FHIT_BOVIN
ID FHIT_BOVIN Reviewed; 149 AA.
AC Q1KZG4; A6QLK1; Q1KZS9;
DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2006, sequence version 1.
DT 03-AUG-2022, entry version 91.
DE RecName: Full=Bis(5'-adenosyl)-triphosphatase;
DE EC=3.6.1.29 {ECO:0000250|UniProtKB:P49789};
DE AltName: Full=AP3A hydrolase;
DE Short=AP3Aase;
DE AltName: Full=Adenosine 5'-monophosphoramidase FHIT {ECO:0000250|UniProtKB:P49789};
DE EC=3.9.1.- {ECO:0000250|UniProtKB:P49789};
DE AltName: Full=Adenylylsulfatase;
DE EC=3.6.2.1 {ECO:0000250|UniProtKB:P49789};
DE AltName: Full=Adenylylsulfate-ammonia adenylyltransferase;
DE EC=2.7.7.51 {ECO:0000250|UniProtKB:P49789};
DE AltName: Full=Diadenosine 5',5'''-P1,P3-triphosphate hydrolase;
DE AltName: Full=Dinucleosidetriphosphatase;
DE AltName: Full=Fragile histidine triad protein;
GN Name=FHIT;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=16611727; DOI=10.1073/pnas.0601015103;
RA Sugimoto M., Fujikawa A., Womack J.E., Sugimoto Y.;
RT "Evidence that bovine forebrain embryonic zinc finger-like gene influences
RT immune response associated with mastitis resistance.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:6454-6459(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-116, AND
RP TISSUE SPECIFICITY.
RX PubMed=16719907; DOI=10.1186/1471-2164-7-123;
RA Uboldi C., Guidi E., Roperto S., Russo V., Roperto F., Di Meo G.P.,
RA Iannuzzi L., Floriot S., Boussaha M., Eggen A., Ferretti L.;
RT "Comparative genomic mapping of the bovine Fragile Histidine Triad (FHIT)
RT tumour suppressor gene: characterization of a 2 Mb BAC contig covering the
RT locus, complete annotation of the gene, analysis of cDNA and of
RT physiological expression profiles.";
RL BMC Genomics 7:123-123(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Basal ganglia;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (JUN-2007) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Possesses dinucleoside triphosphate hydrolase activity (By
CC similarity). Cleaves P(1)-P(3)-bis(5'-adenosyl) triphosphate (Ap3A) to
CC yield AMP and ADP (By similarity). Can also hydrolyze P(1)-P(4)-bis(5'-
CC adenosyl) tetraphosphate (Ap4A), but has extremely low activity with
CC ATP (By similarity). Exhibits adenylylsulfatase activity, hydrolyzing
CC adenosine 5'-phosphosulfate to yield AMP and sulfate (By similarity).
CC Exhibits adenosine 5'-monophosphoramidase activity, hydrolyzing purine
CC nucleotide phosphoramidates with a single phosphate group such as
CC adenosine 5'monophosphoramidate (AMP-NH2) to yield AMP and NH2 (By
CC similarity). Exhibits adenylylsulfate-ammonia adenylyltransferase,
CC catalyzing the ammonolysis of adenosine 5'-phosphosulfate resulting in
CC the formation of adenosine 5'-phosphoramidate (By similarity). Also
CC catalyzes the ammonolysis of adenosine 5-phosphorofluoridate and
CC diadenosine triphosphate (By similarity). Modulates transcriptional
CC activation by CTNNB1 and thereby contributes to regulate the expression
CC of genes essential for cell proliferation and survival, such as CCND1
CC and BIRC5 (By similarity). Plays a role in the induction of apoptosis
CC via SRC and AKT1 signaling pathways (By similarity). Inhibits MDM2-
CC mediated proteasomal degradation of p53/TP53 and thereby plays a role
CC in p53/TP53-mediated apoptosis (By similarity). Induction of apoptosis
CC depends on the ability of FHIT to bind P(1)-P(3)-bis(5'-adenosyl)
CC triphosphate or related compounds, but does not require its catalytic
CC activity (By similarity) Functions as tumor suppressor (By similarity).
CC {ECO:0000250|UniProtKB:O89106, ECO:0000250|UniProtKB:P49789}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + P(1),P(3)-bis(5'-adenosyl) triphosphate = ADP + AMP + 2
CC H(+); Xref=Rhea:RHEA:13893, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:58529, ChEBI:CHEBI:456215, ChEBI:CHEBI:456216;
CC EC=3.6.1.29; Evidence={ECO:0000250|UniProtKB:P49789};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=adenosine 5'-phosphosulfate + H2O = AMP + 2 H(+) + sulfate;
CC Xref=Rhea:RHEA:17041, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16189, ChEBI:CHEBI:58243, ChEBI:CHEBI:456215; EC=3.6.2.1;
CC Evidence={ECO:0000250|UniProtKB:P49789};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=adenosine 5'-phosphosulfate + NH4(+) = adenosine 5'-
CC phosphoramidate + 2 H(+) + sulfate; Xref=Rhea:RHEA:19197,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16189, ChEBI:CHEBI:28938,
CC ChEBI:CHEBI:57890, ChEBI:CHEBI:58243; EC=2.7.7.51;
CC Evidence={ECO:0000250|UniProtKB:P49789};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=adenosine 5'-phosphoramidate + H2O = AMP + NH4(+);
CC Xref=Rhea:RHEA:67916, ChEBI:CHEBI:15377, ChEBI:CHEBI:28938,
CC ChEBI:CHEBI:57890, ChEBI:CHEBI:456215;
CC Evidence={ECO:0000250|UniProtKB:P49789};
CC -!- SUBUNIT: Homodimer. Interacts with UBE2I. Interacts with MDM2.
CC Interacts with CTNNB1. Identified in a complex with CTNNB1 and LEF1 (By
CC similarity). {ECO:0000250|UniProtKB:P49789}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P49789}. Nucleus
CC {ECO:0000250|UniProtKB:P49789}. Mitochondrion
CC {ECO:0000250|UniProtKB:P49789}.
CC -!- TISSUE SPECIFICITY: Expressed in the brain, kidney, spleen, testis and
CC lung. {ECO:0000269|PubMed:16719907}.
CC -!- PTM: Phosphorylation at Tyr-114 by SRC is required for induction of
CC apoptosis. {ECO:0000250|UniProtKB:P49789}.
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DR EMBL; DQ335870; ABC61315.1; -; mRNA.
DR EMBL; DQ310184; ABC61471.1; -; mRNA.
DR EMBL; DQ310183; ABC61470.1; -; mRNA.
DR EMBL; DQ310181; ABC61468.1; -; mRNA.
DR EMBL; DQ310182; ABC61469.1; -; mRNA.
DR EMBL; DQ310179; ABC68307.1; -; Genomic_DNA.
DR EMBL; DQ310176; ABC68307.1; JOINED; Genomic_DNA.
DR EMBL; DQ310177; ABC68307.1; JOINED; Genomic_DNA.
DR EMBL; DQ310178; ABC68307.1; JOINED; Genomic_DNA.
DR EMBL; BC147993; AAI47994.1; -; mRNA.
DR RefSeq; NP_001035736.1; NM_001040646.1.
DR AlphaFoldDB; Q1KZG4; -.
DR SMR; Q1KZG4; -.
DR STRING; 9913.ENSBTAP00000019177; -.
DR PaxDb; Q1KZG4; -.
DR PRIDE; Q1KZG4; -.
DR Ensembl; ENSBTAT00000019177; ENSBTAP00000019177; ENSBTAG00000014418.
DR GeneID; 692183; -.
DR KEGG; bta:692183; -.
DR CTD; 2272; -.
DR VEuPathDB; HostDB:ENSBTAG00000014418; -.
DR VGNC; VGNC:28998; FHIT.
DR eggNOG; KOG3379; Eukaryota.
DR GeneTree; ENSGT00510000047967; -.
DR HOGENOM; CLU_056776_7_1_1; -.
DR InParanoid; Q1KZG4; -.
DR OMA; DAIYGMM; -.
DR OrthoDB; 1198291at2759; -.
DR TreeFam; TF105432; -.
DR Proteomes; UP000009136; Chromosome 22.
DR Bgee; ENSBTAG00000014418; Expressed in oocyte and 102 other tissues.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0001650; C:fibrillar center; IEA:Ensembl.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0043530; F:adenosine 5'-monophosphoramidase activity; ISS:UniProtKB.
DR GO; GO:0047627; F:adenylylsulfatase activity; ISS:UniProtKB.
DR GO; GO:0047352; F:adenylylsulfate-ammonia adenylyltransferase activity; ISS:UniProtKB.
DR GO; GO:0047710; F:bis(5'-adenosyl)-triphosphatase activity; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IBA:GO_Central.
DR GO; GO:0015964; P:diadenosine triphosphate catabolic process; IBA:GO_Central.
DR GO; GO:0072332; P:intrinsic apoptotic signaling pathway by p53 class mediator; ISS:UniProtKB.
DR GO; GO:0032435; P:negative regulation of proteasomal ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0006163; P:purine nucleotide metabolic process; ISS:UniProtKB.
DR CDD; cd01275; FHIT; 1.
DR Gene3D; 3.30.428.10; -; 1.
DR InterPro; IPR039383; FHIT.
DR InterPro; IPR019808; Histidine_triad_CS.
DR InterPro; IPR011146; HIT-like.
DR InterPro; IPR036265; HIT-like_sf.
DR Pfam; PF01230; HIT; 1.
DR SUPFAM; SSF54197; SSF54197; 1.
DR PROSITE; PS00892; HIT_1; 1.
DR PROSITE; PS51084; HIT_2; 1.
PE 2: Evidence at transcript level;
KW Apoptosis; Cytoplasm; Hydrolase; Magnesium; Manganese; Mitochondrion;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Transcription; Transcription regulation; Transferase.
FT CHAIN 1..149
FT /note="Bis(5'-adenosyl)-triphosphatase"
FT /id="PRO_0000288472"
FT DOMAIN 2..109
FT /note="HIT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00464"
FT MOTIF 94..98
FT /note="Histidine triad motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00464"
FT ACT_SITE 96
FT /note="Tele-AMP-histidine intermediate"
FT /evidence="ECO:0000250|UniProtKB:P49789"
FT BINDING 8
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P49789"
FT BINDING 27
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P49789"
FT BINDING 83
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P49789"
FT BINDING 89..92
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P49789"
FT BINDING 98
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P49789"
FT SITE 114
FT /note="Important for induction of apoptosis"
FT /evidence="ECO:0000250|UniProtKB:P49789"
FT MOD_RES 114
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P49789"
FT MOD_RES 147
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P49789"
SQ SEQUENCE 149 AA; 16951 MW; C7E39594A5982F24 CRC64;
MSFRFGQHLI KPSVVFLKTE LSFALVNRKP VVPGHVLVCP LRPVERFRDM SPEEVADLFQ
AAQRVGTVVE KHFQGTSLTF SMQDGPEAGQ TVKHVHVHIL PRKAGDFHRN DSIYDALEKH
DREDKDSPAL WRSEEEMAAE AAALRVYFQ
