SIRT5

Protein identityUniProt · HPA

UniProt accession

Q9NXA8

Gene

SIRT5

Ensembl

ENSG00000124523

Chromosome

6

Canonical length

310 aa

Protein class

Metabolic proteins, Predicted intracellular proteins

Subcellular location

Mitochondria

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene encodes a member of the sirtuin family of proteins, homologs to the yeast Sir2 protein. Members of the sirtuin family are characterized by a sirtuin core domain and grouped into four classes. The functions of human sirtuins have not yet been determined; however, yeast sirtuin proteins are known to regulate epigenetic gene silencing and suppress recombination of rDNA. Studies suggest that the human sirtuins may function as intracellular regulatory proteins with mono-ADP-ribosyltransferase activity. The protein encoded by this gene is included in class III of the sirtuin family. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2010]

Canonical amino-acid sequenceUniProt

310 residues, UniProt reviewed canonical sequence.

>Q9NXA8|SIRT5
     1  MRPLQIVPSR LISQLYCGLK PPASTRNQIC LKMARPSSSM ADFRKFFAKA KHIVIISGAG
    61  VSAESGVPTF RGAGGYWRKW QAQDLATPLA FAHNPSRVWE FYHYRREVMG SKEPNAGHRA
   121  IAECETRLGK QGRRVVVITQ NIDELHRKAG TKNLLEIHGS LFKTRCTSCG VVAENYKSPI
   181  CPALSGKGAP EPGTQDASIP VEKLPRCEEA GCGGLLRPHV VWFGENLDPA ILEEVDRELA
   241  HCDLCLVVGT SSVVYPAAMF APQVAARGVP VAEFNTETTP ATNRFRFHFQ GPCGTTLPEA
   301  LACHENETVS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SIRT5 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Other membrane

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.31

Highest tissue expression

36 nTPM

Expression across tissuesHPA

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.24

gnomAD pLI

0

gnomAD missense Z

0.14

DepMap mean gene effect

0.07

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 8% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• mitochondrion organization
• negative regulation of cardiac muscle cell apoptotic process
• negative regulation of reactive oxygen species metabolic process
• protein deacetylation
• protein deglutarylation
• response to ischemia
• response to nutrient levels
• peptidyl-lysine demalonylation
• peptidyl-lysine desuccinylation
• protein demalonylation
• protein desuccinylation
• regulation of ketone biosynthetic process

Molecular functions

• histone deacetylase activity, NAD-dependent
• NAD+ binding
• NAD-dependent protein lysine deacetylase activity
• protein-glutaryllysine deglutarylase activity
• protein-succinyllysine desuccinylase activity
• zinc ion binding
• protein-malonyllysine demalonylase activity

Cellular components

• cytosol
• mitochondrial inner membrane
• mitochondrial intermembrane space
• mitochondrial matrix
• mitochondrion
• nucleus

Protein domainsUniProt · Pfam · InterPro

• Sirtuin family
• Sirtuin family, catalytic core domain
• Sirtuin, catalytic core small domain superfamily
• DHS-like NAD/FAD-binding domain superfamily
• NAD-dependent sirtuin protein deacylases
• Sir2 family
• Sirtuin, class III

KeywordsUniProt

• Cytoplasm
• Metal-binding
• Mitochondrion
• NAD
• Nucleus
• Transferase
• Transit peptide
• Zinc

InteractionsUniProt · HPA

Protein binding partners of SIRT5 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CPS1
• PCCA
• GLS