate in ligand binding and recognition.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2319158864 137 VLGIPQKPIITGYKSSLREKETATLNCQSSGSKPAAQLTWRKGDQELHGDQTRIQEDPNGKTFTVSSSVSFQVTREDDGA 216
Cdd:cd05884     1 VLGVPEKPQISGFTSPVMEGDHIQLTCKTSGSKPAADIRWFKNDKEVKDVKYLKAEDANRKTFTVSSSLDFHVDRDDDGV 80

                          90       100
                  ....*....|....*....|....
gi 2319158864 217 NIVCSVNHESLKGADRSTSQRIEV 240
Cdd:cd05884    81 AITCRVDHESLTATPQIAMQVLEI 104

Second immunoglobulin (Ig)-like domain of nectin-like molecule 2 (Necl-2); member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of nectin-like molecule 2 (Necl-2; also known as cell adhesion molecule 1 (CADM1)). Nectin-like molecules (Necls) have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1 through Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. Necl-2 has Ca(2+)-independent homophilic and heterophilic cell-cell adhesion activity. Necl-1 is expressed in a wide variety of tissues and is a putative tumour suppressor gene which is downregulated in aggressive neuroblastoma. Ig domains are likely to participate in ligand binding and recognition.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2319158864 141 PQKPIITGYKSSLREKETATLNCQSSGSKPAAQLTWRKGDQELHGDQTriQEDPNGKTFTVSSSVSFQVTREDDGANIVC 220
Cdd:cd05883     4 PRNLVIDIQKDTAVEGEEIELNCTAMASKPAATIRWFKGNKELTGKSE--VEEWYSRMFTVTSQLMLKVTKEDDGVPVIC 81

                          90       100
                  ....*....|....*....|
gi 2319158864 221 SVNHESLKgaDRSTSQRIEV 240
Cdd:cd05883    82 LVDHPAVK--DLQTQRYLEV 99

Second immunoglobulin (Ig)-like domain of nectin-like molecule-4 (Necl-4); member of the I-set of Ig superfamily domains; The members here are composed of the second immunoglobulin (Ig)-like domain of nectin-like molecule-4 (Necl-4; also known as cell adhesion molecule 4 (CADM4)). Nectin-like molecules have similar domain structures to those of nectins. At least five nectin-like molecules have been identified (Necl-1-Necl-5). These have an extracellular region containing three Ig-like domains, one transmembrane region, and one cytoplasmic region. Ig domains are likely to participate in ligand binding and recognition. Necl-4 is expressed on Schwann cells, and plays a key part in initiating peripheral nervous system (PNS) myelination. In injured peripheral nerve cells, the mRNA signal for both Necl-4 and Necl-5 was observed to be elevated. Necl-4 participates in cell-cell adhesion and is proposed to play a role in tumor suppression.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2319158864 141 PQKPIITgYKSSLREKETATLNCQSSGSKPAAQLTWRKGDQELHGDQTRiQEdpNGKTFTVSSSVSFQVTREDDGANIVC 220
Cdd:cd05885     4 PENPVVE-VREQAVEGGEVELSCLVPRSRPAATLRWYRDRKELKGVSSG-QE--NGKVWSVASTVRFRVDRKDDGGIVIC 79

                          90
                  ....*....|....*.
gi 2319158864 221 SVNHESLKGADRSTSQ 236
Cdd:cd05885    80 EAQNQALPSGHSKQTQ 95

Immunoglobulin Constant-1 (C1)-set domain; The members here are composed of C1-set domains, classical Ig-like domains resembling the antibody constant domain. Members of the IgC1 family are components of immunoglobulin, T-cell receptors, CD1 cell surface glycoproteins, secretory glycoproteins A/C, and major histocompatibility complex (MHC) class I/II molecules. In immunoglobulins, each chain is composed of one variable domain (IgV) and one or more IgC domains. These names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. The IgV domain is responsible for antigen binding, while the IgC domain is involved in oligomerization and molecular interactions. 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 strands by G, F, C, and C'.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2319158864 146 ITGYKSSLREKETATLNCQSSGSKPA-AQLTWRKGDQELHGDQTRIQE-DPNGKTFTVSSSVSFQVTREDDGANIVCSVN 223
Cdd:cd00098     4 LLPPSPEEKGGGKVTLVCLVSGFYPKdITVTWLKNGVPLTSGVSTSSPvEPNDGTYSVTSSLTVPPSDWDEGATYTCVVT 83

                  ....*
gi 2319158864 224 HESLK 228
Cdd:cd00098    84 HESLK 88

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2319158864  250 PEPAHPREGQKLLLHCEGRGNPVPQqYVWVKEGSEPPL--------KMTQESALIFPFLNKSDSGTYGCTATSNMGSYTA 321
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPE-VTWYKQGGKLLAesgrfsvsRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASS 79

                   ....*.
gi 2319158864  322 YFTLNV 327
Cdd:smart00410  80 GTTLTV 85

Immunoglobulin constant (IgC)-like domain of antigen receptor Cluster of Differentiation (CD) 80; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin constant (IgC)-like domain of the antigen receptor Cluster of Differentiation (CD) 80. CD80 (also known as glycoprotein B7-1) and CD86 (also known as glycoprotein B7-2) are expressed on antigen-presenting cells and deliver the co-stimulatory signal through CD28 and CTLA-4 (CD152) on T cells. signaling through CD28 augments the T-cell response, whereas CTLA-4 signaling attenuates it. CD80 contains two Ig-like domains, an amino-terminal immunoglobulin variable (IgV)-like domain characteristic of adhesion molecules, and a membrane proximal immunoglobulin constant (IgC)-like domain similar to the constant domains of antigen receptors. Members of the Ig family are components of immunoglobulin, T-cell receptors, CD1 cell surface glycoproteins, secretory glycoproteins A/C, and major histocompatibility complex (MHC) class I/II molecules. In immunoglobulins, each chain is composed of one variable domain (IgV) and one or more IgC domains. These names reflect the fact that the variability in sequences is higher in the variable domain than in the constant domain. The IgV domain is responsible for antigen binding, and the IgC domain is involved in oligomerization and molecular interactions.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2319158864 160 TLNCQSSGSKPAAQLTWRKGDQELHGDQTRIQEDPNGKTFTVSSSVSFQVTREDdgaNIVCSVNH 224
Cdd:cd16083    18 RIICSTSGGFPEPRLSWLENGEELNAINTTVSQDPETELYTVSSELDFNVTYNH---SIVCLIKY 79

Immunoglobulin (Ig) constant domain of the complement receptor of the immunoglobulin superfamily (CRIg); The members here are composed of the Immunoglobulin (Ig) constant domain of the complement receptor of the immunoglobulin superfamily (CRIg). The N-terminal domain of CRIg (also referred to as Z39Ig and V-set and Ig domain-containing 4 (VSIG4)) belongs to the IgV family of immunoglobulin-like domains while the C-terminal domain of CRIg belongs to the IgC family of immunoglobulin-like domains. CRIg plays a role in the complement system, an inhibitor of the alternative pathway convertases, and a negative regulator of T cell activation. 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 such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins such as 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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2319158864 257 EGQKLLLHCEGRGNPvPQQYVWVKE--GSEPPLKMTQESALIFPFLNKSDSGTYGCTATSNMGS 318
Cdd:cd16082    12 QGMRISLQCQAWGSP-PISYVWYKEqtNNQEPIKVAALSTLLFKPAVVADSGSYFCTAKGRVGS 74

Second immunoglobulin (Ig)-like domain of Kirrel (kin of irregular chiasm-like) 3, 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 of Kirrel (kin of irregular chiasm-like) 3 (also known as Neph2). This protein has five Ig-like domains, one transmembrane domain, and a cytoplasmic tail. Included in this group is mammalian Kirrel (Neph1), Kirrel2 (Neph3), and Drosophila RST (irregular chiasm C-roughest) protein. These proteins contain multiple Ig domains, have properties of cell adhesion molecules, and are important in organ development.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2319158864 144 PIITGYKS-SLREKETATLNCQSSGSKPAAQLTWRKGDQELHGDQTRIQEDPNGKTFTVSSSVSFQVTREDDGANIVCSV 222
Cdd:cd05759     2 PVIEGGPViSLQAGVPYNLTCRARGAKPAAEIIWFRDGEQLEGAVYSKELLKDGKRETTVSTLLITPSDLDTGRTFTCRA 81

                          90
                  ....*....|....*...
gi 2319158864 223 NHESLKGAdRSTSQRIEV 240
Cdd:cd05759    82 RNEAIPNG-KETSITLDV 98

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2319158864 153 LREKETATLNCQSSGSKPAAQLTWRKGDQELHgDQTRIQEDPNGKTftvSSSVSFQVTREDDGANIVCSVNHESLKGADR 232
Cdd:pfam00047   8 VLEGDSATLTCSASTGSPGPDVTWSKEGGTLI-ESLKVKHDNGRTT---QSSLLISNVTKEDAGTYTCVVNNPGGSATLS 83

                  ...
gi 2319158864 233 STS 235
Cdd:pfam00047  84 TSL 86

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2319158864 257 EGQKLLLHCEGRGNPVPqQYVWVKEGSEPPLKMTQESALI---FPFLNKS---DSGTYGCTATSNMGS 318
Cdd:cd05848    18 DEKKVILNCEARGNPVP-TYRWLRNGTEIDTESDYRYSLIdgnLIISNPSevkDSGRYQCLATNSIGS 84

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk 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. 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 titin Z1z2 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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2319158864 244 PTAMIRPEPAHPREGQKLLLHCEGRGNPVPqQYVWVKEGSE----PPLKMTQES---ALIFPFLNKSDSGTYGCTATSNM 316
Cdd:cd20972     2 PQFIQKLRSQEVAEGSKVRLECRVTGNPTP-VVRWFCEGKElqnsPDIQIHQEGdlhSLIIAEAFEEDTGRYSCLATNSV 80

                  ....
gi 2319158864 317 GSYT 320
Cdd:cd20972    81 GSDT 84

CH3 domain (third constant Ig domain of the heavy chain) in immunoglobulin heavy alpha, gamma, and delta chains, and CH4 domain (fourth constant Ig domain of the heavy chain) in immunoglobulin heavy alpha, epsilon, and mu chains; member of the C1-set of I; The members here are composed of the third and fourth immunoglobulin constant domain (IgC) of alpha, delta, gamma and alpha, epsilon, and mu heavy chains, respectively. This domain is found on the Fc fragment. The basic structure of Ig molecules is a tetramer of two light chains and two heavy chains linked by disulfide bonds. There are two types of light chains: kappa and lambda; each is composed of a constant domain and a variable domain. There are five types of heavy chains: alpha, delta, epsilon, gamma, and mu, all consisting of a variable domain (VH) with three (alpha, delta and gamma) or four (epsilon and mu) constant domains (CH1 to CH4). Ig molecules are modular proteins, in which the variable and constant domains have clear, conserved sequence patterns.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2319158864 153 LREKETATLNCQSSGSKPA-AQLTWRKGDQEL---HGDQTRIQEDPNGkTFTVSSSVSFQVTREDDGANIVCSVNHESLK 228
Cdd:cd05768    13 LSLNETVTLTCLVKGFYPEdIFVSWLQNGEPLpsaDYKTTAPVPESDG-SFFVYSKLNVSTADWNSGDVFSCVVGHEALP 91

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 2319158864  50 TVVAGGTVVLKCQVK---DHEDSSLQWS------NPAQQTLYFGEKRA--LRDNRIQLVSSTP-HELSISISNVALADEG 117
Cdd:pfam07686   7 TVALGGSVTLPCTYSssmSEASTSVYWYrqppgkGPTFLIAYYSNGSEegVKKGRFSGRGDPSnGDGSLTIQNLTLSDSG 86

                          90
                  ....*....|
gi 2319158864 118 EYTCSIFTMP 127
Cdd:pfam07686  87 TYTCAVIPSG 96

Immunoglobulin C1-set domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2319158864 156 KETATLNCQSSG-SKPAAQLTWRKGDQELHGDQTRIQEDPNGK-TFTVSSSVSFQVTREDDGANIVCSVNHESL 227
Cdd:pfam07654  12 GKPNTLTCLVTGfYPPDITVTWLKNGQEVTEGVKTTPPSPNSDwTYQLSSYLTVTPSDWESGDEYTCRVEHEGL 85

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2319158864 256 REGQKLLLHCEGRGNPVPQQYVWVKEGSEPPLKM---------TQESALIFPfLNKSDSGTYGCTATSNMGSYTAYFTL 325
Cdd:pfam00047   9 LEGDSATLTCSASTGSPGPDVTWSKEGGTLIESLkvkhdngrtTQSSLLISN-VTKEDAGTYTCVVNNPGGSATLSTSL 86

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2319158864  50 TVVAGGTVVLKCQVKDHEDSSLQWsnpaqqtlyfgEK--RALRDNRIQLVSSTPhelSISISNVALA-DEGEYTCSIFTM 126
Cdd:cd20958    11 TAVAGQTLRLHCPVAGYPISSITW-----------EKdgRRLPLNHRQRVFPNG---TLVIENVQRSsDEGEYTCTARNQ 76

                          90
                  ....*....|.
gi 2319158864 127 PVRTAKSLVTV 137
Cdd:cd20958    77 QGQSASRSVFV 87

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

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2319158864 247 MIRPEPAHP--REGQKLLLHCEGRGNPVPQqYVWVKEG-----SEPPLKMTQESALIFPFLNKSDSGTYGCTATSNMGSY 319
Cdd:cd20952     1 IILQGPQNQtvAVGGTVVLNCQATGEPVPT-ISWLKDGvpllgKDERITTLENGSLQIKGAEKSDTGEYTCVALNLSGEA 79

                  ....*...
gi 2319158864 320 TAYFTLNV 327
Cdd:cd20952    80 TWSAVLDV 87

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2319158864 258 GQKLLLHCEGRGNPVPQqYVWVKEGSE-PPLKMTQES---ALIFPFLNKSDSGTYGCTATSNMGSYTAYFTLNV 327
Cdd:cd05731    10 GGVLLLECIAEGLPTPD-IRWIKLGGElPKGRTKFENfnkTLKIENVSEADSGEYQCTASNTMGSARHTISVTV 82

Immunoglobulin I-set domain;

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gi 2319158864 154 REKETATLNCQSSGSkPAAQLTWRKGDQELHGDQT-RIQEDPNGKTFTVSssvsfQVTREDDG 215
Cdd:pfam07679  13 QEGESARFTCTVTGT-PDPEVSWFKDGQPLRSSDRfKVTYEGGTYTLTIS-----NVQPDDSG 69

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk 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. 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 titin Z1z2 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2319158864 256 REGQKLLLHCEGRGNPVPQqYVWVKEG------SEPPLKMT---QESALIFPFLNKSDSGTYGCTATSNMGSYTAYFTLN 326
Cdd:cd20974    13 LEGSTATFEAHVSGKPVPE-VSWFRDGqvistsTLPGVQISfsdGRAKLSIPAVTKANSGRYSLTATNGSGQATSTAELL 91

                  .
gi 2319158864 327 V 327
Cdd:cd20974    92 V 92

Immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor (R) and similar proteins; member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig)-like domain of vascular endothelial growth factor (VEGF) receptor (R) and related proteins. The VEGFRs have an extracellular component with seven Ig-like domains, a transmembrane segment, and an intracellular tyrosine kinase domain interrupted by a kinase-insert domain. The VEGFR family consists of three members: VEGFR-1 (Flt-1), VEGFR-2 (KDR/Flk-1) and VEGFR-3 (Flt-4). VEGF-A interacts with both VEGFR-1 and VEGFR-2. VEGFR-1 binds strongest to VEGF; VEGF-2 binds more weakly. VEGFR-3 appears not to bind VEGF, but binds other members of the VEGF family (VEGF-C and -D). VEGFRs bind VEGFs with high affinity with the IG-like domains. VEGF-A is important to the growth and maintenance of vascular endothelial cells and to the development of new blood- and lymphatic-vessels in physiological and pathological states. VEGFR-2 is a major mediator of the mitogenic, angiogenic, and microvascular permeability-enhancing effects of VEGF-A. VEGFR-1 may play an inhibitory part in these processes by binding VEGF and interfering with its interaction with VEGFR-2. VEGFR-1 has a signaling role in mediating monocyte chemotaxis. VEGFR-1 and VEGFR-2 may mediate a chemotactic and a survival signal in hematopoietic stem cells or leukemia cells. VEGFR-3 has been shown to be involved in tumor angiogenesis and growth. This group also contains alpha-type platelet-derived growth factor receptor precursor (PDGFR)-alpha (CD140a), and PDGFR-beta (CD140b). PDGFRs alpha and beta have an extracellular component with five Ig-like domains, a transmembrane segment, and a cytoplasmic portion that has protein tyrosine kinase activity.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2319158864  50 TVVAGGTVVLKCQV--KDHEDSSLQWSNPAQQTlyfgEKRALRDNRIQLVSSTPHELS--ISISNVALADEGEYTCSIFT 125
Cdd:cd05742    13 VLPQGETLVLNCTAnvNLNEVVDFQWTYPSEKE----GKLALLKPDIKVDWSEPGEFVstLTIPEATLKDSGTYTCAARS 88

                          90
                  ....*....|
gi 2319158864 126 MPVRTAKSLV 135
Cdd:cd05742    89 GVMKKEKQTS 98

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2319158864 256 REGQKLLLHCEGRGNPVPQqYVWVKEGS-------EPPLKMTQESALIFPFLNK-SDSGTYGCTATSNMGSYTAYFTLNV 327
Cdd:cd05763    12 RAGSTARLECAATGHPTPQ-IAWQKDGGtdfpaarERRMHVMPEDDVFFIVDVKiEDTGVYSCTAQNSAGSISANATLTV 90

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; 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. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2319158864 244 PTAMIRPEPAHPrEGQKLLLHCEGRGNPVPQqYVWVKEGSE--------PPLKMTQESALIFPFLNKSDSGTYGCTATSN 315
Cdd:cd05729     6 TEKMEEREHALP-AANKVRLECGAGGNPMPN-ITWLKDGKEfkkehrigGTKVEEKGWSLIIERAIPRDKGKYTCIVENE 83

                          90
                  ....*....|..
gi 2319158864 316 MGSYTAYFTLNV 327
Cdd:cd05729    84 YGSINHTYDVDV 95

Immunoglobulin I-set domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1); The members here are composed of the immunoglobulin I-set (IgI) domain of the Leucine-rich repeat and immunoglobin-like domain-containing protein 1 (Lingo-1). Human Lingo-1 is a central nervous system-specific transmembrane glycoprotein also known as LERN-1, which functions as a negative regulator of neuronal survival, axonal regeneration, and oligodendrocyte differentiation and myelination. Lingo-1 is a key component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors. The ligand-binding ectodomain of human Lingo-1 contains a bimodular, kinked structure composed of leucine-rich repeat (LRR) and immunoglobulin (Ig)-like modules. Diseases associated with Lingo-1 include mental retardation, autosomal recessive 64 and essential tremor. 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 Lingo-1 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2319158864 257 EGQKLLLHCEGRGNPvPQQYVWVKEGSEPPLKMTQESALIFP-------FLNKSDSGTYGCTATSNMG 317
Cdd:cd20969    16 EGHTVQFVCRADGDP-PPAILWLSPRKHLVSAKSNGRLTVFPdgtlevrYAQVQDNGTYLCIAANAGG 82

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.