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Protein

Bis(5'-adenosyl)-triphosphatase

Gene

Fhit

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

Functioni

Cleaves P1-P3-bis(5'-adenosyl) triphosphate (Ap3A) to yield AMP and ADP. Can also hydrolyze P1-P4-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 P1-P3-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

P1-P3-bis(5'-adenosyl) triphosphate + H2O = ADP + AMP.

Cofactori

Mg2+By similarity, Mn2+By similarity, Ca2+By similarity, Co2+By similarityNote: Divalent metal cations. Mg2+, but Mn2+ and to a lesser extent Ca2+ or Co2+ can be substituted; but not Zn2+, Cd2+ or Ni2+.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei8SubstrateBy similarity1
Binding sitei27SubstrateBy similarity1
Binding sitei83SubstrateBy similarity1
Active sitei96Tele-AMP-histidine intermediateBy similarity1
Binding sitei98SubstrateBy similarity1
Sitei114Important for induction of apoptosisBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi89 – 92SubstrateBy similarity4

GO - Molecular functioni

  • bis(5'-adenosyl)-triphosphatase activity Source: UniProtKB
  • catalytic activity Source: ProtInc
  • hydrolase activity Source: UniProtKB
  • identical protein binding Source: MGI
  • nucleotide binding Source: UniProtKB-KW
  • ubiquitin protein ligase binding Source: MGI

GO - Biological processi

Keywordsi

Molecular functionHydrolase
Biological processApoptosis, Transcription, Transcription regulation
LigandMagnesium, 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 14

Organism-specific databases

MGIiMGI:1277947. Fhit.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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)DescriptionActionsGraphical viewLength
ChainiPRO_00001097901 – 150Bis(5'-adenosyl)-triphosphataseAdd BLAST150

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei114Phosphotyrosine; by SRCBy similarity1
Modified residuei147PhosphotyrosineBy similarity1

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

iPTMnetiO89106.
PhosphoSitePlusiO89106.
SwissPalmiO89106.

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

BgeeiENSMUSG00000060579.
CleanExiMM_FHIT.
ExpressionAtlasiO89106. baseline and differential.
GenevisibleiO89106. MM.

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

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000123874.

Structurei

3D structure databases

ProteinModelPortaliO89106.
SMRiO89106.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini2 – 109HITPROSITE-ProRule annotationAdd BLAST108

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi94 – 98Histidine triad motif5

Phylogenomic databases

eggNOGiKOG3379. Eukaryota.
COG0537. LUCA.
GeneTreeiENSGT00510000047967.
HOGENOMiHOG000164170.
HOVERGENiHBG051614.
InParanoidiO89106.
KOiK01522.
PhylomeDBiO89106.

Family and domain databases

Gene3Di3.30.428.10. 1 hit.
InterProiView protein in InterPro
IPR019808. Histidine_triad_CS.
IPR001310. Histidine_triad_HIT.
IPR011146. HIT-like.
IPR036265. HIT-like_sf.
PANTHERiPTHR23089. PTHR23089. 1 hit.
PfamiView protein in Pfam
PF01230. HIT. 1 hit.
SUPFAMiSSF54197. SSF54197. 1 hit.
PROSITEiView protein in PROSITE
PS00892. HIT_1. 1 hit.
PS51084. HIT_2. 1 hit.

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)DescriptionActionsGraphical viewLength
Sequence conflicti135K → E in AAH12662 (PubMed:15489334).Curated1

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_001295215.1. NM_001308286.1.
NP_034340.1. NM_010210.3.
XP_006517990.1. XM_006517927.3.
XP_011243034.1. XM_011244732.2.
XP_017171336.1. XM_017315847.1.
UniGeneiMm.397619.
Mm.441926.

Genome annotation databases

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

Similar proteinsi

Entry informationi

Entry nameiFHIT_MOUSE
AccessioniPrimary (citable) accession number: O89106
Secondary accession number(s): Q6URW5, Q91VL1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: January 23, 2007
Last modified: October 25, 2017
This is version 125 of the entry and version 3 of the sequence. See 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