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Literature summary for 2.3.1.B43 extracted from

  • Greene, K.S.; Lukey, M.J.; Wang, X.; Blank, B.; Druso, J.E.; Lin, M.J.; Stalnecker, C.A.; Zhang, C.; Negron Abril, Y.; Erickson, J.W.; Wilson, K.F.; Lin, H.; Weiss, R.S.; Cerione, R.A.
    SIRT5 stabilizes mitochondrial glutaminase and supports breast cancer tumorigenesis (2019), Proc. Natl. Acad. Sci. USA, 116, 26625-26632 .
    View publication on PubMedView publication on EuropePMC

Application

Application Comment Organism
diagnostics elevated SIRT5 expression in human breast tumors correlates with poor patient prognosis Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
gene SIRT5 Homo sapiens

Protein Variants

Protein Variants Comment Organism
additional information knockdown of SIRT5 in induced onco-Dbl MEFs inhibits cell proliferation. Knockdown of SIRT5 also decreased the volume and number of colonies formed by the induced onco-Dbl MEFs in anchorage-independent growth assays. In breast cancer and lung cancer cell lines, SIRT5 knockdowns again inhibits proliferation and anchorage-independent growth. Expression of RNAi-resistant SIRT5 constructs rescue the proliferative defect caused by the SIRT5-targeted shRNAs Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
mitochondrion
-
Homo sapiens 5739
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
NAD+ + [glutaminase]-N6-succinyl-L-lysine Homo sapiens SIRT5 desuccinylates glutaminase residue K164 to block ubiquitination of K158 nicotinamide + [glutaminase]-L-lysine + 2'-O-succinyl-ADP-ribose
-
?
NAD+ + [protein]-N6-succinyl-L-lysine Homo sapiens
-
nicotinamide + [protein]-L-lysine + 2'-O-succinyl-ADP-ribose
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens Q9NXA8
-
-

Source Tissue

Source Tissue Comment Organism Textmining
breast cancer cell
-
Homo sapiens
-
MDA-MB-231 cell
-
Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
NAD+ + [glutaminase]-N6-succinyl-L-lysine SIRT5 desuccinylates glutaminase residue K164 to block ubiquitination of K158 Homo sapiens nicotinamide + [glutaminase]-L-lysine + 2'-O-succinyl-ADP-ribose
-
?
NAD+ + [glutaminase]-N6-succinyl-L-lysine succinylation of glutaminase residue K164, no activity with K164R-GLS variant Homo sapiens nicotinamide + [glutaminase]-L-lysine + 2'-O-succinyl-ADP-ribose
-
?
NAD+ + [protein]-N6-succinyl-L-lysine
-
Homo sapiens nicotinamide + [protein]-L-lysine + 2'-O-succinyl-ADP-ribose
-
?

Synonyms

Synonyms Comment Organism
mitochondrial NAD+-dependent lysine deacylase
-
Homo sapiens
SIRT5
-
Homo sapiens

Cofactor

Cofactor Comment Organism Structure
NAD+
-
Homo sapiens

Expression

Organism Comment Expression
Homo sapiens SIRT5 is upregulated during cellular transformation and supports proliferation and tumorigenesis up

General Information

General Information Comment Organism
malfunction depletion of SIRT5, a lysine desuccinylase, leads to increased ubiquitination of glutaminase. SIRT5 knockdown acts as a marker for subsequent ubiquitination at residue K158 Homo sapiens
physiological function SIRT5, a mitochondrial NAD+-dependent lysine deacylase, plays a key role in stabilizing glutaminase. In transformed cells, SIRT5 regulates glutamine metabolism by desuccinylating glutaminase and thereby protecting it from ubiquitin-mediated degradation. SIRT5 is upregulated during cellular transformation and supports proliferation and tumorigenesis. SIRT5 is upregulated during oncogenic transformation and stabilizes glutaminase, an enzyme with important functions in cancer-cell metabolic reprogramming. Elevated SIRT5 expression in human breast tumors correlates with poor patient prognosis. Role for SIRT5 in metabolic reprogramming and mammary tumorigenesis. SIRT5 supports proliferation and anchorage-independent growth Homo sapiens