AP4A_HUMAN
ID AP4A_HUMAN Reviewed; 147 AA.
AC P50583; D3DRM0; Q5T589;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=Bis(5'-nucleosyl)-tetraphosphatase [asymmetrical];
DE EC=3.6.1.17 {ECO:0000250|UniProtKB:P50584};
DE AltName: Full=Diadenosine 5',5'''-P1,P4-tetraphosphate asymmetrical hydrolase;
DE Short=Ap4A hydrolase;
DE Short=Ap4Aase;
DE Short=Diadenosine tetraphosphatase;
DE AltName: Full=Nucleoside diphosphate-linked moiety X motif 2;
DE Short=Nudix motif 2;
GN Name=NUDT2; Synonyms=APAH1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver, and Spleen;
RX PubMed=7487923; DOI=10.1042/bj3110717;
RA Thorne N.M.H., Hankin S., Wilkinson M.C., Nunez C., Barraclough R.,
RA McLennan A.G.;
RT "Human diadenosine 5',5''-P1,P4-tetraphosphate pyrophosphohydrolase is a
RT member of the MutT family of nucleotide pyrophosphatases.";
RL Biochem. J. 311:717-721(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pancreas;
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 [5]
RP ACETYLATION AT ALA-2.
RA McLennan A.G.;
RL Submitted (JAN-1997) to UniProtKB.
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [7]
RP STRUCTURE BY NMR.
RX PubMed=15596429; DOI=10.1074/jbc.m412318200;
RA Swarbrick J.D., Buyya S., Gunawardana D., Gayler K.R., McLennan A.G.,
RA Gooley P.R.;
RT "Structure and substrate-binding mechanism of human Ap4A hydrolase.";
RL J. Biol. Chem. 280:8471-8481(2005).
CC -!- FUNCTION: Catalyzes the asymmetric hydrolysis of diadenosine 5',5'''-
CC P1,P4-tetraphosphate (Ap4A) to yield AMP and ATP (By similarity).
CC Exhibits decapping activity towards FAD-capped RNAs and dpCoA-capped
CC RNAs in vitro (By similarity). {ECO:0000250|UniProtKB:P50584,
CC ECO:0000250|UniProtKB:P56380}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + P(1),P(4)-bis(5'-guanosyl) tetraphosphate = GMP + GTP +
CC 2 H(+); Xref=Rhea:RHEA:22484, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:37565, ChEBI:CHEBI:57553, ChEBI:CHEBI:58115; EC=3.6.1.17;
CC Evidence={ECO:0000250|UniProtKB:P50584};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 5'-end CoA-ribonucleoside in mRNA + H2O = (R)-4'-
CC phosphopantetheine + a 5'-end phospho-adenosine-phospho-
CC ribonucleoside in mRNA + 2 H(+); Xref=Rhea:RHEA:67592, Rhea:RHEA-
CC COMP:15719, Rhea:RHEA-COMP:17276, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:61723, ChEBI:CHEBI:144051,
CC ChEBI:CHEBI:172371; Evidence={ECO:0000250|UniProtKB:P56380};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67593;
CC Evidence={ECO:0000250|UniProtKB:P56380};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 5'-end FAD-phospho-ribonucleoside in mRNA + H2O = a 5'-end
CC phospho-adenosine-phospho-ribonucleoside in mRNA + FMN + 2 H(+);
CC Xref=Rhea:RHEA:67588, Rhea:RHEA-COMP:15719, Rhea:RHEA-COMP:17275,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:144051, ChEBI:CHEBI:172372;
CC Evidence={ECO:0000250|UniProtKB:P56380};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67589;
CC Evidence={ECO:0000250|UniProtKB:P56380};
CC -!- COFACTOR:
CC Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240;
CC Evidence={ECO:0000250|UniProtKB:Q9U2M7};
CC Note=Divalent metal ions. {ECO:0000250|UniProtKB:Q9U2M7};
CC -!- INTERACTION:
CC P50583; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-10096247, EBI-742054;
CC P50583; Q14566: MCM6; NbExp=3; IntAct=EBI-10096247, EBI-374900;
CC P50583; Q9H8W4: PLEKHF2; NbExp=3; IntAct=EBI-10096247, EBI-742388;
CC -!- SIMILARITY: Belongs to the Nudix hydrolase family. {ECO:0000305}.
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DR EMBL; U30313; AAC50277.1; -; mRNA.
DR EMBL; AL356494; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471071; EAW58461.1; -; Genomic_DNA.
DR EMBL; CH471071; EAW58462.1; -; Genomic_DNA.
DR EMBL; CH471071; EAW58463.1; -; Genomic_DNA.
DR EMBL; BC004926; AAH04926.1; -; mRNA.
DR CCDS; CCDS6552.1; -.
DR PIR; S60111; S60111.
DR RefSeq; NP_001152.1; NM_001161.4.
DR RefSeq; NP_001231319.1; NM_001244390.1.
DR RefSeq; NP_671701.1; NM_147172.2.
DR RefSeq; NP_671702.1; NM_147173.2.
DR PDB; 1XSA; NMR; -; A=1-147.
DR PDB; 1XSB; NMR; -; A=1-147.
DR PDB; 1XSC; NMR; -; A=2-147.
DR PDB; 3U53; X-ray; 2.70 A; A/B/C/D=1-147.
DR PDB; 4ICK; X-ray; 2.10 A; A/B=1-147.
DR PDB; 4IJX; X-ray; 2.10 A; A/B=1-147.
DR PDBsum; 1XSA; -.
DR PDBsum; 1XSB; -.
DR PDBsum; 1XSC; -.
DR PDBsum; 3U53; -.
DR PDBsum; 4ICK; -.
DR PDBsum; 4IJX; -.
DR AlphaFoldDB; P50583; -.
DR BMRB; P50583; -.
DR SMR; P50583; -.
DR BioGRID; 106815; 7.
DR IntAct; P50583; 5.
DR STRING; 9606.ENSP00000368455; -.
DR BindingDB; P50583; -.
DR ChEMBL; CHEMBL4105863; -.
DR iPTMnet; P50583; -.
DR PhosphoSitePlus; P50583; -.
DR BioMuta; NUDT2; -.
DR EPD; P50583; -.
DR jPOST; P50583; -.
DR MassIVE; P50583; -.
DR MaxQB; P50583; -.
DR PaxDb; P50583; -.
DR PeptideAtlas; P50583; -.
DR PRIDE; P50583; -.
DR ProteomicsDB; 56253; -.
DR TopDownProteomics; P50583; -.
DR Antibodypedia; 25392; 198 antibodies from 26 providers.
DR DNASU; 318; -.
DR Ensembl; ENST00000346365.8; ENSP00000344187.4; ENSG00000164978.18.
DR Ensembl; ENST00000379155.9; ENSP00000368452.5; ENSG00000164978.18.
DR Ensembl; ENST00000379158.7; ENSP00000368455.1; ENSG00000164978.18.
DR Ensembl; ENST00000618590.1; ENSP00000482384.1; ENSG00000164978.18.
DR GeneID; 318; -.
DR KEGG; hsa:318; -.
DR MANE-Select; ENST00000379158.7; ENSP00000368455.1; NM_001161.5; NP_001152.1.
DR UCSC; uc003zub.3; human.
DR CTD; 318; -.
DR DisGeNET; 318; -.
DR GeneCards; NUDT2; -.
DR HGNC; HGNC:8049; NUDT2.
DR HPA; ENSG00000164978; Low tissue specificity.
DR MIM; 602852; gene.
DR neXtProt; NX_P50583; -.
DR OpenTargets; ENSG00000164978; -.
DR PharmGKB; PA31833; -.
DR VEuPathDB; HostDB:ENSG00000164978; -.
DR eggNOG; KOG2839; Eukaryota.
DR GeneTree; ENSGT00390000002416; -.
DR HOGENOM; CLU_037162_14_5_1; -.
DR OMA; WRDYEQA; -.
DR OrthoDB; 1107148at2759; -.
DR PhylomeDB; P50583; -.
DR TreeFam; TF105958; -.
DR BRENDA; 3.6.1.17; 2681.
DR PathwayCommons; P50583; -.
DR Reactome; R-HSA-3299685; Detoxification of Reactive Oxygen Species.
DR SABIO-RK; P50583; -.
DR SignaLink; P50583; -.
DR BioGRID-ORCS; 318; 12 hits in 1077 CRISPR screens.
DR ChiTaRS; NUDT2; human.
DR EvolutionaryTrace; P50583; -.
DR GeneWiki; NUDT2; -.
DR GenomeRNAi; 318; -.
DR Pharos; P50583; Tbio.
DR PRO; PR:P50583; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; P50583; protein.
DR Bgee; ENSG00000164978; Expressed in stromal cell of endometrium and 178 other tissues.
DR Genevisible; P50583; HS.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0004081; F:bis(5'-nucleosyl)-tetraphosphatase (asymmetrical) activity; ISS:UniProtKB.
DR GO; GO:0008803; F:bis(5'-nucleosyl)-tetraphosphatase (symmetrical) activity; TAS:ProtInc.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0006167; P:AMP biosynthetic process; IBA:GO_Central.
DR GO; GO:0006915; P:apoptotic process; ISS:UniProtKB.
DR GO; GO:0006754; P:ATP biosynthetic process; IBA:GO_Central.
DR GO; GO:0034599; P:cellular response to oxidative stress; TAS:Reactome.
DR GO; GO:0006139; P:nucleobase-containing compound metabolic process; TAS:ProtInc.
DR CDD; cd03428; Ap4A_hydrolase_human_like; 1.
DR InterPro; IPR015797; NUDIX_hydrolase-like_dom_sf.
DR InterPro; IPR020084; NUDIX_hydrolase_CS.
DR InterPro; IPR000086; NUDIX_hydrolase_dom.
DR InterPro; IPR003565; Tetra_PHTase.
DR Pfam; PF00293; NUDIX; 1.
DR PRINTS; PR01405; TETRPHPHTASE.
DR SUPFAM; SSF55811; SSF55811; 1.
DR PROSITE; PS51462; NUDIX; 1.
DR PROSITE; PS00893; NUDIX_BOX; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; GTP-binding; Hydrolase; Nucleotide-binding;
KW Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.5"
FT CHAIN 2..147
FT /note="Bis(5'-nucleosyl)-tetraphosphatase [asymmetrical]"
FT /id="PRO_0000057102"
FT DOMAIN 1..139
FT /note="Nudix hydrolase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00794"
FT MOTIF 43..64
FT /note="Nudix box"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|Ref.5"
FT STRAND 5..13
FT /evidence="ECO:0007829|PDB:4ICK"
FT TURN 17..19
FT /evidence="ECO:0007829|PDB:4ICK"
FT STRAND 23..33
FT /evidence="ECO:0007829|PDB:4ICK"
FT STRAND 42..44
FT /evidence="ECO:0007829|PDB:4ICK"
FT STRAND 47..49
FT /evidence="ECO:0007829|PDB:1XSA"
FT HELIX 51..63
FT /evidence="ECO:0007829|PDB:4ICK"
FT HELIX 67..69
FT /evidence="ECO:0007829|PDB:4ICK"
FT STRAND 70..84
FT /evidence="ECO:0007829|PDB:4ICK"
FT STRAND 87..99
FT /evidence="ECO:0007829|PDB:4ICK"
FT STRAND 111..117
FT /evidence="ECO:0007829|PDB:4ICK"
FT HELIX 119..126
FT /evidence="ECO:0007829|PDB:4ICK"
FT HELIX 129..147
FT /evidence="ECO:0007829|PDB:4ICK"
SQ SEQUENCE 147 AA; 16829 MW; 3599B12719F94AB8 CRC64;
MALRACGLII FRRCLIPKVD NNAIEFLLLQ ASDGIHHWTP PKGHVEPGED DLETALRETQ
EEAGIEAGQL TIIEGFKREL NYVARNKPKT VIYWLAEVKD YDVEIRLSHE HQAYRWLGLE
EACQLAQFKE MKAALQEGHQ FLCSIEA
