GenomeNet

Database: UniProt
Entry: P49789
LinkDB: P49789
Original site: P49789 
ID   FHIT_HUMAN              Reviewed;         147 AA.
AC   P49789; A2IAS9; A2IAT0; A2IAT6; A8K1A9; Q45QG9; Q6IU12;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 3.
DT   10-FEB-2021, entry version 187.
DE   RecName: Full=Bis(5'-adenosyl)-triphosphatase;
DE            EC=3.6.1.29;
DE   AltName: Full=AP3A hydrolase;
DE            Short=AP3Aase;
DE   AltName: Full=Diadenosine 5',5'''-P1,P3-triphosphate hydrolase;
DE   AltName: Full=Dinucleosidetriphosphatase;
DE   AltName: Full=Fragile histidine triad protein;
GN   Name=FHIT;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX   PubMed=8598045; DOI=10.1016/s0092-8674(00)81034-x;
RA   Ohta M., Inoue H., Cotticelli M.G., Kastury K., Baffa R., Palazzo J.,
RA   Siprashvili Z., Mori M., McCue P., Druck T., Croce C.M., Huebner K.;
RT   "The FHIT gene, spanning the chromosome 3p14.2 fragile site and renal
RT   carcinoma-associated t(3;8) breakpoint, is abnormal in digestive tract
RT   cancers.";
RL   Cell 84:587-597(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=9012482;
RA   Druck T., Hadaczek P., Fu T.B., Ohta M., Siprashvili Z., Baffa R.,
RA   Negrini M., Kastury K., Veronese M.L., Rosen D., Rothstein J., McCue P.,
RA   Cotticelli M.G., Inoue H., Croce C.M., Huebner K.;
RT   "Structure and expression of the human FHIT gene in normal and tumor
RT   cells.";
RL   Cancer Res. 57:504-512(1997).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=24722188; DOI=10.1038/ncomms4650;
RA   Corominas R., Yang X., Lin G.N., Kang S., Shen Y., Ghamsari L., Broly M.,
RA   Rodriguez M., Tam S., Wanamaker S.A., Fan C., Yi S., Tasan M., Lemmens I.,
RA   Kuang X., Zhao N., Malhotra D., Michaelson J.J., Vacic V., Calderwood M.A.,
RA   Roth F.P., Tavernier J., Horvath S., Salehi-Ashtiani K., Korkin D.,
RA   Sebat J., Hill D.E., Hao T., Vidal M., Iakoucheva L.M.;
RT   "Protein interaction network of alternatively spliced isoforms from brain
RT   links genetic risk factors for autism.";
RL   Nat. Commun. 5:3650-3650(2014).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF
RP   94-146.
RA   Naqvi S.R.A., Malik A., Kukreti H., Chaudhary A., Anand R., Deo S.S.,
RA   Shukla N.K., Husain S.A., Pasha S.T.;
RT   "Mutational analysis of FHIT gene.";
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Colon;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [8]
RP   FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF HIS-35; HIS-94; HIS-96 AND
RP   HIS-98.
RX   PubMed=8794732; DOI=10.1021/bi961415t;
RA   Barnes L.D., Garrison P.N., Siprashvili Z., Guranowski A., Robinson A.K.,
RA   Ingram S.W., Croce C.M., Ohta M., Huebner K.;
RT   "Fhit, a putative tumor suppressor in humans, is a dinucleoside 5',5''-
RT   P1,P3-triphosphate hydrolase.";
RL   Biochemistry 35:11529-11535(1996).
RN   [9]
RP   CHROMOSOMAL TRANSLOCATION WITH RNF139.
RX   PubMed=9689122; DOI=10.1073/pnas.95.16.9572;
RA   Gemmill R.M., West J.D., Boldog F., Tanaka N., Robinson L.J., Smith D.I.,
RA   Li F., Drabkin H.A.;
RT   "The hereditary renal cell carcinoma 3;8 translocation fuses FHIT to a
RT   patched-related gene, TRC8.";
RL   Proc. Natl. Acad. Sci. U.S.A. 95:9572-9577(1998).
RN   [10]
RP   INTERACTION WITH UBE2I.
RX   PubMed=11085938; DOI=10.1042/bj3520443;
RA   Shi Y., Zou M., Farid N.R., Paterson M.C.;
RT   "Association of FHIT (fragile histidine triad), a candidate tumour
RT   suppressor gene, with the ubiquitin-conjugating enzyme hUBC9.";
RL   Biochem. J. 352:443-448(2000).
RN   [11]
RP   FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF ILE-10; LEU-25 AND HIS-96.
RX   PubMed=12574506; DOI=10.1073/pnas.0437915100;
RA   Trapasso F., Krakowiak A., Cesari R., Arkles J., Yendamuri S., Ishii H.,
RA   Vecchione A., Kuroki T., Bieganowski P., Pace H.C., Huebner K., Croce C.M.,
RA   Brenner C.;
RT   "Designed FHIT alleles establish that Fhit-induced apoptosis in cancer
RT   cells is limited by substrate binding.";
RL   Proc. Natl. Acad. Sci. U.S.A. 100:1592-1597(2003).
RN   [12]
RP   ACTIVE SITE, CATALYTIC ACTIVITY, AND MUTAGENESIS OF HIS-96.
RX   PubMed=15182206; DOI=10.1021/bi049762n;
RA   Huang K., Arabshahi A., Wei Y., Frey P.A.;
RT   "The mechanism of action of the fragile histidine triad, Fhit: isolation of
RT   a covalent adenylyl enzyme and chemical rescue of H96G-Fhit.";
RL   Biochemistry 43:7637-7642(2004).
RN   [13]
RP   FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH MDM2.
RX   PubMed=15313915; DOI=10.1158/0008-5472.can-04-0195;
RA   Nishizaki M., Sasaki J., Fang B., Atkinson E.N., Minna J.D., Roth J.A.,
RA   Ji L.;
RT   "Synergistic tumor suppression by coexpression of FHIT and p53 coincides
RT   with FHIT-mediated MDM2 inactivation and p53 stabilization in human non-
RT   small cell lung cancer cells.";
RL   Cancer Res. 64:5745-5752(2004).
RN   [14]
RP   PHOSPHORYLATION BY SRC, SUBUNIT, SUBCELLULAR LOCATION, MASS SPECTROMETRY,
RP   DISEASE, PHOSPHORYLATION AT TYR-114 AND TYR-145, AND MUTAGENESIS OF TYR-114
RP   AND TYR-145.
RX   PubMed=15007172; DOI=10.1073/pnas.0400481101;
RA   Pekarsky Y., Garrison P.N., Palamarchuk A., Zanesi N., Aqeilan R.I.,
RA   Huebner K., Barnes L.D., Croce C.M.;
RT   "Fhit is a physiological target of the protein kinase Src.";
RL   Proc. Natl. Acad. Sci. U.S.A. 101:3775-3779(2004).
RN   [15]
RP   MUTAGENESIS OF TYR-114, AND FUNCTION.
RX   PubMed=16407838; DOI=10.1038/sj.onc.1209323;
RA   Semba S., Trapasso F., Fabbri M., McCorkell K.A., Volinia S., Druck T.,
RA   Iliopoulos D., Pekarsky Y., Ishii H., Garrison P.N., Barnes L.D.,
RA   Croce C.M., Huebner K.;
RT   "Fhit modulation of the Akt-survivin pathway in lung cancer cells: Fhit-
RT   tyrosine 114 (Y114) is essential.";
RL   Oncogene 25:2860-2872(2006).
RN   [16]
RP   INTERACTION WITH CTNNB1, IDENTIFICATION IN A COMPLEX WITH CTNNB1 AND LEF1,
RP   AND FUNCTION.
RX   PubMed=18077326; DOI=10.1073/pnas.0703664105;
RA   Weiske J., Albring K.F., Huber O.;
RT   "The tumor suppressor Fhit acts as a repressor of beta-catenin
RT   transcriptional activity.";
RL   Proc. Natl. Acad. Sci. U.S.A. 104:20344-20349(2007).
RN   [17]
RP   SUBCELLULAR LOCATION, AND FUNCTION IN APOPTOSIS.
RX   PubMed=19622739; DOI=10.1073/pnas.0906484106;
RA   Rimessi A., Marchi S., Fotino C., Romagnoli A., Huebner K., Croce C.M.,
RA   Pinton P., Rizzuto R.;
RT   "Intramitochondrial calcium regulation by the FHIT gene product sensitizes
RT   to apoptosis.";
RL   Proc. Natl. Acad. Sci. U.S.A. 106:12753-12758(2009).
RN   [18]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [19]
RP   X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS).
RX   PubMed=9261067; DOI=10.1016/s0969-2126(97)00231-1;
RA   Lima C.D., D'Amico K.L., Naday I., Rosenbaum G., Westbrook E.M.,
RA   Hendrickson W.A.;
RT   "MAD analysis of FHIT, a putative human tumor suppressor from the HIT
RT   protein family.";
RL   Structure 5:763-774(1997).
RN   [20]
RP   X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEXES WITH SUBSTRATES,
RP   CATALYTIC ACTIVITY, FUNCTION, SUBUNIT, AND ACTIVE SITE.
RX   PubMed=9323207; DOI=10.1126/science.278.5336.286;
RA   Lima C.D., Klein M.G., Hendrickson W.A.;
RT   "Structure-based analysis of catalysis and substrate definition in the HIT
RT   protein family.";
RL   Science 278:286-290(1997).
RN   [21]
RP   X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) IN COMPLEXES WITH SUBSTRATE ANALOGS,
RP   SUBUNIT, CATALYTIC ACTIVITY, AND MUTAGENESIS OF HIS-96.
RX   PubMed=9576908; DOI=10.1073/pnas.95.10.5484;
RA   Pace H.C., Garrison P.N., Robinson A.K., Barnes L.D., Draganescu A.,
RA   Roesler A., Blackburn G.M., Siprashvili Z., Croce C.M., Huebner K.,
RA   Brenner C.;
RT   "Genetic, biochemical, and crystallographic characterization of Fhit-
RT   substrate complexes as the active signaling form of Fhit.";
RL   Proc. Natl. Acad. Sci. U.S.A. 95:5484-5489(1998).
CC   -!- FUNCTION: Cleaves P(1)-P(3)-bis(5'-adenosyl) triphosphate (Ap3A) to
CC       yield AMP and ADP. Can also hydrolyze P(1)-P(4)-bis(5'-adenosyl)
CC       tetraphosphate (Ap4A), but has extremely low activity with ATP.
CC       Modulates transcriptional activation by CTNNB1 and thereby contributes
CC       to regulate the expression of genes essential for cell proliferation
CC       and survival, such as CCND1 and BIRC5. Plays a role in the induction of
CC       apoptosis via SRC and AKT1 signaling pathways. Inhibits MDM2-mediated
CC       proteasomal degradation of p53/TP53 and thereby plays a role in
CC       p53/TP53-mediated apoptosis. Induction of apoptosis depends on the
CC       ability of FHIT to bind P(1)-P(3)-bis(5'-adenosyl) triphosphate or
CC       related compounds, but does not require its catalytic activity, it may
CC       in part come from the mitochondrial form, which sensitizes the low-
CC       affinity Ca(2+) transporters, enhancing mitochondrial calcium uptake.
CC       Functions as tumor suppressor. {ECO:0000269|PubMed:12574506,
CC       ECO:0000269|PubMed:15313915, ECO:0000269|PubMed:16407838,
CC       ECO:0000269|PubMed:18077326, ECO:0000269|PubMed:19622739,
CC       ECO:0000269|PubMed:8794732, ECO:0000269|PubMed:9323207}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + P(1),P(3)-bis(5'-adenosyl) triphosphate = ADP + AMP + 2
CC         H(+); Xref=Rhea:RHEA:13893, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:58529, ChEBI:CHEBI:456215, ChEBI:CHEBI:456216;
CC         EC=3.6.1.29; Evidence={ECO:0000269|PubMed:12574506,
CC         ECO:0000269|PubMed:15182206, ECO:0000269|PubMed:8794732,
CC         ECO:0000269|PubMed:9323207, ECO:0000269|PubMed:9576908};
CC   -!- SUBUNIT: Homodimer. Interacts with UBE2I. Interacts with MDM2.
CC       Interacts with CTNNB1. Identified in a complex with CTNNB1 and LEF1.
CC       {ECO:0000269|PubMed:11085938, ECO:0000269|PubMed:15007172,
CC       ECO:0000269|PubMed:15313915, ECO:0000269|PubMed:18077326,
CC       ECO:0000269|PubMed:9323207, ECO:0000269|PubMed:9576908}.
CC   -!- INTERACTION:
CC       P49789; P35222: CTNNB1; NbExp=4; IntAct=EBI-741760, EBI-491549;
CC       P49789; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-741760, EBI-742054;
CC       P49789; P49789: FHIT; NbExp=13; IntAct=EBI-741760, EBI-741760;
CC       P49789; Q9UJU2: LEF1; NbExp=2; IntAct=EBI-741760, EBI-926131;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm. Mitochondrion. Nucleus.
CC   -!- TISSUE SPECIFICITY: Low levels expressed in all tissues tested.
CC       Phospho-FHIT observed in liver and kidney, but not in brain and lung.
CC       Phospho-FHIT undetected in all tested human tumor cell lines.
CC   -!- PTM: Phosphorylation at Tyr-114 by SRC is required for induction of
CC       apoptosis. {ECO:0000269|PubMed:15007172}.
CC   -!- MASS SPECTROMETRY: Mass=16733; Method=MALDI;
CC       Evidence={ECO:0000269|PubMed:15007172};
CC   -!- DISEASE: Note=A chromosomal aberration involving FHIT has been found in
CC       a lymphoblastoid cell line established from a family with renal cell
CC       carcinoma and thyroid carcinoma. Translocation t(3;8)(p14.2;q24.1) with
CC       RNF139. Although the 3p14.2 breakpoint has been shown to interrupt FHIT
CC       in its 5-prime non-coding region, it is unlikely that FHIT is causally
CC       related to renal or other malignancies. {ECO:0000269|PubMed:15007172}.
CC   -!- DISEASE: Note=Associated with digestive tract cancers. Numerous tumor
CC       types are found to have aberrant forms of FHIT protein due to deletions
CC       in a coding region of chromosome 3p14.2 including the fragile site
CC       locus FRA3B. {ECO:0000269|PubMed:15007172}.
CC   -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC       Haematology;
CC       URL="http://atlasgeneticsoncology.org/Genes/FHITID192ch3p14.html";
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; U46922; AAA99013.1; -; mRNA.
DR   EMBL; U76271; AAB52539.1; -; Genomic_DNA.
DR   EMBL; U76267; AAB52539.1; JOINED; Genomic_DNA.
DR   EMBL; U76268; AAB52539.1; JOINED; Genomic_DNA.
DR   EMBL; U76269; AAB52539.1; JOINED; Genomic_DNA.
DR   EMBL; U76270; AAB52539.1; JOINED; Genomic_DNA.
DR   EMBL; KJ534835; AHW56475.1; -; mRNA.
DR   EMBL; AY625256; AAT37530.1; -; Genomic_DNA.
DR   EMBL; DQ120721; AAZ23623.1; -; mRNA.
DR   EMBL; EF186677; ABM65879.1; -; Genomic_DNA.
DR   EMBL; EF183457; ABM66086.1; -; Genomic_DNA.
DR   EMBL; EF183458; ABM66087.1; -; Genomic_DNA.
DR   EMBL; EF183459; ABM66088.1; -; Genomic_DNA.
DR   EMBL; EF183461; ABM66090.1; -; Genomic_DNA.
DR   EMBL; EF183464; ABM66093.1; -; Genomic_DNA.
DR   EMBL; AK289824; BAF82513.1; -; mRNA.
DR   EMBL; CH471055; EAW65393.1; -; Genomic_DNA.
DR   EMBL; BC032336; AAH32336.1; -; mRNA.
DR   CCDS; CCDS2894.1; -.
DR   PIR; A58802; A58802.
DR   RefSeq; NP_001159715.1; NM_001166243.2.
DR   RefSeq; NP_001307828.1; NM_001320899.1.
DR   RefSeq; NP_001307829.1; NM_001320900.1.
DR   RefSeq; NP_002003.1; NM_002012.3.
DR   PDB; 1FHI; X-ray; 3.10 A; A=1-147.
DR   PDB; 1FIT; X-ray; 1.85 A; A=1-147.
DR   PDB; 2FHI; X-ray; 2.60 A; A=1-147.
DR   PDB; 2FIT; X-ray; 1.90 A; A=1-147.
DR   PDB; 3FIT; X-ray; 2.40 A; A=1-147.
DR   PDB; 4FIT; X-ray; 2.50 A; A=1-147.
DR   PDB; 5FIT; X-ray; 2.30 A; A=1-147.
DR   PDB; 6FIT; X-ray; 2.60 A; A=1-147.
DR   PDBsum; 1FHI; -.
DR   PDBsum; 1FIT; -.
DR   PDBsum; 2FHI; -.
DR   PDBsum; 2FIT; -.
DR   PDBsum; 3FIT; -.
DR   PDBsum; 4FIT; -.
DR   PDBsum; 5FIT; -.
DR   PDBsum; 6FIT; -.
DR   SMR; P49789; -.
DR   BioGRID; 108563; 15.
DR   DIP; DIP-29947N; -.
DR   IntAct; P49789; 9.
DR   STRING; 9606.ENSP00000417480; -.
DR   BindingDB; P49789; -.
DR   ChEMBL; CHEMBL1795151; -.
DR   DrugBank; DB02373; Adenosine monotungstate.
DR   DrugBank; DB04389; Ado-P-Ch2-P-Ps-Ado.
DR   iPTMnet; P49789; -.
DR   PhosphoSitePlus; P49789; -.
DR   BioMuta; FHIT; -.
DR   DMDM; 1706794; -.
DR   EPD; P49789; -.
DR   jPOST; P49789; -.
DR   MassIVE; P49789; -.
DR   PaxDb; P49789; -.
DR   PeptideAtlas; P49789; -.
DR   PRIDE; P49789; -.
DR   ProteomicsDB; 56119; -.
DR   Antibodypedia; 3636; 593 antibodies.
DR   DNASU; 2272; -.
DR   Ensembl; ENST00000468189; ENSP00000417480; ENSG00000189283.
DR   Ensembl; ENST00000476844; ENSP00000417557; ENSG00000189283.
DR   Ensembl; ENST00000492590; ENSP00000418582; ENSG00000189283.
DR   GeneID; 2272; -.
DR   KEGG; hsa:2272; -.
DR   UCSC; uc003dkx.5; human.
DR   CTD; 2272; -.
DR   DisGeNET; 2272; -.
DR   GeneCards; FHIT; -.
DR   HGNC; HGNC:3701; FHIT.
DR   HPA; ENSG00000189283; Low tissue specificity.
DR   MalaCards; FHIT; -.
DR   MIM; 601153; gene.
DR   neXtProt; NX_P49789; -.
DR   OpenTargets; ENSG00000189283; -.
DR   Orphanet; 422526; Hereditary clear cell renal cell carcinoma.
DR   PharmGKB; PA28140; -.
DR   VEuPathDB; HostDB:ENSG00000189283.9; -.
DR   eggNOG; KOG3379; Eukaryota.
DR   GeneTree; ENSGT00510000047967; -.
DR   HOGENOM; CLU_056776_7_1_1; -.
DR   OMA; VHTHIIP; -.
DR   OrthoDB; 1198291at2759; -.
DR   PhylomeDB; P49789; -.
DR   TreeFam; TF105432; -.
DR   BRENDA; 3.6.1.29; 2681.
DR   PathwayCommons; P49789; -.
DR   SABIO-RK; P49789; -.
DR   SIGNOR; P49789; -.
DR   BioGRID-ORCS; 2272; 8 hits in 880 CRISPR screens.
DR   ChiTaRS; FHIT; human.
DR   EvolutionaryTrace; P49789; -.
DR   GeneWiki; FHIT; -.
DR   GenomeRNAi; 2272; -.
DR   Pharos; P49789; Tchem.
DR   PRO; PR:P49789; -.
DR   Proteomes; UP000005640; Chromosome 3.
DR   RNAct; P49789; protein.
DR   Bgee; ENSG00000189283; Expressed in pigmented layer of retina and 149 other tissues.
DR   ExpressionAtlas; P49789; baseline and differential.
DR   Genevisible; P49789; HS.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR   GO; GO:0001650; C:fibrillar center; IDA:HPA.
DR   GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR   GO; GO:0047710; F:bis(5'-adenosyl)-triphosphatase activity; IDA:UniProtKB.
DR   GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR   GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR   GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR   GO; GO:0015964; P:diadenosine triphosphate catabolic process; IDA:UniProtKB.
DR   GO; GO:0072332; P:intrinsic apoptotic signaling pathway by p53 class mediator; IMP:UniProtKB.
DR   GO; GO:0032435; P:negative regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR   GO; GO:0006163; P:purine nucleotide metabolic process; IDA:UniProtKB.
DR   CDD; cd01275; FHIT; 1.
DR   Gene3D; 3.30.428.10; -; 1.
DR   InterPro; IPR039383; FHIT.
DR   InterPro; IPR019808; Histidine_triad_CS.
DR   InterPro; IPR001310; Histidine_triad_HIT.
DR   InterPro; IPR011146; HIT-like.
DR   InterPro; IPR036265; HIT-like_sf.
DR   Pfam; PF01230; HIT; 1.
DR   SUPFAM; SSF54197; SSF54197; 1.
DR   PROSITE; PS00892; HIT_1; 1.
DR   PROSITE; PS51084; HIT_2; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Apoptosis; Chromosomal rearrangement; Cytoplasm; Hydrolase;
KW   Manganese; Mitochondrion; Nucleotide-binding; Nucleus; Phosphoprotein;
KW   Reference proteome; Transcription; Transcription regulation;
KW   Tumor suppressor.
FT   CHAIN           1..147
FT                   /note="Bis(5'-adenosyl)-triphosphatase"
FT                   /id="PRO_0000109789"
FT   DOMAIN          2..109
FT                   /note="HIT"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00464"
FT   NP_BIND         89..92
FT                   /note="Substrate"
FT                   /evidence="ECO:0000244|PDB:5FIT,
FT                   ECO:0000269|PubMed:9323207"
FT   MOTIF           94..98
FT                   /note="Histidine triad motif"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00464"
FT   ACT_SITE        96
FT                   /note="Tele-AMP-histidine intermediate"
FT                   /evidence="ECO:0000269|PubMed:15182206,
FT                   ECO:0000269|PubMed:9323207"
FT   BINDING         8
FT                   /note="Substrate"
FT                   /evidence="ECO:0000244|PDB:3FIT,
FT                   ECO:0000269|PubMed:9261067"
FT   BINDING         27
FT                   /note="Substrate"
FT                   /evidence="ECO:0000244|PDB:5FIT,
FT                   ECO:0000269|PubMed:9323207"
FT   BINDING         83
FT                   /note="Substrate"
FT                   /evidence="ECO:0000244|PDB:5FIT,
FT                   ECO:0000269|PubMed:9323207"
FT   BINDING         98
FT                   /note="Substrate"
FT                   /evidence="ECO:0000244|PDB:5FIT,
FT                   ECO:0000269|PubMed:9323207"
FT   SITE            114
FT                   /note="Important for induction of apoptosis"
FT   MOD_RES         114
FT                   /note="Phosphotyrosine; by SRC"
FT                   /evidence="ECO:0000269|PubMed:15007172"
FT   MOD_RES         145
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000269|PubMed:15007172"
FT   MUTAGEN         10
FT                   /note="I->W: Strongly reduces affinity for substrates and
FT                   impairs apoptosis; when associated with W-25."
FT                   /evidence="ECO:0000269|PubMed:12574506"
FT   MUTAGEN         25
FT                   /note="L->W: Reduces affinity for substrates and impairs
FT                   apoptosis. Strongly reduces affinity for substrates and
FT                   impairs apoptosis; when associated with W-10."
FT                   /evidence="ECO:0000269|PubMed:12574506"
FT   MUTAGEN         35
FT                   /note="H->N: 50% decrease in catalytic activity. No loss in
FT                   substrate binding."
FT                   /evidence="ECO:0000269|PubMed:8794732"
FT   MUTAGEN         94
FT                   /note="H->N: 75% decrease in catalytic activity. No loss in
FT                   substrate binding."
FT                   /evidence="ECO:0000269|PubMed:8794732"
FT   MUTAGEN         96
FT                   /note="H->D: Loss of catalytic activity."
FT                   /evidence="ECO:0000269|PubMed:12574506,
FT                   ECO:0000269|PubMed:15182206, ECO:0000269|PubMed:8794732,
FT                   ECO:0000269|PubMed:9576908"
FT   MUTAGEN         96
FT                   /note="H->G: Total loss of catalytic activity. Rescuable
FT                   with free imidazole."
FT                   /evidence="ECO:0000269|PubMed:12574506,
FT                   ECO:0000269|PubMed:15182206, ECO:0000269|PubMed:8794732,
FT                   ECO:0000269|PubMed:9576908"
FT   MUTAGEN         96
FT                   /note="H->N: Total loss of catalytic activity. No loss in
FT                   substrate binding."
FT                   /evidence="ECO:0000269|PubMed:12574506,
FT                   ECO:0000269|PubMed:15182206, ECO:0000269|PubMed:8794732,
FT                   ECO:0000269|PubMed:9576908"
FT   MUTAGEN         98
FT                   /note="H->N: 98% decrease in catalytic activity."
FT                   /evidence="ECO:0000269|PubMed:8794732"
FT   MUTAGEN         114
FT                   /note="Y->A: Impairs induction of apoptosis. Strongly
FT                   reduced affinity for substrates."
FT                   /evidence="ECO:0000269|PubMed:15007172,
FT                   ECO:0000269|PubMed:16407838"
FT   MUTAGEN         114
FT                   /note="Y->D: Impairs induction of apoptosis. Reduces
FT                   affinity for substrates."
FT                   /evidence="ECO:0000269|PubMed:15007172,
FT                   ECO:0000269|PubMed:16407838"
FT   MUTAGEN         114
FT                   /note="Y->F: Loss of phosphorylation by SRC. Impairs
FT                   induction of apoptosis."
FT                   /evidence="ECO:0000269|PubMed:15007172,
FT                   ECO:0000269|PubMed:16407838"
FT   MUTAGEN         145
FT                   /note="Y->F: No effect on phosphorylation by SRC."
FT                   /evidence="ECO:0000269|PubMed:15007172"
FT   CONFLICT        146
FT                   /note="F -> S (in Ref. 5; BAF82513)"
FT                   /evidence="ECO:0000305"
FT   STRAND          3..5
FT                   /evidence="ECO:0000244|PDB:1FIT"
FT   STRAND          8..10
FT                   /evidence="ECO:0000244|PDB:1FIT"
FT   HELIX           12..14
FT                   /evidence="ECO:0000244|PDB:1FIT"
FT   STRAND          15..18
FT                   /evidence="ECO:0000244|PDB:1FIT"
FT   STRAND          20..26
FT                   /evidence="ECO:0000244|PDB:1FIT"
FT   STRAND          36..42
FT                   /evidence="ECO:0000244|PDB:1FIT"
FT   HELIX           47..49
FT                   /evidence="ECO:0000244|PDB:1FIT"
FT   HELIX           52..72
FT                   /evidence="ECO:0000244|PDB:1FIT"
FT   STRAND          76..82
FT                   /evidence="ECO:0000244|PDB:1FIT"
FT   HELIX           86..88
FT                   /evidence="ECO:0000244|PDB:1FIT"
FT   STRAND          92..94
FT                   /evidence="ECO:0000244|PDB:1FIT"
FT   STRAND          97..102
FT                   /evidence="ECO:0000244|PDB:1FIT"
FT   HELIX           132..144
FT                   /evidence="ECO:0000244|PDB:1FIT"
SQ   SEQUENCE   147 AA;  16858 MW;  14D85961A19ECF3E CRC64;
     MSFRFGQHLI KPSVVFLKTE LSFALVNRKP VVPGHVLVCP LRPVERFHDL RPDEVADLFQ
     TTQRVGTVVE KHFHGTSLTF SMQDGPEAGQ TVKHVHVHVL PRKAGDFHRN DSIYEELQKH
     DKEDFPASWR SEEEMAAEAA ALRVYFQ
//
DBGET integrated database retrieval system