Tchem FHIT Bis(5'-adenosyl)-triphosphatase

Protein Summary

Description

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. 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 Accession IDs

• P49789
• A2IAS9
• A2IAT0
• A2IAT6
• A8K1A9
• Q45QG9
• Q6IU12

Gene Name

• FHIT

Ensembl ID

• ENST00000468189
• ENSP00000417480
• ENSG00000189283
• ENST00000476844
• ENSP00000417557
• ENST00000492590
• ENSP00000418582

Symbol

• FRA3B
• AP3Aase

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
trait	1
disease	0.91
histone modification site profile	0.85
transcription factor binding site profile	0.8
phenotype	0.79

Protein Classes

DTO Classes

Bis(5'-adenosyl)-triphosphatase Enpp4

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 915.75   (req: < 5)

Gene RIFs: 270   (req: <= 3)

Antibodies: 545   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 915.75   (req: >= 5)

Gene RIFs: 270   (req: > 3)

Antibodies: 545   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 10

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 5

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0