FHIT_MOUSE
ID FHIT_MOUSE Reviewed; 150 AA.
AC O89106; Q6URW5; Q91VL1;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 148.
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=9699672;
RA Pekarsky Y., Druck T., Cotticelli M.G., Ohta M., Shou J., Mendrola J.,
RA Montgomery J.C., Buchberg A.M., Siracusa L.D., Manenti G., Fong L.Y.,
RA Dragani T.A., Croce C.M., Huebner K.;
RT "The murine Fhit locus: isolation, characterization, and expression in
RT normal and tumor cells.";
RL Cancer Res. 58:3401-3408(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/10J; TISSUE=Muscle;
RA Glover T.W., Hoge A., Miller D.E., Escara-Wilke J., Adam A.N.,
RA Dagenais S.L., Wilke C.M., Dierick H.A., Beer D.G.;
RL Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 36-150.
RC STRAIN=C57BL/6J; TISSUE=Kidney;
RX PubMed=14630947; DOI=10.1073/pnas.2336256100;
RA Matsuyama A., Shiraishi T., Trapasso F., Kuroki T., Alder H., Mori M.,
RA Huebner K., Croce C.M.;
RT "Fragile site orthologs FHIT/FRA3B and Fhit/Fra14A2: evolutionarily
RT conserved but highly recombinogenic.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:14988-14993(2003).
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=9671749; DOI=10.1073/pnas.95.15.8744;
RA Pekarsky Y., Campiglio M., Siprashvili Z., Druck T., Sedkov Y., Tillib S.,
RA Draganescu A., Wermuth P., Rothman J.H., Huebner K., Buchberg A.M.,
RA Mazo A., Brenner C., Croce C.M.;
RT "Nitrilase and Fhit homologs are encoded as fusion proteins in Drosophila
RT melanogaster and Caenorhabditis elegans.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:8744-8749(1998).
RN [6]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=10758156; DOI=10.1073/pnas.080063497;
RA Fong L.Y., Fidanza V., Zanesi N., Lock L.F., Siracusa L.D., Mancini R.,
RA Siprashvili Z., Ottey M., Martin S.E., Druck T., McCue P.A., Croce C.M.,
RA Huebner K.;
RT "Muir-Torre-like syndrome in Fhit-deficient mice.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:4742-4747(2000).
RN [7]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=11517343; DOI=10.1073/pnas.191345898;
RA Zanesi N., Fidanza V., Fong L.Y., Mancini R., Druck T., Valtieri M.,
RA Rudiger T., McCue P.A., Croce C.M., Huebner K.;
RT "The tumor spectrum in FHIT-deficient mice.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:10250-10255(2001).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Kidney, and Liver;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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
CC (PubMed:10758156, PubMed:11517343). {ECO:0000250|UniProtKB:P49789,
CC ECO:0000269|PubMed:10758156, ECO:0000269|PubMed:11517343}.
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:0000269|PubMed:9699672}. Nucleus
CC {ECO:0000250|UniProtKB:P49789}. Mitochondrion
CC {ECO:0000250|UniProtKB:P49789}.
CC -!- TISSUE SPECIFICITY: Expressed in heart, brain, lung and skeletal
CC muscle. Particularly strong expression in liver, testis and kidney,
CC where it is confined to the tubular epithelium.
CC {ECO:0000269|PubMed:9671749, ECO:0000269|PubMed:9699672}.
CC -!- PTM: Phosphorylation at Tyr-114 by SRC is required for induction of
CC apoptosis. {ECO:0000250|UniProtKB:P49789}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype at birth, but about 30% of
CC the mice lacking one or both copies of Fhit died for unknown reasons at
CC an age of about 19 months. This might be due to increased
CC susceptibility to infections. Mice lacking one or both copies of Fhit
CC show increased susceptibility to carcinogens.
CC {ECO:0000269|PubMed:10758156, ECO:0000269|PubMed:11517343}.
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DR EMBL; AH006186; AAC23967.1; -; Genomic_DNA.
DR EMBL; AF047699; AAC24566.1; -; mRNA.
DR EMBL; AF055573; AAC24117.1; -; mRNA.
DR EMBL; BC012662; AAH12662.1; -; mRNA.
DR EMBL; AH013372; AAR17701.1; -; Genomic_DNA.
DR CCDS; CCDS49400.1; -.
DR RefSeq; NP_001295215.1; NM_001308286.1.
DR RefSeq; NP_034340.1; NM_010210.3.
DR RefSeq; XP_006517990.1; XM_006517927.3.
DR RefSeq; XP_011243034.1; XM_011244732.2.
DR RefSeq; XP_017171336.1; XM_017315847.1.
DR AlphaFoldDB; O89106; -.
DR SMR; O89106; -.
DR BioGRID; 199667; 5.
DR STRING; 10090.ENSMUSP00000124017; -.
DR iPTMnet; O89106; -.
DR PhosphoSitePlus; O89106; -.
DR SwissPalm; O89106; -.
DR jPOST; O89106; -.
DR MaxQB; O89106; -.
DR PaxDb; O89106; -.
DR PRIDE; O89106; -.
DR ProteomicsDB; 270987; -.
DR Antibodypedia; 3636; 646 antibodies from 39 providers.
DR DNASU; 14198; -.
DR Ensembl; ENSMUST00000161302; ENSMUSP00000123874; ENSMUSG00000060579.
DR Ensembl; ENSMUST00000162278; ENSMUSP00000124073; ENSMUSG00000060579.
DR Ensembl; ENSMUST00000179394; ENSMUSP00000136011; ENSMUSG00000060579.
DR GeneID; 14198; -.
DR KEGG; mmu:14198; -.
DR UCSC; uc007sfj.1; mouse.
DR CTD; 2272; -.
DR MGI; MGI:1277947; Fhit.
DR VEuPathDB; HostDB:ENSMUSG00000060579; -.
DR eggNOG; KOG3379; Eukaryota.
DR GeneTree; ENSGT00510000047967; -.
DR InParanoid; O89106; -.
DR OMA; DAIYGMM; -.
DR PhylomeDB; O89106; -.
DR BioGRID-ORCS; 14198; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Fhit; mouse.
DR PRO; PR:O89106; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; O89106; protein.
DR Bgee; ENSMUSG00000060579; Expressed in right kidney and 153 other tissues.
DR ExpressionAtlas; O89106; baseline and differential.
DR Genevisible; O89106; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0001650; C:fibrillar center; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0016151; F:nickel cation binding; ISO:MGI.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0015964; P:diadenosine triphosphate catabolic process; ISS:ARUK-UCL.
DR GO; GO:0006260; P:DNA replication; IDA:MGI.
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 1: Evidence at protein level;
KW Apoptosis; Cytoplasm; Hydrolase; Magnesium; Manganese; Mitochondrion;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Transcription; Transcription regulation; Transferase.
FT CHAIN 1..150
FT /note="Bis(5'-adenosyl)-triphosphatase"
FT /id="PRO_0000109790"
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; by SRC"
FT /evidence="ECO:0000250|UniProtKB:P49789"
FT MOD_RES 147
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P49789"
FT CONFLICT 135
FT /note="K -> E (in Ref. 3; AAH12662)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 150 AA; 17235 MW; 27CBC57C5A4A0E2B CRC64;
MSFRFGQHLI KPSVVFLKTE LSFALVNRKP VVPGHVLVCP LRPVERFRDL HPDEVADLFQ
VTQRVGTVVE KHFQGTSITF SMQDGPEAGQ TVKHVHVHVL PRKAGDFPRN DNIYDELQKH
DREEEDSPAF WRSEKEMAAE AEALRVYFQA
