AP4A_MOUSE
ID AP4A_MOUSE Reviewed; 147 AA.
AC P56380; Q9D2U6; Q9D6V2;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 139.
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 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 [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Cerebellum, and Tongue;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Kidney;
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 [3]
RP PROTEIN SEQUENCE OF 5-12; 43-57; 61-77; 90-99 AND 116-129, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=OF1; TISSUE=Hippocampus;
RA Lubec G., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
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).
RN [5]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=32432673; DOI=10.1093/nar/gkaa402;
RA Sharma S., Grudzien-Nogalska E., Hamilton K., Jiao X., Yang J., Tong L.,
RA Kiledjian M.;
RT "Mammalian Nudix proteins cleave nucleotide metabolite caps on RNAs.";
RL Nucleic Acids Res. 48:6788-6798(2020).
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 (PubMed:32432673). {ECO:0000250|UniProtKB:P50584,
CC ECO:0000269|PubMed:32432673}.
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:0000305|PubMed:32432673};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67593;
CC Evidence={ECO:0000305|PubMed:32432673};
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:0000305|PubMed:32432673};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67589;
CC Evidence={ECO:0000305|PubMed:32432673};
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 -!- SIMILARITY: Belongs to the Nudix hydrolase family. {ECO:0000305}.
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DR EMBL; AK009933; BAB26592.1; -; mRNA.
DR EMBL; AK018771; BAB31399.1; -; mRNA.
DR EMBL; BC025153; AAH25153.1; -; mRNA.
DR CCDS; CCDS18061.1; -.
DR RefSeq; NP_079815.2; NM_025539.2.
DR RefSeq; XP_006538228.1; XM_006538165.3.
DR RefSeq; XP_011248384.1; XM_011250082.2.
DR RefSeq; XP_011248385.1; XM_011250083.1.
DR AlphaFoldDB; P56380; -.
DR SMR; P56380; -.
DR STRING; 10090.ENSMUSP00000030154; -.
DR iPTMnet; P56380; -.
DR PhosphoSitePlus; P56380; -.
DR EPD; P56380; -.
DR jPOST; P56380; -.
DR MaxQB; P56380; -.
DR PaxDb; P56380; -.
DR PeptideAtlas; P56380; -.
DR PRIDE; P56380; -.
DR ProteomicsDB; 296212; -.
DR Antibodypedia; 25392; 198 antibodies from 26 providers.
DR DNASU; 66401; -.
DR Ensembl; ENSMUST00000030154; ENSMUSP00000030154; ENSMUSG00000028443.
DR GeneID; 66401; -.
DR KEGG; mmu:66401; -.
DR UCSC; uc008sis.1; mouse.
DR CTD; 318; -.
DR MGI; MGI:1913651; Nudt2.
DR VEuPathDB; HostDB:ENSMUSG00000028443; -.
DR eggNOG; KOG2839; Eukaryota.
DR GeneTree; ENSGT00390000002416; -.
DR HOGENOM; CLU_037162_14_5_1; -.
DR InParanoid; P56380; -.
DR OMA; WRDYEQA; -.
DR OrthoDB; 1107148at2759; -.
DR PhylomeDB; P56380; -.
DR TreeFam; TF105958; -.
DR Reactome; R-MMU-3299685; Detoxification of Reactive Oxygen Species.
DR BioGRID-ORCS; 66401; 2 hits in 71 CRISPR screens.
DR ChiTaRS; Nudt2; mouse.
DR PRO; PR:P56380; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; P56380; protein.
DR Bgee; ENSMUSG00000028443; Expressed in barrel cortex and 258 other tissues.
DR Genevisible; P56380; MM.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0004081; F:bis(5'-nucleosyl)-tetraphosphatase (asymmetrical) activity; ISS:UniProtKB.
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 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 Acetylation; Direct protein sequencing; GTP-binding; Hydrolase;
KW Nucleotide-binding; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P50583"
FT CHAIN 2..147
FT /note="Bis(5'-nucleosyl)-tetraphosphatase [asymmetrical]"
FT /id="PRO_0000057103"
FT DOMAIN 2..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:0000250|UniProtKB:P50583"
FT CONFLICT 19
FT /note="M -> V (in Ref. 1; BAB31399)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 147 AA; 16989 MW; A634D19F1E8CCE34 CRC64;
MALRACGLII FRRHLIPKMD NSTIEFLLLQ ASDGIHHWTP PKGHVDPGEN DLETALRETR
EETGIEASQL TIIEGFRREL NYVARQKPKT VIYWLAEVKD YNVEIRLSQE HQAYRWLGLE
EACQLAQFKE MKATLQEGHQ FLCSTPA
