UniProtKB - Q3ZBQ0 (SIR5_BOVIN)
Protein
NAD-dependent protein deacylase sirtuin-5, mitochondrial
Gene
SIRT5
Organism
Bos taurus (Bovine)
Status
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
- H2O + N6-malonyl-L-lysyl-[protein] + NAD+ = 2''-O-malonyl-ADP-D-ribose + L-lysyl-[protein] + nicotinamideUniRule annotation
- H2O + N6-succinyl-L-lysyl-[protein] + NAD+ = 2''-O-succinyl-ADP-D-ribose + L-lysyl-[protein] + nicotinamideUniRule annotation
- H2O + N6-glutaryl-L-lysyl-[protein] + NAD+ = 2''-O-glutaryl-ADP-D-ribose + L-lysyl-[protein] + nicotinamideUniRule annotation
Cofactori
Zn2+UniRule annotationNote: Binds 1 zinc ion per subunit.UniRule annotation
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 102 | SubstrateUniRule annotation | 1 | |
Binding sitei | 105 | SubstrateUniRule annotation | 1 | |
Active sitei | 158 | Proton acceptorUniRule annotation | 1 | |
Metal bindingi | 166 | ZincUniRule annotation | 1 | |
Metal bindingi | 169 | ZincUniRule annotation | 1 | |
Metal bindingi | 207 | ZincUniRule annotation | 1 | |
Metal bindingi | 212 | ZincUniRule annotation | 1 | |
Binding sitei | 293 | NAD; via amide nitrogenUniRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 58 – 77 | NADUniRule annotationAdd BLAST | 20 | |
Nucleotide bindingi | 140 – 143 | NADUniRule annotation | 4 | |
Nucleotide bindingi | 249 – 251 | NADUniRule annotation | 3 | |
Nucleotide bindingi | 275 – 277 | NADUniRule annotation | 3 |
GO - Molecular functioni
- NAD+ binding Source: UniProtKB
- protein-glutaryllysine deglutarylase activity Source: GO_Central
- protein-malonyllysine demalonylase activity Source: UniProtKB
- protein-succinyllysine desuccinylase activity Source: UniProtKB
- transferase activity Source: UniProtKB-KW
- zinc ion binding Source: UniProtKB
GO - Biological processi
- negative regulation of reactive oxygen species metabolic process Source: Ensembl
- peptidyl-lysine demalonylation Source: UniProtKB
- peptidyl-lysine desuccinylation Source: UniProtKB
- protein deacetylation Source: UniProtKB
- protein deglutarylation Source: GO_Central
- protein demalonylation Source: UniProtKB
- protein desuccinylation Source: UniProtKB
- regulation of ketone biosynthetic process Source: UniProtKB
- regulation of succinate dehydrogenase activity Source: Ensembl
- response to ischemia Source: Ensembl
Keywordsi
Molecular function | Transferase |
Ligand | Metal-binding, NAD, Zinc |
Names & Taxonomyi
Protein namesi | Recommended name: NAD-dependent protein deacylase sirtuin-5, mitochondrialUniRule annotation (EC:2.3.1.-UniRule annotation)Alternative name(s): Regulatory protein SIR2 homolog 5UniRule annotation SIR2-like protein 5UniRule annotation |
Gene namesi | Name:SIRT5UniRule annotation |
Organismi | Bos taurus (Bovine) |
Taxonomic identifieri | 9913 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Artiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos |
Proteomesi |
|
Organism-specific databases
VGNCi | VGNC:34634, SIRT5 |
Subcellular locationi
Mitochondrion
- Mitochondrion UniRule annotation
Cytosol
- cytosol UniRule annotation
Nucleus
- Nucleus UniRule annotation
Note: Mainly mitochondrial. Also present extramitochondrially, with a fraction present in the cytosol and very small amounts also detected in the nucleus.UniRule annotation
Cytosol
- cytosol Source: UniProtKB
Mitochondrion
- mitochondrial inner membrane Source: Ensembl
- mitochondrial intermembrane space Source: UniProtKB
- mitochondrial matrix Source: UniProtKB
- mitochondrion Source: UniProtKB
Nucleus
- nucleus Source: UniProtKB-SubCell
Keywords - Cellular componenti
Cytoplasm, Mitochondrion, NucleusPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transit peptidei | 1 – 36 | MitochondrionUniRule annotationAdd BLAST | 36 | |
ChainiPRO_0000260444 | 37 – 310 | NAD-dependent protein deacylase sirtuin-5, mitochondrialAdd BLAST | 274 |
Proteomic databases
PaxDbi | Q3ZBQ0 |
PeptideAtlasi | Q3ZBQ0 |
PRIDEi | Q3ZBQ0 |
Expressioni
Gene expression databases
Bgeei | ENSBTAG00000014904, Expressed in brain and 19 other tissues |
Interactioni
Subunit structurei
Monomer. Homodimer.
Interacts with CPS1.
Interacts with PCCA (By similarity).
UniRule annotationBy similarityProtein-protein interaction databases
STRINGi | 9913.ENSBTAP00000019842 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 41 – 309 | Deacetylase sirtuin-typeUniRule annotationAdd BLAST | 269 |
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
Keywords - Domaini
Transit peptidePhylogenomic databases
eggNOGi | KOG2684, Eukaryota |
GeneTreei | ENSGT00940000156080 |
HOGENOMi | CLU_023643_3_1_1 |
InParanoidi | Q3ZBQ0 |
OMAi | SMQVYPA |
OrthoDBi | 1459156at2759 |
TreeFami | TF106183 |
Family and domain databases
CDDi | cd01412, SIRT5_Af1_CobB, 1 hit |
Gene3Di | 3.30.1600.10, 1 hit |
HAMAPi | MF_01121, Sirtuin_ClassIII, 1 hit |
InterProi | View 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 |
Pfami | View protein in Pfam PF02146, SIR2, 1 hit |
SUPFAMi | SSF52467, SSF52467, 1 hit |
PROSITEi | View protein in PROSITE PS50305, SIRTUIN, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
Q3ZBQ0-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MPPLWIIRNR LFSQLYCGLK SPVSTQTKIC LTMARPSSNM ADFRKCFAKA
60 70 80 90 100
KHIVVISGAG ISAESGVPTF RGAGGYWRKW KAQDLATPQA FARNPSQVWE
110 120 130 140 150
FYHYRREVVQ STEPNAGHLA IAECQARLHR QGRQVVVITQ NIDELHRKAG
160 170 180 190 200
TKNLLEIHGS LFKTRCTSCG VVAENYKSPI CPALSGKGAP DPQTQDAGIP
210 220 230 240 250
VEKLPRCEEA GCGGLLRPHV VWFGENLDPA ILEEVDKELA LCDLCLVVGT
260 270 280 290 300
SSVVYPAAMF APQVSARGVP VAEFNMETTP ATERFRFHFQ GPCGTTLPEA
310
LAPHETETVS
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 14 | Q → K in ACS66701 (Ref. 1) Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | GQ166651 mRNA Translation: ACS66701.1 BC103176 mRNA Translation: AAI03177.1 |
RefSeqi | NP_001029467.1, NM_001034295.2 XP_005223802.1, XM_005223745.3 XP_015315433.1, XM_015459947.1 XP_015315434.1, XM_015459948.1 XP_015315435.1, XM_015459949.1 |
Genome annotation databases
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | GQ166651 mRNA Translation: ACS66701.1 BC103176 mRNA Translation: AAI03177.1 |
RefSeqi | NP_001029467.1, NM_001034295.2 XP_005223802.1, XM_005223745.3 XP_015315433.1, XM_015459947.1 XP_015315434.1, XM_015459948.1 XP_015315435.1, XM_015459949.1 |
3D structure databases
SMRi | Q3ZBQ0 |
ModBasei | Search... |
Protein-protein interaction databases
STRINGi | 9913.ENSBTAP00000019842 |
Proteomic databases
PaxDbi | Q3ZBQ0 |
PeptideAtlasi | Q3ZBQ0 |
PRIDEi | Q3ZBQ0 |
Genome annotation databases
Organism-specific databases
CTDi | 23408 |
VGNCi | VGNC:34634, SIRT5 |
Phylogenomic databases
eggNOGi | KOG2684, Eukaryota |
GeneTreei | ENSGT00940000156080 |
HOGENOMi | CLU_023643_3_1_1 |
InParanoidi | Q3ZBQ0 |
OMAi | SMQVYPA |
OrthoDBi | 1459156at2759 |
TreeFami | TF106183 |
Gene expression databases
Bgeei | ENSBTAG00000014904, Expressed in brain and 19 other tissues |
Family and domain databases
CDDi | cd01412, SIRT5_Af1_CobB, 1 hit |
Gene3Di | 3.30.1600.10, 1 hit |
HAMAPi | MF_01121, Sirtuin_ClassIII, 1 hit |
InterProi | View 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 |
Pfami | View protein in Pfam PF02146, SIR2, 1 hit |
SUPFAMi | SSF52467, SSF52467, 1 hit |
PROSITEi | View protein in PROSITE PS50305, SIRTUIN, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | SIR5_BOVIN | |
Accessioni | Q3ZBQ0Primary (citable) accession number: Q3ZBQ0 Secondary accession number(s): C6K7D6 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 28, 2006 |
Last sequence update: | September 27, 2005 | |
Last modified: | December 2, 2020 | |
This is version 108 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families