Phosphorylase b kinase regulatory subunit beta (PHKB)
The protein contains 1093 amino acids for an estimated molecular weight of 124884 Da.
Phosphorylase b kinase catalyzes the phosphorylation of serine in certain substrates, including troponin I. The beta chain acts as a regulatory unit and modulates the activity of the holoenzyme in response to phosphorylation. (updated: March 4, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.
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The reference OMIM entry for this protein is 172490
Phosphorylase kinase, beta subunit; phkb
DESCRIPTION
The PHKB gene encodes the beta subunit of phosphorylase kinase (PHK; EC 2.7.11.19). Phosphorylase kinase is a hexadecameric enzyme comprising 4 copies each of 4 unique subunits encoded by 4 different genes: alpha (PHKA1 (311870) and PHKA2 (300798), the skeletal muscle and hepatic isoforms, respectively); beta (PHKB); gamma (PHKG1 (172470) and PHKG2 (172471), the skeletal muscle and hepatic isoforms, respectively); and delta. The delta subunit can be encoded by 3 different genes (CALM1, 114180, CALM2, 114182, or CALM3, 114183). The beta subunit is the same in both the muscle and hepatic 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
Kilimann et al. (1988) and Zander et al. (1988) cloned DNA sequences encoding the alpha and beta PHK subunits from a rabbit muscle cDNA library. The deduced alpha and beta polypeptides are 1,237 and 1,092 amino acids long, respectively, and contain extensive regions of sequence homology. Wullrich-Schmoll and Kilimann (1996) cloned the human PHKB gene and found that the deduced protein shares 95% amino acid sequence identity with the rabbit protein.GENE STRUCTURE
Wullrich-Schmoll and Kilimann (1996) determined that the PHKB gene contains 33 exons and spans at least 140 kb. Exons 26 and 27 are 2 homologous, mutually exclusively spliced exons in the middle of the gene; exon 2 is a facultatively utilized cassette exon encoding an alternative N terminus of the beta-subunit.MAPPING
By Southern blot analysis of rodent-human somatic cell hybrids and by in situ hybridization, Francke et al. (1989) mapped the human PHKB gene to chromosome 16q12-q13. Wullrich-Schmoll and Kilimann (1996) confirmed location of the PHKB gene to chromosome 16 by screening of a chromosome 16-specific genomic library. Two processed pseudogenes were identified.MOLECULAR GENETICS
In 1 female and 4 male patients with glycogen storage disease IXb (GSD9B; 261750) and PHK deficiency in both liver and muscle, Burwinkel et al. (1997) identified biallelic mutations in the PHKB gene. There were 5 different nonsense mutations (see, e.g., 172490.0002), a 1-bp insertion (172490.0001), a splice site mutation, and a large deletion involving the loss of exon 8. Although the mutations disrupted translation severely and occurred in constitutively expressed sequences of the only known beta-subunit gene of phosphorylase kinase, they were associated with a surprisingly mild clinical phenotype, affecting virtually only the liver, and with a relatively high residual enzyme activity of approximately 10%. Inheritance was autosomal recessive. Roscher et al. (2014) reported 2 novel mutations in the PHKB gene resulting in GSD IXb. ... More on the omim web site
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 172490 was added.