PRKAB1

5'-AMP-activated protein kinase subunit beta-1 is an enzyme that in humans is encoded by the PRKAB1 gene.[5][6]

PRKAB1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesPRKAB1, AMPK, HAMPKb, protein kinase AMP-activated non-catalytic subunit beta 1
External IDsOMIM: 602740 MGI: 1336167 HomoloGene: 38160 GeneCards: PRKAB1
Gene location (Human)
Chr.Chromosome 12 (human)[1]
Band12q24.23Start119,667,864 bp[1]
End119,681,624 bp[1]
RNA expression pattern


More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

5564

19079

Ensembl

ENSG00000111725

ENSMUSG00000029513

UniProt

Q9Y478

Q9R078

RefSeq (mRNA)

NM_006253

NM_031869

RefSeq (protein)

NP_006244
NP_006244.2

NP_114075

Location (UCSC)Chr 12: 119.67 – 119.68 MbChr 5: 116.01 – 116.02 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

The protein encoded by this gene is a regulatory subunit of the AMP-activated protein kinase (AMPK). AMPK is a heterotrimer consisting of an alpha catalytic subunit, and non-catalytic beta and gamma subunits. AMPK is an important energy-sensing enzyme that monitors cellular energy status. In response to cellular metabolic stresses, AMPK is activated, and thus phosphorylates and inactivates acetyl-CoA carboxylase (ACC) and beta-hydroxy beta-methylglutaryl-CoA reductase (HMGCR), key enzymes involved in regulating de novo biosynthesis of fatty acid and cholesterol. This subunit may be a positive regulator of AMPK activity. The myristoylation and phosphorylation of this subunit have been shown to affect the enzyme activity and cellular localization of AMPK. This subunit may also serve as an adaptor molecule mediating the association of the AMPK complex.[6]

Model organisms

Model organisms have been used in the study of PRKAB1 function. A conditional knockout mouse line, called Prkab1tm1a(KOMP)Wtsi[14][15] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[16][17][18]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[12][19] Twenty five tests were carried out on mutant mice and four significant abnormalities were observed.[12] Homozygous mutant males displayed impaired glucose tolerance. Animals of both sex had increased circulating bilirubin levels, increased IgG3 levels, and a number of atypical haematology parameters.[12]

Interactions

PRKAB1 has been shown to interact with PRKAG2[20] and PRKAG1.[20]

The 5'-AMP-activated protein kinase beta subunit interaction domain (AMPKBI) is a conserved domain found in the beta subunit of the 5-AMP-activated protein kinase complex, and its yeast homologues Sip1 (SNF1-interacting protein 1), Sip2 (SNF1-interacting protein 2) and Gal83 (galactose metabolism 83), which are found in the SNF1 (sucrose non-fermenting) kinase complex.[21] This region is sufficient for interaction of this subunit with the kinase complex, but is not solely responsible for the interaction, and the interaction partner is not known.[22]

AMPKBI
Identifiers
SymbolAMPKBI
PfamPF04739
InterProIPR006828

References
  1. GRCh38: Ensembl release 89: ENSG00000111725 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000029513 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Stapleton D, Mitchelhill KI, Gao G, Widmer J, Michell BJ, Teh T, House CM, Fernandez CS, Cox T, Witters LA, Kemp BE (February 1996). "Mammalian AMP-activated protein kinase subfamily". J Biol Chem. 271 (2): 611–4. doi:10.1074/jbc.271.2.611. PMID 8557660.
  6. "Entrez Gene: PRKAB1 protein kinase, AMP-activated, beta 1 non-catalytic subunit".
  7. "Glucose tolerance test data for Prkab1". Wellcome Trust Sanger Institute.
  8. "Clinical chemistry data for Prkab1". Wellcome Trust Sanger Institute.
  9. "Haematology data for Prkab1". Wellcome Trust Sanger Institute.
  10. "Salmonella infection data for Prkab1". Wellcome Trust Sanger Institute.
  11. "Citrobacter infection data for Prkab1". Wellcome Trust Sanger Institute.
  12. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x. S2CID 85911512.
  13. Mouse Resources Portal, Wellcome Trust Sanger Institute.
  14. "International Knockout Mouse Consortium".
  15. "Mouse Genome Informatics".
  16. Skarnes, W. C.; Rosen, B.; West, A. P.; Koutsourakis, M.; Bushell, W.; Iyer, V.; Mujica, A. O.; Thomas, M.; Harrow, J.; Cox, T.; Jackson, D.; Severin, J.; Biggs, P.; Fu, J.; Nefedov, M.; De Jong, P. J.; Stewart, A. F.; Bradley, A. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
  17. Dolgin E (2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  18. Collins FS, Rossant J, Wurst W (2007). "A Mouse for All Reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. S2CID 18872015.
  19. van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biol. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.
  20. Cheung, P C; Salt I P; Davies S P; Hardie D G; Carling D (March 2000). "Characterization of AMP-activated protein kinase gamma-subunit isoforms and their role in AMP binding". Biochem. J. 346 (3): 659–69. doi:10.1042/0264-6021:3460659. ISSN 0264-6021. PMC 1220898. PMID 10698692.
  21. Gao G, Fernandez CS, Stapleton D, Auster AS, Widmer J, Dyck JR, Kemp BE, Witters LA (April 1996). "Non-catalytic beta- and gamma-subunit isoforms of the 5'-AMP-activated protein kinase". J. Biol. Chem. 271 (15): 8675–81. doi:10.1074/jbc.271.15.8675. PMID 8621499.
  22. Yang X, Jiang R, Carlson M (December 1994). "A family of proteins containing a conserved domain that mediates interaction with the yeast SNF1 protein kinase complex". EMBO J. 13 (24): 5878–86. doi:10.1002/j.1460-2075.1994.tb06933.x. PMC 395563. PMID 7813428.

Further reading
  • PDBe-KB provides an overview of all the structure information available in the PDB for Human 5'-AMP-activated protein kinase subunit beta-1 (PRKAB1)
This article incorporates text from the public domain Pfam and InterPro: IPR006828
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