PYGL

Protein identityUniProt · HPA

UniProt accession

P06737

Gene

PYGL

Ensembl

ENSG00000100504

Chromosome

14

Canonical length

847 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Plasma membrane,Cytosol

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene encodes a homodimeric protein that catalyses the cleavage of alpha-1,4-glucosidic bonds to release glucose-1-phosphate from liver glycogen stores. This protein switches from inactive phosphorylase B to active phosphorylase A by phosphorylation of serine residue 15. Activity of this enzyme is further regulated by multiple allosteric effectors and hormonal controls. Humans have three glycogen phosphorylase genes that encode distinct isozymes that are primarily expressed in liver, brain and muscle, respectively. The liver isozyme serves the glycemic demands of the body in general while the brain and muscle isozymes supply just those tissues. In glycogen storage disease type VI, also known as Hers disease, mutations in liver glycogen phosphorylase inhibit the conversion of glycogen to glucose and results in moderate hypoglycemia, mild ketosis, growth retardation and hepatomegaly. Alternative splicing results in multiple transcript variants encoding different isoforms.[provided by RefSeq, Feb 2011]

Canonical amino-acid sequenceUniProt

847 residues, UniProt reviewed canonical sequence.

>P06737|PYGL
     1  MAKPLTDQEK RRQISIRGIV GVENVAELKK SFNRHLHFTL VKDRNVATTR DYYFALAHTV
    61  RDHLVGRWIR TQQHYYDKCP KRVYYLSLEF YMGRTLQNTM INLGLQNACD EAIYQLGLDI
   121  EELEEIEEDA GLGNGGLGRL AACFLDSMAT LGLAAYGYGI RYEYGIFNQK IRDGWQVEEA
   181  DDWLRYGNPW EKSRPEFMLP VHFYGKVEHT NTGTKWIDTQ VVLALPYDTP VPGYMNNTVN
   241  TMRLWSARAP NDFNLRDFNV GDYIQAVLDR NLAENISRVL YPNDNFFEGK ELRLKQEYFV
   301  VAATLQDIIR RFKASKFGST RGAGTVFDAF PDQVAIQLND THPALAIPEL MRIFVDIEKL
   361  PWSKAWELTQ KTFAYTNHTV LPEALERWPV DLVEKLLPRH LEIIYEINQK HLDRIVALFP
   421  KDVDRLRRMS LIEEEGSKRI NMAHLCIVGS HAVNGVAKIH SDIVKTKVFK DFSELEPDKF
   481  QNKTNGITPR RWLLLCNPGL AELIAEKIGE DYVKDLSQLT KLHSFLGDDV FLRELAKVKQ
   541  ENKLKFSQFL ETEYKVKINP SSMFDVQVKR IHEYKRQLLN CLHVITMYNR IKKDPKKLFV
   601  PRTVIIGGKA APGYHMAKMI IKLITSVADV VNNDPMVGSK LKVIFLENYR VSLAEKVIPA
   661  TDLSEQISTA GTEASGTGNM KFMLNGALTI GTMDGANVEM AEEAGEENLF IFGMRIDDVA
   721  ALDKKGYEAK EYYEALPELK LVIDQIDNGF FSPKQPDLFK DIINMLFYHD RFKVFADYEA
   781  YVKCQDKVSQ LYMNPKAWNT MVLKNIAASG KFSSDRTIKE YAQNIWNVEP SDLKISLSNE
   841  SNKVNGN

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PYGL 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

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.21

Highest tissue expression

136 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PYGL.

Disease | AllUniProt

Conditions PYGL is implicated in, by any mechanism.

• Glycogen storage disease 6 (GSD6) MIM:232700

Disease | GeneticClinVar

75 pathogenic / likely-pathogenic of 454 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Glycogen storage disease, type VI
• PYGL-related disorder
• Uveal melanoma
• Uterine corpus endometrial carcinoma
• Thyroid cancer, nonmedullary, 1

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)

0.97

gnomAD pLI

0

gnomAD missense Z

-0.2

DepMap mean gene effect

-0.07

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• glucose homeostasis
• glycogen catabolic process
• glycogen metabolic process
• necroptotic process
• response to bacterium

Molecular functions

• AMP binding
• ATP binding
• bile acid binding
• D-glucose binding
• glycogen phosphorylase activity
• identical protein binding
• purine nucleobase binding
• pyridoxal phosphate binding
• vitamin binding

Cellular components

• cytoplasm
• cytosol
• extracellular exosome
• extracellular region
• ficolin-1-rich granule lumen
• secretory granule lumen

Protein domainsUniProt · Pfam · InterPro

• Glycosyl transferase, family 35
• Glycogen/starch/alpha-glucan phosphorylase
• Phosphorylase pyridoxal-phosphate attachment site
• Carbohydrate phosphorylase

KeywordsUniProt

• Acetylation
• Allosteric enzyme
• Carbohydrate metabolism
• Cytoplasm
• Glycogen metabolism
• Glycogen storage disease
• Glycosyltransferase
• Nucleotide-binding
• Phosphoprotein
• Pyridoxal phosphate
• Transferase

InteractionsUniProt · HPA

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

• PPP1R3B
• RIPK3
• FKBP5
• PYGB