UBE2A (HHR6A)

Ubiquitin-conjugating enzyme E2 A (also known as HHR6A or UBE2A), encoded by human DNA repair genes HHR6A, belongs to the ubiquitin-conjugating enzymes (E2 enzymes) family and is likely to be involved in postreplication repair and induced mutagenesis. UBE2A is described as a CDK2 substrate. It is the human homologue of the product of the Saccharomyces cerevisiae RAD6 / UBC2 gene, a member of the family of ubiquitin-conjugating enzymes. In vivo, HHR6A phosphorylation peaks during the G2/M phase of cell cycle transition, with a concomitant increase in histone H2B ubiquitylation. Mutation of Ser120 to threonine or alanine abolished UBE2A activity, while mutation to aspartate to mimic phosphorylated serine increased UBE2A activity 3-fold. A mutation of UBE2A is consisdered as the cause of a novel X-linked mental retardation (XLMR) syndrome that affects three males in a two-generation family.

UBE2A (HHR6A) Alternative Names

HHR6A, RAD6A, UBC2 [Homo sapiens]

RP23-286I5.4, HHR6A, HR6A, Mhr6a [Mus musculus]

Summaries for UBE2A (HHR6A)

Entrez Gene summary for UBE2A (HHR6A):

The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. UBE2A gene encodes a member of the E2 ubiquitin-conjugating enzyme family. This enzyme is required for post-replicative DNA damage repair. Multiple alternatively spliced transcript variants have been found for UBE2A gene and they encode distinct isoforms. [provided by RefSeq, Jul 2008]

Wikipedia summary for UBE2A (HHR6A):

Ubiquitin-conjugating enzyme E2 A is a protein that in humans is encoded by the UBE2A gene.
The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes a member of the E2 ubiquitin-conjugating enzyme family. This enzyme is required for post-replicative DNA damage repair. Multiple alternatively spliced transcript variants have been found for this gene and they encode distinct isoforms.

Human UBE2A (HHR6A) Protein General Information

 

• Protein names: Ubiquitin-conjugating enzyme E2 A
  Short name=UBE2A
• Sequence length: 152 AA.
• Pathway: Protein modification; protein ubiquitination.
• Sequence similarities: Belongs to the ubiquitin-conjugating enzyme family.
• Catalytic activity: ATP + ubiquitin + protein lysine = AMP + diphosphate + protein N-ubiquityllysine.
• Subunit structure: Interacts with RAD18 and WAC.
• Involvement in disease: Defects in UBE2A are the cause of mental retardation syndromic X-linked Nascimento-type (MRXSN) . Mental retardation is 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.

General information above from UniProt

Function for UBE2A (HHR6A) Protein

UniProtKB:

UBE2A 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), UBE2A 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. UBE2A is required for postreplication repair of UV-damaged DNA.

Genatlas:

• UBE2A is ubiquitin conjugating enzyme E2A, involved in post replication repair of UV-damaged DNA
• Role for UBE2A and HIST2H2BE ubiquitylation during the elongation cycle of transcription, suggesting a mechanism by which H3 methylation may be regulated (Xiao 2005)
• UBE2A catalyzes the covalent attachment of ubiquitin to other proteins
• UBE2A serves as the cognate E2-conjugating enzyme (Kim 2009)
• UBE2A is involved in transcription-coupled HIST2H2BE ubiquitylation and directly stimulates H3K4 methylation in human cells (Kim 2009)

Homology for human UBE2A (HHR6A)

• homolog to yeast RAD6 post replication repair epistatic group,A
• ortholog to S. cerevisiae RAD6/UBC2

Phenotype Information for UBE2A (HHR6A)

• Gene/Locus: UBE2A, RAD6A, MRXSN, MRXS30
• Phenotype: Mental retardation, X-linked syndromic, Nascimento-type

Phenotype Information for UBE2A (HHR6A) from OMIM (Online Mendelian Inheritance in Man)