UBE2T_HUMAN
ID UBE2T_HUMAN Reviewed; 197 AA.
AC Q9NPD8; Q2TU36;
DT 16-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Ubiquitin-conjugating enzyme E2 T;
DE EC=2.3.2.23 {ECO:0000269|PubMed:20061386};
DE AltName: Full=Cell proliferation-inducing gene 50 protein;
DE AltName: Full=E2 ubiquitin-conjugating enzyme T;
DE AltName: Full=Ubiquitin carrier protein T;
DE AltName: Full=Ubiquitin-protein ligase T;
GN Name=UBE2T; ORFNames=HSPC150, PIG50;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Okaze H., Hayashi A., Kozuma S., Saito T.;
RT "Ubiquitin-conjugating enzyme isolog.";
RL Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Adrenal gland;
RX PubMed=10931946; DOI=10.1073/pnas.160270997;
RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X.,
RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W.,
RA Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J., Xu S.-H., Gu J.,
RA Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z.,
RA Chen M.-D., Chen J.-L.;
RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal axis
RT and full-length cDNA cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Blood;
RX PubMed=11042152; DOI=10.1101/gr.140200;
RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G.,
RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W.,
RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.;
RT "Cloning and functional analysis of cDNAs with open reading frames for 300
RT previously undefined genes expressed in CD34+ hematopoietic stem/progenitor
RT cells.";
RL Genome Res. 10:1546-1560(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Carcinoma;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kim J.W.;
RT "Identification of a human cell proliferation inducing gene.";
RL Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP FUNCTION, INTERACTION WITH FANCL, UBIQUITINATION AT LYS-91, AND MUTAGENESIS
RP OF CYS-86.
RX PubMed=16916645; DOI=10.1016/j.molcel.2006.06.024;
RA Machida Y.J., Machida Y., Chen Y., Gurtan A.M., Kupfer G.M., D'Andrea A.D.,
RA Dutta A.;
RT "UBE2T is the E2 in the Fanconi anemia pathway and undergoes negative
RT autoregulation.";
RL Mol. Cell 23:589-596(2006).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH FANCL, AND MUTAGENESIS OF
RP CYS-86.
RX PubMed=17938197; DOI=10.1128/mcb.00504-07;
RA Alpi A., Langevin F., Mosedale G., Machida Y.J., Dutta A., Patel K.J.;
RT "UBE2T, the Fanconi anemia core complex, and FANCD2 are recruited
RT independently to chromatin: a basis for the regulation of FANCD2
RT monoubiquitination.";
RL Mol. Cell. Biol. 27:8421-8430(2007).
RN [11]
RP FUNCTION, INTERACTION WITH FANCL, UBIQUITINATION AT LYS-91 AND LYS-182, AND
RP MUTAGENESIS OF CYS-86; LYS-91 AND 182-LYS--LYS-191.
RX PubMed=19111657; DOI=10.1016/j.molcel.2008.12.003;
RA Alpi A.F., Pace P.E., Babu M.M., Patel K.J.;
RT "Mechanistic insight into site-restricted monoubiquitination of FANCD2 by
RT Ube2t, FANCL, and FANCI.";
RL Mol. Cell 32:767-777(2008).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [13]
RP FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF CYS-86, AND INTERACTION WITH
RP BRCA1.
RX PubMed=19887602; DOI=10.1158/0008-5472.can-09-1809;
RA Ueki T., Park J.H., Nishidate T., Kijima K., Hirata K., Nakamura Y.,
RA Katagiri T.;
RT "Ubiquitination and downregulation of BRCA1 by ubiquitin-conjugating enzyme
RT E2T overexpression in human breast cancer cells.";
RL Cancer Res. 69:8752-8760(2009).
RN [14]
RP FUNCTION, AND MUTAGENESIS OF CYS-86.
RX PubMed=19589784; DOI=10.1074/jbc.c109.038075;
RA Longerich S., San Filippo J., Liu D., Sung P.;
RT "FANCI binds branched DNA and is monoubiquitinated by UBE2T-FANCL.";
RL J. Biol. Chem. 284:23182-23186(2009).
RN [15]
RP FUNCTION, CATALYTIC ACTIVITY, AND AUTOUBIQUITINATION.
RX PubMed=20061386; DOI=10.1074/jbc.m109.089003;
RA David Y., Ziv T., Admon A., Navon A.;
RT "The E2 ubiquitin-conjugating enzymes direct polyubiquitination to
RT preferred lysines.";
RL J. Biol. Chem. 285:8595-8604(2010).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [17]
RP INTERACTION WITH FANCL, AND MUTAGENESIS OF PHE-63.
RX PubMed=21775430; DOI=10.1074/jbc.m111.244632;
RA Hodson C., Cole A.R., Lewis L.P., Miles J.A., Purkiss A., Walden H.;
RT "Structural analysis of human FANCL, the E3 ligase in the Fanconi anemia
RT pathway.";
RL J. Biol. Chem. 286:32628-32637(2011).
RN [18]
RP INDUCTION.
RX PubMed=21722982; DOI=10.1016/j.radonc.2011.05.059;
RA Ramaekers C.H., van den Beucken T., Meng A., Kassam S., Thoms J.,
RA Bristow R.G., Wouters B.G.;
RT "Hypoxia disrupts the Fanconi anemia pathway and sensitizes cells to
RT chemotherapy through regulation of UBE2T.";
RL Radiother. Oncol. 101:190-197(2011).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-184, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [20]
RP INVOLVEMENT IN FANCT, VARIANT FANCT GLU-2, AND CHARACTERIZATION OF VARIANT
RP FANCT GLU-2.
RX PubMed=26046368; DOI=10.1016/j.ajhg.2015.04.022;
RA Hira A., Yoshida K., Sato K., Okuno Y., Shiraishi Y., Chiba K., Tanaka H.,
RA Miyano S., Shimamoto A., Tahara H., Ito E., Kojima S., Kurumizaka H.,
RA Ogawa S., Takata M., Yabe H., Yabe M.;
RT "Mutations in the gene encoding the E2 conjugating enzyme UBE2T cause
RT Fanconi anemia.";
RL Am. J. Hum. Genet. 96:1001-1007(2015).
RN [21]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-191 AND LYS-192, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1-167.
RA Walker J.R., Avvakumov G.V., Newman E.M., Mackenzie F., Kozieradzki I.,
RA Sundstrom M., Arrowsmith C., Edwards A., Bochkarev A., Dhe-Paganon S.;
RT "Ubiquitin-conjugating enzyme HSPC150.";
RL Submitted (FEB-2005) to the PDB data bank.
RN [23] {ECO:0007744|PDB:1YH2}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 1-167, AND AUTOUBIQUITINATION.
RX PubMed=22496338; DOI=10.1074/mcp.o111.013706;
RA Sheng Y., Hong J.H., Doherty R., Srikumar T., Shloush J., Avvakumov G.V.,
RA Walker J.R., Xue S., Neculai D., Wan J.W., Kim S.K., Arrowsmith C.H.,
RA Raught B., Dhe-Paganon S.;
RT "A human ubiquitin conjugating enzyme (E2)-HECT E3 ligase structure-
RT function screen.";
RL Mol. Cell. Proteomics 11:329-341(2012).
RN [24] {ECO:0007744|PDB:4CCG}
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS), INTERACTION WITH FANCL, AND
RP MUTAGENESIS OF SER-5; ARG-60 AND 99-ARG--SER-101.
RX PubMed=24389026; DOI=10.1016/j.str.2013.12.004;
RA Hodson C., Purkiss A., Miles J.A., Walden H.;
RT "Structure of the human FANCL RING-Ube2T complex reveals determinants of
RT cognate E3-E2 selection.";
RL Structure 22:337-344(2014).
RN [25] {ECO:0007744|PDB:5NGZ}
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) IN COMPLEX WITH INHIBITOR
RP 1-(1,3-BENZOTHIAZOL-2-YL)METHANAMINE, FUNCTION, AND MUTAGENESIS OF PRO-73.
RX PubMed=28437106; DOI=10.1021/acs.jmedchem.7b00147;
RA Morreale F.E., Bortoluzzi A., Chaugule V.K., Arkinson C., Walden H.,
RA Ciulli A.;
RT "Allosteric targeting of the Fanconi anemia ubiquitin-conjugating enzyme
RT Ube2T by fragment screening.";
RL J. Med. Chem. 60:4093-4098(2017).
CC -!- FUNCTION: Accepts ubiquitin from the E1 complex and catalyzes its
CC covalent attachment to other proteins. Catalyzes monoubiquitination.
CC Involved in mitomycin-C (MMC)-induced DNA repair. Acts as a specific E2
CC ubiquitin-conjugating enzyme for the Fanconi anemia complex by
CC associating with E3 ubiquitin-protein ligase FANCL and catalyzing
CC monoubiquitination of FANCD2, a key step in the DNA damage pathway
CC (PubMed:16916645, PubMed:17938197, PubMed:19111657, PubMed:19589784,
CC PubMed:28437106). Also mediates monoubiquitination of FANCL and FANCI
CC (PubMed:16916645, PubMed:17938197, PubMed:19111657, PubMed:19589784).
CC May contribute to ubiquitination and degradation of BRCA1
CC (PubMed:19887602). In vitro able to promote polyubiquitination using
CC all 7 ubiquitin Lys residues, but may prefer 'Lys-11'-, 'Lys-27'-,
CC 'Lys-48'- and 'Lys-63'-linked polyubiquitination (PubMed:20061386).
CC {ECO:0000269|PubMed:16916645, ECO:0000269|PubMed:17938197,
CC ECO:0000269|PubMed:19111657, ECO:0000269|PubMed:19589784,
CC ECO:0000269|PubMed:19887602, ECO:0000269|PubMed:20061386,
CC ECO:0000269|PubMed:28437106}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine +
CC [E2 ubiquitin-conjugating enzyme]-L-cysteine = [E1 ubiquitin-
CC activating enzyme]-L-cysteine + S-ubiquitinyl-[E2 ubiquitin-
CC conjugating enzyme]-L-cysteine.; EC=2.3.2.23;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00388, ECO:0000255|PROSITE-
CC ProRule:PRU10133, ECO:0000269|PubMed:20061386};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000255|PROSITE-ProRule:PRU00388}.
CC -!- SUBUNIT: Directly interacts with FANCL (PubMed:16916645,
CC PubMed:17938197, PubMed:19111657, PubMed:21775430, PubMed:24389026).
CC Interacts with BRCA1 (PubMed:19887602). {ECO:0000269|PubMed:16916645,
CC ECO:0000269|PubMed:17938197, ECO:0000269|PubMed:19111657,
CC ECO:0000269|PubMed:19887602, ECO:0000269|PubMed:21775430,
CC ECO:0000269|PubMed:24389026}.
CC -!- INTERACTION:
CC Q9NPD8; Q9NW38-1: FANCL; NbExp=3; IntAct=EBI-2130165, EBI-16088720;
CC Q9NPD8; P62879: GNB2; NbExp=3; IntAct=EBI-2130165, EBI-356942;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:17938197,
CC ECO:0000269|PubMed:19887602}. Note=Accumulates to chromatin.
CC -!- INDUCTION: Down-regulated following hypoxia. Up-regulated in breast
CC cancers. {ECO:0000269|PubMed:21722982}.
CC -!- PTM: Auto-ubiquitinated. Effects of auto-monoubiquitination at Lys-91
CC and Lys-182 are unclear: according to a report, monoubiquitination
CC inactivates E2 enzyme activity (PubMed:16916645). In contrast,
CC according to another report, autoubiquitination does not affect E2
CC enzyme activity (PubMed:19111657). {ECO:0000269|PubMed:16916645,
CC ECO:0000269|PubMed:19111657, ECO:0000269|PubMed:20061386,
CC ECO:0000269|PubMed:22496338}.
CC -!- DISEASE: Fanconi anemia complementation group T (FANCT) [MIM:616435]: A
CC disorder affecting all bone marrow elements and resulting in anemia,
CC leukopenia and thrombopenia. It is associated with cardiac, renal and
CC limb malformations, dermal pigmentary changes, and a predisposition to
CC the development of malignancies. At the cellular level it is associated
CC with hypersensitivity to DNA-damaging agents, chromosomal instability
CC (increased chromosome breakage) and defective DNA repair.
CC {ECO:0000269|PubMed:26046368}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the ubiquitin-conjugating enzyme family.
CC {ECO:0000255|PROSITE-ProRule:PRU00388}.
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DR EMBL; AB032931; BAA93711.1; -; mRNA.
DR EMBL; AF160215; AAF67016.1; -; mRNA.
DR EMBL; AF161499; AAF29114.1; -; mRNA.
DR EMBL; AK000504; BAA91211.1; -; mRNA.
DR EMBL; AY542309; AAT08178.1; -; mRNA.
DR EMBL; AL356953; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471067; EAW91411.1; -; Genomic_DNA.
DR EMBL; BC004152; AAH04152.1; -; mRNA.
DR EMBL; BC019284; AAH19284.1; -; mRNA.
DR CCDS; CCDS1425.1; -.
DR RefSeq; NP_001297255.1; NM_001310326.1.
DR RefSeq; NP_054895.1; NM_014176.3.
DR PDB; 1YH2; X-ray; 2.00 A; A=1-167.
DR PDB; 4CCG; X-ray; 2.40 A; A/B=1-197.
DR PDB; 5NGZ; X-ray; 2.40 A; A=1-197.
DR PDB; 5OJJ; X-ray; 1.85 A; A/B/C/D/E/F=1-154.
DR PDB; 6R75; X-ray; 2.00 A; A=1-197.
DR PDB; 7KZR; EM; 4.20 A; X=1-197.
DR PDB; 7KZS; EM; 4.20 A; X=1-197.
DR PDB; 7KZT; EM; 4.20 A; X=1-197.
DR PDB; 7KZV; EM; 4.20 A; X=1-197.
DR PDBsum; 1YH2; -.
DR PDBsum; 4CCG; -.
DR PDBsum; 5NGZ; -.
DR PDBsum; 5OJJ; -.
DR PDBsum; 6R75; -.
DR PDBsum; 7KZR; -.
DR PDBsum; 7KZS; -.
DR PDBsum; 7KZT; -.
DR PDBsum; 7KZV; -.
DR AlphaFoldDB; Q9NPD8; -.
DR SMR; Q9NPD8; -.
DR BioGRID; 118858; 71.
DR DIP; DIP-52740N; -.
DR IntAct; Q9NPD8; 24.
DR MINT; Q9NPD8; -.
DR STRING; 9606.ENSP00000356243; -.
DR BindingDB; Q9NPD8; -.
DR ChEMBL; CHEMBL4105763; -.
DR GlyGen; Q9NPD8; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9NPD8; -.
DR PhosphoSitePlus; Q9NPD8; -.
DR SwissPalm; Q9NPD8; -.
DR BioMuta; UBE2T; -.
DR DMDM; 73622065; -.
DR CPTAC; CPTAC-3262; -.
DR CPTAC; CPTAC-3263; -.
DR EPD; Q9NPD8; -.
DR jPOST; Q9NPD8; -.
DR MassIVE; Q9NPD8; -.
DR MaxQB; Q9NPD8; -.
DR PaxDb; Q9NPD8; -.
DR PeptideAtlas; Q9NPD8; -.
DR PRIDE; Q9NPD8; -.
DR ProteomicsDB; 81976; -.
DR TopDownProteomics; Q9NPD8; -.
DR Antibodypedia; 1227; 314 antibodies from 35 providers.
DR CPTC; Q9NPD8; 1 antibody.
DR DNASU; 29089; -.
DR Ensembl; ENST00000646651.1; ENSP00000494957.1; ENSG00000077152.11.
DR GeneID; 29089; -.
DR KEGG; hsa:29089; -.
DR MANE-Select; ENST00000646651.1; ENSP00000494957.1; NM_014176.4; NP_054895.1.
DR UCSC; uc001gxx.5; human.
DR CTD; 29089; -.
DR DisGeNET; 29089; -.
DR GeneCards; UBE2T; -.
DR GeneReviews; UBE2T; -.
DR HGNC; HGNC:25009; UBE2T.
DR HPA; ENSG00000077152; Tissue enhanced (lymphoid).
DR MalaCards; UBE2T; -.
DR MIM; 610538; gene.
DR MIM; 616435; phenotype.
DR neXtProt; NX_Q9NPD8; -.
DR OpenTargets; ENSG00000077152; -.
DR Orphanet; 84; Fanconi anemia.
DR PharmGKB; PA142670655; -.
DR VEuPathDB; HostDB:ENSG00000077152; -.
DR eggNOG; KOG0417; Eukaryota.
DR GeneTree; ENSGT00940000157365; -.
DR HOGENOM; CLU_030988_13_2_1; -.
DR InParanoid; Q9NPD8; -.
DR OMA; KMQPKGS; -.
DR OrthoDB; 1431031at2759; -.
DR PhylomeDB; Q9NPD8; -.
DR TreeFam; TF354203; -.
DR BRENDA; 2.3.2.23; 2681.
DR BRENDA; 2.3.2.24; 2681.
DR PathwayCommons; Q9NPD8; -.
DR Reactome; R-HSA-6783310; Fanconi Anemia Pathway.
DR Reactome; R-HSA-8866652; Synthesis of active ubiquitin: roles of E1 and E2 enzymes.
DR SignaLink; Q9NPD8; -.
DR SIGNOR; Q9NPD8; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 29089; 83 hits in 1088 CRISPR screens.
DR ChiTaRS; UBE2T; human.
DR EvolutionaryTrace; Q9NPD8; -.
DR GenomeRNAi; 29089; -.
DR Pharos; Q9NPD8; Tbio.
DR PRO; PR:Q9NPD8; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9NPD8; protein.
DR Bgee; ENSG00000077152; Expressed in oocyte and 154 other tissues.
DR ExpressionAtlas; Q9NPD8; baseline and differential.
DR Genevisible; Q9NPD8; HS.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0061631; F:ubiquitin conjugating enzyme activity; IDA:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IMP:UniProtKB.
DR GO; GO:0006281; P:DNA repair; IMP:UniProtKB.
DR GO; GO:0051865; P:protein autoubiquitination; IDA:UniProtKB.
DR GO; GO:0070979; P:protein K11-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:0044314; P:protein K27-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:0035519; P:protein K29-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:0085020; P:protein K6-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:0070534; P:protein K63-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:0006513; P:protein monoubiquitination; IDA:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; IBA:GO_Central.
DR CDD; cd00195; UBCc; 1.
DR Gene3D; 3.10.110.10; -; 1.
DR InterPro; IPR000608; UBQ-conjugat_E2.
DR InterPro; IPR023313; UBQ-conjugating_AS.
DR InterPro; IPR016135; UBQ-conjugating_enzyme/RWD.
DR Pfam; PF00179; UQ_con; 1.
DR SUPFAM; SSF54495; SSF54495; 1.
DR PROSITE; PS00183; UBC_1; 1.
DR PROSITE; PS50127; UBC_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Disease variant; DNA damage; DNA repair;
KW Fanconi anemia; Isopeptide bond; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Transferase; Ubl conjugation;
KW Ubl conjugation pathway.
FT CHAIN 1..197
FT /note="Ubiquitin-conjugating enzyme E2 T"
FT /id="PRO_0000082509"
FT DOMAIN 2..152
FT /note="UBC core"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00388"
FT REGION 149..197
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 149..178
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 86
FT /note="Glycyl thioester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00388"
FT MOD_RES 184
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CROSSLNK 91
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:16916645,
FT ECO:0000269|PubMed:19111657"
FT CROSSLNK 182
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:19111657"
FT CROSSLNK 191
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 192
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VARIANT 2
FT /note="Q -> E (in FANCT; abolishes FANCD2
FT monoubiquitination; abolishes interaction with FANCL;
FT dbSNP:rs774357609)"
FT /evidence="ECO:0000269|PubMed:26046368"
FT /id="VAR_073861"
FT MUTAGEN 5
FT /note="S->R: No effect on FANCL-binding, nor on FANCL-
FT dependent monoubiquitination of FANCD2."
FT /evidence="ECO:0000269|PubMed:24389026"
FT MUTAGEN 60
FT /note="R->E: Loss of FANCL-binding and of FANCL-dependent
FT monoubiquitination of FANCD2."
FT /evidence="ECO:0000269|PubMed:24389026"
FT MUTAGEN 63
FT /note="F->A: Decreased binding to FANCL."
FT /evidence="ECO:0000269|PubMed:21775430"
FT MUTAGEN 73
FT /note="P->K: Decreased FANCD2 ubiquitination."
FT /evidence="ECO:0000269|PubMed:28437106"
FT MUTAGEN 86
FT /note="C->A: Loss of E2 enzyme activity."
FT /evidence="ECO:0000269|PubMed:16916645,
FT ECO:0000269|PubMed:17938197, ECO:0000269|PubMed:19111657,
FT ECO:0000269|PubMed:19589784, ECO:0000269|PubMed:19887602"
FT MUTAGEN 91
FT /note="K->R: Decreased monoubiquitination."
FT /evidence="ECO:0000269|PubMed:19111657"
FT MUTAGEN 99..101
FT /note="RPS->SPR: No effect on FANCL-binding, nor on FANCL-
FT dependent monoubiquitination of FANCD2."
FT /evidence="ECO:0000269|PubMed:24389026"
FT MUTAGEN 182..191
FT /note="Missing: Decreased monoubiquitination."
FT /evidence="ECO:0000269|PubMed:19111657"
FT HELIX 6..16
FT /evidence="ECO:0007829|PDB:5OJJ"
FT STRAND 22..26
FT /evidence="ECO:0007829|PDB:5OJJ"
FT STRAND 30..39
FT /evidence="ECO:0007829|PDB:5OJJ"
FT TURN 45..48
FT /evidence="ECO:0007829|PDB:5OJJ"
FT STRAND 49..57
FT /evidence="ECO:0007829|PDB:5OJJ"
FT TURN 59..62
FT /evidence="ECO:0007829|PDB:5OJJ"
FT STRAND 67..72
FT /evidence="ECO:0007829|PDB:5OJJ"
FT HELIX 88..90
FT /evidence="ECO:0007829|PDB:5OJJ"
FT TURN 93..95
FT /evidence="ECO:0007829|PDB:5OJJ"
FT HELIX 104..116
FT /evidence="ECO:0007829|PDB:5OJJ"
FT HELIX 126..134
FT /evidence="ECO:0007829|PDB:5OJJ"
FT HELIX 136..150
FT /evidence="ECO:0007829|PDB:5OJJ"
FT STRAND 151..153
FT /evidence="ECO:0007829|PDB:5OJJ"
SQ SEQUENCE 197 AA; 22521 MW; 6C02D774A7FA928A CRC64;
MQRASRLKRE LHMLATEPPP GITCWQDKDQ MDDLRAQILG GANTPYEKGV FKLEVIIPER
YPFEPPQIRF LTPIYHPNID SAGRICLDVL KLPPKGAWRP SLNIATVLTS IQLLMSEPNP
DDPLMADISS EFKYNKPAFL KNARQWTEKH ARQKQKADEE EMLDNLPEAG DSRVHNSTQK
RKASQLVGIE KKFHPDV
