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PRKAB1 (protein kinase, AMP-activated, beta 1 non-catalytic subunit)

Written2007-09Monserrat Sanchez-Cespedes
Molecular Pathology Program, Spanish National Cancer Center (cnio), Melchor Fernandez Almagro, 3, 28029 Madrid, Spain

(Note : for Links provided by Atlas : click)


Alias_namesprotein kinase, AMP-activated, beta 1 non-catalytic subunit
Other aliasAMPK
AMPK beta
LocusID (NCBI) 5564
Atlas_Id 44100
Location 12q24.23  [Link to chromosome band 12q24]
Location_base_pair Starts at 119667956 and ends at 119681624 bp from pter ( according to hg19-Feb_2009)  [Mapping PRKAB1.png]
Local_order Centromere-H11-BC040553-PRKAB1-CIT-RAB35-telomere.
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)


  PRKAB1 gene structure. UTR: untranslated region.
Description The PRKAB1 gene, with a total genomic size of 13639 bp, is composed of 7 coding exons of varying lengths.
Transcription The human PRKAB1 transcript has approximately 2500-bp and contains an open reading frame of 813 bases, resulting in a predicted protein of 270 amino acid residues. PRKAB mRNA is detected in most tissues.


Description PRKAB1 has a molecular mass of 30382 Da; This protein constitutes a regulatory subunit of the AMP-activated protein kinase (AMPK).
AMPK is an heterotrimer of an alpha catalytic, a beta and a gamma non-catalytic regulatory subunits, each encoded by two or three distinct genes (AMPKalpha1-AMPKalpha2; AMPKbeta1-AMPKbeta2; AMPKgamma1-AMPKgamma2-AMPKgamma3) which have varying tissue and subcellular expression.
Post-translational modifications of PRKAB1 include myristoylation and phosphorylation in vivo at Ser24/25, Ser108 and Ser182. Phosphorylation at Ser108 is required for the activation of the AMPK enzyme, whereas phosphorylation at Ser24/25 and Ser182 affects the localization of the complex.
Expression AMPKbeta1 protein expression is highest in the liver, and testis and low in kidney and skeletal muscle. In contrast, expression of PRKAB2, encoded by a different gene, is higher in skeletal muscle. This indicates a tissue specific pattern of expression of these two regulatory beta subunits.
Localisation AMPKbeta1 localises in the cytoplasm. However nuclear translocation is possible because mutations of Ser24/25 and Ser182 to alanine lead to the redistribution of PRKAB1 to the nucleus.
Function AMPKbeta1, may act as a positive regulator of AMPK activity and it may serve as an adaptor molecule for the catalytic subunit. It has also been reported that AMPKbeta1 contains a glycogen-binding domain (GBD) that may target the heterotrimer to glycogen storage sites.
The heterotrimeric protein AMPK senses low intracellular energy levels upon increased in the AMP/ATP ratio. Binding of AMP results in allosteric activation, inducing phosphorylation on Thr-172 of the AMPKa regulatory subunit (PRKAA) by LKB1 in complex with STE20-related adapter-alpha (STRAD alpha). AMPK activation leads to the modulation of the activity of multiple downstream targets to normalize ATP levels.
Among these substrates is the tuberin protein, the product of the tuberous sclerosis complex 2 gene (TSC2) that upon activation by AMPK represses the activity of the mammalian target of rapamycin, mTOR.
It has been reported that PRKAB1 and PRKAB2 contain a glycogen binding domain that targets AMPK to glycogen.
Moreover, it has been shown that expression of PRKAB1 and PRKAB2 genes, in human cells, may be mediated by p53.
Homology There is a AMPKbeta1 isoform, designated AMPKbeta2, encoded by the PRKAB2 gene. The N-terminal region of beta2 differs significantly from that AMPKbeta1 isoform, suggesting that this region could play a role in isoform-specific AMPK activity.
The AMPKbeta subunit is the mammalian homolog of the S. cerevisiae Sip1p/Sip2p/Gal83p family of proteins that interact with the AMPKa homolog, Snf1p, and are involved in glucose regulation of gene expression.


Note No germ-line or somatic mutations have been reported in the PRKAB1 gene.

To be noted

Although PRKAB1 itself does not seem to be directly implicated in human disease, there is an indirect relationship between AMPKbeta and heart disease and cancer due to the implication of other subunits of the AMPK complex or to the implication of other related kinases:

  • AMPK in heart disease:
    Mutations at the PRAAG2 (encoding the gamma2 subunit of AMP-activated protein kinase) causes glycogen overload, Wolff-Parkinson-White syndrome, arrhythmias, and heart failure.

  • AMPK in cancer:
    LKB1 is a serine/threonin kinase that phosphorylates and activates AMPK. Germ-line mutations at LKB1 lead to the cancer-prone syndrome Peutz-Jeghers syndrome whereas somatic mutations are implicated in the development of non-small cell lung cancer.
  • Bibliography

    The regulation of AMPK beta1, TSC2, and PTEN expression by p53: stress, cell and tissue specificity, and the role of these gene products in modulating the IGF-1-AKT-mTOR pathways.
    Feng Z, Hu W, de Stanchina E, Teresky AK, Jin S, Lowe S, Levine AJ
    Cancer research. 2007 ; 67 (7) : 3043-3053.
    PMID 17409411
    Non-catalytic beta- and gamma-subunit isoforms of the 5'-AMP-activated protein kinase.
    Gao G, Fernandez CS, Stapleton D, Auster AS, Widmer J, Dyck JR, Kemp BE, Witters LA
    The Journal of biological chemistry. 1996 ; 271 (15) : 8675-8681.
    PMID 8621499
    Minireview: the AMP-activated protein kinase cascade: the key sensor of cellular energy status.
    Hardie DG
    Endocrinology. 2003 ; 144 (12) : 5179-5183.
    PMID 12960015
    Complexes between the LKB1 tumor suppressor, STRAD alpha/beta and MO25 alpha/beta are upstream kinases in the AMP-activated protein kinase cascade.
    Hawley SA, Boudeau J, Reid JL, Mustard KJ, Udd L, Mäkelä TP, Alessi DR, Hardie DG
    Journal of biology. 2003 ; 2 (4) : page 28.
    PMID 14511394
    TSC2 mediates cellular energy response to control cell growth and survival.
    Inoki K, Zhu T, Guan KL
    Cell. 2003 ; 115 (5) : 577-590.
    PMID 14651849
    AMPK-beta1 subunit is a p53-independent stress responsive protein that inhibits tumor cell growth upon forced expression.
    Li J, Jiang P, Robinson M, Lawrence TS, Sun Y
    Carcinogenesis. 2003 ; 24 (5) : 827-834.
    PMID 12771025
    Posttranslational modifications of the 5'-AMP-activated protein kinase beta1 subunit.
    Mitchelhill KI, Michell BJ, House CM, Stapleton D, Dyck J, Gamble J, Ullrich C, Witters LA, Kemp BE
    The Journal of biological chemistry. 1997 ; 272 (39) : 24475-24479.
    PMID 9305909
    AMPK beta subunit targets metabolic stress sensing to glycogen.
    Polekhina G, Gupta A, Michell BJ, van Denderen B, Murthy S, Feil SC, Jennings IG, Campbell DJ, Witters LA, Parker MW, Kemp BE, Stapleton D
    Current biology : CB. 2003 ; 13 (10) : 867-871.
    PMID 12747837
    A role for LKB1 gene in human cancer beyond the Peutz-Jeghers syndrome.
    Sanchez-Cespedes M
    Oncogene. 2007 ; 26 (57) : 7825-7832.
    PMID 17599048
    AMP-activated protein kinase isoenzyme family: subunit structure and chromosomal location.
    Stapleton D, Woollatt E, Mitchelhill KI, Nicholl JK, Fernandez CS, Michell BJ, Witters LA, Power DA, Sutherland GR, Kemp BE
    FEBS letters. 1997 ; 409 (3) : 452-456.
    PMID 9224708
    Identification of a novel AMP-activated protein kinase beta subunit isoform that is highly expressed in skeletal muscle.
    Thornton C, Snowden MA, Carling D
    The Journal of biological chemistry. 1998 ; 273 (20) : 12443-12450.
    PMID 9575201
    Post-translational modifications of the beta-1 subunit of AMP-activated protein kinase affect enzyme activity and cellular localization.
    Warden SM, Richardson C, O'Donnell J Jr, Stapleton D, Kemp BE, Witters LA
    The Biochemical journal. 2001 ; 354 (Pt 2) : 275-283.
    PMID 11171104
    LKB1 is the upstream kinase in the AMP-activated protein kinase cascade.
    Woods A, Johnstone SR, Dickerson K, Leiper FC, Fryer LG, Neumann D, Schlattner U, Wallimann T, Carlson M, Carling D
    Current biology : CB. 2003 ; 13 (22) : 2004-2008.
    PMID 14614828
    Identification of phosphorylation sites in AMP-activated protein kinase (AMPK) for upstream AMPK kinases and study of their roles by site-directed mutagenesis.
    Woods A, Vertommen D, Neumann D, Turk R, Bayliss J, Schlattner U, Wallimann T, Carling D, Rider MH
    The Journal of biological chemistry. 2003 ; 278 (31) : 28434-28442.
    PMID 12764152


    This paper should be referenced as such :
    Sanchez-Cespedes, M
    PRKAB1 (protein kinase, AMP-activated, beta 1 non-catalytic subunit)
    Atlas Genet Cytogenet Oncol Haematol. 2008;12(2):151-152.
    Free journal version : [ pdf ]   [ DOI ]
    On line version :

    External links

    HGNC (Hugo)PRKAB1   9378
    Entrez_Gene (NCBI)PRKAB1  5564  protein kinase AMP-activated non-catalytic subunit beta 1
    AliasesAMPK; HAMPKb
    GeneCards (Weizmann)PRKAB1
    Ensembl hg19 (Hinxton)ENSG00000111725 [Gene_View]
    Ensembl hg38 (Hinxton)ENSG00000111725 [Gene_View]  ENSG00000111725 [Sequence]  chr12:119667956-119681624 [Contig_View]  PRKAB1 [Vega]
    ICGC DataPortalENSG00000111725
    TCGA cBioPortalPRKAB1
    AceView (NCBI)PRKAB1
    Genatlas (Paris)PRKAB1
    SOURCE (Princeton)PRKAB1
    Genetics Home Reference (NIH)PRKAB1
    Genomic and cartography
    GoldenPath hg38 (UCSC)PRKAB1  -     chr12:119667956-119681624 +  12q24.23   [Description]    (hg38-Dec_2013)
    GoldenPath hg19 (UCSC)PRKAB1  -     12q24.23   [Description]    (hg19-Feb_2009)
    GoldenPathPRKAB1 - 12q24.23 [CytoView hg19]  PRKAB1 - 12q24.23 [CytoView hg38]
    Mapping of homologs : NCBIPRKAB1 [Mapview hg19]  PRKAB1 [Mapview hg38]
    Gene and transcription
    Genbank (Entrez)AF022116 AJ224515 AK127820 AK301165 AK312495
    RefSeq transcript (Entrez)NM_006253
    RefSeq genomic (Entrez)
    Consensus coding sequences : CCDS (NCBI)PRKAB1
    Cluster EST : UnigeneHs.741184 [ NCBI ]
    CGAP (NCI)Hs.741184
    Alternative Splicing GalleryENSG00000111725
    Gene ExpressionPRKAB1 [ NCBI-GEO ]   PRKAB1 [ EBI - ARRAY_EXPRESS ]   PRKAB1 [ SEEK ]   PRKAB1 [ MEM ]
    Gene Expression Viewer (FireBrowse)PRKAB1 [ Firebrowse - Broad ]
    SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
    GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
    BioGPS (Tissue expression)5564
    GTEX Portal (Tissue expression)PRKAB1
    Human Protein AtlasENSG00000111725-PRKAB1 [pathology]   [cell]   [tissue]
    Protein : pattern, domain, 3D structure
    UniProt/SwissProtQ9Y478   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
    NextProtQ9Y478  [Sequence]  [Exons]  [Medical]  [Publications]
    With graphics : InterProQ9Y478
    Splice isoforms : SwissVarQ9Y478
    Domains : Interpro (EBI)AMPK1_CBM    ASC_dom    ASC_dom_sf    Ig-like_fold    Ig_E-set   
    Domain families : Pfam (Sanger)AMPK1_CBM (PF16561)    AMPKBI (PF04739)   
    Domain families : Pfam (NCBI)pfam16561    pfam04739   
    Domain families : Smart (EMBL)AMPKBI (SM01010)  
    Conserved Domain (NCBI)PRKAB1
    DMDM Disease mutations5564
    Blocks (Seattle)PRKAB1
    PDB (RSDB)4CFE    4CFF    4ZHX    5EZV    5ISO   
    PDB Europe4CFE    4CFF    4ZHX    5EZV    5ISO   
    PDB (PDBSum)4CFE    4CFF    4ZHX    5EZV    5ISO   
    PDB (IMB)4CFE    4CFF    4ZHX    5EZV    5ISO   
    Structural Biology KnowledgeBase4CFE    4CFF    4ZHX    5EZV    5ISO   
    SCOP (Structural Classification of Proteins)4CFE    4CFF    4ZHX    5EZV    5ISO   
    CATH (Classification of proteins structures)4CFE    4CFF    4ZHX    5EZV    5ISO   
    Human Protein Atlas [tissue]ENSG00000111725-PRKAB1 [tissue]
    Peptide AtlasQ9Y478
    IPIIPI00220409   IPI01013083   IPI01011405   IPI01011846   
    Protein Interaction databases
    DIP (DOE-UCLA)Q9Y478
    IntAct (EBI)Q9Y478
    Ontologies - Pathways
    Ontology : AmiGOprotein kinase activity  AMP-activated protein kinase activity  protein binding  nucleus  nucleoplasm  cytoplasm  cytosol  protein phosphorylation  fatty acid biosynthetic process  cell cycle arrest  signal transduction  positive regulation of gene expression  macroautophagy  regulation of macroautophagy  protein kinase binding  nucleotide-activated protein kinase complex  nail development  regulation of catalytic activity  protein heterooligomerization  positive regulation of cold-induced thermogenesis  regulation of signal transduction by p53 class mediator  
    Ontology : EGO-EBIprotein kinase activity  AMP-activated protein kinase activity  protein binding  nucleus  nucleoplasm  cytoplasm  cytosol  protein phosphorylation  fatty acid biosynthetic process  cell cycle arrest  signal transduction  positive regulation of gene expression  macroautophagy  regulation of macroautophagy  protein kinase binding  nucleotide-activated protein kinase complex  nail development  regulation of catalytic activity  protein heterooligomerization  positive regulation of cold-induced thermogenesis  regulation of signal transduction by p53 class mediator  
    Pathways : KEGGFoxO signaling pathway    Circadian rhythm    Insulin signaling pathway    Adipocytokine signaling pathway    Non-alcoholic fatty liver disease (NAFLD)    Hypertrophic cardiomyopathy (HCM)   
    REACTOMEQ9Y478 [protein]
    REACTOME PathwaysR-HSA-9619483 [pathway]   
    NDEx NetworkPRKAB1
    Atlas of Cancer Signalling NetworkPRKAB1
    Wikipedia pathwaysPRKAB1
    Orthology - Evolution
    GeneTree (enSembl)ENSG00000111725
    Phylogenetic Trees/Animal Genes : TreeFamPRKAB1
    Homologs : HomoloGenePRKAB1
    Homology/Alignments : Family Browser (UCSC)PRKAB1
    Gene fusions - Rearrangements
    Fusion : FusionGDB339   
    Fusion : Fusion_HubHSP90B1--PRKAB1    PRKAB1--MGEA5    PRKAB1--OGG1    PRKAB1--RPS2    PRKAB1--SPINK1    PRKAB1--TMEM233    TMEM233--PRKAB1   
    Fusion : QuiverPRKAB1
    Polymorphisms : SNP and Copy number variants
    NCBI Variation ViewerPRKAB1 [hg38]
    dbSNP Single Nucleotide Polymorphism (NCBI)PRKAB1
    Exome Variant ServerPRKAB1
    ExAC (Exome Aggregation Consortium)ENSG00000111725
    GNOMAD BrowserENSG00000111725
    Varsome BrowserPRKAB1
    Genetic variants : HAPMAP5564
    Genomic Variants (DGV)PRKAB1 [DGVbeta]
    DECIPHERPRKAB1 [patients]   [syndromes]   [variants]   [genes]  
    CONAN: Copy Number AnalysisPRKAB1 
    ICGC Data PortalPRKAB1 
    TCGA Data PortalPRKAB1 
    Broad Tumor PortalPRKAB1
    OASIS PortalPRKAB1 [ Somatic mutations - Copy number]
    Somatic Mutations in Cancer : COSMICPRKAB1  [overview]  [genome browser]  [tissue]  [distribution]  
    Somatic Mutations in Cancer : COSMIC3DPRKAB1
    Mutations and Diseases : HGMDPRKAB1
    LOVD (Leiden Open Variation Database)Whole genome datasets
    LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
    LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
    BioMutasearch PRKAB1
    DgiDB (Drug Gene Interaction Database)PRKAB1
    DoCM (Curated mutations)PRKAB1 (select the gene name)
    CIViC (Clinical Interpretations of Variants in Cancer)PRKAB1 (select a term)
    NCG5 (London)PRKAB1
    Cancer3DPRKAB1(select the gene name)
    Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
    Genetic Testing Registry PRKAB1
    NextProtQ9Y478 [Medical]
    Target ValidationPRKAB1
    Huge Navigator PRKAB1 [HugePedia]
    snp3D : Map Gene to Disease5564
    BioCentury BCIQPRKAB1
    Clinical trials, drugs, therapy
    Chemical/Protein Interactions : CTD5564
    Chemical/Pharm GKB GenePA33746
    Clinical trialPRKAB1
    canSAR (ICR)PRKAB1 (select the gene name)
    DataMed IndexPRKAB1
    PubMed165 Pubmed reference(s) in Entrez
    GeneRIFsGene References Into Functions (Entrez)
    REVIEW articlesautomatic search in PubMed
    Last year publicationsautomatic search in PubMed

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    indexed on : Wed Nov 13 21:51:18 CET 2019

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