UB2E2_HUMAN
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 03-AUG-2022, entry version 178.
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}.
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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; 93.
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 BioMuta; UBE2E2; -.
DR DMDM; 47606201; -.
DR EPD; Q96LR5; -.
DR jPOST; Q96LR5; -.
DR MassIVE; Q96LR5; -.
DR MaxQB; Q96LR5; -.
DR PaxDb; Q96LR5; -.
DR PeptideAtlas; Q96LR5; -.
DR PRIDE; Q96LR5; -.
DR ProteomicsDB; 77239; -.
DR Antibodypedia; 11339; 181 antibodies from 31 providers.
DR CPTC; Q96LR5; 3 antibodies.
DR DNASU; 7325; -.
DR Ensembl; ENST00000396703.6; ENSP00000379931.1; ENSG00000182247.10.
DR Ensembl; ENST00000425792.5; ENSP00000401053.1; ENSG00000182247.10.
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 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; KTARQWT; -.
DR OrthoDB; 1337945at2759; -.
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 UniPathway; UPA00143; -.
DR BioGRID-ORCS; 7325; 8 hits in 1074 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 182 other tissues.
DR ExpressionAtlas; Q96LR5; baseline and differential.
DR Genevisible; Q96LR5; HS.
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:cellular response to DNA damage stimulus; 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 GO; GO:0000209; P:protein polyubiquitination; IBA:GO_Central.
DR CDD; cd00195; UBCc; 1.
DR Gene3D; 3.10.110.10; -; 1.
DR IDEAL; IID00640; -.
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; 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
