TRIM 62 ( Kr.1p35.1) DEAR1, FLJ10759
- PubMed GENE https://www.ncbi.nlm.nih.gov/gene/55223
- Also known as DEAR1 (Ductal Epithelium Associated RING chromosome 1
- Expression Ubiquitous expression in skin (RPKM 2.0), brain (RPKM 1.3) and 25 other tissues See more Orthologs mouse all
Rakenne. Konservoidut domeenit.
Conserved domains
(4) summary
smart00336
Location:88 → 125
Location:88 → 125
BBOX; B-Box-type
zinc finger
cd13744
Location:284 → 471
Location:284 → 471
SPRY_PRY_TRIM62;
PRY/SPRY domain in tripartite motif-binding protein 62 (TRIM62)
cl17238
Location:11 → 53
Location:11 → 53
RING; RING-finger
(Really Interesting New Gene) domain, a specialized type of Zn-finger
of 40 to 60 residues that binds two atoms of zinc; defined by the
'cross-brace' motif C-X2-C-X(9-39)-C-X(1-3)-
H-X(2-3)-(N/C/H)-X2-C-X(4-48)C-X2-C; probably involved in ...
cl23765
Location:136 → 255
Location:136 → 255
- iSH2_PI3K_IA_R; Inter-Src homology 2 (iSH2) helical domain of Class IA Phosphoinositide 3-kinase Regulatory subunits
Isoformi 1 historia ja rakenne:
E3 ubiquitin-protein ligase TRIM62 isoform 1 [Homo sapiens]
NCBI Reference Sequence: NP_060677.2 Identical Proteins FASTA GraphicsLOCUS NP_060677 475 aa linear PRI 14-MAR-2018 DEFINITION E3 ubiquitin-protein ligase TRIM62 isoform 1 [Homo sapiens]. ACCESSION NP_060677 VERSION NP_060677.2 DBSOURCE REFSEQ: accession NM_018207.2 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 475) AUTHORS Liu TY, Chen J, Shang CL, Shen HW, Huang JM, Liang YC, Wang W, Zhao YH, Liu D, Shu M, Guo LY, Hu Z and Yao SZ. TITLE Tripartite motif containing 62 is a novel prognostic marker and suppresses tumor metastasis via c-Jun/Slug signaling-mediated epithelial-mesenchymal transition in cervical cancer JOURNAL J. Exp. Clin. Cancer Res. 35 (1), 170 (2016) PUBMED 27793172 REMARK GeneRIF: Results found that TRIM62 was frequently down-regulated in both human cervical cancer (CC) cells and tissues. Low expression of TRIM62 in CC tissues was associated with aggressive clinicopathological features of CC patients. Its overexpression inhibits proliferation, migration and invasion of cervical cancer cells. Publication Status: Online-Only REFERENCE 2 (residues 1 to 475) AUTHORS Cao Z, Conway KL, Heath RJ, Rush JS, Leshchiner ES, Ramirez-Ortiz ZG, Nedelsky NB, Huang H, Ng A, Gardet A, Cheng SC, Shamji AF, Rioux JD, Wijmenga C, Netea MG, Means TK, Daly MJ and Xavier RJ. TITLE Ubiquitin Ligase TRIM62 Regulates CARD9-Mediated Anti-fungal Immunity and Intestinal Inflammation JOURNAL Immunity 43 (4), 715-726 (2015) PUBMED 26488816 REMARK GeneRIF: TRIM62 is a CARD9-binding partner. TRIM62 facilitated K27-linked poly-ubiquitination of CARD9. REFERENCE 3 (residues 1 to 475) AUTHORS Quintas-Cardama A, Zhang N, Qiu YH, Post S, Creighton CJ, Cortes J, Coombes KR and Kornblau SM. TITLE Loss of TRIM62 expression is an independent adverse prognostic factor in acute myeloid leukemia JOURNAL Clin Lymphoma Myeloma Leuk 15 (2), 115-127 (2015) PUBMED 25248926 REMARK GeneRIF: Low TRIM62 levels, consistent with a tumor suppressor role, represent an independent adverse prognostic factor in AML. REFERENCE 4 (residues 1 to 475) AUTHORS Chen N, Balasenthil S, Reuther J and Killary AM. TITLE DEAR1, a novel tumor suppressor that regulates cell polarity and epithelial plasticity JOURNAL Cancer Res. 74 (20), 5683-5689 (2014) PUBMED 25261235 REMARK GeneRIF: DEAR1 is important in the regulation of the breast tumor microenvironment, polarity, and epithelial-mesenchymal transition. [Review] Review article REFERENCE 5 (residues 1 to 475) AUTHORS Chen N, Balasenthil S, Reuther J, Frayna A, Wang Y, Chandler DS, Abruzzo LV, Rashid A, Rodriguez J, Lozano G, Cao Y, Lokken E, Chen J, Frazier ML, Sahin AA, Wistuba II, Sen S, Lott ST and Killary AM. TITLE DEAR1 is a chromosome 1p35 tumor suppressor and master regulator of TGF-beta-driven epithelial-mesenchymal transition JOURNAL Cancer Discov 3 (10), 1172-1189 (2013) PUBMED 23838884 REMARK GeneRIF: results provide compelling evidence that DEAR1 is a critical tumor suppressor involved in multiple human cancers and provide a novel paradigm for regulation of TGF-beta-induced EMT through DEAR1's regulation of SMAD3 protein levels REFERENCE 6 (residues 1 to 475) 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 7 (residues 1 to 475) AUTHORS Lott ST, Chen N, Chandler DS, Yang Q, Wang L, Rodriguez M, Xie H, Balasenthil S, Buchholz TA, Sahin AA, Chaung K, Zhang B, Olufemi SE, Chen J, Adams H, Band V, El-Naggar AK, Frazier ML, Keyomarsi K, Hunt KK, Sen S, Haffty B, Hewitt SM, Krahe R and Killary AM. TITLE DEAR1 is a dominant regulator of acinar morphogenesis and an independent predictor of local recurrence-free survival in early-onset breast cancer JOURNAL PLoS Med. 6 (5), e1000068 (2009) PUBMED 19536326 REMARK GeneRIF: The evidence for the genetic alteration and loss of expression of DEAR1 in breast cancer and for the functional role of DEAR1 in the dominant regulation of acinar morphogenesis in 3D culture REFERENCE 8 (residues 1 to 475) AUTHORS Muthuswamy SK. TITLE A new tumor suppressor that regulates tissue architecture JOURNAL PLoS Med. 6 (5), e1000073 (2009) PUBMED 19536324 REMARK GeneRIF: DEAR1 is a predictive biomarker for early onset breast cancer. REFERENCE 9 (residues 1 to 475) 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 10 (residues 1 to 475) AUTHORS Colland F, Jacq X, Trouplin V, Mougin C, Groizeleau C, Hamburger A, Meil A, Wojcik J, Legrain P and Gauthier JM. TITLE Functional proteomics mapping of a human signaling pathway JOURNAL Genome Res. 14 (7), 1324-1332 (2004) PUBMED 15231748 COMMENT VALIDATED REFSEQ: This record has undergone validation or preliminary review. The reference sequence was derived from DA338982.1, BM722392.1, BC007999.1, AK001621.1 and CX872720.1. On Dec 10, 2008 this sequence version replaced NP_060677.1. Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1). 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 :: BC001222.1, AK001621.1 [ECO:0000332] RNAseq introns :: mixed/partial sample support SAMEA1965299, SAMEA1966682 [ECO:0000350] ##Evidence-Data-END## FEATURES Location/Qualifiers source 1..475 /organism="Homo sapiens" /db_xref="taxon:9606" /chromosome="1" /map="1p35.1" Protein 1..475 /product="E3 ubiquitin-protein ligase TRIM62 isoform 1" /EC_number="2.3.2.27" /note="ductal epithelium-associated RING Chromosome 1; tripartite motif-containing protein 62; E3 ubiquitin-protein ligase TRIM62; RING-type E3 ubiquitin transferase TRIM62" /calculated_mol_wt=54137 Region 11..53 /region_name="RING" /note="RING-finger (Really Interesting New Gene) domain, a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc; defined by the 'cross-brace' motif C-X2-C-X(9-39)-C-X(1-3)- H-X(2-3)-(N/C/H)-X2-C-X(4-48)C-X2-C; probably involved in...; cl17238" /db_xref="CDD:302633" Site order(11,14,26,28,31,34,50,53) /site_type="other" /note="cross-brace motif" /db_xref="CDD:238093" Region 88..125 /region_name="BBOX" /note="B-Box-type zinc finger; smart00336" /db_xref="CDD:197662" Site order(93,96,114,120) /site_type="other" /note="Zn2+ binding site [ion binding]" /db_xref="CDD:237988" Region 136..255 /region_name="iSH2_PI3K_IA_R" /note="Inter-Src homology 2 (iSH2) helical domain of Class IA Phosphoinositide 3-kinase Regulatory subunits; cl23765" /db_xref="CDD:304922" Region 284..471 /region_name="SPRY_PRY_TRIM62" /note="PRY/SPRY domain in tripartite motif-binding protein 62 (TRIM62); cd13744" /db_xref="CDD:293978" CDS 1..475 /gene="TRIM62" /gene_synonym="DEAR1" /coded_by="NM_018207.2:639..2066" /note="isoform 1 is encoded by transcript variant 1" /db_xref="CCDS:CCDS376.1" /db_xref="GeneID:55223" /db_xref="HGNC:HGNC:25574" /db_xref="MIM:616755" ORIGIN 1 macslkdell csiclsiyqd pvslgcehyf crrcitehwv rqeaqgardc pecrrtfaep 61 alapslklan iveryssfpl dailnarraa rpcqahdkvk lfcltdrall cffcdepalh 121 eqhqvtgidd afdelqrelk dqlqalqdse rehtealqll krqlaetkss tkslrttige 181 aferlhrllr erqkamleel eadtartltd ieqkvqrysq qlrkvqegaq ilqerlaetd 241 rhtflagvas lserlkgkih etnltyedfp tskytgplqy tiwkslfqdi hpvpaaltld 301 pgtahqrlil sddctivayg nlhpqplqds pkrfdvevsv lgseafssgv hywevvvaek 361 tqwviglahe aasrkgsiqi qpsrgfyciv mhdgnqysac tepwtrlnvr dkldkvgvfl 421 dydqgllify naddmswlyt frekfpgklc syfspgqsha ngknvqplri ntvri //
TRIM62 ja EMT( epiteliaalismesenkymaalinen siirtymä): c-Jun/Slug
-
Tripartite motif containing 62 is a novel prognostic marker and suppresses tumor metastasis via c-Jun/Slug signaling-mediated epithelial-mesenchymal transition in cervical cancer. Liu TY, et al. J Exp Clin Cancer Res, 2016 Oct 28. PMID 27793172, Free PMC Article Furthermore, mechanism study exhibited that TRIM62 could suppress epithelial-mesenchymal transition (EMT) by inhibiting c-Jun/Slug signaling. The inhibitory role of TRIM62 in tumor proliferation might be through regulating cell cycle related proteins CyclinD1 and P27 by targeting c-Jun.
-
Suomennosta: TRIM 62 näyttää olevan usein alassäätyneenä sekä cervixsyöpäsoluissa ja -kudoksissa. TRIM62 geenin matala ilmentymä assosioitui aggressiiviseen kliinispatologiseen kulkuun. Myös kirurgisesti hoidetun CC syövän yleisenä ja taudittoman aikavälin riippumattomana huonon prognoosin merkkinä oli TRIM62:n matala esiintymä. TRIM62:n vahvistettu ilmentymä CC-soluissa esti merkitsevästi syöpäsolujen kykyä proliferoitua, migroitua ja invasoitua in vitro.TRIM62 kykenee estämään EMT:n inhiboimalla c-Jun/Slug signaloinnin. TRIM62:n estävä vaikutus tuumorin proliferaatioon saattaisi johtua solusyklin proteiinien SykliiniD1 ja p27 säätelystä c-Jun- tekijään kohdistumisen kautta.. Johtopäätös: TRIM62 on mahdollinen prognostinen biomerkitsijä CC:ssä ja se tukahduttaa CC-metastasointia estämällä c-Jun/Slug signaloinnin välittämän EMT:n, epiteliaalisen-mesenkymaalisen transition.
TRIM62 ja TGF-beta/SMAD3/SNAIL1/2 välitteinen EMT
-
DEAR1, a novel tumor suppressor that regulates cell polarity and epithelial plasticity. Chen N, et al. Cancer Res, 2014 Oct 15. PMID 25261235, Free PMC Article This review will highlight the role of the novel TRIM protein DEAR1 (annotated as TRIM62) in the regulation of apical-basal polarity and acinar morphogenesis as well as its function as a chromosome 1p35 tumor suppressor and negative regulator of TGFβ-driven epithelial-mesenchymal transition (EMT). DEAR1 binds to and promotes the ubiquitination of SMAD3, the major effector of TGFβ-mediated EMT, as well as downregulates SMAD3 targets SNAIL1/2, master transcriptional regulators of EMT. Cumulative results suggest a novel paradigm for DEAR1 in the regulation of the breast tumor microenvironment, polarity, and EMT. Because DEAR1 undergoes loss-of-function mutations, homozygous deletion, as well as copy-number losses in multiple epithelial cancers, including breast cancer, DEAR1 has clinical use as a predictive and prognostic biomarker as well as for stratifying breast cancers and potentially other epithelial tumor types for targeted therapies aimed at the pathways regulated by DEAR1.
-
Suomennosta: TRIM62 säätelee solun apikaalisbasaalista polariteettia ja akinaarista morfogeneesiä, toimii tuumorisuppressorina ja TGFbeta-välitteisen EMT:n negatiivisena säätelijänä. TRIM62 sitoutuu SMAD3-tekijään ja ubikitinoi sen; säätää alas SMAD3 kohteen SNAIL1/2 , joka säätelee epiteliaalismesenkymaalista transitiota (EMT). TRIM62 tekee mutaatioita, homozygootteja deleetioita, kopioluvun katoa useissa epiteliaalisissa syövissä kuten rintasyövässä, joissa se menettää funktioita. Kliinisenä markkerina sitä voi käyttää, kun suunnitellaan kodhennettuja hoitoja TRIM62-säätelyteihin.
TRIM62 menetys ja vaikutus leukemiakantasolun homeostaasiin
-
Loss of TRIM62 expression is an independent adverse prognostic factor in acute myeloid leukemia. Quintás-Cardama A, et al. Clin Lymphoma Myeloma Leuk, 2015 Feb. PMID 25248926, Free PMC Article TRIM62 loss was associated with altered expression of proteins involved in leukemia stem cell homeostasis (β-catenin and Notch), cell motility, and adhesion (integrin-β3, ras-related C3 botulinum toxin substrate [RAC], and fibronectin), hypoxia (Hypoxia-inducible factor 1-alpha [HIF1α], egl-9 family hypoxia-inducible factor 1 [Egln1], and glucose-regulated protein, 78 kDa [GRP78]), and apoptosis (B-cell lymphoma-extra large (BclXL) and caspase 9).
-
Suomennosta: TRIM62 menetys liittyy monen proteiinin muuntuneeseen ilmentymiseen.Tällaisia proteiineja ovat: leukemiakantasolun homeostaasiin osallistuvat proteiinit (betakateniini ja Notch), solumotiliteettiproteiinit, adheesioproteiinit (integriini-beta3, RAC ja fibronektiini) , hypoksiaan liittyvät proteiinit (HIF1alfa, Egln1 ja GRP78 glukoosin säätelemä proteiini 78kDa) ja apoptoosiin liittyvät proteiinit (BcLXL ja kaspaasi9) .
TRIM62 tuumorisuppressori, joka sääetlee kudosarkkitehtuuria
-
A new tumor suppressor that regulates tissue architecture. Muthuswamy SK. PLoS Med, See all (21) citations in PubMed2009 May 26. PMID 19536324, Free PMC Article
-
TRIM62 is a CARD9-binding partner. TRIM62 facilitated K27-linked poly-ubiquitination of CARD9. …. We identified TRIM62 as a CARD9 binding partner and showed that TRIM62 facilitated K27-linked poly-ubiquitination of CARD9. We identified K125 as the ubiquitinated residue on CARD9 and demonstrated that this ubiquitination was essential for CARD9 activity. Furthermore, we showed that similar to Card9-deficient mice, Trim62-deficient mice had increased susceptibility to fungal infection. In this study, we utilized a rare protective allele to uncover a TRIM62-mediated mechanism for regulation of CARD9 activation. https://www.cell.com/immunity/abstract/S1074-7613%2815%2900405-7
Suomennosta:
TRIM62 sitoutuu CARD9 proteiiniin, joka on sentraalinen komponentti
antifungaalisessa luonnollisessa immuunivasteessa C-tyypisen
lektiinireseptorien kautta tapahtuvassa signaloinnissa. TRIM62
nopeuttaa CARD9 K27-linkkiytynyttä ubikitinaatiota. CARD9:ssä
havaittiin K125 ubikitinaatio, mikä on essentielli
CARD9-aktiivisuudelle. Card9-vajaat hiiret olivat alttiita
sienitulehduksille. Myös Trim62 vajeiset hiiret omasivat
lisääntyneen alttiuden sienitulehduksille.
-
these data indicate that TRIM62, a cytoplasmic protein, is a RING finger domain-dependent E3 ubiquitin ligase that catalyzes self-ubiquitination both in vitro and in vivo. ...Several reports have identified a role for this family in cancer, retroviral infection and innate immunity. In this study, the E3 ubiquitin ligase activity and subcellular localization of TRIM62 were characterized. TRIM62, in association with the E2 enzyme UbcH5b, was found to catalyze self-ubiquitination in vitro, a process that required an intact RING finger domain.
-
Suomennosta: TRIM62 assosioituneena E2 entsyymiin UBE2D2 katalysoi autoubikitinaatiotansa, mikä vaati intaktin RING finger domaanin ja johti TRIM62:n proteosomaaliseen hajoamiseen. TRIM62 on sytoplasminen proteiini.
-
E2 ubikitiiniligaasi joka avustaa TRIM62:n autoubikitinaatiota ja täten hajoamista mikä säätelee sen määrää. (UBE2D2 , UbcH5b kr. 5q31.2) Mm. HIV-1 integraasi tekee interaktion UBE2D2 entsyymiin, mikä on virukselle suotuisa. https://www.ncbi.nlm.nih.gov/gene/7322
PÄIVITYS 7.5. 2018
Inga kommentarer:
Skicka en kommentar