Bis(5'-adenosyl)-triphosphatase

NameBis(5'-adenosyl)-triphosphatase
Synonyms
  • 3.6.1.29
  • AP3A hydrolase
  • AP3Aase
  • Diadenosine 5',5'''-P1,P3-triphosphate hydrolase
  • Dinucleosidetriphosphatase
  • Fragile histidine triad protein
Gene NameFHIT
OrganismHuman
Amino acid sequence
>lcl|BSEQ0020560|Bis(5'-adenosyl)-triphosphatase
MSFRFGQHLIKPSVVFLKTELSFALVNRKPVVPGHVLVCPLRPVERFHDLRPDEVADLFQ
TTQRVGTVVEKHFHGTSLTFSMQDGPEAGQTVKHVHVHVLPRKAGDFHRNDSIYEELQKH
DKEDFPASWRSEEEMAAEAAALRVYFQ
Number of residues147
Molecular Weight16858.11
Theoretical pI7.09
GO Classification
Functions
  • identical protein binding
  • ubiquitin protein ligase binding
  • catalytic activity
  • bis(5'-adenosyl)-triphosphatase activity
  • hydrolase activity
  • nucleotide binding
Processes
  • DNA replication
  • regulation of transcription, DNA-templated
  • transcription, DNA-templated
  • negative regulation of proteasomal ubiquitin-dependent protein catabolic process
  • nucleotide metabolic process
  • purine nucleotide metabolic process
  • intrinsic apoptotic signaling pathway by p53 class mediator
Components
  • mitochondrion
  • nucleus
  • cytosol
  • extracellular exosome
  • cytoplasm
General FunctionUbiquitin protein ligase binding
Specific FunctionCleaves 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.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID1203836
UniProtKB IDP49789
UniProtKB Entry NameFHIT_HUMAN
Cellular LocationCytoplasm
Gene sequence
>lcl|BSEQ0020561|Bis(5'-adenosyl)-triphosphatase (FHIT)
ATGTCGTTCAGATTTGGCCAACATCTCATCAAGCCCTCTGTAGTGTTTCTCAAAACAGAA
CTGTCCTTCGCTCTTGTGAATAGGAAACCTGTGGTACCAGGACATGTCCTTGTGTGCCCG
CTGCGGCCAGTGGAGCGCTTCCATGACCTGCGTCCTGATGAAGTGGCCGATTTGTTTCAG
ACGACCCAGAGAGTCGGGACAGTGGTGGAAAAACATTTCCATGGGACCTCTCTCACCTTT
TCCATGCAGGATGGCCCCGAAGCCGGACAGACTGTGAAGCACGTTCACGTCCATGTTCTT
CCCAGGAAGGCTGGAGACTTTCACAGGAATGACAGCATCTATGAGGAGCTCCAGAAACAT
GACAAGGAGGACTTTCCTGCCTCTTGGAGATCAGAGGAGGAAATGGCAGCAGAAGCCGCA
GCTCTGCGGGTCTACTTTCAGTGA
GenBank Gene IDU46922
GeneCard IDNot Available
GenAtlas IDFHIT
HGNC IDHGNC:3701
Chromosome Location3
Locus3p14.2
References
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  2. Druck T, Hadaczek P, Fu TB, Ohta M, Siprashvili Z, Baffa R, Negrini M, Kastury K, Veronese ML, Rosen D, Rothstein J, McCue P, Cotticelli MG, Inoue H, Croce CM, Huebner K: Structure and expression of the human FHIT gene in normal and tumor cells. Cancer Res. 1997 Feb 1;57(3):504-12. 9012482
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  7. Gemmill RM, West JD, Boldog F, Tanaka N, Robinson LJ, Smith DI, Li F, Drabkin HA: The hereditary renal cell carcinoma 3;8 translocation fuses FHIT to a patched-related gene, TRC8. Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9572-7. 9689122
  8. Shi Y, Zou M, Farid NR, Paterson MC: Association of FHIT (fragile histidine triad), a candidate tumour suppressor gene, with the ubiquitin-conjugating enzyme hUBC9. Biochem J. 2000 Dec 1;352 Pt 2:443-8. 11085938
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