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O89106

- FHIT_MOUSE

UniProt

O89106 - FHIT_MOUSE

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Protein

Bis(5'-adenosyl)-triphosphatase

Gene

Fhit

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

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

Mg2+By similarity, Mn2+By similarity, Ca2+By similarity, Co2+By similarityNote: Divalent metal cations. Mg(2+), but Mn(2+) and to a lesser extent Ca(2+) or Co(2+) can be substituted; but not Zn(2+), Cd(2+) or Ni(2+).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
Complete GO annotation...

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
Complete GO annotation...

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

BgeeiO89106.
CleanExiMM_FHIT.
ExpressionAtlasiO89106. baseline and differential.
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

        10         20         30         40         50
MSFRFGQHLI KPSVVFLKTE LSFALVNRKP VVPGHVLVCP LRPVERFRDL
60 70 80 90 100
HPDEVADLFQ VTQRVGTVVE KHFQGTSITF SMQDGPEAGQ TVKHVHVHVL
110 120 130 140 150
PRKAGDFPRN DNIYDELQKH DREEEDSPAF WRSEKEMAAE AEALRVYFQA
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:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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

Bgeei O89106.
CleanExi MM_FHIT.
ExpressionAtlasi O89106. baseline and differential.
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

« Hide 'large scale' publications
  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: November 26, 2014
This is version 104 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