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lördag 15 juni 2019

BRCC36 (Xq28) , JAMM alaryhmän deubikitinaasi , uusia solusyklin säätelijöitä

 https://www.ncbi.nlm.nih.gov/gene/79184
Official Symbol   BRCC3
Official Full Name  BRCA1/BRCA2-containing complex subunit 3.
Gene type  protein coding
Also known as  C6.1A; BRCC36; CXorf53
Summary: This gene encodes a subunit of the BRCA1-BRCA2-containing complex (BRCC), which is an E3 ubiquitin ligase. This complex plays a role in the DNA damage response, where it is responsible for the stable accumulation of BRCA1 at DNA break sites. The component encoded by this gene can specifically cleave Lys 63-linked polyubiquitin chains, and it regulates the abundance of these polyubiquitin chains in chromatin. The loss of this gene results in abnormal angiogenesis and is associated with syndromic moyamoya, a cerebrovascular angiopathy. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 5. [provided by RefSeq, Jun 2011]
Expression Ubiquitous expression in colon (RPKM 4.9), esophagus (RPKM 3.5) and 25 other tissues See more Orthologs mouse all
 
Preferred Names
lys-63-specific deubiquitinase BRCC36
Names
BRCA1-A complex subunit BRCC36
BRCA1/BRCA2-containing complex subunit 36
BRISC complex subunit BRCC36
https://www.ncbi.nlm.nih.gov/protein/NP_001018065.1
lys-63-specific deubiquitinase BRCC36 isoform 2 [Homo sapiens]
NCBI Reference Sequence: NP_001018065.1
 
Conserved Domains (1) summary
cd08068
Location:13267
MPN_BRCC36; Mov34/MPN/PAD-1 family:
BRCC36, a subunit of BRCA1-A complex
BRCC36 (BRCA1-A complex subunit BRCC36; 
BRCA1/BRCA2-containing complex subunit 36; BRCA1/BRCA2-containing complex subunit 3; BRCC3; BRISC complex subunit BRCC36; BRCC36 isopeptidase complex; Lys-63-specific deubiquitinase BRCC36) and BRCC36-like domains are members of JAMM/MPN+ deubiquitinases (DUBs), possibly with Zn2+-dependent ubiquitin isopeptidase activity. BRCC36 is part of the BRCA1/BRCA2/BARD1-containing nuclear complex that displays an E3 ubiquitin ligase activity. It is targeted to DNA damage foci after irradiation; RAP80 recruits the Abraxas-BRCC36-BRCA1-BARD1 complex to DNA double strand breaks (DSBs) for DNA repair through specific recognition of Lys 63-linked polyubiquitinated proteins by its tandem ubiquitin-interacting motifs. A new protein, MERIT40 (mediator of RAP80 interactions and targeting 40 kDa), also named NBA1 (new component of the BRCA1 A complex), exists in the same BRCA1-containing complex and is essential for the integrity of the complex. There are studies suggesting that MERIT40/NBA1 ties BRCA1 complex integrity, DSB recognition, and ubiquitin chain activities to the DNA damage response. It has also been shown that BRCA1-containing complex resembles the lid complex of the 26S proteasome.
Region          13..267
                     /region_name="MPN_BRCC36"
                     /note="Mov34/MPN/PAD-1 family: BRCC36, a subunit of
                     BRCA1-A complex; cd08068"
                     /db_xref="CDD:163699"
     Site            order(33,122,124,132,135)
                     /site_type="other"
                     /note="MPN+ (JAMM) motif"  
                     /db_xref="CDD:163699"
     Site            order(122,124,135)
                     /site_type="other"
                     /note="Zinc-binding site [ion binding]"
                     /db_xref="CDD:163699"
ORIGIN      
        1 mavqvvqavq avhlesdafl vclnhalste keevmglcig elnddtrsds kfaytgtemr
       61 tvaekvdavr ivhihsviil rrsdkrkdrv eispeqlsaa steaerlael tgrpmrvvgw
      121 yHsHphitvw pshvDvrtqa myqmmdqgfv glifscfied kntktgrvly tcfqsiqaqk
      181 sseyerieip ihivphvtig kvclesavel pkilcqeeqd ayrrihslth ldsvtkihng
      241 svftknlcsq msavsgpllq wledrleqnq qhlqelqqek eelmqelssl e
//
Kommenttini: JAMM motiivista mainitaan jakso 1 ehhsd 
johon sinkki asettuu . Kirjoitin  isoilla kirjaimilla
 sinkkikohdan e- x(88)-H-x-H-x(7)-s-x(2)-D  
Related articles in PubMed
GeneRIFs: Gene References Into Functions


"BRCC36 is a Key Player in Cellular Responses to DSBs
BRCC36, which belongs to the JAMM (JAB1/MPN/Mov34 metallo-enzyme) family of DUBs, is a lysine 63-ubiquitin (K63-Ub)-specific DUB and a member of two protein complexes: the DNA damage-responsive BRCA1–RAP80 complex, and the cytoplasmic BRCC36 isopeptidase complex (BRISC).
BRCC36 was initially isolated from a multi-protein complex containing the HR-promoting factors BRCA1, BRCA2 and Rad51 [145].

The interaction of the BRCA1 BRCT domain with RAP80, a ubiquitin-binding protein, targets a complex containing the BRCA1–BARD1 (BRCA1-associated ring domain protein 1) E3 ligase and BRCC36 to MDC1–γH2AX-dependent lysine(6)- and lysine(63)-linked ubiquitin polymers at sites of DSBs [147].
Interestingly, it appears that concomitant and opposing RNF8–Ubc13 ubiquitin ligase and RAP80–BRCC36 ubiquitin hydrolysis activities are responsible for determining steady-state ubiquitin levels at DSB sites [148, 149].
Recent discoveries have shed some light on the mode-of-action of the BCC36-containing complex. Thus, in striking contrast to other BRCA1-containing complexes that are known to promote homology-directed repair, the BRCA1–RAP80 complex restricts DNA end resection in S/G2 phase of the cell cycle, thereby limiting HR.
Consequently, RAP80 or BRCC36 deficiency was found to result in elevated MRE11–CtIP-dependent 5′ DNA end resection with a concomitant increase in HR mechanisms that rely on 3′ single-stranded overhangs. In this way, the BRCA1–RAP80 complex limits nuclease activities at DSB sites, preventing excessive end resection and potentially deleterious homology-directed DSB repair mechanisms that can impair genome integrity [150].
Notably, the human BRCC36 gene is located at the Xq28 locus, a chromosomal break-point in patients with prolymphocytic T cell leukaemia [151].
 Furthermore, BRCC36 is aberrantly expressed in the majority of breast tumours, indicating a potential role in the pathogenesis of this disease [145].
 Taking these findings together, BRCC36 is clearly a key player in controlling cellular DSB responses through regulating the ubiquitylation status of repair factors at DNA damage sites."

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