Seroatlas · Human Serome Atlas

UBE3A

Ubiquitin-protein ligase E3A

Also known as: ANCR, AS, E6-AP, EPVE6AP, FLJ26981, HPVE6A, UBE3A_HUMAN

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: Q05086
Gene: UBE3A
Ensembl: ENSG00000114062
Chromosome: 15
Canonical length: 875 aa
Protein class: Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins
Subcellular location: Nucleoplasm,Cytosol
Quaternary structure: Homotrimer

OverviewNCBI Gene

This gene encodes an E3 ubiquitin-protein ligase, part of the ubiquitin protein degradation system. This imprinted gene is maternally expressed in brain and biallelically expressed in other tissues. Maternally inherited deletion of this gene causes Angelman Syndrome, characterized by severe motor and intellectual retardation, ataxia, hypotonia, epilepsy, absence of speech, and characteristic facies. The protein also interacts with the E6 protein of human papillomavirus types 16 and 18, resulting in ubiquitination and proteolysis of tumor protein p53. Alternative splicing of this gene results in three transcript variants encoding three isoforms with different N-termini. Additional transcript variants have been described, but their full length nature has not been determined. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

875 residues, UniProt reviewed canonical sequence.

>Q05086|UBE3A
     1  MEKLHQCYWK SGEPQSDDIE ASRMKRAAAK HLIERYYHQL TEGCGNEACT NEFCASCPTF
    61  LRMDNNAAAI KALELYKINA KLCDPHPSKK GASSAYLENS KGAPNNSCSE IKMNKKGARI
   121  DFKDVTYLTE EKVYEILELC REREDYSPLI RVIGRVFSSA EALVQSFRKV KQHTKEELKS
   181  LQAKDEDKDE DEKEKAACSA AAMEEDSEAS SSRIGDSSQG DNNLQKLGPD DVSVDIDAIR
   241  RVYTRLLSNE KIETAFLNAL VYLSPNVECD LTYHNVYSRD PNYLNLFIIV MENRNLHSPE
   301  YLEMALPLFC KAMSKLPLAA QGKLIRLWSK YNADQIRRMM ETFQQLITYK VISNEFNSRN
   361  LVNDDDAIVA ASKCLKMVYY ANVVGGEVDT NHNEEDDEEP IPESSELTLQ ELLGEERRNK
   421  KGPRVDPLET ELGVKTLDCR KPLIPFEEFI NEPLNEVLEM DKDYTFFKVE TENKFSFMTC
   481  PFILNAVTKN LGLYYDNRIR MYSERRITVL YSLVQGQQLN PYLRLKVRRD HIIDDALVRL
   541  EMIAMENPAD LKKQLYVEFE GEQGVDEGGV SKEFFQLVVE EIFNPDIGMF TYDESTKLFW
   601  FNPSSFETEG QFTLIGIVLG LAIYNNCILD VHFPMVVYRK LMGKKGTFRD LGDSHPVLYQ
   661  SLKDLLEYEG NVEDDMMITF QISQTDLFGN PMMYDLKENG DKIPITNENR KEFVNLYSDY
   721  ILNKSVEKQF KAFRRGFHMV TNESPLKYLF RPEEIELLIC GSRNLDFQAL EETTEYDGGY
   781  TRDSVLIREF WEIVHSFTDE QKRLFLQFTT GTDRAPVGGL GKLKMIIAKN GPDTERLPTS
   841  HTCFNVLLLP EYSSKEKLKE RLLKAITYAK GFGML

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against UBE3A can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Intracellular
Secreted: No
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0.31
Highest tissue expression: 102 nTPM

Expression across tissuesHPA

Tissue

skeletal muscle: 102 nTPM
tongue: 86 nTPM
testis: 43 nTPM
liver: 39 nTPM
thyroid gland: 39 nTPM
thymus: 39 nTPM

Single-cell type

retinal ganglion cells: 533 nCPM
myonuclei: 498 nCPM
thymic myoid cells: 480 nCPM
brain inhibitory neurons: 320 nCPM
brain excitatory neurons: 316 nCPM
other brain neurons: 291 nCPM

Immune cell

NK-cell: 30 nTPM
naive B-cell: 23 nTPM
non-classical monocyte: 22 nTPM
naive CD4 T-cell: 21 nTPM
memory CD8 T-cell: 21 nTPM
MAIT T-cell: 20 nTPM

Brain region

cerebellum: 121 nTPM
cerebral cortex: 107 nTPM
hippocampal formation: 97 nTPM
hypothalamus: 91 nTPM
white matter: 90 nTPM
basal ganglia: 89 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about UBE3A.

Disease | AllUniProt

Conditions UBE3A is implicated in, by any mechanism.

Angelman syndrome (AS) MIM:105830

Disease | GeneticClinVar

284 pathogenic / likely-pathogenic of 1,055 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 0.21
gnomAD pLI: 1
gnomAD missense Z: 4.4
DepMap mean gene effect: -0.08
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

HECT domain
HECT, E3 ligase catalytic domain
Ubiquitin-protein ligase E3A/B/C-like
HECT-domain (ubiquitin-transferase)
Ubiquitin-protein ligase E3A
Ubiquitin-protein ligase E3A, N-terminal zinc-binding domain
Ubiquitin-protein ligase E3A, N-terminal zinc-binding domain superfamily
Amino-terminal Zinc-binding domain of ubiquitin ligase E3A

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of UBE3A in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads UBE3A as an antibody target. Whether an autoantibody or antibody against UBE3A could matter depends on whether native UBE3A is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

UBE3A is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label UBE3A as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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