P49459 (UBE2A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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	152 AA.
Sequence status	Complete.
Protein existence	Evidence 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
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 adaptative 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.12
Sequence similarities	Belongs to the ubiquitin-conjugating enzyme family.

Ontologies

Keywords
Biological process	DNA damage DNA repair Ubl conjugation pathway
Coding sequence diversity	Alternative splicing
Disease	Disease mutation Mental retardation
Ligand	ATP-binding Nucleotide-binding
Molecular function	Chromatin regulator Ligase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	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: Compara maternal process involved in female pregnancy Inferred from electronic annotation. Source: Compara 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 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_component	HULC complex Inferred from direct assay PubMed 19410543. Source: UniProtKB XY body Inferred from electronic annotation. Source: Compara cytosol Traceable author statement. Source: Reactome nuclear chromatin Inferred from electronic annotation. Source: Compara
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW ubiquitin-protein ligase 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 152	152	Ubiquitin-conjugating enzyme E2 A		PRO_0000082445
Sites
	Active site	88	1	Glycyl thioester intermediate By similarity
Natural variations
	Alternative sequence	1 – 75	75	Missing in isoform 3.		VSP_043851
	Alternative sequence	51 – 80	30	Missing in isoform 2.		VSP_043852
	Natural variant	11	1	R → Q in MRXSN. Ref.12		VAR_066627
	Natural variant	23	1	G → R in MRXSN. Ref.12		VAR_066628
Experimental info
	Sequence conflict	49	1	E → G in AAA35981. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified August 4, 2003. Version 2. Checksum: 0AAEB5B7770E47E2	FASTA	152	17,315
	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
	Isoform 2 [UniParc]. Checksum: FE5B4840CF115701	FASTA	122	13,777
	10 20 30 40 50 60 MSTPARRRLM RDFKRLQEDP PAGVSGAPSE NNIMVWNAVI FGPEGTPFED VYADGSICLD 70 80 90 100 110 120 ILQNRWSPTY DVSSILTSIQ SLLDEPNPNS PANSQAAQLY QENKREYEKR VSAIVEQSWR DC
	Isoform 3 [UniParc]. Checksum: E947FEF59BB7F0AE	FASTA	77	8,833
	10 20 30 40 50 60 MFHPNVYADG SICLDILQNR WSPTYDVSSI LTSIQSLLDE PNPNSPANSQ AAQLYQENKR 70 EYEKRVSAIV EQSWRDC

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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]	"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

NIEHS-SNPs

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.
IPI	IPI00746451.
PIR	A41222.
RefSeq	NP_003327.2. NM_003336.2. NP_861427.1. NM_181762.1. NP_861442.1. NM_181777.1.
UniGene	Hs.379466.
3D structure databases
ProteinModelPortal	P49459.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-24260N.
IntAct	P49459. 16 interactions.
STRING	9606.ENSP00000360613.
PTM databases
PhosphoSite	P49459.
Polymorphism databases
DMDM	33518639.
Proteomic databases
PaxDb	P49459.
PRIDE	P49459.
Protocols and materials databases
DNASU	7319.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000346330; ENSP00000335027; ENSG00000077721. ENST00000371558; ENSP00000360613; ENSG00000077721. ENST00000371569; ENSP00000360624; ENSG00000077721.
GeneID	7319.
KEGG	hsa:7319.
UCSC	uc004erl.3. human.
Organism-specific databases
CTD	7319.
GeneCards	GC0XP118708.
HGNC	HGNC:12472. UBE2A.
MIM	300860. phenotype. 312180. gene.
neXtProt	NX_P49459.
Orphanet	163956. Intellectual deficit, X-linked, Nascimento type.
PharmGKB	PA37122.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5078.
HOGENOM	HOG000233454.
HOVERGEN	HBG063308.
InParanoid	P49459.
KO	K10573.
OMA	YANGELC.
OrthoDB	EOG4RJG2S.
PhylomeDB	P49459.
Enzyme and pathway databases
Reactome	REACT_6900. Immune System.
UniPathway	UPA00143.
Gene expression databases
ArrayExpress	P49459.
Bgee	P49459.
CleanEx	HS_UBE2A.
Genevestigator	P49459.
GermOnline	ENSG00000077721. Homo sapiens.
Family and domain databases
Gene3D	3.10.110.10. 1 hit.
InterPro	IPR000608. UBQ-conjugat_E2. IPR023313. UBQ-conjugating_AS. IPR016135. UBQ-conjugating_enzyme/RWD. [Graphical view]
Pfam	PF00179. UQ_con. 1 hit. [Graphical view]
SUPFAM	SSF54495. UBQ-conjugat/RWD-like. 1 hit.
PROSITE	PS00183. UBIQUITIN_CONJUGAT_1. 1 hit. PS50127. UBIQUITIN_CONJUGAT_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	UBE2A. human.
GenomeRNAi	7319.
NextBio	28614.
SOURCE	Search...

Entry information

Entry name

UBE2A_HUMAN

Accession

Primary (citable) accession number: P49459
Secondary accession number(s): A6NFE9 , A6NGR2, A6NMF5, B2R7R9, D3DWI1, Q4TTG1, Q96FX4

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	August 4, 2003
Last modified:	May 1, 2013
This is version 121 of the entry and version 2 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.