UIMC1

Last updated
UIMC1
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases UIMC1 , RAP80, X2HRIP110, ubiquitin interaction motif containing 1
External IDs OMIM: 609433; MGI: 103185; HomoloGene: 9455; GeneCards: UIMC1; OMA:UIMC1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001199297
NM_001199298
NM_016290
NM_001317961

NM_001293660
NM_011307
NM_001359757
NM_001359758

RefSeq (protein)

NP_001186226
NP_001186227
NP_001304890
NP_057374

NP_001280589
NP_035437
NP_001346686
NP_001346687

Location (UCSC) Chr 5: 176.91 – 177.02 Mb Chr 13: 55.18 – 55.25 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

BRCA1-A complex subunit RAP80 is a protein that in humans is encoded by the UIMC1 gene. [5] [6]

Contents

Repair of DNA damage

RAP80, the protein product of the UIMC1 gene, is a core component of the deubiquitin complex BRCA1-A. [7] Other core components of the BRCA1-A complex are the BRCC36 protein (BRCC3 gene), BRE protein (BRE (gene)), and MERIT40 protein (BABAM1 gene). [7]

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). [7] The role of BRCA1-A complex 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 NHEJ in preference to HR.

Related Research Articles

<span class="mw-page-title-main">BRCA1</span> Gene known for its role in breast cancer

Breast cancer type 1 susceptibility protein is a protein that in humans is encoded by the BRCA1 gene. Orthologs are common in other vertebrate species, whereas invertebrate genomes may encode a more distantly related gene. BRCA1 is a human tumor suppressor gene and is responsible for repairing DNA.

<span class="mw-page-title-main">DNA repair</span> Cellular mechanism

DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA damage, resulting in tens of thousands of individual molecular lesions per cell per day. Many of these lesions cause structural damage to the DNA molecule and can alter or eliminate the cell's ability to transcribe the gene that the affected DNA encodes. Other lesions induce potentially harmful mutations in the cell's genome, which affect the survival of its daughter cells after it undergoes mitosis. As a consequence, the DNA repair process is constantly active as it responds to damage in the DNA structure. When normal repair processes fail, and when cellular apoptosis does not occur, irreparable DNA damage may occur. This can eventually lead to malignant tumors, or cancer as per the two-hit hypothesis.

<span class="mw-page-title-main">BRCA2</span> Gene known for its role in breast cancer

BRCA2 and BRCA2 are human genes and their protein products, respectively. The official symbol and the official name are maintained by the HUGO Gene Nomenclature Committee. One alternative symbol, FANCD1, recognizes its association with the FANC protein complex. Orthologs, styled Brca2 and Brca2, are common in other vertebrate species. BRCA2 is a human tumor suppressor gene, found in all humans; its protein, also called by the synonym breast cancer type 2 susceptibility protein, is responsible for repairing DNA.

<span class="mw-page-title-main">Non-homologous end joining</span> Pathway that repairs double-strand breaks in DNA

Non-homologous end joining (NHEJ) is a pathway that repairs double-strand breaks in DNA. It is called "non-homologous" because the break ends are directly ligated without the need for a homologous template, in contrast to homology directed repair (HDR), which requires a homologous sequence to guide repair. NHEJ is active in both non-dividing and proliferating cells, while HDR is not readily accessible in non-dividing cells. The term "non-homologous end joining" was coined in 1996 by Moore and Haber.

<span class="mw-page-title-main">Ataxia telangiectasia and Rad3 related</span> Protein kinase that detects DNA damage and halts cell division

Serine/threonine-protein kinase ATR, also known as ataxia telangiectasia and Rad3-related protein (ATR) or FRAP-related protein 1 (FRP1), is an enzyme that, in humans, is encoded by the ATR gene. It is a large kinase of about 301.66 kDa. ATR belongs to the phosphatidylinositol 3-kinase-related kinase protein family. ATR is activated in response to single strand breaks, and works with ATM to ensure genome integrity.

<span class="mw-page-title-main">CHEK2</span> Protein-coding gene in humans

CHEK2 is a tumor suppressor gene that encodes the protein CHK2, a serine-threonine kinase. CHK2 is involved in DNA repair, cell cycle arrest or apoptosis in response to DNA damage. Mutations to the CHEK2 gene have been linked to a wide range of cancers.

<span class="mw-page-title-main">BARD1</span> Protein-coding gene in the species Homo sapiens

BRCA1-associated RING domain protein 1 is a protein that in humans is encoded by the BARD1 gene. The human BARD1 protein is 777 amino acids long and contains a RING finger domain, four ankyrin repeats, and two tandem BRCT domains.

<span class="mw-page-title-main">NEDD8</span>

NEDD8 is a protein that in humans is encoded by the NEDD8 gene. This ubiquitin-like (UBL) protein becomes covalently conjugated to a limited number of cellular proteins, in a process called NEDDylation similar to ubiquitination. Human NEDD8 shares 60% amino acid sequence identity to ubiquitin. The primary known substrates of NEDD8 modification are the cullin subunits of cullin-based E3 ubiquitin ligases, which are active only when NEDDylated. Their NEDDylation is critical for the recruitment of E2 to the ligase complex, thus facilitating ubiquitin conjugation. NEDD8 modification has therefore been implicated in cell cycle progression and cytoskeletal regulation.

<span class="mw-page-title-main">TP53BP1</span> Protein-coding gene in the species Homo sapiens

Tumor suppressor p53-binding protein 1 also known as p53-binding protein 1 or 53BP1 is a protein that in humans is encoded by the TP53BP1 gene.

<span class="mw-page-title-main">Rad50</span> Protein-coding gene in the species Homo sapiens

DNA repair protein RAD50, also known as RAD50, is a protein that in humans is encoded by the RAD50 gene.

<span class="mw-page-title-main">FANCD2</span> Protein-coding gene in the species Homo sapiens

Fanconi anemia group D2 protein is a protein that in humans is encoded by the FANCD2 gene. The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ, FANCL, FANCM, FANCN and FANCO. Fanconi anemia proteins, including FANCD2, are an emerging therapeutic target in cancer

<span class="mw-page-title-main">APPBP1</span> Protein-coding gene in the species Homo sapiens

NEDD8-activating enzyme E1 regulatory subunit is a protein that in humans is encoded by the NAE1 gene.

<span class="mw-page-title-main">UBE2B</span> Protein-coding gene in the species Homo sapiens

Ubiquitin-conjugating enzyme E2 B is a protein that in humans is encoded by the UBE2B gene.

<span class="mw-page-title-main">FANCL</span> Protein-coding gene in the species Homo sapiens

E3 ubiquitin-protein ligase FANCL is an enzyme that in humans is encoded by the FANCL gene.

<span class="mw-page-title-main">SETMAR</span> Protein-coding gene in the species Homo sapiens

Histone-lysine N-methyltransferase SETMAR is an enzyme that in humans is encoded by the SETMAR gene.

<span class="mw-page-title-main">RNF8</span> Protein-coding gene in the species Homo sapiens

E3 ubiquitin-protein ligase RNF8 is an enzyme that in humans is encoded by the RNF8 gene. RNF8 has activity both in immune system functions and in DNA repair.

<span class="mw-page-title-main">BRE (gene)</span> Protein-coding gene in the species Homo sapiens

BRCA1-A complex subunit BRE is a protein that in humans is encoded by the BRE gene.

<span class="mw-page-title-main">BRCC3</span> Protein-coding gene in humans

Lys-63-specific deubiquitinase BRCC36 is an enzyme that in humans is encoded by the BRCC3 gene.

<span class="mw-page-title-main">BABAM1</span> Protein-coding gene in the species Homo sapiens

BRCA1-A complex subunit MERIT40 is a protein that in humans is encoded by the BABAM1 gene.

<span class="mw-page-title-main">Double-strand break repair model</span>

A double-strand break repair model refers to the various models of pathways that cells undertake to repair double strand-breaks (DSB). DSB repair is an important cellular process, as the accumulation of unrepaired DSB could lead to chromosomal rearrangements, tumorigenesis or even cell death. In human cells, there are two main DSB repair mechanisms: Homologous recombination (HR) and non-homologous end joining (NHEJ). HR relies on undamaged template DNA as reference to repair the DSB, resulting in the restoration of the original sequence. NHEJ modifies and ligates the damaged ends regardless of homology. In terms of DSB repair pathway choice, most mammalian cells appear to favor NHEJ rather than HR. This is because the employment of HR may lead to gene deletion or amplification in cells which contains repetitive sequences. In terms of repair models in the cell cycle, HR is only possible during the S and G2 phases, while NHEJ can occur throughout whole process. These repair pathways are all regulated by the overarching DNA damage response mechanism. Besides HR and NHEJ, there are also other repair models which exists in cells. Some are categorized under HR, such as synthesis-dependent strain annealing, break-induced replication, and single-strand annealing; while others are an entirely alternate repair model, namely, the pathway microhomology-mediated end joining (MMEJ).

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000087206 Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000025878 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. Yan Z, Kim YS, Jetten AM (Aug 2002). "RAP80, a novel nuclear protein that interacts with the retinoid-related testis-associated receptor". J Biol Chem. 277 (35): 32379–88. doi: 10.1074/jbc.M203475200 . PMID   12080054.
  6. "Entrez Gene: UIMC1 ubiquitin interaction motif containing 1".
  7. 1 2 3 Rabl J (October 2020). "BRCA1-A and BRISC: Multifunctional Molecular Machines for Ubiquitin Signaling". Biomolecules. 10 (11). doi: 10.3390/biom10111503 . PMC   7692841 . PMID   33142801.

Further reading