Names & Taxonomy
- Uniprot ID:
- P49789
- Entry Name:
- FHIT_HUMAN
- Status:
- reviewed
- Protein Names:
- Bis(5'-adenosyl)-triphosphatase (EC 3.6.1.29) (AP3A hydrolase) (AP3Aase) (Diadenosine 5',5'''-P1,P3-triphosphate hydrolase) (Dinucleosidetriphosphatase) (Fragile histidine triad protein)
- Gene Names:
- FHIT
- Gene Names Primary:
- FHIT
- Organism:
- Homo sapiens (Human)
Structure
- Length:
- 147
- Sequence:
- MSFRFGQHLIKPSVVFLKTELSFALVNRKPVVPGHVLVCPLRPVERFHDLRPDEVADLFQTTQRVGTVVEKHFHGTSLTFSMQDGPEAGQTVKHVHVHVLPRKAGDFHRNDSIYEELQKHDKEDFPASWRSEEEMAAEAAALRVYFQ
- Proteomes:
- UP000005640
Subcellular location
- Subcellular Location:
- Cytoplasm. Mitochondrion. Nucleus.
Function
- Function:
- 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.
- Catalytic Activity:
- P(1)-P(3)-bis(5'-adenosyl) triphosphate + H(2)O = ADP + AMP.
- Active Site:
- ACT_SITE 96 96 Tele-AMP-histidine intermediate.
- Gene Ontology Go:
- cytoplasm
cytosol
extracellular exosome
mitochondrion
nucleus
bis(5'-adenosyl)-triphosphatase activity
catalytic activity
hydrolase activity
identical protein binding
nucleotide binding
ubiquitin protein ligase binding
intrinsic apoptotic signaling pathway by p53 class mediator
negative regulation of proteasomal ubiquitin-dependent protein catabolic process
nucleotide metabolic process
purine nucleotide metabolic process
regulation of transcription, DNA-templated
transcription, DNA-templated - Gene Ontology Biological Process:
- intrinsic apoptotic signaling pathway by p53 class mediator
negative regulation of proteasomal ubiquitin-dependent protein catabolic process
nucleotide metabolic process
purine nucleotide metabolic process
regulation of transcription, DNA-templated
transcription, DNA-templated - Gene Ontology Molecular Function:
- bis(5'-adenosyl)-triphosphatase activity
catalytic activity
hydrolase activity
identical protein binding
nucleotide binding
ubiquitin protein ligase binding - Gene Ontology Cellular Component:
- cytoplasm
cytosol
extracellular exosome
mitochondrion
nucleus - Keywords:
- 3D-structure
Apoptosis
Chromosomal rearrangement
Complete proteome
Cytoplasm
Hydrolase
Manganese
Mitochondrion
Nucleotide-binding
Nucleus
Phosphoprotein
Reference proteome
Transcription
Transcription regulation
Tumor suppressor - Interacts With:
- Itself; P22570; P10809; P61604