FHIT_RAT
ID FHIT_RAT Reviewed; 150 AA.
AC Q9JIX3;
DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 103.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Fischer 344; TISSUE=Liver;
RA Luceri C., De Filippo C., Caderni G., Dolara P.;
RT "Identification of FHIT gene in rat Fisher 344.";
RL Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP PROTEIN SEQUENCE OF 5-18 AND 49-64, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Hippocampus;
RA Lubec G., Chen W.-Q.;
RL Submitted (APR-2007) to UniProtKB.
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 -!- PTM: Phosphorylation at Tyr-114 by SRC is required for induction of
CC apoptosis. {ECO:0000250|UniProtKB:P49789}.
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DR EMBL; AF170064; AAF89328.1; -; mRNA.
DR RefSeq; NP_068542.1; NM_021774.1.
DR AlphaFoldDB; Q9JIX3; -.
DR SMR; Q9JIX3; -.
DR STRING; 10116.ENSRNOP00000009393; -.
DR iPTMnet; Q9JIX3; -.
DR PhosphoSitePlus; Q9JIX3; -.
DR PaxDb; Q9JIX3; -.
DR PRIDE; Q9JIX3; -.
DR GeneID; 60398; -.
DR KEGG; rno:60398; -.
DR CTD; 2272; -.
DR RGD; 620448; Fhit.
DR eggNOG; KOG3379; Eukaryota.
DR InParanoid; Q9JIX3; -.
DR OrthoDB; 1198291at2759; -.
DR PhylomeDB; Q9JIX3; -.
DR PRO; PR:Q9JIX3; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
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; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0016151; F:nickel cation binding; IDA:RGD.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:RGD.
DR GO; GO:0015964; P:diadenosine triphosphate catabolic process; IDA:RGD.
DR GO; GO:0006260; P:DNA replication; ISO:RGD.
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; Direct protein sequencing; Hydrolase; Magnesium;
KW Manganese; Mitochondrion; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Transcription; Transcription regulation; Transferase.
FT CHAIN 1..150
FT /note="Bis(5'-adenosyl)-triphosphatase"
FT /id="PRO_0000288473"
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 150 AA; 17348 MW; E0C466FB045EE714 CRC64;
MSFKFGQHLI KPSVVFLKTE LSFALVNRKP VVPGHVLMCP LRPVERFRDL RPDEVADLFQ
VTQRVGTVVE KHFQGTSITF SMQDGPEAGQ TVKHVHVHIL PRKSGDFRRN DNIYDELQKH
DREEEDSPAF WRSEEEMAAE AEVLRAYFQA
