Overview
| Uniprot ID | P49789 |
| Protein Name | Bis(5'-adenosyl)-triphosphatase |
| Gene Name | FHIT |
| Organism | Homo sapiens |
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 122 |
EELQKHDKEDFPASW |
Function
Possesses dinucleoside triphosphate hydrolase activity (PubMed:12574506, PubMed:15182206, PubMed:8794732, PubMed:9323207, PubMed:9543008, PubMed:9576908). Cleaves P(1)-P(3)-bis(5'-adenosyl) triphosphate (Ap3A) to yield AMP and ADP (PubMed:12574506, PubMed:15182206, PubMed:8794732, PubMed:9323207, PubMed:9543008, PubMed:9576908). Can also hydrolyze P(1)-P(4)-bis(5'-adenosyl) tetraphosphate (Ap4A), but has extremely low activity with ATP (PubMed:8794732). Exhibits adenylylsulfatase activity, hydrolyzing adenosine 5'-phosphosulfate to yield AMP and sulfate (PubMed:18694747). Exhibits adenosine 5'-monophosphoramidase activity, hydrolyzing purine nucleotide phosphoramidates with a single phosphate group such as adenosine 5'monophosphoramidate (AMP-NH2) to yield AMP and NH2 (PubMed:18694747). Exhibits adenylylsulfate-ammonia adenylyltransferase, catalyzing the ammonolysis of adenosine 5'-phosphosulfate resulting in the formation of adenosine 5'-phosphoramidate (PubMed:26181368). Also catalyzes the ammonolysis of adenosine 5-phosphorofluoridate and diadenosine triphosphate (PubMed:26181368). 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 (PubMed:18077326). Plays a role in the induction of apoptosis via SRC and AKT1 signaling pathways (PubMed:16407838). Inhibits MDM2-mediated proteasomal degradation of p53/TP53 and thereby plays a role in p53/TP53-mediated apoptosis (PubMed:15313915). 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 (PubMed:12574506, PubMed:19622739). Functions as a tumor suppressor (By similarity)
Protein Sequence
10
MSFRFGQHLI
20
KPSVVFLKTE
30
LSFALVNRKP
40
VVPGHVLVCP
50
LRPVERFHDL
60
RPDEVADLFQ
70
TTQRVGTVVE
80
KHFHGTSLTF
90
SMQDGPEAGQ
100
TVKHVHVHVL
110
PRKAGDFHRN
120
DSIYEELQKH
130
DKEDFPASWR
140
SEEEMAAEAA
ALRVYFQ
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0005737 |
cytoplasm |
| Cellular Component |
GO:0005829 |
cytosol |
| Cellular Component |
GO:0005739 |
mitochondrion |
| Cellular Component |
GO:0005634 |
nucleus |
| Cellular Component |
GO:0005886 |
plasma membrane |
| Molecular Function |
GO:0043530 |
adenosine 5'-monophosphoramidase activity |
| Molecular Function |
GO:0047627 |
adenylylsulfatase activity |
| Molecular Function |
GO:0047352 |
adenylylsulfate-ammonia adenylyltransferase activity |
| Molecular Function |
GO:0047710 |
bis(5'-adenosyl)-triphosphatase activity |
| Molecular Function |
GO:0042802 |
identical protein binding |
| Molecular Function |
GO:0000166 |
nucleotide binding |
| Molecular Function |
GO:0031625 |
ubiquitin protein ligase binding |
| Biological Process |
GO:0015964 |
diadenosine triphosphate catabolic process |
| Biological Process |
GO:0006351 |
DNA-templated transcription |
| Biological Process |
GO:0072332 |
intrinsic apoptotic signaling pathway by p53 class mediator |
| Biological Process |
GO:0032435 |
negative regulation of proteasomal ubiquitin-dependent protein catabolic process |
| Biological Process |
GO:0006163 |
purine nucleotide metabolic process |
Reference
[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.