FHIT

Gene Information

Official Symbol: FHIT
Official Name: fragile histidine triad diadenosine triphosphatase
Aliases and Previous Symbols: N/A
Entrez ID: 2272
UniProt: P49789
Interactions: BioGRID
PubMed articles: Open PubMed
OMIM: Open OMIM

Function Summary

Entrez Summary: The protein encoded by this gene is a P1-P3-bis(5'-adenosyl) triphosphate hydrolase involved in purine metabolism. This gene encompasses the common fragile site FRA3B on chromosome 3, where carcinogen-induced damage can lead to translocations and aberrant transcripts. In fact, aberrant transcripts from this gene have been found in about half of all esophageal, stomach, and colon carcinomas. The encoded protein is also a tumor suppressor, as loss of its activity results in replication stress and DNA damage. [provided by RefSeq, Aug 2017].
UniProt Summary: Cleaves P(1)-P(3)-bis(5'-adenosyl) triphosphate (Ap3A) to yield AMP and ADP. Can also hydrolyze P(1)-P(4)-bis(5'- adenosyl) tetraphosphate (Ap4A), but has extremely low activity with ATP. Modulates transcriptional activation by CTNNB1 and thereby contributes to regulate the expression of genes essential for cell proliferation and survival, such as CCND1 and BIRC5. Plays a role in the induction of apoptosis via SRC and AKT1 signaling pathways. Inhibits MDM2-mediated proteasomal degradation of p53/TP53 and thereby plays a role in p53/TP53-mediated apoptosis. Induction of apoptosis depends on the ability of FHIT to bind P(1)-P(3)-bis(5'-adenosyl) triphosphate or related compounds, but does not require its catalytic activity, it may in part come from the mitochondrial form, which sensitizes the low- affinity Ca(2+) transporters, enhancing mitochondrial calcium uptake. Functions as tumor suppressor. {ECO:0000269|PubMed:12574506, ECO:0000269|PubMed:15313915, ECO:0000269|PubMed:16407838, ECO:0000269|PubMed:18077326, ECO:0000269|PubMed:19622739, ECO:0000269|PubMed:8794732, ECO:0000269|PubMed:9323207}.

Pfam Domains GO Terms

CRISPR Data

Compound Hit Most Correlated Genes in Chemogenomics Tissues where Essential in the Avana Dataset (DepMap 20Q1)

Global Fraction of Cell Lines Where Essential: 0/739

Tissue	Fraction Of Cell Lines Where Essential
1290807.0	0/1
909776.0	0/1
bile duct	0/28
blood	0/28
bone	0/26
breast	0/33
central nervous system	0/56
cervix	0/4
colorectal	0/17
esophagus	0/13
fibroblast	0/1
gastric	0/16
kidney	0/21
liver	0/20
lung	0/75
lymphocyte	0/16
ovary	0/26
pancreas	0/24
peripheral nervous system	0/16
plasma cell	0/15
prostate	0/1
skin	0/24
soft tissue	0/9
thyroid	0/2
upper aerodigestive	0/22
urinary tract	0/29
uterus	0/5

Essentiality in NALM6

Essentiality Rank: 8998
Expression level (log2 read counts): 1.97

Expression Distribution

DcpS C
HIT

bis(5-adenosyl)-triphosphatase activity
negative regulation of proteasomal ubiquitin-dependent protein catabolic process
catalytic activity
negative regulation of ubiquitin-dependent protein catabolic process
intrinsic apoptotic signaling pathway by p53 class mediator
negative regulation of proteasomal protein catabolic process
nucleotide binding
negative regulation of proteolysis involved in cellular protein catabolic process
hydrolase activity
negative regulation of cellular protein catabolic process
signal transduction by p53 class mediator
regulation of proteasomal ubiquitin-dependent protein catabolic process
fibrillar center
negative regulation of protein catabolic process
intrinsic apoptotic signaling pathway
regulation of ubiquitin-dependent protein catabolic process
regulation of proteasomal protein catabolic process
regulation of proteolysis involved in cellular protein catabolic process
regulation of cellular protein catabolic process
negative regulation of cellular catabolic process
apoptotic signaling pathway
ubiquitin protein ligase binding
negative regulation of catabolic process
purine nucleotide metabolic process
negative regulation of proteolysis
purine-containing compound metabolic process
regulation of protein catabolic process
nucleotide metabolic process
nucleoside phosphate metabolic process
nucleobase-containing small molecule metabolic process
regulation of proteolysis
regulation of cellular catabolic process
organophosphate metabolic process
apoptotic process
regulation of catabolic process
negative regulation of cellular protein metabolic process
programmed cell death
identical protein binding
cell death
negative regulation of protein metabolic process