FHIT

Bis(5'-adenosyl)-triphosphatase also known as fragile histidine triad protein (FHIT) is an enzyme that in humans is encoded by the FHIT gene.[5][6]

FHIT
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1FHI, 2FHI, 2FIT, 5FIT, 3FIT, 1FIT, 4FIT, 6FIT
Identifiers
Aliases	FHIT, AP3Aase, FRA3B, fragile histidine triad, tríada histidina fràgil, fragile histidine triad diadenosine triphosphatase
External IDs	OMIM: 601153 MGI: 1277947 HomoloGene: 21661 GeneCards: FHIT
Gene location (Human) Chr. Chromosome 3 (human)[1] Band 3p14.2 Start 59,747,277 bp[1] End 61,251,459 bp[1]
Gene location (Mouse) Chr. Chromosome 14 (mouse)[2] Band 14 A1|14 5.61 cM Start 9,550,092 bp[2] End 11,162,035 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • bis(5'-adenosyl)-triphosphatase activity • nucleotide binding • catalytic activity • hydrolase activity • GO:0001948 protein binding • ubiquitin protein ligase binding • identical protein binding Cellular component • cytoplasm • cytosol • mitochondrion • cell nucleus • fibrillar center • cell membrane Biological process • negative regulation of proteasomal ubiquitin-dependent protein catabolic process • purine nucleotide metabolic process • regulation of transcription, DNA-templated • nucleotide metabolic process • transcription, DNA-templated • intrinsic apoptotic signaling pathway by p53 class mediator • apoptotic process Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	2272	14198
Ensembl	ENSG00000189283	ENSMUSG00000060579
UniProt	P49789	O89106
RefSeq (mRNA)	NM_001166243 NM_002012 NM_001320899 NM_001320900 NM_001320901 NM_001354589 NM_001354590	NM_010210 NM_001308285 NM_001308286 NM_001360141
RefSeq (protein)	NP_001159715 NP_001307828 NP_001307829 NP_001307830 NP_002003 NP_001341518 NP_001341519	NP_001295214 NP_001295215 NP_034340 NP_001347070
Location (UCSC)	Chr 3: 59.75 – 61.25 Mb	Chr 14: 9.55 – 11.16 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

FHIT is also known as human accelerated region 10. It may, therefore, have played a key role in differentiating humans from apes.[7]

This gene, a member of the histidine triad gene family, encodes a diadenosine P1,P3-bis(5'-adenosyl)-triphosphate adenylohydrolase involved in purine metabolism. The gene encompasses the common fragile site FRA3B on chromosome 3, where carcinogen-induced damage can lead to translocations and aberrant transcripts of this gene. In fact, aberrant transcripts from this gene have been found in about half of all esophageal, stomach, and colon carcinomas.[8]

Though the exact molecular function of FHIT is still partially unclear, the gene works as a tumor suppressor as it has been demonstrated in animal studies.[9][10][11] Furthermore FHIT has been shown to synergize with VHL, another tumor suppressor, in protecting against chemically - induced lung cancer.[12]

FHIT also acts as a tumor suppressor of HER2/neu driven breast cancer.[13]

Interactions

FHIT has been shown to interact with UBE2I.[14]

References

1. GRCh38: Ensembl release 89: ENSG00000189283 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000060579 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Ohta MH, Cotticelli MG, Kastury K, Baffa R, Palazzo J, Siprashvili Z, Mori M, McCue P, Druck T, Croce CM, Huebner K (Apr 1996). "The FHIT gene, spanning the chromosome 3p14.2 fragile site and renal carcinoma-associated t(3;8) breakpoint, is abnormal in digestive tract cancers". Cell. 84 (4): 587–97. doi:10.1016/S0092-8674(00)81034-X. PMID 8598045. S2CID 18792069.
6. Pekarsky Y, Campiglio M, Siprashvili Z, Druck T, Sedkov Y, Tillib S, Draganescu A, Wermuth P, Rothman JH, Huebner K, Buchberg AM, Mazo A, Brenner C, Croce CM (Aug 1998). "Nitrilase and Fhit homologs are encoded as fusion proteins in Drosophila melanogaster and Caenorhabditis elegans". Proc. Natl. Acad. Sci. U.S.A. 95 (15): 8744–9. doi:10.1073/pnas.95.15.8744. PMC 21147. PMID 9671749.
7. Pollard KS, Salama SR, Lambert N, Lambot MA, Coppens S, Pedersen JS, Katzman S, King B, Onodera C, Siepel A, Kern AD, Dehay C, Igel H, Ares M, Vanderhaeghen P, Haussler D (2006-08-16). "An RNA gene expressed during cortical development evolved rapidly in humans" (PDF). Nature. 443 (7108): 167–72. doi:10.1038/nature05113. PMID 16915236. S2CID 18107797. supplement
8. "Entrez Gene: FHIT fragile histidine triad gene".
9. Fong LY, Fidanza V, Zanesi N, Lock LF, Siracusa LD, Mancini R, Siprashvili Z, Ottey M, Martin SE, Druck T, McCue PA, Croce CM, Huebner K (April 2000). "Muir-Torre-like syndrome in Fhit-deficient mice". Proc. Natl. Acad. Sci. U.S.A. 97 (9): 4742–7. doi:10.1073/pnas.080063497. PMC 18303. PMID 10758156.
10. Zanesi N, Fidanza V, Fong LY, Mancini R, Druck T, Valtieri M, Rüdiger T, McCue PA, Croce CM, Huebner K (August 2001). "The tumor spectrum in FHIT-deficient mice". Proc. Natl. Acad. Sci. U.S.A. 98 (18): 10250–5. doi:10.1073/pnas.191345898. PMC 56947. PMID 11517343.
11. Zanesi N, Pekarsky Y, Croce CM (December 2005). "A mouse model of the fragile gene FHIT: From carcinogenesis to gene therapy and cancer prevention". Mutat. Res. 591 (1–2): 103–9. doi:10.1016/j.mrfmmm.2005.05.016. PMID 16085127.
12. Zanesi N, Mancini R, Sevignani C, Vecchione A, Kaou M, Valtieri M, Calin GA, Pekarsky Y, Gnarra JR, Croce CM, Huebner K (August 2005). "Lung cancer susceptibility in Fhit-deficient mice is increased by Vhl haploinsufficiency". Cancer Res. 65 (15): 6576–82. doi:10.1158/0008-5472.CAN-05-1128. PMID 16061637.
13. Bianchi F, Tagliabue E, Ménard S, Campiglio M (March 2007). "Fhit expression protects against HER2-driven breast tumor development: unraveling the molecular interconnections". Cell Cycle. 6 (6): 643–6. doi:10.4161/cc.6.6.4033. PMID 17374991.
14. Shi Y, Zou M, Farid NR, Paterson MC (December 2000). "Association of FHIT (fragile histidine triad), a candidate tumour suppressor gene, with the ubiquitin-conjugating enzyme hUBC9". Biochem. J. 352 Pt 2 (2): 443–8. doi:10.1042/0264-6021:3520443. PMC 1221476. PMID 11085938.

External links

• Overview of all the structural information available in the PDB for UniProt: P49789 (Bis(5'-adenosyl)-triphosphatase) at the PDBe-KB.