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FLASH GENE

Symbol

TP53BP2

contributors: mct - updated : 27-03-2013

HGNC name	tumor protein p53 binding protein, 2
HGNC id	12000

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	1q41      Physical location : 223.967.595 - 224.033.674
Synonym name	BCL2-binding protein, apoptosis-stimulating protein of p53, 2
	NY-REN-51 antigen
	BCL2-binding protein
	tumor suppressor p53-binding protein 2
Synonym symbol(s)	PPP1R13A, ASPP2, 53BP2, BBP

DNA

TYPE	functioning gene
STRUCTURE	65.08 kb     18 Exon(s)

Genomic sequence alignment details
10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed - - - 4500 - 105 - 2013 2324830 NM_001031685 18 - 4670 NP_001026855 - 1134 - 2013 2324830 53BP2L NM_005426 19 - 4802 NP_005417 - 1005 - 2013 2324830 BBP (also known as 53BP2S) an alternatively spliced ASPP2 isoform lacking the N terminus, and defective in binding Ras-GTP and stimulating Raf/MEK/ERK signaling

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive esophagus       highly Endocrine parathyroid       highly Nervous brain       highly

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N-terminal beta-GRASP ubiquitin-like fold suggesting a possible role in binding to other proteins in the apoptotic response network and thus mediating their selective pro-apoptotic functiona proline-rich sequence,
	a small G protein Ras-association domain
	the ASPP2 N terminus
	a proline-rich domain
	C terminus containing four ankyrin (Ank) repeats and a SH3 domain, which mediate its interactions with numerous partner proteins such as TP53, NFB, and BCL2, important for promoting TP53-dependent apoptosis

HOMOLOGY

interspecies	homolog to murine Tp53bp2
	homolog to C.elegans F11E6.7

intraspecies

homolog to PPP1R12a

Homologene

FAMILY

apoptosis stimulating proteins of p53 (ASPP) family

CATEGORY

adaptor , regulatory , signaling

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,cytosolic,granule
	intracellular,cytoplasm,cytosolic,vesicle
	intracellular,nucleus
text	localizes to the cytoplasm and plasma membrane to mediate extranuclear functions

basic FUNCTION	enhancing p53-induced apoptosis, the DNA binding and transactivation function of TP53
	impeding cell cycle progression at G2/M (cell cycle control)
	playing a role in TP53-related signal transduction pathways
	regulating the tumor suppression function of TP53
	SH3/SH2 adaptor protein
	haploinsufficient tumor suppressor that shares overlapping function with TP53 in tumor suppression
	induces apoptosis by inhibiting functional sites of the antiapoptotic BCL2 proteins
	specifically stimulates the apoptotic response mediated by the tumor suppressor TP53, by enhancing the transactivation function of TP53 on promoters of proapoptotic genes
	having ability to regulate the apoptotic function of TP53 and its family members, TP63 and TP73
	regulates epithelial cell polarity in cooperation with PARD3 to form an active PAR complex
	mediates HRAS-induced senescence and inhibits autophagy
	having tumor suppressor function via direct interaction with Ras-GTP to stimulate Ras-induced senescence in nontransformed human cells
	is an important component of Ras-induced senescence, expanding on the complexity of TP53BP2 tumor suppressor function
	implicated in control of cell adhesion and polarity through its effect on the PAR complex
	implicated in control of cell adhesion and polarity through its effect on the PAR complex
	ability of TP53BP2 to maintain cellular polarity is vital to CNS development, suggesting that the identified STAT1/TP53BP2 pathway may connect tumor suppression and cell polarity to neuroinflammation

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

signal transduction

a component

TP53BP2–Bcl complex may maintain the balance between the pro- and antiapoptotic activity of both proteins

INTERACTION

DNA

RNA

small molecule

protein	binding directly to p53, p63 and p73 (to central region of wild type TP53)
	BCL2, P65RelA, APCL
	transcriptional targets of E2F1 (provides another mechanism by which E2F cooperates with TP53 to induce apoptosis)
	facilitates the interaction between TAZ and PPP1CA to promote TAZ dephosphorylation
	modulates oncogenic HRAS-induced autophagic activity to dictate the cellular response to HRAS: to proliferate or senescence
	binds to RAS GTP, at the plasma membrane and stimulates RAS-induced signaling and pERK1/2 levels via promoting RAS GTP loading
	interacts with activated GTP-bound Ras independent of TP53
	SIAH2 controls TP53BP2 availability, with concomitant effect on epithelial cell polarity, and is involved in regulation of tight junction (TJ) integrity and cell polarity under hypoxia, through its regulation of TP53BP2 stability

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   by hypermethylation of the 5'-untranslated region in cancer cell lines retaining wild-type TP53 tumoral     --low   frequently downregulated in breast carcinoma expressing wild--type TP53

Susceptibility

to gastric cancer

Variant & Polymorphism other	variant increasing the risk of gastric cancer

Candidate gene	important potential target for the development of anticancer drugs that will stimulate apoptosis by interfering with its regulation; the TP53BP2–BCL2 interaction at the molecular and cellular levels could serve as a basis for such novel anticancer drug leads
Marker
Therapy target	target for cancer therapy

ANIMAL & CELL MODELS