ID   UB2D4_HUMAN             Reviewed;         147 AA.
AC   Q9Y2X8; A4D1V0;
DT   09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1999, sequence version 1.
DT   22-FEB-2023, entry version 168.
DE   RecName: Full=Ubiquitin-conjugating enzyme E2 D4;
DE            EC=2.3.2.23 {ECO:0000269|PubMed:20061386};
DE   AltName: Full=E2 ubiquitin-conjugating enzyme D4;
DE   AltName: Full=HBUCE1;
DE   AltName: Full=Ubiquitin carrier protein D4;
DE   AltName: Full=Ubiquitin-protein ligase D4;
GN   Name=UBE2D4; Synonyms=UBCH5D;
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].
RC   TISSUE=Brain;
RA   Li G., Jin J., Hu S., Li W., Yuan J., Qiang B.;
RT   "Molecular cloning and screening of two ubiquitin conjugation enzymes.";
RL   Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases.
RN   [2]
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., 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 GENOMIC DNA].
RX   PubMed=12690205; DOI=10.1126/science.1083423;
RA   Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA   Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA   Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA   Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA   Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA   Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA   Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA   Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA   Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA   Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA   Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA   Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA   Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA   Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA   Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA   Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA   Adams M.D., Tsui L.-C.;
RT   "Human chromosome 7: DNA sequence and biology.";
RL   Science 300:767-772(2003).
RN   [4]
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   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Ovary;
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   [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).
CC   -!- FUNCTION: Accepts ubiquitin from the E1 complex and catalyzes its
CC       covalent attachment to other proteins. In vitro able to promote
CC       polyubiquitination using all 7 ubiquitin Lys residues, but may prefer
CC       'Lys-11' and 'Lys-48'-linked polyubiquitination.
CC       {ECO:0000269|PubMed:20061386}.
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       Q9Y2X8; Q15038: DAZAP2; NbExp=3; IntAct=EBI-745527, EBI-724310;
CC       Q9Y2X8; Q86UW9: DTX2; NbExp=13; IntAct=EBI-745527, EBI-740376;
CC       Q9Y2X8; Q8N9I9: DTX3; NbExp=4; IntAct=EBI-745527, EBI-2340258;
CC       Q9Y2X8; P62879: GNB2; NbExp=3; IntAct=EBI-745527, EBI-356942;
CC       Q9Y2X8; P42858: HTT; NbExp=3; IntAct=EBI-745527, EBI-466029;
CC       Q9Y2X8; Q9Y6K9: IKBKG; NbExp=3; IntAct=EBI-745527, EBI-81279;
CC       Q9Y2X8; Q0VD86: INCA1; NbExp=3; IntAct=EBI-745527, EBI-6509505;
CC       Q9Y2X8; Q8TBB1: LNX1; NbExp=5; IntAct=EBI-745527, EBI-739832;
CC       Q9Y2X8; O15344: MID1; NbExp=4; IntAct=EBI-745527, EBI-2340316;
CC       Q9Y2X8; Q9UJV3-2: MID2; NbExp=6; IntAct=EBI-745527, EBI-10172526;
CC       Q9Y2X8; Q9UHC7: MKRN1; NbExp=3; IntAct=EBI-745527, EBI-373524;
CC       Q9Y2X8; Q9H000: MKRN2; NbExp=6; IntAct=EBI-745527, EBI-2341005;
CC       Q9Y2X8; Q96FW1: OTUB1; NbExp=9; IntAct=EBI-745527, EBI-1058491;
CC       Q9Y2X8; Q9BWX1: PHF7; NbExp=3; IntAct=EBI-745527, EBI-4307517;
CC       Q9Y2X8; P19388: POLR2E; NbExp=3; IntAct=EBI-745527, EBI-395189;
CC       Q9Y2X8; Q04864-2: REL; NbExp=3; IntAct=EBI-745527, EBI-10829018;
CC       Q9Y2X8; Q06587: RING1; NbExp=4; IntAct=EBI-745527, EBI-752313;
CC       Q9Y2X8; Q9Y3C5: RNF11; NbExp=10; IntAct=EBI-745527, EBI-396669;
CC       Q9Y2X8; Q9Y4L5: RNF115; NbExp=12; IntAct=EBI-745527, EBI-2129242;
CC       Q9Y2X8; Q9BV68: RNF126; NbExp=3; IntAct=EBI-745527, EBI-357322;
CC       Q9Y2X8; Q9UBS8: RNF14; NbExp=5; IntAct=EBI-745527, EBI-2130308;
CC       Q9Y2X8; Q96A37: RNF166; NbExp=4; IntAct=EBI-745527, EBI-2130320;
CC       Q9Y2X8; Q9P0P0: RNF181; NbExp=4; IntAct=EBI-745527, EBI-2129136;
CC       Q9Y2X8; Q96GF1: RNF185; NbExp=4; IntAct=EBI-745527, EBI-2340249;
CC       Q9Y2X8; Q99496: RNF2; NbExp=4; IntAct=EBI-745527, EBI-722416;
CC       Q9Y2X8; Q96BH1: RNF25; NbExp=3; IntAct=EBI-745527, EBI-2129220;
CC       Q9Y2X8; Q99942: RNF5; NbExp=7; IntAct=EBI-745527, EBI-348482;
CC       Q9Y2X8; Q9HCM9: TRIM39; NbExp=5; IntAct=EBI-745527, EBI-739510;
CC       Q9Y2X8; Q9HCM9-2: TRIM39; NbExp=7; IntAct=EBI-745527, EBI-11523450;
CC       Q9Y2X8; Q86XT4: TRIM50; NbExp=3; IntAct=EBI-745527, EBI-9867283;
CC       Q9Y2X8; Q9BYV2: TRIM54; NbExp=3; IntAct=EBI-745527, EBI-2130429;
CC       Q9Y2X8; Q9BVG3: TRIM62; NbExp=3; IntAct=EBI-745527, EBI-6929619;
CC       Q9Y2X8; Q9BZR9: TRIM8; NbExp=4; IntAct=EBI-745527, EBI-2340370;
CC       Q9Y2X8; Q9HAC8: UBTD1; NbExp=9; IntAct=EBI-745527, EBI-745871;
CC       Q9Y2X8; Q8WUN7: UBTD2; NbExp=3; IntAct=EBI-745527, EBI-12867288;
CC       Q9Y2X8; Q8ND25: ZNRF1; NbExp=6; IntAct=EBI-745527, EBI-2129250;
CC   -!- SIMILARITY: Belongs to the ubiquitin-conjugating enzyme family.
CC       {ECO:0000255|PROSITE-ProRule:PRU00388}.
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DR   EMBL; AF125044; AAD31180.1; -; mRNA.
DR   EMBL; AK001446; BAA91697.1; -; mRNA.
DR   EMBL; CH236951; EAL24010.1; -; Genomic_DNA.
DR   EMBL; CH471073; EAW94182.1; -; Genomic_DNA.
DR   EMBL; BC004104; AAH04104.1; -; mRNA.
DR   CCDS; CCDS5474.1; -.
DR   RefSeq; NP_057067.1; NM_015983.3.
DR   AlphaFoldDB; Q9Y2X8; -.
DR   SMR; Q9Y2X8; -.
DR   BioGRID; 119641; 121.
DR   IntAct; Q9Y2X8; 100.
DR   MINT; Q9Y2X8; -.
DR   STRING; 9606.ENSP00000222402; -.
DR   MoonDB; Q9Y2X8; Predicted.
DR   iPTMnet; Q9Y2X8; -.
DR   PhosphoSitePlus; Q9Y2X8; -.
DR   SwissPalm; Q9Y2X8; -.
DR   BioMuta; UBE2D4; -.
DR   DMDM; 74753478; -.
DR   EPD; Q9Y2X8; -.
DR   jPOST; Q9Y2X8; -.
DR   MassIVE; Q9Y2X8; -.
DR   MaxQB; Q9Y2X8; -.
DR   PaxDb; Q9Y2X8; -.
DR   PeptideAtlas; Q9Y2X8; -.
DR   ProteomicsDB; 85931; -.
DR   Antibodypedia; 26903; 183 antibodies from 28 providers.
DR   DNASU; 51619; -.
DR   Ensembl; ENST00000222402.8; ENSP00000222402.2; ENSG00000078967.13.
DR   GeneID; 51619; -.
DR   KEGG; hsa:51619; -.
DR   MANE-Select; ENST00000222402.8; ENSP00000222402.2; NM_015983.4; NP_057067.1.
DR   UCSC; uc003tja.3; human.
DR   AGR; HGNC:21647; -.
DR   CTD; 51619; -.
DR   GeneCards; UBE2D4; -.
DR   HGNC; HGNC:21647; UBE2D4.
DR   HPA; ENSG00000078967; Tissue enhanced (skeletal).
DR   neXtProt; NX_Q9Y2X8; -.
DR   OpenTargets; ENSG00000078967; -.
DR   PharmGKB; PA134954568; -.
DR   VEuPathDB; HostDB:ENSG00000078967; -.
DR   eggNOG; KOG0417; Eukaryota.
DR   GeneTree; ENSGT00940000160915; -.
DR   HOGENOM; CLU_030988_13_3_1; -.
DR   InParanoid; Q9Y2X8; -.
DR   OMA; PIWHPNF; -.
DR   OrthoDB; 5478564at2759; -.
DR   PhylomeDB; Q9Y2X8; -.
DR   TreeFam; TF101108; -.
DR   BRENDA; 2.3.2.24; 2681.
DR   PathwayCommons; Q9Y2X8; -.
DR   Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR   SignaLink; Q9Y2X8; -.
DR   SIGNOR; Q9Y2X8; -.
DR   UniPathway; UPA00143; -.
DR   BioGRID-ORCS; 51619; 22 hits in 1149 CRISPR screens.
DR   GenomeRNAi; 51619; -.
DR   Pharos; Q9Y2X8; Tbio.
DR   PRO; PR:Q9Y2X8; -.
DR   Proteomes; UP000005640; Chromosome 7.
DR   RNAct; Q9Y2X8; protein.
DR   Bgee; ENSG00000078967; Expressed in pancreatic ductal cell and 200 other tissues.
DR   ExpressionAtlas; Q9Y2X8; baseline and differential.
DR   Genevisible; Q9Y2X8; HS.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0000151; C:ubiquitin ligase complex; IBA:GO_Central.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0061631; F:ubiquitin conjugating enzyme activity; IDA:MGI.
DR   GO; GO:0031625; F:ubiquitin protein ligase binding; IBA:GO_Central.
DR   GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB.
DR   GO; GO:0070979; P:protein K11-linked ubiquitination; IDA:UniProtKB.
DR   GO; GO:0044314; P:protein K27-linked ubiquitination; IDA:UniProtKB.
DR   GO; GO:0035519; P:protein K29-linked ubiquitination; IDA:UniProtKB.
DR   GO; GO:0070936; P:protein K48-linked ubiquitination; IDA:UniProtKB.
DR   GO; GO:0085020; P:protein K6-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   GO; GO:0016567; P:protein ubiquitination; IDA:MGI.
DR   GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR   CDD; cd00195; UBCc; 1.
DR   Gene3D; 3.10.110.10; Ubiquitin Conjugating Enzyme; 1.
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:SF24; UBIQUITIN-CONJUGATING ENZYME E2 D4; 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.
PE   1: Evidence at protein level;
KW   ATP-binding; Nucleotide-binding; Reference proteome; Transferase;
KW   Ubl conjugation pathway.
FT   CHAIN           1..147
FT                   /note="Ubiquitin-conjugating enzyme E2 D4"
FT                   /id="PRO_0000270202"
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"
SQ   SEQUENCE   147 AA;  16649 MW;  5F91A2C6BC667254 CRC64;
     MALKRIQKEL TDLQRDPPAQ CSAGPVGDDL FHWQATIMGP NDSPYQGGVF FLTIHFPTDY
     PFKPPKVAFT TKIYHPNINS NGSICLDILR SQWSPALTVS KVLLSICSLL CDPNPDDPLV
     PEIAHTYKAD REKYNRLARE WTQKYAM
//