PNC1_YEAST
ID PNC1_YEAST Reviewed; 216 AA.
AC P53184; D6VUA2;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Nicotinamidase;
DE EC=3.5.1.19 {ECO:0000269|PubMed:17382284};
DE AltName: Full=Nicotinamide deamidase;
DE Short=NAMase;
GN Name=PNC1; OrderedLocusNames=YGL037C;
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=9169869;
RA Tettelin H., Agostoni-Carbone M.L., Albermann K., Albers M., Arroyo J.,
RA Backes U., Barreiros T., Bertani I., Bjourson A.J., Brueckner M.,
RA Bruschi C.V., Carignani G., Castagnoli L., Cerdan E., Clemente M.L.,
RA Coblenz A., Coglievina M., Coissac E., Defoor E., Del Bino S., Delius H.,
RA Delneri D., de Wergifosse P., Dujon B., Durand P., Entian K.-D., Eraso P.,
RA Escribano V., Fabiani L., Fartmann B., Feroli F., Feuermann M.,
RA Frontali L., Garcia-Gonzalez M., Garcia-Saez M.I., Goffeau A.,
RA Guerreiro P., Hani J., Hansen M., Hebling U., Hernandez K., Heumann K.,
RA Hilger F., Hofmann B., Indge K.J., James C.M., Klima R., Koetter P.,
RA Kramer B., Kramer W., Lauquin G., Leuther H., Louis E.J., Maillier E.,
RA Marconi A., Martegani E., Mazon M.J., Mazzoni C., McReynolds A.D.K.,
RA Melchioretto P., Mewes H.-W., Minenkova O., Mueller-Auer S., Nawrocki A.,
RA Netter P., Neu R., Nombela C., Oliver S.G., Panzeri L., Paoluzi S.,
RA Plevani P., Portetelle D., Portillo F., Potier S., Purnelle B., Rieger M.,
RA Riles L., Rinaldi T., Robben J., Rodrigues-Pousada C.,
RA Rodriguez-Belmonte E., Rodriguez-Torres A.M., Rose M., Ruzzi M.,
RA Saliola M., Sanchez-Perez M., Schaefer B., Schaefer M., Scharfe M.,
RA Schmidheini T., Schreer A., Skala J., Souciet J.-L., Steensma H.Y.,
RA Talla E., Thierry A., Vandenbol M., van der Aart Q.J.M., Van Dyck L.,
RA Vanoni M., Verhasselt P., Voet M., Volckaert G., Wambutt R., Watson M.D.,
RA Weber N., Wedler E., Wedler H., Wipfli P., Wolf K., Wright L.F.,
RA Zaccaria P., Zimmermann M., Zollner A., Kleine K.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome VII.";
RL Nature 387:81-84(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 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., Raphael J.,
RA Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J.,
RA Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D.,
RA LaBaer J.;
RT "Approaching a complete repository of sequence-verified protein-encoding
RT clones for Saccharomyces cerevisiae.";
RL Genome Res. 17:536-543(2007).
RN [4]
RP PROTEIN SEQUENCE OF 1-11, FUNCTION, AND INDUCTION.
RX PubMed=11816029; DOI=10.1002/yea.810.abs;
RA Ghislain M., Talla E., Francois J.M.;
RT "Identification and functional analysis of the Saccharomyces cerevisiae
RT nicotinamidase gene, PNC1.";
RL Yeast 19:215-224(2002).
RN [5]
RP BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY 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 [6]
RP BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY REGULATION.
RX PubMed=4326215; DOI=10.1016/s0021-9258(18)62089-7;
RA Calbreath D.F., Joshi J.G.;
RT "Inhibition of nicotinamidase by nicotinamide adenine dinucleotide.";
RL J. Biol. Chem. 246:4334-4339(1971).
RN [7]
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 restriction in
RT Saccharomyces cerevisiae.";
RL Nature 423:181-185(2003).
RN [8]
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 [9]
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 [10]
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 silencing
RT and longevity.";
RL Mol. Cell. Biol. 24:1301-1312(2004).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 phosphoproteome
RT analysis.";
RL Mol. Cell. Proteomics 7:1389-1396(2008).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) IN COMPLEX WITH ZINC IONS, CATALYTIC
RP ACTIVITY, AND BIOPHYSICOCHEMICAL 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 in
CC the NAD(+) salvage pathway. Positively regulates SIR2-mediated
CC silencing and longevity by preventing the accumulation of intracellular
CC nicotinamide, an inhibitor of SIR2, during times of stress. Acts also
CC on nicotinyl hydroxamate. {ECO:0000269|PubMed:11816029,
CC ECO:0000269|PubMed:12736687, ECO:0000269|PubMed:14729974}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + nicotinamide = NH4(+) + nicotinate;
CC Xref=Rhea:RHEA:14545, ChEBI:CHEBI:15377, ChEBI:CHEBI:17154,
CC ChEBI:CHEBI:28938, ChEBI:CHEBI:32544; EC=3.5.1.19;
CC Evidence={ECO:0000269|PubMed:17382284};
CC -!- ACTIVITY REGULATION: Inhibited by N-ethylmaleimide, HgCl(2) and PCMB.
CC Competitively inhibited by NAD, NMN and 3-acetylpyridine.
CC {ECO:0000269|PubMed:4326215, ECO:0000269|PubMed:6058082}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=5.8 uM for nicotinamide {ECO:0000269|PubMed:17382284,
CC ECO:0000269|PubMed:4326215, ECO:0000269|PubMed:6058082};
CC KM=32 uM for nicotinyl hydroxamate {ECO:0000269|PubMed:17382284,
CC ECO:0000269|PubMed:4326215, ECO:0000269|PubMed:6058082};
CC KM=0.2 mM for pyrazinamide {ECO:0000269|PubMed:17382284,
CC ECO:0000269|PubMed:4326215, ECO:0000269|PubMed:6058082};
CC Vmax=50.2 umol/min/mg enzyme for nicotinamide
CC {ECO:0000269|PubMed:17382284, ECO:0000269|PubMed:4326215,
CC ECO:0000269|PubMed:6058082};
CC Vmax=59.4 umol/min/mg enzyme for pyrazinamide
CC {ECO:0000269|PubMed:17382284, ECO:0000269|PubMed:4326215,
CC ECO:0000269|PubMed:6058082};
CC pH dependence:
CC Optimum pH is 6.5-7.5. {ECO:0000269|PubMed:17382284,
CC ECO:0000269|PubMed:4326215, ECO:0000269|PubMed:6058082};
CC Temperature dependence:
CC Heating at 60 degrees Celsius inactivates the enzyme. Heating at 60
CC degrees Celsius in the presence of substrate prevents inactivation.
CC {ECO:0000269|PubMed:17382284, ECO:0000269|PubMed:4326215,
CC ECO:0000269|PubMed:6058082};
CC -!- PATHWAY: Cofactor biosynthesis; nicotinate biosynthesis; nicotinate
CC from nicotinamide: step 1/1.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12736687}. Nucleus
CC {ECO:0000269|PubMed:12736687}. Peroxisome {ECO:0000269|PubMed:12736687,
CC ECO:0000269|PubMed:14562095}. Note=Concentrates in peroxisomes
CC (PubMed:12736687). {ECO:0000269|PubMed:12736687}.
CC -!- INDUCTION: Induced during the stationary phase of growth, by calorie
CC restriction, by various hyperosmotic shocks or by low-intensity stress
CC (at protein level). {ECO:0000269|PubMed:11816029,
CC ECO:0000269|PubMed:12736687}.
CC -!- MISCELLANEOUS: Has a cis-peptide bond at 162-Val-Ala-163.
CC -!- MISCELLANEOUS: Present with 7720 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the isochorismatase family. {ECO:0000305}.
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DR EMBL; Z72559; CAA96739.1; -; Genomic_DNA.
DR EMBL; AY558481; AAS56807.1; -; Genomic_DNA.
DR EMBL; BK006941; DAA08063.1; -; Genomic_DNA.
DR PIR; S64039; S64039.
DR RefSeq; NP_011478.3; NM_001180902.3.
DR PDB; 2H0R; X-ray; 2.90 A; A/B/C/D/E/F/G=1-216.
DR PDB; 3V8E; X-ray; 2.71 A; A/B/C/D/E/F/G=1-216.
DR PDBsum; 2H0R; -.
DR PDBsum; 3V8E; -.
DR AlphaFoldDB; P53184; -.
DR SMR; P53184; -.
DR BioGRID; 33210; 91.
DR DIP; DIP-2070N; -.
DR IntAct; P53184; 11.
DR MINT; P53184; -.
DR STRING; 4932.YGL037C; -.
DR BindingDB; P53184; -.
DR iPTMnet; P53184; -.
DR MaxQB; P53184; -.
DR PaxDb; P53184; -.
DR PRIDE; P53184; -.
DR TopDownProteomics; P53184; -.
DR EnsemblFungi; YGL037C_mRNA; YGL037C; YGL037C.
DR GeneID; 852846; -.
DR KEGG; sce:YGL037C; -.
DR SGD; S000003005; PNC1.
DR VEuPathDB; FungiDB:YGL037C; -.
DR eggNOG; KOG4003; Eukaryota.
DR HOGENOM; CLU_068979_13_0_1; -.
DR InParanoid; P53184; -.
DR OMA; DFVDSWP; -.
DR BioCyc; MetaCyc:YGL037C-MON; -.
DR BioCyc; YEAST:YGL037C-MON; -.
DR BRENDA; 3.5.1.19; 984.
DR UniPathway; UPA00830; UER00790.
DR EvolutionaryTrace; P53184; -.
DR PRO; PR:P53184; -.
DR Proteomes; UP000002311; Chromosome VII.
DR RNAct; P53184; protein.
DR GO; GO:0000781; C:chromosome, telomeric region; IEA:GOC.
DR GO; GO:0005737; C:cytoplasm; IDA:SGD.
DR GO; GO:0005634; C:nucleus; IDA:SGD.
DR GO; GO:0005777; C:peroxisome; IDA:SGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008936; F:nicotinamidase activity; IMP:SGD.
DR GO; GO:1904524; P:negative regulation of DNA amplification; IMP:SGD.
DR GO; GO:0019358; P:nicotinate nucleotide salvage; IMP:SGD.
DR GO; GO:0000183; P:rDNA heterochromatin assembly; IMP:SGD.
DR GO; GO:0031509; P:subtelomeric heterochromatin assembly; IMP:SGD.
DR Gene3D; 3.40.50.850; -; 1.
DR InterPro; IPR000868; Isochorismatase-like.
DR InterPro; IPR036380; Isochorismatase-like_sf.
DR Pfam; PF00857; Isochorismatase; 1.
DR SUPFAM; SSF52499; SSF52499; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Direct protein sequencing; Hydrolase;
KW Metal-binding; Nucleus; Peroxisome; Pyridine nucleotide biosynthesis;
KW Reference proteome; Zinc.
FT CHAIN 1..216
FT /note="Nicotinamidase"
FT /id="PRO_0000206558"
FT ACT_SITE 8
FT /evidence="ECO:0000255"
FT ACT_SITE 122
FT /evidence="ECO:0000255"
FT ACT_SITE 167
FT /note="Nucleophile"
FT /evidence="ECO:0000255"
FT BINDING 51
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:17382284,
FT ECO:0007744|PDB:2H0R"
FT BINDING 53
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:17382284,
FT ECO:0007744|PDB:2H0R"
FT BINDING 94
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:17382284,
FT ECO:0007744|PDB:2H0R"
FT STRAND 2..7
FT /evidence="ECO:0007829|PDB:3V8E"
FT HELIX 11..14
FT /evidence="ECO:0007829|PDB:3V8E"
FT HELIX 25..28
FT /evidence="ECO:0007829|PDB:3V8E"
FT HELIX 29..37
FT /evidence="ECO:0007829|PDB:3V8E"
FT HELIX 39..41
FT /evidence="ECO:0007829|PDB:3V8E"
FT STRAND 43..51
FT /evidence="ECO:0007829|PDB:3V8E"
FT HELIX 61..63
FT /evidence="ECO:0007829|PDB:3V8E"
FT STRAND 72..76
FT /evidence="ECO:0007829|PDB:3V8E"
FT STRAND 85..89
FT /evidence="ECO:0007829|PDB:3V8E"
FT HELIX 100..102
FT /evidence="ECO:0007829|PDB:3V8E"
FT HELIX 106..115
FT /evidence="ECO:0007829|PDB:3V8E"
FT STRAND 118..122
FT /evidence="ECO:0007829|PDB:3V8E"
FT STRAND 132..135
FT /evidence="ECO:0007829|PDB:3V8E"
FT HELIX 145..151
FT /evidence="ECO:0007829|PDB:3V8E"
FT STRAND 156..162
FT /evidence="ECO:0007829|PDB:3V8E"
FT HELIX 164..168
FT /evidence="ECO:0007829|PDB:3V8E"
FT HELIX 169..177
FT /evidence="ECO:0007829|PDB:3V8E"
FT STRAND 181..190
FT /evidence="ECO:0007829|PDB:3V8E"
FT HELIX 196..208
FT /evidence="ECO:0007829|PDB:3V8E"
FT STRAND 212..214
FT /evidence="ECO:0007829|PDB:3V8E"
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
