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Protein

NAD-dependent protein deacylase sirtuin-5, mitochondrial

Gene

Sirt5

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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 (By similarity). Modulates ketogenesis through the desuccinylation and activation of HMGCS2 (By similarity). 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 (By similarity).By similarity

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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei102 – 1021SubstrateUniRule annotation
Binding sitei105 – 1051SubstrateUniRule annotation
Active sitei158 – 1581Proton acceptorUniRule annotation
Metal bindingi166 – 1661ZincUniRule annotation
Metal bindingi169 – 1691ZincUniRule annotation
Metal bindingi207 – 2071ZincUniRule annotation
Metal bindingi212 – 2121ZincUniRule annotation
Binding sitei293 – 2931NAD; via amide nitrogenUniRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi58 – 7720NADUniRule annotationAdd
BLAST
Nucleotide bindingi140 – 1434NADUniRule annotation
Nucleotide bindingi249 – 2513NADUniRule annotation
Nucleotide bindingi275 – 2773NADUniRule annotation

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Ligandi

Metal-binding, NAD, Zinc

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 17

Organism-specific databases

RGDi1303285. Sirt5.

Subcellular locationi

  • Mitochondrion UniRule annotation
  • Cytoplasmcytosol UniRule annotation
  • Nucleus UniRule annotation

  • Note: Mainly mitochondrial. Also present extramitochondrially: a fraction is present in the cytosol and very small amounts are also detected in the nucleus.UniRule annotation

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Mitochondrion, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transit peptidei1 – 3636MitochondrionUniRule annotationAdd
BLAST
Chaini37 – 310274NAD-dependent protein deacylase sirtuin-5, mitochondrialPRO_0000260445Add
BLAST

Proteomic databases

PaxDbiQ68FX9.
PRIDEiQ68FX9.

PTM databases

iPTMnetiQ68FX9.
PhosphoSiteiQ68FX9.

Expressioni

Gene expression databases

GenevisibleiQ68FX9. RN.

Interactioni

Subunit structurei

Monomer. Homodimer. Interacts with CPS1.UniRule annotation

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000024067.

Structurei

3D structure databases

ProteinModelPortaliQ68FX9.
SMRiQ68FX9. Positions 36-302.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini41 – 310270Deacetylase sirtuin-typeUniRule annotationAdd
BLAST

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
Contains 1 deacetylase sirtuin-type domain.UniRule annotation

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG2684. Eukaryota.
COG0846. LUCA.
GeneTreeiENSGT00740000115330.
HOGENOMiHOG000085950.
HOVERGENiHBG056009.
InParanoidiQ68FX9.
KOiK11415.
OMAiLIHMHGE.
OrthoDBiEOG77Q4XG.
PhylomeDBiQ68FX9.
TreeFamiTF106183.

Family and domain databases

Gene3Di3.30.1600.10. 2 hits.
3.40.50.1220. 3 hits.
HAMAPiMF_01121. Sirtuin_ClassIII.
InterProiIPR029035. DHS-like_NAD/FAD-binding_dom.
IPR003000. Sirtuin.
IPR026591. Sirtuin_cat_small_dom.
IPR027546. Sirtuin_class_III.
IPR026590. Ssirtuin_cat_dom.
[Graphical view]
PANTHERiPTHR11085. PTHR11085. 1 hit.
PfamiPF02146. SIR2. 1 hit.
[Graphical view]
SUPFAMiSSF52467. SSF52467. 1 hit.
PROSITEiPS50305. SIRTUIN. 1 hit.
[Graphical view]

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_006253802.1.
XP_006253865.1. XM_006253803.2.
XP_006253866.1. XM_006253804.2.
UniGeneiRn.137920.

Genome annotation databases

EnsembliENSRNOT00000024066; ENSRNOP00000024067; ENSRNOG00000017866.
GeneIDi306840.
KEGGirno:306840.

Cross-referencesi

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_006253802.1.
XP_006253865.1. XM_006253803.2.
XP_006253866.1. XM_006253804.2.
UniGeneiRn.137920.

3D structure databases

ProteinModelPortaliQ68FX9.
SMRiQ68FX9. Positions 36-302.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000024067.

PTM databases

iPTMnetiQ68FX9.
PhosphoSiteiQ68FX9.

Proteomic databases

PaxDbiQ68FX9.
PRIDEiQ68FX9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000024066; ENSRNOP00000024067; ENSRNOG00000017866.
GeneIDi306840.
KEGGirno:306840.

Organism-specific databases

CTDi23408.
RGDi1303285. Sirt5.

Phylogenomic databases

eggNOGiKOG2684. Eukaryota.
COG0846. LUCA.
GeneTreeiENSGT00740000115330.
HOGENOMiHOG000085950.
HOVERGENiHBG056009.
InParanoidiQ68FX9.
KOiK11415.
OMAiLIHMHGE.
OrthoDBiEOG77Q4XG.
PhylomeDBiQ68FX9.
TreeFamiTF106183.

Miscellaneous databases

NextBioi656583.
PROiQ68FX9.

Gene expression databases

GenevisibleiQ68FX9. RN.

Family and domain databases

Gene3Di3.30.1600.10. 2 hits.
3.40.50.1220. 3 hits.
HAMAPiMF_01121. Sirtuin_ClassIII.
InterProiIPR029035. DHS-like_NAD/FAD-binding_dom.
IPR003000. Sirtuin.
IPR026591. Sirtuin_cat_small_dom.
IPR027546. Sirtuin_class_III.
IPR026590. Ssirtuin_cat_dom.
[Graphical view]
PANTHERiPTHR11085. PTHR11085. 1 hit.
PfamiPF02146. SIR2. 1 hit.
[Graphical view]
SUPFAMiSSF52467. SSF52467. 1 hit.
PROSITEiPS50305. SIRTUIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  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: Kidney.

Entry informationi

Entry nameiSIR5_RAT
AccessioniPrimary (citable) accession number: Q68FX9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 28, 2006
Last sequence update: October 11, 2004
Last modified: January 20, 2016
This is version 92 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.