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Reviewed, UniProtKB/Swiss-Prot Q05086 (UBE3A_HUMAN)

Last modified November 25, 2008. Version 91. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Ubiquitin-protein ligase E3A
    EC=6.3.2.-
Alternative name(s):
    E6AP ubiquitin-protein ligase
    Oncogenic protein-associated protein E6-AP
    Human papillomavirus E6-associated protein
    Renal carcinoma antigen NY-REN-54
Gene names
Name: UBE3A
Synonyms: E6AP, EPVE6AP, HPVE6A
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length875 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

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 tumor-suppressor protein for ubiquitin-mediated proteolysis. It is an E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. It can target itself for ubiquitination in vitro and efficiently promotes its own degradation in vivo. It appears that only unmodified E6-AP molecules can bind efficiently to p53 in the presence of the HPV E6 oncoprotein.

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.

Subcellular location

NucleusProbable.

Post-translational modification

Phosphorylated upon DNA damage, probably by ATM or ATR.

Involvement in disease

Defects in UBE3A are a cause of Angelman syndrome (AS) [MIM:105830]; also known as 'happy puppet syndrome'. AS is characterized by features of severe motor and intellectual retardation, microcephaly, ataxia, frequent jerky limb movements and flapping of the arms and hands, hypotonia, hyperactivity, hypopigmentation, seizures, absence of speech, frequent smiling and episodes of paroxysmal laughter, and an unusual facies characterized by macrostomia, a large mandible and open-mouthed expression, a great propensity for protruding the tongue ('tongue thrusting'), and an occipital groove.

Miscellaneous

A cysteine residue is required for ubiquitin-thioester formation.

Sequence similarities

Contains 1 HECT (E6AP-type E3 ubiquitin-protein ligase) domain.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

E6P064631EBI-954357,EBI-1186926From a different organism.
TP53P046371EBI-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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 875875Ubiquitin-protein ligase E3A
PRO_0000194980

Regions

Domain776 – 875100HECT
Region401 – 41818E6-binding
Region418 – 517100Interaction with HCV core protein
Compositional bias394 – 3996Asp/Glu-rich (acidic)

Sites

Active site8431Glycyl thioester intermediate

Amino acid modifications

Modified residue2181Phosphoserine

Natural variations

Alternative sequence1 – 2323Missing in isoform I.
VSP_006705
Alternative sequence1 – 1010MEKLHQCYWK → MATACKR in isoform III.
VSP_006706
Natural variant441C → Y Probable polymorphism.
VAR_007852
Natural variant621R → H
VAR_008142
Natural variant2011A → T
VAR_007853
Natural variant2901V → G: dbSNP rs1059383.
VAR_047516
Natural variant3721S → P
VAR_008143
Natural variant8261I → II in AS.
VAR_008144

Experimental info

Sequence conflict3591R → RNLVNEFNSR AA sequence Ref.5
Sequence conflict4231P → L in AAA35542. Ref.5
Sequence conflict647 – 6493TFR → LFV in AAA35542. Ref.5
Sequence conflict6691E → V in AAA35542. Ref.5
Sequence conflict6861D → N in AAA35542. Ref.5

Secondary structure

................................................................. 875
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform II [UniParc].

Last modified November 25, 2008. Version 4.
Checksum: F80F0502B3B3838A

FASTA875100,688
        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 

« Hide

Isoform I [UniParc].

Checksum: 3C061DA8D216055A
Show »

85297,968
Isoform III [UniParc].

Checksum: AB4C9B22356C9556
Show »

872100,102

References

« Hide '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: 9143503] [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: 8988171] [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: 8988172] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM I), VARIANTS TYR-44 AND THR-201.
[4]"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. expand/collapse author list , 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: 16572171] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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.</