Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary for 2.3.1.B43 extracted from

  • Wang, F.; Wang, K.; Xu, W.; Zhao, S.; Ye, D.; Wang, Y.; Xu, Y.; Zhou, L.; Chu, Y.; Zhang, C.; Qin, X.; Yang, P.; Yu, H.
    SIRT5 desuccinylates and activates pyruvate kinase M2 to block macrophage IL-1beta production and to prevent DSS-induced colitis in mice (2017), Cell Rep., 19, 2331-2344 .
    View publication on PubMed
Search for more literature for 2.3.1.B43

Cloned(Commentary)

Cloned (Comment) Organism
gene SIRT5, recombinant expression of tagged SIRT5 in HEK-293T cells, coexpression of wild-type and mutant protein kinase M2s, i.e. wild-type and mutants K62R/E, K135R/E, K311R/E, K498R/E, K311R/K498R, and K311E/K498E. Interactions between endogenous PKM2 and ectopically expressed FLAG-tagged PKM2, including the wild-type PKM2, the K311R mutant, and the succinylation-mimic K311E mutant, overview Mus musculus

Protein Variants

Protein Variants Comment Organism
additional information generation of Sirt5-KO mice Mus musculus

Localization

Localization Comment Organism GeneOntology No. Textmining
mitochondrion
-
 Mus musculus 5739
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
NAD+ + [pyruvate kinase M2]-N6-succinyl-L-lysine311 Mus musculus SIRT5 desuccinylates and activates PKM2 nicotinamide + [pyruvate kinase M2]-L-lysine311 + 2'-O-succinyl-ADP-ribose
-
 ?

Organism

Organism UniProt Comment Textmining
Mus musculus A0A1Y7VM56
-
-

Source Tissue

Source Tissue Comment Organism Textmining

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
NAD+ + [pyruvate kinase M2]-N6-succinyl-L-lysine311 SIRT5 desuccinylates and activates PKM2 Mus musculus nicotinamide + [pyruvate kinase M2]-L-lysine311 + 2'-O-succinyl-ADP-ribose
-
 ?
NAD+ + [pyruvate kinase M2]-N6-succinyl-L-lysine311 SIRT5 also desuccinylates recombinant Flag-tagged PKM2 substrate, but does not but affect its malonylation and glutarylation. The K311E mutation and K311E/K498E double mutation of PKM2 both increase the succinylation level of PKM2 by about 25%, while mutations K62R/E, K135R/E, and K498R/E have no significant effect Mus musculus nicotinamide + [pyruvate kinase M2]-L-lysine311 + 2'-O-succinyl-ADP-ribose
-
 ?

Synonyms

Synonyms Comment Organism
SIRT5
-
 Mus musculus

Cofactor

Cofactor Comment Organism Structure
NAD+
-
 Mus musculus

General Information

General Information Comment Organism
malfunction Sirt5-deficiency-mediated IL-1beta upregulation in LPS-stimulated macrophages, which can be attenuated by activation of PKM2 using TEPP-46. Sirt5-deficient mice are more susceptible to dextran sodium sulfate (DSS)-induced colitis, which is associated with Sirt5 deficiency prompted PKM2 hypersuccinylation and boosted IL-1beta production. Both activation of PKM2 and neutralization of IL-1beta in vivo confer protection against dextran sodium sulfate (DSS)-induced colitis in Sirt5-deficiency mice Mus musculus
physiological function SIRT5 plays an important role in inhibiting inflammation. SIRT5 suppresses the pro-inflammatory response in macrophages at least in part by regulating PKM2 succinylation, activity, and function. SIRT5 desuccinylates and activates pyruvate kinase M2 (PKM2) to block macrophage IL-1beta production and to prevent DSS-induced colitis in mice. Lys311 is a key succinylated site in the regulation of PKM2 activity. SIRT5-regulated hypersuccinylation inhibits the pyruvate kinase activity of PKM2 by promoting its tetramer-to-dimer transition. A succinylation-mimetic PKM2 K311E mutation promotes nuclear accumulation and increases protein kinase activity. SIRT5-dependent succinylation promotes PKM2 entry into nucleus, where a complex of PKM2-HIF1alpha is formed at the promoter of interleukin-1beta gene in LPS-stimulated macrophages. SIRT5-dependent succinylation promotes PKM2 dimerization and increases its protein kinase activity Mus musculus