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Information on EC 2.7.11.19 - phosphorylase kinase and Organism(s) Homo sapiens and UniProt Accession Q16816
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2.7.11.19 phosphorylase kinaseIUBMB Comments
Requires Ca2+ and calmodulin for activity. The enzyme phosphorylates a specific serine residue in each of the subunits of the dimeric phosphorylase b. For muscle phosphorylase but not liver phosphorylase, this is accompanied by a further dimerization to form a tetrameric phosphorylase. The enzyme couples muscle contraction with energy production via glycogenolysis---glycolysis by catalysing the Ca2+-dependent phosphorylation and activation of glycogen phosphorylase b . The gamma subunit of the tetrameric enzyme is the catalytic subunit.
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Word Map
- 2.7.11.19
- calmodulin
-
camp-dependent
- amp
- phosphatases
- myosin
- glycogenosis
- casein
- autophosphorylation
-
holoenzyme
- alpha-subunits
- glucagon
- troponin
-
nonactivated
-
x-linked
-
calmodulin-dependent
- phosphoprotein
-
gamma-subunits
-
glycogenolytic
- mgatp
- hepatomegaly
-
calmodulin-binding
-
sarcoplasmic
-
cohen
- inhibitor-1
- phosphopeptide
-
hexadecameric
-
phosphorylatable
-
delta4
-
debranching
-
2.4.1.1
- trifluoperazine
-
bisbeta-aminoethyl
-
phosphatase-2a
-
amp-independent
- phosvitin
- amylo-1,6-glucosidase
-
cyclic-amp-dependent
-
kinase-catalyzed
-
3':5'-monophosphate
-
kinase-deficient
-
seryl
- gizzard
-
carlson
-
calmodulin-sepharose
-
delta-subunits
- medicine
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Synonyms
phosphorylase kinase, phosphorylase b kinase, glycogen phosphorylase kinase, phkg1, phk alpha, dphk-gamma, glycogen phosphorylase b kinase, psk-c3, kpi-2 kinase, phosphorylase kinase beta, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
dephosphophosphorylase kinase
-
-
-
-
EC 2.7.1.38
Glycogen phosphorylase kinase
kinase, phosphorylase (phosphorylating)
-
-
-
-
PhK
PHKB
Phosphorylase b kinase
phosphorylase B kinase gamma catalytic chain, testis/liver isoform
-
phosphorylase kinase beta
PSK-C3
-
-
-
-
Glycogen phosphorylase kinase
-
-
-
-
Phosphorylase b kinase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phospho group transfer
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP:phosphorylase-b phosphotransferase
Requires Ca2+ and calmodulin for activity. The enzyme phosphorylates a specific serine residue in each of the subunits of the dimeric phosphorylase b. For muscle phosphorylase but not liver phosphorylase, this is accompanied by a further dimerization to form a tetrameric phosphorylase. The enzyme couples muscle contraction with energy production via glycogenolysis---glycolysis by catalysing the Ca2+-dependent phosphorylation and activation of glycogen phosphorylase b [5]. The gamma subunit of the tetrameric enzyme is the catalytic subunit.
CAS REGISTRY NUMBER
COMMENTARY
9001-88-1
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
2 ATP + glycogen phosphorylase b
2 ADP + glycogen phosphorylase a
-
-
-
?
2 ATP + glycogen phosphorylase b
2 ADP + glycogen phosphorylase a
glycogen phosphorylase brain form, PYGB
-
-
?
ATP + glycogen phosphorylase b
ADP + glycogen phosphorylase a
-
activation of glycogen phosphorylase which acts as a Ca2+-dependent blood glucose sensor liberating glucose from glycogen as needed, involved in regulation of the glycogen phosphorylase
-
-
?
ATP + phosphorylase b
ADP + phosphorylated phosphorylase b
-
KPI-2 reacts with Ser residues either preceded by or followed by Pro residues, does not strictly require an adjacent Pro residue
-
-
?
additional information
?
-
muscle-specific enzyme deficiency causes glycogen storage disease
-
-
?
additional information
?
-
muscle-specific enzyme deficiency causes glycogen storage disease
-
-
?
additional information
?
-
-
muscle-specific enzyme deficiency causes glycogen storage disease
-
-
?
additional information
?
-
mutations in PHKG2, the catalytic gamma subunit, are associated with an increased cirrhosis risk
-
-
?
additional information
?
-
-
mutations in PHKG2, the catalytic gamma subunit, are associated with an increased cirrhosis risk
-
-
?
additional information
?
-
-
modeling of glycogen phosphorylase regulation by Ca2+-oscillations, and dephosphorylation and phosphorylation involving the enzyme and a phosphatase, overview
-
-
?
additional information
?
-
muscle-specific enzyme deficiency causes glycogen storage disease
-
-
?
additional information
?
-
muscle-specific enzyme deficiency causes glycogen storage disease
-
-
?
additional information
?
-
-
muscle-specific enzyme deficiency causes glycogen storage disease
-
-
?
additional information
?
-
-
correlation of gene transcriptional processing and catalytic regulation of PhK subunits, overview
-
-
?
additional information
?
-
-
hormonal regulation of KPI-2, kinase KPI-2 reveals reactivity with cystic fibrosis transmembrane conductance regulator and phosphorylase
-
-
?
additional information
?
-
-
phosphorylase-b kinase deficient patients, suffering glycogen storage disease GSD IXa, show an accumulation of fat in the liver that resolves with aging, overview
-
-
?
additional information
?
-
plays a regulatory role in a cascade of enzymatic reactions controlling glycogen breakdown
-
-
?
additional information
?
-
-
plays a regulatory role in a cascade of enzymatic reactions controlling glycogen breakdown
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
2 ATP + glycogen phosphorylase b
2 ADP + glycogen phosphorylase a
-
-
-
?
ATP + glycogen phosphorylase b
ADP + glycogen phosphorylase a
-
activation of glycogen phosphorylase which acts as a Ca2+-dependent blood glucose sensor liberating glucose from glycogen as needed, involved in regulation of the glycogen phosphorylase
-
-
?
additional information
?
-
muscle-specific enzyme deficiency causes glycogen storage disease
-
-
?
additional information
?
-
muscle-specific enzyme deficiency causes glycogen storage disease
-
-
?
additional information
?
-
-
muscle-specific enzyme deficiency causes glycogen storage disease
-
-
?
additional information
?
-
mutations in PHKG2, the catalytic gamma subunit, are associated with an increased cirrhosis risk
-
-
?
additional information
?
-
-
mutations in PHKG2, the catalytic gamma subunit, are associated with an increased cirrhosis risk
-
-
?
additional information
?
-
-
modeling of glycogen phosphorylase regulation by Ca2+-oscillations, and dephosphorylation and phosphorylation involving the enzyme and a phosphatase, overview
-
-
?
additional information
?
-
muscle-specific enzyme deficiency causes glycogen storage disease
-
-
?
additional information
?
-
muscle-specific enzyme deficiency causes glycogen storage disease
-
-
?
additional information
?
-
-
muscle-specific enzyme deficiency causes glycogen storage disease
-
-
?
additional information
?
-
-
correlation of gene transcriptional processing and catalytic regulation of PhK subunits, overview
-
-
?
additional information
?
-
-
hormonal regulation of KPI-2, kinase KPI-2 reveals reactivity with cystic fibrosis transmembrane conductance regulator and phosphorylase
-
-
?
additional information
?
-
-
phosphorylase-b kinase deficient patients, suffering glycogen storage disease GSD IXa, show an accumulation of fat in the liver that resolves with aging, overview
-
-
?
additional information
?
-
plays a regulatory role in a cascade of enzymatic reactions controlling glycogen breakdown
-
-
?
additional information
?
-
-
plays a regulatory role in a cascade of enzymatic reactions controlling glycogen breakdown
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Calmodulin
-
mediates Ca2+-sensitivity of the enzyme, calmodulin is identical with the delta-subunit
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
Mg2+
Ca2+
-
Ca2+-sensitivity of the enzyme is mediated by the delta-subunit which is identical with calmodulin
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
LLRDPYALRSVRHLIDNCAFRL
-
autoregulatory pseudosubstrate sequence of the gamma subunit, residues 336-357
additional information
-
synthesis of peptides behaving as pseudosubstrates, determination of inhibitory potential
-
additional information
-
KPI-2 is inhibited in living cells by addition of nerve growth factor or serum
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
KIAA1199 enhanced the phosphorylation of glycogen phosphorylase brain form
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
Ki values of the pseudosubstrates in nano- to micromolar range
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
gene PHKG1; the subunits of the muscle isozyme are encoded by different genes
SwissProt
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
postmortem tissue, 8fold increase in glycogen concentration and no detectable phosphorylase kinase activity
additional information
-
PhK shows a wide tissue distribution, expression of subunits, overview
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
proposed model of glycogen metabolism through the activation of PHK and PYG pathways in cancer cells with or without KIAA1199 overexpression, overview. PYG plays a central role in the mobilization of carbohydrate reserves in a wide variety of organs and tissues
physiological function
malfunction
-
PhKG1 knockdown reduces human umbilical vein endothelial cell tube formation and migration
malfunction
KIAA1199 protein silencing by siRNA results in a marked reduction in the phosphorylation of glycogen phosphorylase brain form, PYGB, by PHK
malfunction
-
phosphorylase kinase beta knockdown impairs proliferation of colorectal cancer in vitro and in vivo and induced cell cycle arrest
physiological function
-
phosphorylase kinase subunit G1 (PhKG1) is implicated in angiogenesis
physiological function
glycogen phosphorylase kinase (PHK) is a serine/threonine-specific protein kinase that phosphorylates a serine residue in glycogen phosphorylase (PYG), triggering the activation of this latter enzyme that catalyzes the phosphorolytic cleavage of the alpha-1,4 glycosidic linkages of glycogen, releasing glucose-1-phosphate as the reaction product. The glycogen phosphorylase kinase beta-subunit (PHKB) interacts with the C-terminal region of KIAA1199 protein, that is associated with cancer cell migration or invasion and a poor prognosis and with non-syndromic hearing loss. KIAA1199 protein also interacts with glycogen phosphorylase brain form (PYGB) under serum-free conditions. The interaction promotes glycogen breakdown and cancer cell survival. KIAA1199 binding protein pull down assay, overview
physiological function
-
the over (or high) expression of enzyme subunit PHKB greatly hinders hepatocellular carcinoma cell invasion and increases apoptosis rates. The enzyme subunit PHKB inhibits AKT and STAT3 signaling pathway activation in hepatocellular carcinoma
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). PHKG1_HUMAN
387
0
45024
Swiss-Prot
other Location (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hexadecamer
additional information
additional information
PHK is an enzyme comprised of four subunits, of which the gamma-subunit possesses enzymatic activity that is tightly regulated by the other three regulatory subunits in response to changes in intracellular Ca2+ concentrations (sensed by the delta-subunit, calmodulin) and cAMP levels that stimulate protein kinase A to phosphorylate the alpha- and beta-subunits (PHKA and PHKB). Upon phosphorylation, these two subunits, which basically inhibit the activity of the gamma-subunit, reduce their function as gamma-inhibitors, resulting in the enzymatic activation of PHK
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D299V
naturally occurring mutation in gene PHKB, encoding subunit beta, missense mutation leads to enzyme deficiency in vivo
Q657K
naturally occurring heterozygous single amino acid replacement in gene PHKB, might not be significant for enzyme deficiency disease, patient shows low enzyme activity
Y770C
naturally occurring heterozygous single amino acid replacement in gene PHKB, might not be significant for enzyme deficiency disease, patient shows low enzyme activity
D299V
naturally occurring mutation in gene PHKB, encoding subunit beta, missense mutation leads to enzyme deficiency in vivo
DELTA189-190
naturally occurring mutation in XLG II patient, increased activity blood cells
E1125K
naturally occurring mutation in XLG I patient, low activity in blood cells
Q1169X
naturally occurring mutation in XLG I patient, CAG codon is replaced by a TAG stop codon, very low activity in blood cells
Q657K
naturally occurring heterozygous single amino acid replacement in gene PHKB, might not be significant for enzyme deficiency disease, patient shows low enzyme activity
R295H
naturally occurring mutation in XLG I and XLG II patients, very low activity in blood cells and liver
Y770C
naturally occurring heterozygous single amino acid replacement in gene PHKB, might not be significant for enzyme deficiency disease, patient shows low enzyme activity
additional information
additional information
regulatory enzyme of glycogen metabolism, mutations in the testis/liver isoform of the phosphorylase kinase gamma subunit cause autosomal liver glycogenosis. Mutation V106E, G189E and D215N are responsible for autosomal form of Phk deficiency
additional information
-
regulatory enzyme of glycogen metabolism, mutations in the testis/liver isoform of the phosphorylase kinase gamma subunit cause autosomal liver glycogenosis. Mutation V106E, G189E and D215N are responsible for autosomal form of Phk deficiency
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant c-Myc-/His6-tagged full-length KPI-2 from Sf9 cells by nickel affinity and ion exchange chromatography, and gel filtration
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
DNA sequence determination and structural analysis, genetic organization, the subunits of the muscle isozyme are encoded by different genes, subunit gamma is encoded by gene PHKG1, genes PHKA1, PHKB1, PHKG1, CALM1, CALM2, and CALM3 are involved, relation to several pseudogenes
DNA sequence determination and structural analysis, genetic organization, the subunits of the muscle isozyme are encoded by different genes, subunit alpha is encoded by gene PHKA1, genes PHKA1, PHKB1, PHKG1, CALM1, CALM2, and CALM3 are involved, relation to several pseudogenes
expression of c-Myc-/His6-tagged full-length KPI-2 and minimal kinase fold, residues 137-407 plus an additional C-terminal segment in HEK-293 cells and in Spodoptera frugiperda Sf9 cells using the baculovirus transfection system
-
PhK isozymes, DNA sequence and genomic localization determination and analysis, genetic organization, the genes encoding the alpha, beta, and gamma subunits of PhK undergo extensive transcriptional processing, e.g. exon 6 of PhKG1 is a 3' composite terminal exon due to the presence of weak polyadenylation and cleavage site in intron 6
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
PhKG1 is upregulated in human tumor samples from a range of tumor types. PhKG1 mRNA levels are elevated by more than 2fold in the majority of human tumors tested, no upregulation of PhKG1 is detected in prostate cancer
-
phosphorylase kinase beta mRNA and protein are overexpressed in colorectal cancer tissue compared to the levels in normal mucosa
-
the expression of subunit PHKB is significantly decreased in hepatocellular carcinoma tissues
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
-
elevated expression of phosphorylase kinase beta is an independent prognostic factor in patients with colorectal cancer
medicine
-
the low expression of enzyme subunit PHKB can serve as an independent indicator for predicting poor prognosis in hepatocellular carcinoma
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Kemp, B.E.; Pearson, R.B.; House, M.
Pseudosubstrate-based peptide inhibitors
Methods Enzymol.
201
287-304
1991
Oryctolagus cuniculus, Homo sapiens, Mus musculus
Hanks, S.K.
Homology probing: identification of cDNA clones encoding members of the protein-serine kinase family
Proc. Natl. Acad. Sci. USA
84
388-392
1987
Homo sapiens (P15735)
Burwinkel, B.; Shiomi, S.; Al Zaben, A.; Kilimann, M.W.
Liver glycogenosis due to phosphorylase kinase deficiency: PHKG2 gene structure and mutations associated with cirrhosis
Hum. Mol. Genet.
7
149-154
1998
Homo sapiens (P15735), Homo sapiens
Hanks, S.K.
Messenger ribonucleic acid encoding an apparent isoform of phosphorylase kinase catalytic subunit is abundant in the adult testis
Mol. Endocrinol.
3
110-116
1989
Homo sapiens (P15735), Homo sapiens
Maichele, A.J.; Burwinkel, B.; Maire, I.; Sovik, O.; Kilimann, M.W.
Mutations in the testis/liver isoform of the phosphorylase kinase gamma subunit (PHKG2) cause autosomal liver glycogenosis in the gsd rat and in humans
Nat. Genet.
14
337-340
1996
Homo sapiens (P15735), Homo sapiens
Wehner, M.; Kilimann, M.W.
Human cDNA encoding the muscle isoform of the phosphorylase kinase gamma subunit (PHKG1)
Hum. Genet.
96
616-618
1995
Homo sapiens (Q16816), Homo sapiens
Rozi, A.; Jia, Y.
A theoretical study of effects of cytosolic Ca2+ oscillations on activation of glycogen phosphorylase
Biophys. Chem.
106
193-202
2003
Homo sapiens
Burwinkel, B.; Hu, B.; Schroers, A.; Clemens, P.R.; Moses, S.W.; Shin, Y.S.; Pongratz, D.; Vorgerd, M.; Kilimann, M.W.
Muscle glycogenosis with low phosphorylase kinase activity: mutations in PHKA1, PHKG1 or six other candidate genes explain only a minority of cases
Eur. J. Hum. Genet.
11
516-526
2003
Homo sapiens (P46020), Homo sapiens (Q16816), Homo sapiens
Sijens, P.E.; Smit, G.P.; Borgdorff, M.A.; Kappert, P.; Oudkerk, M.
Multiple voxel 1H MR spectroscopy of phosphorylase-b kinase deficient patients (GSD IXa) showing an accumulation of fat in the liver that resolves with aging
J. Hepatol.
45
851-855
2006
Homo sapiens
Wang, H.; Brautigan, D.L.
Peptide microarray analysis of substrate specificity of the transmembrane Ser/Thr kinase KPI-2 reveals reactivity with cystic fibrosis transmembrane conductance regulator and phosphorylase
Mol. Cell. Proteomics
5
2124-2130
2006
Homo sapiens
Winchester, J.S.; Rouchka, E.C.; Rowland, N.S.; Rice, N.A.
In silico characterization of phosphorylase kinase: evidence for an alternate intronic polyadenylation site in PHKG1
Mol. Genet. Metab.
92
234-242
2007
Homo sapiens
Hendrickx, J.; Lee, P.; Keating, J.P.; Carton, D.; Sardharwalla, I.B.; Tuchman, M.; Baussan, C.; Willems, P.J.
Complete genomic structure and mutational spectrum of PHKA2 in patients with x-linked liver glycogenosis type I and II
Am. J. Hum. Genet.
64
1541-15499
1999
Homo sapiens (P46019), Homo sapiens
Akman, H.O.; Sampayo, J.N.; Ross, F.A.; Scott, J.W.; Wilson, G.; Benson, L.; Bruno, C.; Shanske, S.; Hardie, D.G.; Dimauro, S.
Fatal infantile cardiac glycogenosis with phosphorylase kinase deficiency and a mutation in the gamma2-subunit of AMP-activated protein kinase
Pediatr. Res.
62
499-504
2007
Homo sapiens
Camus, S.; Quevedo, C.; Menendez, S.; Paramonov, I.; Stouten, P.F.; Janssen, R.A.; Rueb, S.; He, S.; Snaar-Jagalska, B.E.; Laricchia-Robbio, L.; Izpisua Belmonte, J.C.
Identification of phosphorylase kinase as a novel therapeutic target through high-throughput screening for anti-angiogenesis compounds in zebrafish
Oncogene
31
4333-4342
2012
Danio rerio, Homo sapiens
Terashima, M.; Fujita, Y.; Togashi, Y.; Sakai, K.; De Velasco, M.A.; Tomida, S.; Nishio, K.
KIAA1199 interacts with glycogen phosphorylase kinase beta-subunit (PHKB) to promote glycogen breakdown and cancer cell survival
Oncotarget
5
7040-7050
2014
Homo sapiens (Q93100)
Yang, W.; Zhang, C.; Li, Y.; Jin, A.; Sun, Y.; Yang, X.; Wang, B.; Guo, W.
Phosphorylase kinase beta represents a novel prognostic biomarker and inhibits malignant phenotypes of liver cancer cell
Int. J. Biol. Sci.
15
2596-2606
2019
Homo sapiens
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