UB2D2_HUMAN
ID UB2D2_HUMAN Reviewed; 147 AA.
AC P62837; D3DQC9; P51669; Q3MN78; Q96RP6;
DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2004, sequence version 1.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=Ubiquitin-conjugating enzyme E2 D2;
DE EC=2.3.2.23 {ECO:0000269|PubMed:18042044, ECO:0000269|PubMed:18703417, ECO:0000269|PubMed:19854139, ECO:0000269|PubMed:20061386};
DE AltName: Full=(E3-independent) E2 ubiquitin-conjugating enzyme D2;
DE EC=2.3.2.24 {ECO:0000269|PubMed:17588522};
DE AltName: Full=E2 ubiquitin-conjugating enzyme D2;
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;
DE AltName: Full=p53-regulated ubiquitin-conjugating enzyme 1;
GN Name=UBE2D2; Synonyms=PUBC1, UBC4, UBC5B, UBCH4, UBCH5B;
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).
RC TISSUE=Peripheral blood lymphocyte;
RX 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 conjugating
RT enzymes.";
RL J. Biol. Chem. 270:30408-30414(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7724550; DOI=10.1073/pnas.92.8.3264;
RA Rolfe M., Beer-Romero P., Glass S., Eckstein J., Berdo I., Theodoras A.,
RA Pagano M., Draetta G.;
RT "Reconstitution of p53-ubiquitinylation reactions from purified components:
RT the role of human ubiquitin-conjugating enzyme UBC4 and E6-associated
RT protein (E6AP).";
RL Proc. Natl. Acad. Sci. U.S.A. 92:3264-3268(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Testis;
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 acute
RT myeloid leukaemia.";
RL Biochem. Biophys. Res. Commun. 335:1293-1304(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Yin Y.;
RT "Cloning and identification of a p53-regulated ubiquitin-conjugating
RT enzyme, PUBC1.";
RL Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Teratocarcinoma;
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=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP PROTEIN SEQUENCE OF 73-90, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Brain, and Cajal-Retzius cell;
RA Lubec G., Afjehi-Sadat L.;
RL Submitted (MAR-2007) to UniProtKB.
RN [10]
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., Yamanaka K.,
RA Pagano M., Iwai K., Ciechanover A.;
RT "Identification of the ubiquitin carrier proteins, E2s, involved in signal-
RT induced conjugation and subsequent degradation of IkappaBalpha.";
RL J. Biol. Chem. 274:14823-14830(1999).
RN [11]
RP INTERACTION WITH SCF COMPLEX.
RX 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 kappa B
RT alpha catalyzed by Ubc3 and Ubc4.";
RL Oncogene 19:3529-3536(2000).
RN [12]
RP INTERACTION WITH PJA1 AND PJA2.
RX PubMed=12036302; DOI=10.1006/geno.2002.6770;
RA Yu P., Chen Y., Tagle D.A., Cai T.;
RT "PJA1, encoding a RING-H2 finger ubiquitin ligase, is a novel human X
RT chromosome gene abundantly expressed in brain.";
RL Genomics 79:869-874(2002).
RN [13]
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 vivo.";
RL J. Biol. Chem. 279:42169-42181(2004).
RN [14]
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 [15]
RP CATALYTIC ACTIVITY AS E3-INDEPENDENT E2 UBIQUITIN-CONJUGATING ENZYME.
RX PubMed=17588522; DOI=10.1016/j.molcel.2007.05.014;
RA Hoeller D., Hecker C.M., Wagner S., Rogov V., Doetsch V., Dikic I.;
RT "E3-independent monoubiquitination of ubiquitin-binding proteins.";
RL Mol. Cell 26:891-898(2007).
RN [16]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=18042044; DOI=10.1042/bj20071338;
RA Windheim M., Peggie M., Cohen P.;
RT "Two different classes of E2 ubiquitin-conjugating enzymes are required for
RT the mono-ubiquitination of proteins and elongation by polyubiquitin chains
RT with a specific topology.";
RL Biochem. J. 409:723-729(2008).
RN [17]
RP FUNCTION, CATALYTIC ACTIVITY, 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 and WD
RT repeat domain containing 2)-mediated human GCM1 (glial cell missing homolog
RT 1) ubiquitination and degradation.";
RL Biol. Reprod. 79:914-920(2008).
RN [18]
RP FUNCTION.
RX PubMed=18359941; DOI=10.1074/jbc.m800402200;
RA Grou C.P., Carvalho A.F., Pinto M.P., Wiese S., Piechura H., Meyer H.E.,
RA 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 [19]
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, AND CATALYTIC ACTIVITY.
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 of
RT IRF3.";
RL Mol. Cell 36:315-325(2009).
RN [20]
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., Chen Z.J.;
RT "Reconstitution of the RIG-I pathway reveals a signaling role of unanchored
RT polyubiquitin chains in innate immunity.";
RL Cell 141:315-330(2010).
RN [21]
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 [22]
RP FUNCTION, INTERACTION WITH CBLC, AND MUTAGENESIS OF CYS-85.
RX PubMed=20525694; DOI=10.1074/jbc.m109.091157;
RA Ryan P.E., Sivadasan-Nair N., Nau M.M., Nicholas S., Lipkowitz S.;
RT "The N terminus of Cbl-c regulates ubiquitin ligase activity by modulating
RT affinity for the ubiquitin-conjugating enzyme.";
RL J. Biol. Chem. 285:23687-23698(2010).
RN [23]
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 [24]
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 [25]
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).
RN [26] {ECO:0007744|PDB:5D0K, ECO:0007744|PDB:5D0M}
RP X-RAY CRYSTALLOGRAPHY (1.91 ANGSTROMS) IN COMPLEX WITH RNF165.
RX PubMed=26656854; DOI=10.1038/nsmb.3142;
RA Wright J.D., Mace P.D., Day C.L.;
RT "Secondary ubiquitin-RING docking enhances Arkadia and Ark2C E3 ligase
RT activity.";
RL Nat. Struct. Mol. Biol. 23:45-52(2016).
CC -!- FUNCTION: Accepts ubiquitin from the E1 complex and catalyzes its
CC covalent attachment to other proteins. In vitro catalyzes 'Lys-48'-
CC linked polyubiquitination. Mediates the selective degradation of short-
CC lived and abnormal proteins. Functions in the E6/E6-AP-induced
CC ubiquitination of p53/TP53. Mediates ubiquitination of PEX5 and
CC autoubiquitination of STUB1 and TRAF6. Involved in the signal-induced
CC conjugation and subsequent degradation of NFKBIA, FBXW2-mediated GCM1
CC ubiquitination and degradation, MDM2-dependent degradation of p53/TP53
CC and the activation of MAVS in the mitochondria by DDX58/RIG-I in
CC response to viral infection. Essential for viral activation of IRF3.
CC {ECO:0000269|PubMed:10329681, ECO:0000269|PubMed:15280377,
CC ECO:0000269|PubMed:18042044, ECO:0000269|PubMed:18359941,
CC ECO:0000269|PubMed:18703417, ECO:0000269|PubMed:19854139,
CC ECO:0000269|PubMed:20061386, ECO:0000269|PubMed:20403326,
CC ECO:0000269|PubMed:20525694}.
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:18042044,
CC ECO:0000269|PubMed:18703417, ECO:0000269|PubMed:19854139,
CC ECO:0000269|PubMed:20061386};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E1 ubiquitin-activating enzyme]-L-
CC cysteine + N(6)-monoubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.24; Evidence={ECO:0000269|PubMed:17588522};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000255|PROSITE-ProRule:PRU00388}.
CC -!- SUBUNIT: Interacts with SCF (SKP1-CUL1-F-box protein) E3 ubiquitin
CC ligase complex. Interacts with CNOT4 (via RING domain). Interacts with
CC E3 ubiquitin-protein ligases CBLC, PJA1 and PJA2. Interacts with
CC PDZRN3. Interacts with PPP1R11 (By similarity).
CC {ECO:0000250|UniProtKB:P62838, ECO:0000269|PubMed:10918611,
CC ECO:0000269|PubMed:12036302, ECO:0000269|PubMed:15001359,
CC ECO:0000269|PubMed:20525694}.
CC -!- INTERACTION:
CC P62837; P05067: APP; NbExp=3; IntAct=EBI-347677, EBI-77613;
CC P62837; Q96B67: ARRDC3; NbExp=5; IntAct=EBI-347677, EBI-2875665;
CC P62837; Q13489: BIRC3; NbExp=2; IntAct=EBI-347677, EBI-517709;
CC P62837; P22681: CBL; NbExp=4; IntAct=EBI-347677, EBI-518228;
CC P62837; Q13191-1: CBLB; NbExp=2; IntAct=EBI-347677, EBI-15555129;
CC P62837; Q96EP1-2: CHFR; NbExp=3; IntAct=EBI-347677, EBI-12344389;
CC P62837; Q9NWM3: CUEDC1; NbExp=3; IntAct=EBI-347677, EBI-5838167;
CC P62837; Q86UW9: DTX2; NbExp=3; IntAct=EBI-347677, EBI-740376;
CC P62837; P62879: GNB2; NbExp=3; IntAct=EBI-347677, EBI-356942;
CC P62837; Q92993: KAT5; NbExp=3; IntAct=EBI-347677, EBI-399080;
CC P62837; O15151: MDM4; NbExp=2; IntAct=EBI-347677, EBI-398437;
CC P62837; O15344: MID1; NbExp=4; IntAct=EBI-347677, EBI-2340316;
CC P62837; Q9UJV3-2: MID2; NbExp=3; IntAct=EBI-347677, EBI-10172526;
CC P62837; Q96FW1: OTUB1; NbExp=16; IntAct=EBI-347677, EBI-1058491;
CC P62837; Q9BWX1: PHF7; NbExp=3; IntAct=EBI-347677, EBI-4307517;
CC P62837; Q06587: RING1; NbExp=4; IntAct=EBI-347677, EBI-752313;
CC P62837; Q9Y3C5: RNF11; NbExp=10; IntAct=EBI-347677, EBI-396669;
CC P62837; Q9Y4L5: RNF115; NbExp=6; IntAct=EBI-347677, EBI-2129242;
CC P62837; Q96GF1: RNF185; NbExp=4; IntAct=EBI-347677, EBI-2340249;
CC P62837; Q99496: RNF2; NbExp=4; IntAct=EBI-347677, EBI-722416;
CC P62837; Q96BH1: RNF25; NbExp=3; IntAct=EBI-347677, EBI-2129220;
CC P62837; Q96EP0: RNF31; NbExp=3; IntAct=EBI-347677, EBI-948111;
CC P62837; Q68DV7: RNF43; NbExp=2; IntAct=EBI-347677, EBI-1647060;
CC P62837; Q99942: RNF5; NbExp=9; IntAct=EBI-347677, EBI-348482;
CC P62837; O76064: RNF8; NbExp=4; IntAct=EBI-347677, EBI-373337;
CC P62837; Q9Y4K3: TRAF6; NbExp=5; IntAct=EBI-347677, EBI-359276;
CC P62837; Q9HCM9-2: TRIM39; NbExp=5; IntAct=EBI-347677, EBI-11523450;
CC P62837; Q86XT4: TRIM50; NbExp=3; IntAct=EBI-347677, EBI-9867283;
CC P62837; Q9BYV2: TRIM54; NbExp=3; IntAct=EBI-347677, EBI-2130429;
CC P62837; O95155-1: UBE4B; NbExp=2; IntAct=EBI-347677, EBI-15869194;
CC P62837; Q9HAC8: UBTD1; NbExp=7; IntAct=EBI-347677, EBI-745871;
CC P62837; P98170: XIAP; NbExp=2; IntAct=EBI-347677, EBI-517127;
CC P62837; Q8ND25: ZNRF1; NbExp=7; IntAct=EBI-347677, EBI-2129250;
CC P62837; Q99PZ6: ospG; Xeno; NbExp=3; IntAct=EBI-347677, EBI-9316527;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P62837-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P62837-2; Sequence=VSP_045180;
CC -!- SIMILARITY: Belongs to the ubiquitin-conjugating enzyme family.
CC {ECO:0000255|PROSITE-ProRule:PRU00388}.
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DR EMBL; U39317; AAA91460.1; -; mRNA.
DR EMBL; L40146; AAC41750.1; -; Genomic_DNA.
DR EMBL; AY651263; AAX35690.1; -; mRNA.
DR EMBL; AF317220; AAK93958.1; -; mRNA.
DR EMBL; AK001311; BAG50891.1; -; mRNA.
DR EMBL; AK001428; BAG50911.1; -; mRNA.
DR EMBL; AC010378; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471062; EAW62095.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW62096.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW62097.1; -; Genomic_DNA.
DR EMBL; BC033349; AAH33349.1; -; mRNA.
DR CCDS; CCDS43369.1; -. [P62837-1]
DR CCDS; CCDS47275.1; -. [P62837-2]
DR PIR; I59365; I59365.
DR RefSeq; NP_003330.1; NM_003339.2. [P62837-1]
DR RefSeq; NP_862821.1; NM_181838.1. [P62837-2]
DR PDB; 1UR6; NMR; -; A=1-147.
DR PDB; 1W4U; NMR; -; A=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=2-147.
DR PDB; 3JW0; X-ray; 3.10 A; A/B=2-147.
DR PDB; 3L1Y; X-ray; 1.60 A; A=1-147.
DR PDB; 3TGD; X-ray; 1.80 A; A=1-147.
DR PDB; 3ZNI; X-ray; 2.21 A; C/G/K/O=2-147.
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; A/B/C/J/K/L=1-147.
DR PDB; 4DDI; X-ray; 3.80 A; D/E/F/G/H/I=2-20.
DR PDB; 4LDT; X-ray; 1.90 A; C=1-147.
DR PDB; 4V3K; X-ray; 2.04 A; A/D=2-147.
DR PDB; 4V3L; X-ray; 1.53 A; A=2-147.
DR PDB; 4WZ3; X-ray; 2.70 A; A=1-147.
DR PDB; 5D0K; X-ray; 2.65 A; A/D/G/J=1-147.
DR PDB; 5D0M; X-ray; 1.91 A; A=1-147.
DR PDB; 5D1K; X-ray; 1.78 A; A=1-147.
DR PDB; 5D1L; X-ray; 1.62 A; A=1-147.
DR PDB; 5D1M; X-ray; 1.58 A; A=1-147.
DR PDB; 5EDV; X-ray; 3.48 A; C/D/I=2-147.
DR PDB; 5MNJ; X-ray; 2.16 A; A/E=1-147.
DR PDB; 5ULF; X-ray; 1.80 A; A/C=1-147.
DR PDB; 5ULH; X-ray; 1.95 A; A=1-147.
DR PDB; 5ULK; X-ray; 2.38 A; A=1-147.
DR PDB; 5VZW; X-ray; 2.28 A; A/B=1-147.
DR PDB; 5ZBU; X-ray; 3.20 A; B/C=1-147.
DR PDB; 6HPR; X-ray; 1.70 A; C=1-147.
DR PDB; 6M2C; X-ray; 2.70 A; A/B/C/D=1-147.
DR PDB; 6SQO; X-ray; 1.41 A; B/E=2-147.
DR PDB; 6SQR; X-ray; 2.18 A; B/E/H/K=2-147.
DR PDB; 6SQS; X-ray; 1.83 A; B/E=2-147.
DR PDB; 6TTU; EM; 3.70 A; D=1-147.
DR PDB; 6W7Z; X-ray; 1.80 A; A=1-147.
DR PDB; 6W9D; X-ray; 3.19 A; A/D/G=1-147.
DR PDB; 7AI0; X-ray; 1.56 A; BBB/EEE=1-147.
DR PDB; 7AI1; X-ray; 2.07 A; BBB/EEE=1-147.
DR PDB; 7BOL; X-ray; 1.80 A; A=1-147.
DR PDB; 7R71; X-ray; 2.80 A; C=1-147.
DR PDBsum; 1UR6; -.
DR PDBsum; 1W4U; -.
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; 3ZNI; -.
DR PDBsum; 4A49; -.
DR PDBsum; 4A4B; -.
DR PDBsum; 4A4C; -.
DR PDBsum; 4AUQ; -.
DR PDBsum; 4DDG; -.
DR PDBsum; 4DDI; -.
DR PDBsum; 4LDT; -.
DR PDBsum; 4V3K; -.
DR PDBsum; 4V3L; -.
DR PDBsum; 4WZ3; -.
DR PDBsum; 5D0K; -.
DR PDBsum; 5D0M; -.
DR PDBsum; 5D1K; -.
DR PDBsum; 5D1L; -.
DR PDBsum; 5D1M; -.
DR PDBsum; 5EDV; -.
DR PDBsum; 5MNJ; -.
DR PDBsum; 5ULF; -.
DR PDBsum; 5ULH; -.
DR PDBsum; 5ULK; -.
DR PDBsum; 5VZW; -.
DR PDBsum; 5ZBU; -.
DR PDBsum; 6HPR; -.
DR PDBsum; 6M2C; -.
DR PDBsum; 6SQO; -.
DR PDBsum; 6SQR; -.
DR PDBsum; 6SQS; -.
DR PDBsum; 6TTU; -.
DR PDBsum; 6W7Z; -.
DR PDBsum; 6W9D; -.
DR PDBsum; 7AI0; -.
DR PDBsum; 7AI1; -.
DR PDBsum; 7BOL; -.
DR PDBsum; 7R71; -.
DR AlphaFoldDB; P62837; -.
DR BMRB; P62837; -.
DR SMR; P62837; -.
DR BioGRID; 113170; 318.
DR CORUM; P62837; -.
DR DIP; DIP-29267N; -.
DR IntAct; P62837; 134.
DR MINT; P62837; -.
DR STRING; 9606.ENSP00000381717; -.
DR ChEMBL; CHEMBL4105990; -.
DR DrugBank; DB02418; (R,R)-2,3-Butanediol.
DR MoonDB; P62837; Predicted.
DR TCDB; 3.A.20.1.1; the peroxisomal protein importer (ppi) family.
DR iPTMnet; P62837; -.
DR PhosphoSitePlus; P62837; -.
DR SwissPalm; P62837; -.
DR BioMuta; UBE2D2; -.
DR DMDM; 51338685; -.
DR EPD; P62837; -.
DR jPOST; P62837; -.
DR MassIVE; P62837; -.
DR MaxQB; P62837; -.
DR PaxDb; P62837; -.
DR PeptideAtlas; P62837; -.
DR PRIDE; P62837; -.
DR ProteomicsDB; 57432; -. [P62837-1]
DR Antibodypedia; 7407; 391 antibodies from 31 providers.
DR DNASU; 7322; -.
DR Ensembl; ENST00000398733.8; ENSP00000381717.3; ENSG00000131508.16. [P62837-1]
DR Ensembl; ENST00000398734.8; ENSP00000381718.4; ENSG00000131508.16. [P62837-1]
DR Ensembl; ENST00000505548.5; ENSP00000424941.1; ENSG00000131508.16. [P62837-2]
DR Ensembl; ENST00000511725.5; ENSP00000429613.1; ENSG00000131508.16. [P62837-2]
DR GeneID; 7322; -.
DR KEGG; hsa:7322; -.
DR MANE-Select; ENST00000398733.8; ENSP00000381717.3; NM_003339.3; NP_003330.1.
DR UCSC; uc003ler.3; human. [P62837-1]
DR CTD; 7322; -.
DR DisGeNET; 7322; -.
DR GeneCards; UBE2D2; -.
DR HGNC; HGNC:12475; UBE2D2.
DR HPA; ENSG00000131508; Low tissue specificity.
DR MIM; 602962; gene.
DR neXtProt; NX_P62837; -.
DR OpenTargets; ENSG00000131508; -.
DR PharmGKB; PA37125; -.
DR VEuPathDB; HostDB:ENSG00000131508; -.
DR eggNOG; KOG0417; Eukaryota.
DR GeneTree; ENSGT00940000153169; -.
DR HOGENOM; CLU_030988_13_3_1; -.
DR InParanoid; P62837; -.
DR OMA; VHFTTRI; -.
DR OrthoDB; 1337945at2759; -.
DR PhylomeDB; P62837; -.
DR TreeFam; TF101108; -.
DR BioCyc; MetaCyc:HS05542-MON; -.
DR BRENDA; 2.3.2.23; 2681.
DR BRENDA; 2.3.2.24; 2681.
DR BRENDA; 2.3.2.B8; 2681.
DR PathwayCommons; P62837; -.
DR Reactome; R-HSA-1234176; Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.
DR Reactome; R-HSA-168927; TICAM1, RIP1-mediated IKK complex recruitment.
DR Reactome; R-HSA-202424; Downstream TCR signaling.
DR Reactome; R-HSA-2871837; FCERI mediated NF-kB activation.
DR Reactome; R-HSA-5607764; CLEC7A (Dectin-1) signaling.
DR Reactome; R-HSA-8866652; Synthesis of active ubiquitin: roles of E1 and E2 enzymes.
DR Reactome; R-HSA-8866654; E3 ubiquitin ligases ubiquitinate target proteins.
DR Reactome; R-HSA-8951664; Neddylation.
DR Reactome; R-HSA-9033241; Peroxisomal protein import.
DR Reactome; R-HSA-936440; Negative regulators of DDX58/IFIH1 signaling.
DR Reactome; R-HSA-937041; IKK complex recruitment mediated by RIP1.
DR Reactome; R-HSA-9705462; Inactivation of CSF3 (G-CSF) signaling.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; P62837; -.
DR SIGNOR; P62837; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 7322; 50 hits in 1053 CRISPR screens.
DR ChiTaRS; UBE2D2; human.
DR EvolutionaryTrace; P62837; -.
DR GeneWiki; UBE2D2; -.
DR GenomeRNAi; 7322; -.
DR Pharos; P62837; Tbio.
DR PRO; PR:P62837; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; P62837; protein.
DR Bgee; ENSG00000131508; Expressed in ventricular zone and 211 other tissues.
DR ExpressionAtlas; P62837; baseline and differential.
DR Genevisible; P62837; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0032991; C:protein-containing complex; IDA:MGI.
DR GO; GO:0000151; C:ubiquitin ligase complex; IDA:BHF-UCL.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0061631; F:ubiquitin conjugating enzyme activity; IDA:ParkinsonsUK-UCL.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:GO_Central.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB.
DR GO; GO:0051865; P:protein autoubiquitination; IDA:ParkinsonsUK-UCL.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:0036211; P:protein modification process; TAS:ProtInc.
DR GO; GO:0000209; P:protein polyubiquitination; IDA:BHF-UCL.
DR GO; GO:0016567; P:protein ubiquitination; IDA:ParkinsonsUK-UCL.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; TAS:ProtInc.
DR CDD; cd00195; UBCc; 1.
DR Gene3D; 3.10.110.10; -; 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; SSF54495; 1.
DR PROSITE; PS00183; UBC_1; 1.
DR PROSITE; PS50127; UBC_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Direct protein sequencing;
KW Nucleotide-binding; Reference proteome; Transferase;
KW Ubl conjugation pathway.
FT CHAIN 1..147
FT /note="Ubiquitin-conjugating enzyme E2 D2"
FT /id="PRO_0000082462"
FT DOMAIN 1..147
FT /note="UBC core"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00388"
FT ACT_SITE 85
FT /note="Glycyl thioester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00388,
FT ECO:0000255|PROSITE-ProRule:PRU10133"
FT VAR_SEQ 1..29
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_045180"
FT MUTAGEN 63
FT /note="K->A,E: Strongly reduced interaction with CNTO4."
FT /evidence="ECO:0000269|PubMed:15001359"
FT MUTAGEN 85
FT /note="C->A: Catalytically inactive. Loss of ability to
FT promote FBXW2-mediated GCM1 ubiquitination. Inhibition of
FT TNF-alpha-induced degradation of NFKBIA."
FT /evidence="ECO:0000269|PubMed:10329681,
FT ECO:0000269|PubMed:18703417, ECO:0000269|PubMed:20525694"
FT CONFLICT 128
FT /note="K -> Q (in Ref. 2; AAC41750)"
FT /evidence="ECO:0000305"
FT HELIX 1..15
FT /evidence="ECO:0007829|PDB:2ESK"
FT STRAND 19..28
FT /evidence="ECO:0007829|PDB:2ESK"
FT STRAND 32..38
FT /evidence="ECO:0007829|PDB:2ESK"
FT STRAND 41..43
FT /evidence="ECO:0007829|PDB:6SQO"
FT TURN 44..47
FT /evidence="ECO:0007829|PDB:2ESK"
FT STRAND 49..55
FT /evidence="ECO:0007829|PDB:2ESK"
FT TURN 58..61
FT /evidence="ECO:0007829|PDB:2ESK"
FT STRAND 66..71
FT /evidence="ECO:0007829|PDB:2ESK"
FT STRAND 76..78
FT /evidence="ECO:0007829|PDB:4A4B"
FT STRAND 82..84
FT /evidence="ECO:0007829|PDB:6M2C"
FT HELIX 87..89
FT /evidence="ECO:0007829|PDB:2ESK"
FT TURN 90..92
FT /evidence="ECO:0007829|PDB:2ESK"
FT HELIX 99..111
FT /evidence="ECO:0007829|PDB:2ESK"
FT STRAND 115..117
FT /evidence="ECO:0007829|PDB:4V3L"
FT HELIX 121..129
FT /evidence="ECO:0007829|PDB:2ESK"
FT HELIX 131..145
FT /evidence="ECO:0007829|PDB:2ESK"
SQ SEQUENCE 147 AA; 16735 MW; C942BE7853CBC355 CRC64;
MALKRIHKEL NDLARDPPAQ CSAGPVGDDM FHWQATIMGP NDSPYQGGVF FLTIHFPTDY
PFKPPKVAFT TRIYHPNINS NGSICLDILR SQWSPALTIS KVLLSICSLL CDPNPDDPLV
PEIARIYKTD REKYNRIARE WTQKYAM
