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Protein

NAD-dependent protein deacylase sirtuin-5, mitochondrial

Gene

Sirt5

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at transcript leveli

Functioni

NAD-dependent lysine demalonylase, desuccinylase and deglutarylase that specifically removes malonyl, succinyl and glutaryl groups on target proteins. Activates CPS1 and contributes to the regulation of blood ammonia levels during prolonged fasting: acts by mediating desuccinylation and deglutarylation of CPS1, thereby increasing CPS1 activity in response to elevated NAD levels during fasting. Activates SOD1 by mediating its desuccinylation, leading to reduced reactive oxygen species. Activates SHMT2 by mediating its desuccinylation. Modulates ketogenesis through the desuccinylation and activation of HMGCS2. 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 such as UOX.UniRule annotation

Catalytic activityi

NAD+ + a malonylprotein = nicotinamide + O-malonyl-ADP-ribose + a protein.UniRule annotation
NAD+ + a succinylprotein = nicotinamide + O-succinyl-ADP-ribose + a protein.UniRule annotation
NAD+ + a glutarylprotein = nicotinamide + O-glutaryl-ADP-ribose + a protein.UniRule annotation

Cofactori

Zn2+UniRule annotationNote: Binds 1 zinc ion per subunit.UniRule annotation

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei102SubstrateUniRule annotation1
Binding sitei105SubstrateUniRule annotation1
Active sitei158Proton acceptorUniRule annotation1
Metal bindingi166ZincUniRule annotation1
Metal bindingi169ZincUniRule annotation1
Metal bindingi207ZincUniRule annotation1
Metal bindingi212ZincUniRule annotation1
Binding sitei293NAD; via amide nitrogenUniRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi58 – 77NADUniRule annotationAdd BLAST20
Nucleotide bindingi140 – 143NADUniRule annotation4
Nucleotide bindingi249 – 251NADUniRule annotation3
Nucleotide bindingi275 – 277NADUniRule annotation3

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase
LigandMetal-binding, NAD, Zinc

Enzyme and pathway databases

ReactomeiR-RNO-2151201 Transcriptional activation of mitochondrial biogenesis

Names & Taxonomyi

Protein namesi
Recommended name:
NAD-dependent protein deacylase sirtuin-5, mitochondrialUniRule annotation (EC:3.5.1.-UniRule annotation)
Alternative name(s):
Regulatory protein SIR2 homolog 5UniRule annotation
SIR2-like protein 5UniRule annotation
Gene namesi
Name:Sirt5
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 17

Organism-specific databases

RGDi1303285 Sirt5

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Mitochondrion, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 36MitochondrionUniRule annotationAdd BLAST36
ChainiPRO_000026044537 – 310NAD-dependent protein deacylase sirtuin-5, mitochondrialAdd BLAST274

Proteomic databases

PaxDbiQ68FX9
PRIDEiQ68FX9

PTM databases

iPTMnetiQ68FX9
PhosphoSitePlusiQ68FX9

Expressioni

Gene expression databases

BgeeiENSRNOG00000017866
GenevisibleiQ68FX9 RN

Interactioni

Subunit structurei

Monomer. Homodimer. Interacts with CPS1. Interacts with PCCA (By similarity).UniRule annotationBy similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000024067

Structurei

3D structure databases

ProteinModelPortaliQ68FX9
SMRiQ68FX9
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini41 – 310Deacetylase sirtuin-typeUniRule annotationAdd BLAST270

Domaini

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.UniRule annotation

Sequence similaritiesi

Belongs to the sirtuin family. Class III subfamily.UniRule annotation

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG2684 Eukaryota
COG0846 LUCA
GeneTreeiENSGT00870000136443
HOGENOMiHOG000085950
HOVERGENiHBG056009
InParanoidiQ68FX9
KOiK11415
OMAiSMQVYPA
OrthoDBiEOG091G0KF2
PhylomeDBiQ68FX9
TreeFamiTF106183

Family and domain databases

CDDicd01412 SIRT5_Af1_CobB, 1 hit
Gene3Di3.30.1600.10, 2 hits
HAMAPiMF_01121 Sirtuin_ClassIII, 1 hit
InterProiView protein in InterPro
IPR029035 DHS-like_NAD/FAD-binding_dom
IPR003000 Sirtuin
IPR026591 Sirtuin_cat_small_dom_sf
IPR027546 Sirtuin_class_III
IPR026590 Ssirtuin_cat_dom
PfamiView protein in Pfam
PF02146 SIR2, 1 hit
SUPFAMiSSF52467 SSF52467, 1 hit
PROSITEiView protein in PROSITE
PS50305 SIRTUIN, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q68FX9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRPLPVAPGR LFSQLCCGPK PSASPQSKIC LTMARPSSNM ADFRKCFANA
60 70 80 90 100
KHIVIISGAG VSAESGVPTF RGTGGYWRKW QAQHLATPLA FAHNPSQVWE
110 120 130 140 150
FYHYRREVMR NKEPNPGHLA IAQCEARLRD QGRRVVVITQ NIDELHRKAG
160 170 180 190 200
TKNLLEIHGT LFKTRCTSCG NVAENYKSPI CPALLGKGAP EPDTQESRIP
210 220 230 240 250
VHKLPRCEEA GCGGLLRPHV VWFGENLDPA ILKEVDRELA RCDLCLVVGT
260 270 280 290 300
SSVVYPAAMF APQVASRGVP VAEFNMETTP ATNRFRFHFP GPCGVTLPEA
310
LAPHETERIS
Length:310
Mass (Da):34,098
Last modified:October 11, 2004 - v1
Checksum:i3AF68B4A66441D4D
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC078958 mRNA Translation: AAH78958.1
RefSeqiNP_001004256.1, NM_001004256.1
XP_006253863.1, XM_006253801.1
XP_006253864.1, XM_006253802.2
XP_006253865.1, XM_006253803.3
XP_006253866.1, XM_006253804.3
XP_017456010.1, XM_017600521.1
UniGeneiRn.137920

Genome annotation databases

EnsembliENSRNOT00000024066; ENSRNOP00000024067; ENSRNOG00000017866
GeneIDi306840
KEGGirno:306840

Similar proteinsi

Entry informationi

Entry nameiSIR5_RAT
AccessioniPrimary (citable) accession number: Q68FX9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 28, 2006
Last sequence update: October 11, 2004
Last modified: March 28, 2018
This is version 106 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
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Main funding by: National Institutes of Health