FHIT_DICDI
ID FHIT_DICDI Reviewed; 149 AA.
AC Q86KK2; Q555P7;
DT 01-JUL-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 99.
DE RecName: Full=Bis(5'-adenosyl)-triphosphatase;
DE EC=3.6.1.29;
DE AltName: Full=AP3A hydrolase;
DE Short=AP3Aase;
DE AltName: Full=Diadenosine 5',5'''-P1,P3-triphosphate hydrolase;
DE AltName: Full=Dinucleosidetriphosphatase;
DE AltName: Full=Fragile histidine triad protein homolog;
GN Name=fhit; ORFNames=DDB_G0274257;
OS Dictyostelium discoideum (Slime mold).
OC Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC Dictyosteliaceae; Dictyostelium.
OX NCBI_TaxID=44689;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=12097910; DOI=10.1038/nature00847;
RA Gloeckner G., Eichinger L., Szafranski K., Pachebat J.A., Bankier A.T.,
RA Dear P.H., Lehmann R., Baumgart C., Parra G., Abril J.F., Guigo R.,
RA Kumpf K., Tunggal B., Cox E.C., Quail M.A., Platzer M., Rosenthal A.,
RA Noegel A.A.;
RT "Sequence and analysis of chromosome 2 of Dictyostelium discoideum.";
RL Nature 418:79-85(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=15875012; DOI=10.1038/nature03481;
RA Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT "The genome of the social amoeba Dictyostelium discoideum.";
RL Nature 435:43-57(2005).
CC -!- FUNCTION: Cleaves P(1)-P(3)-bis(5'-adenosyl) triphosphate (Ap3A) to
CC yield AMP and ADP. Can also hydrolyze P(1)-P(4)-bis(5'-adenosyl)
CC tetraphosphate (Ap4A), but has extremely low activity with ATP.
CC Modulates transcriptional activation by CTNNB1 and thereby contributes
CC to regulate the expression of genes essential for cell proliferation
CC and survival. Plays a role in the induction of apoptosis via p53/TP53,
CC SRC and AKT1 signaling pathways. Induction of apoptosis depends on the
CC ability of FHIT to bind P(1)-P(3)-bis(5'-adenosyl) triphosphate or
CC related compounds, but does not require its catalytic activity (By
CC similarity). {ECO:0000250}.
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;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};
CC Note=Divalent metal cations. Mg(2+) or Mn(2+). {ECO:0000250};
CC -!- SUBUNIT: Homodimer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
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DR EMBL; AAFI02000012; EAL70021.1; -; Genomic_DNA.
DR RefSeq; XP_644016.1; XM_638924.1.
DR AlphaFoldDB; Q86KK2; -.
DR SMR; Q86KK2; -.
DR STRING; 44689.DDB0167807; -.
DR PaxDb; Q86KK2; -.
DR EnsemblProtists; EAL70021; EAL70021; DDB_G0274257.
DR GeneID; 8619446; -.
DR KEGG; ddi:DDB_G0274257; -.
DR dictyBase; DDB_G0274257; fhit.
DR eggNOG; KOG3379; Eukaryota.
DR HOGENOM; CLU_056776_7_3_1; -.
DR InParanoid; Q86KK2; -.
DR OMA; DAIYGMM; -.
DR PhylomeDB; Q86KK2; -.
DR PRO; PR:Q86KK2; -.
DR Proteomes; UP000002195; Chromosome 2.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0047710; F:bis(5'-adenosyl)-triphosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR CDD; cd01275; FHIT; 1.
DR Gene3D; 3.30.428.10; -; 1.
DR InterPro; IPR039383; FHIT.
DR InterPro; IPR019808; Histidine_triad_CS.
DR InterPro; IPR001310; Histidine_triad_HIT.
DR InterPro; IPR011146; HIT-like.
DR InterPro; IPR036265; HIT-like_sf.
DR Pfam; PF01230; HIT; 1.
DR PRINTS; PR00332; HISTRIAD.
DR SUPFAM; SSF54197; SSF54197; 1.
DR PROSITE; PS00892; HIT_1; 1.
DR PROSITE; PS51084; HIT_2; 1.
PE 3: Inferred from homology;
KW Apoptosis; Cytoplasm; Hydrolase; Nucleotide-binding; Reference proteome;
KW Transcription; Transcription regulation.
FT CHAIN 1..149
FT /note="Bis(5'-adenosyl)-triphosphatase"
FT /id="PRO_0000342401"
FT DOMAIN 1..115
FT /note="HIT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00464"
FT REGION 120..149
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 95..99
FT /note="Histidine triad motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00464"
FT ACT_SITE 97
FT /note="Tele-AMP-histidine intermediate"
FT /evidence="ECO:0000250"
FT BINDING 28
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 84
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 90..93
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 99
FT /ligand="substrate"
FT /evidence="ECO:0000250"
SQ SEQUENCE 149 AA; 17499 MW; 2F44495136FBA7C9 CRC64;
MTTTYFGPWL IRQSEIFFTT ELSFALVNLK PVLPGHVLVC PKRIVPRVKD LTKEEFTDLW
LSAQRISSVV EEHFNGDGIT FAIQDGKNAG QTVEHVHIHI IPRKKFDFEN NDQIYNEIEK
EREPRSYEEM EKESSELRPL FEENKNKTF
