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 27894324   380 YVVYPrnyksSTDGASRVEHFVHQILPDVleNKCGYTLCIYGRDMLPGEDVVTAVETNIRKSRRHIFILTPQITHNKEFA 459
Cdd:pfam01582   1 YDVFL-----SFRGSDTREWFVSHLLKEL--KQKGIKLFIDDRDLEPGEAIAPELLSAIEKSRRSVVVLSPNYASSGWCL 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27894324   460 YEQEVALHCALiQNDAKVILIEMEALSELDMLQAEALQDSLQHLMKV---QGTIKWREDH--IAN-----KRSLNSKFWK 529
Cdd:pfam01582  74 DELVKILECAL-DLGQKVIPIFYEVDPSDVRKQTGSFGKAFKKHKKVlteEKVLKWRGALneVANiwhskSVSDESKFWK 152

                  ....*.
gi 27894324   530 HVRYQM 535
Cdd:pfam01582 153 KIAYDI 158

IL-beta-binding protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27894324   27 LENEALIVRCPR-----QGKPSYTVDWYY--SQTNKSIPTQernrvfaSGQLLKFLPAAVADSGIYTCIVRSPTFNRTGY 99
Cdd:PHA02785  39 LENEPVILPCPQintlsSGYNILDILWEKrgADNDRIIPID-------NGSNMLILNPTQSDSGIYICITKNETYCDMMS 111

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27894324  100 ANVTIYKkQSDCNVpDYLMYSTVSGSEKNSKIYCPTIDLY---NWTAPLEWfKNCQALQGSRYRAHK-SFLVIDNVMTED 175
Cdd:PHA02785 112 LNLTIVS-VSESNI-DLISYPQIVNERSTGEMVCPNINAFiasNVNADIIW-SGHRRLRNKRLKQRTpGIITIEDVRKND 188

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27894324  176 AGDYTCKFIHNENGANYSVTATRSFTVKDEQgfsLFPVIGAPaqnEIKEVEIGKNANLTCSACFGKGTQFlAAVLWQLNG 255
Cdd:PHA02785 189 AGYYTCVLKYIYGDKTYNVTRIVKLEVRDRI---IPPTMQLP---EGVVTSIGSNLTIACRVSLRPPTTD-ADVFWISNG 261

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 27894324  256 TKITDfgepriQQEEGQNQ-SFSNGLACLDM------VLRIADVKEEDlLLQYDCLALNLHGLRRhTVRLS 319
Cdd:PHA02785 262 MYYEE------DDEDGDGRiSVANKIYTTDKrrvitsRLNINPVKEED-ATTFTCMAFTIPSISK-TVTIS 324

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 27894324   380 YVVYPrnyksSTDGASRVEHFVHQILPDVleNKCGYTLCIYGRDMLPGEDVVTAVETNIRKSRRHIFILTPQITHNKEFA 459
Cdd:pfam01582   1 YDVFL-----SFRGSDTREWFVSHLLKEL--KQKGIKLFIDDRDLEPGEAIAPELLSAIEKSRRSVVVLSPNYASSGWCL 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27894324   460 YEQEVALHCALiQNDAKVILIEMEALSELDMLQAEALQDSLQHLMKV---QGTIKWREDH--IAN-----KRSLNSKFWK 529
Cdd:pfam01582  74 DELVKILECAL-DLGQKVIPIFYEVDPSDVRKQTGSFGKAFKKHKKVlteEKVLKWRGALneVANiwhskSVSDESKFWK 152

                  ....*.
gi 27894324   530 HVRYQM 535
Cdd:pfam01582 153 KIAYDI 158

Toll - interleukin 1 - resistance;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27894324    377 YDAYVVYPRNyksstdgasrvEHFVHQILPDVLENKCGYTLCIYGRDMLPGEDVVTAVETNIRKSRRHIFILTPQITHNK 456
Cdd:smart00255   2 YDVFISYSGK-----------EDVRNEFLSHLLEKLRGYGLCVFIDDFEPGGGDLEEIDEAIEKSRIAIVVLSPNYAESE 70

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27894324    457 EFAYEQEVALHCALIQNDAKVILIEMEALSEldmlQAEALQDSLQHLMKVQgTIKWREDHIAnkrslnsKFWKHVRYQMP 536
Cdd:smart00255  71 WCLDELVAALENALEEGGLRVIPIFYEVIPS----DVRKQPGKFRKVFKKN-YLKWPEDEKE-------QFWKKALYAVP 138

                   ..
gi 27894324    537 VP 538
Cdd:smart00255 139 SK 140

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 27894324  22 KQSWGLENEALIVRCPRQGKPS-----YTVDWYYSQTNKSIPTQERNRVFASGQLLKFLPAAVADSGIYTCIVRSPTF 94
Cdd:cd05756   8 KILVVLEGEPDVIKCPLFPNFLaqsagLNLTWYKNDSETPISFEPDSRIHQEKDKLWFVPALLEDSGNYYCVVRNSTY 85

Immunoglobulin I-set domain;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 27894324   146 EWFKNCQAL-QGSRYRAHK----SFLVIDNVMTEDAGDYTCKfIHNENGanySVTATRSFTV 202
Cdd:pfam07679  33 SWFKDGQPLrSSDRFKVTYeggtYTLTISNVQPDDSGKYTCV-ATNSAG---EAEASAELTV 90

Immunoglobulin I-set domain;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 27894324    28 ENEALIVRCPRQGKPSYTVDWYYSqtNKSIPTQERNRVFASGQL--LKFLPAAVADSGIYTCIV 89
Cdd:pfam07679  14 EGESARFTCTVTGTPDPEVSWFKD--GQPLRSSDRFKVTYEGGTytLTISNVQPDDSGKYTCVA 75

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 27894324   380 YVVYPrnyksSTDGASRVEHFVHQILPDVleNKCGYTLCIYGRDMLPGEDVVTAVETNIRKSRRHIFILTPQITHNKEFA 459
Cdd:pfam01582   1 YDVFL-----SFRGSDTREWFVSHLLKEL--KQKGIKLFIDDRDLEPGEAIAPELLSAIEKSRRSVVVLSPNYASSGWCL 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27894324   460 YEQEVALHCALiQNDAKVILIEMEALSELDMLQAEALQDSLQHLMKV---QGTIKWREDH--IAN-----KRSLNSKFWK 529
Cdd:pfam01582  74 DELVKILECAL-DLGQKVIPIFYEVDPSDVRKQTGSFGKAFKKHKKVlteEKVLKWRGALneVANiwhskSVSDESKFWK 152

                  ....*.
gi 27894324   530 HVRYQM 535
Cdd:pfam01582 153 KIAYDI 158

Toll - interleukin 1 - resistance;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27894324    377 YDAYVVYPRNyksstdgasrvEHFVHQILPDVLENKCGYTLCIYGRDMLPGEDVVTAVETNIRKSRRHIFILTPQITHNK 456
Cdd:smart00255   2 YDVFISYSGK-----------EDVRNEFLSHLLEKLRGYGLCVFIDDFEPGGGDLEEIDEAIEKSRIAIVVLSPNYAESE 70

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27894324    457 EFAYEQEVALHCALIQNDAKVILIEMEALSEldmlQAEALQDSLQHLMKVQgTIKWREDHIAnkrslnsKFWKHVRYQMP 536
Cdd:smart00255  71 WCLDELVAALENALEEGGLRVIPIFYEVIPS----DVRKQPGKFRKVFKKN-YLKWPEDEKE-------QFWKKALYAVP 138

                   ..
gi 27894324    537 VP 538
Cdd:smart00255 139 SK 140

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 27894324 130 KIYCPTIDLY----NWTAPLEWFKNCQALQGS--RYRAHKSFLVIDNVMTEDAGDYTCKFIHNENGANYSVTATRSFTVK 203
Cdd:cd20994  14 RIVCPHLDFFkdenNNLPKVQWYKDCKPLLLDdkRFAGLESDLLIFNVTVQDQGNYTCHTSYTYMGKQYNISRTISLIVL 93

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27894324     21 SKQSWGLENEALIVRCPRQGKPSYTVDWYYsQTNKSIPTQERNRVFASGQL--LKFLPAAVADSGIYTCIVRSPTFNRTG 98
Cdd:smart00410   1 PPSVTVKEGESVTLSCEASGSPPPEVTWYK-QGGKLLAESGRFSVSRSGSTstLTISNVTPEDSGTYTCAATNSSGSASS 79

                   ....*.
gi 27894324     99 YANVTI 104
Cdd:smart00410  80 GTTLTV 85

Immunoglobulin I-set domain;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 27894324   146 EWFKNCQAL-QGSRYRAHK----SFLVIDNVMTEDAGDYTCKfIHNENGanySVTATRSFTV 202
Cdd:pfam07679  33 SWFKDGQPLrSSDRFKVTYeggtYTLTISNVQPDDSGKYTCV-ATNSAG---EAEASAELTV 90

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 27894324  32 LIVRCPRQGKPSYTVDWYYSQTNKSIPTQERNRVFASGQLLKFLPAAVADSGIYTCIVRSP 92
Cdd:cd00096   1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNS 61

Immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins; member of the I-set of IgSF domains; This group contains the immunoglobulin domain of human Synaptic Adhesion-Like Molecule 5 (SALM5) and similar proteins. The SALM (for synaptic adhesion-like molecules; also known as Lrfn for leucine-rich repeat and fibronectin type III domain containing) family of adhesion molecules consists of five known members: SALM1/Lrfn2, SALM2/Lrfn1, SALM3/Lrfn4, SALM4/Lrfn3, and SALM5/Lrfn5. SALMs share a similar domain structure, containing leucine-rich repeats (LRRs), an immunoglobulin (Ig) domain, and a fibronectin III (FNIII) domain, followed by a transmembrane domain and a C-terminal PDZ-binding motif. SALM5 is implicated in autism spectrum disorders (ASDs) and schizophrenia, induces presynaptic differentiation in contacting axons. SALM5 interacts with the Ig domains of LAR (Leukocyte common Antigen-Related) family receptor protein tyrosine phosphatases (LAR-RPTPs; LAR, PTPdelta, and PTPsigma). In addition, PTPdelta is implicated in ASDs, ADHD, bipolar disorder, and restless leg syndrome. Studies have shown that LAR-RPTPs are novel and splicing-dependent presynaptic ligands for SALM5, and that they mediate SALM5-dependent presynaptic differentiation. Furthermore, SALM5 maintains AMPA receptor (AMPAR)-mediated excitatory synaptic transmission through mechanisms involving the interaction of SALM5 with LAR-RPTPs. This group belongs to the I-set of immunoglobulin superfamily (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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27894324  18 AKFSKQSWGLENEALIVRCPRQGKPSYTVDWYySQTNKSIPTQERNRVFASGQLlKFLPAAVADSGIYTCIVRSPTFNRT 97
Cdd:cd05764   4 TRHTHELRVLEGQRATLRCKARGDPEPAIHWI-SPEGKLISNSSRTLVYDNGTL-DILITTVKDTGAFTCIASNPAGEAT 81

                ....*..
gi 27894324  98 GYANVTI 104
Cdd:cd05764  82 ARVELHI 88

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 27894324 212 PVIGAPAqNEIKEVEIGKNANLTCSACfgkgTQFLAAVLWQLNGTKITD----FGEPRIQQEEGQNQSFSNglacLDMVL 287
Cdd:cd20932   1 PVIVSPA-NETMEVDLGSQIQLICNVT----GQLSDLAYWKWNGSEIDEddpvLGEDYYSVENPANKRKST----LITVL 71

                        90       100       110
                ....*....|....*....|....*....|.
gi 27894324 288 RIADVKEEDLLLQYDCLALNLHGLRRHTVRL 318
Cdd:cd20932  72 NISEIESRFYKHPFTCFAKNTHGLDAAYVQL 102

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 27894324  27 LENEALIVRCPRQGKPSYTVDWYysQTNKSIPTQERNRVFASGQLLKFLPAAVADSGIYTCIVRSP---TFNRTGYANV 102
Cdd:cd20958  13 VAGQTLRLHCPVAGYPISSITWE--KDGRRLPLNHRQRVFPNGTLVIENVQRSSDEGEYTCTARNQqgqSASRSVFVKV 89

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 27894324  28 ENEALIVRCPRQGK-PSYTVDWYY--SQTNKSIPTQERNRVFASGQLLKFLPAAVADSGIYTCIVRSPTFNRTGYANVTI 104
Cdd:cd05750  13 EGSKLVLKCEATSEnPSPRYRWFKdgKELNRKRPKNIKIRNKKKNSELQINKAKLEDSGEYTCVVENILGKDTVTGNVTV 92

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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 27894324  19 KFSKQSWGLENEALIVRCPRQGKPSYTVDWYYSQTNK-SIPTQERNRVFASGQLlKFLPAAVADSGIYTCI 88
Cdd:cd20969   7 RKAQQVFVDEGHTVQFVCRADGDPPPAILWLSPRKHLvSAKSNGRLTVFPDGTL-EVRYAQVQDNGTYLCI 76

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27894324    120 STVSGSEKNS-KIYCPTIDlyNWTAPLEWFKNCQAL--QGSRYRAHKS----FLVIDNVMTEDAGDYTCkFIHNENGaNY 192
Cdd:smart00410   2 PSVTVKEGESvTLSCEASG--SPPPEVTWYKQGGKLlaESGRFSVSRSgstsTLTISNVTPEDSGTYTC-AATNSSG-SA 77

                   ....*
gi 27894324    193 SVTAT 197
Cdd:smart00410  78 SSGTT 82

TIR domain; This is a family of Toll-like receptors.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 27894324   400 FVHQILpDVLENKcGYTLCIYGRDMLPGEDVVTAVETNIRKSRRHIFILTPQITHNKEFAYEQEVALhcALIQNDAKVIL 479
Cdd:pfam13676  12 WAEWLA-DALEAA-GYRVWLDRWDIRPGDDWVEEIEEAIENSDRVLVVLSPNYLESPWCRAEWEAAL--ADPEGRKRLIP 87

                          90
                  ....*....|...
gi 27894324   480 IEMEALSELDMLQ 492
Cdd:pfam13676  88 VRLECDLELPGLA 100