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 27-MAR-2024, entry version 196. 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; Q8WUY3: PRUNE2; NbExp=3; IntAct=EBI-473850, EBI-743880; 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 140. DR DIP; DIP-32524N; -. DR IntAct; P61086; 89. 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; 9606-ENSP00000261427; -. DR PeptideAtlas; P61086; -. DR ProteomicsDB; 10126; -. DR ProteomicsDB; 57262; -. [P61086-1] DR ProteomicsDB; 57263; -. [P61086-2] DR Pumba; P61086; -. DR TopDownProteomics; P61086-1; -. [P61086-1] DR Antibodypedia; 11733; 454 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 AGR; HGNC:4914; -. 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; TGYFKGP; -. DR OrthoDB; 102270at2759; -. 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 SIGNOR; P61086; -. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 3093; 82 hits in 1166 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 202 other cell types or tissues. DR ExpressionAtlas; P61086; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IC:UniProt. 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; 1.10.8.10; DNA helicase RuvA subunit, C-terminal domain; 1. DR Gene3D; 3.10.110.10; Ubiquitin Conjugating Enzyme; 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 PANTHER; PTHR24067:SF347; E2 UBIQUITIN-CONJUGATING ENZYME; 1. DR PANTHER; PTHR24067; UBIQUITIN-CONJUGATING ENZYME E2; 1. DR Pfam; PF00627; UBA; 1. DR Pfam; PF00179; UQ_con; 1. DR SMART; SM00165; UBA; 1. DR SMART; SM00212; UBCc; 1. DR SUPFAM; SSF46934; UBA-like; 1. DR SUPFAM; SSF54495; UBC-like; 1. DR PROSITE; PS50030; UBA; 1. DR PROSITE; PS00183; UBC_1; 1. DR PROSITE; PS50127; UBC_2; 1. DR Genevisible; P61086; HS. 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 //