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Protein

Bis(5'-adenosyl)-triphosphatase

Gene

FHIT

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 4 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. Functions as tumor suppressor (By similarity).By similarity

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. 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)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

GO - Biological processi

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

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 149149Bis(5'-adenosyl)-triphosphatasePRO_0000288472Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei114 – 1141PhosphotyrosineBy 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

PaxDbiQ1KZG4.
PRIDEiQ1KZG4.

Expressioni

Tissue specificityi

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

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

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000019177.

Structurei

3D structure databases

ProteinModelPortaliQ1KZG4.
SMRiQ1KZG4. 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 motifPROSITE-ProRule annotation

Sequence similaritiesi

Contains 1 HIT domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG3379. Eukaryota.
COG0537. LUCA.
GeneTreeiENSGT00510000047967.
HOGENOMiHOG000164170.
HOVERGENiHBG051614.
InParanoidiQ1KZG4.
KOiK01522.
OMAiWANNDDI.
OrthoDBiEOG7XDBGD.
TreeFamiTF105432.

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.

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.

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliQ1KZG4.
SMRiQ1KZG4. Positions 2-149.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000019177.

Proteomic databases

PaxDbiQ1KZG4.
PRIDEiQ1KZG4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000019177; ENSBTAP00000019177; ENSBTAG00000014418.
GeneIDi692183.
KEGGibta:692183.

Organism-specific databases

CTDi2272.

Phylogenomic databases

eggNOGiKOG3379. Eukaryota.
COG0537. LUCA.
GeneTreeiENSGT00510000047967.
HOGENOMiHOG000164170.
HOVERGENiHBG051614.
InParanoidiQ1KZG4.
KOiK01522.
OMAiWANNDDI.
OrthoDBiEOG7XDBGD.
TreeFamiTF105432.

Miscellaneous databases

NextBioi20902465.

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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Evidence that bovine forebrain embryonic zinc finger-like gene influences immune response associated with mastitis resistance."
    Sugimoto M., Fujikawa A., Womack J.E., Sugimoto Y.
    Proc. Natl. Acad. Sci. U.S.A. 103:6454-6459(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Comparative genomic mapping of the bovine Fragile Histidine Triad (FHIT) tumour suppressor gene: characterization of a 2 Mb BAC contig covering the locus, complete annotation of the gene, analysis of cDNA and of physiological expression profiles."
    Uboldi C., Guidi E., Roperto S., Russo V., Roperto F., Di Meo G.P., Iannuzzi L., Floriot S., Boussaha M., Eggen A., Ferretti L.
    BMC Genomics 7:123-123(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-116, TISSUE SPECIFICITY.
  3. NIH - Mammalian Gene Collection (MGC) project
    Submitted (JUN-2007) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: Hereford.
    Tissue: Basal ganglia.

Entry informationi

Entry nameiFHIT_BOVIN
AccessioniPrimary (citable) accession number: Q1KZG4
Secondary accession number(s): A6QLK1, Q1KZS9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 29, 2007
Last sequence update: May 30, 2006
Last modified: May 11, 2016
This is version 66 of the entry and version 1 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. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.