Reviewed, UniProtKB/Swiss-Prot P53184 (PNC1_YEAST)

Names and origin

Protein names

Recommended name:
    Nicotinamidase
    EC=3.5.1.19
Alternative name(s):
    Nicotine deamidase
      Short name=NAMase

Gene names

Name:	PNC1
Ordered Locus Names:	YGL037C

Organism

Saccharomyces cerevisiae (Baker's yeast) [Complete proteome]

Taxonomic identifier

4932 [NCBI]

Taxonomic lineage

Eukaryota › Fungi › Dikarya › Ascomycota › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces

Protein attributes

Sequence length	216 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Catalyzes the deamidation of nicotinamide, an early step in the NAD+ salvage pathway. Positively regulates SIR2-mediated silencing and longevity by preventing the accumulation of intracellular nicotinamide, an inhibitor of SIR2, during times of stress. Acts also on nicotinyl hydroxamate. Ref.3 Ref.6 Ref.9
Catalytic activity	Nicotinamide + H2O = nicotinate + NH3.
Enzyme regulation	Inhibited by N-ethylmaleimide, HgCl2 and PCMB. Competitively inhibited by NAD, NMN and 3-acetylpyridine. Ref.4 Ref.5
Pathway	Cofactor biosynthesis; nicotinate biosynthesis; nicotinate from nicotinamide: step 1/1.
Subcellular location	Cytoplasm. Nucleus. Peroxisome. Note: Concentrates in peroxisomes. Ref.6 Ref.7
Induction	Induced during the stationary phase of growth, by calorie restriction, by various hyperosmotic shocks or by low-intensity stress (at protein level). Ref.3 Ref.6
Miscellaneous	Has a cis-peptide bond at 162-Val-Ala-163. Present with 7720 molecules/cell in log phase SD medium. Ref.8
Sequence similarities	Belongs to the pncA family.
Biophysicochemical properties	Kinetic parameters: KM=5.8 µM for nicotinamide KM=32 µM for nicotinyl hydroxamate KM=0.2 mM for pyrazinamide Vmax=50.2 µmol/min/mg enzyme for nicotinamide Vmax=59.4 µmol/min/mg enzyme for pyrazinamide pH dependence: Optimum pH is 6.5-7.5. Temperature dependence: Heating at 60 degrees Celsius inactivates the enzyme. Heating at 60 degrees Celsius in the presence of substrate prevents inactivation.

Ontologies

Keywords
Biological process	Pyridine nucleotide biosynthesis
Cellular component	Cytoplasm Nucleus Peroxisome
Ligand	Metal-binding Zinc
Molecular function	Hydrolase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	chromatin silencing at rDNA Inferred from mutant phenotype. Source: SGD chromatin silencing at telomere Inferred from mutant phenotype. Source: SGD pyridine nucleotide biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW replicative cell aging Ref.6 Inferred from expression pattern. Source: SGD
Cellular component	nucleus Ref.6 Inferred from direct assay. Source: SGD peroxisome Ref.6 Inferred from direct assay. Source: SGD
Molecular function	nicotinamidase activity Inferred from mutant phenotype. Source: SGD protein binding Inferred from physical interaction. Source: IntAct zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
SRP1	Q02821	1	EBI-23741,EBI-1797

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 216

216

Nicotinamidase

PRO_0000206558

Sites

Active site

8

1

Active site

122

1

Active site

167

1

Metal binding

51

1

Zinc

Metal binding

53

1

Zinc

Metal binding

94

1

Zinc

Amino acid modifications

Modified residue

174

1

Phosphoserine Ref.10

Secondary structure

1

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216

Helix Strand Turn

Details...

Beta strand

2 – 7

6

Helix

11 – 14

4

Helix

26 – 28

3

Helix

29 – 37

9

Helix

39 – 41

3

Beta strand

44 – 51

8

Helix

61 – 63

3

Beta strand

71 – 76

6

Beta strand

85 – 91

7

Helix

100 – 102

3

Helix

106 – 114

9

Beta strand

118 – 123

6

Beta strand

132 – 135

4

Helix

145 – 151

7

Beta strand

155 – 162

8

Turn

164 – 166

3

Helix

167 – 177

11

Beta strand

181 – 189

9

Helix

197 – 208

12

Beta strand

212 – 214

3

Sequences

	Sequence		Length	Mass (Da)
	P53184-1 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: C40B23C4228B6E3A	FASTA	216	24,993
	10 20 30 40 50 60 MKTLIVVDMQ NDFISPLGSL TVPKGEELIN PISDLMQDAD RDWHRIVVTR DWHPSRHISF 70 80 90 100 110 120 AKNHKDKEPY STYTYHSPRP GDDSTQEGIL WPVHCVKNTW GSQLVDQIMD QVVTKHIKIV 130 140 150 160 170 180 DKGFLTDREY YSAFHDIWNF HKTDMNKYLE KHHTDEVYIV GVALEYCVKA TAISAAELGY 190 200 210 KTTVLLDYTR PISDDPEVIN KVKEELKAHN INVVDK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The nucleotide sequence of Saccharomyces cerevisiae chromosome VII." Tettelin H., Agostoni-Carbone M.L., Albermann K., Albers M., Arroyo J., Backes U., Barreiros T., Bertani I., Bjourson A.J., Brueckner M., Bruschi C.V., Carignani G., Castagnoli L., Cerdan E., Clemente M.L., Coblenz A., Coglievina M., Coissac E. , Defoor E., Del Bino S., Delius H., Delneri D., de Wergifosse P., Dujon B., Durand P., Entian K.-D., Eraso P., Escribano V., Fabiani L., Fartmann B., Feroli F., Feuermann M., Frontali L., Garcia-Gonzalez M., Garcia-Saez M.I., Goffeau A., Guerreiro P., Hani J., Hansen M., Hebling U., Hernandez K., Heumann K., Hilger F., Hofmann B., Indge K.J., James C.M., Klima R., Koetter P., Kramer B., Kramer W., Lauquin G., Leuther H., Louis E.J., Maillier E., Marconi A., Martegani E., Mazon M.J., Mazzoni C., McReynolds A.D.K., Melchioretto P., Mewes H.-W., Minenkova O., Mueller-Auer S., Nawrocki A., Netter P., Neu R., Nombela C., Oliver S.G., Panzeri L., Paoluzi S., Plevani P., Portetelle D., Portillo F., Potier S., Purnelle B., Rieger M., Riles L., Rinaldi T., Robben J., Rodrigues-Pousada C., Rodriguez-Belmonte E., Rodriguez-Torres A.M., Rose M., Ruzzi M., Saliola M., Sanchez-Perez M., Schaefer B., Schaefer M., Scharfe M., Schmidheini T., Schreer A., Skala J., Souciet J.-L., Steensma H.Y., Talla E., Thierry A., Vandenbol M., van der Aart Q.J.M., Van Dyck L., Vanoni M., Verhasselt P., Voet M., Volckaert G., Wambutt R., Watson M.D., Weber N., Wedler E., Wedler H., Wipfli P., Wolf K., Wright L.F., Zaccaria P., Zimmermann M., Zollner A., Kleine K. Nature 387:81-84(1997) [PubMed: 9169869] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 96604 / S288c / FY1679.
[2]	"Approaching a complete repository of sequence-verified protein-encoding clones for Saccharomyces cerevisiae." Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F., Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J., Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J. , Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D., LaBaer J. Genome Res. 17:536-543(2007) [PubMed: 17322287] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 204508 / S288c.
[3]	"Identification and functional analysis of the Saccharomyces cerevisiae nicotinamidase gene, PNC1." Ghislain M., Talla E., Francois J.M. Yeast 19:215-224(2002) [PubMed: 11816029] [Abstract] Cited for: PROTEIN SEQUENCE OF 1-11, FUNCTION, INDUCTION.
[4]	"Hydrolysis of nicotinyl hydroxamate by a yeast nicotinamidase." Bernheim M.L.C. Arch. Biochem. Biophys. 120:186-191(1967) [PubMed: 6058082] [Abstract] Cited for: BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION.
[5]	"Inhibition of nicotinamidase by nicotinamide adenine dinucleotide." Calbreath D.F., Joshi J.G. J. Biol. Chem. 246:4334-4339(1971) [PubMed: 4326215] [Abstract] Cited for: BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION.
[6]	"Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae." Anderson R.M., Bitterman K.J., Wood J.G., Medvedik O., Sinclair D.A. Nature 423:181-185(2003) [PubMed: 12736687] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INDUCTION.
[7]	"Global analysis of protein localization in budding yeast." Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W., Weissman J.S., O'Shea E.K. Nature 425:686-691(2003) [PubMed: 14562095] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
[8]	"Global analysis of protein expression in yeast." Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., O'Shea E.K., Weissman J.S. Nature 425:737-741(2003) [PubMed: 14562106] [Abstract] Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
[9]	"Nicotinamide clearance by Pnc1 directly regulates Sir2-mediated silencing and longevity." Gallo C.M., Smith D.L. Jr., Smith J.S. Mol. Cell. Biol. 24:1301-1312(2004) [PubMed: 14729974] [Abstract] Cited for: FUNCTION.
[10]	"A multidimensional chromatography technology for in-depth phosphoproteome analysis." Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H. Mol. Cell. Proteomics 7:1389-1396(2008) [PubMed: 18407956] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-174, MASS SPECTROMETRY.
[11]	"Crystal structure of the yeast nicotinamidase Pnc1p." Hu G., Taylor A.B., McAlister-Henn L., Hart P.J. Arch. Biochem. Biophys. 461:66-75(2007) [PubMed: 17382284] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS), BIOPHYSICOCHEMICAL PROPERTIES.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

Z72559 Genomic DNA. Translation: CAA96739.1.
AY558481 Genomic DNA. Translation: AAS56807.1.

PIR

S64039.

RefSeq

NP_011478.1.

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2H0R	X-ray	2.90	A/B/C/D/E/F/G	1-216	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:2070N.

IntAct

P53184. 10 interactions.

Proteomic databases

PeptideAtlas

P53184.

PRIDE

P53184.

Genome annotation databases

Ensembl

YGL037C. Saccharomyces cerevisiae. [Contig view]

GeneID

852846.

GenomeReviews

Gene locus YGL037C in contig Y13135_GR.

KEGG

sce:YGL037C.

NMPDR

fig|4932.3.peg.2585.

Organism-specific databases

CYGD

YGL037c.

SGD

S000003005. PNC1.

Yeast-GFP

Search...

Phylogenomic databases

HOGENOM

P53184.

OMA

P53184. LHSIGAR.

Enzyme and pathway databases

BRENDA

3.5.1.19. 250.

Gene expression databases

ArrayExpress

P53184.

GermOnline

YGL037C. Saccharomyces cerevisiae.

Family and domain databases

InterPro

IPR000868. Isochorismatase-like.
[Graphical view]

Gene3D

G3DSA:3.40.50.850. Isochorismatase_hydro. 1 hit.

Pfam

PF00857. Isochorismatase. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

972431.

Entry information

Entry name

PNC1_YEAST

Accession

Primary (citable) accession number: P53184

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	June 16, 2009
This is version 74 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

FPAP (Fungal Proteome Annotation Project)