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Information on EC 2.7.11.31 - [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase

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EC Tree
IUBMB Comments
The enzyme is activated by AMP. EC 1.1.1.34, hydroxymethylglutaryl-CoA reductase (NADPH) is inactivated by the phosphorylation of the enzyme protein. Histones can also act as acceptors. The enzyme can also phosphorylate hepatic acetyl-CoA carboxylase (EC 6.4.1.2) and adipose hormone-sensitive lipase (EC 3.1.1.79) . Thr-172 within the catalytic subunit (alpha-subunit) is the major site phosphorylated by the AMP-activated protein kinase kinase . GTP can act instead of ATP
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This record set is specific for:
UNIPROT: Q04739
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Word Map
The enzyme appears in viruses and cellular organisms
Synonyms
adenosine monophosphate-activated protein kinase, amp-activated kinase, 5'-amp-activated protein kinase, prkaa1, snf1 kinase, adenosine 5'-monophosphate-activated protein kinase, ampkalpha1, reductase kinase, aak-2, ampk alpha2, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
AMP-activated protein kinase
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SNF1-interacting protein 3
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3-hydroxy-3-methylglutaryl coenzyme A reductase kinase
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3-hydroxy-3-methylglutaryl-CoA reductase kinase
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AMP-activated protein kinase
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AMPK
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beta-hydroxy-beta-methylglutaryl-CoA reductase kinase
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hydroxymethylglutaryl coenzyme A reductase kinase
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hydroxymethylglutaryl coenzyme A reductase kinase (phosphorylating)
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reductase kinase
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[hydroxymethylglutaryl-CoA reductase (NADPH2)] kinase
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phospho group transfer
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SYSTEMATIC NAME
IUBMB Comments
ATP:[hydroxymethylglutaryl-CoA reductase (NADPH)] phosphotransferase
The enzyme is activated by AMP. EC 1.1.1.34, hydroxymethylglutaryl-CoA reductase (NADPH) is inactivated by the phosphorylation of the enzyme protein. Histones can also act as acceptors. The enzyme can also phosphorylate hepatic acetyl-CoA carboxylase (EC 6.4.1.2) and adipose hormone-sensitive lipase (EC 3.1.1.79) [5]. Thr-172 within the catalytic subunit (alpha-subunit) is the major site phosphorylated by the AMP-activated protein kinase kinase [7]. GTP can act instead of ATP [4]
CAS REGISTRY NUMBER
COMMENTARY hide
172522-01-9
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SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + Mig1 protein
ADP + phosphorylated Mig1 protein
show the reaction diagram
ATP + Mig2 protein
ADP + phosphorylated Mig2 protein
show the reaction diagram
additional information
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + Mig1 protein
ADP + phosphorylated Mig1 protein
show the reaction diagram
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-
-
?
ATP + Mig2 protein
ADP + phosphorylated Mig2 protein
show the reaction diagram
alkaline stress leads to the activation of all three isoforms yet only the Gal83 isoform translocates to the nucleus and phosphorylates Mig2
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
beta subunit Gal83, equivalent to subunit beta 3
UniProt
Manually annotated by BRENDA team
beta subunit Gal83, equivalent to subunit beta 3
UniProt
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
beta subunit Gal83-containing isozyme after activation by alkaline stress, when the Gal83 isoform is activated by the other Snf1-activating kinases, Tos3 and Elm1, the Gal83 isoform is unable to translocate to the nucleus
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
Saccharomyces cerevisiae expresses three isoforms of Snf1 kinase that differ by which beta subunit is present, Gal83, Sip1 or Sip2, abundance, activation, localization and signaling specificity of the three Snf1 isoforms, by quantitative immunoblotting and fluorescence microscopy, overview. The Gal83 containing isoform is the most abundant in all assays while the abundance of the Sip1 and Sip2 isoforms is typically underestimated especially in glass-bead extractions
malfunction
deletion of the SAK1 gene blocks nuclear translocation of Gal83 and signaling to Mig2
physiological function
Snf1 signaling specificity is mediated by localization of the different Snf1 isoforms. The phosphorylation of both zinc-finger transcriptions factors Mig1 and Mig2 is Snf1-dependent. Any of the three isoforms is capable of phosphorylating Mig1 in response to glucose stress. In contrast, the Gal83 isoform of Snf1 is both necessary and sufficient for the phosphorylation of Mig2 protein in response to alkaline stress. The nuclear localization of the Gal83 isoform of Snf1 is necessary for its ability to phosphorylate Mig2
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
GAL83_YEAST
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
417
0
46648
Swiss-Prot
Secretory Pathway (Reliability: 1)
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
heterotrimer
Snf1 alphabetagamma structure
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
when the Gal83 isoform is activated by the other Snf1-activating kinases, Tos3 and Elm1, the Gal83 isoform is unable to translocate to the nucleus
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
H379A
site-directed mutagenesis, mutation of beta subunit Gal83 with little effect on Gal83 function
H384A
site-directed mutagenesis, mutation of beta subunit Gal83 causing a severe loss of function when assayed for growth on alternative carbon sources, the mutation does not affect heterotrimer association
additional information
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant expression of C-terminally HA-tagged or N-terminally triple-FLAG-tagged isozyme in an enzyme-deficient Saccharomyces cerevisiae strain, expression of C-terminally GFP-tagged isozyme in haploid Saccharomyces cerevisiae
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Chandrashekarappa, D.G.; McCartney, R.R.; ODonnell, A.F.; Schmidt, M.C.
The beta subunit of yeast AMP-activated protein kinase directs substrate specificity in response to alkaline stress
Cell. Signal.
28
1881-1893
2016
Saccharomyces cerevisiae (P32578), Saccharomyces cerevisiae (P34164), Saccharomyces cerevisiae (Q04739), Saccharomyces cerevisiae, Saccharomyces cerevisiae S228C (P32578), Saccharomyces cerevisiae S228C (P34164), Saccharomyces cerevisiae S228C (Q04739)
Manually annotated by BRENDA team