CPLM-011274

Genbank Nucleotide ID

Ubiquitin-protein ligase E3A

Protein Synonyms/Alias

E6AP ubiquitin-protein ligase; Human papillomavirus E6-associated protein; Oncogenic protein-associated protein E6-AP; Renal carcinoma antigen NY-REN-54

E6AP; EPVE6AP; HPVE6A

Homo sapiens (Human)

Position	Peptide	Type	References
30	RMKRAAAKHLIERYY	ubiquitination	[1, 2, 3, 4, 5, 6, 7]
71	DNNAAAIKALELYKI	ubiquitination	[1, 4, 5, 6, 8, 9]
77	IKALELYKINAKLCD	ubiquitination	[1, 3, 4, 5, 6, 7, 10]
81	ELYKINAKLCDPHPS	ubiquitination	[5]
90	CDPHPSKKGASSAYL	ubiquitination	[5, 10]
101	SAYLENSKGAPNNSC	ubiquitination	[3, 4, 5, 7]
112	NNSCSEIKMNKKGAR	ubiquitination	[5, 7]
123	KGARIDFKDVTYLTE	ubiquitination	[1, 3, 4, 5, 6, 7, 10, 11]
132	VTYLTEEKVYEILEL	ubiquitination	[2]
184	ELKSLQAKDEDKDED	ubiquitination	[10]
226	QGDNNLQKLGPDDVS	ubiquitination	[3, 5, 7, 10, 11]
311	MALPLFCKAMSKLPL	ubiquitination	[1, 5, 6, 7, 12]
315	LFCKAMSKLPLAAQG	ubiquitination	[4, 5, 7]
323	LPLAAQGKLIRLWSK	ubiquitination	[1, 4, 5, 6, 7, 10]
330	KLIRLWSKYNADQIR	ubiquitination	[1, 4, 5, 6, 7, 10]
350	FQQLITYKVISNEFN	ubiquitination	[1, 4, 5, 6, 11]
373	DAIVAASKCLKMVYY	ubiquitination	[1, 3, 4, 5, 6, 7, 12]
421	GEERRNKKGPRVDPL	ubiquitination	[5]
435	LETELGVKTLDCRKP	ubiquitination	[3, 4, 5, 7]
441	VKTLDCRKPLIPFEE	ubiquitination	[11]
468	DKDYTFFKVETENKF	ubiquitination	[1, 4, 6, 11]
474	FKVETENKFSFMTCP	ubiquitination	[5]
552	MENPADLKKQLYVEF	ubiquitination	[5, 10, 11]
553	ENPADLKKQLYVEFE	ubiquitination	[5, 7, 10]
702	DLKENGDKIPITNEN	ubiquitination	[5, 7]
711	PITNENRKEFVNLYS	ubiquitination	[1, 4, 5, 6]
724	YSDYILNKSVEKQFK	ubiquitination	[1, 5, 6, 7, 11]
728	ILNKSVEKQFKAFRR	ubiquitination	[1, 6]
731	KSVEKQFKAFRRGFH	ubiquitination	[5]
802	HSFTDEQKRLFLQFT	ubiquitination	[5, 7, 10, 11]
822	APVGGLGKLKMIIAK	ubiquitination	[5, 7, 10, 12]
824	VGGLGKLKMIIAKNG	ubiquitination	[5, 7]
829	KLKMIIAKNGPDTER	ubiquitination	[5, 7, 10, 11]
857	PEYSSKEKLKERLLK	ubiquitination	[5]
864	KLKERLLKAITYAKG	ubiquitination	[3, 5, 7, 12]
870	LKAITYAKGFGML**	ubiquitination	[3, 4, 5, 7, 11, 12]

[1] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
[2] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931]
[3] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
[4] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
[5] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
[6] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
Chen Z, Zhou Y, Song J, Zhang Z.
Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
[7] Integrated proteomic analysis of post-translational modifications by serial enrichment.
Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
[8] Global analysis of lysine ubiquitination by ubiquitin remnant immunoaffinity profiling.
Xu G, Paige JS, Jaffrey SR.
Nat Biotechnol. 2010 Aug;28(8):868-73. [PMID: 20639865]
[9] A data set of human endogenous protein ubiquitination sites.
Shi Y, Chan DW, Jung SY, Malovannaya A, Wang Y, Qin J.
Mol Cell Proteomics. 2011 May;10(5):M110.002089. [PMID: 20972266]
[10] Systematic and quantitative assessment of the ubiquitin-modified proteome.
Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
[11] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
[12] Global identification of modular cullin-RING ligase substrates.
Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]

Functional Description

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. Catalyzes the high-risk human papilloma virus E6-mediated ubiquitination of p53/TP53, contributing to the neoplastic progression of cells infected by these viruses. 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.

DOMAIN 776 875 HECT.
REGION 401 418 E6-binding.
REGION 418 517 Interaction with HCV core protein.
ACT_SITE 843 843 Glycyl thioester intermediate.
MOD_RES 218 218 Phosphoserine.

3D-structure; Alternative splicing; Complete proteome; Direct protein sequencing; Disease mutation; Host-virus interaction; Ligase; Nucleus; Phosphoprotein; Polymorphism; Proteasome; Reference proteome; Ubl conjugation pathway.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0005737; C:cytoplasm; IBA:RefGenome.
GO:0005829; C:cytosol; IEA:Compara.
GO:0005634; C:nucleus; IBA:RefGenome.
GO:0000502; C:proteasome complex; IEA:UniProtKB-KW.
GO:0003713; F:transcription coactivator activity; IEA:Compara.
GO:0004842; F:ubiquitin-protein ligase activity; IDA:UniProtKB.
GO:0030521; P:androgen receptor signaling pathway; IBA:RefGenome.
GO:0007420; P:brain development; TAS:ProtInc.
GO:0001541; P:ovarian follicle development; IEA:Compara.
GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase cascade; IEA:Compara.
GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IEA:Compara.
GO:0060736; P:prostate gland growth; IEA:Compara.
GO:0070936; P:protein K48-linked ubiquitination; IDA:UniProtKB.
GO:0042787; P:protein ubiquitination involved in ubiquitin-dependent protein catabolic process; IBA:RefGenome.
GO:0035037; P:sperm entry; IEA:Compara.
GO:0019048; P:virus-host interaction; IEA:UniProtKB-KW.

IPR000569; HECT.
IPR017134; Ubiquitin-protein_ligase_E6-AP.