PHKA2

Protein identityUniProt · HPA

UniProt accession

P46019

Gene

PHKA2

Ensembl

ENSG00000044446

Chromosome

X

Canonical length

1235 aa

Protein class

Disease related genes, Human disease related genes, Metabolic proteins, Predicted intracellular proteins

Subcellular location

Nucleoplasm

OverviewNCBI Gene

Phosphorylase kinase is a polymer of 16 subunits, four each of alpha, beta, gamma and delta. The alpha subunit includes the skeletal muscle and hepatic isoforms, and the hepatic isoform is encoded by this gene. The beta subunit is the same in both the muscle and hepatic isoforms, and encoded by one gene. The gamma subunit also includes the skeletal muscle and hepatic isoforms, which are encoded by two different genes. The delta subunit is a calmodulin and can be encoded by three different genes. The gamma subunits contain the active site of the enzyme, whereas the alpha and beta subunits have regulatory functions controlled by phosphorylation. The delta subunit mediates the dependence of the enzyme on calcium concentration. Mutations in this gene cause glycogen storage disease type 9A, also known as X-linked liver glycogenosis. Alternatively spliced transcript variants have been reported, but the full-length nature of these variants has not been determined.[provided by RefSeq, Feb 2010]

Canonical amino-acid sequenceUniProt

1235 residues, UniProt reviewed canonical sequence.

>P46019|PHKA2
     1  MRSRSNSGVR LDGYARLVQQ TILCYQNPVT GLLSASHEQK DAWVRDNIYS ILAVWGLGMA
    61  YRKNADRDED KAKAYELEQN VVKLMRGLLQ CMMRQVAKVE KFKHTQSTKD SLHAKYNTAT
   121  CGTVVGDDQW GHLQVDATSL FLLFLAQMTA SGLRIIFTLD EVAFIQNLVF YIEAAYKVAD
   181  YGMWERGDKT NQGIPELNAS SVGMAKAALE AIDELDLFGA HGGRKSVIHV LPDEVEHCQS
   241  ILFSMLPRAS TSKEIDAGLL SIISFPAFAV EDVNLVNVTK NEIISKLQGR YGCCRFLRDG
   301  YKTPREDPNR LHYDPAELKL FENIECEWPV FWTYFIIDGV FSGDAVQVQE YREALEGILI
   361  RGKNGIRLVP ELYAVPPNKV DEEYKNPHTV DRVPMGKVPH LWGQSLYILS SLLAEGFLAA
   421  GEIDPLNRRF STSVKPDVVV QVTVLAENNH IKDLLRKHGV NVQSIADIHP IQVQPGRILS
   481  HIYAKLGRNK NMNLSGRPYR HIGVLGTSKL YVIRNQIFTF TPQFTDQHHF YLALDNEMIV
   541  EMLRIELAYL CTCWRMTGRP TLTFPISRTM LTNDGSDIHS AVLSTIRKLE DGYFGGARVK
   601  LGNLSEFLTT SFYTYLTFLD PDCDEKLFDN ASEGTFSPDS DSDLVGYLED TCNQESQDEL
   661  DHYINHLLQS TSLRSYLPPL CKNTEDRHVF SAIHSTRDIL SVMAKAKGLE VPFVPMTLPT
   721  KVLSAHRKSL NLVDSPQPLL EKVPESDFQW PRDDHGDVDC EKLVEQLKDC SNLQDQADIL
   781  YILYVIKGPS WDTNLSGQHG VTVQNLLGEL YGKAGLNQEW GLIRYISGLL RKKVEVLAEA
   841  CTDLLSHQKQ LTVGLPPEPR EKIISAPLPP EELTKLIYEA SGQDISIAVL TQEIVVYLAM
   901  YVRAQPSLFV EMLRLRIGLI IQVMATELAR SLNCSGEEAS ESLMNLSPFD MKNLLHHILS
   961  GKEFGVERSV RPIHSSTSSP TISIHEVGHT GVTKTERSGI NRLRSEMKQM TRRFSADEQF
  1021  FSVGQAASSS AHSSKSARSS TPSSPTGTSS SDSGGHHIGW GERQGQWLRR RRLDGAINRV
  1081  PVGFYQRVWK ILQKCHGLSI DGYVLPSSTT REMTPHEIKF AVHVESVLNR VPQPEYRQLL
  1141  VEAIMVLTLL SDTEMTSIGG IIHVDQIVQM ASQLFLQDQV SIGAMDTLEK DQATGICHFF
  1201  YDSAPSGAYG TMTYLTRAVA SYLQELLPNS GCQMQ

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PHKA2 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

Cell surface

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.26

Highest tissue expression

37 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PHKA2.

Disease | AllUniProt

Conditions PHKA2 is implicated in, by any mechanism.

• Glycogen storage disease 9A (GSD9A) MIM:306000

Disease | GeneticClinVar

124 pathogenic / likely-pathogenic of 938 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Glycogen storage disease IXa1
• Glycogen storage disease IXa2
• Thyroid cancer, nonmedullary, 1
• PHKA2-related disorder
• Inborn genetic diseases

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)

0.37

gnomAD pLI

0.38

gnomAD missense Z

1.82

DepMap mean gene effect

0.07

DepMap dependency class

none

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

• carbohydrate metabolic process
• generation of precursor metabolites and energy
• glycogen metabolic process
• protein modification process

Molecular functions

• calmodulin binding
• phosphorylase kinase activity

Cellular components

• cytosol
• phosphorylase kinase complex
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Phosphorylase kinase alpha/beta subunit
• Six-hairpin glycosidase superfamily
• GH15-like domain
• Six-hairpin glycosidase-like superfamily
• Phosphorylase b kinase regulatory subunit alpha/beta, C-terminal domain
• Glycosyl hydrolases family 15
• Phosphorylase b kinase C-terminal domain

KeywordsUniProt

• Calmodulin-binding
• Carbohydrate metabolism
• Cell membrane
• Glycogen metabolism
• Glycogen storage disease
• Lipoprotein
• Membrane
• Phosphoprotein
• Prenylation

InteractionsUniProt · HPA

Protein binding partners of PHKA2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CALM1
• PHKG2