The reference OMIM entry for this protein is 300798

Phosphorylase kinase, liver, alpha-2 subunit; phka2

DESCRIPTION

The PHKA2 gene on chromosome Xp22 encodes the alpha subunit of hepatic phosphorylase kinase (PHK; EC 2.7.11.19). Hepatic phosphorylase kinase is a hexadecameric enzyme comprising 4 copies each of 4 unique subunits encoded by 4 different genes: alpha (PHKA2), beta (PHKB, 172490), gamma (PHKG2, (172471)), and delta. The delta subunit can be encoded by 3 different genes (CALM1, 114180; CALM2, 114182; or CALM3, 114183). The PHKA1 (311870) and PHKG1 (172470) genes encode the alpha and gamma subunits, respectively, of muscle phosphorylase kinase; the beta subunit is the same in both isoforms. 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, which encodes calmodulin, mediates the dependence of the enzyme on calcium concentration (Beauchamp et al., 2007).

CLONING

Davidson et al. (1992) isolated clones corresponding to the Phka2 gene from a rabbit cDNA library. The deduced 1,235-residue protein showed 68% sequence similarity to the rabbit Phka1 gene. The placement of nucleotide and residue differences indicated that Phka1 and Phka2 are encoded by 2 separate genes, rather than being generated by alternative splicing of a single gene. Northern blot analysis identified a 4.3-kb mRNA Phka2 transcript with high expression in liver and brain, but not in muscle. Hendrickx et al. (1992, 1993) isolated a clone for the human PHKA2 gene from a human hepatoma cDNA library. The protein showed 93.5% homology to the rabbit protein. Two calmodulin binding sites identified in rabbit Phka1 are highly conserved in rabbit and human PHKA2. Differential splicing was observed.

MAPPING

Using the rabbit Phka2 gene, Davidson et al. (1992) mapped the human homolog, PHKA2, to chromosome Xp22.2-p22.1. By in situ hybridization, Wauters et al. (1992) demonstrated that the PHKA2 gene is located in the distal part of Xp in the same region as the mutation for X-linked liver glycogenosis (GSD IXa; 306000). By fluorescence in situ hybridization, Hendrickx et al. (1992, 1993) mapped the human PHKA2 gene to Xp22. It is noteworthy that PHKA1 and PHKA2 are located on Xq and Xp, respectively. In the mouse, Ryder-Cook et al. (1989) mapped the alpha subunit of phosphorylase kinase to the X chromosome. They noted that the beta, gamma, and delta subunits are autosomal.

GENE STRUCTURE

Hendrickx et al. (1999) determined that the human PHKA2 gene contains 33 exons and spans 65 kb or more.

MOLECULAR GENETICS

In patients with X-linked hepatic glycogen storage disease (GSD9A; see 306000), Hendrickx et al. (1995) identified 4 different mutations in the PHKA2 gene (300798.0001-300798.0004). Van den Berg et al. (1995) identified mutations in the PHKA2 gene (300798.0005 and 300798.0006) in affected members of 2 Dutch families with GSD IXa1. One of the families had been reported by Huijing and Fernandez (1969). Burwinkel et al. (1996) identified mutations in the PHKA2 gene in patients with GSD IXa2 (306000.0007-306000.0010). The mutations appeared to cluster in limited sequence regions. Burwinkel et al. (1996) stressed that the clustering of GSD IXa2 mutations would further facilitate analysis by RT-PCR of blood cell mRNA and thus help avoid liver biopsy in the diagnosis. In a Japanese boy with classic GSD IXa2, Fukao et al. (2007) identified a hemizygous 10-kb deletion in the PHKA2 gene, resulting in the deletion o ... More on the omim web site

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Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 300798 was added.