P58681
SS
Gene name |
Tlr7 |
Protein name |
Toll-like receptor 7 |
Names |
|
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:170743 |
EC number |
|
Protein Class |
|
Descriptions
TLR7 (Toll-like receptor 7) is an endosomal receptor that plays a key role in innate and adaptive immunity by recognizing pathogen-associated molecular patterns. TLR7 triggers antiviral immune responses by recognizing viral single-stranded RNA in endosomes. TLR7 is a type I transmembrane protein characterized by an extracellular leucine-rich repeat (LRR) domain, a transmembrane helix, and an intracellular Toll/interleukin-1 receptor (TIR) homology domain. Upon binding to agonists, TLR7 undergoes dimerization that brings TIR domains from the two molecules into direct contact, leading to the recruitment of TIR-containing downstream adapter MYD88 through homotypic interaction. TLR7 is also proteolytically cleaved in different human immune and nonimmune cells and that cleavage processing is required for functional activity. TLR7 cleavage generates within the loop between LRRs 14 and 15 and requires calcium-dependent serine proteases of the furin-like PC family.
Autoinhibitory domains (AIDs)
Target domain |
27-846 (LRR domains) |
Relief mechanism |
Cleavage |
Assay |
|
Accessory elements
No accessory elements
References
- Hipp MM et al. (2013) "Processing of human toll-like receptor 7 by furin-like proprotein convertases is required for its accumulation and activity in endosomes", Immunity, 39, 711-21
- Tanji H et al. (2016) "Autoinhibition and relief mechanism by the proteolytic processing of Toll-like receptor 8", Proceedings of the National Academy of Sciences of the United States of America, 113, 3012-7
Autoinhibited structure
Activated structure
1 structures for P58681
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-P58681-F1 | Predicted | AlphaFoldDB |
58 variants for P58681
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs31639849 | 21 | V>L | No | EVA | |
| rs3389491350 | 32 | K>N | No | EVA | |
| rs253546462 | 39 | K>E | No | EVA | |
| rs233888144 | 43 | P>Q | No | EVA | |
| rs3389562828 | 43 | P>VSDG* | No | EVA | |
| rs3389583562 | 47 | V>L | No | EVA | |
| rs3389586998 | 80 | I>T | No | EVA | |
| rs3389533344 | 117 | Q>* | No | EVA | |
| rs3389589664 | 125 | G>R | No | EVA | |
| rs3389581512 | 129 | L>F | No | EVA | |
| rs244868347 | 151 | H>Q | No | EVA | |
| rs3389592387 | 158 | N>I | No | EVA | |
| rs3389589597 | 163 | I>V | No | EVA | |
| rs31639847 | 172 | V>I | No | EVA | |
| rs3389589477 | 240 | I>F | No | EVA | |
| rs211881097 | 243 | N>D | No | EVA | |
| rs3389576373 | 247 | N>K | No | EVA | |
| rs3389577079 | 249 | N>D | No | EVA | |
| rs3412527070 | 280 | Q>H | No | EVA | |
| rs3389581480 | 283 | D>N | No | EVA | |
| rs3412643299 | 292 | L>S | No | EVA | |
| rs3412561013 | 302 | L>HHVGGTC* | No | EVA | |
| rs1133816742 | 312 | N>D | No | EVA | |
| rs1133390057 | 322 | S>C | No | EVA | |
| rs3411256955 | 343 | V>I | No | EVA | |
| rs233643224 | 364 | H>N | No | EVA | |
| rs3389576392 | 444 | F>L | No | EVA | |
| rs3389533353 | 448 | A>D | No | EVA | |
| rs239554154 | 463 | L>I | No | EVA | |
| rs3412945857 | 487 | P>T | No | EVA | |
| rs3412833469 | 499 | L>I | No | EVA | |
| rs3411257015 | 527 | G>E | No | EVA | |
| rs3389562846 | 608 | D>G | No | EVA | |
| rs3389583629 | 623 | R>Q | No | EVA | |
| rs3389578706 | 624 | I>M | No | EVA | |
| rs3412527046 | 633 | D>G | No | EVA | |
| rs3389540446 | 638 | A>S | No | EVA | |
| rs3412560979 | 638 | A>V | No | EVA | |
| rs3412945837 | 641 | N>K | No | EVA | |
| rs3389578700 | 651 | F>L | No | EVA | |
| rs220807359 | 692 | F>I | No | EVA | |
| rs266177713 | 692 | F>S | No | EVA | |
| rs247647296 | 695 | R>K | No | EVA | |
| rs225240804 | 703 | E>K | No | EVA | |
| rs3389540527 | 714 | K>E | No | EVA | |
| rs3555115249 | 738 | Q>K | No | EVA | |
| rs232994627 | 777 | E>K | No | EVA | |
| rs220246438 | 778 | M>I | No | EVA | |
| rs3389583560 | 897 | V>M | No | EVA | |
| rs3412807713 | 927 | L>* | No | EVA | |
| rs3389583573 | 961 | K>I | No | EVA | |
| rs3389577046 | 964 | K>M | No | EVA | |
| rs3389491392 | 971 | A>T | No | EVA | |
| rs3389584092 | 976 | H>Q | No | EVA | |
| rs3389550894 | 994 | K>R | No | EVA | |
| rs3389533420 | 1008 | L>I | No | EVA | |
| rs3389576389 | 1033 | A>V | No | EVA | |
| rs259850407 | 1045 | M>V | No | EVA |
No associated diseases with P58681
No regional properties for P58681
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| No domain, repeats, and functional sites for P58681 | |||
Functions
9 GO annotations of cellular component
| Name | Definition |
|---|---|
| cytoplasm | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. |
| early phagosome | A membrane-bounded intracellular vesicle as initially formed upon the ingestion of particulate material by phagocytosis. |
| endoplasmic reticulum | The irregular network of unit membranes, visible only by electron microscopy, that occurs in the cytoplasm of many eukaryotic cells. The membranes form a complex meshwork of tubular channels, which are often expanded into slitlike cavities called cisternae. The ER takes two forms, rough (or granular), with ribosomes adhering to the outer surface, and smooth (with no ribosomes attached). |
| endoplasmic reticulum membrane | The lipid bilayer surrounding the endoplasmic reticulum. |
| endosome | A vacuole to which materials ingested by endocytosis are delivered. |
| endosome membrane | The lipid bilayer surrounding an endosome. |
| lysosome | A small lytic vacuole that has cell cycle-independent morphology found in most animal cells and that contains a variety of hydrolases, most of which have their maximal activities in the pH range 5-6. The contained enzymes display latency if properly isolated. About 40 different lysosomal hydrolases are known and lysosomes have a great variety of morphologies and functions. |
| plasma membrane | The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins. |
| receptor complex | Any protein complex that undergoes combination with a hormone, neurotransmitter, drug or intracellular messenger to initiate a change in cell function. |
4 GO annotations of molecular function
| Name | Definition |
|---|---|
| double-stranded RNA binding | Binding to double-stranded RNA. |
| pattern recognition receptor activity | Combining with a pathogen-associated molecular pattern (PAMP), a structure conserved among microbial species to initiate an innate immune response. |
| single-stranded RNA binding | Binding to single-stranded RNA. |
| siRNA binding | Binding to a small interfering RNA, a 21-23 nucleotide RNA that is processed from double stranded RNA (dsRNA) by an RNAse enzyme. |
22 GO annotations of biological process
| Name | Definition |
|---|---|
| cellular response to mechanical stimulus | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a mechanical stimulus. |
| cellular response to virus | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus from a virus. |
| defense response to virus | Reactions triggered in response to the presence of a virus that act to protect the cell or organism. |
| I-kappaB kinase/NF-kappaB signaling | The process in which a signal is passed on to downstream components within the cell through the I-kappaB-kinase (IKK)-dependent activation of NF-kappaB. The cascade begins with activation of a trimeric IKK complex (consisting of catalytic kinase subunits IKKalpha and/or IKKbeta, and the regulatory scaffold protein NEMO) and ends with the regulation of transcription of target genes by NF-kappaB. In a resting state, NF-kappaB dimers are bound to I-kappaB proteins, sequestering NF-kappaB in the cytoplasm. Phosphorylation of I-kappaB targets I-kappaB for ubiquitination and proteasomal degradation, thus releasing the NF-kappaB dimers, which can translocate to the nucleus to bind DNA and regulate transcription. |
| I-kappaB phosphorylation | The process of introducing a phosphate group into an inhibitor of kappa B (I-kappaB) protein. Phosphorylation of I-kappaB targets I-kappaB for ubiquitination and proteasomal degradation, thus releasing bound NF-kappaB dimers, which can translocate to the nucleus to bind DNA and regulate transcription. |
| inflammatory response | The immediate defensive reaction (by vertebrate tissue) to infection or injury caused by chemical or physical agents. The process is characterized by local vasodilation, extravasation of plasma into intercellular spaces and accumulation of white blood cells and macrophages. |
| innate immune response | Innate immune responses are defense responses mediated by germline encoded components that directly recognize components of potential pathogens. |
| JNK cascade | An intracellular protein kinase cascade containing at least a JNK (a MAPK), a JNKK (a MAPKK) and a JUN3K (a MAP3K). The cascade can also contain an additional tier |
| MAPK cascade | An intracellular protein kinase cascade containing at least a MAPK, a MAPKK and a MAP3K. The cascade can also contain an additional tiers |
| positive regulation of chemokine production | Any process that activates or increases the frequency, rate, or extent of chemokine production. |
| positive regulation of interferon-alpha production | Any process that activates or increases the frequency, rate, or extent of interferon-alpha production. |
| positive regulation of interferon-beta production | Any process that activates or increases the frequency, rate, or extent of interferon-beta production. |
| positive regulation of interleukin-6 production | Any process that activates or increases the frequency, rate, or extent of interleukin-6 production. |
| positive regulation of interleukin-8 production | Any process that activates or increases the frequency, rate, or extent of interleukin-8 production. |
| positive regulation of macrophage cytokine production | Any process that increases the rate, frequency or extent of macrophage cytokine production. Macrophage cytokine production is the appearance of a chemokine due to biosynthesis or secretion following a cellular stimulus, resulting in an increase in its intracellular or extracellular levels. |
| positive regulation of NIK/NF-kappaB signaling | Any process that activates or increases the frequency, rate or extent of NIK/NF-kappaB signaling. |
| positive regulation of transcription by RNA polymerase II | Any process that activates or increases the frequency, rate or extent of transcription from an RNA polymerase II promoter. |
| positive regulation of type II interferon production | Any process that activates or increases the frequency, rate, or extent of interferon-gamma production. Interferon-gamma is also known as type II interferon. |
| regulation of protein phosphorylation | Any process that modulates the frequency, rate or extent of addition of phosphate groups into an amino acid in a protein. |
| response to cGMP | Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a cGMP (cyclic GMP, guanosine 3',5'-cyclophosphate) stimulus. |
| toll-like receptor 7 signaling pathway | The series of molecular signals initiated by a ligand binding to the endolysosomal toll-like receptor 7. |
| toll-like receptor signaling pathway | The series of molecular signals initiated by a ligand binding to a toll-like receptor of a target cell. Toll-like receptors directly bind pattern motifs from a variety of microbial sources to initiate an innate immune response. |
10 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| Q5I2M7 | TLR9 | Toll-like receptor 9 | Felis catus (Cat) (Felis silvestris catus) | SS |
| Q5I2M8 | TLR9 | Toll-like receptor 9 | Canis lupus familiaris (Dog) (Canis familiaris) | SS |
| P08953 | Tl | Protein toll | Drosophila melanogaster (Fruit fly) | PR |
| Q2EEY0 | TLR9 | Toll-like receptor 9 | Equus caballus (Horse) | SS |
| Q9NR96 | TLR9 | Toll-like receptor 9 | Homo sapiens (Human) | EV |
| Q9NYK1 | TLR7 | Toll-like receptor 7 | Homo sapiens (Human) | EV |
| P58682 | Tlr8 | Toll-like receptor 8 | Mus musculus (Mouse) | SS |
| Q9EQU3 | Tlr9 | Toll-like receptor 9 | Mus musculus (Mouse) | SS |
| Q5I2M3 | TLR9 | Toll-like receptor 9 | Sus scrofa (Pig) | SS |
| A5H2Z9 | Tlr7 | Toll-like receptor 7 | Rattus norvegicus (Rat) | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MVFSMWTRKR | QILIFLNMLL | VSRVFGFRWF | PKTLPCEVKV | NIPEAHVIVD | CTDKHLTEIP |
| 70 | 80 | 90 | 100 | 110 | 120 |
| EGIPTNTTNL | TLTINHIPSI | SPDSFRRLNH | LEEIDLRCNC | VPVLLGSKAN | VCTKRLQIRP |
| 130 | 140 | 150 | 160 | 170 | 180 |
| GSFSGLSDLK | ALYLDGNQLL | EIPQDLPSSL | HLLSLEANNI | FSITKENLTE | LVNIETLYLG |
| 190 | 200 | 210 | 220 | 230 | 240 |
| QNCYYRNPCN | VSYSIEKDAF | LVMRNLKVLS | LKDNNVTAVP | TTLPPNLLEL | YLYNNIIKKI |
| 250 | 260 | 270 | 280 | 290 | 300 |
| QENDFNNLNE | LQVLDLSGNC | PRCYNVPYPC | TPCENNSPLQ | IHDNAFNSLT | ELKVLRLHSN |
| 310 | 320 | 330 | 340 | 350 | 360 |
| SLQHVPPTWF | KNMRNLQELD | LSQNYLAREI | EEAKFLHFLP | NLVELDFSFN | YELQVYHASI |
| 370 | 380 | 390 | 400 | 410 | 420 |
| TLPHSLSSLE | NLKILRVKGY | VFKELKNSSL | SVLHKLPRLE | VLDLGTNFIK | IADLNIFKHF |
| 430 | 440 | 450 | 460 | 470 | 480 |
| ENLKLIDLSV | NKISPSEESR | EVGFCPNAQT | SVDRHGPQVL | EALHYFRYDE | YARSCRFKNK |
| 490 | 500 | 510 | 520 | 530 | 540 |
| EPPSFLPLNA | DCHIYGQTLD | LSRNNIFFIK | PSDFQHLSFL | KCLNLSGNTI | GQTLNGSELW |
| 550 | 560 | 570 | 580 | 590 | 600 |
| PLRELRYLDF | SNNRLDLLYS | TAFEELQSLE | VLDLSSNSHY | FQAEGITHML | NFTKKLRLLD |
| 610 | 620 | 630 | 640 | 650 | 660 |
| KLMMNDNDIS | TSASRTMESD | SLRILEFRGN | HLDVLWRAGD | NRYLDFFKNL | FNLEVLDISR |
| 670 | 680 | 690 | 700 | 710 | 720 |
| NSLNSLPPEV | FEGMPPNLKN | LSLAKNGLKS | FFWDRLQLLK | HLEILDLSHN | QLTKVPERLA |
| 730 | 740 | 750 | 760 | 770 | 780 |
| NCSKSLTTLI | LKHNQIRQLT | KYFLEDALQL | RYLDISSNKI | QVIQKTSFPE | NVLNNLEMLV |
| 790 | 800 | 810 | 820 | 830 | 840 |
| LHHNRFLCNC | DAVWFVWWVN | HTDVTIPYLA | TDVTCVGPGA | HKGQSVISLD | LYTCELDLTN |
| 850 | 860 | 870 | 880 | 890 | 900 |
| LILFSVSISS | VLFLMVVMTT | SHLFFWDMWY | IYYFWKAKIK | GYQHLQSMES | CYDAFIVYDT |
| 910 | 920 | 930 | 940 | 950 | 960 |
| KNSAVTEWVL | QELVAKLEDP | REKHFNLCLE | ERDWLPGQPV | LENLSQSIQL | SKKTVFVMTQ |
| 970 | 980 | 990 | 1000 | 1010 | 1020 |
| KYAKTESFKM | AFYLSHQRLL | DEKVDVIILI | FLEKPLQKSK | FLQLRKRLCR | SSVLEWPANP |
| 1030 | 1040 | ||||
| QAHPYFWQCL | KNALTTDNHV | AYSQMFKETV |