BRCC3

Lys-63-specific deubiquitinase BRCC36 is an enzyme that in humans is encoded by the BRCC3 gene.[5][6][7]

BRCC3
Identifiers
AliasesBRCC3, BRCC36, C6.1A, CXorf53, BRCA1/BRCA2-containing complex subunit 3
External IDsOMIM: 300617 MGI: 2389572 HomoloGene: 11530 GeneCards: BRCC3
Orthologs
SpeciesHumanMouse
Entrez

79184

210766

Ensembl

ENSG00000185515

ENSMUSG00000031201

UniProt

P46736

P46737

RefSeq (mRNA)

NM_001018055
NM_001242640
NM_024332

NM_001166457
NM_001166459
NM_145956
NM_001358736
NM_001358737

RefSeq (protein)

NP_001018065
NP_001229569
NP_077308

NP_001159929
NP_001159931
NP_666068
NP_001345665
NP_001345666

Location (UCSC)Chr X: 155.07 – 155.12 MbChr X: 74.46 – 74.5 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Function

This gene encodes a subunit of the BRCA1-BRCA2-containing complex (BRCC), which is an E3 ubiquitin ligase. This protein is also thought to be involved in the cellular response to ionizing radiation and progression through the G2/M checkpoint. Alternative splicing results in multiple transcript variants.[7]

Repair of DNA damage

BRCC36, the protein product of the BRCC3 gene, is a deubiquitinating enzyme and a core component of the deubiquitin complex BRCA1-A.[8] BRCA1, as distinct from BRCA1-A, is employed in the repair of chromosomal damage with an important role in the error-free homologous recombinational (HR) repair of DNA double-strand breaks. Sequestration of BRCA1 away from the DNA damage site suppresses homologous recombination and redirects the cell in the direction of repair by the process of non-homologous end joining (NHEJ).[8] The role of BRCA1-A appears to be to bind BRCA1 with high affinity and withdraw it away from the site of DNA damage to the periphery where it remains sequestered, thus promoting DNA repair by NHEJ in preference to HR.

Interactions

BRCC3 has been shown to interact with BRE,[6][9] BRCA2,[6] RAD51,[6] BRCA1,[6] P53[6] and BARD1.[6]

References

  1. GRCh38: Ensembl release 89: ENSG00000185515 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000031201 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Kenwrick S, Levinson B, Taylor S, Shapiro A, Gitschier J (Jun 1992). "Isolation and sequence of two genes associated with a CpG island 5' of the factor VIII gene". Human Molecular Genetics. 1 (3): 179–86. doi:10.1093/hmg/1.3.179. PMID 1303175.
  6. Dong Y, Hakimi MA, Chen X, Kumaraswamy E, Cooch NS, Godwin AK, Shiekhattar R (Nov 2003). "Regulation of BRCC, a holoenzyme complex containing BRCA1 and BRCA2, by a signalosome-like subunit and its role in DNA repair". Molecular Cell. 12 (5): 1087–99. doi:10.1016/S1097-2765(03)00424-6. PMID 14636569.
  7. "Entrez Gene: BRCC3 BRCA1/BRCA2-containing complex, subunit 3".
  8. Rabl, J. (2020). "BRCA1-A and BRISC: Multifunctional Molecular Machines for Ubiquitin Signaling". Biomolecules. 10 (11): 1503. doi:10.3390/biom10111503. PMC 7692841. PMID 33142801.
  9. Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.

Further reading


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