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apoptosis-stimulating of p53 protein 2; tumor suppressor p53-binding protein 2; p53-binding protein 2; p53BP2; 53BP2; Bcl2-binding protein; Bbp; renal carcinoma antigen NY-REN-51 (TP53BP2, ASPP2, BBP)
Function:
- plays a role in regulation of apoptosis & cell growth
- regulates TP53 by enhancing DNA binding & transactivation of TP53 on promoters of proapoptotic genes in vivo
- inhibits ability of APPBP1 to conjugate NEDD8 to CUL1, & thus decreases APPBP1 ability to induce apoptosis
- impedes cell cycle progression at G2/M
- binds to the central domain of TP53 as well as to BCL2
- interacts with protein phosphatase 1
- interacts with RELA NF-kappa-B subunit; this interaction probably prevents activation of apoptosis, possibly by preventing its interaction with TP53
- interacts with APC2 & APPBP1
Structure:
- the ankyrin repeats & the SH3 domain are required for a specific interactions with TP53
- belongs to the ASPP family
- contains 2 ANK repeats
- contains 1 SH3 domain
Compartment:
- cytoplasm, perinuclear region. nucleus
- predominantly found in the perinuclear region
- some small fraction is nuclear
Alternative splicing:
- named isoforms=2
- due to Alu sequence insertion that creates a shorter but existing form that may have an alternative function
Expression:
- widely expressed
- expressed in spleen, thymus, prostate, testis, ovary, small intestine, colon & peripheral blood leukocyte
- reduced expression in breast carcinomas expressing a wild-type TP53 protein
- overexpressed in lung cancer cell lines
- expressed following DNA damage induced by UV irradiation
- down-regulated by wild-type, but not mutant, TP53
Interactions
molecular events
General
ankyrin repeat domain protein (ANKRD)
apoptosis stimulating protein of p53; p53-binding protein (ASPP)
Properties
SIZE: entity length = 1128 aa
MW = 126 kD
COMPARTMENT: cytoplasm
cell nucleus
MOTIF: glutamine-rich region {132-173}
MOTIF: glutamine residue (SEVERAL)
APPBP1 interaction {332-348}
Ser phosphorylation site {S480}
Ser phosphorylation site {S556}
Ser phosphorylation site {S569}
Ser phosphorylation site {S698}
proline-rich region
SITE: 824-902
MOTIF: proline residue (SEVERAL)
SH3-binding site
NAME: SH3-binding site
SITE: 866-875
Mediates interaction with APC2 {876-1128}
MOTIF: ankyrin repeat
NAME: ankyrin repeat
SITE: 958-990
ankyrin repeat
NAME: ankyrin repeat
SITE: 991-1023
src homology 3 [SH3] domain
SITE: 1057-1119
Database Correlations
OMIM 602143
UniProt Q13625
PFAM correlations
Entrez Gene 7159
Kegg hsa:7159
References
- UniProt :accession Q13625
- Samuels-Lev Y et al.
ASPP proteins specifically stimulate the apoptotic function of p53.
Molecular Cell 8:781-94. 2001
PMID: 11684014
- Entrez Gene :accession 7159
Component-of
molecular complex