ID PNC1_YEAST Reviewed; 216 AA. AC P53184; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1996, sequence version 1. DT 16-JUN-2009, entry version 74. DE RecName: Full=Nicotinamidase; DE EC=3.5.1.19; DE AltName: Full=Nicotine deamidase; DE Short=NAMase; GN Name=PNC1; OrderedLocusNames=YGL037C; OS Saccharomyces cerevisiae (Baker's yeast). OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; OC Saccharomycetes; Saccharomycetales; Saccharomycetaceae; Saccharomyces. OX NCBI_TaxID=4932; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 96604 / S288c / FY1679; RX MEDLINE=97313265; PubMed=9169869; RA Tettelin H., Agostoni-Carbone M.L., Albermann K., Albers M., RA Arroyo J., Backes U., Barreiros T., Bertani I., Bjourson A.J., RA Brueckner M., Bruschi C.V., Carignani G., Castagnoli L., Cerdan E., RA Clemente M.L., Coblenz A., Coglievina M., Coissac E., Defoor E., RA Del Bino S., Delius H., Delneri D., de Wergifosse P., Dujon B., RA Durand P., Entian K.-D., Eraso P., Escribano V., Fabiani L., RA Fartmann B., Feroli F., Feuermann M., Frontali L., Garcia-Gonzalez M., RA Garcia-Saez M.I., Goffeau A., Guerreiro P., Hani J., Hansen M., RA Hebling U., Hernandez K., Heumann K., Hilger F., Hofmann B., RA Indge K.J., James C.M., Klima R., Koetter P., Kramer B., Kramer W., RA Lauquin G., Leuther H., Louis E.J., Maillier E., Marconi A., RA Martegani E., Mazon M.J., Mazzoni C., McReynolds A.D.K., RA Melchioretto P., Mewes H.-W., Minenkova O., Mueller-Auer S., RA Nawrocki A., Netter P., Neu R., Nombela C., Oliver S.G., Panzeri L., RA Paoluzi S., Plevani P., Portetelle D., Portillo F., Potier S., RA Purnelle B., Rieger M., Riles L., Rinaldi T., Robben J., RA Rodrigues-Pousada C., Rodriguez-Belmonte E., Rodriguez-Torres A.M., RA Rose M., Ruzzi M., Saliola M., Sanchez-Perez M., Schaefer B., RA Schaefer M., Scharfe M., Schmidheini T., Schreer A., Skala J., RA Souciet J.-L., Steensma H.Y., Talla E., Thierry A., Vandenbol M., RA van der Aart Q.J.M., Van Dyck L., Vanoni M., Verhasselt P., Voet M., RA Volckaert G., Wambutt R., Watson M.D., Weber N., Wedler E., Wedler H., RA Wipfli P., Wolf K., Wright L.F., Zaccaria P., Zimmermann M., RA Zollner A., Kleine K.; RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome VII."; RL Nature 387:81-84(1997). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=ATCC 204508 / S288c; RX PubMed=17322287; DOI=10.1101/gr.6037607; RA Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F., RA Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., RA Raphael J., Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., RA Williamson J., Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., RA Kolodner R.D., LaBaer J.; RT "Approaching a complete repository of sequence-verified protein- RT encoding clones for Saccharomyces cerevisiae."; RL Genome Res. 17:536-543(2007). RN [3] RP PROTEIN SEQUENCE OF 1-11, FUNCTION, AND INDUCTION. RX MEDLINE=21675004; PubMed=11816029; DOI=10.1002/yea.810.abs; RA Ghislain M., Talla E., Francois J.M.; RT "Identification and functional analysis of the Saccharomyces RT cerevisiae nicotinamidase gene, PNC1."; RL Yeast 19:215-224(2002). RN [4] RP BIOPHYSICOCHEMICAL PROPERTIES, AND ENZYME REGULATION. RX PubMed=6058082; DOI=10.1016/0003-9861(67)90612-1; RA Bernheim M.L.C.; RT "Hydrolysis of nicotinyl hydroxamate by a yeast nicotinamidase."; RL Arch. Biochem. Biophys. 120:186-191(1967). RN [5] RP BIOPHYSICOCHEMICAL PROPERTIES, AND ENZYME REGULATION. RX PubMed=4326215; RA Calbreath D.F., Joshi J.G.; RT "Inhibition of nicotinamidase by nicotinamide adenine dinucleotide."; RL J. Biol. Chem. 246:4334-4339(1971). RN [6] RP FUNCTION, SUBCELLULAR LOCATION, AND INDUCTION. RX PubMed=12736687; DOI=10.1038/nature01578; RA Anderson R.M., Bitterman K.J., Wood J.G., Medvedik O., Sinclair D.A.; RT "Nicotinamide and PNC1 govern lifespan extension by calorie RT restriction in Saccharomyces cerevisiae."; RL Nature 423:181-185(2003). RN [7] RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. RX MEDLINE=22923954; 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 [8] RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS]. RX MEDLINE=22923965; PubMed=14562106; DOI=10.1038/nature02046; RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., RA Dephoure N., O'Shea E.K., Weissman J.S.; RT "Global analysis of protein expression in yeast."; RL Nature 425:737-741(2003). RN [9] RP FUNCTION. RX PubMed=14729974; DOI=10.1128/MCB.24.3.1301-1312.2004; RA Gallo C.M., Smith D.L. Jr., Smith J.S.; RT "Nicotinamide clearance by Pnc1 directly regulates Sir2-mediated RT silencing and longevity."; RL Mol. Cell. Biol. 24:1301-1312(2004). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-174, AND MASS RP SPECTROMETRY. RX PubMed=18407956; DOI=10.1074/mcp.M700468-MCP200; RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.; RT "A multidimensional chromatography technology for in-depth RT phosphoproteome analysis."; RL Mol. Cell. Proteomics 7:1389-1396(2008). RN [11] RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS), AND BIOPHYSICOCHEMICAL RP PROPERTIES. RX PubMed=17382284; DOI=10.1016/j.abb.2007.01.037; RA Hu G., Taylor A.B., McAlister-Henn L., Hart P.J.; RT "Crystal structure of the yeast nicotinamidase Pnc1p."; RL Arch. Biochem. Biophys. 461:66-75(2007). CC -!- FUNCTION: Catalyzes the deamidation of nicotinamide, an early step CC in the NAD(+) salvage pathway. Positively regulates SIR2-mediated CC silencing and longevity by preventing the accumulation of CC intracellular nicotinamide, an inhibitor of SIR2, during times of CC stress. Acts also on nicotinyl hydroxamate. CC -!- CATALYTIC ACTIVITY: Nicotinamide + H(2)O = nicotinate + NH(3). CC -!- ENZYME REGULATION: Inhibited by N-ethylmaleimide, HgCl(2) and CC PCMB. Competitively inhibited by NAD, NMN and 3-acetylpyridine. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=5.8 uM for nicotinamide; CC KM=32 uM for nicotinyl hydroxamate; CC KM=0.2 mM for pyrazinamide; CC Vmax=50.2 umol/min/mg enzyme for nicotinamide; CC Vmax=59.4 umol/min/mg enzyme for pyrazinamide; CC pH dependence: CC Optimum pH is 6.5-7.5; CC Temperature dependence: CC Heating at 60 degrees Celsius inactivates the enzyme. Heating at CC 60 degrees Celsius in the presence of substrate prevents CC inactivation; CC -!- PATHWAY: Cofactor biosynthesis; nicotinate biosynthesis; CC nicotinate from nicotinamide: step 1/1. CC -!- INTERACTION: CC Q02821:SRP1; NbExp=1; IntAct=EBI-23741, EBI-1797; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Peroxisome. CC Note=Concentrates in peroxisomes. CC -!- INDUCTION: Induced during the stationary phase of growth, by CC calorie restriction, by various hyperosmotic shocks or by low- CC intensity stress (at protein level). CC -!- MISCELLANEOUS: Has a cis-peptide bond at 162-Val-Ala-163. CC -!- MISCELLANEOUS: Present with 7720 molecules/cell in log phase SD CC medium. CC -!- SIMILARITY: Belongs to the pncA family. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; Z72559; CAA96739.1; -; Genomic_DNA. DR EMBL; AY558481; AAS56807.1; -; Genomic_DNA. DR PIR; S64039; S64039. DR RefSeq; NP_011478.1; -. DR PDB; 2H0R; X-ray; 2.90 A; A/B/C/D/E/F/G=1-216. DR PDBsum; 2H0R; -. DR DIP; DIP:2070N; -. DR IntAct; P53184; 10. DR PeptideAtlas; P53184; -. DR PRIDE; P53184; -. DR Ensembl; YGL037C; Saccharomyces cerevisiae. DR GeneID; 852846; -. DR GenomeReviews; Y13135_GR; YGL037C. DR KEGG; sce:YGL037C; -. DR NMPDR; fig|4932.3.peg.2585; -. DR CYGD; YGL037c; -. DR SGD; S000003005; PNC1. DR HOGENOM; P53184; -. DR OMA; P53184; LHSIGAR. DR BRENDA; 3.5.1.19; 250. DR NextBio; 972431; -. DR ArrayExpress; P53184; -. DR GermOnline; YGL037C; Saccharomyces cerevisiae. DR GO; GO:0005634; C:nucleus; IDA:SGD. DR GO; GO:0005777; C:peroxisome; IDA:SGD. DR GO; GO:0008936; F:nicotinamidase activity; IMP:SGD. DR GO; GO:0005515; F:protein binding; IPI:IntAct. DR GO; GO:0008270; F:zinc ion binding; IEA:UniProtKB-KW. DR GO; GO:0000183; P:chromatin silencing at rDNA; IMP:SGD. DR GO; GO:0006348; P:chromatin silencing at telomere; IMP:SGD. DR GO; GO:0019363; P:pyridine nucleotide biosynthetic process; IEA:UniProtKB-KW. DR GO; GO:0001302; P:replicative cell aging; IEP:SGD. DR InterPro; IPR000868; Isochorismatase-like. DR Gene3D; G3DSA:3.40.50.850; Isochorismatase_hydro; 1. DR Pfam; PF00857; Isochorismatase; 1. PE 1: Evidence at protein level; KW 3D-structure; Complete proteome; Cytoplasm; Direct protein sequencing; KW Hydrolase; Metal-binding; Nucleus; Peroxisome; Phosphoprotein; KW Pyridine nucleotide biosynthesis; Zinc. FT CHAIN 1 216 Nicotinamidase. FT /FTId=PRO_0000206558. FT ACT_SITE 8 8 FT ACT_SITE 122 122 FT ACT_SITE 167 167 FT METAL 51 51 Zinc. FT METAL 53 53 Zinc. FT METAL 94 94 Zinc. FT MOD_RES 174 174 Phosphoserine. FT STRAND 2 7 FT HELIX 11 14 FT HELIX 26 28 FT HELIX 29 37 FT HELIX 39 41 FT STRAND 44 51 FT HELIX 61 63 FT STRAND 71 76 FT STRAND 85 91 FT HELIX 100 102 FT HELIX 106 114 FT STRAND 118 123 FT STRAND 132 135 FT HELIX 145 151 FT STRAND 155 162 FT TURN 164 166 FT HELIX 167 177 FT STRAND 181 189 FT HELIX 197 208 FT STRAND 212 214 SQ SEQUENCE 216 AA; 24993 MW; C40B23C4228B6E3A CRC64; MKTLIVVDMQ NDFISPLGSL TVPKGEELIN PISDLMQDAD RDWHRIVVTR DWHPSRHISF AKNHKDKEPY STYTYHSPRP GDDSTQEGIL WPVHCVKNTW GSQLVDQIMD QVVTKHIKIV DKGFLTDREY YSAFHDIWNF HKTDMNKYLE KHHTDEVYIV GVALEYCVKA TAISAAELGY KTTVLLDYTR PISDDPEVIN KVKEELKAHN INVVDK //