PRKAB1

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Protein kinase, AMP-activated, beta 1 non-catalytic subunit
Protein PRKAB1 PDB 1z0m.png
PDB rendering based on 1z0m.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols PRKAB1 ; AMPK; HAMPKb
External IDs OMIM602740 MGI1336167 HomoloGene38160 ChEMBL: 3847 GeneCards: PRKAB1 Gene
RNA expression pattern
PBB GE PRKAB1 201835 s at tn.png
PBB GE PRKAB1 201834 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 5564 19079
Ensembl ENSG00000111725 ENSMUSG00000029513
UniProt Q9Y478 Q9R078
RefSeq (mRNA) NM_006253 NM_031869
RefSeq (protein) NP_006244 NP_114075
Location (UCSC) Chr 12:
120.11 – 120.12 Mb
Chr 5:
116.01 – 116.02 Mb
PubMed search [1] [2]

5'-AMP-activated protein kinase subunit beta-1 is an enzyme that in humans is encoded by the PRKAB1 gene.[1][2]

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.[2]

Model organisms[edit]

Model organisms have been used in the study of PRKAB1 function. A conditional knockout mouse line, called Prkab1tm1a(KOMP)Wtsi[10][11] 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.[12][13][14]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[8][15] Twenty five tests were carried out on mutant mice and four significant abnormalities were observed.[8] 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.[8]

Interactions[edit]

PRKAB1 has been shown to interact with PRKAG2[16] and PRKAG1.[16]

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, Sip2 and Gal83, which are found in the SNF1 kinase complex.[17] 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.[18]

AMPKBI
Identifiers
Symbol AMPKBI
Pfam PF04739
InterPro IPR006828

References[edit]

  1. ^ 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. 
  2. ^ a b "Entrez Gene: PRKAB1 protein kinase, AMP-activated, beta 1 non-catalytic subunit". 
  3. ^ "Glucose tolerance test data for Prkab1". Wellcome Trust Sanger Institute. 
  4. ^ "Clinical chemistry data for Prkab1". Wellcome Trust Sanger Institute. 
  5. ^ "Haematology data for Prkab1". Wellcome Trust Sanger Institute. 
  6. ^ "Salmonella infection data for Prkab1". Wellcome Trust Sanger Institute. 
  7. ^ "Citrobacter infection data for Prkab1". Wellcome Trust Sanger Institute. 
  8. ^ a b c d 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. 
  9. ^ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  10. ^ "International Knockout Mouse Consortium". 
  11. ^ "Mouse Genome Informatics". 
  12. ^ 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.  edit
  13. ^ Dolgin E (2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718. 
  14. ^ 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. 
  15. ^ 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. 
  16. ^ a b 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. (ENGLAND) 346 (3): 659–69. doi:10.1042/0264-6021:3460659. ISSN 0264-6021. PMC 1220898. PMID 10698692. 
  17. ^ 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. 
  18. ^ 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. PMC 395563. PMID 7813428. 

Further reading[edit]


This article incorporates text from the public domain Pfam and InterPro IPR006828