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P49459 (UBE2A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 134. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Ubiquitin-conjugating enzyme E2 A

EC=6.3.2.19
Alternative name(s):
RAD6 homolog A
Short name=HR6A
Short name=hHR6A
Ubiquitin carrier protein A
Ubiquitin-protein ligase A
Gene names
Name:UBE2A
Synonyms:RAD6A
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length152 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.7 Ref.9

Catalytic activity

ATP + ubiquitin + protein lysine = AMP + diphosphate + protein N-ubiquityllysine.

Pathway

Protein modification; protein ubiquitination.

Subunit structure

Interacts with RAD18 and WAC. Ref.11

Post-translational modification

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

Involvement in disease

Mental retardation, X-linked, syndromic, Nascimento-type (MRXSN) [MIM:300860]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8 Ref.13

Sequence similarities

Belongs to the ubiquitin-conjugating enzyme family.

Ontologies

Keywords
   Biological processDNA damage
DNA repair
Ubl conjugation pathway
   Coding sequence diversityAlternative splicing
   DiseaseDisease mutation
Mental retardation
   LigandATP-binding
Nucleotide-binding
   Molecular functionChromatin regulator
Ligase
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA repair

Inferred from genetic interaction Ref.1. Source: UniProtKB

antigen processing and presentation of peptide antigen via MHC class I

Traceable author statement. Source: Reactome

histone H2A ubiquitination

Inferred from direct assay PubMed 11953320. Source: UniProtKB

in utero embryonic development

Inferred from electronic annotation. Source: Ensembl

maternal process involved in female pregnancy

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell proliferation

Inferred from direct assay PubMed 11953320. Source: UniProtKB

postreplication repair

Non-traceable author statement PubMed 1559696. Source: UniProtKB

protein K11-linked ubiquitination

Inferred from direct assay Ref.9. Source: UniProtKB

protein K48-linked ubiquitination

Inferred from direct assay Ref.9. Source: UniProtKB

protein autoubiquitination

Inferred from direct assay PubMed 11953320. Source: UniProtKB

protein polyubiquitination

Traceable author statement. Source: Reactome

response to UV

Inferred from genetic interaction Ref.1. Source: UniProtKB

ubiquitin-dependent protein catabolic process

Non-traceable author statement PubMed 1559696. Source: UniProtKB

   Cellular_componentHULC complex

Inferred from direct assay PubMed 19410543. Source: UniProtKB

XY body

Inferred from electronic annotation. Source: Ensembl

chromatin

Inferred from sequence or structural similarity. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

nuclear chromatin

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction Ref.11. Source: UniProtKB

ubiquitin protein ligase binding

Inferred from physical interaction PubMed 10908344. Source: UniProtKB

ubiquitin-protein transferase activity

Inferred from direct assay PubMed 11953320Ref.9. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P49459-1)

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 2 (identifier: P49459-2)

The sequence of this isoform differs from the canonical sequence as follows:
     51-80: Missing.
Isoform 3 (identifier: P49459-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-75: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 152152Ubiquitin-conjugating enzyme E2 A
PRO_0000082445

Sites

Active site881Glycyl thioester intermediate By similarity

Amino acid modifications

Modified residue1201Phosphoserine; by CDK9 Ref.12

Natural variations

Alternative sequence1 – 7575Missing in isoform 3.
VSP_043851
Alternative sequence51 – 8030Missing in isoform 2.
VSP_043852
Natural variant111R → Q in MRXSN. Ref.13
VAR_066627
Natural variant231G → R in MRXSN. Ref.13
VAR_066628

Experimental info

Sequence conflict491E → G in AAA35981. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified August 4, 2003. Version 2.
Checksum: 0AAEB5B7770E47E2

FASTA15217,315
        10         20         30         40         50         60 
MSTPARRRLM RDFKRLQEDP PAGVSGAPSE NNIMVWNAVI FGPEGTPFED GTFKLTIEFT 

        70         80         90        100        110        120 
EEYPNKPPTV RFVSKMFHPN VYADGSICLD ILQNRWSPTY DVSSILTSIQ SLLDEPNPNS 

       130        140        150 
PANSQAAQLY QENKREYEKR VSAIVEQSWR DC 

« Hide

Isoform 2 [UniParc].

Checksum: FE5B4840CF115701
Show »

FASTA12213,777
Isoform 3 [UniParc].

Checksum: E947FEF59BB7F0AE
Show »

FASTA778,833

References

« Hide 'large scale' references
[1]"Structural and functional conservation of two human homologs of the yeast DNA repair gene RAD6."
Koken M.H.M., Reynolds P., Jaspers-Dekker I., Prakash L., Prakash S., Bootsma D., Hoeijmakers J.H.J.
Proc. Natl. Acad. Sci. U.S.A. 88:8865-8869(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"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. expand/collapse author list , 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] (ISOFORMS 1 AND 2).
Tissue: Subthalamic nucleus.
[3]NIEHS SNPs program
Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"The DNA sequence of the human X chromosome."
Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. expand/collapse author list , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R.
Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]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. expand/collapse author list , 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Skin.
[7]"The human homolog of yeast BRE1 functions as a transcriptional coactivator through direct activator interactions."
Kim J., Hake S.B., Roeder R.G.
Mol. Cell 20:759-770(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[8]"UBE2A, which encodes a ubiquitin-conjugating enzyme, is mutated in a novel X-linked mental retardation syndrome."
Nascimento R.M., Otto P.A., de Brouwer A.P., Vianna-Morgante A.M.
Am. J. Hum. Genet. 79:549-555(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN MRXSN.
[9]"The E2 ubiquitin-conjugating enzymes direct polyubiquitination to preferred lysines."
David Y., Ziv T., Admon A., Navon A.
J. Biol. Chem. 285:8595-8604(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[10]"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].
[11]"WAC, a functional partner of RNF20/40, regulates histone H2B ubiquitination and gene transcription."
Zhang F., Yu X.
Mol. Cell 41:384-397(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH WAC.
[12]"Phosphorylation by cyclin-dependent kinase-9 controls ubiquitin-conjugating enzyme-2A function."
Shchebet A., Karpiuk O., Kremmer E., Eick D., Johnsen S.A.
Cell Cycle 11:2122-2127(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-120.
[13]"Novel missense mutations in the ubiquitination-related gene UBE2A cause a recognizable X-linked mental retardation syndrome."
Budny B., Badura-Stronka M., Materna-Kiryluk A., Tzschach A., Raynaud M., Latos-Bielenska A., Ropers H.H.
Clin. Genet. 77:541-551(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MRXSN GLN-11 AND ARG-23.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS14580.1. [P49459-1]
CCDS14581.1. [P49459-2]
PIRA41222.
RefSeqNP_001269090.1. NM_001282161.1.
NP_003327.2. NM_003336.3. [P49459-1]
NP_861427.1. NM_181762.2. [P49459-2]
UniGeneHs.379466.

3D structure databases

ProteinModelPortalP49459.
SMRP49459. Positions 2-149.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113167. 44 interactions.
DIPDIP-24260N.
IntActP49459. 18 interactions.
MINTMINT-267059.
STRING9606.ENSP00000360613.

PTM databases

PhosphoSiteP49459.

Polymorphism databases

DMDM33518639.

Proteomic databases

MaxQBP49459.
PaxDbP49459.
PRIDEP49459.

Protocols and materials databases

DNASU7319.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000346330; ENSP00000335027; ENSG00000077721. [P49459-2]
ENST00000371558; ENSP00000360613; ENSG00000077721. [P49459-1]
ENST00000371569; ENSP00000360624; ENSG00000077721. [P49459-3]
GeneID7319.
KEGGhsa:7319.
UCSCuc004erl.3. human. [P49459-1]
uc004erm.3. human. [P49459-2]

Organism-specific databases

CTD7319.
GeneCardsGC0XP118708.
HGNCHGNC:12472. UBE2A.
MIM300860. phenotype.
312180. gene.
neXtProtNX_P49459.
Orphanet163956. intellectual disability, X-linked, Nascimento type.
PharmGKBPA37122.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5078.
HOGENOMHOG000233454.
HOVERGENHBG063308.
InParanoidP49459.
KOK10573.
OMAPVPDNVM.
OrthoDBEOG7M0NTH.
PhylomeDBP49459.
TreeFamTF101128.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.
SignaLinkP49459.
UniPathwayUPA00143.

Gene expression databases

ArrayExpressP49459.
BgeeP49459.
CleanExHS_UBE2A.
GenevestigatorP49459.

Family and domain databases

Gene3D3.10.110.10. 1 hit.
InterProIPR000608. UBQ-conjugat_E2.
IPR023313. UBQ-conjugating_AS.
IPR016135. UBQ-conjugating_enzyme/RWD.
[Graphical view]
PfamPF00179. UQ_con. 1 hit.
[Graphical view]
SUPFAMSSF54495. SSF54495. 1 hit.
PROSITEPS00183. UBIQUITIN_CONJUGAT_1. 1 hit.
PS50127. UBIQUITIN_CONJUGAT_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSUBE2A. human.
GeneWikiUBE2A.
GenomeRNAi7319.
NextBio28614.
PROP49459.
SOURCESearch...

Entry information

Entry nameUBE2A_HUMAN
AccessionPrimary (citable) accession number: P49459
Secondary accession number(s): A6NFE9 expand/collapse secondary AC list , A6NGR2, A6NMF5, B2R7R9, D3DWI1, Q4TTG1, Q96FX4
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: August 4, 2003
Last modified: July 9, 2014
This is version 134 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome X

Human chromosome X: entries, gene names and cross-references to MIM