Last update 01 Nov 2024

PHKG2

Last update 01 Nov 2024

Basic Info

Synonyms

PHK-gamma-LT, PHK-gamma-T, PHKG2

+ [5]

Introduction

Catalytic subunit of the phosphorylase b kinase (PHK), which mediates the neural and hormonal regulation of glycogen breakdown (glycogenolysis) by phosphorylating and thereby activating glycogen phosphorylase. May regulate glycogeneolysis in the testis. In vitro, phosphorylates PYGM (By similarity).

Drugs associated with PHKG2

AAV9-LSP-hPHKG2

Target

PHKG2

Mechanism

PHKG2 modulators

Active Org.

Kriya Therapeutics, Inc.Startup [+1]

Originator Org.

Duke University [+1]

Active Indication

Glycogen Storage Disease Type Ix

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with PHKG2

100 Translational Medicine associated with PHKG2

0 Patents (Medical) associated with PHKG2

Literatures (Medical) associated with PHKG2

15 May 2023·Archives of biochemistry and biophysics

PHKG2 regulates RSL3-induced ferroptosis in Helicobacter pylori related gastric cancer.

Article

Author: Xing, Yuanxin ; Wang, Yunshan ; Jia, Yanfei ; Liu, Duanrui ; Lu, Yi ; Ma, Xiaoli ; Zhu, Jingyu ; Zhu, Wenshuai ; Sun, Jingguo ; Ji, Mingyu

Ferroptosis is a newly discovered form of regulatory cell death induced by iron-dependent lipid peroxidation. Infection with Helicobacter pylori (H. pylori) is regarded as a high-risk factor for the development of gastric cancer (GC) and is associated with an increase in the levels of reactive oxygen species with activation of oncogenic signaling pathways. However, whether GC arising in the context of infection with H. pylori is correlated with ferroptosis is still unknown. In this study, we demonstrate that H. pylori infection increased the sensitivity of GC cells to RSL3 (RAS-selective lethal3)-induced ferroptosis. The molecular subtypes mediated by ferroptosis-related genes are associated with tumor microenvironment (TME) cell infiltration and patient survival. Importantly, we identified that the expression of phosphorylase kinase G2 (PHKG2) was remarkably correlated with H. pylori infection, metabolic biological processes, patient survival and therapy response. We further found the mechanism of H. pylori-induced cell sensitivity to ferroptosis, which involves PHKG2 regulation of the lipoxygenase enzyme Arachidonate 5-Lipoxygenase (ALOX5). In conclusion, PHKG2 facilitates RSL3-induced ferroptosis in H. pylori-positive GC cells by promoting ALOX5 expression. These findings may contribute to a better understanding of the unique pathogenesis of H. pylori-induced GC and allow for maximum efficacy of genetic, cellular, and immune therapies for controlling ferroptosis in diverse contexts.

01 Jan 2023·Computational and Structural Biotechnology Journal

TWN-RENCOD: A novel method for protein binding site comparison

Article

Author: Balupuri, Anand ; Choi, Kwang-Eun ; Kang, Nam Sook

Several diverse proteins possess similar binding sites. Protein binding site comparison provides valuable insights for the drug discovery and development. Binding site similarities are useful in understanding polypharmacology, identifying potential off-targets and repurposing of known drugs. Many binding site analysis and comparison methods are available today, however, these methods may not be adequate to explain variation in the activity of a drug or a small molecule against a number of similar proteins. Water molecules surrounding the protein surface contribute to structure and function of proteins. Water molecules form diverse types of hydrogen-bonded cyclic water-ring networks known as topological water networks (TWNs). Analysis of TWNs in binding site of proteins may improve understanding of the characteristics of binding sites. We propose TWN-based residue encoding (TWN-RENCOD), a novel binding site comparison method which compares the aqueous environment in binding sites of similar proteins. As compared to other existing methods, results obtained using our method correlated better with differences in wide range of activity of a known drug (Sunitinib) against nine different protein kinases (KIT, PDGFRA, VEGFR2, PHKG2, ITK, HPK1, MST3, PAK6 and CDK2).

01 Dec 2022·BMC Pediatrics

A very rare case report of glycogen storage disease type IXc with novel PHKG2 variants

Article

Author: Liu, Li ; Jiang, Minyan ; Huang, Yonglan ; Li, Taolin ; Xu, Jianan ; Zheng, Ruidan ; Shao, Yongxian ; Li, Xiuzhen

AbstractBackgroundPathogenic mutations in the PHKG2 are associated with a very rare disease—glycogen storage disease IXc (GSD-IXc)—and are characterized by severe liver disease.Case presentationHere, we report a patient with jaundice, hypoglycaemia, growth retardation, progressive increase in liver transaminase and prominent hepatomegaly from the neonatal period. Genetic testing revealed two novel, previously unreported PHKG2 mutations (F233S and R320DfsX5). Functional experiments indicated that both F223S and R320DfsX5 lead to a decrease in key phosphorylase b kinase enzyme activity. With raw cornstarch therapy, hypoglycaemia and lactic acidosis were ameliorated and serum aminotransferases decreased.ConclusionThese findings expand the gene spectrum and contribute to the interpretation of clinical presentations of these two novel PHKG2 mutations.

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PHKG2

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