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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

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	6p23      Physical location : 13.574.791 - 13.614.783
Synonym name	SIR2-like protein 5
	sirtuin 5
Synonym symbol(s)	SIR2L5, FLJ36950
EC.number	3.5.1.-

DNA

TYPE	functioning gene
STRUCTURE	40.94 kb     10 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_012241 10 splicing 4564 NP_036373 33.9 310 - 2005 16079181 containing a distinct 5' UTR, C-terminal coding region, and 3' UTR as compared to transcript variant 2 NM_031244 10 splicing 2426 NP_112534 32.7 299 - 2005 16079181 containing a distinct 5' UTR, C-terminal coding region, and 3' UTR as compared to transcript variant 1 NM_001376799 10 - 3402 NP_001363728 - 310 - 2005 16079181 NM_001376801 11 - 3585 NP_001363730 - 310 - 2005 16079181 NM_001376798 11 - 3464 NP_001363727 - 310 mitochondria-localized 2018 29932920 iso 1 having high deacetylase activity NM_001376809 9 - 3278 NP_001363738 - 283 - 2005 16079181 NM_001376800 10 - 3523 NP_001363729 - 310 - 2005 16079181 NM_001193267 9 - 4462 NP_001180196 - 292 mitochondria-localized 2018 29932920 Iso 3 NM_001242827 9 - 4382 NP_001229756 - 202 localized mainly in cytoplasm 2018 29932920 iso 4 had little deacylase activity NM_001376811 11 - 3742 NP_001363740 - 271 - 2005 16079181 NM_001376807 10 - 3601 NP_001363736 - 310 - 2005 16079181 NM_001376814 8 - 3389 NP_001363743 - 201 - 2005 16079181 NM_001376806 11 - 3435 NP_001363735 - 310 - 2005 16079181 NM_001376805 10 - 3468 NP_001363734 - 310 - 2005 16079181 NM_001376804 10 - 3409 NP_001363733 - 310 - 2005 16079181 NM_001376812 10 - 3400 NP_001363741 - 202 - 2005 16079181 NM_001376803 10 - 3393 NP_001363732 - 310 - 2005 16079181 NM_001376810 9 - 3269 NP_001363739 - 283 - 2005 16079181 NM_001376815 6 - 2821 NP_001363744 - 81 - 2005 16079181 NM_001376813 8 - 3181 NP_001363742 - 201 - 2005 16079181 NM_001376802 9 - 3234 NP_001363731 - 310 - 2005 16079181 NM_001376808 11 - 2609 NP_001363737 - 299 mitochondria-localized 2018 29932920 iso 2 little deacylase activity

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart       moderately Lymphoid/Immune lymph node       moderately   thymus       predominantly Reproductive female system uterus     highly   male system testis         male system prostate     highly Urinary bladder       highly   kidney       moderately

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective bone

cell lineage
cell lines	retinoblastoma
fluid/secretion

at STAGE

physiological period

fetal

Text

tissues

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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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
	System Type Disorder Pubmed cancer lung   SIRT5/SUN2 axis may prove to be useful for the development of new strategies for treating the patients with lung cancer cancer digestive liver may function as a novel potential therapeutic target for HCC cancer lung   drug target for intervention in non-small cell lung cancer

ANIMAL & CELL MODELS

Sirt5-deficient mice are resistant to viral infection (