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FHIT

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FHIT
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesFHIT, AP3Aase, FRA3B, fragile histidine triad, tríada histidina fràgil, fragile histidine triad diadenosine triphosphatase
External IDsOMIM: 601153; MGI: 1277947; HomoloGene: 21661; GeneCards: FHIT; OMA:FHIT - orthologs
Orthologs
SpeciesHumanMouse
Entrez

2272

14198

Ensembl

ENSG00000189283

ENSMUSG00000060579

UniProt

P49789

O89106

RefSeq (mRNA)

NM_010210
NM_001308285
NM_001308286
NM_001360141

RefSeq (protein)

NP_001295214
NP_001295215
NP_034340
NP_001347070

Location (UCSC)Chr 3: 59.75 – 61.25 MbChr 14: 11.31 – 12.92 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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]

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. ^ a b c GRCh38: Ensembl release 89: ENSG00000189283 – Ensembl, May 2017
  2. ^ a b c 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. Bibcode:1998PNAS...95.8744P. 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. Bibcode:2006Natur.443..167P. 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. Bibcode:2000PNAS...97.4742F. 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. Bibcode:2001PNAS...9810250Z. 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.
  • Overview of all the structural information available in the PDB for UniProt: P49789 (Bis(5'-adenosyl)-triphosphatase) at the PDBe-KB.


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