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Protein

Ubiquitin-conjugating enzyme E2 A

Gene

UBE2A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In association with the E3 enzyme BRE1 (RNF20 and/or RNF40), it plays a role in transcription regulation by catalyzing the monoubiquitination of histone H2B at 'Lys-120' to form H2BK120ub1. H2BK120ub1 gives a specific tag for epigenetic transcriptional activation, elongation by RNA polymerase II, telomeric silencing, and is also a prerequisite for H3K4me and H3K79me formation. In vitro catalyzes 'Lys-11', as well as 'Lys-48'-linked polyubiquitination. Required for postreplication repair of UV-damaged DNA.2 Publications

Catalytic activityi

S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [E2 ubiquitin-conjugating enzyme]-L-cysteine = [E1 ubiquitin-activating enzyme]-L-cysteine + S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine.PROSITE-ProRule annotation1 Publication

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.PROSITE-ProRule annotation
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei88Glycyl thioester intermediatePROSITE-ProRule annotation1

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • ubiquitin binding Source: Reactome
  • ubiquitin conjugating enzyme activity Source: MGI
  • ubiquitin protein ligase activity Source: GO_Central
  • ubiquitin protein ligase binding Source: UniProtKB
  • ubiquitin-protein transferase activity Source: UniProtKB

GO - Biological processi

  • DNA repair Source: UniProtKB
  • histone H2A ubiquitination Source: UniProtKB
  • in utero embryonic development Source: Ensembl
  • maternal process involved in female pregnancy Source: Ensembl
  • positive regulation of cell proliferation Source: UniProtKB
  • postreplication repair Source: UniProtKB
  • proteasome-mediated ubiquitin-dependent protein catabolic process Source: GO_Central
  • protein autoubiquitination Source: UniProtKB
  • protein K11-linked ubiquitination Source: UniProtKB
  • protein K48-linked ubiquitination Source: UniProtKB
  • protein polyubiquitination Source: Reactome
  • protein ubiquitination Source: Reactome
  • response to UV Source: UniProtKB
  • ubiquitin-dependent protein catabolic process Source: UniProtKB

Keywordsi

Molecular functionChromatin regulator, Transferase
Biological processDNA damage, DNA repair, Ubl conjugation pathway
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.3.2.B6 2681
ReactomeiR-HSA-8866652 Synthesis of active ubiquitin: roles of E1 and E2 enzymes
R-HSA-8866654 E3 ubiquitin ligases ubiquitinate target proteins
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
SignaLinkiP49459
SIGNORiP49459
UniPathwayiUPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin-conjugating enzyme E2 A (EC:2.3.2.231 Publication)
Alternative name(s):
E2 ubiquitin-conjugating enzyme A
RAD6 homolog A
Short name:
HR6A
Short name:
hHR6A
Ubiquitin carrier protein A
Ubiquitin-protein ligase A
Gene namesi
Name:UBE2A
Synonyms:RAD6A
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi

Organism-specific databases

EuPathDBiHostDB:ENSG00000077721.15
HGNCiHGNC:12472 UBE2A
MIMi312180 gene
neXtProtiNX_P49459

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Involvement in diseasei

Mental retardation, X-linked, syndromic, Nascimento-type (MRXSN)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRXSN features include dysmorphic facies, hirsutism, skin and nails abnormalities, obesity, speech anomalies and seizures.
See also OMIM:300860
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06662711R → Q in MRXSN. 1 PublicationCorresponds to variant dbSNP:rs387906728EnsemblClinVar.1
Natural variantiVAR_06662823G → R in MRXSN. 1 Publication1

Keywords - Diseasei

Disease mutation, Mental retardation

Organism-specific databases

DisGeNETi7319
MalaCardsiUBE2A
MIMi300860 phenotype
OpenTargetsiENSG00000077721
Orphaneti163956 X-linked intellectual disability, Nascimento type
PharmGKBiPA37122

Polymorphism and mutation databases

DMDMi33518639

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000824451 – 152Ubiquitin-conjugating enzyme E2 AAdd BLAST152

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei120Phosphoserine; by CDK91 Publication1

Post-translational modificationi

Phosphorylation at Ser-120 by CDK9 increases activity towards histone H2B.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP49459
MaxQBiP49459
PaxDbiP49459
PeptideAtlasiP49459
PRIDEiP49459
TopDownProteomicsiP49459-1 [P49459-1]
P49459-2 [P49459-2]

PTM databases

iPTMnetiP49459
PhosphoSitePlusiP49459

Expressioni

Gene expression databases

BgeeiENSG00000077721
CleanExiHS_UBE2A
ExpressionAtlasiP49459 baseline and differential
GenevisibleiP49459 HS

Organism-specific databases

HPAiHPA003875
HPA051765
HPA065898

Interactioni

Subunit structurei

Interacts with RAD18 and WAC.1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

  • ubiquitin binding Source: Reactome
  • ubiquitin protein ligase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi113167, 202 interactors
CORUMiP49459
DIPiDIP-24260N
IntActiP49459, 27 interactors
MINTiP49459
STRINGi9606.ENSP00000360613

Structurei

3D structure databases

ProteinModelPortaliP49459
SMRiP49459
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the ubiquitin-conjugating enzyme family.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0419 Eukaryota
COG5078 LUCA
GeneTreeiENSGT00900000140930
HOGENOMiHOG000233454
HOVERGENiHBG063308
InParanoidiP49459
KOiK10573
OMAiRENMKEY
OrthoDBiEOG091G0UM8
PhylomeDBiP49459
TreeFamiTF101128

Family and domain databases

CDDicd00195 UBCc, 1 hit
Gene3Di3.10.110.10, 1 hit
InterProiView protein in InterPro
IPR000608 UBQ-conjugat_E2
IPR023313 UBQ-conjugating_AS
IPR016135 UBQ-conjugating_enzyme/RWD
PfamiView protein in Pfam
PF00179 UQ_con, 1 hit
SUPFAMiSSF54495 SSF54495, 1 hit
PROSITEiView protein in PROSITE
PS00183 UBIQUITIN_CONJUGAT_1, 1 hit
PS50127 UBIQUITIN_CONJUGAT_2, 1 hit

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P49459-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MSTPARRRLM RDFKRLQEDP PAGVSGAPSE NNIMVWNAVI FGPEGTPFED
60 70 80 90 100
GTFKLTIEFT EEYPNKPPTV RFVSKMFHPN VYADGSICLD ILQNRWSPTY
110 120 130 140 150
DVSSILTSIQ SLLDEPNPNS PANSQAAQLY QENKREYEKR VSAIVEQSWR

DC
Length:152
Mass (Da):17,315
Last modified:August 4, 2003 - v2
Checksum:i0AAEB5B7770E47E2
GO
Isoform 2 (identifier: P49459-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     51-80: Missing.

Show »
Length:122
Mass (Da):13,777
Checksum:iFE5B4840CF115701
GO
Isoform 3 (identifier: P49459-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-75: Missing.

Note: No experimental confirmation available.
Show »
Length:77
Mass (Da):8,833
Checksum:iE947FEF59BB7F0AE
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti49E → G in AAA35981 (PubMed:1717990).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06662711R → Q in MRXSN. 1 PublicationCorresponds to variant dbSNP:rs387906728EnsemblClinVar.1
Natural variantiVAR_06662823G → R in MRXSN. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0438511 – 75Missing in isoform 3. CuratedAdd BLAST75
Alternative sequenceiVSP_04385251 – 80Missing in isoform 2. 1 PublicationAdd BLAST30

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M74524 mRNA Translation: AAA35981.1
AK297696 mRNA Translation: BAG60054.1
AK313092 mRNA Translation: BAG35916.1
DQ068065 Genomic DNA Translation: AAY46159.1
AC004913 Genomic DNA No translation available.
CH471161 Genomic DNA Translation: EAW89861.1
CH471161 Genomic DNA Translation: EAW89862.1
CH471161 Genomic DNA Translation: EAW89863.1
BC010175 mRNA Translation: AAH10175.1
CCDSiCCDS14580.1 [P49459-1]
CCDS14581.1 [P49459-2]
PIRiA41222
RefSeqiNP_001269090.1, NM_001282161.1
NP_003327.2, NM_003336.3 [P49459-1]
NP_861427.1, NM_181762.2 [P49459-2]
UniGeneiHs.379466

Genome annotation databases

EnsembliENST00000371558; ENSP00000360613; ENSG00000077721 [P49459-1]
ENST00000625938; ENSP00000486599; ENSG00000077721 [P49459-2]
ENST00000630695; ENSP00000486550; ENSG00000077721 [P49459-3]
GeneIDi7319
KEGGihsa:7319
UCSCiuc004erl.5 human [P49459-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiUBE2A_HUMAN
AccessioniPrimary (citable) accession number: P49459
Secondary accession number(s): A6NFE9
, A6NGR2, A6NMF5, B2R7R9, D3DWI1, Q4TTG1, Q96FX4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: August 4, 2003
Last modified: April 25, 2018
This is version 169 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. SIMILARITY comments
    Index of protein domains and families

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