TRIM11 (Kr.
1q42.13), RNF92
TRIM11 geeni koodaa
tripartiittimotiivin omaavaa proteiinia TRIM-perheestä. Motiiviin
kuuluu kolme sinkkiä sitovaa domeenia: RING, Bbox1, Bbox2 ja
Coiled-Coil (RBBCC) . C-terminaalin perusteella se kuuluu alaryhmään
C_UC, PRYSPRY. Proteiini lokalisoituu tumaan ja sytoplasmaan. Sen
funktio ei ollut vielä vuonna 2008 tunnistettu. Geeniä esiintyy
yleisesiti luuytimessä, pernassa ja 25 muussa kudoksessa. Se
tunnetaan myös nimillä B1A1 ja RNF9 ( Ring Finger Protein) .
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- Also known as BIA1; RNF92. Summary The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. This protein localizes to the nucleus and the cytoplasm. Its function has not been identified. [provided by RefSeq, Jul 2008] Expression Ubiquitous expression in bone marrow (RPKM 7.7), spleen (RPKM 6.4) and 25 other tissues See more
TRIM11 rakenne Konservoidut domeenit
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Conserved Domains (3) summary
cd15811
Location:288 → 456
Location:288 → 456
SPRY_PRY_TRIM11;
PRY/SPRY domain of tripartite motif-binding protein 11 (TRIM11), also
known as RING finger protein 92 (RNF92)
pfam00643
Location:87 → 128
Location:87 → 128
zf-B_box; B-box zinc
finger
cd16594
Location:13 → 57
Location:13 → 57
RING-HC_TRIM11_like_C-IV;
RING finger, HC subclass, found in tripartite motif-containing
proteins, TRIM11 and TRIM27, and similar proteins
E3 ubiquitin-protein ligase TRIM11 [Homo sapiens]
NCBI Reference Sequence: NP_660215.1Identical Proteins FASTA Graphics
LOCUS NP_660215 468 aa linear PRI 08-APR-2018 DEFINITION E3 ubiquitin-protein ligase TRIM11 [Homo sapiens]. ACCESSION NP_660215 VERSION NP_660215.1 DBSOURCE REFSEQ: accession NM_145214.2 KEYWORDS RefSeq. SOURCE Homo sapiens (human) ORGANISM Homo sapiens Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo. REFERENCE 1 (residues 1 to 468) AUTHORS Zhang,Z., Xu,C., Zhang,X., Huang,L., Zheng,C., Chen,H., Wang,Y., Ju,H. and Yao,Q. TITLE TRIM11 Upregulation Contributes to Proliferation, Invasion, and EMT of Hepatocellular Carcinoma Cells JOURNAL Oncol. Res. 25 (5), 691-699 (2017) PUBMED 28244856 REMARK GeneRIF: TRIM11 to be overexpressed in HCC tissues and cell lines. Downregulation of TRIM11 inhibited HCC cell proliferation and invasion in vitro and in vivo as well as suppressed the epithelial-mesenchymal transition (EMT) process. REFERENCE 2 (residues 1 to 468) AUTHORS Chen Y, Li L, Qian X, Ge Y and Xu G. TITLE High expression of TRIM11 correlates with poor prognosis in patients with hepatocellular carcinoma JOURNAL Clin Res Hepatol Gastroenterol 41 (2), 190-196 (2017) PUBMED 28065743 REMARK GeneRIF: data showed that tripartite motif-containing protein 11(TRIM11) expression was significantly elevated in hepatocellular carcinoma(HCC) tissues and overexpression of TRIM11 is closely associated with HCC progression and poor survival REFERENCE 3 (residues 1 to 468) AUTHORS Liu J, Rao J, Lou X, Zhai J, Ni Z and Wang X. TITLE Upregulated TRIM11 Exerts its Oncogenic Effects in Hepatocellular Carcinoma Through Inhibition of P53 JOURNAL Cell. Physiol. Biochem. 44 (1), 255-266 (2017) PUBMED 29190611 REMARK GeneRIF: TRIM11 promotes the development and progression of HCC through regulating p53 and its downstream signals. REFERENCE 4 (residues 1 to 468) AUTHORS Yin Y, Zhong J, Li SW, Li JZ, Zhou M, Chen Y, Sang Y and Liu L. TITLE TRIM11, a direct target of miR-24-3p, promotes cell proliferation and inhibits apoptosis in colon cancer JOURNAL Oncotarget 7 (52), 86755-86765 (2016) PUBMED 27888625 REMARK GeneRIF: Data show that miR-24-3p downregulation contributes to tripartite motif-containing protein 11 (TRIM11) upregulation in cancer (CC). REFERENCE 5 (residues 1 to 468) AUTHORS Yuan T, Yao W, Tokunaga K, Yang R and Sun B. TITLE An HIV-1 capsid binding protein TRIM11 accelerates viral uncoating JOURNAL Retrovirology 13 (1), 72 (2016) PUBMED 27737691 REMARK GeneRIF: study identified TRIM11 as a new HIV-1 capsid binding protein; data also reveal that TRIM11 restricts HIV-1 reverse transcription by accelerating viral uncoating, and microtubule dynamics is implicated in TRIM11-imposed block to early events of HIV-1 replication Publication Status: Online-Only REFERENCE 6 (residues 1 to 468) AUTHORS Uchil PD, Quinlan BD, Chan WT, Luna JM and Mothes W. TITLE TRIM E3 ligases interfere with early and late stages of the retroviral life cycle JOURNAL PLoS Pathog. 4 (2), e16 (2008) PUBMED 18248090 REMARK GeneRIF: Downregulation of TRIM11 and TRIM15 enhanced virus release suggesting that these proteins contribute to the endogenous restriction of retroviruses in cells. REFERENCE 7 (residues 1 to 468) AUTHORS Ishikawa H, Tachikawa H, Miura Y and Takahashi N. TITLE TRIM11 binds to and destabilizes a key component of the activator-mediated cofactor complex (ARC105) through the ubiquitin-proteasome system JOURNAL FEBS Lett. 580 (20), 4784-4792 (2006) PUBMED 16904669 REMARK GeneRIF: These results suggest that TRIM11, with the ubiquitin-proteasome pathway, regulates ARC105 function in TGFbeta signaling. REFERENCE 8 (residues 1 to 468) AUTHORS Cooper ST and Hanson IM. TITLE A screen for proteins that interact with PAX6: C-terminal mutations disrupt interaction with HOMER3, DNCL1 and TRIM11 JOURNAL BMC Genet. 6, 43 (2005) PUBMED 16098226 REMARK GeneRIF: PAX6 interacts with HOMER3, DNCL1, and TRIM11. Three C-terminal PAX6 mutations, previously identified in patients with eye malformations, all reduced or abolished the interactions. Publication Status: Online-Only REFERENCE 9 (residues 1 to 468) AUTHORS Niikura T, Hashimoto Y, Tajima H, Ishizaka M, Yamagishi Y, Kawasumi M, Nawa M, Terashita K, Aiso S and Nishimoto I. TITLE A tripartite motif protein TRIM11 binds and destabilizes Humanin, a neuroprotective peptide against Alzheimer's disease-relevant insults JOURNAL Eur. J. Neurosci. 17 (6), 1150-1158 (2003) PUBMED 12670303 REFERENCE 10 (residues 1 to 468) AUTHORS Reymond A, Meroni G, Fantozzi A, Merla G, Cairo S, Luzi L, Riganelli D, Zanaria E, Messali S, Cainarca S, Guffanti A, Minucci S, Pelicci PG and Ballabio A. TITLE The tripartite motif family identifies cell compartments JOURNAL EMBO J. 20 (9), 2140-2151 (2001) PUBMED 11331580 COMMENT REVIEWED REFSEQ: This record has been curated by NCBI staff. The reference sequence was derived from AF327056.1. Summary: The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. This protein localizes to the nucleus and the cytoplasm. Its function has not been identified. [provided by RefSeq, Jul 2008]. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: AF327056.1, SRR1163655.627443.1 [ECO:0000332] RNAseq introns :: single sample supports all introns SAMEA1966682, SAMEA2145544 [ECO:0000348] ##Evidence-Data-END## FEATURES Location/Qualifiers source 1..468 /organism="Homo sapiens" /db_xref="taxon:9606" /chromosome="1" /map="1q42.13" Protein 1..468 /product="E3 ubiquitin-protein ligase TRIM11" /EC_number="2.3.2.27" /note="tripartite motif-containing protein 11; RING finger protein 92; RING-type E3 ubiquitin transferase TRIM11" /calculated_mol_wt=52643 Region 13..57 /region_name="RING-HC_TRIM11_like_C-IV" /note="RING finger, HC subclass, found in tripartite motif-containing proteins, TRIM11 and TRIM27, and similar proteins; cd16594" /db_xref="CDD:319508" Region 16..56 /region_name="RING-HC finger (C3HC4-type)" /note="RING-HC finger (C3HC4-type) [structural motif]" /db_xref="CDD:319508" Site order(16,19,31,33,36,39,53,56) /site_type="other" /note="Zn binding site [ion binding]" /db_xref="CDD:319508" Site 85 /site_type="phosphorylation" /experiment="experimental evidence, no additional details recorded" /note="Phosphoserine. {ECO:0000244|PubMed:24275569}; propagated from UniProtKB/Swiss-Prot (Q96F44.2)" Region 87..128 /region_name="zf-B_box" /note="B-box zinc finger; pfam00643" /db_xref="CDD:306989" Site order(92,95,114,120) /site_type="other" /note="Zn2+ binding site [ion binding]" /db_xref="CDD:237988" Region 288..456 /region_name="SPRY_PRY_TRIM11" /note="PRY/SPRY domain of tripartite motif-binding protein 11 (TRIM11), also known as RING finger protein 92 (RNF92); cd15811" /db_xref="CDD:293983" CDS 1..468 /gene="TRIM11" /gene_synonym="BIA1; RNF92" /coded_by="NM_145214.2:256..1662" /db_xref="CCDS:CCDS31048.1" /db_xref="GeneID:81559" /db_xref="HGNC:HGNC:16281" /db_xref="MIM:607868" ORIGIN 1 maapdlstnl qeeatcaicl dyftdpvmtd cghnfcreci rrcwgqpegp yacpecrels 61 pqrnlrpnrp lakmaemarr lhppspvpqg vcpahrepla afcgdelrll caacersgeh 121 wahrvrplqd aaedlkakle kslehlrkqm qdallfqaqa detcvlwqkm vesqrqnvlg 181 eferlrrlla eeeqqllqrl eeeelevlpr lregaahlgq qsahlaelia elegrcqlpa 241 lgllqdikda lrrvqdvklq ppevvpmelr tvcrvpglve tlrrfrgdvt ldpdtanpel 301 ilsedrrsvq rgdlrqalpd sperfdpgpc vlgqerftsg rhywevevgd rtswalgvcr 361 envnrkekge lsagngfwil vflgsyynss eralaplrdp prrvgifldy eaghlsfysa 421 tdgsllfifp eipfsgtlrp lfsplssspt pmticrpkgg sgdtlapq //
TRIM11 ja HIV1
| Pr55(Gag) | gag | HIV-1 infection is modestly restricted by human TRIM11 and downregulation of TRIM11 enhances virus release, suggesting the interaction between HIV-1 Gag and TRIM11 | PubMed |
| Vpr | vpr | HIV-1 Vpr may indirectly regulate TRIM11 in a dose-dependent manner, which is independent of the ubiquitin system or VprBP-mediated pathway | PubMed |
TRIM11-onkogeeni ja maksasyöpä
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Upregulated TRIM11 Exerts its Oncogenic Effects in Hepatocellular Carcinoma Through Inhibition of P53. Liu J, et al. Cell Physiol Biochem, 2017. PMID 29190611
SUOMENNOS: Ylössäätynyt TRIM 11
vaikuttaa onkogeenisesti maksasolusyövässä estämällä p54.
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TRIM11 Upregulation Contributes to Proliferation, Invasion, and EMT of Hepatocellular Carcinoma Cells. Zhang Z, et al. Oncol Res, 2017 May 24. PMID 28244856
SUOMENNOS: TRIM11 ylössäätyminen
osaltaan vaikuttaa maksasolusyövässä proliferaatiota,
invasoitumista ja epiteliaalisesta mesenkymaaliseen transitiota(EMT).
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High expression of TRIM11 correlates with poor prognosis in patients with hepatocellular carcinoma. Chen Y, et al. Clin Res Hepatol Gastroenterol, 2017 Mar. PMID 28065743
SUOMENNOS: TRIM1 korkea ilmentyminen
korreloi maksasolusyövässä huonoon prognoosiin.
TRIM-onkogeeni ja keuhkosyöpä
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TRIM11 overexpression promotes proliferation, migration and invasion of lung cancer cells. Wang X, et al. J Exp Clin Cancer Res, 2016 Jun 21. PMID 27329103, Free PMC Article
SUOMENNOS: TRIM11 yliilmentyminen
edistää keuhkosyöpäsolun proliferoitumista, migroitumista ja
invasoitumista.
TRIM11-onkogeeni ja maligni gliooma
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TRIM11
is overexpressed in high-grade gliomas and promotes proliferation,
invasion, migration and glial tumor growth. Di K, et al.
Oncogene, 2013 Oct 17. PMID 23178488, Free
PMC Article
See all (32) citations in PubMed
TRIM11-miR-24-3p akseli ja kolorektaalisyöpä
SUOMENNOSTA. TRIM11
on osoitettu onkogeeniksi malignissa glioomassa ja keuhkosyövässä
ja tässä artikkelisas raprotoidaan myös sen yliesiintyminen
kolorektaalisyöpäkudoksessa verrattuna normaaliin kudokseen.
Lisäksi korkeat TRIM11 pitoisuudet olivat syöpäpotilalle huonon
ennusteen merkki elossapysymisestä ja tautivapaasta väliajasta.
Mekanistisesti tutkijat osoittivat , että mikroRNA miR-24-3p:n
alassäätö vaikutti osaltaan TRIM11:n ylössäätymisen. TRIM11n
ylössäätyminen edisti soluproliferaatiota ja kolonisaatiota ja
esti apoptoosia syöpäsoluissa. Mutta TRIM11-poistogeenisyys
geenimuovauksella esti soluproliferaation ja indusoi apoptoosin.
Hiljennetty TRIM11 in vivo vähensi tuumorikasvua. Löydöt
viittaavat siihen, että TRIM11 nopuettaa kolorektaalia syöpää
soluproliferaatiolla ja estämällä apotoosin; uusi havainto
mikroRNA miR-24-3p/TRIM11-akselista saattaa olla hyödyksi
kolorektaalipotilaiden kohdennetussa terapiassa.
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TRIM11 (tripartite motif-containing protein 11) is an E3 ubiquitin ligase recently identified as an oncogene in malignant glioma and lung cancer. In the present study, we report that expression of TRIM11 was increased in colon cancer (CC) tissue relative to paired normal tissues and that higher TRIM11 levels predicted poor overall survival (OS) and disease-free survival (DFS) in CC patients. Mechanistically, we showed that miR-24-3p downregulation contributes to TRIM11 upregulation in CC. We also demonstrated that TRIM11 overexpression promotes cell proliferation and colony formation and inhibits apoptosis in CC, while knocking down TRIM11 using CRISPR/Cas9-mediated genome editing inhibited cell proliferation and induced apoptosis. Silencing TRIM11 in vivo decreased tumor growth. These findings indicate that TRIM11 facilitates CC progression by promoting cell proliferation and inhibiting apoptosis and that the novel miR-24-3p/TRIM11 axis may be a useful new target for treating patients with CC.
TRIM11 johtaa inflammasomia AIM2 autofagosytoosilla hajoitettavaksi p62 välitteisesti
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TRIM11 Suppresses AIM2 Inflammasome by Degrading AIM2 via p62-Dependent Selective Autophagy. Liu T, Tang Q, Liu K, Xie W, Liu X, Wang H, Wang RF,
SUOMENNOSTA: AIM2-
inflammasomi on sytosolinen kompleksi, joka aktivoituu dsDNA:sta
johtaen proinflamamtoristen sytokiinien kypsymiseen ja näitä ovat IL-1Beta ja IL-18. Jos AIM2-inflammasomi toimii huonosti, ihmisellä
esiintyy tulehdustauteja ja syöpää, mikä viitaa siihen että
tämän infalmmasomin täytyy olla tiukasti säädelty. TRIM11 on
tämän inflammasomin eräsavainasemassa oleva negatiivinen
säätelijä. Kun soluun tulee DNA-virusinfektio, TRIM11 sitoutuu
AIM2:teen sen PS-domaanin välityksellä ja käy itse läpi
auto-polyubikitinaation lysiiniin K458, mikä edistää TRIM11:n
ja autofagisen kuorman reseptorin p62 assosioitumista välittämään
AIM2:n hajottamista selektiivisellä autofagialla. Nämä löydöt
tunnistavat TRIM11:n osuuden AIM2 inflammasomin aktivaatiossa, josa
TRIM11 toimii sekundäärisenä reseptorina johtamassa AIM2
hajoitettavaksi selektiivisella autofagialla 62:sta riippuvalla
tavalla.KTS: kuva
https://www.sciencedirect.com/science/article/pii/S2211124716309056
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The AIM2 inflammasome is a key cytosolic signaling complex that is activated by double-stranded DNA, leading to the maturation of proinflammatory cytokines such as interleukin-1β (IL-1β) and IL-18. Dysregulated AIM2 inflammasome activity is associated with human inflammatory diseases and cancers, suggesting that its activity must be tightly regulated. However, the precise molecular mechanisms that control AIM2 levels and activity are still poorly understood. Here, we report tripartite motif 11 (TRIM11) as a key negative regulator of the AIM2 inflammasome. Upon DNA virus infection, TRIM11 binds to AIM2 via its PS domain and undergoes auto-polyubiquitination at K458 to promote an association between TRIM11 and the autophagic cargo receptor p62 to mediate AIM2 degradation via selective autophagy. These findings identify a role for TRIMs in AIM2 inflammasome activation where TRIM11 acts as a secondary receptor to deliver AIM2 to the autophagosomes for degradation in a p62-dependent manner. KEYWORDS: AIM2 inflammasome; TRIM11; p62; protein degradation; selective autophagy
TRIM11 esti RIG-1 välitteistä IFNbeta tuotantoa kohdentamalla TBK1-signaalikompleksiin
SUOMENNOS:
Luonnollinen immuuivaste on isäntäsolun puolustusmekanimsi
viruksien ja bakteerienaiheuttamaa infektiota vastaan. Ykköstyypin
interferoneilla (INFalfa/beta) on ratkaiseva osuus luonnollisessa
immuunivasteessa. Jos IFN-tuotanto ei ole tiukasti kontrolloitua
normaalitilassa ja immuunivasteissa, tuotanto voi suistua
raiteiltaan johtaen tulehduksellisiin ja autoimmuunitauteihin. Tässä
artikkelissa raportoidaan, miten TRIM11 on IFNbeta-tuotannon
negatiivinen säätelijä. TRIM11:n ektooppinen ilmentäminen vähensi
IFNbeta-promoottorin aktiivisuutta, jonka oli indusoinut poly( I:C)
stimulaatio tai RIG-1-signaaliketjunn komponenttien RIG-IN, MAVS ja
TBK1 yli-ilmentäminen. TRIM11-poistogeenisyys taas lisäsi sitä
IFNbeta-promoottorin aktiivisuutta, mitä edellä mainittu
signaaliketju aiheuttaa, sillä IRF3 pääsi fosforyloitumaan ja
dimerisoitumaan, siirtymään tumaan ja aiheuttamaan tuottui
IFNbeta mRNA:n ilmenemistä.
TRIM11:n
yli-ilmentäminen esti IRF3-fosforylaation ja dimerisaation ja
IFNbeta mRNA:n ilmenemisen.
Tutkijat
havaitsivat, että TRIM11 teki interaktion TBK1-siganaalikompleksin
aknssa. TBK-1 on avainasemassa oleva kinaasi RIG-1 signaalitiessä ja
fosforyloi IRF3:n. TRIM11:n interaktio sen kanssa lisääntyi, jos
läsä oli lisäksi TBK1adaptoriproteiini NAP1 tai SINTBAD tai TANK.
Koska TRIM11:n
yli-esiintymä esti RIG-1 välitteistä interferonin tuotantoa, se
lisäsi viruksen infektiivisyyttä ja poistogeenisyydellä oli
päinvastainen vaikutus. Yhteenvetona: TRIM11 esti RIG-1 välitteisen
IFNbetan tuotannon kohdentamalla estovaikutuksen
TBK1-signalointikompleksiin.
(TBK1 = TANK
binding kinase 1;
NAP1 = NF-kB
activating kinase-associated protein 1; NF-kB:n aktivoivaan
kinaasiin assosioitunut proteiini 1
SINTBAD = Similar to
NAP1 TBK1 adaptor; NAP1:n kaltainen TBK1-sovite eli adaptori;
TANK = TRAF family
member-associated NF-kB activator); TRAF- perheenjäseneen
assosioitunut sovite eli adaptori
TRAF= TNF Receptor
Associated Factor; TNF reseptoriin assosioitunut faktori
TNF , Tumor Nectors
factor; tuumorinekroosifaktori )
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The innate immune response is a host defense mechanism against infection by viruses and bacteria. Type I interferons (IFNα/β) play a crucial role in innate immunity. If not tightly regulated under normal conditions and during immune responses, IFN production can become aberrant, leading to inflammatory and autoimmune diseases. In this study, we identified TRIM11 (tripartite motif containing 11) as a novel negative regulator of IFNβ production. Ectopic expression of TRIM11 decreased IFNβ promoter activity induced by poly (I:C) stimulation or overexpression of RIG-I (retinoic acid-inducible gene-I) signaling cascade components RIG-IN (constitutively active form of RIG-I), MAVS (mitochondrial antiviral signaling protein), or TBK1 (TANK-binding kinase-1). Conversely, TRIM11 knockdown enhanced IFNβ promoter activity induced by these stimuli. Moreover, TRIM11 overexpression inhibited the phosphorylation and dimerization of IRF3 and expression of IFNβ mRNA. By contrast, TRIM11 knockdown increased the IRF3 phosphorylation and IFNβ mRNA expression. We also found that TRIM11 and TBK1, a key kinase that phosphorylates IRF3 in the RIG-I pathway, interacted with each other through CC and CC2 domain, respectively. This interaction was enhanced in the presence of the TBK1 adaptor proteins, NAP1 (NF-κB activating kinase-associated protein-1), SINTBAD (similar to NAP1 TBK1 adaptor) or TANK (TRAF family member-associated NF-κB activator). Consistent with its inhibitory role in RIG-I-mediated IFNβ signaling, TRIM11 overexpression enhanced viral infectivity, whereas TRIM11 knockdown produced the opposite effect. Collectively, our results suggest that TRIM11 inhibits RIG-I-mediated IFNβ production by targeting the TBK1 signaling complex.
Lisätetoa
TRIM11; muita nimiä
ovat RNF92 eli se on RING finger proteiini 92. Lisäksi sillä on
nimi: proteiini B1A1.
Ubikitinaatiokohteet:
Se edistää liukenemattomien ubikitinoitujen proteiinien
hajoittamista.
PAX6,ym. Tässä olen kirjoitanut aiemmin.
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