Recombinant Mouse Bis (5′-adenosyl)-triphosphatase (Fhit)

Function

Possesses dinucleoside triphosphate hydrolase activity (By similarity). Cleaves P(1)-P(3)-bis(5'-adenosyl) triphosphate (Ap3A) to yield AMP and ADP (By similarity). Can also hydrolyze P(1)-P(4)-bis(5'-adenosyl) tetraphosphate (Ap4A), but has extremely low activity with ATP (By similarity). Exhibits adenylylsulfatase activity, hydrolyzing adenosine 5'-phosphosulfate to yield AMP and sulfate (By similarity). 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 (By similarity). Exhibits adenylylsulfate-ammonia adenylyltransferase, catalyzing the ammonolysis of adenosine 5'-phosphosulfate resulting in the formation of adenosine 5'-phosphoramidate (By similarity). Also catalyzes the ammonolysis of adenosine 5-phosphorofluoridate and diadenosine triphosphate (By similarity). 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 (By similarity). Plays a role in the induction of apoptosis via SRC and AKT1 signaling pathways (By similarity). Inhibits MDM2-mediated proteasomal degradation of p53/TP53 and thereby plays a role in p53/TP53-mediated apoptosis (By similarity). 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 (By similarity). Functions as a tumor suppressor (PubMed:10758156, PubMed:11517343)

Subcellular Location

Cytoplasm; Nucleus; Mitochondrion

Tissue Specificity

Expressed in heart, brain, lung and skeletal muscle. Particularly strong expression in liver, testis and kidney, where it is confined to the tubular epithelium

Subunit

Homodimer. Interacts with UBE2I. Interacts with MDM2. Interacts with CTNNB1. Identified in a complex with CTNNB1 and LEF1 (By similarity)

• Pekarsky Y. et al. The murine Fhit locus: isolation, characterization, and expression in normal and tumor cells. — Cancer Res. (1998)
• Glover T.W. et al. PubMed: CI-48TSMH859I2HN (MAR-)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Matsuyama A. et al. Fragile site orthologs FHIT/FRA3B and Fhit/Fra14A2: evolutionarily conserved but highly recombinogenic. — Proc. Natl. Acad. Sci. U.S.A. (2003)
• Pekarsky Y. et al. Nitrilase and Fhit homologs are encoded as fusion proteins in Drosophila melanogaster and Caenorhabditis elegans. — Proc. Natl. Acad. Sci. U.S.A. (1998)
• Fong L.Y. et al. Muir-Torre-like syndrome in Fhit-deficient mice. — Proc. Natl. Acad. Sci. U.S.A. (2000)
• Zanesi N. et al. The tumor spectrum in FHIT-deficient mice. — Proc. Natl. Acad. Sci. U.S.A. (2001)
• Huttlin E.L. et al. A tissue-specific atlas of mouse protein phosphorylation and expression. — Cell (2010)