NAD-dependent protein deacylase sirtuin-5, mitochondrial precursor

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Q8K2C6 (SIR5_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 84. History...

Clusters with 100%, 90%, 50% identity |

Documents (2) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
NAD-dependent protein deacylase sirtuin-5, mitochondrial
EC=3.5.1.-

Alternative name(s):
Regulatory protein SIR2 homolog 5
SIR2-like protein 5

Gene names

Name:	Sirt5
Synonyms:	Sir2l5

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	310 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	NAD-dependent lysine demalonylase and desuccinylase that specifically removes malonyl and succinyl groups on target proteins. Activates CPS1 and contributes to the regulation of blood ammonia levels during prolonged fasting: acts by mediating desuccinylation of CPS1, thereby increasing CPS1 activity in response to elevated NAD levels during fasting. Has weak NAD-dependent protein deacetylase activity; however this activity may not be physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) and a number of other proteins in vitro. Ref.2 Ref.3 Ref.4
Catalytic activity	NAD⁺ + a malonylprotein = nicotinamide + O-malonyl-ADP-ribose + a protein. HAMAP-Rule MF_03160 NAD⁺ + a succinylprotein = nicotinamide + O-succinyl-ADP-ribose + a protein. HAMAP-Rule MF_03160
Cofactor	Binds 1 zinc ion per subunit By similarity.
Subunit structure	Monomer. Homodimer. Interacts with CPS1. Ref.2
Subcellular location	Mitochondrion Ref.2.
Tissue specificity	Detected in brain, liver, heart, kidney, lung, thymus, spleen, skeletal muscle, intestine, pancreas and testis (at protein level). Ref.2
Domain	In contrast to class I sirtuins, class III sirtuins have only weak deacetylase activity. Difference in substrate specificity is probably due to a larger hydrophobic pocket with 2 residues (Tyr-102 and Arg-105) that bind to malonylated and succinylated substrates and define the specificity By similarity. HAMAP-Rule MF_03160
Disruption phenotype	No visible phenotype. After 48 hours of fasting, the absence of Cps1 activation leads to elevated blood ammonia levels, possibly due to the presence of succinylation at 'Lys-1291' in Cps1. Ref.2 Ref.3 Ref.4
Sequence similarities	Belongs to the sirtuin family. Class III subfamily. Contains 1 deacetylase sirtuin-type domain.

Ontologies

Keywords
Cellular component	Mitochondrion
Domain	Transit peptide
Ligand	Metal-binding NAD Zinc
Molecular function	Hydrolase
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	protein deacetylation Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	mitochondrial intermembrane space Inferred from sequence or structural similarity. Source: UniProtKB mitochondrial matrix Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	NAD+ binding Inferred from electronic annotation. Source: Compara protein-malonyllysine demalonylase activity Inferred from mutant phenotype Ref.3. Source: UniProtKB protein-succinyllysine desuccinylase activity Inferred from mutant phenotype Ref.3 Ref.4. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Cps1	Q8C196	2	EBI-2348809,EBI-2348828

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 36

Mitochondrion Ref.2

Chain

37 – 310

274

NAD-dependent protein deacylase sirtuin-5, mitochondrial HAMAP-Rule MF_03160

PRO_0000110267

Regions

Domain

41 – 309

269

Deacetylase sirtuin-type

Nucleotide binding

58 – 77

NAD By similarity

Nucleotide binding

140 – 143

NAD By similarity

Nucleotide binding

249 – 251

NAD By similarity

Nucleotide binding

275 – 277

NAD By similarity

Sites

Active site

158

Proton acceptor

Metal binding

166

Zinc By similarity

Metal binding

169

Zinc By similarity

Metal binding

207

Zinc By similarity

Metal binding

212

Zinc By similarity

Binding site

102

Substrate By similarity

Binding site

105

Substrate By similarity

Binding site

293

NAD; via amide nitrogen By similarity

Experimental info

Mutagenesis

158

H → Y: Loss of enzyme activity. Ref.2

Sequences

Sequence

Length

Mass (Da)

Tools

Q8K2C6 [UniParc].

Last modified October 1, 2002. Version 1.
Checksum: A0C4962D5E6F8729
Show »

FASTA

310

34,134

        10         20         30         40         50         60 
MRPLLIAPGR FISQLCCRRK PPASPQSKIC LTMARPSSNM ADFRKCFANA KHIAIISGAG 

        70         80         90        100        110        120 
VSAESGVPTF RGAGGYWRKW QAQDLATPQA FARNPSQVWE FYHYRREVMR SKEPNPGHLA 

       130        140        150        160        170        180 
IAQCEARLRD QGRRVVVITQ NIDELHRKAG TKNLLEIHGT LFKTRCTSCG TVAENYRSPI 

       190        200        210        220        230        240 
CPALAGKGAP EPETQDARIP VDKLPRCEEA GCGGLLRPHV VWFGENLDPA ILEEVDRELA 

       250        260        270        280        290        300 
LCDLCLVVGT SSVVYPAAMF APQVASRGVP VAEFNMETTP ATDRFRFHFP GPCGKTLPEA 

       310 
LAPHETERTS

« Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Mammary tumor.
[2]	"SIRT5 Deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle." Nakagawa T., Lomb D.J., Haigis M.C., Guarente L. Cell 137:560-570(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF N-TERMINUS, FUNCTION, MUTAGENESIS OF HIS-158, SUBCELLULAR LOCATION, INTERACTION WITH CPS1, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY.
[3]	"The first identification of lysine malonylation substrates and its regulatory enzyme." Peng C., Lu Z., Xie Z., Cheng Z., Chen Y., Tan M., Luo H., Zhang Y., He W., Yang K., Zwaans B.M., Tishkoff D., Ho L., Lombard D., He T.C., Dai J., Verdin E., Ye Y., Zhao Y. Mol. Cell. Proteomics 10:M111.012658.01-M111.012658.12(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[4]	"Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase." Du J., Zhou Y., Su X., Yu J.J., Khan S., Jiang H., Kim J., Woo J., Kim J.H., Choi B.H., He B., Chen W., Zhang S., Cerione R.A., Auwerx J., Hao Q., Lin H. Science 334:806-809(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	BC031770 mRNA. Translation: AAH31770.1.
IPI	IPI00169883.
RefSeq	NP_849179.1. NM_178848.3.
UniGene	Mm.35325.
3D structure databases
ProteinModelPortal	Q8K2C6.
SMR	Q8K2C6. Positions 34-302.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8K2C6. 2 interactions.
PTM databases
PhosphoSite	Q8K2C6.
Proteomic databases
PaxDb	Q8K2C6.
PRIDE	Q8K2C6.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000066804; ENSMUSP00000071048; ENSMUSG00000054021.
GeneID	68346.
KEGG	mmu:68346.
UCSC	uc007qfz.1. mouse.
Organism-specific databases
CTD	23408.
MGI	MGI:1915596. Sirt5.
Phylogenomic databases
eggNOG	COG0846.
GeneTree	ENSGT00680000099776.
HOGENOM	HOG000085950.
HOVERGEN	HBG056009.
InParanoid	Q8K2C6.
KO	K11415.
OMA	VLHMHGE.
OrthoDB	EOG41VK3H.
Gene expression databases
ArrayExpress	Q8K2C6.
Bgee	Q8K2C6.
Genevestigator	Q8K2C6.
GermOnline	ENSMUSG00000054021. Mus musculus.
Family and domain databases
Gene3D	3.30.1600.10. 2 hits.
HAMAP	MF_01121. Sirtuin_ClassIII.
InterPro	IPR003000. Sirtuin. IPR026591. Sirtuin_cat_small_dom. IPR026590. Ssirtuin_cat_dom. [Graphical view]
PANTHER	PTHR11085. PTHR11085. 1 hit.
Pfam	PF02146. SIR2. 1 hit. [Graphical view]
PROSITE	PS50305. SIRTUIN. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	327033.
SOURCE	Search...

Entry information

Entry name

SIR5_MOUSE

Accession

Primary (citable) accession number: Q8K2C6

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 31, 2003
Last sequence update:	October 1, 2002
Last modified:	April 3, 2013
This is version 84 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Sites

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents