UBE2H_HUMAN
ID UBE2H_HUMAN Reviewed; 183 AA.
AC P62256; A4D1L6; C9JY93; P37286; Q7Z6F4;
DT 05-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Ubiquitin-conjugating enzyme E2 H;
DE EC=2.3.2.23 {ECO:0000269|PubMed:17588522, ECO:0000269|PubMed:20061386, ECO:0000269|PubMed:22496338, ECO:0000269|PubMed:29911972, ECO:0000269|PubMed:8132613};
DE AltName: Full=(E3-independent) E2 ubiquitin-conjugating enzyme H;
DE EC=2.3.2.24 {ECO:0000269|PubMed:17588522, ECO:0000269|PubMed:8132613};
DE AltName: Full=E2 ubiquitin-conjugating enzyme H;
DE AltName: Full=UbcH2;
DE AltName: Full=Ubiquitin carrier protein H;
DE AltName: Full=Ubiquitin-conjugating enzyme E2-20K;
DE AltName: Full=Ubiquitin-protein ligase H;
GN Name=UBE2H;
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), FUNCTION, CATALYTIC ACTIVITY, AND
RP PATHWAY.
RX PubMed=8132613; DOI=10.1016/s0021-9258(17)37039-4;
RA Kaiser P., Seufert W., Hoefferer L., Kofler B., Sachsenmaier C., Herzog H.,
RA Jentsch S., Schweiger M., Schneider R.;
RT "A human ubiquitin-conjugating enzyme homologous to yeast UBC8.";
RL J. Biol. Chem. 269:8797-8802(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Lin L., Li S., Li H., Zhou G., Shen C., Zheng G., Ke R., Zhong G., Yu R.,
RA Yang S.;
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
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 [8]
RP FUNCTION, CATALYTIC ACTIVITY AS E3-INDEPENDENT E2 UBIQUITIN-CONJUGATING
RP ENZYME, AND PATHWAY.
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 [9]
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 [10]
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 [11]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, IDENTIFICATION IN THE CTLH COMPLEX,
RP AND INTERACTION WITH WDR26 AND ARMC8.
RX PubMed=29911972; DOI=10.7554/elife.35528;
RA Lampert F., Stafa D., Goga A., Soste M.V., Gilberto S., Olieric N.,
RA Picotti P., Stoffel M., Peter M.;
RT "The multi-subunit GID/CTLH E3 ligase promotes proliferation and targets
RT the transcription factor Hbp1 for degradation.";
RL Elife 7:0-0(2018).
RN [12] {ECO:0007744|PDB:2Z5D}
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 1-160, CATALYTIC ACTIVITY, AND
RP 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 (PubMed:8132613, PubMed:17588522,
CC PubMed:20061386). E2 ubiquitin conjugating enzyme that transfers
CC ubiquitin to MAEA, a core component of the CTLH E3 ubiquitin-protein
CC ligase complex (PubMed:29911972). In vitro catalyzes 'Lys-11'- and
CC 'Lys-48'-linked polyubiquitination (PubMed:20061386). Capable, in
CC vitro, to ubiquitinate histone H2A (PubMed:8132613).
CC {ECO:0000269|PubMed:17588522, ECO:0000269|PubMed:20061386,
CC ECO:0000269|PubMed:29911972, ECO:0000269|PubMed:8132613}.
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:17588522,
CC ECO:0000269|PubMed:20061386, ECO:0000269|PubMed:22496338,
CC ECO:0000269|PubMed:29911972, ECO:0000269|PubMed:8132613};
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 ECO:0000269|PubMed:8132613};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000255|PROSITE-ProRule:PRU00388, ECO:0000269|PubMed:17588522,
CC ECO:0000269|PubMed:29911972, ECO:0000269|PubMed:8132613}.
CC -!- SUBUNIT: Interacts with MAEA and WDR26, components of the CTLH complex
CC that contains GID4, RANBP9 and/or RANBP10, MKLN1, MAEA, RMND5A (or
CC alternatively its paralog RMND5B), GID8, ARMC8, WDR26 and YPEL5.
CC {ECO:0000269|PubMed:29911972}.
CC -!- INTERACTION:
CC P62256; P62879: GNB2; NbExp=3; IntAct=EBI-2129909, EBI-356942;
CC P62256; P42858: HTT; NbExp=3; IntAct=EBI-2129909, EBI-466029;
CC P62256; P43356: MAGEA2B; NbExp=2; IntAct=EBI-2129909, EBI-5650739;
CC P62256; Q9UBF1: MAGEC2; NbExp=3; IntAct=EBI-2129909, EBI-5651487;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P62256-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P62256-2; Sequence=VSP_044580;
CC -!- PTM: Autoubiquitinated in vitro in the presence of NEDD4L.
CC {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; Z29328; CAA82525.1; -; mRNA.
DR EMBL; Z29330; CAA82527.1; -; mRNA.
DR EMBL; Z29331; CAA82528.1; -; mRNA.
DR EMBL; AY302138; AAP57630.1; -; mRNA.
DR EMBL; BT006756; AAP35402.1; -; mRNA.
DR EMBL; AC073320; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC084865; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH236950; EAL24099.1; -; Genomic_DNA.
DR EMBL; CH471070; EAW83736.1; -; Genomic_DNA.
DR EMBL; BC006277; AAH06277.1; -; mRNA.
DR CCDS; CCDS47710.1; -. [P62256-2]
DR CCDS; CCDS5814.1; -. [P62256-1]
DR PIR; A53516; A53516.
DR RefSeq; NP_001189427.1; NM_001202498.1.
DR RefSeq; NP_003335.1; NM_003344.3. [P62256-1]
DR RefSeq; NP_874356.1; NM_182697.2. [P62256-2]
DR PDB; 2Z5D; X-ray; 2.10 A; A/B=1-160.
DR PDBsum; 2Z5D; -.
DR AlphaFoldDB; P62256; -.
DR SMR; P62256; -.
DR BioGRID; 113176; 106.
DR IntAct; P62256; 53.
DR STRING; 9606.ENSP00000347836; -.
DR ChEMBL; CHEMBL4105951; -.
DR MoonDB; P62256; Predicted.
DR iPTMnet; P62256; -.
DR MetOSite; P62256; -.
DR PhosphoSitePlus; P62256; -.
DR BioMuta; UBE2H; -.
DR DMDM; 51338683; -.
DR EPD; P62256; -.
DR jPOST; P62256; -.
DR MassIVE; P62256; -.
DR MaxQB; P62256; -.
DR PaxDb; P62256; -.
DR PeptideAtlas; P62256; -.
DR PRIDE; P62256; -.
DR ProteomicsDB; 57376; -. [P62256-1]
DR ProteomicsDB; 621; -.
DR Antibodypedia; 1149; 210 antibodies from 29 providers.
DR DNASU; 7328; -.
DR Ensembl; ENST00000355621.8; ENSP00000347836.3; ENSG00000186591.13. [P62256-1]
DR Ensembl; ENST00000473814.6; ENSP00000419097.2; ENSG00000186591.13. [P62256-2]
DR GeneID; 7328; -.
DR KEGG; hsa:7328; -.
DR MANE-Select; ENST00000355621.8; ENSP00000347836.3; NM_003344.4; NP_003335.1.
DR UCSC; uc003vpf.3; human. [P62256-1]
DR CTD; 7328; -.
DR DisGeNET; 7328; -.
DR GeneCards; UBE2H; -.
DR HGNC; HGNC:12484; UBE2H.
DR HPA; ENSG00000186591; Low tissue specificity.
DR MIM; 601082; gene.
DR neXtProt; NX_P62256; -.
DR OpenTargets; ENSG00000186591; -.
DR PharmGKB; PA37133; -.
DR VEuPathDB; HostDB:ENSG00000186591; -.
DR eggNOG; KOG0416; Eukaryota.
DR GeneTree; ENSGT00390000004852; -.
DR InParanoid; P62256; -.
DR OMA; EFCVKFY; -.
DR PhylomeDB; P62256; -.
DR TreeFam; TF101121; -.
DR BRENDA; 2.3.2.23; 2681.
DR BRENDA; 2.3.2.24; 2681.
DR PathwayCommons; P62256; -.
DR Reactome; R-HSA-8866652; Synthesis of active ubiquitin: roles of E1 and E2 enzymes.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; P62256; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 7328; 335 hits in 1094 CRISPR screens.
DR ChiTaRS; UBE2H; human.
DR EvolutionaryTrace; P62256; -.
DR GeneWiki; UBE2H; -.
DR GenomeRNAi; 7328; -.
DR Pharos; P62256; Tbio.
DR PRO; PR:P62256; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; P62256; protein.
DR Bgee; ENSG00000186591; Expressed in secondary oocyte and 197 other tissues.
DR ExpressionAtlas; P62256; baseline and differential.
DR Genevisible; P62256; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0061631; F:ubiquitin conjugating enzyme activity; IBA:GO_Central.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IEA:Ensembl.
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:0000209; P:protein polyubiquitination; IBA:GO_Central.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR CDD; cd00195; UBCc; 1.
DR Gene3D; 3.10.110.10; -; 1.
DR IDEAL; IID00637; -.
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; Alternative splicing; ATP-binding;
KW Nucleotide-binding; Reference proteome; Transferase; Ubl conjugation;
KW Ubl conjugation pathway.
FT CHAIN 1..183
FT /note="Ubiquitin-conjugating enzyme E2 H"
FT /id="PRO_0000082486"
FT DOMAIN 1..150
FT /note="UBC core"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00388"
FT REGION 152..183
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 87
FT /note="Glycyl thioester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00388,
FT ECO:0000255|PROSITE-ProRule:PRU10133"
FT MOD_RES 60
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P62257"
FT VAR_SEQ 69..99
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_044580"
FT CONFLICT 165
FT /note="S -> P (in Ref. 2; AAP57630)"
FT /evidence="ECO:0000305"
FT HELIX 6..20
FT /evidence="ECO:0007829|PDB:2Z5D"
FT STRAND 21..23
FT /evidence="ECO:0007829|PDB:2Z5D"
FT STRAND 25..30
FT /evidence="ECO:0007829|PDB:2Z5D"
FT STRAND 33..39
FT /evidence="ECO:0007829|PDB:2Z5D"
FT TURN 45..48
FT /evidence="ECO:0007829|PDB:2Z5D"
FT STRAND 50..56
FT /evidence="ECO:0007829|PDB:2Z5D"
FT TURN 59..63
FT /evidence="ECO:0007829|PDB:2Z5D"
FT STRAND 67..72
FT /evidence="ECO:0007829|PDB:2Z5D"
FT TURN 81..83
FT /evidence="ECO:0007829|PDB:2Z5D"
FT HELIX 88..94
FT /evidence="ECO:0007829|PDB:2Z5D"
FT HELIX 103..106
FT /evidence="ECO:0007829|PDB:2Z5D"
FT HELIX 108..114
FT /evidence="ECO:0007829|PDB:2Z5D"
FT HELIX 124..132
FT /evidence="ECO:0007829|PDB:2Z5D"
FT HELIX 134..148
FT /evidence="ECO:0007829|PDB:2Z5D"
FT HELIX 151..154
FT /evidence="ECO:0007829|PDB:2Z5D"
SQ SEQUENCE 183 AA; 20655 MW; 3DD5D365945F708C CRC64;
MSSPSPGKRR MDTDVVKLIE SKHEVTILGG LNEFVVKFYG PQGTPYEGGV WKVRVDLPDK
YPFKSPSIGF MNKIFHPNID EASGTVCLDV INQTWTALYD LTNIFESFLP QLLAYPNPID
PLNGDAAAMY LHRPEEYKQK IKEYIQKYAT EEALKEQEEG TGDSSSESSM SDFSEDEAQD
MEL
