Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

O89106 (FHIT_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 101. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Fhit
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length150 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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. Ref.6 Ref.7

Catalytic activity

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

Cofactor

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

Subunit structure

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

Subcellular location

Cytoplasm Ref.1.

Tissue specificity

Expressed in heart, brain, lung and skeletal muscle. Particularly strong expression in liver, testis and kidney, where it is confined to the tubular epithelium. Ref.1 Ref.5

Post-translational modification

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

Disruption phenotype

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. Ref.6 Ref.7

Sequence similarities

Contains 1 HIT domain.

Ontologies

Keywords
   Biological processApoptosis
Transcription
Transcription regulation
   Cellular componentCytoplasm
   LigandMagnesium
Manganese
Nucleotide-binding
   Molecular functionHydrolase
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA replication

Inferred from direct assay PubMed 15254237. Source: MGI

intrinsic apoptotic signaling pathway by p53 class mediator

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of proteasomal ubiquitin-dependent protein catabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

nucleotide metabolic process

Traceable author statement PubMed 8794732. Source: ProtInc

purine nucleotide metabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasm

Inferred from direct assay Ref.1. Source: UniProtKB

cytosol

Inferred from sequence or structural similarity. Source: UniProtKB

intracellular membrane-bounded organelle

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionbis(5'-adenosyl)-triphosphatase activity

Inferred from direct assay PubMed 8794732. Source: UniProtKB

catalytic activity

Traceable author statement PubMed 8598045. Source: ProtInc

hydrolase activity

Inferred from direct assay PubMed 8794732. Source: UniProtKB

nucleotide binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 150150Bis(5'-adenosyl)-triphosphatase
PRO_0000109790

Regions

Domain2 – 109108HIT
Nucleotide binding89 – 924Substrate By similarity
Motif94 – 985Histidine triad motif

Sites

Active site961Tele-AMP-histidine intermediate By similarity
Binding site81Substrate By similarity
Binding site271Substrate By similarity
Binding site831Substrate By similarity
Binding site981Substrate By similarity
Site1141Important for induction of apoptosis By similarity

Amino acid modifications

Modified residue1141Phosphotyrosine; by SRC By similarity
Modified residue1471Phosphotyrosine By similarity

Experimental info

Sequence conflict1351K → E in AAH12662. Ref.3

Sequences

Sequence LengthMass (Da)Tools
O89106 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: 27CBC57C5A4A0E2B

FASTA15017,235
        10         20         30         40         50         60 
MSFRFGQHLI KPSVVFLKTE LSFALVNRKP VVPGHVLVCP LRPVERFRDL HPDEVADLFQ 

        70         80         90        100        110        120 
VTQRVGTVVE KHFQGTSITF SMQDGPEAGQ TVKHVHVHVL PRKAGDFPRN DNIYDELQKH 

       130        140        150 
DREEEDSPAF WRSEKEMAAE AEALRVYFQA 

« Hide

References

« Hide 'large scale' references
[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]"Muir-Torre-like syndrome in Fhit-deficient mice."
Fong L.Y., Fidanza V., Zanesi N., Lock L.F., Siracusa L.D., Mancini R., Siprashvili Z., Ottey M., Martin S.E., Druck T., McCue P.A., Croce C.M., Huebner K.
Proc. Natl. Acad. Sci. U.S.A. 97:4742-4747(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, FUNCTION.
[7]"The tumor spectrum in FHIT-deficient mice."
Zanesi N., Fidanza V., Fong L.Y., Mancini R., Druck T., Valtieri M., Rudiger T., McCue P.A., Croce C.M., Huebner K.
Proc. Natl. Acad. Sci. U.S.A. 98:10250-10255(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS49400.1.
RefSeqNP_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.
UniGeneMm.397619.
Mm.441926.

3D structure databases

ProteinModelPortalO89106.
SMRO89106. Positions 2-149.
ModBaseSearch...
MobiDBSearch...

PTM databases

PhosphoSiteO89106.

Proteomic databases

MaxQBO89106.
PaxDbO89106.
PRIDEO89106.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000161302; ENSMUSP00000123874; ENSMUSG00000060579.
ENSMUST00000162278; ENSMUSP00000124073; ENSMUSG00000060579.
ENSMUST00000179394; ENSMUSP00000136011; ENSMUSG00000060579.
GeneID14198.
KEGGmmu:14198.
UCSCuc007sfj.1. mouse.

Organism-specific databases

CTD2272.
MGIMGI:1277947. Fhit.

Phylogenomic databases

eggNOGCOG0537.
GeneTreeENSGT00510000047967.
HOGENOMHOG000164170.
HOVERGENHBG051614.
InParanoidO89106.
KOK01522.
OrthoDBEOG7XDBGD.
PhylomeDBO89106.

Gene expression databases

ArrayExpressO89106.
BgeeO89106.
CleanExMM_FHIT.
GenevestigatorO89106.

Family and domain databases

Gene3D3.30.428.10. 1 hit.
InterProIPR019808. Histidine_triad_CS.
IPR001310. Histidine_triad_HIT.
IPR011146. HIT-like.
[Graphical view]
PANTHERPTHR23089. PTHR23089. 1 hit.
PfamPF01230. HIT. 1 hit.
[Graphical view]
SUPFAMSSF54197. SSF54197. 1 hit.
PROSITEPS00892. HIT_1. 1 hit.
PS51084. HIT_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio285422.
PROO89106.
SOURCESearch...

Entry information

Entry nameFHIT_MOUSE
AccessionPrimary (citable) accession number: O89106
Secondary accession number(s): Q6URW5, Q91VL1
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: January 23, 2007
Last modified: July 9, 2014
This is version 101 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot