Q05086 (UBE3A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ubiquitin-protein ligase E3A
EC=6.3.2.-

Alternative name(s):
E6AP ubiquitin-protein ligase
Human papillomavirus E6-associated protein
Oncogenic protein-associated protein E6-AP
Renal carcinoma antigen NY-REN-54

Gene names

Name:	UBE3A
Synonyms:	E6AP, EPVE6AP, HPVE6A

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	875 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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. 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. Ref.11 Ref.17 Ref.18 Ref.19 Ref.20 Ref.23
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Binds UBQLN1 and UBQLN2. Interacts with the 26S proteasome. Interacts with HCV core protein and targets it to degradation. Interacts with the E6 protein of the cancer-associated human papillomavirus types 16 and 18. The E6/E6-AP complex binds to and targets the p53/TP53 tumor-suppressor protein for ubiquitin-mediated proteolysis. Interacts with BPY2. Interacts with HIF1AN, MAPK6 AND NEURL4; interaction with MAPK6 may be mediated by NEURL4. Interacts with the proteasomal subunit PSMD4. Ref.12 Ref.13 Ref.15 Ref.23
Subcellular location	Nucleus Probable.
Involvement in disease	Angelman syndrome (AS) [MIM:105830]: A neurodevelopmental disorder characterized by severe motor and intellectual retardation, ataxia, frequent jerky limb movements and flapping of the arms and hands, hypotonia, seizures, absence of speech, frequent smiling and episodes of paroxysmal laughter, open-mouthed expression revealing the tongue. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10 Ref.26
Miscellaneous	A cysteine residue is required for ubiquitin-thioester formation.
Sequence similarities	Contains 1 HECT (E6AP-type E3 ubiquitin-protein ligase) domain.
Sequence caution	The sequence AAA35542.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Host-virus interaction Ubl conjugation pathway
Cellular component	Nucleus Proteasome
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Molecular function	Ligase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	androgen receptor signaling pathway Inferred from Biological aspect of Ancestor. Source: RefGenome brain development Traceable author statement Ref.2. Source: ProtInc ovarian follicle development Inferred from electronic annotation. Source: Compara positive regulation of phosphatidylinositol 3-kinase cascade Inferred from electronic annotation. Source: Compara positive regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara prostate gland growth Inferred from electronic annotation. Source: Compara protein K48-linked ubiquitination Inferred from direct assay PubMed 12890688. Source: UniProtKB protein ubiquitination involved in ubiquitin-dependent protein catabolic process Inferred from Biological aspect of Ancestor. Source: RefGenome sperm entry Inferred from electronic annotation. Source: Compara virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from Biological aspect of Ancestor. Source: RefGenome cytosol Inferred from electronic annotation. Source: Compara nucleus Inferred from Biological aspect of Ancestor. Source: RefGenome proteasome complex Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	transcription coactivator activity Inferred from electronic annotation. Source: Compara ubiquitin-protein ligase activity Inferred from direct assay PubMed 12890688. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
E6	P06463	2	EBI-954357,EBI-1186926	From a different organism.
TP53	P04637	2	EBI-954357,EBI-366083

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform II (identifier: Q05086-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform I (identifier: Q05086-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-23: Missing.

Isoform III (identifier: Q05086-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-10: MEKLHQCYWK → MATACKR

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 875

875

Ubiquitin-protein ligase E3A

PRO_0000194980

Regions

Domain

776 – 875

100

HECT

Region

401 – 418

18

E6-binding

Region

418 – 517

100

Interaction with HCV core protein

Compositional bias

394 – 399

6

Asp/Glu-rich (acidic)

Sites

Active site

843

1

Glycyl thioester intermediate

Amino acid modifications

Modified residue

218

1

Phosphoserine Ref.16 Ref.21

Natural variations

Alternative sequence

1 – 23

23

Missing in isoform I.

VSP_006705

Alternative sequence

1 – 10

10

MEKLHQCYWK → MATACKR in isoform III.

VSP_006706

Natural variant

44

1

C → Y Probable polymorphism. Ref.3

VAR_007852

Natural variant

62

1

R → H. Ref.26

VAR_008142

Natural variant

201

1

A → T. Ref.3 Ref.26

VAR_007853

Natural variant

290

1

V → G. Ref.1 Ref.7 Ref.9
Corresponds to variant rs1059383 [ dbSNP | Ensembl ].

VAR_047516

Natural variant

372

1

S → P. Ref.26

VAR_008143

Natural variant

826

1

I → II in AS. Ref.26

VAR_008144

Experimental info

Sequence conflict

359

1

R → RNLVNEFNSR AA sequence Ref.7

Sequence conflict

423

1

P → L in AAA35542. Ref.7

Sequence conflict

647 – 649

3

TFR → LFV in AAA35542. Ref.7

Sequence conflict

669

1

E → V in AAA35542. Ref.7

Sequence conflict

686

1

D → N in AAA35542. Ref.7

Secondary structure

1

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875

Helix Strand Turn

Details...

Helix

27 – 41

15

Helix

65 – 78

14

Helix

406 – 413

8

Beta strand

525 – 527

3

Beta strand

529 – 531

3

Helix

532 – 545

14

Helix

548 – 552

5

Beta strand

557 – 559

3

Helix

569 – 582

14

Helix

585 – 587

3

Beta strand

589 – 592

4

Turn

594 – 596

3

Beta strand

599 – 601

3

Helix

609 – 624

16

Helix

635 – 641

7

Helix

648 – 654

7

Helix

656 – 667

12

Helix

672 – 675

4

Beta strand

679 – 684

6

Turn

687 – 689

3

Beta strand

692 – 697

6

Turn

698 – 702

5

Turn

707 – 709

3

Helix

710 – 722

13

Helix

727 – 741

15

Beta strand

742 – 744

3

Helix

753 – 760

8

Turn

768 – 770

3

Beta strand

775 – 779

5

Helix

785 – 795

11

Helix

799 – 809

11

Beta strand

810 – 815

6

Helix

820 – 823

4

Beta strand

826 – 833

8

Beta strand

839 – 841

3

Helix

842 – 844

3

Beta strand

846 – 851

6

Helix

855 – 868

14

Sequences

	Sequence		Length	Mass (Da)
	Isoform II [UniParc]. Last modified November 25, 2008. Version 4. Checksum: F80F0502B3B3838A	FASTA	875	100,688
	10 20 30 40 50 60 MEKLHQCYWK SGEPQSDDIE ASRMKRAAAK HLIERYYHQL TEGCGNEACT NEFCASCPTF 70 80 90 100 110 120 LRMDNNAAAI KALELYKINA KLCDPHPSKK GASSAYLENS KGAPNNSCSE IKMNKKGARI 130 140 150 160 170 180 DFKDVTYLTE EKVYEILELC REREDYSPLI RVIGRVFSSA EALVQSFRKV KQHTKEELKS 190 200 210 220 230 240 LQAKDEDKDE DEKEKAACSA AAMEEDSEAS SSRIGDSSQG DNNLQKLGPD DVSVDIDAIR 250 260 270 280 290 300 RVYTRLLSNE KIETAFLNAL VYLSPNVECD LTYHNVYSRD PNYLNLFIIV MENRNLHSPE 310 320 330 340 350 360 YLEMALPLFC KAMSKLPLAA QGKLIRLWSK YNADQIRRMM ETFQQLITYK VISNEFNSRN 370 380 390 400 410 420 LVNDDDAIVA ASKCLKMVYY ANVVGGEVDT NHNEEDDEEP IPESSELTLQ ELLGEERRNK 430 440 450 460 470 480 KGPRVDPLET ELGVKTLDCR KPLIPFEEFI NEPLNEVLEM DKDYTFFKVE TENKFSFMTC 490 500 510 520 530 540 PFILNAVTKN LGLYYDNRIR MYSERRITVL YSLVQGQQLN PYLRLKVRRD HIIDDALVRL 550 560 570 580 590 600 EMIAMENPAD LKKQLYVEFE GEQGVDEGGV SKEFFQLVVE EIFNPDIGMF TYDESTKLFW 610 620 630 640 650 660 FNPSSFETEG QFTLIGIVLG LAIYNNCILD VHFPMVVYRK LMGKKGTFRD LGDSHPVLYQ 670 680 690 700 710 720 SLKDLLEYEG NVEDDMMITF QISQTDLFGN PMMYDLKENG DKIPITNENR KEFVNLYSDY 730 740 750 760 770 780 ILNKSVEKQF KAFRRGFHMV TNESPLKYLF RPEEIELLIC GSRNLDFQAL EETTEYDGGY 790 800 810 820 830 840 TRDSVLIREF WEIVHSFTDE QKRLFLQFTT GTDRAPVGGL GKLKMIIAKN GPDTERLPTS 850 860 870 HTCFNVLLLP EYSSKEKLKE RLLKAITYAK GFGML
	Isoform I [UniParc]. Checksum: 3C061DA8D216055A	FASTA	852	97,968
	10 20 30 40 50 60 MKRAAAKHLI ERYYHQLTEG CGNEACTNEF CASCPTFLRM DNNAAAIKAL ELYKINAKLC 70 80 90 100 110 120 DPHPSKKGAS SAYLENSKGA PNNSCSEIKM NKKGARIDFK DVTYLTEEKV YEILELCRER 130 140 150 160 170 180 EDYSPLIRVI GRVFSSAEAL VQSFRKVKQH TKEELKSLQA KDEDKDEDEK EKAACSAAAM 190 200 210 220 230 240 EEDSEASSSR IGDSSQGDNN LQKLGPDDVS VDIDAIRRVY TRLLSNEKIE TAFLNALVYL 250 260 270 280 290 300 SPNVECDLTY HNVYSRDPNY LNLFIIVMEN RNLHSPEYLE MALPLFCKAM SKLPLAAQGK 310 320 330 340 350 360 LIRLWSKYNA DQIRRMMETF QQLITYKVIS NEFNSRNLVN DDDAIVAASK CLKMVYYANV 370 380 390 400 410 420 VGGEVDTNHN EEDDEEPIPE SSELTLQELL GEERRNKKGP RVDPLETELG VKTLDCRKPL 430 440 450 460 470 480 IPFEEFINEP LNEVLEMDKD YTFFKVETEN KFSFMTCPFI LNAVTKNLGL YYDNRIRMYS 490 500 510 520 530 540 ERRITVLYSL VQGQQLNPYL RLKVRRDHII DDALVRLEMI AMENPADLKK QLYVEFEGEQ 550 560 570 580 590 600 GVDEGGVSKE FFQLVVEEIF NPDIGMFTYD ESTKLFWFNP SSFETEGQFT LIGIVLGLAI 610 620 630 640 650 660 YNNCILDVHF PMVVYRKLMG KKGTFRDLGD SHPVLYQSLK DLLEYEGNVE DDMMITFQIS 670 680 690 700 710 720 QTDLFGNPMM YDLKENGDKI PITNENRKEF VNLYSDYILN KSVEKQFKAF RRGFHMVTNE 730 740 750 760 770 780 SPLKYLFRPE EIELLICGSR NLDFQALEET TEYDGGYTRD SVLIREFWEI VHSFTDEQKR 790 800 810 820 830 840 LFLQFTTGTD RAPVGGLGKL KMIIAKNGPD TERLPTSHTC FNVLLLPEYS SKEKLKERLL 850 KAITYAKGFG ML
	Isoform III [UniParc]. Checksum: AB4C9B22356C9556	FASTA	872	100,102
	10 20 30 40 50 60 MATACKRSGE PQSDDIEASR MKRAAAKHLI ERYYHQLTEG CGNEACTNEF CASCPTFLRM 70 80 90 100 110 120 DNNAAAIKAL ELYKINAKLC DPHPSKKGAS SAYLENSKGA PNNSCSEIKM NKKGARIDFK 130 140 150 160 170 180 DVTYLTEEKV YEILELCRER EDYSPLIRVI GRVFSSAEAL VQSFRKVKQH TKEELKSLQA 190 200 210 220 230 240 KDEDKDEDEK EKAACSAAAM EEDSEASSSR IGDSSQGDNN LQKLGPDDVS VDIDAIRRVY 250 260 270 280 290 300 TRLLSNEKIE TAFLNALVYL SPNVECDLTY HNVYSRDPNY LNLFIIVMEN RNLHSPEYLE 310 320 330 340 350 360 MALPLFCKAM SKLPLAAQGK LIRLWSKYNA DQIRRMMETF QQLITYKVIS NEFNSRNLVN 370 380 390 400 410 420 DDDAIVAASK CLKMVYYANV VGGEVDTNHN EEDDEEPIPE SSELTLQELL GEERRNKKGP 430 440 450 460 470 480 RVDPLETELG VKTLDCRKPL IPFEEFINEP LNEVLEMDKD YTFFKVETEN KFSFMTCPFI 490 500 510 520 530 540 LNAVTKNLGL YYDNRIRMYS ERRITVLYSL VQGQQLNPYL RLKVRRDHII DDALVRLEMI 550 560 570 580 590 600 AMENPADLKK QLYVEFEGEQ GVDEGGVSKE FFQLVVEEIF NPDIGMFTYD ESTKLFWFNP 610 620 630 640 650 660 SSFETEGQFT LIGIVLGLAI YNNCILDVHF PMVVYRKLMG KKGTFRDLGD SHPVLYQSLK 670 680 690 700 710 720 DLLEYEGNVE DDMMITFQIS QTDLFGNPMM YDLKENGDKI PITNENRKEF VNLYSDYILN 730 740 750 760 770 780 KSVEKQFKAF RRGFHMVTNE SPLKYLFRPE EIELLICGSR NLDFQALEET TEYDGGYTRD 790 800 810 820 830 840 SVLIREFWEI VHSFTDEQKR LFLQFTTGTD RAPVGGLGKL KMIIAKNGPD TERLPTSHTC 850 860 870 FNVLLLPEYS SKEKLKERLL KAITYAKGFG ML

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The human E6-AP gene (UBE3A) encodes three potential protein isoforms generated by differential splicing." Yamamoto Y., Huibregtse J.M., Howley P.M. Genomics 41:263-266(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS I; II AND III), VARIANT GLY-290. Tissue: Keratinocyte.
[2]	"UBE3A/E6-AP mutations cause Angelman syndrome." Kishino T., Lalande M., Wagstaff J. Nat. Genet. 15:70-73(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM I). Tissue: Fetal brain.
[3]	"De novo truncating mutations in E6-AP ubiquitin-protein ligase gene (UBE3A) in Angelman syndrome." Matsuura T., Sutcliffe J.S., Fang P., Galjaard R.-J., Jiang Y.-H., Benton C.S., Rommens J.M., Beaudet A.L. Nat. Genet. 15:74-77(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM I), VARIANTS TYR-44 AND THR-201.
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM III). Tissue: Testis.
[5]	"Analysis of the DNA sequence and duplication history of human chromosome 15." Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C. Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"Cloning and expression of the cDNA for E6-AP, a protein that mediates the interaction of the human papillomavirus E6 oncoprotein with p53." Huibregtse J.M., Scheffner M., Howley P.M. Mol. Cell. Biol. 13:775-784(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 11-875, PARTIAL PROTEIN SEQUENCE, CHARACTERIZATION, VARIANT GLY-290. Tissue: Keratinocyte.
[8]	"The ubiquitin-protein ligase E6-associated protein (E6-AP) serves as its own substrate." Nuber U., Schwarz S.E., Scheffner M. Eur. J. Biochem. 254:643-649(1998) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION.
[9]	"Mutations in the E6-AP gene (UBE3A) in patients with Angelman syndrome." Hennies H.C., Buerger J., Sperling K., Reis A. Submitted (AUG-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 25-787, VARIANT GLY-290.
[10]	"Antigens recognized by autologous antibody in patients with renal-cell carcinoma." Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H., Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T., Old L.J. Int. J. Cancer 83:456-464(1999) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION AS A RENAL CANCER ANTIGEN. Tissue: Renal cell carcinoma.
[11]	"Identification of HHR23A as a substrate for E6-associated protein-mediated ubiquitination." Kumar S., Talis A.L., Howley P.M. J. Biol. Chem. 274:18785-18792(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[12]	"The hPLIC proteins may provide a link between the ubiquitination machinery and the proteasome." Kleijnen M.F., Shih A.H., Zhou P., Kumar S., Soccio R.E., Kedersha N.L., Gill G., Howley P.M. Mol. Cell 6:409-419(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH UBQLN1 AND UBQLN2.
[13]	"VCY2 protein interacts with the HECT domain of ubiquitin-protein ligase E3A." Wong E.Y., Tse J.Y., Yao K.M., Tam P.C., Yeung W.S. Biochem. Biophys. Res. Commun. 296:1104-1111(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH BPY2.
[14]	"Mass spectrometric characterization of the affinity-purified human 26S proteasome complex." Wang X., Chen C.-F., Baker P.R., Chen P.-L., Kaiser P., Huang L. Biochemistry 46:3553-3565(2007) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Embryonic kidney.
[15]	"E6AP ubiquitin ligase mediates ubiquitylation and degradation of hepatitis C virus core protein." 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 P.M., Miyamura T., Shoji I. J. Virol. 81:1174-1185(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HCV CORE PROTEIN.
[16]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-218, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[17]	"E6AP promotes the degradation of the PML tumor suppressor." Louria-Hayon I., Alsheich-Bartok O., Levav-Cohen Y., Silberman I., Berger M., Grossman T., Matentzoglu K., Jiang Y.H., Muller S., Scheffner M., Haupt S., Haupt Y. Cell Death Differ. 16:1156-1166(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[18]	"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." Mishra A., Godavarthi S.K., Maheshwari M., Goswami A., Jana N.R. J. Biol. Chem. 284:10537-10545(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[19]	"Identification of annexin A1 as a novel substrate for E6AP-mediated ubiquitylation." 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. J. Cell. Biochem. 106:1123-1135(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[20]	"UBE3A/E6-AP regulates cell proliferation by promoting proteasomal degrADation of p27." Mishra A., Godavarthi S.K., Jana N.R. Neurobiol. Dis. 36:26-34(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[21]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-218, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[22]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[23]	"Identification and proteomic analysis of distinct UBE3A/E6AP protein complexes." Martinez-Noel G., Galligan J.T., Sowa M.E., Arndt V., Overton T.M., Harper J.W., Howley P.M. Mol. Cell. Biol. 32:3095-3106(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH HIF1AN; MAPK6; NEURL4 AND PSMD4.
[24]	"Structure of an E6AP-UbcH7 complex: insights into ubiquitination by the E2-E3 enzyme cascade." Huang L., Kinnucan E., Wang G., Beaudenon S., Howley P.M., Huibregtse J.M., Pavletich N.P. Science 286:1321-1326(1999) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 495-852 IN COMPLEX WITH UBE2L3.
[25]	"Solution structure determination and mutational analysis of the papillomavirus E6 interacting peptide of E6AP." Be X., Hong Y., Wei J., Androphy E.J., Chen J.J., Baleja J.D. Biochemistry 40:1293-1299(2001) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 401-418.
[26]	"Mutation analysis of UBE3A in Angelman syndrome patients." Malzac P., Webber H., Moncla A., Graham J.M. Jr., Kukolich M., Williams C., Pagon R.A., Ramsdell L.A., Kishino T., Wagstaff J. Am. J. Hum. Genet. 62:1353-1360(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT AS ILE-826 INS, VARIANTS HIS-62; THR-201 AND PRO-372.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X98021 , X98027, X98022, X98023, X98024, X98025, X98026, X98028, X98029, X98030 Genomic DNA. Translation: CAA66653.1.
X98031 mRNA. Translation: CAA66654.1.
X98032 mRNA. Translation: CAA66655.1.
X98033 mRNA. Translation: CAA66656.1.
AC100774 Genomic DNA. No translation available.
AK292514 mRNA. Translation: BAF85203.1.
AC124997 Genomic DNA. No translation available.
CH471151 Genomic DNA. Translation: EAW57645.1.
L07557 mRNA. Translation: AAA35542.1. Different initiation.
AF016708 , AF016703, AF016704, AF016705, AF016706, AF016707 Genomic DNA. Translation: AAB69154.1.
U84404 mRNA. Translation: AAB49301.1.
AJ001107 Genomic DNA. Translation: CAA04534.1.
AJ001108 Genomic DNA. Translation: CAA04535.1.
AJ001109 Genomic DNA. Translation: CAA04536.1.
AJ001110 Genomic DNA. Translation: CAA04537.1.
AJ001111 Genomic DNA. Translation: CAA04538.1.
AJ001112 Genomic DNA. Translation: CAA04539.1.

IPI

IPI00011609.
IPI00219197.
IPI00219198.

RefSeq

NP_000453.2. NM_000462.3.
NP_570853.1. NM_130838.1.
NP_570854.1. NM_130839.2.

UniGene

Hs.598862.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1C4Z	X-ray	2.60	A/B/C	518-875	[»]
1D5F	X-ray	2.80	A/B/C	518-875	[»]
1EQX	NMR	-	A	401-418	[»]
2KR1	NMR	-	A	24-87	[»]
4GIZ	X-ray	2.55	A/B	406-417	[»]

ProteinModelPortal

Q05086.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-6002N.

IntAct

Q05086. 11 interactions.

MINT

MINT-147444.

PTM databases

PhosphoSite

Q05086.

Polymorphism databases

DMDM

215274240.

Proteomic databases

PaxDb

Q05086.

PRIDE

Q05086.

Protocols and materials databases

DNASU

7337.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000232165; ENSP00000232165; ENSG00000114062.
ENST00000397954; ENSP00000381045; ENSG00000114062.
ENST00000428984; ENSP00000401265; ENSG00000114062.
ENST00000438097; ENSP00000411258; ENSG00000114062.
ENST00000566215; ENSP00000457771; ENSG00000114062.

GeneID

7337.

KEGG

hsa:7337.

UCSC

uc001zaq.3. human.
uc001zas.3. human.

Organism-specific databases

CTD

7337.

GeneCards

GC15M025582.

HGNC

HGNC:12496. UBE3A.

HPA

HPA039410.

MIM

105830. phenotype.
601623. gene.

neXtProt

NX_Q05086.

Orphanet

72. Angelman syndrome.
98794. Angelman syndrome due to maternal 15q11q13 deletion.

PharmGKB

PA37144.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5021.

HOVERGEN

HBG059326.

InParanoid

Q05086.

KO

K10587.

OMA

NEPLNDV.

Enzyme and pathway databases

Pathway_Interaction_DB

ar_pathway. Coregulation of Androgen receptor activity.
telomerasepathway. Regulation of Telomerase.

Reactome

REACT_6900. Immune System.

UniPathway

UPA00143.

Gene expression databases

ArrayExpress

Q05086.

Bgee

Q05086.

Genevestigator

Q05086.

GermOnline

ENSG00000114062. Homo sapiens.

Family and domain databases

InterPro

IPR000569. HECT.
IPR017134. Ubiquitin-protein_ligase_E6-AP.
[Graphical view]

Pfam

PF00632. HECT. 1 hit.
[Graphical view]

PIRSF

PIRSF037201. Ubiquitin-protein_ligase_E6-AP. 1 hit.

SMART

SM00119. HECTc. 1 hit.
[Graphical view]

SUPFAM

SSF56204. HECT. 1 hit.

PROSITE

PS50237. HECT. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

UBE3A. human.

EvolutionaryTrace

Q05086.

GenomeRNAi

7337.

NextBio

28722.

SOURCE

Search...

Entry information

Entry name

UBE3A_HUMAN

Accession

Primary (citable) accession number: Q05086
Secondary accession number(s): A8K8Z9 , P78355, Q93066, Q9UEP4, Q9UEP5, Q9UEP6, Q9UEP7, Q9UEP8, Q9UEP9

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 25, 2008
Last modified:	May 1, 2013
This is version 136 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.