# FHIT

> Mediated Wiki article. Canonical URL: https://mediated.wiki/source/FHIT
> Markdown URL: https://mediated.wiki/source/FHIT.md
> Source: https://en.wikipedia.org/wiki/FHIT
> Source revision: 1301320577
> License: Creative Commons Attribution-ShareAlike 4.0 International (https://creativecommons.org/licenses/by-sa/4.0/)

Protein-coding gene in the species Homo sapiens

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; OMA:FHIT - orthologs 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 11,307,738 bp[2] End 12,919,681 bp[2] RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right adrenal gland right adrenal cortex left adrenal cortex apex of heart C1 segment gallbladder oocyte right auricle of heart testicle human kidney Top expressed in right kidney lumbar spinal ganglion transitional epithelium of urinary bladder Epithelium of choroid plexus motor neuron saccule proximal tubule choroid plexus of fourth ventricle seminal vesicula morula More reference expression data BioGPS More reference expression data Gene ontology Molecular function bis(5'-adenosyl)-triphosphatase activity nucleotide binding catalytic activity hydrolase activity protein binding ubiquitin protein ligase binding identical protein binding Cellular component cytoplasm cytosol mitochondrion nucleus fibrillar center plasma 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: 11.31 – 12.92 Mb PubMed search [3] [4] Wikidata View/Edit Human View/Edit Mouse

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

## Function

FHIT is also known as [human accelerated region](/source/Human_accelerated_regions) 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](/source/Purine_metabolism). The gene encompasses the common fragile site FRA3B on chromosome 3, where [carcinogen](/source/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](/source/Carcinoma).[8]

Though the exact molecular function of FHIT is still partially unclear, the gene works as a [tumor suppressor](/source/Tumor_suppressor_gene) as it has been demonstrated in animal studies.[9][10][11] Furthermore FHIT has been shown to synergize with [VHL](/source/Von_Hippel%E2%80%93Lindau_tumor_suppressor), another tumor suppressor, in protecting against chemically - induced lung cancer.[12]

FHIT also acts as a tumor suppressor of [HER2/neu](/source/HER2%2Fneu) driven breast cancer.[13]

## Interactions

FHIT has been shown to [interact](/source/Protein-protein_interaction) with [UBE2I](/source/UBE2I).[14]

## References

1. ^ [***a***](#cite_ref-refGRCh38Ensembl_1-0) [***b***](#cite_ref-refGRCh38Ensembl_1-1) [***c***](#cite_ref-refGRCh38Ensembl_1-2) [GRCh38: Ensembl release 89: ENSG00000189283](http://May2017.archive.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000189283) – [Ensembl](/source/Ensembl_genome_database_project), May 2017

1. ^ [***a***](#cite_ref-refGRCm38Ensembl_2-0) [***b***](#cite_ref-refGRCm38Ensembl_2-1) [***c***](#cite_ref-refGRCm38Ensembl_2-2) [GRCm38: Ensembl release 89: ENSMUSG00000060579](http://May2017.archive.ensembl.org/Mus_musculus/Gene/Summary?db=core;g=ENSMUSG00000060579) – [Ensembl](/source/Ensembl_genome_database_project), May 2017

1. **[^](#cite_ref-3)** ["Human PubMed Reference:"](https://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Link&LinkName=gene_pubmed&from_uid=2272). *National Center for Biotechnology Information, U.S. National Library of Medicine*.

1. **[^](#cite_ref-4)** ["Mouse PubMed Reference:"](https://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Link&LinkName=gene_pubmed&from_uid=14198). *National Center for Biotechnology Information, U.S. National Library of Medicine*.

1. **[^](#cite_ref-pmid8598045_5-0)** 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"](https://doi.org/10.1016%2FS0092-8674%2800%2981034-X). *Cell*. **84** (4): 587–97. [doi](/source/Doi_(identifier)):[10.1016/S0092-8674(00)81034-X](https://doi.org/10.1016%2FS0092-8674%2800%2981034-X). [PMID](/source/PMID_(identifier)) [8598045](https://pubmed.ncbi.nlm.nih.gov/8598045). [S2CID](/source/S2CID_(identifier)) [18792069](https://api.semanticscholar.org/CorpusID:18792069).

1. **[^](#cite_ref-pmid9671749_6-0)** 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"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC21147). *Proc. Natl. Acad. Sci. U.S.A*. **95** (15): 8744–9. [Bibcode](/source/Bibcode_(identifier)):[1998PNAS...95.8744P](https://ui.adsabs.harvard.edu/abs/1998PNAS...95.8744P). [doi](/source/Doi_(identifier)):[10.1073/pnas.95.15.8744](https://doi.org/10.1073%2Fpnas.95.15.8744). [PMC](/source/PMC_(identifier)) [21147](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC21147). [PMID](/source/PMID_(identifier)) [9671749](https://pubmed.ncbi.nlm.nih.gov/9671749).

1. **[^](#cite_ref-Pollard2006_7-0)** [Pollard KS](/source/Katherine_Pollard), 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"](https://dipot.ulb.ac.be/dspace/bitstream/2013/51805/3/pollard2006.pdf) (PDF). *Nature*. **443** (7108): 167–72. [Bibcode](/source/Bibcode_(identifier)):[2006Natur.443..167P](https://ui.adsabs.harvard.edu/abs/2006Natur.443..167P). [doi](/source/Doi_(identifier)):[10.1038/nature05113](https://doi.org/10.1038%2Fnature05113). [PMID](/source/PMID_(identifier)) [16915236](https://pubmed.ncbi.nlm.nih.gov/16915236). [S2CID](/source/S2CID_(identifier)) [18107797](https://api.semanticscholar.org/CorpusID:18107797). [supplement](http://www.nature.com/nature/journal/v443/n7108/extref/nature05113-s1.doc)

1. **[^](#cite_ref-8)** ["Entrez Gene: FHIT fragile histidine triad gene"](https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=2272).

1. **[^](#cite_ref-pmid10758156_9-0)** 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"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC18303). *Proc. Natl. Acad. Sci. U.S.A*. **97** (9): 4742–7. [Bibcode](/source/Bibcode_(identifier)):[2000PNAS...97.4742F](https://ui.adsabs.harvard.edu/abs/2000PNAS...97.4742F). [doi](/source/Doi_(identifier)):[10.1073/pnas.080063497](https://doi.org/10.1073%2Fpnas.080063497). [PMC](/source/PMC_(identifier)) [18303](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC18303). [PMID](/source/PMID_(identifier)) [10758156](https://pubmed.ncbi.nlm.nih.gov/10758156).

1. **[^](#cite_ref-pmid11517343_10-0)** 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"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC56947). *Proc. Natl. Acad. Sci. U.S.A*. **98** (18): 10250–5. [Bibcode](/source/Bibcode_(identifier)):[2001PNAS...9810250Z](https://ui.adsabs.harvard.edu/abs/2001PNAS...9810250Z). [doi](/source/Doi_(identifier)):[10.1073/pnas.191345898](https://doi.org/10.1073%2Fpnas.191345898). [PMC](/source/PMC_(identifier)) [56947](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC56947). [PMID](/source/PMID_(identifier)) [11517343](https://pubmed.ncbi.nlm.nih.gov/11517343).

1. **[^](#cite_ref-pmid16085127_11-0)** 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](/source/Doi_(identifier)):[10.1016/j.mrfmmm.2005.05.016](https://doi.org/10.1016%2Fj.mrfmmm.2005.05.016). [PMID](/source/PMID_(identifier)) [16085127](https://pubmed.ncbi.nlm.nih.gov/16085127).

1. **[^](#cite_ref-pmid16061637_12-0)** 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](/source/Doi_(identifier)):[10.1158/0008-5472.CAN-05-1128](https://doi.org/10.1158%2F0008-5472.CAN-05-1128). [PMID](/source/PMID_(identifier)) [16061637](https://pubmed.ncbi.nlm.nih.gov/16061637).

1. **[^](#cite_ref-pmid17374991_13-0)** Bianchi F, Tagliabue E, Ménard S, Campiglio M (March 2007). ["Fhit expression protects against HER2-driven breast tumor development: unraveling the molecular interconnections"](https://doi.org/10.4161%2Fcc.6.6.4033). *Cell Cycle*. **6** (6): 643–6. [doi](/source/Doi_(identifier)):[10.4161/cc.6.6.4033](https://doi.org/10.4161%2Fcc.6.6.4033). [hdl](/source/Hdl_(identifier)):[2434/810034](https://hdl.handle.net/2434%2F810034). [PMID](/source/PMID_(identifier)) [17374991](https://pubmed.ncbi.nlm.nih.gov/17374991).

1. **[^](#cite_ref-pmid11085938_14-0)** 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"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1221476). *Biochem. J*. 352 Pt 2 (2): 443–8. [doi](/source/Doi_(identifier)):[10.1042/0264-6021:3520443](https://doi.org/10.1042%2F0264-6021%3A3520443). [PMC](/source/PMC_(identifier)) [1221476](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1221476). [PMID](/source/PMID_(identifier)) [11085938](https://pubmed.ncbi.nlm.nih.gov/11085938).

## External links

- Overview of all the structural information available in the [PDB](/source/Protein_Data_Bank) for [UniProt](/source/UniProt): *[P49789](https://www.ebi.ac.uk/pdbe/pdbe-kb/proteins/P49789)* (Bis(5'-adenosyl)-triphosphatase) at the [PDBe-KB](/source/PDBe-KB).

v t e PDB gallery 1fhi: SUBSTRATE ANALOG (IB2) COMPLEX WITH THE FRAGILE HISTIDINE TRIAD PROTEIN, FHIT 1fit: FHIT (FRAGILE HISTIDINE TRIAD PROTEIN) 2fhi: SUBSTRATE ANALOG (IB2) COMPLEX WITH THE HIS 96 ASN SUBSTITUTION OF THE FRAGILE HISTIDINE TRIAD PROTEIN, FHIT 2fit: FHIT (FRAGILE HISTIDINE TRIAD PROTEIN) 3fit: FHIT (FRAGILE HISTIDINE TRIAD PROTEIN) IN COMPLEX WITH ADENOSINE/SULFATE AMP ANALOG 4fit: FHIT-APO 5fit: FHIT-SUBSTRATE ANALOG 6fit: FHIT-TRANSITION STATE ANALOG

This article on a gene on human chromosome 3 is a stub. You can help Wikipedia by adding missing information.

- [v](https://en.wikipedia.org/wiki/Template:Gene-3-stub)
- [t](/source/Template_talk%3AGene-3-stub)
- [e](https://en.wikipedia.org/wiki/Special:EditPage/Template:Gene-3-stub)

---
Adapted from the Wikipedia article [FHIT](https://en.wikipedia.org/wiki/FHIT) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/FHIT?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.