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O89106

- FHIT_MOUSE

UniProt

O89106 - FHIT_MOUSE

Protein

Bis(5'-adenosyl)-triphosphatase

Gene

Fhit

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
  1. Functioni

    Cleaves P(1)-P(3)-bis(5'-adenosyl) triphosphate (Ap3A) to yield AMP and ADP. Can also hydrolyze P(1)-P(4)-bis(5'-adenosyl) tetraphosphate (Ap4A), but has extremely low activity with ATP. Modulates transcriptional activation by CTNNB1 and thereby contributes to regulate the expression of genes essential for cell proliferation and survival, such as CCND1 and BIRC5. Plays a role in the induction of apoptosis via SRC and AKT1 signaling pathways. Inhibits MDM2-mediated proteasomal degradation of p53/TP53 and thereby plays a role in p53/TP53-mediated apoptosis. Induction of apoptosis depends on the ability of FHIT to bind P(1)-P(3)-bis(5'-adenosyl) triphosphate or related compounds, but does not require its catalytic activity By similarity. Functions as tumor suppressor.By similarity2 Publications

    Catalytic activityi

    P(1)-P(3)-bis(5'-adenosyl) triphosphate + H2O = ADP + AMP.

    Cofactori

    Divalent cations. Magnesium, but manganese and to a lesser extent calcium or cobalt can be substituted; but not zinc, cadmium or nickel By similarity.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei8 – 81SubstrateBy similarity
    Binding sitei27 – 271SubstrateBy similarity
    Binding sitei83 – 831SubstrateBy similarity
    Active sitei96 – 961Tele-AMP-histidine intermediateBy similarity
    Binding sitei98 – 981SubstrateBy similarity
    Sitei114 – 1141Important for induction of apoptosisBy similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi89 – 924SubstrateBy similarity

    GO - Molecular functioni

    1. bis(5'-adenosyl)-triphosphatase activity Source: UniProtKB
    2. catalytic activity Source: ProtInc
    3. hydrolase activity Source: UniProtKB
    4. nucleotide binding Source: UniProtKB-KW

    GO - Biological processi

    1. DNA replication Source: MGI
    2. intrinsic apoptotic signaling pathway by p53 class mediator Source: UniProtKB
    3. negative regulation of proteasomal ubiquitin-dependent protein catabolic process Source: UniProtKB
    4. nucleotide metabolic process Source: ProtInc
    5. purine nucleotide metabolic process Source: UniProtKB
    6. regulation of transcription, DNA-templated Source: UniProtKB-KW
    7. transcription, DNA-templated Source: UniProtKB-KW

    Keywords - Molecular functioni

    Hydrolase

    Keywords - Biological processi

    Apoptosis, Transcription, Transcription regulation

    Keywords - Ligandi

    Magnesium, Manganese, Nucleotide-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Bis(5'-adenosyl)-triphosphatase (EC:3.6.1.29)
    Alternative name(s):
    AP3A hydrolase
    Short name:
    AP3Aase
    Diadenosine 5',5'''-P1,P3-triphosphate hydrolase
    Dinucleosidetriphosphatase
    Fragile histidine triad protein
    Gene namesi
    Name:Fhit
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 14

    Organism-specific databases

    MGIiMGI:1277947. Fhit.

    Subcellular locationi

    Cytoplasm 1 Publication

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. cytosol Source: UniProtKB
    3. intracellular membrane-bounded organelle Source: Ensembl

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Disruption phenotypei

    No visible phenotype at birth, but about 30% of the mice lacking one or both copies of Fhit died for unknown reasons at an age of about 19 months. This might be due to increased susceptibility to infections. Mice lacking one or both copies of Fhit show increased susceptibility to carcinogens.2 Publications

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 150150Bis(5'-adenosyl)-triphosphatasePRO_0000109790Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei114 – 1141Phosphotyrosine; by SRCBy similarity
    Modified residuei147 – 1471PhosphotyrosineBy similarity

    Post-translational modificationi

    Phosphorylation at Tyr-114 by SRC is required for induction of apoptosis.By similarity

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiO89106.
    PaxDbiO89106.
    PRIDEiO89106.

    PTM databases

    PhosphoSiteiO89106.

    Expressioni

    Tissue specificityi

    Expressed in heart, brain, lung and skeletal muscle. Particularly strong expression in liver, testis and kidney, where it is confined to the tubular epithelium.2 Publications

    Gene expression databases

    ArrayExpressiO89106.
    BgeeiO89106.
    CleanExiMM_FHIT.
    GenevestigatoriO89106.

    Interactioni

    Subunit structurei

    Homodimer. Interacts with UBE2I. Interacts with MDM2. Interacts with CTNNB1. Identified in a complex with CTNNB1 and LEF1 By similarity.By similarity

    Structurei

    3D structure databases

    ProteinModelPortaliO89106.
    SMRiO89106. Positions 2-149.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini2 – 109108HITPROSITE-ProRule annotationAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi94 – 985Histidine triad motif

    Sequence similaritiesi

    Contains 1 HIT domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG0537.
    GeneTreeiENSGT00510000047967.
    HOGENOMiHOG000164170.
    HOVERGENiHBG051614.
    InParanoidiO89106.
    KOiK01522.
    OrthoDBiEOG7XDBGD.
    PhylomeDBiO89106.

    Family and domain databases

    Gene3Di3.30.428.10. 1 hit.
    InterProiIPR019808. Histidine_triad_CS.
    IPR001310. Histidine_triad_HIT.
    IPR011146. HIT-like.
    [Graphical view]
    PANTHERiPTHR23089. PTHR23089. 1 hit.
    PfamiPF01230. HIT. 1 hit.
    [Graphical view]
    SUPFAMiSSF54197. SSF54197. 1 hit.
    PROSITEiPS00892. HIT_1. 1 hit.
    PS51084. HIT_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    O89106-1 [UniParc]FASTAAdd to Basket

    « Hide

    MSFRFGQHLI KPSVVFLKTE LSFALVNRKP VVPGHVLVCP LRPVERFRDL    50
    HPDEVADLFQ VTQRVGTVVE KHFQGTSITF SMQDGPEAGQ TVKHVHVHVL 100
    PRKAGDFPRN DNIYDELQKH DREEEDSPAF WRSEKEMAAE AEALRVYFQA 150
    Length:150
    Mass (Da):17,235
    Last modified:January 23, 2007 - v3
    Checksum:i27CBC57C5A4A0E2B
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti135 – 1351K → E in AAH12662. (PubMed:15489334)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AH006186 Genomic DNA. Translation: AAC23967.1.
    AF047699 mRNA. Translation: AAC24566.1.
    AF055573 mRNA. Translation: AAC24117.1.
    BC012662 mRNA. Translation: AAH12662.1.
    AH013372 Genomic DNA. Translation: AAR17701.1.
    CCDSiCCDS49400.1.
    RefSeqiNP_034340.1. NM_010210.2.
    XP_006517988.1. XM_006517925.1.
    XP_006517989.1. XM_006517926.1.
    XP_006517990.1. XM_006517927.1.
    XP_006517991.1. XM_006517928.1.
    UniGeneiMm.397619.
    Mm.441926.

    Genome annotation databases

    EnsembliENSMUST00000161302; ENSMUSP00000123874; ENSMUSG00000060579.
    ENSMUST00000162278; ENSMUSP00000124073; ENSMUSG00000060579.
    ENSMUST00000179394; ENSMUSP00000136011; ENSMUSG00000060579.
    GeneIDi14198.
    KEGGimmu:14198.
    UCSCiuc007sfj.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AH006186 Genomic DNA. Translation: AAC23967.1 .
    AF047699 mRNA. Translation: AAC24566.1 .
    AF055573 mRNA. Translation: AAC24117.1 .
    BC012662 mRNA. Translation: AAH12662.1 .
    AH013372 Genomic DNA. Translation: AAR17701.1 .
    CCDSi CCDS49400.1.
    RefSeqi NP_034340.1. NM_010210.2.
    XP_006517988.1. XM_006517925.1.
    XP_006517989.1. XM_006517926.1.
    XP_006517990.1. XM_006517927.1.
    XP_006517991.1. XM_006517928.1.
    UniGenei Mm.397619.
    Mm.441926.

    3D structure databases

    ProteinModelPortali O89106.
    SMRi O89106. Positions 2-149.
    ModBasei Search...
    MobiDBi Search...

    PTM databases

    PhosphoSitei O89106.

    Proteomic databases

    MaxQBi O89106.
    PaxDbi O89106.
    PRIDEi O89106.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000161302 ; ENSMUSP00000123874 ; ENSMUSG00000060579 .
    ENSMUST00000162278 ; ENSMUSP00000124073 ; ENSMUSG00000060579 .
    ENSMUST00000179394 ; ENSMUSP00000136011 ; ENSMUSG00000060579 .
    GeneIDi 14198.
    KEGGi mmu:14198.
    UCSCi uc007sfj.1. mouse.

    Organism-specific databases

    CTDi 2272.
    MGIi MGI:1277947. Fhit.

    Phylogenomic databases

    eggNOGi COG0537.
    GeneTreei ENSGT00510000047967.
    HOGENOMi HOG000164170.
    HOVERGENi HBG051614.
    InParanoidi O89106.
    KOi K01522.
    OrthoDBi EOG7XDBGD.
    PhylomeDBi O89106.

    Miscellaneous databases

    NextBioi 285422.
    PROi O89106.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O89106.
    Bgeei O89106.
    CleanExi MM_FHIT.
    Genevestigatori O89106.

    Family and domain databases

    Gene3Di 3.30.428.10. 1 hit.
    InterProi IPR019808. Histidine_triad_CS.
    IPR001310. Histidine_triad_HIT.
    IPR011146. HIT-like.
    [Graphical view ]
    PANTHERi PTHR23089. PTHR23089. 1 hit.
    Pfami PF01230. HIT. 1 hit.
    [Graphical view ]
    SUPFAMi SSF54197. SSF54197. 1 hit.
    PROSITEi PS00892. HIT_1. 1 hit.
    PS51084. HIT_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "The murine Fhit locus: isolation, characterization, and expression in normal and tumor cells."
      Pekarsky Y., Druck T., Cotticelli M.G., Ohta M., Shou J., Mendrola J., Montgomery J.C., Buchberg A.M., Siracusa L.D., Manenti G., Fong L.Y., Dragani T.A., Croce C.M., Huebner K.
      Cancer Res. 58:3401-3408(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    2. Glover T.W., Hoge A., Miller D.E., Escara-Wilke J., Adam A.N., Dagenais S.L., Wilke C.M., Dierick H.A., Beer D.G.
      Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: C57BL/10J.
      Tissue: Muscle.
    3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: FVB/N.
      Tissue: Mammary gland.
    4. "Fragile site orthologs FHIT/FRA3B and Fhit/Fra14A2: evolutionarily conserved but highly recombinogenic."
      Matsuyama A., Shiraishi T., Trapasso F., Kuroki T., Alder H., Mori M., Huebner K., Croce C.M.
      Proc. Natl. Acad. Sci. U.S.A. 100:14988-14993(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 36-150.
      Strain: C57BL/6J.
      Tissue: Kidney.
    5. "Nitrilase and Fhit homologs are encoded as fusion proteins in Drosophila melanogaster and Caenorhabditis elegans."
      Pekarsky Y., Campiglio M., Siprashvili Z., Druck T., Sedkov Y., Tillib S., Draganescu A., Wermuth P., Rothman J.H., Huebner K., Buchberg A.M., Mazo A., Brenner C., Croce C.M.
      Proc. Natl. Acad. Sci. U.S.A. 95:8744-8749(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.
    6. Cited for: DISRUPTION PHENOTYPE, FUNCTION.
    7. Cited for: DISRUPTION PHENOTYPE, FUNCTION.

    Entry informationi

    Entry nameiFHIT_MOUSE
    AccessioniPrimary (citable) accession number: O89106
    Secondary accession number(s): Q6URW5, Q91VL1
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 15, 1999
    Last sequence update: January 23, 2007
    Last modified: October 1, 2014
    This is version 102 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3