ID UB2D2_HUMAN Reviewed; 147 AA. AC P62837; D3DQC9; P51669; Q3MN78; DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot. DT 16-AUG-2004, sequence version 1. DT 03-OCT-2012, entry version 102. DE RecName: Full=Ubiquitin-conjugating enzyme E2 D2; DE EC=6.3.2.19; DE AltName: Full=Ubiquitin carrier protein D2; DE AltName: Full=Ubiquitin-conjugating enzyme E2(17)KB 2; DE AltName: Full=Ubiquitin-conjugating enzyme E2-17 kDa 2; DE AltName: Full=Ubiquitin-protein ligase D2; GN Name=UBE2D2; Synonyms=UBC4, UBC5B, UBCH4, UBCH5B; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX MEDLINE=96107191; PubMed=8530467; DOI=10.1074/jbc.270.51.30408; RA Jensen J.P., Bates P.W., Yang M., Vierstra R.D., Weissman A.M.; RT "Identification of a family of closely related human ubiquitin RT conjugating enzymes."; RL J. Biol. Chem. 270:30408-30414(1995). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX MEDLINE=95241484; PubMed=7724550; DOI=10.1073/pnas.92.8.3264; RA Rolfe M., Beer-Romero P., Glass S., Eckstein J., Berdo I., RA Theodoras A., Pagano M., Draetta G.; RT "Reconstitution of p53-ubiquitinylation reactions from purified RT components: the role of human ubiquitin-conjugating enzyme UBC4 and RT E6-associated protein (E6AP)."; RL Proc. Natl. Acad. Sci. U.S.A. 92:3264-3268(1995). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=16112646; DOI=10.1016/j.bbrc.2005.08.024; RA Guinn B.-A., Bland E.A., Lodi U., Liggins A.P., Tobal K., Petters S., RA Wells J.W., Banham A.H., Mufti G.J.; RT "Humoral detection of leukaemia-associated antigens in presentation RT acute myeloid leukaemia."; RL Biochem. Biophys. Res. Commun. 335:1293-1304(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Testis; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP PROTEIN SEQUENCE OF 73-90, AND MASS SPECTROMETRY. RC TISSUE=Brain, and Cajal-Retzius cell; RA Lubec G., Afjehi-Sadat L.; RL Submitted (MAR-2007) to UniProtKB. RN [8] RP FUNCTION, AND MUTAGENESIS OF CYS-85. RX PubMed=10329681; DOI=10.1074/jbc.274.21.14823; RA Gonen H., Bercovich B., Orian A., Carrano A., Takizawa C., RA Yamanaka K., Pagano M., Iwai K., Ciechanover A.; RT "Identification of the ubiquitin carrier proteins, E2s, involved in RT signal-induced conjugation and subsequent degradation of RT IkappaBalpha."; RL J. Biol. Chem. 274:14823-14830(1999). RN [9] RP INTERACTION WITH SCF COMPLEX. RX MEDLINE=20379358; PubMed=10918611; DOI=10.1038/sj.onc.1203647; RA Strack P., Caligiuri M., Pelletier M., Boisclair M., Theodoras A., RA Beer-Romero P., Glass S., Parsons T., Copeland R.A., Auger K.R., RA Benfield P., Brizuela L., Rolfe M.; RT "SCF(beta-TRCP) and phosphorylation dependent ubiquitination of I RT kappa B alpha catalyzed by Ubc3 and Ubc4."; RL Oncogene 19:3529-3536(2000). RN [10] RP FUNCTION. RX PubMed=15280377; DOI=10.1074/jbc.M403362200; RA Saville M.K., Sparks A., Xirodimas D.P., Wardrop J., Stevenson L.F., RA Bourdon J.C., Woods Y.L., Lane D.P.; RT "Regulation of p53 by the ubiquitin-conjugating enzymes UbcH5B/C in RT vivo."; RL J. Biol. Chem. 279:42169-42181(2004). RN [11] RP INTERACTION WITH CNOT4, AND MUTAGENESIS OF LYS-63. RX PubMed=15001359; DOI=10.1016/j.jmb.2004.01.031; RA Winkler G.S., Albert T.K., Dominguez C., Legtenberg Y.I., Boelens R., RA Timmers H.T.; RT "An altered-specificity ubiquitin-conjugating enzyme/ubiquitin-protein RT ligase pair."; RL J. Mol. Biol. 337:157-165(2004). RN [12] RP FUNCTION. RX PubMed=18042044; DOI=10.1042/BJ20071338; RA Windheim M., Peggie M., Cohen P.; RT "Two different classes of E2 ubiquitin-conjugating enzymes are RT required for the mono-ubiquitination of proteins and elongation by RT polyubiquitin chains with a specific topology."; RL Biochem. J. 409:723-729(2008). RN [13] RP FUNCTION, AND MUTAGENESIS OF CYS-85. RX PubMed=18703417; DOI=10.1095/biolreprod.108.071407; RA Chiang M.H., Chen L.F., Chen H.; RT "Ubiquitin-conjugating enzyme UBE2D2 is responsible for FBXW2 (F-box RT and WD repeat domain containing 2)-mediated human GCM1 (glial cell RT missing homolog 1) ubiquitination and degradation."; RL Biol. Reprod. 79:914-920(2008). RN [14] RP FUNCTION. RX PubMed=18359941; DOI=10.1074/jbc.M800402200; RA Grou C.P., Carvalho A.F., Pinto M.P., Wiese S., Piechura H., RA Meyer H.E., Warscheid B., Sa-Miranda C., Azevedo J.E.; RT "Members of the E2D (UbcH5) family mediate the ubiquitination of the RT conserved cysteine of Pex5p, the peroxisomal import receptor."; RL J. Biol. Chem. 283:14190-14197(2008). RN [15] RP IDENTIFICATION BY MASS SPECTROMETRY, AND FUNCTION. RX PubMed=19854139; DOI=10.1016/j.molcel.2009.09.037; RA Zeng W., Xu M., Liu S., Sun L., Chen Z.J.; RT "Key role of Ubc5 and lysine-63 polyubiquitination in viral activation RT of IRF3."; RL Mol. Cell 36:315-325(2009). RN [16] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-8, AND MASS SPECTROMETRY. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., 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 [17] RP FUNCTION. RX PubMed=20403326; DOI=10.1016/j.cell.2010.03.029; RA Zeng W., Sun L., Jiang X., Chen X., Hou F., Adhikari A., Xu M., RA Chen Z.J.; RT "Reconstitution of the RIG-I pathway reveals a signaling role of RT unanchored polyubiquitin chains in innate immunity."; RL Cell 141:315-330(2010). RN [18] RP FUNCTION. 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 [19] 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., RA Buerckstuemmer T., 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 [20] RP STRUCTURE BY NMR. RX PubMed=15522302; DOI=10.1016/j.jmb.2004.09.054; RA Houben K., Dominguez C., van Schaik F.M., Timmers H.T., Bonvin A.M., RA Boelens R.; RT "Solution structure of the ubiquitin-conjugating enzyme UbcH5B."; RL J. Mol. Biol. 344:513-526(2004). RN [21] RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS). RX PubMed=20152160; DOI=10.1016/j.str.2009.11.007; RA Sakata E., Satoh T., Yamamoto S., Yamaguchi Y., Yagi-Utsumi M., RA Kurimoto E., Tanaka K., Wakatsuki S., Kato K.; RT "Crystal structure of UbcH5b~ubiquitin intermediate: insight into the RT formation of the self-assembled E2~Ub conjugates."; RL Structure 18:138-147(2010). CC -!- FUNCTION: Accepts ubiquitin from the E1 complex and catalyzes its CC covalent attachment to other proteins. In vitro catalyzes 'Lys- CC 48'-linked polyubiquitination. Mediates the selective degradation CC of short-lived and abnormal proteins. Functions in the E6/E6-AP- CC induced ubiquitination of p53/TP53. Mediates ubiquitination of CC PEX5 and autoubiquitination of STUB1 and TRAF6. Involved in the CC signal-induced conjugation and subsequent degradation of NFKBIA, CC FBXW2-mediated GCM1 ubiquitination and degradation, MDM2-dependent CC degradation of p53/TP53 and the activation of MAVS in the CC mitochondria by DDX58/RIG-I in response to viral infection. CC Essential for viral activation of IRF3. CC -!- CATALYTIC ACTIVITY: ATP + ubiquitin + protein lysine = AMP + CC diphosphate + protein N-ubiquityllysine. CC -!- PATHWAY: Protein modification; protein ubiquitination. CC -!- SUBUNIT: Interacts with SCF (SKP1-CUL1-F-box protein) E3 ubiquitin CC ligase complex and with E3 ubiquitin-protein ligase PJA2 (By CC similarity). Interacts with PDZRN3 (By similarity). Interacts with CC CNOT4 (via RING domain). CC -!- INTERACTION: CC O15151:MDM4; NbExp=2; IntAct=EBI-347677, EBI-398437; CC Q96FW1:OTUB1; NbExp=2; IntAct=EBI-347677, EBI-1058491; CC Q9Y3C5:RNF11; NbExp=4; IntAct=EBI-347677, EBI-396669; CC Q68DV7:RNF43; NbExp=2; IntAct=EBI-347677, EBI-1647060; CC Q99942:RNF5; NbExp=3; IntAct=EBI-347677, EBI-348482; CC Q9Y4K3:TRAF6; NbExp=2; IntAct=EBI-347677, EBI-359276; CC P98170:XIAP; NbExp=2; IntAct=EBI-347677, EBI-517127; CC Q8ND25:ZNRF1; NbExp=4; IntAct=EBI-347677, EBI-2129250; CC -!- SIMILARITY: Belongs to the ubiquitin-conjugating enzyme family. 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; U39317; AAA91460.1; -; mRNA. DR EMBL; L40146; AAC41750.1; -; Genomic_DNA. DR EMBL; AY651263; AAX35690.1; -; mRNA. DR EMBL; AK001311; BAG50891.1; -; mRNA. DR EMBL; AK001428; BAG50911.1; -; mRNA. DR EMBL; CH471062; EAW62095.1; -; Genomic_DNA. DR EMBL; CH471062; EAW62096.1; -; Genomic_DNA. DR EMBL; BC033349; AAH33349.1; -; mRNA. DR IPI; IPI00332376; -. DR PIR; I59365; I59365. DR RefSeq; NP_003330.1; NM_003339.2. DR RefSeq; NP_862821.1; NM_181838.1. DR UniGene; Hs.108332; -. DR PDB; 1UR6; NMR; -; A=1-147. DR PDB; 1W4U; NMR; -; A=1-147. DR PDB; 2C4O; X-ray; 1.94 A; A/B/C/D=1-147. DR PDB; 2CLW; X-ray; 1.94 A; A/B/C/D=1-147. DR PDB; 2ESK; X-ray; 1.36 A; A=1-147. DR PDB; 2ESO; X-ray; 1.50 A; A=1-147. DR PDB; 2ESP; X-ray; 1.52 A; A=1-147. DR PDB; 2ESQ; X-ray; 1.44 A; A=1-147. DR PDB; 3A33; X-ray; 2.20 A; A=1-147. DR PDB; 3JVZ; X-ray; 3.30 A; A/B=4-147. DR PDB; 3JW0; X-ray; 3.10 A; A/B=4-147. DR PDB; 3L1Y; X-ray; 1.60 A; A=1-147. DR PDB; 3TGD; X-ray; 1.80 A; A=1-147. DR PDB; 4A49; X-ray; 2.21 A; B=1-147. DR PDB; 4A4B; X-ray; 2.79 A; C=1-147. DR PDB; 4A4C; X-ray; 2.70 A; C=1-147. DR PDB; 4AUQ; X-ray; 2.18 A; A/D=1-147. DR PDB; 4DDG; X-ray; 3.30 A; C/D/H/N/R/V=1-147. DR PDB; 4DDI; X-ray; 3.80 A; D/E/F=1-147. DR PDBsum; 1UR6; -. DR PDBsum; 1W4U; -. DR PDBsum; 2C4O; -. DR PDBsum; 2CLW; -. DR PDBsum; 2ESK; -. DR PDBsum; 2ESO; -. DR PDBsum; 2ESP; -. DR PDBsum; 2ESQ; -. DR PDBsum; 3A33; -. DR PDBsum; 3JVZ; -. DR PDBsum; 3JW0; -. DR PDBsum; 3L1Y; -. DR PDBsum; 3TGD; -. DR PDBsum; 4A49; -. DR PDBsum; 4A4B; -. DR PDBsum; 4A4C; -. DR PDBsum; 4AUQ; -. DR PDBsum; 4DDG; -. DR PDBsum; 4DDI; -. DR ProteinModelPortal; P62837; -. DR SMR; P62837; 1-147. DR DIP; DIP-29267N; -. DR IntAct; P62837; 95. DR MINT; MINT-1035011; -. DR STRING; P62837; -. DR PhosphoSite; P62837; -. DR DMDM; 51338685; -. DR PRIDE; P62837; -. DR Ensembl; ENST00000398733; ENSP00000381717; ENSG00000131508. DR Ensembl; ENST00000398734; ENSP00000381718; ENSG00000131508. DR GeneID; 7322; -. DR KEGG; hsa:7322; -. DR UCSC; uc003leq.3; human. DR CTD; 7322; -. DR GeneCards; GC05P138920; -. DR H-InvDB; HIX0019025; -. DR H-InvDB; HIX0028451; -. DR HGNC; HGNC:12475; UBE2D2. DR HPA; HPA003920; -. DR MIM; 602962; gene. DR neXtProt; NX_P62837; -. DR PharmGKB; PA37125; -. DR eggNOG; COG5078; -. DR GeneTree; ENSGT00630000089469; -. DR HOGENOM; HOG000233455; -. DR HOVERGEN; HBG063308; -. DR KO; K06689; -. DR OMA; KVNFTTR; -. DR OrthoDB; EOG4RR6JK; -. DR PhylomeDB; P62837; -. DR Reactome; REACT_107772; Immune System. DR Reactome; REACT_120956; Cellular responses to stress. DR Reactome; REACT_6900; Immune System. DR UniPathway; UPA00143; -. DR EvolutionaryTrace; P62837; -. DR GenomeRNAi; 7322; -. DR NextBio; 28630; -. DR ArrayExpress; P62837; -. DR Bgee; P62837; -. DR CleanEx; HS_UBE2D2; -. DR Genevestigator; P62837; -. DR GermOnline; ENSG00000131508; Homo sapiens. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004842; F:ubiquitin-protein ligase activity; IDA:UniProtKB. DR GO; GO:0070936; P:protein K48-linked ubiquitination; IDA:UniProtKB. DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; TAS:ProtInc. DR Gene3D; G3DSA:3.10.110.10; UBQ-conjugat_E2; 1. DR InterPro; IPR000608; UBQ-conjugat_E2. DR InterPro; IPR023313; UBQ-conjugating_AS. DR InterPro; IPR016135; UBQ-conjugating_enzyme/RWD. DR Pfam; PF00179; UQ_con; 1. DR SUPFAM; SSF54495; UBQ-conjugat/RWD-like; 1. DR PROSITE; PS00183; UBIQUITIN_CONJUGAT_1; 1. DR PROSITE; PS50127; UBIQUITIN_CONJUGAT_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; ATP-binding; Complete proteome; KW Direct protein sequencing; Ligase; Nucleotide-binding; KW Reference proteome; Ubl conjugation pathway. FT CHAIN 1 147 Ubiquitin-conjugating enzyme E2 D2. FT /FTId=PRO_0000082462. FT ACT_SITE 85 85 Glycyl thioester intermediate (By FT similarity). FT MOD_RES 8 8 N6-acetyllysine. FT MUTAGEN 63 63 K->A,E: Strongly reduced interaction with FT CNTO4. FT MUTAGEN 85 85 C->A: Loss of ability to promote FBXW2- FT mediated GCM1 ubiquitination. Inhibition FT of TNF-alpha-induced degradation of FT NFKBIA. FT CONFLICT 128 128 K -> Q (in Ref. 2; AAC41750). FT HELIX 1 15 FT STRAND 19 28 FT STRAND 32 38 FT STRAND 41 43 FT TURN 44 47 FT STRAND 49 55 FT TURN 58 61 FT STRAND 66 71 FT STRAND 76 78 FT STRAND 82 84 FT HELIX 87 89 FT TURN 90 92 FT HELIX 99 111 FT HELIX 121 129 FT HELIX 131 145 SQ SEQUENCE 147 AA; 16735 MW; C942BE7853CBC355 CRC64; MALKRIHKEL NDLARDPPAQ CSAGPVGDDM FHWQATIMGP NDSPYQGGVF FLTIHFPTDY PFKPPKVAFT TRIYHPNINS NGSICLDILR SQWSPALTIS KVLLSICSLL CDPNPDDPLV PEIARIYKTD REKYNRIARE WTQKYAM //