- Tällä TRIM38 geenillä on muita nimiäkin RNF15 , Zinc finger protein RoRet, ja RORET. (Ro/SSA Ribonucleoprotein homolog) Kromosomisijainti on tarkistettu. Ennen oli tieto 6p21.3 ja nyt 6p22.2. Rakenne on C IV alaryhmää: RING, B-box tyyppi Zn finger ja SPRY domeeni. Tämän proteiinin funktiota ei ole tunnistettu PubMed tiedon mkaan , mutta uusia tutkimuksia on siitä tehty. Tämän geenin pseudogeeni on kr. 4.:n pitkässä haarassa. TRIM38 geeniä ilmenee pernassa, imusolmukkeessa ja 24 muussa kudoksessa.
- RNF15; RORET Summary.This gene encodes a member of the tripartite motif (TRIM) family. The encoded protein contains a RING-type zinc finger, B box-type zinc finger and SPRY domain. The function of this protein has not been identified. A pseudogene of this gene is located on the long arm of chromosome 4. [provided by RefSeq, Jul 2012] Expression: Ubiquitous expression in spleen (RPKM 9.0), lymph node (RPKM 8.4) and 24 other tissues See more
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Enterovirus 71 induces degradation of TRIM38, a potential E3 ubiquitin ligase. Liu X, et al. Virol J, 2011 Feb 10. PMID 21306652, Free PMC Article .. (Suomennosta) TRIM38 funktiot ovat suureksi osaksi tuntemattomia. Tässä tutkijat selvittivät, että se sijaitsee sytoplasmassa ja lisää soluproteiinien ubikitinoitumista ja katalysoi autoubikitinaatiota. Se edistää myös K63- ja K48-välitteistä soluproteiinien ubikitinaatiota. Intakti RING- domeeni on sen funktioille tärkeä. Lisätieto: Enterovirus 71 infektio indusoi TRIM38 proteiinin hajomisen tämän virusinfektion aikana. Nämä havainnot viittaisivat luonnollisen immuniteetin signaalitgeihin.
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TRIM38 is a member of the TRIM protein family, which we studied in more detail here as its functions are largely unknown. Our study shows that, similar to other TRIM family members, TRIM38 is localized in the cytoplasm. TRIM38 increases ubiquitination of other cellular proteins and catalyzes self-ubiquitination. TRIM38 also promotes K63- and K48-linked ubiquitination of cellular proteins. An intact RING domain is important for the functions of TRIM38. In addition, enterovirus 71 infection induces TRIM38 degradation.Our observations demonstrate that TRIM38 has E3 ubiquitin ligase activity and can be degraded during virus infection. These findings may provide insight into innate immune signaling pathways
2. [Identification
A novel protein TRIM38 that activate NF-kappaB signaling pathways].
Liu XL, et al. Zhonghua Shi Yan He Lin Chuang Bing Du Xue
Za Zhi, 2011 Feb. PMID 21789858 .(Suomennosta) Tutkijat halusivat
tietää, vaikuttaako TRIM38 NF-kB-signaalitiehen ja tulivat
johtopäätökseen, että TRIM38 voi aktivoida NF-kB-signaloinititien
ja tässä ei vaikuta SPRYdomaanin deleetiokaan..
-
TRIM38 could activate NF-kappaB signaling pathway. The mutants of TRIM38 affected the function of TRIM38. Only the mutant of SPRY domain deletion had no obviously influence of the function of TRIM38. Our study reveals that NF-kappaB is activated in response to TRIM38.
3. NLRP6
facilitates the interaction between TAB2/3 and TRIM38 in rheumatoid
arthritis fibroblast-like synoviocytes. Lin Y, et al.
FEBS Lett, 2017 Apr. PMID 28295271
(Suomennosta: NLRP6 on tunnettu
negatiivinen säätelijä suolistotulehduksissa ja tumorigeneesissä, ja sen mRNA ja proteiini ovat heikentyneet nivelreumassa. Myos
proinflammatoristen sytokiinien tuotto ja NFkB aktivaatio olivat
heikentyneet RA-FLS soluissa (fibroblastin kaltaisissa
synoviosyyteissä nivelreumassa) . Tässä tutkimuksessa on selvitetty TRIM38
osuutta . NLRP6 näyttää toimivan alustana TRIM38 ja TAB2/3
interaktiolle. NLRP6 yliexpressoituminen edistää TAB2/3
välitteistä lysosomaalisen degradaation tietä.
4. TRIM38
negatively regulates TLR3-mediated IFN-β signaling by targeting
TRIF for degradation. Xue Q, et al. PLoS One, 2012.
PMID 23056470, Free
PMC Article (Suomennosta. Patogeenien voittamisessa Tollin
kaltaisilla reseptoreilla on immuunivasteessa erittäin tärkeä
merkitys. TRIM-proteiinit taas ovat osallistumassa lukuisiin
biologisiin ja fysiologisiin prosesseihin. Jotkut TRIMperheen
jäsenet ovat tärkeitä luonnollisen immuniteetin säätelijöitä.
On kyllä osoitettu, että TRIM38 säätelee negatiivisesti
luonnollista immuniteettia, mutta millä mekanismeilla, se taas on ollut
osin ratkaisematta. Tässä tutkimuksessa osoitetaan, että
TRIM38 säätelee negatiivisesti TLR3- reseptorivälitteistä
1-tyypin interferonin signalointia kohdentamalla TIR-domaanin
sisältävään adaptoriin, joka indusoi IFN-betaa (TRIF). Jos
TRIM38 on ylimäärissä , se estää TLR-3 välitteisen 1-tyypin
interferonin signaloinnin. TRIM38- poistogeenisyys taas palauttaa
vaikutuksen. Edelleen tutkijat osoittivat, että TRIM38 kohdentuu
TRIF- proteiiniin, joka on kriittinen adaptori TLR3 signaloinnin
alavirrassa. TRIF ja TRIM38 immunosaostuvat yhdessä Ja TRIM38
proteiinin PRYSPRY domeeni tekee interaktion TRIF- proteiinin
N-terminaalin kanssa. Jos TRIM38 ilmenee ylimäärissä se vaikuttaa
että TRIF-yliexpressio ja endogeenisen TRIF:in määrä vähenevät.
MG132 käsitelyllä tämä vaikutus poistuu. Lisäksi TRIM38
proteiinin RING/Bbox domaani on tärkeä TRIF-proteiinin K48-
polyubikitinaatiossa ja proteosomihajoitukseen ohjaamisessa.
Yhteenvetona: TRIM38 toimii uutena negatiivisena säätelijänä
TlR3 välitteiselle INF-1 signaloinnille kohdentamalla TRIF-
proteiinin proteosomisilppuriin.
-
Toll-like receptors (TLRs) mediated immune response is crucial for combating pathogens and must be tightly controlled. Tripartite motif (TRIM) proteins are a family of proteins that is involved in a variety of biological and physiological processes. Some members of the TRIM family are important in the regulation of innate immunity. Although it has been shown that TRIM38 negatively regulates innate immunity, the mechanisms by which it does so have not been fully addressed. In this study, we demonstrated that TRIM38 negatively regulates Toll-like receptor 3 (TLR3)-mediated type I interferon signaling by targeting TIR domain-containing adaptor inducing IFN-β (TRIF). We found that overexpression of TRIM38 inhibits TLR3-mediated type I interferon signaling, whereas knockdown of TRIM38 has the reverse effects. We further showed that TRIM38 targets TRIF, a critical adaptor protein downstream of TLR3. TRIF is co-immunoprecipitated with TRIM38, and domain mapping experiments show that PRYSPRY of TRIM38 interacts with the N-terminus of TRIF. Overexpression of TRIM38 decreased expression of overexpressed and endogenous TRIF. This effect could be inhibited by MG132 treatment. Furthermore, the RING/B-box domain of TRIM38 is critical for K48-linked polyubiquitination and proteasomal degradation of TRIF. Collectively, our results suggest that TRIM38 may act as a novel negative regulator for TLR3-mediated type I interferon signaling by targeting TRIF for degradation.
- 5. E3
ubiquitin ligase tripartite motif 38 negatively regulates
TLR-mediated immune responses by proteasomal degradation of TNF
receptor-associated factor 6 in macrophages. Zhao W, et al.
J Immunol, 2012 Mar 15. PMID 22323536 (Suomennosta: Tollin
reseptorivälitteisen (TLR) signaloinnin aktivaatio luonnollisen
immuunivasteen soluissa on kriittinen seikka, jotta keho pystyy
eliminoimaan invasoituvia mikro-organismeja. Mutta toisaalta:
kontrolloimaton aktivaatio saattaa johtaa autoimmuuni- ja
tulehdustauteihin. Tässä artikkelin työssä raportoidaan TRIM38
proteiinista, joka on tunnistettu TLR-signaloinnin negatiivisena
takaisinsyöttösäätelijänä siten että se kohdentaa TRAF6
tekijään (Tuumorinekroosifaktori reseptori 6) . TRIM38
indudoituu makrofagisoluissa TLR-stimulaatiosta
NF-kB-riippuvaisella tavalla. Jos TRIM38 geenin ilmenemä
poistetaan (siRNA tekniikalla) vahvistuu NF-kB aktivaatio ja MAPK
signaalitie, proinflammatoristen sytokiinien lisääntynyt ilmenemä.
Jos taas TRIM38 geeni-ilmenemä vahvistetaan, vaikutus oli
päinvastainen. E3 ubikitiiniligaasina TRIM38 sitoutuu
TRAF6-proteiiniin ja edistää sen sen K48-polyubikitinoitumista (
mikä johtaa TRAF6:n proteiinisilppuriin hajoamaan) .
Johdonmukaisesti TRIM38 poistogeenisyys tuottaa TRAF6:n korkeita
pitoisuuksia primäärisissä makrofageissa. Nämä löydöt
määrittelevät uuden funktion TRIM38 : se estää liiallaista
TLR-välitteistä tulehduksellista vastetta johtamalla TRAF6:n
proteosomaaliseen hajoitukseen ( proteosomisilppuriin).
- Activation of TLR signaling in the innate immune cells is critical for the elimination of invading microorganisms. However, uncontrolled activation may lead to autoimmune and inflammatory diseases. In this article, we report the identification of tripartite motif (TRIM) 38 as a negative feedback regulator in TLR signaling by targeting TNFR-associated factor 6 (TRAF6). TRIM38 was induced by TLR stimulation in an NF-κB-dependent manner in macrophages. Knockdown of TRIM38 expression by small interfering RNA resulted in augmented activation of NF-κB and MAPKs, and enhanced expression of proinflammatory cytokines, whereas overexpression of TRIM38 has an opposite effect. As an E3 ligase, TRIM38 bound to TRAF6 and promoted K48-linked polyubiquitination, which led to the proteasomal degradation of TRAF6. Consistently, knockdown of TRIM38 expression resulted in higher protein level of TRAF6 in primary macrophages. Our findings defined a novel function for TRIM38 to prevent excessive TLR-induced inflammatory responses through proteasomal degradation of TRAF6.
Rakenteesta lisätietoja: Nimet
- Names
- RING-type E3 ubiquitin transferase TRIM38
- Ro/SSA ribonucleoprotein homolog
- ring finger protein 15
- tripartite motif-containing protein 38
- zinc finger protein RoRet
LOCUS NP_006346 465 aa linear PRI 11-FEB-2018 DEFINITION E3 ubiquitin-protein ligase TRIM38 [Homo sapiens]. ACCESSION NP_006346 VERSION NP_006346.1 DBSOURCE REFSEQ: accession NM_006355.4 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 465) AUTHORS Lin Y and Luo Z. TITLE NLRP6 facilitates the interaction between TAB2/3 and TRIM38 in rheumatoid arthritis fibroblast-like synoviocytes JOURNAL FEBS Lett. 591 (8), 1141-1149 (2017) PUBMED 28295271 REMARK GeneRIF: Data suggest that mRNA/protein levels of NLRP6 are down-regulated in synovial tissues and synoviocytes of rheumatoid arthritis (RA) patients compared to osteoarthritis patients; NLRP6 provides docking site to facilitate interaction between TAB2/3 and TRIM38 in RA synoviocytes in response to TNFalpha. (NLRP6 = ; TAB2/3 = transforming growth factor-b-activated kinase 1-binding protein 2/3; TRIM38 = tripartite motif 38) REFERENCE 2 (residues 1 to 465) AUTHORS Zhong Q, Pevzner SJ, Hao T, Wang Y, Mosca R, Menche J, Taipale M, Tasan M, Fan C, Yang X, Haley P, Murray RR, Mer F, Gebreab F, Tam S, MacWilliams A, Dricot A, Reichert P, Santhanam B, Ghamsari L, Calderwood MA, Rolland T, Charloteaux B, Lindquist S, Barabasi AL, Hill DE, Aloy P, Cusick ME, Xia Y, Roth FP and Vidal M. TITLE An inter-species protein-protein interaction network across vast evolutionary distance JOURNAL Mol. Syst. Biol. 12 (4), 865 (2016) PUBMED 27107014 REMARK Publication Status: Online-Only REFERENCE 3 (residues 1 to 465) AUTHORS Sahni N, Yi S, Taipale M, Fuxman Bass JI, Coulombe-Huntington J, Yang F, Peng J, Weile J, Karras GI, Wang Y, Kovacs IA, Kamburov A, Krykbaeva I, Lam MH, Tucker G, Khurana V, Sharma A, Liu YY, Yachie N, Zhong Q, Shen Y, Palagi A, San-Miguel A, Fan C, Balcha D, Dricot A, Jordan DM, Walsh JM, Shah AA, Yang X, Stoyanova AK, Leighton A, Calderwood MA, Jacob Y, Cusick ME, Salehi-Ashtiani K, Whitesell LJ, Sunyaev S, Berger B, Barabasi AL, Charloteaux B, Hill DE, Hao T, Roth FP, Xia Y, Walhout AJM, Lindquist S and Vidal M. TITLE Widespread macromolecular interaction perturbations in human genetic disorders JOURNAL Cell 161 (3), 647-660 (2015) PUBMED 25910212 REFERENCE 4 (residues 1 to 465) AUTHORS Uchil PD, Hinz A, Siegel S, Coenen-Stass A, Pertel T, Luban J and Mothes W. TITLE TRIM protein-mediated regulation of inflammatory and innate immune signaling and its association with antiretroviral activity JOURNAL J. Virol. 87 (1), 257-272 (2013) PUBMED 23077300 REFERENCE 5 (residues 1 to 465) AUTHORS Xue Q, Zhou Z, Lei X, Liu X, He B, Wang J and Hung T. TITLE TRIM38 negatively regulates TLR3-mediated IFN-beta signaling by targeting TRIF for degradation JOURNAL PLoS ONE 7 (10), e46825 (2012) PUBMED 23056470 REMARK GeneRIF: TRIM38 may act as a novel negative regulator for TLR3-mediated type I interferon signaling by targeting TRIF for degradation REFERENCE 6 (residues 1 to 465) 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 REFERENCE 7 (residues 1 to 465) AUTHORS Matsuda A, Suzuki Y, Honda G, Muramatsu S, Matsuzaki O, Nagano Y, Doi T, Shimotohno K, Harada T, Nishida E, Hayashi H and Sugano S. TITLE Large-scale identification and characterization of human genes that activate NF-kappaB and MAPK signaling pathways JOURNAL Oncogene 22 (21), 3307-3318 (2003) PUBMED 12761501 REFERENCE 8 (residues 1 to 465) AUTHORS Chen D, Li X, Zhai Z and Shu HB. TITLE A novel zinc finger protein interacts with receptor-interacting protein (RIP) and inhibits tumor necrosis factor (TNF)- and IL1-induced NF-kappa B activation JOURNAL J. Biol. Chem. 277 (18), 15985-15991 (2002) PUBMED 11854271 REFERENCE 9 (residues 1 to 465) 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 REFERENCE 10 (residues 1 to 465) AUTHORS Ruddy DA, Kronmal GS, Lee VK, Mintier GA, Quintana L, Domingo R Jr, Meyer NC, Irrinki A, McClelland EE, Fullan A, Mapa FA, Moore T, Thomas W, Loeb DB, Harmon C, Tsuchihashi Z, Wolff RK, Schatzman RC and Feder JN. TITLE A 1.1-Mb transcript map of the hereditary hemochromatosis locus JOURNAL Genome Res. 7 (5), 441-456 (1997) PUBMED 9149941 COMMENT REVIEWED REFSEQ: This record has been curated by NCBI staff. The reference sequence was derived from DA603151.1, AK313248.1, U91328.1 and KC877159.1. Summary: This gene encodes a member of the tripartite motif (TRIM) family. The encoded protein contains a RING-type zinc finger, B box-type zinc finger and SPRY domain. The function of this protein has not been identified. A pseudogene of this gene is located on the long arm of chromosome 4. [provided by RefSeq, Jul 2012]. Sequence Note: This RefSeq record was created from transcript and genomic sequence data to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on transcript alignments. 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 :: SRR1803615.184496.1, SRR1803614.214222.1 [ECO:0000332] RNAseq introns :: single sample supports all introns SAMEA1965299, SAMEA1966682 [ECO:0000348] ##Evidence-Data-END## FEATURES Location/Qualifiers source 1..465 /organism="Homo sapiens" /db_xref="taxon:9606" /chromosome="6" /map="6p22.2" Protein 1..465 /product="E3 ubiquitin-protein ligase TRIM38" /EC_number="2.3.2.27" /note="Ro/SSA ribonucleoprotein homolog; ring finger protein 15; tripartite motif-containing protein 38; zinc finger protein RoRet; RING-type E3 ubiquitin transferase TRIM38" /calculated_mol_wt=53285 Region 13..63 /region_name="RING-HC_TRIM38_C-IV" /note="RING finger, HC subclass, found in tripartite motif-containing protein 38 (TRIM38) and similar proteins; cd16600" /db_xref="CDD:319514" Region 16..62 /region_name="RING-HC finger (C3HC4-type)" /note="RING-HC finger (C3HC4-type) [structural motif]" /db_xref="CDD:319514" Site order(16,19,31,33,36,39,59,62) /site_type="other" /note="Zn binding site [ion binding]" /db_xref="CDD:319514" Site 70 /site_type="phosphorylation" /experiment="experimental evidence, no additional details recorded" /note="Phosphoserine. {ECO:0000244|PubMed:24275569}; propagated from UniProtKB/Swiss-Prot (O00635.1)" Region 88..129 /region_name="BBOX" /note="B-Box-type zinc finger; smart00336" /db_xref="CDD:197662" Site order(93,96,115,121) /site_type="other" /note="Zn2+ binding site [ion binding]" /db_xref="CDD:237988" Region 280..461 /region_name="SPRY_PRY_TRIM38" /note="PRY/SPRY domain of tripartite motif-binding protein 38 (TRIM38), also known as Ring finger protein 15 (RNF15); cd15815" /db_xref="CDD:293987" CDS 1..465 /gene="TRIM38" /gene_synonym="RNF15; RORET" /coded_by="NM_006355.4:590..1987" /db_xref="CCDS:CCDS4568.1" /db_xref="GeneID:10475" /db_xref="HGNC:HGNC:10059" ORIGIN 1 masttstkkm meeatcsicl slmtnpvsin cghsychlci tdffknpsqk qlrqetfccp 61 qcrapfhmds lrpnkqlgsl iealketdqe msceehgeqf hlfcedegql icwrcerapq 121 hkghttalve dvcqgykekl qkavtklkql edrcteqkls tamritkwke kvqiqrqkir 181 sdfknlqcfl heeeksylwr lekeeqqtls rlrdyeaglg lksnelkshi leleekcqgs 241 aqkllqnvnd tlsrswavkl etseavslel htmcnvskly fdvkkmlrsh qvsvtldpdt 301 ahhelilsed rrqvtrgytq enqdtssrrf tafpcvlgce gftsgrryfe vdvgegtgwd 361 lgvcmenvqr gtgmkqepqs gfwtlrlckk kgyvaltspp tslhlheqpl lvgifldyea 421 gvvsfyngnt gchiftfpka sfsdtlrpyf qvyqysplfl pppgd //Muistiin 5.4. 2018
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