PRKAG2

Protein identityUniProt · HPA

UniProt accession

Q9UGJ0

Gene

PRKAG2

Ensembl

ENSG00000106617

Chromosome

7

Canonical length

569 aa

Protein class

Disease related genes, FDA approved drug targets, Human disease related genes, Plasma proteins, Predicted intracellular proteins

Subcellular location

Nucleoplasm

OverviewNCBI Gene

AMP-activated protein kinase (AMPK) is a heterotrimeric protein composed of a catalytic alpha subunit, a noncatalytic beta subunit, and a noncatalytic regulatory gamma subunit. Various forms of each of these subunits exist, encoded by different genes. AMPK is an important energy-sensing enzyme that monitors cellular energy status and functions by inactivating key enzymes involved in regulating de novo biosynthesis of fatty acid and cholesterol. This gene is a member of the AMPK gamma subunit family. Mutations in this gene have been associated with Wolff-Parkinson-White syndrome, familial hypertrophic cardiomyopathy, and glycogen storage disease of the heart. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jan 2015]

Canonical amino-acid sequenceUniProt

569 residues, UniProt reviewed canonical sequence.

>Q9UGJ0|PRKAG2
     1  MGSAVMDTKK KKDVSSPGGS GGKKNASQKR RSLRVHIPDL SSFAMPLLDG DLEGSGKHSS
    61  RKVDSPFGPG SPSKGFFSRG PQPRPSSPMS APVRPKTSPG SPKTVFPFSY QESPPRSPRR
   121  MSFSGIFRSS SKESSPNSNP ATSPGGIRFF SRSRKTSGLS SSPSTPTQVT KQHTFPLESY
   181  KHEPERLENR IYASSSPPDT GQRFCPSSFQ SPTRPPLASP THYAPSKAAA LAAALGPAEA
   241  GMLEKLEFED EAVEDSESGV YMRFMRSHKC YDIVPTSSKL VVFDTTLQVK KAFFALVANG
   301  VRAAPLWESK KQSFVGMLTI TDFINILHRY YKSPMVQIYE LEEHKIETWR ELYLQETFKP
   361  LVNISPDASL FDAVYSLIKN KIHRLPVIDP ISGNALYILT HKRILKFLQL FMSDMPKPAF
   421  MKQNLDELGI GTYHNIAFIH PDTPIIKALN IFVERRISAL PVVDESGKVV DIYSKFDVIN
   481  LAAEKTYNNL DITVTQALQH RSQYFEGVVK CNKLEILETI VDRIVRAEVH RLVVVNEADS
   541  IVGIISLSDI LQALILTPAG AKQKETETE

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PRKAG2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.47

Highest tissue expression

122 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PRKAG2.

Disease | AllUniProt

Conditions PRKAG2 is implicated in, by any mechanism.

• Wolff-Parkinson-White syndrome (WPW) MIM:194200
• Cardiomyopathy, familial hypertrophic, 6 (CMH6) MIM:600858
• Glycogen storage disease of heart lethal congenital (GSDH) MIM:261740

Disease | GeneticClinVar

27 pathogenic / likely-pathogenic of 1,490 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Lethal congenital glycogen storage disease of heart
• Hypertrophic cardiomyopathy
• Hypertrophic cardiomyopathy 6
• Cardiovascular phenotype
• Cardiomyopathy

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.26

gnomAD pLI

1

gnomAD missense Z

1.65

DepMap mean gene effect

0.04

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• ATP biosynthetic process
• cellular response to glucose starvation
• cellular response to nutrient levels
• fatty acid biosynthetic process
• glycogen metabolic process
• intracellular signal transduction
• positive regulation of gluconeogenesis
• regulation of carbon utilization
• regulation of cell cycle
• regulation of D-glucose import
• regulation of fatty acid metabolic process
• regulation of fatty acid oxidation
• regulation of glycolytic process
• sterol biosynthetic process

Molecular functions

• ADP binding
• AMP binding
• AMP-activated protein kinase activity
• ATP binding
• cAMP-dependent protein kinase inhibitor activity
• cAMP-dependent protein kinase regulator activity
• protein kinase activator activity
• protein kinase binding
• protein kinase regulator activity
• phosphorylase kinase regulator activity

Cellular components

• cytoplasm
• cytosol
• extracellular space
• nucleoplasm
• nucleotide-activated protein kinase complex
• nucleus

Protein domainsUniProt · Pfam · InterPro

• CBS domain
• CBS domain superfamily
• AMP-activated protein kinase gamma/SDS23 families
• CBS domain

KeywordsUniProt

• ATP-binding
• Cardiomyopathy
• CBS domain
• Fatty acid biosynthesis
• Fatty acid metabolism
• Glycogen storage disease
• Glycoprotein
• Lipid biosynthesis
• Lipid metabolism
• Nucleotide-binding
• Phosphoprotein
• Repeat

InteractionsUniProt · HPA

Protein binding partners of PRKAG2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• FNIP1
• FNIP2
• PRKAA1