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Showing Protein Ubiquitin-protein ligase E3A (HMDBP09313)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 4 metabolites
Identification
HMDB Protein ID HMDBP09313
Secondary Accession Numbers
  • 15147
Name Ubiquitin-protein ligase E3A
Synonyms
  1. E6AP ubiquitin-protein ligase
  2. Human papillomavirus E6-associated protein
  3. Oncogenic protein-associated protein E6-AP
  4. Renal carcinoma antigen NY-REN-54
Gene Name UBE3A
Protein Type Enzyme
Biological Properties
General Function Involved in acid-amino acid ligase activity
Specific Function E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and transfers it to its substrates. Several substrates have been identified including the RAD23A and RAD23B, MCM7 (which is involved in DNA replication), annexin A1, the PML tumor suppressor, and the cell cycle regulator CDKN1B. Additionally, may function as a cellular quality control ubiquitin ligase by helping the degradation of the cytoplasmic misfolded proteins. Finally, UBE3A also promotes its own degradation in vivo
Pathways Not Available
Reactions Not Available
GO Classification
Component
cell part
intracellular
Function
catalytic activity
ligase activity
ligase activity, forming carbon-nitrogen bonds
acid-amino acid ligase activity
Process
metabolic process
macromolecule metabolic process
macromolecule modification
protein modification process
Cellular Location
  1. Nucleus (Probable)
Gene Properties
Chromosome Location Chromosome:1
Locus 15q11.2
SNPs UBE3A
Gene Sequence 
>2628 bp
ATGGAGAAGCTGCACCAGTGTTATTGGAAATCAGGAGAACCTCAGTCTGACGACATTGAA
GCTAGCCGAATGAAGCGAGCAGCTGCAAAGCATCTAATAGAACGCTACTACCACCAGTTA
ACTGAGGGCTGTGGAAATGAAGCCTGCACGAATGAGTTTTGTGCTTCCTGTCCAACTTTT
CTTCGTATGGATAATAATGCAGCAGCTATTAAAGCCCTCGAGCTTTATAAGATTAATGCA
AAACTCTGTGATCCTCATCCCTCCAAGAAAGGAGCAAGCTCAGCTTACCTTGAGAACTCG
AAAGGTGCCCCCAACAACTCCTGCTCTGAGATAAAAATGAACAAGAAAGGCGCTAGAATT
GATTTTAAAGATGTGACTTACTTAACAGAAGAGAAGGTATATGAAATTCTTGAATTATGT
AGAGAAAGAGAGGATTATTCCCCTTTAATCCGTGTTATTGGAAGAGTTTTTTCTAGTGCT
GAGGCATTGGTACAGAGCTTCCGGAAAGTTAAACAACACACCAAGGAAGAACTGAAATCT
CTTCAAGCAAAAGATGAAGACAAAGATGAAGATGAAAAGGAAAAAGCTGCATGTTCTGCT
GCTGCTATGGAAGAAGACTCAGAAGCATCTTCCTCAAGGATAGGTGATAGCTCACAGGGA
GACAACAATTTGCAAAAATTAGGCCCTGATGATGTGTCTGTGGATATTGATGCCATTAGA
AGGGTCTACACCAGATTGCTCTCTAATGAAAAAATTGAAACTGCCTTTCTCAATGCACTT
GTATATTTGTCACCTAACGTGGAATGTGACTTGACGTATCACAATGTATACTCTCGAGAT
CCTAATTATCTGAATTTGTTCATTATCGTAATGGAGAATAGAAATCTCCACAGTCCTGAA
TATCTGGAAATGGCTTTGCCATTATTTTGCAAAGCGATGAGCAAGCTACCCCTTGCAGCC
CAAGGAAAACTGATCAGACTGTGGTCTAAATACAATGCAGACCAGATTCGGAGAATGATG
GAGACATTTCAGCAACTTATTACTTATAAAGTCATAAGCAATGAATTTAACAGTCGAAAT
CTAGTGAATGATGATGATGCCATTGTTGCTGCTTCGAAGTGCTTGAAAATGGTTTACTAT
GCAAATGTAGTGGGAGGGGAAGTGGACACAAATCACAATGAAGAAGATGATGAAGAGCCC
ATCCCTGAGTCCAGCGAGCTGACACTTCAGGAACTTTTGGGAGAAGAAAGAAGAAACAAG
AAAGGTCCTCGAGTGGACCCCCTGGAAACTGAACTTGGTGTTAAAACCCTGGATTGTCGA
AAACCACTTATCCCTTTTGAAGAGTTTATTAATGAACCACTGAATGAGGTTCTAGAAATG
GATAAAGATTATACTTTTTTCAAAGTAGAAACAGAGAACAAATTCTCTTTTATGACATGT
CCCTTTATATTGAATGCTGTCACAAAGAATTTGGGATTATATTATGACAATAGAATTCGC
ATGTACAGTGAACGAAGAATCACTGTTCTCTACAGCTTAGTTCAAGGACAGCAGTTGAAT
CCATATTTGAGACTCAAAGTTAGACGTGACCATATCATAGATGATGCACTTGTCCGGCTA
GAGATGATCGCTATGGAAAATCCTGCAGACTTGAAGAAGCAGTTGTATGTGGAATTTGAA
GGAGAACAAGGAGTTGATGAGGGAGGTGTTTCCAAAGAATTTTTTCAGCTGGTTGTGGAG
GAAATCTTCAATCCAGATATTGGTATGTTCACATACGATGAATCTACAAAATTGTTTTGG
TTTAATCCATCTTCTTTTGAAACTGAGGGTCAGTTTACTCTGATTGGCATAGTACTGGGT
CTGGCTATTTACAATAACTGTATACTGGATGTACATTTTCCCATGGTTGTCTACAGGAAG
CTAATGGGGAAAAAAGGAACTTTTCGTGACTTGGGAGACTCTCACCCAGTTCTATATCAG
AGTTTAAAAGATTTATTGGAGTATGAAGGGAATGTGGAAGATGACATGATGATCACTTTC
CAGATATCACAGACAGATCTTTTTGGTAACCCAATGATGTATGATCTAAAGGAAAATGGT
GATAAAATTCCAATTACAAATGAAAACAGGAAGGAATTTGTCAATCTTTATTCTGACTAC
ATTCTCAATAAATCAGTAGAAAAACAGTTCAAGGCTTTTCGGAGAGGTTTTCATATGGTG
ACCAATGAATCTCCCTTAAAGTACTTATTCAGACCAGAAGAAATTGAATTGCTTATATGT
GGAAGCCGGAATCTAGATTTCCAAGCACTAGAAGAAACTACAGAATATGACGGTGGCTAT
ACCAGGGACTCTGTTCTGATTAGGGAGTTCTGGGAAATCGTTCATTCATTTACAGATGAA
CAGAAAAGACTCTTCTTGCAGTTTACAACGGGCACAGACAGAGCACCTGTGGGAGGACTA
GGAAAATTAAAGATGATTATAGCCAAAAATGGCCCAGACACAGAAAGGTTACCTACATCT
CATACTTGCTTTAATGTGCTTTTACTTCCGGAATACTCAAGCAAAGAAAAACTTAAAGAG
AGATTGTTGAAGGCCATCACGTATGCCAAAGGATTTGGCATGCTGTAA
Protein Properties
Number of Residues 875
Molecular Weight 100686.7
Theoretical pI 4.86
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence 
>Ubiquitin-protein ligase E3A
MEKLHQCYWKSGEPQSDDIEASRMKRAAAKHLIERYYHQLTEGCGNEACTNEFCASCPTF
LRMDNNAAAIKALELYKINAKLCDPHPSKKGASSAYLENSKGAPNNSCSEIKMNKKGARI
DFKDVTYLTEEKVYEILELCREREDYSPLIRVIGRVFSSAEALVQSFRKVKQHTKEELKS
LQAKDEDKDEDEKEKAACSAAAMEEDSEASSSRIGDSSQGDNNLQKLGPDDVSVDIDAIR
RVYTRLLSNEKIETAFLNALVYLSPNVECDLTYHNVYSRDPNYLNLFIIVMENRNLHSPE
YLEMALPLFCKAMSKLPLAAQGKLIRLWSKYNADQIRRMMETFQQLITYKVISNEFNSRN
LVNDDDAIVAASKCLKMVYYANVVGGEVDTNHNEEDDEEPIPESSELTLQELLGEERRNK
KGPRVDPLETELGVKTLDCRKPLIPFEEFINEPLNEVLEMDKDYTFFKVETENKFSFMTC
PFILNAVTKNLGLYYDNRIRMYSERRITVLYSLVQGQQLNPYLRLKVRRDHIIDDALVRL
EMIAMENPADLKKQLYVEFEGEQGVDEGGVSKEFFQLVVEEIFNPDIGMFTYDESTKLFW
FNPSSFETEGQFTLIGIVLGLAIYNNCILDVHFPMVVYRKLMGKKGTFRDLGDSHPVLYQ
SLKDLLEYEGNVEDDMMITFQISQTDLFGNPMMYDLKENGDKIPITNENRKEFVNLYSDY
ILNKSVEKQFKAFRRGFHMVTNESPLKYLFRPEEIELLICGSRNLDFQALEETTEYDGGY
TRDSVLIREFWEIVHSFTDEQKRLFLQFTTGTDRAPVGGLGKLKMIIAKNGPDTERLPTS
HTCFNVLLLPEYSSKEKLKERLLKAITYAKGFGML
GenBank ID Protein 19718766
UniProtKB/Swiss-Prot ID Q05086
UniProtKB/Swiss-Prot Entry Name UBE3A_HUMAN
PDB IDs
GenBank Gene ID NM_000462.2
GeneCard ID UBE3A
GenAtlas ID UBE3A
HGNC ID HGNC:12496
References
General References
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  2. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [PubMed:19690332 ]
  3. Matsuoka S, Ballif BA, Smogorzewska A, McDonald ER 3rd, Hurov KE, Luo J, Bakalarski CE, Zhao Z, Solimini N, Lerenthal Y, Shiloh Y, Gygi SP, Elledge SJ: ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science. 2007 May 25;316(5828):1160-6. [PubMed:17525332 ]
  4. Scanlan MJ, Gordan JD, Williamson B, Stockert E, Bander NH, Jongeneel V, Gure AO, Jager D, Jager E, Knuth A, Chen YT, Old LJ: Antigens recognized by autologous antibody in patients with renal-cell carcinoma. Int J Cancer. 1999 Nov 12;83(4):456-64. [PubMed:10508479 ]
  5. Zody MC, Garber M, Sharpe T, Young SK, Rowen L, O'Neill K, Whittaker CA, Kamal M, Chang JL, Cuomo CA, Dewar K, FitzGerald MG, Kodira CD, Madan A, Qin S, Yang X, Abbasi N, Abouelleil A, Arachchi HM, Baradarani L, Birditt B, Bloom S, Bloom T, Borowsky ML, Burke J, Butler J, Cook A, DeArellano K, DeCaprio D, Dorris L 3rd, Dors M, Eichler EE, Engels R, Fahey J, Fleetwood P, Friedman C, Gearin G, Hall JL, Hensley G, Johnson E, Jones C, Kamat A, Kaur A, Locke DP, Madan A, Munson G, Jaffe DB, Lui A, Macdonald P, Mauceli E, Naylor JW, Nesbitt R, Nicol R, O'Leary SB, Ratcliffe A, Rounsley S, She X, Sneddon KM, Stewart S, Sougnez C, Stone SM, Topham K, Vincent D, Wang S, Zimmer AR, Birren BW, Hood L, Lander ES, Nusbaum C: Analysis of the DNA sequence and duplication history of human chromosome 15. Nature. 2006 Mar 30;440(7084):671-5. [PubMed:16572171 ]
  6. Huang L, Kinnucan E, Wang G, Beaudenon S, Howley PM, Huibregtse JM, Pavletich NP: Structure of an E6AP-UbcH7 complex: insights into ubiquitination by the E2-E3 enzyme cascade. Science. 1999 Nov 12;286(5443):1321-6. [PubMed:10558980 ]
  7. Wang X, Chen CF, Baker PR, Chen PL, Kaiser P, Huang L: Mass spectrometric characterization of the affinity-purified human 26S proteasome complex. Biochemistry. 2007 Mar 20;46(11):3553-65. Epub 2007 Feb 27. [PubMed:17323924 ]
  8. Yamamoto Y, Huibregtse JM, Howley PM: The human E6-AP gene (UBE3A) encodes three potential protein isoforms generated by differential splicing. Genomics. 1997 Apr 15;41(2):263-6. [PubMed:9143503 ]
  9. Kishino T, Lalande M, Wagstaff J: UBE3A/E6-AP mutations cause Angelman syndrome. Nat Genet. 1997 Jan;15(1):70-3. [PubMed:8988171 ]
  10. Matsuura T, Sutcliffe JS, Fang P, Galjaard RJ, Jiang YH, Benton CS, Rommens JM, Beaudet AL: De novo truncating mutations in E6-AP ubiquitin-protein ligase gene (UBE3A) in Angelman syndrome. Nat Genet. 1997 Jan;15(1):74-7. [PubMed:8988172 ]
  11. Huibregtse JM, Scheffner M, Howley PM: Cloning and expression of the cDNA for E6-AP, a protein that mediates the interaction of the human papillomavirus E6 oncoprotein with p53. Mol Cell Biol. 1993 Feb;13(2):775-84. [PubMed:8380895 ]
  12. Nuber U, Schwarz SE, Scheffner M: The ubiquitin-protein ligase E6-associated protein (E6-AP) serves as its own substrate. Eur J Biochem. 1998 Jun 15;254(3):643-9. [PubMed:9688277 ]
  13. Kumar S, Talis AL, Howley PM: Identification of HHR23A as a substrate for E6-associated protein-mediated ubiquitination. J Biol Chem. 1999 Jun 25;274(26):18785-92. [PubMed:10373495 ]
  14. Kleijnen MF, Shih AH, Zhou P, Kumar S, Soccio RE, Kedersha NL, Gill G, Howley PM: The hPLIC proteins may provide a link between the ubiquitination machinery and the proteasome. Mol Cell. 2000 Aug;6(2):409-19. [PubMed:10983987 ]
  15. Shirakura M, Murakami K, Ichimura T, Suzuki R, Shimoji T, Fukuda K, Abe K, Sato S, Fukasawa M, Yamakawa Y, Nishijima M, Moriishi K, Matsuura Y, Wakita T, Suzuki T, Howley PM, Miyamura T, Shoji I: E6AP ubiquitin ligase mediates ubiquitylation and degradation of hepatitis C virus core protein. J Virol. 2007 Feb;81(3):1174-85. Epub 2006 Nov 15. [PubMed:17108031 ]
  16. Louria-Hayon I, Alsheich-Bartok O, Levav-Cohen Y, Silberman I, Berger M, Grossman T, Matentzoglu K, Jiang YH, Muller S, Scheffner M, Haupt S, Haupt Y: E6AP promotes the degradation of the PML tumor suppressor. Cell Death Differ. 2009 Aug;16(8):1156-66. doi: 10.1038/cdd.2009.31. Epub 2009 Mar 27. [PubMed:19325566 ]
  17. Mishra A, Godavarthi SK, Maheshwari M, Goswami A, Jana NR: The ubiquitin ligase E6-AP is induced and recruited to aggresomes in response to proteasome inhibition and may be involved in the ubiquitination of Hsp70-bound misfolded proteins. J Biol Chem. 2009 Apr 17;284(16):10537-45. doi: 10.1074/jbc.M806804200. Epub 2009 Feb 20. [PubMed:19233847 ]
  18. Shimoji T, Murakami K, Sugiyama Y, Matsuda M, Inubushi S, Nasu J, Shirakura M, Suzuki T, Wakita T, Kishino T, Hotta H, Miyamura T, Shoji I: Identification of annexin A1 as a novel substrate for E6AP-mediated ubiquitylation. J Cell Biochem. 2009 Apr 15;106(6):1123-35. doi: 10.1002/jcb.22096. [PubMed:19204938 ]
  19. Mishra A, Godavarthi SK, Jana NR: UBE3A/E6-AP regulates cell proliferation by promoting proteasomal degradation of p27. Neurobiol Dis. 2009 Oct;36(1):26-34. doi: 10.1016/j.nbd.2009.06.010. Epub 2009 Jul 8. [PubMed:19591933 ]
  20. Be X, Hong Y, Wei J, Androphy EJ, Chen JJ, Baleja JD: Solution structure determination and mutational analysis of the papillomavirus E6 interacting peptide of E6AP. Biochemistry. 2001 Feb 6;40(5):1293-9. [PubMed:11170455 ]
  21. Malzac P, Webber H, Moncla A, Graham JM, Kukolich M, Williams C, Pagon RA, Ramsdell LA, Kishino T, Wagstaff J: Mutation analysis of UBE3A in Angelman syndrome patients. Am J Hum Genet. 1998 Jun;62(6):1353-60. [PubMed:9585605 ]