ID UB2E2_HUMAN Reviewed; 201 AA. AC Q96LR5; DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2001, sequence version 1. DT 27-MAR-2024, entry version 187. DE RecName: Full=Ubiquitin-conjugating enzyme E2 E2; DE EC=2.3.2.23 {ECO:0000269|PubMed:20061386}; DE AltName: Full=E2 ubiquitin-conjugating enzyme E2; DE AltName: Full=UbcH8; DE AltName: Full=Ubiquitin carrier protein E2; DE AltName: Full=Ubiquitin-protein ligase E2; GN Name=UBE2E2; Synonyms=UBCH8; 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], AND FUNCTION. RX PubMed=9371400; DOI=10.1159/000134639; RA Kimura M., Hattori T., Matsuda Y., Yoshioka T., Sumi N., Umeda Y., RA Nakashima S., Okano Y.; RT "cDNA cloning, characterization, and chromosome mapping of UBE2E2 encoding RT a human ubiquitin-conjugating E2 enzyme."; RL Cytogenet. Cell Genet. 78:107-111(1997). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Prostate; 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 [4] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [5] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [6] 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 [7] RP FUNCTION. RX PubMed=20133869; DOI=10.1073/pnas.0909144107; RA Zhao C., Hsiang T.Y., Kuo R.L., Krug R.M.; RT "ISG15 conjugation system targets the viral NS1 protein in influenza A RT virus-infected cells."; RL Proc. Natl. Acad. Sci. U.S.A. 107:2253-2258(2010). RN [8] 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 [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [10] RP IDENTIFICATION BY 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 [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-11; SER-15 AND SER-18, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [12] {ECO:0007744|PDB:1Y6L} RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 55-201, 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). CC -!- FUNCTION: Accepts ubiquitin from the E1 complex and catalyzes its CC covalent attachment to other proteins. In vitro catalyzes 'Lys-11'- and CC 'Lys-48'-, as well as 'Lys-63'-linked polyubiquitination. Catalyzes the CC ISGylation of influenza A virus NS1 protein. CC {ECO:0000269|PubMed:20061386, ECO:0000269|PubMed:20133869, CC ECO:0000269|PubMed:9371400}. 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 -!- INTERACTION: CC Q96LR5; Q96B67: ARRDC3; NbExp=8; IntAct=EBI-2129763, EBI-2875665; CC Q96LR5; Q96EP1-2: CHFR; NbExp=3; IntAct=EBI-2129763, EBI-12344389; CC Q96LR5; Q9NWM3: CUEDC1; NbExp=3; IntAct=EBI-2129763, EBI-5838167; CC Q96LR5; Q15038: DAZAP2; NbExp=3; IntAct=EBI-2129763, EBI-724310; CC Q96LR5; Q86Y13: DZIP3; NbExp=4; IntAct=EBI-2129763, EBI-948630; CC Q96LR5; Q8IZU0: FAM9B; NbExp=3; IntAct=EBI-2129763, EBI-10175124; CC Q96LR5; O15344: MID1; NbExp=12; IntAct=EBI-2129763, EBI-2340316; CC Q96LR5; Q9UJV3-2: MID2; NbExp=6; IntAct=EBI-2129763, EBI-10172526; CC Q96LR5; Q96FW1: OTUB1; NbExp=8; IntAct=EBI-2129763, EBI-1058491; CC Q96LR5; Q9NXJ5-2: PGPEP1; NbExp=6; IntAct=EBI-2129763, EBI-12813581; CC Q96LR5; Q9Y4L5: RNF115; NbExp=6; IntAct=EBI-2129763, EBI-2129242; CC Q96LR5; Q96EQ8: RNF125; NbExp=5; IntAct=EBI-2129763, EBI-2339208; CC Q96LR5; Q96GF1: RNF185; NbExp=4; IntAct=EBI-2129763, EBI-2340249; CC Q96LR5; Q99496: RNF2; NbExp=6; IntAct=EBI-2129763, EBI-722416; CC Q96LR5; Q99942: RNF5; NbExp=10; IntAct=EBI-2129763, EBI-348482; CC Q96LR5; O75382: TRIM3; NbExp=3; IntAct=EBI-2129763, EBI-2129889; CC Q96LR5; Q9HCM9: TRIM39; NbExp=6; IntAct=EBI-2129763, EBI-739510; CC Q96LR5; Q9HCM9-2: TRIM39; NbExp=8; IntAct=EBI-2129763, EBI-11523450; CC Q96LR5; Q86XT4: TRIM50; NbExp=6; IntAct=EBI-2129763, EBI-9867283; CC Q96LR5; O00308: WWP2; NbExp=3; IntAct=EBI-2129763, EBI-743923; CC Q96LR5; Q99PZ6: ospG; Xeno; NbExp=2; IntAct=EBI-2129763, EBI-9316527; CC -!- PTM: Autoubiquitinated in vitro. {ECO:0000269|PubMed:22496338}. 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; AK057886; BAB71605.1; -; mRNA. DR EMBL; BC022332; AAH22332.1; -; mRNA. DR CCDS; CCDS2637.1; -. DR RefSeq; NP_689866.1; NM_152653.3. DR RefSeq; XP_005265489.1; XM_005265432.2. DR PDB; 1Y6L; X-ray; 1.85 A; A/B/C=55-201. DR PDB; 6W9A; X-ray; 2.30 A; A/C=30-201. DR PDBsum; 1Y6L; -. DR PDBsum; 6W9A; -. DR AlphaFoldDB; Q96LR5; -. DR SMR; Q96LR5; -. DR BioGRID; 113173; 95. DR DIP; DIP-52704N; -. DR IntAct; Q96LR5; 54. DR MINT; Q96LR5; -. DR STRING; 9606.ENSP00000379931; -. DR MoonDB; Q96LR5; Predicted. DR GlyGen; Q96LR5; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q96LR5; -. DR PhosphoSitePlus; Q96LR5; -. DR SwissPalm; Q96LR5; -. DR BioMuta; UBE2E2; -. DR DMDM; 47606201; -. DR EPD; Q96LR5; -. DR jPOST; Q96LR5; -. DR MassIVE; Q96LR5; -. DR MaxQB; Q96LR5; -. DR PaxDb; 9606-ENSP00000379931; -. DR PeptideAtlas; Q96LR5; -. DR ProteomicsDB; 77239; -. DR Pumba; Q96LR5; -. DR Antibodypedia; 11339; 203 antibodies from 31 providers. DR CPTC; Q96LR5; 3 antibodies. DR DNASU; 7325; -. DR Ensembl; ENST00000396703.6; ENSP00000379931.1; ENSG00000182247.11. DR Ensembl; ENST00000425792.5; ENSP00000401053.1; ENSG00000182247.11. DR GeneID; 7325; -. DR KEGG; hsa:7325; -. DR MANE-Select; ENST00000396703.6; ENSP00000379931.1; NM_152653.4; NP_689866.1. DR UCSC; uc003ccg.3; human. DR AGR; HGNC:12478; -. DR CTD; 7325; -. DR DisGeNET; 7325; -. DR GeneCards; UBE2E2; -. DR HGNC; HGNC:12478; UBE2E2. DR HPA; ENSG00000182247; Low tissue specificity. DR MIM; 602163; gene. DR neXtProt; NX_Q96LR5; -. DR OpenTargets; ENSG00000182247; -. DR PharmGKB; PA37128; -. DR VEuPathDB; HostDB:ENSG00000182247; -. DR eggNOG; KOG0417; Eukaryota. DR GeneTree; ENSGT00940000155985; -. DR HOGENOM; CLU_030988_14_4_1; -. DR InParanoid; Q96LR5; -. DR OMA; CTSEKRI; -. DR OrthoDB; 5478564at2759; -. DR PhylomeDB; Q96LR5; -. DR TreeFam; TF101117; -. DR BRENDA; 2.3.2.23; 2681. DR BRENDA; 2.3.2.24; 2681. DR PathwayCommons; Q96LR5; -. DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation. DR SignaLink; Q96LR5; -. DR SIGNOR; Q96LR5; -. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 7325; 13 hits in 1151 CRISPR screens. DR ChiTaRS; UBE2E2; human. DR EvolutionaryTrace; Q96LR5; -. DR GeneWiki; UBE2E2; -. DR GenomeRNAi; 7325; -. DR Pharos; Q96LR5; Tbio. DR PRO; PR:Q96LR5; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; Q96LR5; Protein. DR Bgee; ENSG00000182247; Expressed in sural nerve and 183 other cell types or tissues. DR ExpressionAtlas; Q96LR5; baseline and differential. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0042296; F:ISG15 transferase activity; IDA:HGNC-UCL. DR GO; GO:0061631; F:ubiquitin conjugating enzyme activity; IDA:MGI. DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB. DR GO; GO:0006974; P:DNA damage response; IMP:MGI. DR GO; GO:0032020; P:ISG15-protein conjugation; IDA:HGNC-UCL. DR GO; GO:1900087; P:positive regulation of G1/S transition of mitotic cell cycle; IGI:MGI. DR GO; GO:0070979; P:protein K11-linked ubiquitination; IDA:UniProtKB. DR GO; GO:0070936; P:protein K48-linked ubiquitination; IDA:UniProtKB. DR GO; GO:0070534; P:protein K63-linked ubiquitination; IDA:UniProtKB. DR CDD; cd00195; UBCc; 1. DR Gene3D; 3.10.110.10; Ubiquitin Conjugating Enzyme; 1. DR IDEAL; IID00640; -. DR InterPro; IPR000608; UBQ-conjugat_E2. DR InterPro; IPR023313; UBQ-conjugating_AS. DR InterPro; IPR016135; UBQ-conjugating_enzyme/RWD. DR PANTHER; PTHR24068; UBIQUITIN-CONJUGATING ENZYME E2; 1. DR PANTHER; PTHR24068:SF429; UBIQUITIN-CONJUGATING ENZYME E2 E2; 1. DR Pfam; PF00179; UQ_con; 1. DR SMART; SM00212; UBCc; 1. DR SUPFAM; SSF54495; UBC-like; 1. DR PROSITE; PS00183; UBC_1; 1. DR PROSITE; PS50127; UBC_2; 1. DR Genevisible; Q96LR5; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; ATP-binding; Nucleotide-binding; Phosphoprotein; KW Reference proteome; Transferase; Ubl conjugation; Ubl conjugation pathway. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:19413330" FT CHAIN 2..201 FT /note="Ubiquitin-conjugating enzyme E2 E2" FT /id="PRO_0000082472" FT DOMAIN 55..201 FT /note="UBC core" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00388" FT REGION 1..55 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1..24 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 25..47 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 139 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-acetylserine" FT /evidence="ECO:0007744|PubMed:19413330" FT MOD_RES 11 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 15 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 18 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 19 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" FT HELIX 55..69 FT /evidence="ECO:0007829|PDB:1Y6L" FT STRAND 75..82 FT /evidence="ECO:0007829|PDB:1Y6L" FT STRAND 86..92 FT /evidence="ECO:0007829|PDB:1Y6L" FT TURN 98..101 FT /evidence="ECO:0007829|PDB:1Y6L" FT STRAND 103..109 FT /evidence="ECO:0007829|PDB:1Y6L" FT TURN 112..115 FT /evidence="ECO:0007829|PDB:1Y6L" FT STRAND 120..125 FT /evidence="ECO:0007829|PDB:1Y6L" FT HELIX 141..143 FT /evidence="ECO:0007829|PDB:1Y6L" FT TURN 144..146 FT /evidence="ECO:0007829|PDB:1Y6L" FT HELIX 153..165 FT /evidence="ECO:0007829|PDB:1Y6L" FT HELIX 175..183 FT /evidence="ECO:0007829|PDB:1Y6L" FT HELIX 185..199 FT /evidence="ECO:0007829|PDB:1Y6L" SQ SEQUENCE 201 AA; 22255 MW; 3286FB51E2B9CD3E CRC64; MSTEAQRVDD SPSTSGGSSD GDQRESVQQE PEREQVQPKK KEGKISSKTA AKLSTSAKRI QKELAEITLD PPPNCSAGPK GDNIYEWRST ILGPPGSVYE GGVFFLDITF SPDYPFKPPK VTFRTRIYHC NINSQGVICL DILKDNWSPA LTISKVLLSI CSLLTDCNPA DPLVGSIATQ YMTNRAEHDR MARQWTKRYA T //