ID   NPP1_YEAST              Reviewed;         742 AA.
AC   P25353; D6VR36; Q8NIL9;
DT   01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT   27-JUN-2003, sequence version 2.
DT   27-MAR-2024, entry version 180.
DE   RecName: Full=Ectonucleotide pyrophosphatase/phosphodiesterase 1;
DE            Short=E-NPP 1;
DE   Includes:
DE     RecName: Full=Alkaline phosphodiesterase 1;
DE              EC=3.1.4.1 {ECO:0000305};
DE   Includes:
DE     RecName: Full=Nucleotide pyrophosphatase;
DE              Short=NPPase;
DE              EC=3.6.1.9 {ECO:0000305};
DE     AltName: Full=Nucleotide diphosphatase {ECO:0000305};
GN   Name=NPP1; OrderedLocusNames=YCR026C; ORFNames=YCR246, YCR26C;
OS   Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC   Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX   NCBI_TaxID=559292;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=1574125; DOI=10.1038/357038a0;
RA   Oliver S.G., van der Aart Q.J.M., Agostoni-Carbone M.L., Aigle M.,
RA   Alberghina L., Alexandraki D., Antoine G., Anwar R., Ballesta J.P.G.,
RA   Benit P., Berben G., Bergantino E., Biteau N., Bolle P.-A.,
RA   Bolotin-Fukuhara M., Brown A., Brown A.J.P., Buhler J.-M., Carcano C.,
RA   Carignani G., Cederberg H., Chanet R., Contreras R., Crouzet M.,
RA   Daignan-Fornier B., Defoor E., Delgado M.D., Demolder J., Doira C.,
RA   Dubois E., Dujon B., Duesterhoeft A., Erdmann D., Esteban M., Fabre F.,
RA   Fairhead C., Faye G., Feldmann H., Fiers W., Francingues-Gaillard M.-C.,
RA   Franco L., Frontali L., Fukuhara H., Fuller L.J., Galland P., Gent M.E.,
RA   Gigot D., Gilliquet V., Glansdorff N., Goffeau A., Grenson M., Grisanti P.,
RA   Grivell L.A., de Haan M., Haasemann M., Hatat D., Hoenicka J.,
RA   Hegemann J.H., Herbert C.J., Hilger F., Hohmann S., Hollenberg C.P.,
RA   Huse K., Iborra F., Indge K.J., Isono K., Jacq C., Jacquet M., James C.M.,
RA   Jauniaux J.-C., Jia Y., Jimenez A., Kelly A., Kleinhans U., Kreisl P.,
RA   Lanfranchi G., Lewis C., van der Linden C.G., Lucchini G.,
RA   Lutzenkirchen K., Maat M.J., Mallet L., Mannhaupt G., Martegani E.,
RA   Mathieu A., Maurer C.T.C., McConnell D., McKee R.A., Messenguy F.,
RA   Mewes H.-W., Molemans F., Montague M.A., Muzi Falconi M., Navas L.,
RA   Newlon C.S., Noone D., Pallier C., Panzeri L., Pearson B.M., Perea J.,
RA   Philippsen P., Pierard A., Planta R.J., Plevani P., Poetsch B., Pohl F.M.,
RA   Purnelle B., Ramezani Rad M., Rasmussen S.W., Raynal A., Remacha M.A.,
RA   Richterich P., Roberts A.B., Rodriguez F., Sanz E.,
RA   Schaaff-Gerstenschlaeger I., Scherens B., Schweitzer B., Shu Y., Skala J.,
RA   Slonimski P.P., Sor F., Soustelle C., Spiegelberg R., Stateva L.I.,
RA   Steensma H.Y., Steiner S., Thierry A., Thireos G., Tzermia M.,
RA   Urrestarazu L.A., Valle G., Vetter I., van Vliet-Reedijk J.C., Voet M.,
RA   Volckaert G., Vreken P., Wang H., Warmington J.R., von Wettstein D.,
RA   Wicksteed B.L., Wilson C., Wurst H., Xu G., Yoshikawa A., Zimmermann F.K.,
RA   Sgouros J.G.;
RT   "The complete DNA sequence of yeast chromosome III.";
RL   Nature 357:38-46(1992).
RN   [2]
RP   SEQUENCE REVISION.
RA   Valles G., Volckaerts G.;
RL   Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   GENOME REANNOTATION.
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=24374639; DOI=10.1534/g3.113.008995;
RA   Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA   Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA   Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT   "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL   G3 (Bethesda) 4:389-398(2014).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 244-742.
RX   PubMed=1574926; DOI=10.1002/yea.320080306;
RA   Bolle P.-A., Gilliquet V., Berben G., Dumont J., Hilger F.;
RT   "The complete sequence of K3B, a 7.9 kb fragment between PGK1 and CRY1 on
RT   chromosome III, reveals the presence of seven open reading frames.";
RL   Yeast 8:205-213(1992).
RN   [5]
RP   LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX   PubMed=14562106; DOI=10.1038/nature02046;
RA   Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA   O'Shea E.K., Weissman J.S.;
RT   "Global analysis of protein expression in yeast.";
RL   Nature 425:737-741(2003).
RN   [6]
RP   FUNCTION, NPP ACTIVITY, INDUCTION, AND AUTOPHOSPHORYLATION.
RX   PubMed=16278456; DOI=10.1128/ec.4.11.1892-1901.2005;
RA   Kennedy E.J., Pillus L., Ghosh G.;
RT   "Pho5p and newly identified nucleotide pyrophosphatases/ phosphodiesterases
RT   regulate extracellular nucleotide phosphate metabolism in Saccharomyces
RT   cerevisiae.";
RL   Eukaryot. Cell 4:1892-1901(2005).
RN   [7]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS].
RX   PubMed=19756047; DOI=10.1038/msb.2009.64;
RA   Kung L.A., Tao S.-C., Qian J., Smith M.G., Snyder M., Zhu H.;
RT   "Global analysis of the glycoproteome in Saccharomyces cerevisiae reveals
RT   new roles for protein glycosylation in eukaryotes.";
RL   Mol. Syst. Biol. 5:308-308(2009).
CC   -!- FUNCTION: Mediates extracellular nucleotide derived phosphate
CC       hydrolysis along with NPP2 and PHO5. {ECO:0000269|PubMed:16278456}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Hydrolytically removes 5'-nucleotides successively from the
CC         3'-hydroxy termini of 3'-hydroxy-terminated oligonucleotides.;
CC         EC=3.1.4.1; Evidence={ECO:0000305};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-
CC         phosphate + diphosphate + H(+); Xref=Rhea:RHEA:23996,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019,
CC         ChEBI:CHEBI:58043, ChEBI:CHEBI:61557; EC=3.6.1.9;
CC         Evidence={ECO:0000305};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + H2O = a 2'-
CC         deoxyribonucleoside 5'-phosphate + diphosphate + H(+);
CC         Xref=Rhea:RHEA:44644, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:65317; EC=3.6.1.9;
CC         Evidence={ECO:0000305};
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type II
CC       membrane protein {ECO:0000305}.
CC   -!- INDUCTION: Up-regulated during phosphate starvation.
CC       {ECO:0000269|PubMed:16278456}.
CC   -!- PTM: Autophosphorylated as part of the catalytic cycle of
CC       phosphodiesterase/pyrophosphatase activity.
CC   -!- PTM: N-glycosylated. {ECO:0000269|PubMed:19756047}.
CC   -!- MISCELLANEOUS: Present with 3420 molecules/cell in log phase SD medium.
CC       {ECO:0000269|PubMed:14562106}.
CC   -!- SIMILARITY: Belongs to the nucleotide pyrophosphatase/phosphodiesterase
CC       family. {ECO:0000305}.
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DR   EMBL; X59720; CAC42978.1; -; Genomic_DNA.
DR   EMBL; BK006937; DAA07505.1; -; Genomic_DNA.
DR   PIR; S19437; S19437.
DR   PIR; S27380; S27380.
DR   RefSeq; NP_009955.2; NM_001178741.1.
DR   AlphaFoldDB; P25353; -.
DR   SMR; P25353; -.
DR   BioGRID; 31008; 76.
DR   STRING; 4932.YCR026C; -.
DR   GlyCosmos; P25353; 5 sites, No reported glycans.
DR   GlyGen; P25353; 5 sites.
DR   iPTMnet; P25353; -.
DR   MaxQB; P25353; -.
DR   PaxDb; 4932-YCR026C; -.
DR   PeptideAtlas; P25353; -.
DR   EnsemblFungi; YCR026C_mRNA; YCR026C; YCR026C.
DR   GeneID; 850391; -.
DR   KEGG; sce:YCR026C; -.
DR   AGR; SGD:S000000621; -.
DR   SGD; S000000621; NPP1.
DR   VEuPathDB; FungiDB:YCR026C; -.
DR   eggNOG; KOG2645; Eukaryota.
DR   GeneTree; ENSGT00940000167607; -.
DR   HOGENOM; CLU_017594_3_1_1; -.
DR   InParanoid; P25353; -.
DR   OMA; SEPIWET; -.
DR   OrthoDB; 1366859at2759; -.
DR   BioCyc; YEAST:G3O-29341-MONOMER; -.
DR   Reactome; R-SCE-196843; Vitamin B2 (riboflavin) metabolism.
DR   Reactome; R-SCE-6798695; Neutrophil degranulation.
DR   Reactome; R-SCE-6814848; Glycerophospholipid catabolism.
DR   Reactome; R-SCE-9840310; Glycosphingolipid catabolism.
DR   BioGRID-ORCS; 850391; 0 hits in 10 CRISPR screens.
DR   PRO; PR:P25353; -.
DR   Proteomes; UP000002311; Chromosome III.
DR   RNAct; P25353; Protein.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0047429; F:nucleoside triphosphate diphosphatase activity; IDA:SGD.
DR   GO; GO:0004528; F:phosphodiesterase I activity; IEA:UniProtKB-EC.
DR   GO; GO:0017111; F:ribonucleoside triphosphate phosphatase activity; IMP:SGD.
DR   GO; GO:0016036; P:cellular response to phosphate starvation; IMP:SGD.
DR   GO; GO:0009141; P:nucleoside triphosphate metabolic process; IMP:SGD.
DR   CDD; cd16018; Enpp; 1.
DR   Gene3D; 3.30.1360.180; -; 1.
DR   Gene3D; 3.40.720.10; Alkaline Phosphatase, subunit A; 1.
DR   InterPro; IPR017850; Alkaline_phosphatase_core_sf.
DR   InterPro; IPR002591; Phosphodiest/P_Trfase.
DR   PANTHER; PTHR10151:SF120; BIS(5'-ADENOSYL)-TRIPHOSPHATASE; 1.
DR   PANTHER; PTHR10151; ECTONUCLEOTIDE PYROPHOSPHATASE/PHOSPHODIESTERASE; 1.
DR   Pfam; PF01663; Phosphodiest; 1.
DR   SUPFAM; SSF53649; Alkaline phosphatase-like; 1.
PE   1: Evidence at protein level;
KW   Glycoprotein; Hydrolase; Membrane; Multifunctional enzyme; Phosphoprotein;
KW   Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix.
FT   CHAIN           1..742
FT                   /note="Ectonucleotide pyrophosphatase/phosphodiesterase 1"
FT                   /id="PRO_0000202566"
FT   TOPO_DOM        1..113
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        114..134
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        135..742
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   REGION          168..545
FT                   /note="Phosphodiesterase"
FT   REGION          640..670
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          686..711
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        643..659
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        219
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        161
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        204
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        264
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        296
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        403
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   742 AA;  84734 MW;  83BD5F00D69B09C5 CRC64;
     MELQNDLESL DNELNDFSED PFRDDFITDE DAVRSGWRSA WTRMKYWFYK NRLKWTNNPI
     VIGDAKDSRD GSNFRRGIPL YELDANGQPI DTELVDENEL SFGTGFHSKV PFKIIFRTLF
     GSLVFAIFLI LMINIAKPHH STRVLSHFGS PEFDPYVKYF NGTHEFFPLT IVISLDGFHP
     SLISKRNTPF LHDLYELKYD GGMNITSTPF MVPSFPTETF PNHWTLVTGQ YPIHHGIVSN
     VFWDPDLNEE FHPGVLDPRI WNNNDTEPIW QTVQSAFDGD IPFKAATHMW PGSDVNYTKY
     NEEKLQPEHK NPIARERTPF YFDEFNAKEP LSQKLSKIIE YVDMSTLNER PQLILGYVPN
     VDAFGHKHGY PSESEYYYED FTETLGEVDT FLKQLVESLQ ERNLTSFTNL VIVSDHGMSD
     IVVPSNVIIW EDLLDEKLRK DYVSHAYLEG PMMAISLKDS GNINEVYHNL KTSIDEDKYT
     VYVNGNFPKE WNFNDGKNHH MASIWIVPEP GYAVMKKEQL KKVAKGDHKD KNEDNVFTIG
     SHGYDNNAID MRSVFIGMGP YFPQGYIEPF QNTEIYNLLC DICGVAEKDR NSNDGTGMLM
     NQLREPQSSE EVEIEDDFDY LVSKFGEFST YNIIWGGYPE ETEQDNVDND NDDNDDGNTD
     EIAAMPSSSL TIKLEMTTSI PSATETLLGE TSPSSRSSSS SSIQASATAS TVGDWLQDII
     NDAKDLIDDI IDSIDDLVDS DT
//