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Identification
HMDB Protein ID HMDBP00635
Secondary Accession Numbers
  • 5907
Name SUMO-conjugating enzyme UBC9
Synonyms
  1. SUMO-protein ligase
  2. Ubiquitin carrier protein 9
  3. Ubiquitin carrier protein I
  4. Ubiquitin-conjugating enzyme E2 I
  5. Ubiquitin-protein ligase I
  6. p18
Gene Name UBE2I
Protein Type Enzyme
Biological Properties
General Function Involved in acid-amino acid ligase activity
Specific Function Accepts the ubiquitin-like proteins SUMO1, SUMO2, SUMO3 and SUMO4 from the UBLE1A-UBLE1B E1 complex and catalyzes their covalent attachment to other proteins with the help of an E3 ligase such as RANBP2 or CBX4. Can catalyze the formation of poly-SUMO chains. Necessary for sumoylation of FOXL2 and KAT5. Essential for nuclear architecture and chromosome segregation.
Pathways
  • NF-kappa B signaling pathway
  • Nucleocytoplasmic transport
  • protein sumoylation
  • Ubiquitin mediated proteolysis
Reactions
Adenosine triphosphate + SUMO + protein lysine → Adenosine monophosphate + Pyrophosphate + protein N-SUMOyllysine details
GO Classification
Biological Process
cell division
ubiquitin-dependent protein catabolic process
chromosome segregation
positive regulation of intracellular steroid hormone receptor signaling pathway
positive regulation of sequence-specific DNA binding transcription factor activity
virus-host interaction
negative regulation of transcription from RNA polymerase II promoter
protein sumoylation
regulation of receptor activity
proteasomal ubiquitin-dependent protein catabolic process
mitosis
Cellular Component
cytoplasm
dendrite
fibrillar center
synaptonemal complex
PML body
synapse
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
SUMO ligase activity
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. Nucleus
  2. Cytoplasm
Gene Properties
Chromosome Location 16
Locus 16p13.3
SNPs UBE2I
Gene Sequence
>477 bp
ATGTCGGGGATCGCCCTCAGCAGACTCGCCCAGGAGAGGAAAGCATGGAGGAAAGACCAC
CCATTTGGTTTCGTGGCTGTCCCAACAAAAAATCCCGATGGCACGATGAACCTCATGAAC
TGGGAGTGCGCCATTCCAGGAAAGAAAGGGACTCCGTGGGAAGGAGGCTTGTTTAAACTA
CGGATGCTTTTCAAAGATGATTATCCATCTTCGCCACCAAAATGTAAATTCGAACCACCA
TTATTTCACCCGAATGTGTACCCTTCGGGGACAGTGTGCCTGTCCATCTTAGAGGAGGAC
AAGGACTGGAGGCCAGCCATCACAATCAAACAGATCCTATTAGGAATACAGGAACTTCTA
AATGAACCAAATATCCAAGACCCAGCTCAAGCAGAGGCCTACACGATTTACTGCCAAAAC
AGAGTGGAGTACGAGAAAAGGGTCCGAGCACAAGCCAAGAAGTTTGCGCCCTCATAA
Protein Properties
Number of Residues 158
Molecular Weight 18006.665
Theoretical pI 8.659
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>SUMO-conjugating enzyme UBC9
MSGIALSRLAQERKAWRKDHPFGFVAVPTKNPDGTMNLMNWECAIPGKKGTPWEGGLFKL
RMLFKDDYPSSPPKCKFEPPLFHPNVYPSGTVCLSILEEDKDWRPAITIKQILLGIQELL
NEPNIQDPAQAEAYTIYCQNRVEYEKRVRAQAKKFAPS
GenBank ID Protein 4507785
UniProtKB/Swiss-Prot ID P63279
UniProtKB/Swiss-Prot Entry Name UBC9_HUMAN
PDB IDs
GenBank Gene ID NM_003345.3
GeneCard ID UBE2I
GenAtlas ID UBE2I
HGNC ID HGNC:12485
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [PubMed:19608861 ]
  3. Cheng Z, Ke Y, Ding X, Wang F, Wang H, Wang W, Ahmed K, Liu Z, Xu Y, Aikhionbare F, Yan H, Liu J, Xue Y, Yu J, Powell M, Liang S, Wu Q, Reddy SE, Hu R, Huang H, Jin C, Yao X: Functional characterization of TIP60 sumoylation in UV-irradiated DNA damage response. Oncogene. 2008 Feb 7;27(7):931-41. Epub 2007 Aug 20. [PubMed:17704809 ]
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  5. Daniels RJ, Peden JF, Lloyd C, Horsley SW, Clark K, Tufarelli C, Kearney L, Buckle VJ, Doggett NA, Flint J, Higgs DR: Sequence, structure and pathology of the fully annotated terminal 2 Mb of the short arm of human chromosome 16. Hum Mol Genet. 2001 Feb 15;10(4):339-52. [PubMed:11157797 ]
  6. Meierhofer D, Wang X, Huang L, Kaiser P: Quantitative analysis of global ubiquitination in HeLa cells by mass spectrometry. J Proteome Res. 2008 Oct;7(10):4566-76. doi: 10.1021/pr800468j. Epub 2008 Sep 10. [PubMed:18781797 ]
  7. Yasugi T, Howley PM: Identification of the structural and functional human homolog of the yeast ubiquitin conjugating enzyme UBC9. Nucleic Acids Res. 1996 Jun 1;24(11):2005-10. [PubMed:8668529 ]
  8. Tachibana M, Iwata N, Watanabe A, Nobukuni Y, Ploplis B, Kajigaya S: Assignment of the gene for a ubiquitin-conjugating enzyme (UBE2I) to human chromosome band 16p13.3 by in situ hybridization. Cytogenet Cell Genet. 1996;75(4):222-3. [PubMed:9067428 ]
  9. Watanabe TK, Fujiwara T, Kawai A, Shimizu F, Takami S, Hirano H, Okuno S, Ozaki K, Takeda S, Shimada Y, Nagata M, Takaichi A, Takahashi E, Nakamura Y, Shin S: Cloning, expression, and mapping of UBE2I, a novel gene encoding a human homologue of yeast ubiquitin-conjugating enzymes which are critical for regulating the cell cycle. Cytogenet Cell Genet. 1996;72(1):86-9. [PubMed:8565643 ]
  10. Masson M, Menissier-de Murcia J, Mattei MG, de Murcia G, Niedergang CP: Poly(ADP-ribose) polymerase interacts with a novel human ubiquitin conjugating enzyme: hUbc9. Gene. 1997 May 6;190(2):287-96. [PubMed:9197546 ]
  11. Kovalenko OV, Plug AW, Haaf T, Gonda DK, Ashley T, Ward DC, Radding CM, Golub EI: Mammalian ubiquitin-conjugating enzyme Ubc9 interacts with Rad51 recombination protein and localizes in synaptonemal complexes. Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):2958-63. [PubMed:8610150 ]
  12. Jiang W, Koltin Y: Two-hybrid interaction of a human UBC9 homolog with centromere proteins of Saccharomyces cerevisiae. Mol Gen Genet. 1996 May 23;251(2):153-60. [PubMed:8668125 ]
  13. Wang ZY, Qiu QQ, Seufert W, Taguchi T, Testa JR, Whitmore SA, Callen DF, Welsh D, Shenk T, Deuel TF: Molecular cloning of the cDNA and chromosome localization of the gene for human ubiquitin-conjugating enzyme 9. J Biol Chem. 1996 Oct 4;271(40):24811-6. [PubMed:8798754 ]
  14. Hahn SL, Wasylyk B, Criqui-Filipe P: Modulation of ETS-1 transcriptional activity by huUBC9, a ubiquitin-conjugating enzyme. Oncogene. 1997 Sep 18;15(12):1489-95. [PubMed:9333025 ]
  15. Hateboer G, Hijmans EM, Nooij JB, Schlenker S, Jentsch S, Bernards R: mUBC9, a novel adenovirus E1A-interacting protein that complements a yeast cell cycle defect. J Biol Chem. 1996 Oct 18;271(42):25906-11. [PubMed:8824223 ]
  16. Hu G, Zhang S, Vidal M, Baer JL, Xu T, Fearon ER: Mammalian homologs of seven in absentia regulate DCC via the ubiquitin-proteasome pathway. Genes Dev. 1997 Oct 15;11(20):2701-14. [PubMed:9334332 ]
  17. Poukka H, Aarnisalo P, Karvonen U, Palvimo JJ, Janne OA: Ubc9 interacts with the androgen receptor and activates receptor-dependent transcription. J Biol Chem. 1999 Jul 2;274(27):19441-6. [PubMed:10383460 ]
  18. Tatham MH, Jaffray E, Vaughan OA, Desterro JM, Botting CH, Naismith JH, Hay RT: Polymeric chains of SUMO-2 and SUMO-3 are conjugated to protein substrates by SAE1/SAE2 and Ubc9. J Biol Chem. 2001 Sep 21;276(38):35368-74. Epub 2001 Jul 12. [PubMed:11451954 ]
  19. Eloranta JJ, Hurst HC: Transcription factor AP-2 interacts with the SUMO-conjugating enzyme UBC9 and is sumolated in vivo. J Biol Chem. 2002 Aug 23;277(34):30798-804. Epub 2002 Jun 18. [PubMed:12072434 ]
  20. Tatham MH, Chen Y, Hay RT: Role of two residues proximal to the active site of Ubc9 in substrate recognition by the Ubc9.SUMO-1 thiolester complex. Biochemistry. 2003 Mar 25;42(11):3168-79. [PubMed:12641448 ]
  21. Tatham MH, Kim S, Yu B, Jaffray E, Song J, Zheng J, Rodriguez MS, Hay RT, Chen Y: Role of an N-terminal site of Ubc9 in SUMO-1, -2, and -3 binding and conjugation. Biochemistry. 2003 Aug 26;42(33):9959-69. [PubMed:12924945 ]
  22. Pichler A, Knipscheer P, Saitoh H, Sixma TK, Melchior F: The RanBP2 SUMO E3 ligase is neither HECT- nor RING-type. Nat Struct Mol Biol. 2004 Oct;11(10):984-91. Epub 2004 Sep 19. [PubMed:15378033 ]
  23. Tatham MH, Kim S, Jaffray E, Song J, Chen Y, Hay RT: Unique binding interactions among Ubc9, SUMO and RanBP2 reveal a mechanism for SUMO paralog selection. Nat Struct Mol Biol. 2005 Jan;12(1):67-74. Epub 2004 Dec 19. [PubMed:15608651 ]
  24. Li T, Santockyte R, Shen RF, Tekle E, Wang G, Yang DC, Chock PB: A general approach for investigating enzymatic pathways and substrates for ubiquitin-like modifiers. Arch Biochem Biophys. 2006 Sep 1;453(1):70-4. Epub 2006 Mar 20. [PubMed:16620772 ]
  25. Pan X, Li H, Zhang P, Jin B, Man J, Tian L, Su G, Zhao J, Li W, Liu H, Gong W, Zhou T, Zhang X: Ubc9 interacts with SOX4 and represses its transcriptional activity. Biochem Biophys Res Commun. 2006 Jun 9;344(3):727-34. Epub 2006 Apr 17. [PubMed:16631117 ]
  26. Tomoiu A, Gravel A, Tanguay RM, Flamand L: Functional interaction between human herpesvirus 6 immediate-early 2 protein and ubiquitin-conjugating enzyme 9 in the absence of sumoylation. J Virol. 2006 Oct;80(20):10218-28. [PubMed:17005699 ]
  27. Carbia-Nagashima A, Gerez J, Perez-Castro C, Paez-Pereda M, Silberstein S, Stalla GK, Holsboer F, Arzt E: RSUME, a small RWD-containing protein, enhances SUMO conjugation and stabilizes HIF-1alpha during hypoxia. Cell. 2007 Oct 19;131(2):309-23. [PubMed:17956732 ]
  28. Lee B, Muller MT: SUMOylation enhances DNA methyltransferase 1 activity. Biochem J. 2009 Jul 15;421(3):449-61. doi: 10.1042/BJ20090142. [PubMed:19450230 ]
  29. Kuo FT, Bentsi-Barnes IK, Barlow GM, Bae J, Pisarska MD: Sumoylation of forkhead L2 by Ubc9 is required for its activity as a transcriptional repressor of the Steroidogenic Acute Regulatory gene. Cell Signal. 2009 Dec;21(12):1935-44. doi: 10.1016/j.cellsig.2009.09.001. Epub 2009 Sep 8. [PubMed:19744555 ]
  30. Figueroa-Romero C, Iniguez-Lluhi JA, Stadler J, Chang CR, Arnoult D, Keller PJ, Hong Y, Blackstone C, Feldman EL: SUMOylation of the mitochondrial fission protein Drp1 occurs at multiple nonconsensus sites within the B domain and is linked to its activity cycle. FASEB J. 2009 Nov;23(11):3917-27. doi: 10.1096/fj.09-136630. Epub 2009 Jul 28. [PubMed:19638400 ]
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  33. Bernier-Villamor V, Sampson DA, Matunis MJ, Lima CD: Structural basis for E2-mediated SUMO conjugation revealed by a complex between ubiquitin-conjugating enzyme Ubc9 and RanGAP1. Cell. 2002 Feb 8;108(3):345-56. [PubMed:11853669 ]
  34. Reverter D, Lima CD: Insights into E3 ligase activity revealed by a SUMO-RanGAP1-Ubc9-Nup358 complex. Nature. 2005 Jun 2;435(7042):687-92. [PubMed:15931224 ]
  35. Yunus AA, Lima CD: Lysine activation and functional analysis of E2-mediated conjugation in the SUMO pathway. Nat Struct Mol Biol. 2006 Jun;13(6):491-9. Epub 2006 May 28. [PubMed:16732283 ]