Bis(5'-adenosyl)-triphosphatase

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functionⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityⁱ

• H₂O

  • Search proteins in UniProtKB for this molecule.
  • Search chemical reactions in Rhea for this molecule.
  • See the description of this molecule in ChEBI.

  + P¹,P³-bis(5'-adenosyl) triphosphate

  • Search proteins in UniProtKB for this molecule.
  • Search chemical reactions in Rhea for this molecule.
  • See the description of this molecule in ChEBI.

  = ADP

  • Search proteins in UniProtKB for this molecule.
  • Search chemical reactions in Rhea for this molecule.
  • See the description of this molecule in ChEBI.

  + AMP

  • Search proteins in UniProtKB for this molecule.
  • Search chemical reactions in Rhea for this molecule.
  • See the description of this molecule in ChEBI.

  + 2 H⁺

  • Search proteins in UniProtKB for this molecule.
  • Search chemical reactions in Rhea for this molecule.
  • See the description of this molecule in ChEBI.

  5 Publications

  Manual assertion based on experiment inⁱ

  • Ref.8

    "Fhit, a putative tumor suppressor in humans, is a dinucleoside 5',5''-P1,P3-triphosphate hydrolase."
    Barnes L.D., Garrison P.N., Siprashvili Z., Guranowski A., Robinson A.K., Ingram S.W., Croce C.M., Ohta M., Huebner K.
    Biochemistry 35:11529-11535(1996) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF HIS-35; HIS-94; HIS-96 AND HIS-98.
  • Ref.11

    "Designed FHIT alleles establish that Fhit-induced apoptosis in cancer cells is limited by substrate binding."
    Trapasso F., Krakowiak A., Cesari R., Arkles J., Yendamuri S., Ishii H., Vecchione A., Kuroki T., Bieganowski P., Pace H.C., Huebner K., Croce C.M., Brenner C.
    Proc. Natl. Acad. Sci. U.S.A. 100:1592-1597(2003) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF ILE-10; LEU-25 AND HIS-96.
  • Ref.12

    "The mechanism of action of the fragile histidine triad, Fhit: isolation of a covalent adenylyl enzyme and chemical rescue of H96G-Fhit."
    Huang K., Arabshahi A., Wei Y., Frey P.A.
    Biochemistry 43:7637-7642(2004) [PubMed] [Europe PMC] [Abstract]

    Cited for: ACTIVE SITE, CATALYTIC ACTIVITY, MUTAGENESIS OF HIS-96.
  • Ref.20

    "Structure-based analysis of catalysis and substrate definition in the HIT protein family."
    Lima C.D., Klein M.G., Hendrickson W.A.
    Science 278:286-290(1997) [PubMed] [Europe PMC] [Abstract]

    Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEXES WITH SUBSTRATES, CATALYTIC ACTIVITY, FUNCTION, SUBUNIT, ACTIVE SITE.
  • Ref.21

    "Genetic, biochemical, and crystallographic characterization of Fhit-substrate complexes as the active signaling form of Fhit."
    Pace H.C., Garrison P.N., Robinson A.K., Barnes L.D., Draganescu A., Roesler A., Blackburn G.M., Siprashvili Z., Croce C.M., Huebner K., Brenner C.
    Proc. Natl. Acad. Sci. U.S.A. 95:5484-5489(1998) [PubMed] [Europe PMC] [Abstract]

    Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) IN COMPLEXES WITH SUBSTRATE ANALOGS, SUBUNIT, CATALYTIC ACTIVITY, MUTAGENESIS OF HIS-96.
  EC:3.6.1.29
  • Search proteins in UniProtKB for this EC number.
  • See the description of this EC number in ENZYME.
  5 Publications

  Manual assertion based on experiment inⁱ

  • Ref.8

    "Fhit, a putative tumor suppressor in humans, is a dinucleoside 5',5''-P1,P3-triphosphate hydrolase."
    Barnes L.D., Garrison P.N., Siprashvili Z., Guranowski A., Robinson A.K., Ingram S.W., Croce C.M., Ohta M., Huebner K.
    Biochemistry 35:11529-11535(1996) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF HIS-35; HIS-94; HIS-96 AND HIS-98.
  • Ref.11

    "Designed FHIT alleles establish that Fhit-induced apoptosis in cancer cells is limited by substrate binding."
    Trapasso F., Krakowiak A., Cesari R., Arkles J., Yendamuri S., Ishii H., Vecchione A., Kuroki T., Bieganowski P., Pace H.C., Huebner K., Croce C.M., Brenner C.
    Proc. Natl. Acad. Sci. U.S.A. 100:1592-1597(2003) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF ILE-10; LEU-25 AND HIS-96.
  • Ref.12

    "The mechanism of action of the fragile histidine triad, Fhit: isolation of a covalent adenylyl enzyme and chemical rescue of H96G-Fhit."
    Huang K., Arabshahi A., Wei Y., Frey P.A.
    Biochemistry 43:7637-7642(2004) [PubMed] [Europe PMC] [Abstract]

    Cited for: ACTIVE SITE, CATALYTIC ACTIVITY, MUTAGENESIS OF HIS-96.
  • Ref.20

    "Structure-based analysis of catalysis and substrate definition in the HIT protein family."
    Lima C.D., Klein M.G., Hendrickson W.A.
    Science 278:286-290(1997) [PubMed] [Europe PMC] [Abstract]

    Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEXES WITH SUBSTRATES, CATALYTIC ACTIVITY, FUNCTION, SUBUNIT, ACTIVE SITE.
  • Ref.21

    "Genetic, biochemical, and crystallographic characterization of Fhit-substrate complexes as the active signaling form of Fhit."
    Pace H.C., Garrison P.N., Robinson A.K., Barnes L.D., Draganescu A., Roesler A., Blackburn G.M., Siprashvili Z., Croce C.M., Huebner K., Brenner C.
    Proc. Natl. Acad. Sci. U.S.A. 95:5484-5489(1998) [PubMed] [Europe PMC] [Abstract]

    Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) IN COMPLEXES WITH SUBSTRATE ANALOGS, SUBUNIT, CATALYTIC ACTIVITY, MUTAGENESIS OF HIS-96.
  Source: Rhea

  • Search for this reaction in UniProtKB.
  • See the description of this reaction in Rhea.

  . Show »« Hide
  H₂O

  • Search proteins in UniProtKB for this molecule.
  • Search chemical reactions in Rhea for this molecule.
  • See the description of this molecule in ChEBI.

  

  +

  P¹,P³-bis(5'-adenosyl) triphosphate

  • Search proteins in UniProtKB for this molecule.
  • Search chemical reactions in Rhea for this molecule.
  • See the description of this molecule in ChEBI.

  zoom

  =

  ADP

  • Search proteins in UniProtKB for this molecule.
  • Search chemical reactions in Rhea for this molecule.
  • See the description of this molecule in ChEBI.

  

  +

  AMP

  • Search proteins in UniProtKB for this molecule.
  • Search chemical reactions in Rhea for this molecule.
  • See the description of this molecule in ChEBI.

  

  +

  2

  H⁺

  • Search proteins in UniProtKB for this molecule.
  • Search chemical reactions in Rhea for this molecule.
  • See the description of this molecule in ChEBI.

  

Sites

Regions

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functionⁱ

• bis(5'-adenosyl)-triphosphatase activity Source: UniProtKB <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ
  • Ref.8

    "Fhit, a putative tumor suppressor in humans, is a dinucleoside 5',5''-P1,P3-triphosphate hydrolase."
    Barnes L.D., Garrison P.N., Siprashvili Z., Guranowski A., Robinson A.K., Ingram S.W., Croce C.M., Ohta M., Huebner K.
    Biochemistry 35:11529-11535(1996) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF HIS-35; HIS-94; HIS-96 AND HIS-98.
  • Ref.20

    "Structure-based analysis of catalysis and substrate definition in the HIT protein family."
    Lima C.D., Klein M.G., Hendrickson W.A.
    Science 278:286-290(1997) [PubMed] [Europe PMC] [Abstract]

    Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEXES WITH SUBSTRATES, CATALYTIC ACTIVITY, FUNCTION, SUBUNIT, ACTIVE SITE.
• catalytic activity Source: ProtInc <p>Traceable Author Statement</p> <p>Used for information from review articles where the original experiments are traceable through that article and also for information from text books or dictionaries.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#tas">GO evidence code guide</a></p> Traceable author statementⁱ
  • Ref.1

    "The FHIT gene, spanning the chromosome 3p14.2 fragile site and renal carcinoma-associated t(3;8) breakpoint, is abnormal in digestive tract cancers."
    Ohta M., Inoue H., Cotticelli M.G., Kastury K., Baffa R., Palazzo J., Siprashvili Z., Mori M., McCue P., Druck T., Croce C.M., Huebner K.
    Cell 84:587-597(1996) [PubMed] [Europe PMC] [Abstract]

    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
• hydrolase activity Source: UniProtKBInferred from direct assayⁱ
  • Ref.8

    "Fhit, a putative tumor suppressor in humans, is a dinucleoside 5',5''-P1,P3-triphosphate hydrolase."
    Barnes L.D., Garrison P.N., Siprashvili Z., Guranowski A., Robinson A.K., Ingram S.W., Croce C.M., Ohta M., Huebner K.
    Biochemistry 35:11529-11535(1996) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF HIS-35; HIS-94; HIS-96 AND HIS-98.
• identical protein binding Source: IntAct <p>Inferred from Physical Interaction</p> <p>Covers physical interactions between the gene product of interest and another molecule (or ion, or complex).</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#ipi">GO evidence code guide</a></p> Inferred from physical interactionⁱ
  • "Towards a proteome-scale map of the human protein-protein interaction network."
    Rual J.F., Venkatesan K., Hao T., Hirozane-Kishikawa T., Dricot A., Li N., Berriz G.F., Gibbons F.D., Dreze M., Ayivi-Guedehoussou N., Klitgord N., Simon C., Boxem M., Milstein S., Rosenberg J., Goldberg D.S., Zhang L.V., Wong S.L.

    , Franklin G., Li S., Albala J.S., Lim J., Fraughton C., Llamosas E., Cevik S., Bex C., Lamesch P., Sikorski R.S., Vandenhaute J., Zoghbi H.Y., Smolyar A., Bosak S., Sequerra R., Doucette-Stamm L., Cusick M.E., Hill D.E., Roth F.P., Vidal M.
    Nature 437:1173-1178(2005) [PubMed] [Europe PMC] [Abstract]
  • Ref.16

    "The tumor suppressor Fhit acts as a repressor of beta-catenin transcriptional activity."
    Weiske J., Albring K.F., Huber O.
    Proc. Natl. Acad. Sci. U.S.A. 104:20344-20349(2007) [PubMed] [Europe PMC] [Abstract]

    Cited for: INTERACTION WITH CTNNB1, IDENTIFICATION IN A COMPLEX WITH CTNNB1 AND LEF1, FUNCTION.
  • Ref.3

    "Protein interaction network of alternatively spliced isoforms from brain links genetic risk factors for autism."
    Corominas R., Yang X., Lin G.N., Kang S., Shen Y., Ghamsari L., Broly M., Rodriguez M., Tam S., Wanamaker S.A., Fan C., Yi S., Tasan M., Lemmens I., Kuang X., Zhao N., Malhotra D., Michaelson J.J.

    , Vacic V., Calderwood M.A., Roth F.P., Tavernier J., Horvath S., Salehi-Ashtiani K., Korkin D., Sebat J., Hill D.E., Hao T., Vidal M., Iakoucheva L.M.
    Nat. Commun. 5:3650-3650(2014) [PubMed] [Europe PMC] [Abstract]

    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  • "A proteome-scale map of the human interactome network."
    Rolland T., Tasan M., Charloteaux B., Pevzner S.J., Zhong Q., Sahni N., Yi S., Lemmens I., Fontanillo C., Mosca R., Kamburov A., Ghiassian S.D., Yang X., Ghamsari L., Balcha D., Begg B.E., Braun P., Brehme M.

    , Broly M.P., Carvunis A.R., Convery-Zupan D., Corominas R., Coulombe-Huntington J., Dann E., Dreze M., Dricot A., Fan C., Franzosa E., Gebreab F., Gutierrez B.J., Hardy M.F., Jin M., Kang S., Kiros R., Lin G.N., Luck K., MacWilliams A., Menche J., Murray R.R., Palagi A., Poulin M.M., Rambout X., Rasla J., Reichert P., Romero V., Ruyssinck E., Sahalie J.M., Scholz A., Shah A.A., Sharma A., Shen Y., Spirohn K., Tam S., Tejeda A.O., Trigg S.A., Twizere J.C., Vega K., Walsh J., Cusick M.E., Xia Y., Barabasi A.L., Iakoucheva L.M., Aloy P., De Las Rivas J., Tavernier J., Calderwood M.A., Hill D.E., Hao T., Roth F.P., Vidal M.
    Cell 159:1212-1226(2014) [PubMed] [Europe PMC] [Abstract]
  • "Pooled-matrix protein interaction screens using Barcode Fusion Genetics."
    Yachie N., Petsalaki E., Mellor J.C., Weile J., Jacob Y., Verby M., Ozturk S.B., Li S., Cote A.G., Mosca R., Knapp J.J., Ko M., Yu A., Gebbia M., Sahni N., Yi S., Tyagi T., Sheykhkarimli D.

    , Roth J.F., Wong C., Musa L., Snider J., Liu Y.C., Yu H., Braun P., Stagljar I., Hao T., Calderwood M.A., Pelletier L., Aloy P., Hill D.E., Vidal M., Roth F.P.
    Mol Syst Biol 12:863-863(2016) [PubMed] [Europe PMC] [Abstract]
  • "Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations."
    Fragoza R., Das J., Wierbowski S.D., Liang J., Tran T.N., Liang S., Beltran J.F., Rivera-Erick C.A., Ye K., Wang T.Y., Yao L., Mort M., Stenson P.D., Cooper D.N., Wei X., Keinan A., Schimenti J.C., Clark A.G., Yu H.
    Nat Commun 10:4141-4141(2019) [PubMed] [Europe PMC] [Abstract]
  • "A reference map of the human binary protein interactome."
    Luck K., Kim D.K., Lambourne L., Spirohn K., Begg B.E., Bian W., Brignall R., Cafarelli T., Campos-Laborie F.J., Charloteaux B., Choi D., Cote A.G., Daley M., Deimling S., Desbuleux A., Dricot A., Gebbia M., Hardy M.F.

    , Kishore N., Knapp J.J., Kovacs I.A., Lemmens I., Mee M.W., Mellor J.C., Pollis C., Pons C., Richardson A.D., Schlabach S., Teeking B., Yadav A., Babor M., Balcha D., Basha O., Bowman-Colin C., Chin S.F., Choi S.G., Colabella C., Coppin G., D'Amata C., De Ridder D., De Rouck S., Duran-Frigola M., Ennajdaoui H., Goebels F., Goehring L., Gopal A., Haddad G., Hatchi E., Helmy M., Jacob Y., Kassa Y., Landini S., Li R., van Lieshout N., MacWilliams A., Markey D., Paulson J.N., Rangarajan S., Rasla J., Rayhan A., Rolland T., San-Miguel A., Shen Y., Sheykhkarimli D., Sheynkman G.M., Simonovsky E., Tasan M., Tejeda A., Tropepe V., Twizere J.C., Wang Y., Weatheritt R.J., Weile J., Xia Y., Yang X., Yeger-Lotem E., Zhong Q., Aloy P., Bader G.D., De Las Rivas J., Gaudet S., Hao T., Rak J., Tavernier J., Hill D.E., Vidal M., Roth F.P., Calderwood M.A.
    Nature 580:402-408(2020) [PubMed] [Europe PMC] [Abstract]
  • Ref.19

    "MAD analysis of FHIT, a putative human tumor suppressor from the HIT protein family."
    Lima C.D., D'Amico K.L., Naday I., Rosenbaum G., Westbrook E.M., Hendrickson W.A.
    Structure 5:763-774(1997) [PubMed] [Europe PMC] [Abstract]

    Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS).
  • Ref.21

    "Genetic, biochemical, and crystallographic characterization of Fhit-substrate complexes as the active signaling form of Fhit."
    Pace H.C., Garrison P.N., Robinson A.K., Barnes L.D., Draganescu A., Roesler A., Blackburn G.M., Siprashvili Z., Croce C.M., Huebner K., Brenner C.
    Proc. Natl. Acad. Sci. U.S.A. 95:5484-5489(1998) [PubMed] [Europe PMC] [Abstract]

    Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) IN COMPLEXES WITH SUBSTRATE ANALOGS, SUBUNIT, CATALYTIC ACTIVITY, MUTAGENESIS OF HIS-96.
• nucleotide binding Source: UniProtKB-KW
• ubiquitin protein ligase binding Source: UniProtKBInferred from physical interactionⁱ
  • Ref.13

    "Synergistic tumor suppression by coexpression of FHIT and p53 coincides with FHIT-mediated MDM2 inactivation and p53 stabilization in human non-small cell lung cancer cells."
    Nishizaki M., Sasaki J., Fang B., Atkinson E.N., Minna J.D., Roth J.A., Ji L.
    Cancer Res. 64:5745-5752(2004) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH MDM2.

GO - Biological processⁱ

• diadenosine triphosphate catabolic process Source: GO_Central <p>Inferred from Biological aspect of Ancestor</p> <p>A type of phylogenetic evidence whereby an aspect of a descendent is inferred through the characterization of an aspect of a ancestral gene.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#iba">GO evidence code guide</a></p> Inferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief Bioinform 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
• intrinsic apoptotic signaling pathway by p53 class mediator Source: UniProtKB <p>Inferred from Mutant Phenotype</p> <p>Describes annotations that are concluded from looking at variations or changes in a gene product such as mutations or abnormal levels and includes techniques such as knockouts, overexpression, anti-sense experiments and use of specific protein inhibitors.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#imp">GO evidence code guide</a></p> Inferred from mutant phenotypeⁱ
  • Ref.13

    "Synergistic tumor suppression by coexpression of FHIT and p53 coincides with FHIT-mediated MDM2 inactivation and p53 stabilization in human non-small cell lung cancer cells."
    Nishizaki M., Sasaki J., Fang B., Atkinson E.N., Minna J.D., Roth J.A., Ji L.
    Cancer Res. 64:5745-5752(2004) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH MDM2.
• negative regulation of proteasomal ubiquitin-dependent protein catabolic process Source: UniProtKBInferred from mutant phenotypeⁱ
  • Ref.13

    "Synergistic tumor suppression by coexpression of FHIT and p53 coincides with FHIT-mediated MDM2 inactivation and p53 stabilization in human non-small cell lung cancer cells."
    Nishizaki M., Sasaki J., Fang B., Atkinson E.N., Minna J.D., Roth J.A., Ji L.
    Cancer Res. 64:5745-5752(2004) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH MDM2.
• nucleotide metabolic process Source: ProtIncTraceable author statementⁱ
  • Ref.8

    "Fhit, a putative tumor suppressor in humans, is a dinucleoside 5',5''-P1,P3-triphosphate hydrolase."
    Barnes L.D., Garrison P.N., Siprashvili Z., Guranowski A., Robinson A.K., Ingram S.W., Croce C.M., Ohta M., Huebner K.
    Biochemistry 35:11529-11535(1996) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF HIS-35; HIS-94; HIS-96 AND HIS-98.
• purine nucleotide metabolic process Source: UniProtKBInferred from direct assayⁱ
  • Ref.20

    "Structure-based analysis of catalysis and substrate definition in the HIT protein family."
    Lima C.D., Klein M.G., Hendrickson W.A.
    Science 278:286-290(1997) [PubMed] [Europe PMC] [Abstract]

    Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEXES WITH SUBSTRATES, CATALYTIC ACTIVITY, FUNCTION, SUBUNIT, ACTIVE SITE.

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsⁱ

Enzyme and pathway databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyⁱ

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationⁱ

Keywords - Cellular componentⁱ

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechⁱ

<p>This subsection of the 'Pathology and Biotech' section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseaseⁱ

Mutagenesis

Keywords - Diseaseⁱ

Organism-specific databases

Miscellaneous databases

Chemistry databases

Polymorphism and mutation databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingⁱ

Molecule processing

Amino acid modifications

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationⁱ

Keywords - PTMⁱ

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressionⁱ

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityⁱ

Gene expression databases

Organism-specific databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactionⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structureⁱ

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection">Interaction</a>' section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsⁱ

GO - Molecular functionⁱ

• identical protein binding Source: IntActInferred from physical interactionⁱ
  • "Towards a proteome-scale map of the human protein-protein interaction network."
    Rual J.F., Venkatesan K., Hao T., Hirozane-Kishikawa T., Dricot A., Li N., Berriz G.F., Gibbons F.D., Dreze M., Ayivi-Guedehoussou N., Klitgord N., Simon C., Boxem M., Milstein S., Rosenberg J., Goldberg D.S., Zhang L.V., Wong S.L.

    , Franklin G., Li S., Albala J.S., Lim J., Fraughton C., Llamosas E., Cevik S., Bex C., Lamesch P., Sikorski R.S., Vandenhaute J., Zoghbi H.Y., Smolyar A., Bosak S., Sequerra R., Doucette-Stamm L., Cusick M.E., Hill D.E., Roth F.P., Vidal M.
    Nature 437:1173-1178(2005) [PubMed] [Europe PMC] [Abstract]
  • Ref.16

    "The tumor suppressor Fhit acts as a repressor of beta-catenin transcriptional activity."
    Weiske J., Albring K.F., Huber O.
    Proc. Natl. Acad. Sci. U.S.A. 104:20344-20349(2007) [PubMed] [Europe PMC] [Abstract]

    Cited for: INTERACTION WITH CTNNB1, IDENTIFICATION IN A COMPLEX WITH CTNNB1 AND LEF1, FUNCTION.
  • Ref.3

    "Protein interaction network of alternatively spliced isoforms from brain links genetic risk factors for autism."
    Corominas R., Yang X., Lin G.N., Kang S., Shen Y., Ghamsari L., Broly M., Rodriguez M., Tam S., Wanamaker S.A., Fan C., Yi S., Tasan M., Lemmens I., Kuang X., Zhao N., Malhotra D., Michaelson J.J.

    , Vacic V., Calderwood M.A., Roth F.P., Tavernier J., Horvath S., Salehi-Ashtiani K., Korkin D., Sebat J., Hill D.E., Hao T., Vidal M., Iakoucheva L.M.
    Nat. Commun. 5:3650-3650(2014) [PubMed] [Europe PMC] [Abstract]

    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  • "A proteome-scale map of the human interactome network."
    Rolland T., Tasan M., Charloteaux B., Pevzner S.J., Zhong Q., Sahni N., Yi S., Lemmens I., Fontanillo C., Mosca R., Kamburov A., Ghiassian S.D., Yang X., Ghamsari L., Balcha D., Begg B.E., Braun P., Brehme M.

    , Broly M.P., Carvunis A.R., Convery-Zupan D., Corominas R., Coulombe-Huntington J., Dann E., Dreze M., Dricot A., Fan C., Franzosa E., Gebreab F., Gutierrez B.J., Hardy M.F., Jin M., Kang S., Kiros R., Lin G.N., Luck K., MacWilliams A., Menche J., Murray R.R., Palagi A., Poulin M.M., Rambout X., Rasla J., Reichert P., Romero V., Ruyssinck E., Sahalie J.M., Scholz A., Shah A.A., Sharma A., Shen Y., Spirohn K., Tam S., Tejeda A.O., Trigg S.A., Twizere J.C., Vega K., Walsh J., Cusick M.E., Xia Y., Barabasi A.L., Iakoucheva L.M., Aloy P., De Las Rivas J., Tavernier J., Calderwood M.A., Hill D.E., Hao T., Roth F.P., Vidal M.
    Cell 159:1212-1226(2014) [PubMed] [Europe PMC] [Abstract]
  • "Pooled-matrix protein interaction screens using Barcode Fusion Genetics."
    Yachie N., Petsalaki E., Mellor J.C., Weile J., Jacob Y., Verby M., Ozturk S.B., Li S., Cote A.G., Mosca R., Knapp J.J., Ko M., Yu A., Gebbia M., Sahni N., Yi S., Tyagi T., Sheykhkarimli D.

    , Roth J.F., Wong C., Musa L., Snider J., Liu Y.C., Yu H., Braun P., Stagljar I., Hao T., Calderwood M.A., Pelletier L., Aloy P., Hill D.E., Vidal M., Roth F.P.
    Mol Syst Biol 12:863-863(2016) [PubMed] [Europe PMC] [Abstract]
  • "Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations."
    Fragoza R., Das J., Wierbowski S.D., Liang J., Tran T.N., Liang S., Beltran J.F., Rivera-Erick C.A., Ye K., Wang T.Y., Yao L., Mort M., Stenson P.D., Cooper D.N., Wei X., Keinan A., Schimenti J.C., Clark A.G., Yu H.
    Nat Commun 10:4141-4141(2019) [PubMed] [Europe PMC] [Abstract]
  • "A reference map of the human binary protein interactome."
    Luck K., Kim D.K., Lambourne L., Spirohn K., Begg B.E., Bian W., Brignall R., Cafarelli T., Campos-Laborie F.J., Charloteaux B., Choi D., Cote A.G., Daley M., Deimling S., Desbuleux A., Dricot A., Gebbia M., Hardy M.F.

    , Kishore N., Knapp J.J., Kovacs I.A., Lemmens I., Mee M.W., Mellor J.C., Pollis C., Pons C., Richardson A.D., Schlabach S., Teeking B., Yadav A., Babor M., Balcha D., Basha O., Bowman-Colin C., Chin S.F., Choi S.G., Colabella C., Coppin G., D'Amata C., De Ridder D., De Rouck S., Duran-Frigola M., Ennajdaoui H., Goebels F., Goehring L., Gopal A., Haddad G., Hatchi E., Helmy M., Jacob Y., Kassa Y., Landini S., Li R., van Lieshout N., MacWilliams A., Markey D., Paulson J.N., Rangarajan S., Rasla J., Rayhan A., Rolland T., San-Miguel A., Shen Y., Sheykhkarimli D., Sheynkman G.M., Simonovsky E., Tasan M., Tejeda A., Tropepe V., Twizere J.C., Wang Y., Weatheritt R.J., Weile J., Xia Y., Yang X., Yeger-Lotem E., Zhong Q., Aloy P., Bader G.D., De Las Rivas J., Gaudet S., Hao T., Rak J., Tavernier J., Hill D.E., Vidal M., Roth F.P., Calderwood M.A.
    Nature 580:402-408(2020) [PubMed] [Europe PMC] [Abstract]
  • Ref.19

    "MAD analysis of FHIT, a putative human tumor suppressor from the HIT protein family."
    Lima C.D., D'Amico K.L., Naday I., Rosenbaum G., Westbrook E.M., Hendrickson W.A.
    Structure 5:763-774(1997) [PubMed] [Europe PMC] [Abstract]

    Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS).
  • Ref.21

    "Genetic, biochemical, and crystallographic characterization of Fhit-substrate complexes as the active signaling form of Fhit."
    Pace H.C., Garrison P.N., Robinson A.K., Barnes L.D., Draganescu A., Roesler A., Blackburn G.M., Siprashvili Z., Croce C.M., Huebner K., Brenner C.
    Proc. Natl. Acad. Sci. U.S.A. 95:5484-5489(1998) [PubMed] [Europe PMC] [Abstract]

    Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) IN COMPLEXES WITH SUBSTRATE ANALOGS, SUBUNIT, CATALYTIC ACTIVITY, MUTAGENESIS OF HIS-96.
• ubiquitin protein ligase binding Source: UniProtKBInferred from physical interactionⁱ
  • Ref.13

    "Synergistic tumor suppression by coexpression of FHIT and p53 coincides with FHIT-mediated MDM2 inactivation and p53 stabilization in human non-small cell lung cancer cells."
    Nishizaki M., Sasaki J., Fang B., Atkinson E.N., Minna J.D., Roth J.A., Ji L.
    Cancer Res. 64:5745-5752(2004) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH MDM2.

Protein-protein interaction databases

Chemistry databases

Miscellaneous databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structureⁱ

Secondary structure

3D structure databases

Miscellaneous databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsⁱ

Domains and Repeats

Motif

Phylogenomic databases

Family and domain databases

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequence (1+)ⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusⁱ: Complete.

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

        10         20         30         40         50
MSFRFGQHLI KPSVVFLKTE LSFALVNRKP VVPGHVLVCP LRPVERFHDL 
        60         70         80         90        100
RPDEVADLFQ TTQRVGTVVE KHFHGTSLTF SMQDGPEAGQ TVKHVHVHVL 
       110        120        130        140 
PRKAGDFHRN DSIYEELQKH DKEDFPASWR SEEEMAAEAA ALRVYFQ    

Experimental Info

<p>This subsection of the 'Sequence' section reports information derived from mass spectrometry experiments done on the entire protein or on biologically active derived peptide(s).<p><a href='/help/mass_spectrometry' target='_top'>More...</a></p>Mass spectrometryⁱ

Sequence databases

Genome annotation databases

Keywords - Coding sequence diversityⁱ

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsⁱ

• 100% Identity
• 90% Identity
• 50% Identity

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesⁱ

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross%5Freferences%5Fsection">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesⁱ

Sequence databases

3D structure databases

Protein-protein interaction databases

Chemistry databases

PTM databases

Polymorphism and mutation databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationⁱ

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousⁱ

Keywords - Technical termⁱ

Documents

1. Human chromosome 3
   Human chromosome 3: entries, gene names and cross-references to MIM
2. MIM cross-references
   Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
3. PDB cross-references
   Index of Protein Data Bank (PDB) cross-references