UBE2K_HUMAN
ID UBE2K_HUMAN Reviewed; 200 AA.
AC P61086; A6NJC1; A8K5Y9; B2RDF8; C9JGP1; O54806; P27924; Q16721; Q9CVV9;
AC Q9Y2D3;
DT 26-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=Ubiquitin-conjugating enzyme E2 K;
DE EC=2.3.2.23 {ECO:0000269|PubMed:20061386};
DE AltName: Full=E2 ubiquitin-conjugating enzyme K;
DE AltName: Full=Huntingtin-interacting protein 2;
DE Short=HIP-2;
DE AltName: Full=Ubiquitin carrier protein;
DE AltName: Full=Ubiquitin-conjugating enzyme E2-25 kDa;
DE Short=Ubiquitin-conjugating enzyme E2(25K);
DE Short=Ubiquitin-conjugating enzyme E2-25K;
DE AltName: Full=Ubiquitin-protein ligase;
GN Name=UBE2K; Synonyms=HIP2, LIG;
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] (ISOFORM 1), FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=8702625; DOI=10.1074/jbc.271.32.19385;
RA Kalchman M.A., Graham R.K., Xia G., Koide H.B., Hodgson J.G., Graham K.C.,
RA Goldberg Y.P., Gietz R.D., Pickart C.M., Hayden M.R.;
RT "Huntingtin is ubiquitinated and interacts with a specific ubiquitin-
RT conjugating enzyme.";
RL J. Biol. Chem. 271:19385-19394(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, TISSUE
RP SPECIFICITY, AND INDUCTION.
RX PubMed=10634809; DOI=10.1161/01.atv.20.1.128;
RA Kikuchi J., Furukawa Y., Kubo N., Tokura A., Hayashi N., Nakamura M.,
RA Matsuda M., Sakurabayashi I.;
RT "Induction of ubiquitin-conjugating enzyme by aggregated low density
RT lipoprotein in human macrophages and its implications for
RT atherosclerosis.";
RL Arterioscler. Thromb. Vasc. Biol. 20:128-134(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, TISSUE
RP SPECIFICITY, AND INDUCTION.
RX PubMed=10675012;
RX DOI=10.1002/(sici)1522-2683(20000101)21:2<338::aid-elps338>3.0.co;2-9;
RA Furukawa Y., Kubo N., Kikuchi J., Tokura A., Fujita N., Sakurabayashi I.;
RT "Regulation of macrophage-specific gene expression by degenerated
RT lipoproteins.";
RL Electrophoresis 21:338-346(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Placenta;
RA Li W.B., Gruber C., Jessee J., Polayes D.;
RT "Full-length cDNA libraries and normalization.";
RL Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
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] (ISOFORM 1).
RC TISSUE=Brain, and Uterus;
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 PROTEIN SEQUENCE OF 2-10; 62-72; 79-97 AND 166-186, FUNCTION,
RP IDENTIFICATION BY MASS SPECTROMETRY, AND INTERACTION WITH RNF138.
RX PubMed=16714285; DOI=10.1074/jbc.m602089200;
RA Yamada M., Ohnishi J., Ohkawara B., Iemura S., Satoh K., Hyodo-Miura J.,
RA Kawachi K., Natsume T., Shibuya H.;
RT "NARF, an nemo-like kinase (NLK)-associated ring finger protein regulates
RT the ubiquitylation and degradation of T cell factor/lymphoid enhancer
RT factor (TCF/LEF).";
RL J. Biol. Chem. 281:20749-20760(2006).
RN [10]
RP PROTEIN SEQUENCE OF 2-8.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R.,
RA Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass spectrometric
RT identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [11]
RP PROTEIN SEQUENCE OF 2-8; 56-72 AND 177-186, CLEAVAGE OF INITIATOR
RP METHIONINE, ACETYLATION AT ALA-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Colon carcinoma;
RA Bienvenut W.V., Bilsland A.E., Keith W.N.;
RL Submitted (JAN-2010) to UniProtKB.
RN [12]
RP FUNCTION IN DEGRADATION OF MHC CLASS I HEAVY CHAINS.
RX PubMed=16868077; DOI=10.1073/pnas.0605215103;
RA Flierman D., Coleman C.S., Pickart C.M., Rapoport T.A., Chau V.;
RT "E2-25K mediates US11-triggered retro-translocation of MHC class I heavy
RT chains in a permeabilized cell system.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:11589-11594(2006).
RN [13]
RP FUNCTION IN POLYUBIQUITINATION, AND INTERACTION WITH BRCA1.
RX PubMed=17873885; DOI=10.1038/nsmb1295;
RA Christensen D.E., Brzovic P.S., Klevit R.E.;
RT "E2-BRCA1 RING interactions dictate synthesis of mono- or specific
RT polyubiquitin chain linkages.";
RL Nat. Struct. Mol. Biol. 14:941-948(2007).
RN [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-14, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [15]
RP FUNCTION, AND CATALYTIC ACTIVITY.
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 FUNCTION IN VIRUS-INDUCED DEGRADATION OF RB1.
RX PubMed=19906396; DOI=10.1016/j.virol.2009.10.018;
RA Oh K.J., Kalinina A., Bagchi S.;
RT "Destabilization of Rb by human papillomavirus E7 is cell cycle dependent:
RT E2-25K is involved in the proteolysis.";
RL Virology 396:118-124(2010).
RN [17]
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 [18]
RP MUTAGENESIS OF ASP-94.
RX PubMed=21532592; DOI=10.1038/nature09966;
RA Wenzel D.M., Lissounov A., Brzovic P.S., Klevit R.E.;
RT "UBCH7 reactivity profile reveals parkin and HHARI to be RING/HECT
RT hybrids.";
RL Nature 474:105-108(2011).
RN [19]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [20]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-159, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
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 [22]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-14, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25114211; DOI=10.1073/pnas.1413825111;
RA Impens F., Radoshevich L., Cossart P., Ribet D.;
RT "Mapping of SUMO sites and analysis of SUMOylation changes induced by
RT external stimuli.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:12432-12437(2014).
RN [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (1.86 ANGSTROMS).
RX PubMed=19407372; DOI=10.1107/s1744309109011117;
RA Wilson R.C., Hughes R.C., Flatt J.W., Meehan E.J., Ng J.D., Twigg P.D.;
RT "Structure of full-length ubiquitin-conjugating enzyme E2-25K (Huntingtin-
RT interacting protein 2).";
RL Acta Crystallogr. F 65:440-444(2009).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) IN COMPLEX WITH UBE2I.
RG Structural genomics consortium (SGC);
RT "A novel and unexpected complex between the SUMO-1-conjugating enzyme UBC9
RT and the ubiquitin-conjugating enzyme E2-25 kDA.";
RL Submitted (FEB-2009) to the PDB data bank.
RN [26]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
RG Structural genomics consortium (SGC);
RT "Ubiquitin-conjugating enzyme E2-25 kDA (Huntington-interacting protein
RT 2).";
RL Submitted (FEB-2009) to the PDB data bank.
CC -!- FUNCTION: Accepts ubiquitin from the E1 complex and catalyzes its
CC covalent attachment to other proteins. In vitro, in the presence or in
CC the absence of BRCA1-BARD1 E3 ubiquitin-protein ligase complex,
CC catalyzes the synthesis of 'Lys-48'-linked polyubiquitin chains. Does
CC not transfer ubiquitin directly to but elongates monoubiquitinated
CC substrate protein. Mediates the selective degradation of short-lived
CC and abnormal proteins, such as the endoplasmic reticulum-associated
CC degradation (ERAD) of misfolded lumenal proteins. Ubiquitinates
CC huntingtin. May mediate foam cell formation by the suppression of
CC apoptosis of lipid-bearing macrophages through ubiquitination and
CC subsequence degradation of p53/TP53. Proposed to be involved in
CC ubiquitination and proteolytic processing of NF-kappa-B; in vitro
CC supports ubiquitination of NFKB1. In case of infection by
CC cytomegaloviruses may be involved in the US11-dependent degradation of
CC MHC class I heavy chains following their export from the ER to the
CC cytosol. In case of viral infections may be involved in the HPV E7
CC protein-dependent degradation of RB1. {ECO:0000269|PubMed:10634809,
CC ECO:0000269|PubMed:10675012, ECO:0000269|PubMed:16714285,
CC ECO:0000269|PubMed:16868077, ECO:0000269|PubMed:17873885,
CC ECO:0000269|PubMed:19906396, ECO:0000269|PubMed:20061386,
CC ECO:0000269|PubMed:8702625}.
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: Interacts with RNF138/NARF. Interacts with BRCA1.
CC {ECO:0000269|PubMed:16714285, ECO:0000269|PubMed:17873885,
CC ECO:0000269|Ref.25}.
CC -!- INTERACTION:
CC P61086; Q6DHV7-2: ADAL; NbExp=3; IntAct=EBI-473850, EBI-18899653;
CC P61086; Q9NZS9: BFAR; NbExp=6; IntAct=EBI-473850, EBI-2130199;
CC P61086; Q96CA5: BIRC7; NbExp=3; IntAct=EBI-473850, EBI-517623;
CC P61086; Q6PIA0: BIRC8; NbExp=3; IntAct=EBI-473850, EBI-2129837;
CC P61086; Q8WUW1: BRK1; NbExp=3; IntAct=EBI-473850, EBI-2837444;
CC P61086; Q9UQM7: CAMK2A; NbExp=3; IntAct=EBI-473850, EBI-1383687;
CC P61086; Q9ULV8: CBLC; NbExp=3; IntAct=EBI-473850, EBI-2341018;
CC P61086; P14635: CCNB1; NbExp=2; IntAct=EBI-473850, EBI-495332;
CC P61086; P24863: CCNC; NbExp=3; IntAct=EBI-473850, EBI-395261;
CC P61086; Q9Y3D0: CIAO2B; NbExp=3; IntAct=EBI-473850, EBI-744045;
CC P61086; Q8WTU0: DDI1; NbExp=3; IntAct=EBI-473850, EBI-748248;
CC P61086; Q9NX09: DDIT4; NbExp=3; IntAct=EBI-473850, EBI-715104;
CC P61086; A0A024RCP2: DOM3Z; NbExp=3; IntAct=EBI-473850, EBI-25847826;
CC P61086; Q8N9I9: DTX3; NbExp=10; IntAct=EBI-473850, EBI-2340258;
CC P61086; Q8TDB6: DTX3L; NbExp=3; IntAct=EBI-473850, EBI-2340392;
CC P61086; Q15024: EXOSC7; NbExp=3; IntAct=EBI-473850, EBI-371841;
CC P61086; Q96GL9: FAM163A; NbExp=3; IntAct=EBI-473850, EBI-11793142;
CC P61086; Q7L8L6: FASTKD5; NbExp=3; IntAct=EBI-473850, EBI-747570;
CC P61086; Q4G1C9-2: GLIPR1L2; NbExp=3; IntAct=EBI-473850, EBI-20835942;
CC P61086; P62879: GNB2; NbExp=3; IntAct=EBI-473850, EBI-356942;
CC P61086; Q96LI6: HSFY2; NbExp=3; IntAct=EBI-473850, EBI-3957665;
CC P61086; P42858: HTT; NbExp=24; IntAct=EBI-473850, EBI-466029;
CC P61086; O00522: KRIT1; NbExp=3; IntAct=EBI-473850, EBI-1573121;
CC P61086; Q6IAA8: LAMTOR1; NbExp=3; IntAct=EBI-473850, EBI-715385;
CC P61086; Q86UD3: MARCHF3; NbExp=3; IntAct=EBI-473850, EBI-2341065;
CC P61086; Q9H992: MARCHF7; NbExp=3; IntAct=EBI-473850, EBI-949983;
CC P61086; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-473850, EBI-16439278;
CC P61086; O15344: MID1; NbExp=3; IntAct=EBI-473850, EBI-2340316;
CC P61086; Q9UJV3-2: MID2; NbExp=3; IntAct=EBI-473850, EBI-10172526;
CC P61086; Q8TD10: MIPOL1; NbExp=6; IntAct=EBI-473850, EBI-2548751;
CC P61086; Q13064: MKRN3; NbExp=3; IntAct=EBI-473850, EBI-2340269;
CC P61086; Q15843: NEDD8; NbExp=3; IntAct=EBI-473850, EBI-716247;
CC P61086; P26367: PAX6; NbExp=3; IntAct=EBI-473850, EBI-747278;
CC P61086; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-473850, EBI-79165;
CC P61086; A0A0C4DFM3: PRUNE2; NbExp=3; IntAct=EBI-473850, EBI-25830870;
CC P61086; Q9BYM8: RBCK1; NbExp=3; IntAct=EBI-473850, EBI-2340624;
CC P61086; Q9BYM8-4: RBCK1; NbExp=3; IntAct=EBI-473850, EBI-25867896;
CC P61086; Q04864: REL; NbExp=3; IntAct=EBI-473850, EBI-307352;
CC P61086; Q06587: RING1; NbExp=9; IntAct=EBI-473850, EBI-752313;
CC P61086; Q6ZNA4-2: RNF111; NbExp=3; IntAct=EBI-473850, EBI-21535400;
CC P61086; Q9Y508: RNF114; NbExp=3; IntAct=EBI-473850, EBI-723587;
CC P61086; Q8WVD3: RNF138; NbExp=11; IntAct=EBI-473850, EBI-749039;
CC P61086; Q96A37: RNF166; NbExp=3; IntAct=EBI-473850, EBI-2130320;
CC P61086; Q9H6Y7: RNF167; NbExp=3; IntAct=EBI-473850, EBI-1055214;
CC P61086; Q8N6D2: RNF182; NbExp=3; IntAct=EBI-473850, EBI-2130099;
CC P61086; Q96D59: RNF183; NbExp=3; IntAct=EBI-473850, EBI-743938;
CC P61086; Q96GF1: RNF185; NbExp=3; IntAct=EBI-473850, EBI-2340249;
CC P61086; Q99496: RNF2; NbExp=3; IntAct=EBI-473850, EBI-722416;
CC P61086; Q9H0A6-4: RNF32; NbExp=3; IntAct=EBI-473850, EBI-25868153;
CC P61086; Q9H4P4: RNF41; NbExp=3; IntAct=EBI-473850, EBI-2130266;
CC P61086; Q99942: RNF5; NbExp=11; IntAct=EBI-473850, EBI-348482;
CC P61086; O00560: SDCBP; NbExp=3; IntAct=EBI-473850, EBI-727004;
CC P61086; Q8IUQ4: SIAH1; NbExp=4; IntAct=EBI-473850, EBI-747107;
CC P61086; Q8IUQ4-2: SIAH1; NbExp=6; IntAct=EBI-473850, EBI-11522811;
CC P61086; Q96BD6: SPSB1; NbExp=3; IntAct=EBI-473850, EBI-2659201;
CC P61086; Q99619: SPSB2; NbExp=3; IntAct=EBI-473850, EBI-2323209;
CC P61086; O60506-4: SYNCRIP; NbExp=3; IntAct=EBI-473850, EBI-11123832;
CC P61086; O15273: TCAP; NbExp=3; IntAct=EBI-473850, EBI-954089;
CC P61086; Q12888: TP53BP1; NbExp=3; IntAct=EBI-473850, EBI-396540;
CC P61086; Q9BWF2: TRAIP; NbExp=3; IntAct=EBI-473850, EBI-1756205;
CC P61086; Q9C040: TRIM2; NbExp=3; IntAct=EBI-473850, EBI-749840;
CC P61086; P14373: TRIM27; NbExp=12; IntAct=EBI-473850, EBI-719493;
CC P61086; Q9BZY9: TRIM31; NbExp=11; IntAct=EBI-473850, EBI-747544;
CC P61086; Q9UPQ4-2: TRIM35; NbExp=6; IntAct=EBI-473850, EBI-17716262;
CC P61086; Q9HCM9: TRIM39; NbExp=3; IntAct=EBI-473850, EBI-739510;
CC P61086; Q9HCM9-2: TRIM39; NbExp=8; IntAct=EBI-473850, EBI-11523450;
CC P61086; Q96BQ3: TRIM43; NbExp=3; IntAct=EBI-473850, EBI-2129899;
CC P61086; Q9C035-3: TRIM5; NbExp=6; IntAct=EBI-473850, EBI-12840050;
CC P61086; Q86XT4: TRIM50; NbExp=3; IntAct=EBI-473850, EBI-9867283;
CC P61086; Q15631: TSN; NbExp=3; IntAct=EBI-473850, EBI-1044160;
CC P61086; P09936: UCHL1; NbExp=3; IntAct=EBI-473850, EBI-714860;
CC P61086; P40337-2: VHL; NbExp=3; IntAct=EBI-473850, EBI-12157263;
CC P61086; Q9H270: VPS11; NbExp=3; IntAct=EBI-473850, EBI-373380;
CC P61086; O76024: WFS1; NbExp=3; IntAct=EBI-473850, EBI-720609;
CC P61086; Q99PZ6: ospG; Xeno; NbExp=2; IntAct=EBI-473850, EBI-9316527;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P61085}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P61086-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P61086-2; Sequence=VSP_011798;
CC Name=3;
CC IsoId=P61086-3; Sequence=VSP_046211;
CC -!- TISSUE SPECIFICITY: Expressed in all tissues tested, including spleen,
CC thymus, prostate, testis, ovary, small intestine, colon, peripheral
CC blood leukocytes, T-lymphocytes, monocytes, granulocytes and bone
CC marrow mononuclear cells. Highly expressed in brain, with highest
CC levels found in cortex and striatum and at lower levels in cerebellum
CC and brainstem. {ECO:0000269|PubMed:10634809,
CC ECO:0000269|PubMed:10675012, ECO:0000269|PubMed:8702625}.
CC -!- INDUCTION: By aggregated low-density lipoprotein.
CC {ECO:0000269|PubMed:10634809, ECO:0000269|PubMed:10675012}.
CC -!- PTM: Sumoylation at Lys-14 impairs catalytic activity.
CC {ECO:0000250|UniProtKB:P61085}.
CC -!- MISCELLANEOUS: [Isoform 2]: May be inactive. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the ubiquitin-conjugating enzyme family.
CC {ECO:0000255|PROSITE-ProRule:PRU00388}.
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DR EMBL; U58522; AAC50633.1; -; mRNA.
DR EMBL; AB022435; BAA78555.1; -; mRNA.
DR EMBL; AB022436; BAA78556.1; -; mRNA.
DR EMBL; BX339118; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AK291454; BAF84143.1; -; mRNA.
DR EMBL; AK315524; BAG37905.1; -; mRNA.
DR EMBL; AC105287; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC108471; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471069; EAW92948.1; -; Genomic_DNA.
DR EMBL; BC022804; AAH22804.1; -; mRNA.
DR EMBL; BC050600; AAH50600.1; -; mRNA.
DR CCDS; CCDS33976.1; -. [P61086-1]
DR CCDS; CCDS47043.1; -. [P61086-3]
DR CCDS; CCDS47044.1; -. [P61086-2]
DR RefSeq; NP_001104582.1; NM_001111112.1. [P61086-3]
DR RefSeq; NP_001104583.1; NM_001111113.1. [P61086-2]
DR RefSeq; NP_005330.1; NM_005339.4. [P61086-1]
DR PDB; 1YLA; X-ray; 2.40 A; A/B=1-200.
DR PDB; 2O25; X-ray; 2.60 A; A/B=1-200.
DR PDB; 3E46; X-ray; 1.86 A; A=1-200.
DR PDB; 3F92; X-ray; 2.23 A; A=1-200.
DR PDB; 3K9O; X-ray; 1.80 A; A=1-200.
DR PDB; 3K9P; X-ray; 2.80 A; A=1-200.
DR PDB; 5DFL; X-ray; 2.10 A; A=1-200.
DR PDB; 6IF1; X-ray; 2.47 A; A/B=1-199.
DR PDB; 6JB6; X-ray; 2.70 A; A=1-200.
DR PDB; 6JB7; X-ray; 2.10 A; A=1-200.
DR PDB; 7MYF; X-ray; 3.00 A; A=2-200.
DR PDB; 7MYH; X-ray; 2.39 A; A=2-200.
DR PDB; 7OJX; X-ray; 2.40 A; B=1-200.
DR PDBsum; 1YLA; -.
DR PDBsum; 2O25; -.
DR PDBsum; 3E46; -.
DR PDBsum; 3F92; -.
DR PDBsum; 3K9O; -.
DR PDBsum; 3K9P; -.
DR PDBsum; 5DFL; -.
DR PDBsum; 6IF1; -.
DR PDBsum; 6JB6; -.
DR PDBsum; 6JB7; -.
DR PDBsum; 7MYF; -.
DR PDBsum; 7MYH; -.
DR PDBsum; 7OJX; -.
DR AlphaFoldDB; P61086; -.
DR BMRB; P61086; -.
DR SMR; P61086; -.
DR BioGRID; 109340; 127.
DR DIP; DIP-32524N; -.
DR IntAct; P61086; 88.
DR MINT; P61086; -.
DR STRING; 9606.ENSP00000261427; -.
DR ChEMBL; CHEMBL4105835; -.
DR MoonDB; P61086; Predicted.
DR GlyGen; P61086; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P61086; -.
DR MetOSite; P61086; -.
DR PhosphoSitePlus; P61086; -.
DR SwissPalm; P61086; -.
DR BioMuta; UBE2K; -.
DR DMDM; 46577658; -.
DR OGP; P27924; -.
DR EPD; P61086; -.
DR jPOST; P61086; -.
DR MassIVE; P61086; -.
DR MaxQB; P61086; -.
DR PaxDb; P61086; -.
DR PeptideAtlas; P61086; -.
DR PRIDE; P61086; -.
DR ProteomicsDB; 10126; -.
DR ProteomicsDB; 57262; -. [P61086-1]
DR ProteomicsDB; 57263; -. [P61086-2]
DR TopDownProteomics; P61086-1; -. [P61086-1]
DR Antibodypedia; 11733; 432 antibodies from 41 providers.
DR DNASU; 3093; -.
DR Ensembl; ENST00000261427.10; ENSP00000261427.5; ENSG00000078140.14. [P61086-1]
DR Ensembl; ENST00000445950.2; ENSP00000390483.2; ENSG00000078140.14. [P61086-3]
DR Ensembl; ENST00000503368.5; ENSP00000421203.1; ENSG00000078140.14. [P61086-2]
DR GeneID; 3093; -.
DR KEGG; hsa:3093; -.
DR MANE-Select; ENST00000261427.10; ENSP00000261427.5; NM_005339.5; NP_005330.1.
DR UCSC; uc003gus.5; human. [P61086-1]
DR CTD; 3093; -.
DR DisGeNET; 3093; -.
DR GeneCards; UBE2K; -.
DR HGNC; HGNC:4914; UBE2K.
DR HPA; ENSG00000078140; Low tissue specificity.
DR MIM; 602846; gene.
DR neXtProt; NX_P61086; -.
DR OpenTargets; ENSG00000078140; -.
DR PharmGKB; PA162407874; -.
DR VEuPathDB; HostDB:ENSG00000078140; -.
DR eggNOG; KOG0418; Eukaryota.
DR GeneTree; ENSGT00670000098059; -.
DR HOGENOM; CLU_030988_13_1_1; -.
DR InParanoid; P61086; -.
DR OMA; HHLKGSF; -.
DR OrthoDB; 1418652at2759; -.
DR PhylomeDB; P61086; -.
DR TreeFam; TF101127; -.
DR BRENDA; 2.3.2.23; 2681.
DR BRENDA; 2.3.2.24; 2681.
DR PathwayCommons; P61086; -.
DR Reactome; R-HSA-8866652; Synthesis of active ubiquitin: roles of E1 and E2 enzymes.
DR Reactome; R-HSA-936440; Negative regulators of DDX58/IFIH1 signaling.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; P61086; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 3093; 79 hits in 1088 CRISPR screens.
DR ChiTaRS; UBE2K; human.
DR EvolutionaryTrace; P61086; -.
DR GeneWiki; HIP2; -.
DR GenomeRNAi; 3093; -.
DR Pharos; P61086; Tbio.
DR PRO; PR:P61086; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; P61086; protein.
DR Bgee; ENSG00000078140; Expressed in sperm and 200 other tissues.
DR ExpressionAtlas; P61086; baseline and differential.
DR Genevisible; P61086; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0032433; C:filopodium tip; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0061631; F:ubiquitin conjugating enzyme activity; IBA:GO_Central.
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:0034450; F:ubiquitin-ubiquitin ligase activity; IDA:UniProtKB.
DR GO; GO:0035458; P:cellular response to interferon-beta; IMP:UniProtKB.
DR GO; GO:0010994; P:free ubiquitin chain polymerization; IDA:UniProtKB.
DR GO; GO:0010800; P:positive regulation of peptidyl-threonine phosphorylation; IDA:UniProtKB.
DR GO; GO:1903265; P:positive regulation of tumor necrosis factor-mediated signaling pathway; IMP:FlyBase.
DR GO; GO:0060340; P:positive regulation of type I interferon-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; IBA:GO_Central.
DR GO; GO:0032434; P:regulation of proteasomal ubiquitin-dependent protein catabolic process; IEA:Ensembl.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; TAS:ProtInc.
DR CDD; cd14390; UBA_II_E2_UBE2K; 1.
DR CDD; cd00195; UBCc; 1.
DR Gene3D; 3.10.110.10; -; 1.
DR InterPro; IPR015940; UBA.
DR InterPro; IPR009060; UBA-like_sf.
DR InterPro; IPR042599; UBE2K_UBA.
DR InterPro; IPR000608; UBQ-conjugat_E2.
DR InterPro; IPR023313; UBQ-conjugating_AS.
DR InterPro; IPR016135; UBQ-conjugating_enzyme/RWD.
DR Pfam; PF00627; UBA; 1.
DR Pfam; PF00179; UQ_con; 1.
DR SMART; SM00165; UBA; 1.
DR SUPFAM; SSF46934; SSF46934; 1.
DR SUPFAM; SSF54495; SSF54495; 1.
DR PROSITE; PS50030; UBA; 1.
DR PROSITE; PS00183; UBC_1; 1.
DR PROSITE; PS50127; UBC_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; ATP-binding; Cytoplasm;
KW Direct protein sequencing; Isopeptide bond; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Transferase; Ubl conjugation;
KW Ubl conjugation pathway.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:12665801,
FT ECO:0000269|PubMed:16714285, ECO:0000269|Ref.11,
FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378"
FT CHAIN 2..200
FT /note="Ubiquitin-conjugating enzyme E2 K"
FT /id="PRO_0000082443"
FT DOMAIN 4..154
FT /note="UBC core"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00388"
FT DOMAIN 160..200
FT /note="UBA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00212"
FT ACT_SITE 92
FT /note="Glycyl thioester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00388,
FT ECO:0000255|PROSITE-ProRule:PRU10133"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|Ref.11, ECO:0007744|PubMed:22223895,
FT ECO:0007744|PubMed:22814378"
FT MOD_RES 14
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 159
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CROSSLNK 14
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO1); alternate"
FT /evidence="ECO:0007744|PubMed:25114211"
FT VAR_SEQ 22..72
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10634809,
FT ECO:0000303|PubMed:10675012, ECO:0000303|PubMed:14702039"
FT /id="VSP_011798"
FT VAR_SEQ 134..176
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_046211"
FT MUTAGEN 94
FT /note="D->E: Decreased lysine reactivity and impaired
FT formation of free polyubiquitin chains."
FT /evidence="ECO:0000269|PubMed:21532592"
FT HELIX 6..17
FT /evidence="ECO:0007829|PDB:3K9O"
FT HELIX 20..23
FT /evidence="ECO:0007829|PDB:3K9O"
FT STRAND 26..31
FT /evidence="ECO:0007829|PDB:3K9O"
FT STRAND 33..35
FT /evidence="ECO:0007829|PDB:2O25"
FT STRAND 36..44
FT /evidence="ECO:0007829|PDB:3K9O"
FT STRAND 47..49
FT /evidence="ECO:0007829|PDB:1YLA"
FT TURN 50..53
FT /evidence="ECO:0007829|PDB:3K9O"
FT STRAND 55..61
FT /evidence="ECO:0007829|PDB:3K9O"
FT TURN 64..68
FT /evidence="ECO:0007829|PDB:3K9O"
FT STRAND 72..77
FT /evidence="ECO:0007829|PDB:3K9O"
FT TURN 86..88
FT /evidence="ECO:0007829|PDB:3K9O"
FT HELIX 94..96
FT /evidence="ECO:0007829|PDB:3K9O"
FT TURN 97..99
FT /evidence="ECO:0007829|PDB:3K9O"
FT HELIX 106..118
FT /evidence="ECO:0007829|PDB:3K9O"
FT HELIX 128..136
FT /evidence="ECO:0007829|PDB:3K9O"
FT HELIX 138..153
FT /evidence="ECO:0007829|PDB:3K9O"
FT HELIX 160..170
FT /evidence="ECO:0007829|PDB:3K9O"
FT TURN 171..173
FT /evidence="ECO:0007829|PDB:3K9O"
FT HELIX 176..185
FT /evidence="ECO:0007829|PDB:3K9O"
FT TURN 186..188
FT /evidence="ECO:0007829|PDB:3K9O"
FT HELIX 190..199
FT /evidence="ECO:0007829|PDB:3K9O"
SQ SEQUENCE 200 AA; 22407 MW; E40668099ED25828 CRC64;
MANIAVQRIK REFKEVLKSE ETSKNQIKVD LVDENFTELR GEIAGPPDTP YEGGRYQLEI
KIPETYPFNP PKVRFITKIW HPNISSVTGA ICLDILKDQW AAAMTLRTVL LSLQALLAAA
EPDDPQDAVV ANQYKQNPEM FKQTARLWAH VYAGAPVSSP EYTKKIENLC AMGFDRNAVI
VALSSKSWDV ETATELLLSN
