General Information of Target

Target ID LDTP04308
Target Name Bis(5'-adenosyl)-triphosphatase (FHIT)
Gene Name FHIT
Gene ID 2272
Synonyms
Bis(5'-adenosyl)-triphosphatase; EC 3.6.1.29; AP3A hydrolase; AP3Aase; Adenosine 5'-monophosphoramidase FHIT; EC 3.9.1.-; Adenylylsulfatase; EC 3.6.2.1; Adenylylsulfate-ammonia adenylyltransferase; EC 2.7.7.51; Diadenosine 5',5'''-P1,P3-triphosphate hydrolase; Dinucleosidetriphosphatase; Fragile histidine triad protein
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MSFRFGQHLIKPSVVFLKTELSFALVNRKPVVPGHVLVCPLRPVERFHDLRPDEVADLFQ
TTQRVGTVVEKHFHGTSLTFSMQDGPEAGQTVKHVHVHVLPRKAGDFHRNDSIYEELQKH
DKEDFPASWRSEEEMAAEAAALRVYFQ
Target Type
Successful
Target Bioclass
Enzyme
Subcellular location
Cytoplasm
Function
Possesses dinucleoside triphosphate hydrolase activity . 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. Exhibits adenylylsulfatase activity, hydrolyzing adenosine 5'-phosphosulfate to yield AMP and sulfate. 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. Exhibits adenylylsulfate-ammonia adenylyltransferase, catalyzing the ammonolysis of adenosine 5'-phosphosulfate resulting in the formation of adenosine 5'-phosphoramidate. Also catalyzes the ammonolysis of adenosine 5-phosphorofluoridate and diadenosine triphosphate. 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 a tumor suppressor.
TTD ID
T59720
Uniprot ID
P49789
DrugMap ID
TTMS54D
Ensemble ID
ENST00000468189.5
HGNC ID
HGNC:3701
ChEMBL ID
CHEMBL1795151

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 2 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
DBIA
 Probe Info 
C39(1.48)  LDD3370  [1]
HHS-475
 Probe Info 
Y114(2.23)  LDD0264  [2]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0116  HHS-0101 DM93 Y114(2.23)  LDD0264  [2]
 LDCM0117  HHS-0201 DM93 Y114(0.57)  LDD0265  [2]
 LDCM0118  HHS-0301 DM93 Y114(0.96)  LDD0266  [2]
 LDCM0119  HHS-0401 DM93 Y114(0.07)  LDD0267  [2]
 LDCM0120  HHS-0701 DM93 Y114(2.00)  LDD0268  [2]
 LDCM0022  KB02 A2058 C39(1.66)  LDD2253  [1]
 LDCM0023  KB03 A2058 C39(2.01)  LDD2670  [1]
 LDCM0024  KB05 OCI-AML-2 C39(1.48)  LDD3370  [1]

References

1 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840
2 Discovery of a Cell-Active SuTEx Ligand of Prostaglandin Reductase 2. Chembiochem. 2021 Jun 15;22(12):2134-2139. doi: 10.1002/cbic.202000879. Epub 2021 Apr 29.