ID SIW14_YEAST Reviewed; 281 AA. AC P53965; D6W1E7; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1996, sequence version 1. DT 27-MAR-2024, entry version 167. DE RecName: Full=Inositol phosphatase SIW14 {ECO:0000303|PubMed:30548067}; DE EC=3.6.1.52; DE AltName: Full=5-PP-InsP phosphatase {ECO:0000303|PubMed:29540476}; DE AltName: Full=Inositol pyrophosphate phosphatase SIW14 {ECO:0000303|PubMed:26828065}; DE AltName: Full=Oxidant-induced cell-cycle arrest protein 3; DE AltName: Full=Synthetic interaction with WHI2 protein 14; GN Name=SIW14; Synonyms=OCA3; GN OrderedLocusNames=YNL032W {ECO:0000312|SGD:S000004977}; GN ORFNames=N2746; 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=9169873; RA Philippsen P., Kleine K., Poehlmann R., Duesterhoeft A., Hamberg K., RA Hegemann J.H., Obermaier B., Urrestarazu L.A., Aert R., Albermann K., RA Altmann R., Andre B., Baladron V., Ballesta J.P.G., Becam A.-M., RA Beinhauer J.D., Boskovic J., Buitrago M.J., Bussereau F., Coster F., RA Crouzet M., D'Angelo M., Dal Pero F., De Antoni A., del Rey F., Doignon F., RA Domdey H., Dubois E., Fiedler T.A., Fleig U., Floeth M., Fritz C., RA Gaillardin C., Garcia-Cantalejo J.M., Glansdorff N., Goffeau A., RA Gueldener U., Herbert C.J., Heumann K., Heuss-Neitzel D., Hilbert H., RA Hinni K., Iraqui Houssaini I., Jacquet M., Jimenez A., Jonniaux J.-L., RA Karpfinger-Hartl L., Lanfranchi G., Lepingle A., Levesque H., Lyck R., RA Maftahi M., Mallet L., Maurer C.T.C., Messenguy F., Mewes H.-W., Moestl D., RA Nasr F., Nicaud J.-M., Niedenthal R.K., Pandolfo D., Pierard A., RA Piravandi E., Planta R.J., Pohl T.M., Purnelle B., Rebischung C., RA Remacha M.A., Revuelta J.L., Rinke M., Saiz J.E., Sartorello F., RA Scherens B., Sen-Gupta M., Soler-Mira A., Urbanus J.H.M., Valle G., RA Van Dyck L., Verhasselt P., Vierendeels F., Vissers S., Voet M., RA Volckaert G., Wach A., Wambutt R., Wedler H., Zollner A., Hani J.; RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XIV and its RT evolutionary implications."; RL Nature 387:93-98(1997). RN [2] 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 [3] RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. RX PubMed=14562095; DOI=10.1038/nature02026; RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W., RA Weissman J.S., O'Shea E.K.; RT "Global analysis of protein localization in budding yeast."; RL Nature 425:686-691(2003). RN [4] 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 [5] RP FUNCTION. RX PubMed=15020461; DOI=10.1534/genetics.166.2.707; RA Care A., Vousden K.A., Binley K.M., Radcliffe P., Trevethick J., RA Mannazzu I., Sudbery P.E.; RT "A synthetic lethal screen identifies a role for the cortical actin RT patch/endocytosis complex in the response to nutrient deprivation in RT Saccharomyces cerevisiae."; RL Genetics 166:707-719(2004). RN [6] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-94, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC STRAIN=ADR376; RX PubMed=17330950; DOI=10.1021/pr060559j; RA Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J., RA Elias J.E., Gygi S.P.; RT "Large-scale phosphorylation analysis of alpha-factor-arrested RT Saccharomyces cerevisiae."; RL J. Proteome Res. 6:1190-1197(2007). RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-94, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19779198; DOI=10.1126/science.1172867; RA Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.; RT "Global analysis of Cdk1 substrate phosphorylation sites provides insights RT into evolution."; RL Science 325:1682-1686(2009). RN [8] RP CATALYTIC ACTIVITY. RX PubMed=21409566; DOI=10.1007/s00438-011-0611-6; RA Roma-Mateo C., Sacristan-Reviriego A., Beresford N.J., RA Caparros-Martin J.A., Culianez-Macia F.A., Martin H., Molina M., RA Tabernero L., Pulido R.; RT "Phylogenetic and genetic linkage between novel atypical dual-specificity RT phosphatases from non-metazoan organisms."; RL Mol. Genet. Genomics 285:341-354(2011). RN [9] RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND RP MUTAGENESIS OF CYS-214. RX PubMed=26828065; DOI=10.1074/jbc.m116.714907; RA Steidle E.A., Chong L.S., Wu M., Crooke E., Fiedler D., Resnick A.C., RA Rolfes R.J.; RT "A novel inositol pyrophosphate phosphatase in Saccharomyces cerevisiae: RT Siw14 protein selectively cleaves the beta-phosphate from 5- RT diphosphoinositol pentakisphosphate (5pp-ip5)."; RL J. Biol. Chem. 291:6772-6783(2016). RN [10] RP FUNCTION IN PRION SUPPRESSION. RX PubMed=28923943; DOI=10.1073/pnas.1714361114; RA Wickner R.B., Kelly A.C., Bezsonov E.E., Edskes H.K.; RT "[PSI+] prion propagation is controlled by inositol polyphosphates."; RL Proc. Natl. Acad. Sci. U.S.A. 114:E8402-E8410(2017). RN [11] RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 116-281, SUBUNIT, AND MUTAGENESIS RP OF CYS-214 AND ARG-220. RX PubMed=29540476; DOI=10.1074/jbc.ra117.001670; RA Wang H., Gu C., Rolfes R.J., Jessen H.J., Shears S.B.; RT "Structural and biochemical characterization of Siw14: A protein-tyrosine RT phosphatase fold that metabolizes inositol pyrophosphates."; RL J. Biol. Chem. 293:6905-6914(2018). RN [12] RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 113-281. RX PubMed=30548067; DOI=10.1021/acs.biochem.8b01044; RA Florio T.J., Lokareddy R.K., Gillilan R.E., Cingolani G.; RT "Molecular architecture of the inositol phosphatase Siw14."; RL Biochemistry 58:534-545(2019). CC -!- FUNCTION: Selectively cleaves the beta-phosphate at the 5-position of CC soluble inositol pyrophosphates. Converts 5-diphosphoinositol CC tetrakisphosphate (5-PP-InsP(4)) into inositol pentakisphosphate CC (InsP(5)), 5-diphosphoinositol pentakisphosphate (5-PP-IP(5) or 5- CC InsP(7)) into inositol hexakisphosphate (IP(6) or InsP(6)), and 1,5- CC bisdiphosphoinositol tetrakisphosphate (1,5-PP-IP(5) or InsP(8)) into CC 1-diphosphoinositol pentakisphosphate (1-PP-IP(5) or 1-InsP(7)) CC (PubMed:26828065, PubMed:29540476). Modulates inositol pyrophosphate CC metabolism that may have an influence in stress response CC (PubMed:26828065). Plays a role in actin filament organization and CC endocytosis (PubMed:15020461). Functions as a prion suppressing factor CC possibly due to its phosphatase activity against inositol CC pyrophosphates, which are signal transduction molecules involved in CC prion propagation (PubMed:28923943). {ECO:0000269|PubMed:15020461, CC ECO:0000269|PubMed:26828065, ECO:0000269|PubMed:28923943, CC ECO:0000269|PubMed:29540476}. CC -!- CATALYTIC ACTIVITY: CC Reaction=5-diphospho-1D-myo-inositol 1,2,3,4,6-pentakisphosphate + H2O CC = 1D-myo-inositol hexakisphosphate + H(+) + phosphate; CC Xref=Rhea:RHEA:22384, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58130, ChEBI:CHEBI:58628; EC=3.6.1.52; CC Evidence={ECO:0000269|PubMed:26828065, ECO:0000269|PubMed:29540476}; CC -!- CATALYTIC ACTIVITY: CC Reaction=5-diphospho-1D-myo-inositol 1,3,4,6-tetrakisphosphate + H2O = CC 1D-myo-inositol 1,3,4,5,6-pentakisphosphate + H(+) + phosphate; CC Xref=Rhea:RHEA:59500, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:57733, ChEBI:CHEBI:142939; CC EC=3.6.1.52; Evidence={ECO:0000269|PubMed:29540476}; CC -!- CATALYTIC ACTIVITY: CC Reaction=3,5-bis(diphospho)-1D-myo-inositol 1,2,4,6-tetrakisphosphate + CC H2O = 3-diphospho-1D-myo-inositol 1,2,4,5,6-pentakisphosphate + 2 CC H(+) + phosphate; Xref=Rhea:RHEA:56312, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:43474, ChEBI:CHEBI:140372, CC ChEBI:CHEBI:140374; EC=3.6.1.52; CC Evidence={ECO:0000269|PubMed:29540476}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=34 uM for 5-diphosphoinositol pentakisphosphate CC {ECO:0000269|PubMed:26828065}; CC KM=10.4 uM for 5-diphosphoinositol pentakisphosphate CC {ECO:0000269|PubMed:29540476}; CC KM=56.8 uM for 5-diphosphoinositol tetrakisphosphate CC {ECO:0000269|PubMed:29540476}; CC KM=10.1 uM for 1,5-bisdiphosphoinositol tetrakisphosphate CC {ECO:0000269|PubMed:29540476}; CC Note=kcat is 0.0025 sec(-1) with 5-diphosphoinositol CC pentakisphosphate as substrate (PubMed:26828065). kcat is 1.31 CC sec(-1) with 5-diphosphoinositol pentakisphosphate as substrate, 0.77 CC sec(-1) with 5-diphosphoinositol tetrakisphosphate as substrate, and CC 0.63 sec(-1) with 1,5-bisdiphosphoinositol tetrakisphosphate as CC substrate (PubMed:29540476). {ECO:0000269|PubMed:26828065, CC ECO:0000269|PubMed:29540476}; CC pH dependence: CC Optimum pH is 6. {ECO:0000269|PubMed:26828065}; CC Temperature dependence: CC Optimum temperature is 37 degrees Celsius. CC {ECO:0000269|PubMed:26828065}; CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:29540476}. CC -!- INTERACTION: CC P53965; P50946: OCA1; NbExp=4; IntAct=EBI-28668, EBI-28814; CC P53965; P53949: OCA2; NbExp=3; IntAct=EBI-28668, EBI-28725; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14562095}. CC -!- MISCELLANEOUS: Present with 4070 molecules/cell in log phase SD medium. CC {ECO:0000269|PubMed:14562106}. CC -!- SIMILARITY: Belongs to the protein-tyrosine phosphatase family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; Z71308; CAA95895.1; -; Genomic_DNA. DR EMBL; BK006947; DAA10513.1; -; Genomic_DNA. DR PIR; S62954; S62954. DR RefSeq; NP_014366.3; NM_001182871.3. DR PDB; 6BYF; X-ray; 2.35 A; A/B/C/D/E/F/G/H/I=116-281. DR PDB; 6E3B; X-ray; 2.50 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/V/W/X/Y=113-281. DR PDBsum; 6BYF; -. DR PDBsum; 6E3B; -. DR AlphaFoldDB; P53965; -. DR SMR; P53965; -. DR BioGRID; 35795; 456. DR DIP; DIP-1990N; -. DR IntAct; P53965; 30. DR MINT; P53965; -. DR STRING; 4932.YNL032W; -. DR iPTMnet; P53965; -. DR MaxQB; P53965; -. DR PaxDb; 4932-YNL032W; -. DR PeptideAtlas; P53965; -. DR EnsemblFungi; YNL032W_mRNA; YNL032W; YNL032W. DR GeneID; 855699; -. DR KEGG; sce:YNL032W; -. DR AGR; SGD:S000004977; -. DR SGD; S000004977; SIW14. DR VEuPathDB; FungiDB:YNL032W; -. DR eggNOG; KOG1572; Eukaryota. DR GeneTree; ENSGT00940000176301; -. DR HOGENOM; CLU_047845_1_0_1; -. DR InParanoid; P53965; -. DR OMA; RLEYENC; -. DR OrthoDB; 131574at2759; -. DR BioCyc; MetaCyc:G3O-33069-MONOMER; -. DR BioCyc; YEAST:G3O-33069-MONOMER; -. DR BRENDA; 3.1.3.48; 984. DR SABIO-RK; P53965; -. DR BioGRID-ORCS; 855699; 0 hits in 10 CRISPR screens. DR PRO; PR:P53965; -. DR Proteomes; UP000002311; Chromosome XIV. DR RNAct; P53965; Protein. DR GO; GO:0005737; C:cytoplasm; HDA:SGD. DR GO; GO:0005829; C:cytosol; HDA:SGD. DR GO; GO:0052840; F:inositol diphosphate tetrakisphosphate diphosphatase activity; IBA:GO_Central. DR GO; GO:0052847; F:inositol-1,5-bisdiphosphate-2,3,4,6-tetrakisphosphate 5-diphosphatase activity; IDA:SGD. DR GO; GO:0052848; F:inositol-3,5-bisdiphosphate-2,3,4,6-tetrakisphosphate 5-diphosphatase activity; IEA:RHEA. DR GO; GO:0052845; F:inositol-5-diphosphate-1,2,3,4,6-pentakisphosphate diphosphatase activity; IDA:SGD. DR GO; GO:0106211; F:inositol-5-diphosphate-1,3,4,6-tetrakisphosphate diphosphatase activity; IDA:SGD. DR GO; GO:0016791; F:phosphatase activity; IBA:GO_Central. DR GO; GO:0004721; F:phosphoprotein phosphatase activity; IEA:UniProtKB-KW. DR GO; GO:0007015; P:actin filament organization; IMP:SGD. DR GO; GO:0016311; P:dephosphorylation; IEA:InterPro. DR CDD; cd14528; PFA-DSP_Siw14; 1. DR Gene3D; 3.90.190.10; Protein tyrosine phosphatase superfamily; 1. DR InterPro; IPR020428; PFA-DSPs. DR InterPro; IPR029021; Prot-tyrosine_phosphatase-like. DR InterPro; IPR004861; Siw14-like. DR InterPro; IPR016130; Tyr_Pase_AS. DR InterPro; IPR020422; TYR_PHOSPHATASE_DUAL_dom. DR PANTHER; PTHR31126:SF78; INOSITOL PHOSPHATASE SIW14; 1. DR PANTHER; PTHR31126; TYROSINE-PROTEIN PHOSPHATASE; 1. DR Pfam; PF03162; Y_phosphatase2; 1. DR PRINTS; PR01911; PFDSPHPHTASE. DR SUPFAM; SSF52799; (Phosphotyrosine protein) phosphatases II; 1. DR PROSITE; PS00383; TYR_PHOSPHATASE_1; 1. DR PROSITE; PS50054; TYR_PHOSPHATASE_DUAL; 1. PE 1: Evidence at protein level; KW 3D-structure; Cytoplasm; Hydrolase; Phosphoprotein; Protein phosphatase; KW Reference proteome. FT CHAIN 1..281 FT /note="Inositol phosphatase SIW14" FT /id="PRO_0000094922" FT DOMAIN 121..271 FT /note="Tyrosine-protein phosphatase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160" FT REGION 1..20 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 214 FT /note="Phosphocysteine intermediate" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00160, FT ECO:0000305|PubMed:29540476" FT SITE 220 FT /note="Transition state stabilizer" FT /evidence="ECO:0000305|PubMed:29540476" FT MOD_RES 94 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17330950, FT ECO:0007744|PubMed:19779198" FT MUTAGEN 214 FT /note="C->S: Abolishes catalytic activity." FT /evidence="ECO:0000269|PubMed:26828065, FT ECO:0000269|PubMed:29540476" FT MUTAGEN 220 FT /note="R->A: Abolishes catalytic activity." FT /evidence="ECO:0000269|PubMed:29540476" FT STRAND 123..126 FT /evidence="ECO:0007829|PDB:6BYF" FT STRAND 129..133 FT /evidence="ECO:0007829|PDB:6BYF" FT HELIX 137..139 FT /evidence="ECO:0007829|PDB:6BYF" FT HELIX 140..145 FT /evidence="ECO:0007829|PDB:6BYF" FT STRAND 150..154 FT /evidence="ECO:0007829|PDB:6BYF" FT STRAND 156..158 FT /evidence="ECO:0007829|PDB:6BYF" FT HELIX 162..171 FT /evidence="ECO:0007829|PDB:6BYF" FT STRAND 174..177 FT /evidence="ECO:0007829|PDB:6BYF" FT STRAND 182..187 FT /evidence="ECO:0007829|PDB:6E3B" FT HELIX 192..203 FT /evidence="ECO:0007829|PDB:6BYF" FT HELIX 205..207 FT /evidence="ECO:0007829|PDB:6BYF" FT STRAND 209..213 FT /evidence="ECO:0007829|PDB:6BYF" FT STRAND 215..219 FT /evidence="ECO:0007829|PDB:6BYF" FT HELIX 220..231 FT /evidence="ECO:0007829|PDB:6BYF" FT HELIX 236..247 FT /evidence="ECO:0007829|PDB:6BYF" FT HELIX 253..261 FT /evidence="ECO:0007829|PDB:6BYF" FT HELIX 265..274 FT /evidence="ECO:0007829|PDB:6BYF" SQ SEQUENCE 281 AA; 32755 MW; 88BD8AFC620B4570 CRC64; MGLYQAKNDE GSDPKSSSKI DDLIENEAEI IRLIKEDGKL LIDNGDGRDI HNIIQEDKLL SVEFNEVLKR FHGEEKSDIP RKEFDEDEDD GYDSNEHHQK TIEVMNTLNH VINKEVIPPE NFSHVVGEIY RSSFPRQENF SFLHERLKLK SILVLIPEEY PQENLNFLKL TGIKLYQVGM SGNKEPFVNI PSHLLTKALE IVLNPANQPI LIHCNRGKHR TGCLIGCIRK LQNWSLTMIF DEYRRFAFPK ARALDQQFIE MYDDDEIKRI ASKNNWLPLQ W //