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Identification
HMDB Protein ID HMDBP00610
Secondary Accession Numbers
  • 5882
Name Ubiquitin-conjugating enzyme E2 D3
Synonyms
  1. Ubiquitin carrier protein D3
  2. Ubiquitin-conjugating enzyme E2(17)KB 3
  3. Ubiquitin-conjugating enzyme E2-17 kDa 3
  4. Ubiquitin-protein ligase D3
Gene Name UBE2D3
Protein Type Enzyme
Biological Properties
General Function Involved in acid-amino acid ligase activity
Specific Function Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-11'-, as well as 'Lys-48'-linked polyubiquitination. Cooperates with the E2 CDC34 and the SCF(FBXW11) E3 ligase complex for the polyubiquitination of NFKBIA leading to its subsequent proteasomal degradation. Acts as an initiator E2, priming the phosphorylated NFKBIA target at positions 'Lys-21' and/or 'Lys-22' with a monoubiquitin. Ubiquitin chain elongation is then performed by CDC34, building ubiquitin chains from the UBE2D3-primed NFKBIA-linked ubiquitin. Acts also as an initiator E2, in conjunction with RNF8, for the priming of PCNA. Monoubiquitination of PCNA, and its subsequent polyubiquitination, are essential events in the operation of the DNA damage tolerance (DDT) pathway that is activated after DNA damage caused by UV or chemical agents during S-phase. Associates with the BRCA1/BARD1 E3 ligase complex to perform ubiquitination at DNA damage sites following ionizing radiation leading to DNA repair. Targets DAPK3 for ubiquitination which influences promyelocytic leukemia protein nuclear body (PML-NB) formation in the nucleus. In conjunction with the MDM2 and TOPORS E3 ligases, functions ubiquitination of p53/TP53. Supports NRDP1-mediated ubiquitination and degradation of ERBB3 and of BRUCE which triggers apoptosis. In conjunction with the CBL E3 ligase, targets EGFR for polyubiquitination at the plasma membrane as well as during its internalization and transport on endosomes. In conjunction with the STUB1 E3 quality control E3 ligase, ubiquitinates unfolded proteins to catalyze their immediate destruction (By similarity).
Pathways
  • Protein processing in endoplasmic reticulum
  • protein ubiquitination
  • Ubiquitin mediated proteolysis
Reactions
Adenosine triphosphate + ubiquitin + protein lysine → Adenosine monophosphate + Pyrophosphate + protein N-ubiquityllysine details
GO Classification
Biological Process
apoptotic process
DNA repair
BMP signaling pathway
protein K48-linked ubiquitination
protein K11-linked ubiquitination
protein monoubiquitination
negative regulation of type I interferon production
innate immune response
negative regulation of transcription from RNA polymerase II promoter
regulation of transcription from RNA polymerase II promoter in response to hypoxia
transforming growth factor beta receptor signaling pathway
proteasomal ubiquitin-dependent protein catabolic process
transcription initiation from RNA polymerase II promoter
Cellular Component
cytosol
plasma membrane
nucleoplasm
endosome membrane
Function
catalytic activity
small conjugating protein ligase activity
ligase activity
ligase activity, forming carbon-nitrogen bonds
acid-amino acid ligase activity
Molecular Function
ubiquitin-protein ligase activity
ATP binding
Process
metabolic process
regulation of protein metabolic process
macromolecule metabolic process
biological regulation
regulation of biological process
regulation of metabolic process
regulation of macromolecule metabolic process
post-translational protein modification
macromolecule modification
protein modification process
Cellular Location
  1. Cell membrane
  2. Peripheral membrane protein
  3. Peripheral membrane protein
  4. Endosome membrane
Gene Properties
Chromosome Location 4
Locus 4q24
SNPs UBE2D3
Gene Sequence
>444 bp
ATGGCGCTGAAACGGATTAATAAGGAACTTAGTGATTTGGCCCGTGACCCTCCAGCACAA
TGTTCTGCAGGTCCAGTTGGGGATGATATGTTTCATTGGCAAGCCACAATTATGGGACCT
AATGACAGCCCATATCAAGGCGGTGTATTCTTTTTGACAATTCATTTTCCTACAGACTAC
CCCTTCAAACCACCTAAGGTTGCATTTACAACAAGAATTTATCATCCAAATATTAACAGT
AATGGCAGCATTTGTCTCGATATTCTAAGATCACAGTGGTCGCCTGCTTTAACAATTTCT
AAAGTTCTTTTATCCATTTGTTCACTGCTATGTGATCCAAACCCAGATGACCCCCTAGTG
CCAGAGATTGCACGGATCTATAAAACAGACAGAGATAAGTACAACAGAATATCTCGGGAA
TGGACTCAGAAGTATGCCATGTGA
Protein Properties
Number of Residues 147
Molecular Weight 16686.96
Theoretical pI 7.804
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Ubiquitin-conjugating enzyme E2 D3
MALKRINKELSDLARDPPAQCSAGPVGDDMFHWQATIMGPNDSPYQGGVFFLTIHFPTDY
PFKPPKVAFTTRIYHPNINSNGSICLDILRSQWSPALTISKVLLSICSLLCDPNPDDPLV
PEIARIYKTDRDKYNRISREWTQKYAM
GenBank ID Protein 4507777
UniProtKB/Swiss-Prot ID P61077
UniProtKB/Swiss-Prot Entry Name UB2D3_HUMAN
PDB IDs
GenBank Gene ID NM_003340.5
GeneCard ID UBE2D3
GenAtlas ID UBE2D3
HGNC ID HGNC:12476
References
General References
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  7. Saville MK, Sparks A, Xirodimas DP, Wardrop J, Stevenson LF, Bourdon JC, Woods YL, Lane DP: Regulation of p53 by the ubiquitin-conjugating enzymes UbcH5B/C in vivo. J Biol Chem. 2004 Oct 1;279(40):42169-81. Epub 2004 Jul 26. [PubMed:15280377 ]
  8. Murata S, Minami Y, Minami M, Chiba T, Tanaka K: CHIP is a chaperone-dependent E3 ligase that ubiquitylates unfolded protein. EMBO Rep. 2001 Dec;2(12):1133-8. Epub 2001 Nov 21. [PubMed:11743028 ]
  9. Yogosawa S, Miyauchi Y, Honda R, Tanaka H, Yasuda H: Mammalian Numb is a target protein of Mdm2, ubiquitin ligase. Biochem Biophys Res Commun. 2003 Mar 21;302(4):869-72. [PubMed:12646252 ]
  10. Rajendra R, Malegaonkar D, Pungaliya P, Marshall H, Rasheed Z, Brownell J, Liu LF, Lutzker S, Saleem A, Rubin EH: Topors functions as an E3 ubiquitin ligase with specific E2 enzymes and ubiquitinates p53. J Biol Chem. 2004 Aug 27;279(35):36440-4. Epub 2004 Jul 9. [PubMed:15247280 ]
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  15. Umebayashi K, Stenmark H, Yoshimori T: Ubc4/5 and c-Cbl continue to ubiquitinate EGF receptor after internalization to facilitate polyubiquitination and degradation. Mol Biol Cell. 2008 Aug;19(8):3454-62. doi: 10.1091/mbc.E07-10-0988. Epub 2008 May 28. [PubMed:18508924 ]
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  17. Kubori T, Hyakutake A, Nagai H: Legionella translocates an E3 ubiquitin ligase that has multiple U-boxes with distinct functions. Mol Microbiol. 2008 Mar;67(6):1307-19. doi: 10.1111/j.1365-2958.2008.06124.x. Epub 2008 Feb 13. [PubMed:18284575 ]
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