TIR domain; The Toll/interleukin-1 receptor (TIR) homology domain is an intracellular signalling domain found in MyD88, interleukin 1 receptor and the Toll receptor. It contains three highly-conserved regions, and mediates protein-protein interactions between the Toll-like receptors (TLRs) and signal-transduction components. TIR-like motifs are also found in plant proteins thought to be involved in resistance to disease. When activated, TIR domains recruit cytoplasmic adaptor proteins MyD88 and TOLLIP (Toll interacting protein). In turn, these associate with various kinases to set off signalling cascades.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905610  389 YVLYPKYpRGSqgHDVDTLVLKILPEVleKQCGYKLFIFGRDEFPGQAVASVIDENIKLCRRLMVFVAPESSSFGflKNL 468
Cdd:pfam01582   1 YDVFLSF-RGS--DTREWFVSHLLKEL--KQKGIKLFIDDRDLEPGEAIAPELLSAIEKSRRSVVVLSPNYASSG--WCL 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905610  469 SEEQIAVYNALiQHGMKVILIELEKVKDYS-----TMPESIQYIRQKH---GAIQWDGDFTE-------QSQCAKTKFWK 533
Cdd:pfam01582  74 DELVKILECAL-DLGQKVIPIFYEVDPSDVrkqtgSFGKAFKKHKKVLteeKVLKWRGALNEvaniwhsKSVSDESKFWK 152

                  ....*.
gi 568905610  534 KVRYHM 539
Cdd:pfam01582 153 KIAYDI 158

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 568905610 135 YQQILPIGKSGSLNCHLYFPESCA--LDSIKWYKGCEEIKAGKKYSPSGAKLLVNNVAVEDGGSYACSARLTHLGRHFTI 212
Cdd:cd05757    3 YKQKLPITKGGKITCPDLDDYKNEnvLPPIQWYKDCKPLQGDKRFIPKGSKLLIQNVTEEDAGNYTCKFTYTHNGKQYNV 82

                         90
                 ....*....|
gi 568905610 213 RNYIAVNTKE 222
Cdd:cd05757   83 TRTISLTVTE 92

TIR domain; The Toll/interleukin-1 receptor (TIR) homology domain is an intracellular signalling domain found in MyD88, interleukin 1 receptor and the Toll receptor. It contains three highly-conserved regions, and mediates protein-protein interactions between the Toll-like receptors (TLRs) and signal-transduction components. TIR-like motifs are also found in plant proteins thought to be involved in resistance to disease. When activated, TIR domains recruit cytoplasmic adaptor proteins MyD88 and TOLLIP (Toll interacting protein). In turn, these associate with various kinases to set off signalling cascades.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905610  389 YVLYPKYpRGSqgHDVDTLVLKILPEVleKQCGYKLFIFGRDEFPGQAVASVIDENIKLCRRLMVFVAPESSSFGflKNL 468
Cdd:pfam01582   1 YDVFLSF-RGS--DTREWFVSHLLKEL--KQKGIKLFIDDRDLEPGEAIAPELLSAIEKSRRSVVVLSPNYASSG--WCL 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905610  469 SEEQIAVYNALiQHGMKVILIELEKVKDYS-----TMPESIQYIRQKH---GAIQWDGDFTE-------QSQCAKTKFWK 533
Cdd:pfam01582  74 DELVKILECAL-DLGQKVIPIFYEVDPSDVrkqtgSFGKAFKKHKKVLteeKVLKWRGALNEvaniwhsKSVSDESKFWK 152

                  ....*.
gi 568905610  534 KVRYHM 539
Cdd:pfam01582 153 KIAYDI 158

First immunoglobulin (Ig)-like domain of interleukin-1 receptor (IL1R), and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain of interleukin-1 receptor (IL1R; also known as cluster of differentiation (CD) 121). IL-1 alpha and IL-1 beta are cytokines which participate in the regulation of inflammation, immune responses, and hematopoiesis. These cytokines bind to the IL-1 receptor type 1 (IL1R1), which is activated on additional association with interleukin-1 receptor accessory protein (IL1RAP). IL-1 also binds a second receptor designated type II (IL1R2). Mature IL1R1 consists of three Ig-like domains, a transmembrane domain, and a large cytoplasmic domain. Mature IL1R2 is organized similarly except that it has a short cytoplasmic domain. The latter does not initiate signal transduction. A naturally occurring cytokine IL-1RA (IL-1 receptor antagonist) is widely expressed and binds to IL-1 receptors, inhibiting the binding of IL-1 alpha and IL-1 beta.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905610  25 EDIFMHNVIISEGQPFPFNC---TYPPETNGAVNLTWYKTPSKSPVSNNRHLRVHQDQTWILFLPLTLEDSGIYQCVIRN 101
Cdd:cd05756    3 WGEDIKILVVLEGEPDVIKCplfPNFLAQSAGLNLTWYKNDSETPISFEPDSRIHQEKDKLWFVPALLEDSGNYYCVVRN 82

                         90
                 ....*....|....
gi 568905610 102 AHNCYQIAVNLTVL 115
Cdd:cd05756   83 STYCSKVSISLEVV 96

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905610    31 NVIISEGQPFPFNCTYPPETNgaVNLTWYKTPSKSPVSNNRHLRVHQDQTWILFLP-LTLEDSGIYQCVIRNAHNCYQIA 109
Cdd:smart00410   3 SVTVKEGESVTLSCEASGSPP--PEVTWYKQGGKLLAESGRFSVSRSGSTSTLTISnVTPEDSGTYTCAATNSSGSASSG 80

                   ....*
gi 568905610   110 VNLTV 114
Cdd:smart00410  81 TTLTV 85

Third immunoglobulin (Ig)-like domain of interleukin-1 receptor (IL1R), and similar domains; The members here are composed of the third immunoglobulin (Ig)-like domain of interleukin-1 receptor (IL1R) and similar proteins. Members of this family are characterized by extracellular immunoglobulin-like domains and intracellular Toll/Interleukin-1R (TIR) domain. Three naturally occurring ligands for the IL-1 receptor (IL1R) are known: the agonists IL-1alpha and IL-1beta and the IL-1-receptor antagonist IL1RA. IL-1Rs are involved in immune host defense and hematopoiesis. After binding to interleukin-1, IL1R associates with the coreceptor IL1RAP (interleukin 1 receptor accessory protein, also known as IL-1R3) to form the high affinity interleukin-1 receptor complex, which induces multiple cellular responses including NF-kappa-B activation, IL-2 secretion, and IL-2 promoter activation. Signaling involves the recruitment of adapter molecules such as TOLLIP, MYD88, and IRAK1 or IRAK2 via the respective TIR domains of the receptor/coreceptor subunits. IL1R binds ligands with comparable affinity to its antagonist IL1RA, and binding of IL1RA to IL1R, prevents association of the latter with IL1RAP to form a signaling complex.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905610 230 PNITYPKNNSIEVPLGSTLIVNCNITDtkENTNLRCWRVNNTLVD--------DYYKdskriqegIETNVSLRdqiRYTV 301
Cdd:cd20932    1 PVIVSPANETMEVDLGSQIQLICNVTG--QLSDLAYWKWNGSEIDeddpvlgeDYYS--------VENPANKR---KSTL 67

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 568905610 302 nITFL---KVKMEDYGRPFTCHA----GVSAAYIILIY 332
Cdd:cd20932   68 -ITVLnisEIESRFYKHPFTCFAknthGLDAAYVQLIY 104

Immunoglobulin I-set domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905610   26 DIFMHNVIISEGQPFPFNCT---YPPETngavnLTWYKtpSKSPVSNNRHLRVHQDQ--TWILFLPLTLEDSGIYQCVIR 100
Cdd:pfam07679   4 TQKPKDVEVQEGESARFTCTvtgTPDPE-----VSWFK--DGQPLRSSDRFKVTYEGgtYTLTISNVQPDDSGKYTCVAT 76

                          90
                  ....*....|....
gi 568905610  101 NAHNCYQIAVNLTV 114
Cdd:pfam07679  77 NSAGEAEASAELTV 90

TIR domain; The Toll/interleukin-1 receptor (TIR) homology domain is an intracellular signalling domain found in MyD88, interleukin 1 receptor and the Toll receptor. It contains three highly-conserved regions, and mediates protein-protein interactions between the Toll-like receptors (TLRs) and signal-transduction components. TIR-like motifs are also found in plant proteins thought to be involved in resistance to disease. When activated, TIR domains recruit cytoplasmic adaptor proteins MyD88 and TOLLIP (Toll interacting protein). In turn, these associate with various kinases to set off signalling cascades.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905610  389 YVLYPKYpRGSqgHDVDTLVLKILPEVleKQCGYKLFIFGRDEFPGQAVASVIDENIKLCRRLMVFVAPESSSFGflKNL 468
Cdd:pfam01582   1 YDVFLSF-RGS--DTREWFVSHLLKEL--KQKGIKLFIDDRDLEPGEAIAPELLSAIEKSRRSVVVLSPNYASSG--WCL 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905610  469 SEEQIAVYNALiQHGMKVILIELEKVKDYS-----TMPESIQYIRQKH---GAIQWDGDFTE-------QSQCAKTKFWK 533
Cdd:pfam01582  74 DELVKILECAL-DLGQKVIPIFYEVDPSDVrkqtgSFGKAFKKHKKVLteeKVLKWRGALNEvaniwhsKSVSDESKFWK 152

                  ....*.
gi 568905610  534 KVRYHM 539
Cdd:pfam01582 153 KIAYDI 158

First immunoglobulin (Ig)-like domain of interleukin-1 receptor (IL1R), and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain of interleukin-1 receptor (IL1R; also known as cluster of differentiation (CD) 121). IL-1 alpha and IL-1 beta are cytokines which participate in the regulation of inflammation, immune responses, and hematopoiesis. These cytokines bind to the IL-1 receptor type 1 (IL1R1), which is activated on additional association with interleukin-1 receptor accessory protein (IL1RAP). IL-1 also binds a second receptor designated type II (IL1R2). Mature IL1R1 consists of three Ig-like domains, a transmembrane domain, and a large cytoplasmic domain. Mature IL1R2 is organized similarly except that it has a short cytoplasmic domain. The latter does not initiate signal transduction. A naturally occurring cytokine IL-1RA (IL-1 receptor antagonist) is widely expressed and binds to IL-1 receptors, inhibiting the binding of IL-1 alpha and IL-1 beta.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905610  25 EDIFMHNVIISEGQPFPFNC---TYPPETNGAVNLTWYKTPSKSPVSNNRHLRVHQDQTWILFLPLTLEDSGIYQCVIRN 101
Cdd:cd05756    3 WGEDIKILVVLEGEPDVIKCplfPNFLAQSAGLNLTWYKNDSETPISFEPDSRIHQEKDKLWFVPALLEDSGNYYCVVRN 82

                         90
                 ....*....|....
gi 568905610 102 AHNCYQIAVNLTVL 115
Cdd:cd05756   83 STYCSKVSISLEVV 96

First immunoglobulin (Ig)-like domain of interleukin-1 receptor (IL1R), and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain of interleukin-1 receptor (IL1R). IL-1 alpha and IL-1 beta are cytokines which participate in the regulation of inflammation, immune responses, and hematopoiesis. These cytokines bind to the IL-1 receptor type 1 (IL1R1), which is activated on additional association with interleukin-1 receptor accessory protein (IL1RAP). IL-1 also binds a second receptor designated type II (IL1R2). Mature IL1R1 consists of three Ig-like domains, a transmembrane domain, and a large cytoplasmic domain. Mature IL1R2 is organized similarly except that it has a short cytoplasmic domain. The latter does not initiate signal transduction. IL-1 receptor antagonist (IL-1RA), a naturally occurring cytokine, is widely expressed and binds to IL-1 receptors, inhibiting the binding of IL-1 alpha and IL-1 beta.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568905610  47 PPETNGavNLTWYKTPSKSPVSNNRHLRVHQDQTWILFLPLTLEDSGIYQCVIRNAHNCYQIAVNLTVL 115
Cdd:cd20991   25 PNESKG--TITWYKNDSKTPISMEQDSRIHQYKEKLWFVPAKVEDSGHYYCVVRNSTYCLKIKITAKFV 91

Second immunoglobulin (Ig)-like domain of interleukin-1 receptor (IL1R), and similar domains; The members here are composed of the second immunoglobulin (Ig)-like domain of interleukin-1 receptor (IL1R). IL-1 alpha and IL-1 beta are cytokines which participate in the regulation of inflammation, immune responses, and hematopoiesis. These cytokines bind to the IL-1 receptor type 1 (IL1R1), which is activated on additional association with interleukin-1 receptor accessory protein (IL1RAP). IL-1 also binds a second receptor designated type II (IL1R2). Mature IL1R1 consists of three IG-like domains, a transmembrane domain, and a large cytoplasmic domain. Mature IL1R2 is organized similarly except that it has a short cytoplasmic domain. The latter does not initiate signal transduction. A naturally occurring cytokine IL-1RA (IL-1 receptor antagonist) is widely expressed and binds to IL-1 receptors, inhibiting the binding of IL-1 alpha and IL-1 beta. This group also contains ILIR-like 1 (IL1R1L) which maps to the same chromosomal location as IL1R1 and IL1R2.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905610 133 DVYQQILPIGKSGSLNC-HLYF--PESCALDSIKWYKGCEEIK-AGKKYSPSGAKLLVNNVAVEDGGSYACSARLTHLGR 208
Cdd:cd20994    1 DFYKQKVPFTSGGRIVCpHLDFfkDENNNLPKVQWYKDCKPLLlDDKRFAGLESDLLIFNVTVQDQGNYTCHTSYTYMGK 80

                         90
                 ....*....|....
gi 568905610 209 HFTIRNYIAVNTKE 222
Cdd:cd20994   81 QYNISRTISLIVLE 94

Third immunoglobulin (Ig)-like domain of interleukin-1 receptor (IL1R), and similar domains; The members here are composed of the third immunoglobulin (Ig)-like domain of interleukin-1 receptor (IL1R) and similar proteins. Members of this family are characterized by extracellular immunoglobulin-like domains and intracellular Toll/Interleukin-1R (TIR) domain. Three naturally occurring ligands for the IL-1 receptor (IL1R) are known: the agonists IL-1alpha and IL-1beta and the IL-1-receptor antagonist IL1RA. IL-1Rs are involved in immune host defense and hematopoiesis. After binding to interleukin-1, IL1R associates with the coreceptor IL1RAP (interleukin 1 receptor accessory protein, also known as IL-1R3) to form the high affinity interleukin-1 receptor complex, which induces multiple cellular responses including NF-kappa-B activation, IL-2 secretion, and IL-2 promoter activation. Signaling involves the recruitment of adapter molecules such as TOLLIP, MYD88, and IRAK1 or IRAK2 via the respective TIR domains of the receptor/coreceptor subunits. IL1R binds ligands with comparable affinity to its antagonist IL1RA, and binding of IL1RA to IL1R, prevents association of the latter with IL1RAP to form a signaling complex.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905610 230 PNITYPKNNSIEVPLGSTLIVNCNITDtkENTNLRCWRVNNTLVD--------DYYKdskriqegIETNVSLRdqiRYTV 301
Cdd:cd20932    1 PVIVSPANETMEVDLGSQIQLICNVTG--QLSDLAYWKWNGSEIDeddpvlgeDYYS--------VENPANKR---KSTL 67

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 568905610 302 nITFL---KVKMEDYGRPFTCHA----GVSAAYIILIY 332
Cdd:cd20932   68 -ITVLnisEIESRFYKHPFTCFAknthGLDAAYVQLIY 104

First immunoglobulin (Ig)-like domain of X-linked interleukin-1 receptor accessory protein-like 1 (IL1RAPL-1), and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain of X-linked interleukin-1 receptor accessory protein-like 1 (IL1RAPL-1). IL-1 alpha and IL-1 beta are cytokines which participate in the regulation of inflammation, immune responses, and hematopoiesis. These cytokines bind to the IL-1 receptor type 1 (IL1R1), which is activated on additional association with interleukin-1 receptor accessory protein (IL1RAP). IL-1 also binds a second receptor designated type II (IL1R2). Mature IL1R1 consists of three Ig-like domains, a transmembrane domain, and a large cytoplasmic domain. Mature IL1R2 is organized similarly except that it has a short cytoplasmic domain. The latter does not initiate signal transduction. A naturally occurring cytokine IL-1RA (IL-1 receptor antagonist) is widely expressed and binds to IL-1 receptors, inhibiting the binding of IL-1 alpha and IL-1 beta. IL1RAPL is encoded by a gene on the X-chromosome, this gene is wholly or partially deleted in multiple cases of non-syndromic intellectual disability. This group also contains IL1RAPL-2 which is also encoded by a gene on the X-chromosome and is a candidate for another non-syndromic intellectual disability loci.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905610  37 GQPFPFNCT---------YPPETNGAVNLTWYKTPS----KSPVSNNrHLRVHQDQTWILFLPLTLEDSGIYQCVIRNAH 103
Cdd:cd05896   15 GEPVRIKCAlfygyirtnYSMAQSAGLSLMWYKSSGpgdfEEPIIFD-GVRMSKEEDSIWFRPAELQDSGLYTCVLRNST 93

                         90
                 ....*....|.
gi 568905610 104 NCYQIAVNLTV 114
Cdd:cd05896   94 YCMKVSMSLTV 104

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568905610  42 FNCTYPPetNGAVNLTWYKTPSKSPVSNNRHLRVHQDQTWILFLPLTLEDSGIYQCVIRNAH 103
Cdd:cd00096    3 LTCSASG--NPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSA 62

First immunoglobulin (Ig)-like domain of interleukin-1 receptor (IL1R), and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain of interleukin-1 receptor (IL1R). IL-1 alpha and IL-1 beta are cytokines which participate in the regulation of inflammation, immune responses, and hematopoiesis. These cytokines bind to the IL-1 receptor type 1 (IL1R1), which is activated on additional association with interleukin-1 receptor accessory protein (IL1RAP). IL-1 also binds a second receptor designated type II (IL1R2). Mature IL1R1 consists of three Ig-like domains, a transmembrane domain, and a large cytoplasmic domain. Mature IL1R2 is organized similarly except that it has a short cytoplasmic domain. The latter does not initiate signal transduction. A naturally occurring cytokine IL-1RA (IL-1 receptor antagonist) is widely expressed and binds to IL-1 receptors, inhibiting the binding of IL-1 alpha and IL-1 beta.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905610  29 MHNVIISEGQPFPFNC---------TYPPETNGAVNLTWYKTPS----KSPVsNNRH--LRVHQDQTWILFLPLTLEDSG 93
Cdd:cd20992    8 MRQIQVFEGEPARIKCplfehflkyNYSTAHSAGLTLIWYWTRQdrdlEEPI-NFRLpdNRISKEKDVLWFRPTLLNDTG 86

                         90       100
                 ....*....|....*....|..
gi 568905610  94 IYQCVIRNAHNCYQIAVNLTVL 115
Cdd:cd20992   87 NYTCMLRNTTYCSKVAFPLEVV 108

Third immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the Constant 2 (C2)-set of IgSF domains; The members here are composed of the third 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. 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 belongs to the C2-set of IgSF domains, having A, B, and E strands in one beta-sheet and A', G, F, C, and C' in the other. Unlike other Ig domain sets, the C2-set lacks the D strand.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905610  37 GQPFPFNCTYppETNGAVNLTWYKtpskspvsNNRHL----RVHQDQTWILFLP-LTLEDSGIYQCVIRN 101
Cdd:cd20957   16 GRTAVFNCSV--TGNPIHTVLWMK--------DGKPLghssRVQILSEDVLVIPsVKREDKGMYQCFVRN 75

Immunoglobulin (Ig) variable (V) domain of T-cell receptor (TCR) alpha chain and similar proteins; The members here are composed of the immunoglobulin (Ig) variable domain of the alpha chain of alpha/beta T-cell antigen receptors (TCRs). TCRs mediate antigen recognition by T lymphocytes, and are composed of alpha and beta, or gamma and delta polypeptide chains with variable (V) and constant (C) regions. This group represents the variable domain of the alpha chain of TCRs and also includes the variable domain of delta chains of TCRs. Alpha/beta TCRs recognize antigen as peptide fragments presented by major histocompatibility complex (MHC) molecules. The variable domain of TCRs is responsible for antigen recognition, and is located at the N-terminus of the receptor. Gamma/delta TCRs recognize intact protein antigens directly without antigen processing and recognize MHC independently of the bound peptide. Members of this group contain standard Ig superfamily V-set AGFCC'C"/DEB domain topology.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905610  32 VIISEGQPFPFNCTYppETNGAVNLTWYKT-PSKSPVS-----------NNRHLRVHQDQTWILFL----PLTLEDSGIY 95
Cdd:cd04983    8 LSVQEGENVTLNCNY--STSTFYYLFWYRQyPGQGPQFliyissdsgnkKKGRFSATLDKSRKSSSlhisAAQLSDSAVY 85

                         90
                 ....*....|...
gi 568905610  96 QCVIRNAHNCYQI 108
Cdd:cd04983   86 FCALSESGGTGKL 98

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568905610   142 GKSGSLNCHLYFPEScalDSIKWYK-GCEEIKAGKKYS----PSGAKLLVNNVAVEDGGSYACSARLTH 205
Cdd:smart00410   9 GESVTLSCEASGSPP---PEVTWYKqGGKLLAESGRFSvsrsGSTSTLTISNVTPEDSGTYTCAATNSS 74

Immunoglobulin I-set domain;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568905610  141 IGKSGSLNCHLY-FPEScaldSIKWYKGCEEIKAGKKYS----PSGAKLLVNNVAVEDGGSYACSA 201
Cdd:pfam07679  14 EGESARFTCTVTgTPDP----EVSWFKDGQPLRSSDRFKvtyeGGTYTLTISNVQPDDSGKYTCVA 75

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568905610   35 SEGQPFPFNCTYPP-ETNGAVNLTWYKTPSKSP-------VSNNRHLRVHQDQ-TW----------ILFLPLTLEDSGIY 95
Cdd:pfam07686   9 ALGGSVTLPCTYSSsMSEASTSVYWYRQPPGKGptfliayYSNGSEEGVKKGRfSGrgdpsngdgsLTIQNLTLSDSGTY 88

                          90       100
                  ....*....|....*....|.
gi 568905610   96 QCVIR-NAHNCYQIAVNLTVL 115
Cdd:pfam07686  89 TCAVIpSGEGVFGKGTRLTVL 109

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 568905610 161 SIKWYKGCEEIKAGKKYS----PSGAKLLVNNVAVEDGGSYACSARLTHLGR 208
Cdd:cd00096   14 TITWYKNGKPLPPSSRDSrrseLGNGTLTISNVTLEDSGTYTCVASNSAGGS 65