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Protein

Bis(5'-adenosyl)-triphosphatase

Gene

FHIT

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: -Experimental evidence at transcript 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. Functions as tumor suppressor (By similarity).By similarity

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

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
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 22

Organism-specific databases

VGNCiVGNC:28998 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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002884721 – 149Bis(5'-adenosyl)-triphosphataseAdd BLAST149

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei114PhosphotyrosineBy 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

PaxDbiQ1KZG4
PRIDEiQ1KZG4

Expressioni

Tissue specificityi

Expressed in the brain, kidney, spleen, testis and lung.1 Publication

Gene expression databases

BgeeiENSBTAG00000014418

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

STRINGi9913.ENSBTAP00000019177

Structurei

3D structure databases

ProteinModelPortaliQ1KZG4
SMRiQ1KZG4
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 motifPROSITE-ProRule annotation5

Phylogenomic databases

eggNOGiKOG3379 Eukaryota
COG0537 LUCA
GeneTreeiENSGT00510000047967
HOGENOMiHOG000164170
HOVERGENiHBG051614
InParanoidiQ1KZG4
KOiK01522
OMAiKFGPFEV
OrthoDBiEOG091G0RR0
TreeFamiTF105432

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.

Q1KZG4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSFRFGQHLI KPSVVFLKTE LSFALVNRKP VVPGHVLVCP LRPVERFRDM
60 70 80 90 100
SPEEVADLFQ AAQRVGTVVE KHFQGTSLTF SMQDGPEAGQ TVKHVHVHIL
110 120 130 140
PRKAGDFHRN DSIYDALEKH DREDKDSPAL WRSEEEMAAE AAALRVYFQ
Length:149
Mass (Da):16,951
Last modified:May 30, 2006 - v1
Checksum:iC7E39594A5982F24
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
DQ335870 mRNA Translation: ABC61315.1
DQ310184 mRNA Translation: ABC61471.1
DQ310183 mRNA Translation: ABC61470.1
DQ310181 mRNA Translation: ABC61468.1
DQ310182 mRNA Translation: ABC61469.1
DQ310179
, DQ310176, DQ310177, DQ310178 Genomic DNA Translation: ABC68307.1
BC147993 mRNA Translation: AAI47994.1
RefSeqiNP_001035736.1, NM_001040646.1
UniGeneiBt.26240

Genome annotation databases

EnsembliENSBTAT00000019177; ENSBTAP00000019177; ENSBTAG00000014418
GeneIDi692183
KEGGibta:692183

Similar proteinsi

Entry informationi

Entry nameiFHIT_BOVIN
AccessioniPrimary (citable) accession number: Q1KZG4
Secondary accession number(s): A6QLK1, Q1KZS9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 29, 2007
Last sequence update: May 30, 2006
Last modified: March 28, 2018
This is version 76 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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