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FLASH GENE
Symbol SIRT5 contributors: mct/npt - updated : 29-04-2020
HGNC name sirtuin (silent mating type information regulation 2 homolog) 5 (S. cerevisiae)
HGNC id 14933
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a deacetylase sirtuin-type core domain
  • HOMOLOGY
    interspecies homolog to yeast Sir2
    homolog to E.coli CobB
    ortholog to rattus Sirt5
    ortholog to murine Sirt5
    Homologene
    FAMILY
  • NAD+-dependent sirtuin family of protein deacylase
  • CATEGORY enzyme , regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria,inner
    intracellular,cytoplasm,organelle,mitochondria,interspace
    intracellular,cytoplasm,organelle,mitochondria,matrix
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    text can indeed be translocated into the mitochondrial intermembrane space, but also into the matrix (localization might contribute to SIRT5 regulation and substrate selection) (Schlicker 2008)
    basic FUNCTION
  • NAD(+) ADP ribosyltransferase with a protein deacetylase activity
  • can deacetylate and thereby activate a central metabolic regulator in the mitochondrial matrix, glutamate dehydrogenase (Schlicker 2008)
  • can deacetylate cytochrome c, a protein of the mitochondrial intermembrane space with a central function in oxidative metabolism, as well as apoptosis initiation (Schlicker 2008)
  • by participating in the stress response to genomic insults, sirtuins are thought to protect against cancer, but they are also emerging as direct participants in the growth of some cancers (Saunders 2007)
  • plays a pivotal role in ammonia detoxification and disposal by activating CPS1 (Nakagawa 2009)
  • protein lysine succinylation may represent a posttranslational modification that can be reversed by SIRT5
  • is a global regulator of lysine malonylation
  • SIRT5-dependent mechanism that regulates cellular NADPH homeostasis and redox potential by promoting IDH2 desuccinylation and G6PD deglutarylation
  • mitochondrial SIRT5 is essential for starvation induced mitochondrial elongation
  • lysine desuccinylase known to regulate mitochondrial fatty acid oxidation and the urea cycle
  • is likely targeted to protein complexes on the inner mitochondrial membrane via affinity for cardiolipin to promote respiratory chain function
  • has an important regulatory role in liver carcinogenesis
  • roles of SIRT5 as a significant regulator of cellular homeostasis, in a context- and cell-type specific manner, and regulates protein substrates involved in glycolysis, the TCA cycle, fatty acid oxidation, electron transport chain, ketone body formation
  • predominant desuccinylase and demalonylase in mitochondria
  • is a potentially protective factor for pancreatic beta cells against glucolipotoxicity-induced apoptosis and cell dysfunction
  • in the mitochondria, catalyzes deacetylation, demalonylation, desuccinylation, and deglutarylation of lysine to regulate metabolic and oxidative stress response pathways
  • important role of SIRT5 in regulating cellular energy metabolism and AMPK activation in response to energy stress
  • new biological function of SIRT5 in brown adipocyte differentiation
  • SIRT5-mediated protein desuccinylation played an important role in promoting the migration of hypoxic gastric cancer cells
  • associated with keratinocyte differentiation, melanoma, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)
  • CELLULAR PROCESS nucleotide, transcription, regulation
    protein, post translation
    PHYSIOLOGICAL PROCESS
    text chromatin silencing, protein ADP ribosylation
    PATHWAY
    metabolism
    signaling
    a component
  • chromatin silencing complex
  • INTERACTION
    DNA binding
    RNA
    small molecule metal binding, cofactor, nucleotide,
  • Zn2+
  • NAD
  • protein
  • interacts with carbamoyl phosphate synthetase 1 (CPS1), an enzyme, catalyzing the initial step of the urea cycle for ammonia detoxification and disposal (Nakagawa 2009)
  • SIRT5 acts, at least partly, as a negative regulator of SUN2
  • SIRT5 desuccinylates and deglutarylates isocitrate dehydrogenase 2 (IDH2) and glucose-6-phosphate dehydrogenase (G6PD), respectively, and thus activates both NADPH-producing enzymes
  • MAVS is a physiological substrate of SIRT5
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in human breast tumors correlates with poor patient prognosis
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • may serve as a potential prognostic factor for intervention in non-small cell lung cancer
  • Therapy target
    SystemTypeDisorderPubmed
    cancerlung 
    SIRT5/SUN2 axis may prove to be useful for the development of new strategies for treating the patients with lung cancer
    cancerdigestiveliver
    may function as a novel potential therapeutic target for HCC
    cancerlung 
    drug target for intervention in non-small cell lung cancer
    ANIMAL & CELL MODELS
  • Sirt5-deficient mice are resistant to viral infection (