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PRKAA1 (protein kinase AMP-activated catalytic subunit alpha 1)

Written2018-07Esin Gülce Seza, Ismail Güderer, Çagdas Ermis, Sreeparna Banerjee
Department of Biology, Middle East Technical University, 06800 Ankara, Turkey; banerjee@metu.edu.tr

Abstract Protein kinase AMP-activated catalytic subunit alpha 1 (PRKAA1), also known as AMPK α1, is an energy sensor that plays a key role in the regulation of cellular energy metabolism. AMPK α1 is the catalytic subunit of the heterotrimeric AMPK protein with a length of 548 amino acids. A key switch to activate this protein is an alteration in the AMP/ATP ratio. The protein is dysregulated in several human diseases including diabetes and metabolic syndrome, cardiovascular diseases, neurodegenerative diseases and many cancer types (Steinberg and Kemp, 2009). Two isoforms of AMPK exist including AMPK α1 and AMPK α2; however, discrimination between these isoforms for their involvement in certain diseases is currently not possible.

Keywords AMP-activated catalytic subunit alpha 1, PRKAA1, AMPK α1, diabetes, neurodegenerative diseases, cancer

(Note : for Links provided by Atlas : click)

Identity

Alias_namesalpha
1
Alias_symbol (synonym)AMPKa1
Other aliasProtein Kinase AMP-Activated Catalytic Subunit Alpha 1
Protein Kinase, AMP-Activated, Alpha 1 Catalytic Subunit
Hydroxymethylglutaryl-CoA Reductase Kinase
Tau-Protein Kinase PRKAA1
Acetyl-CoA Carboxylase Kinase
AMPK Subunit Alpha-1
EC 2.7.11.1
HMGCR Kinase
ACACA Kinase
AMP-Activated Protein Kinase, Catalytic, Alpha-1
5-AMP-Activated Protein Kinase, Catalytic Alpha-1 Chain
5-AMP-Activated Protein Kinase Catalytic Subunit Alpha-1
AMPK
AMPK1
AMPK Alpha 1
AMP -Activate Kinase Alpha 1 Subunit
EC 2.7.11
EC 2.7.11.26
EC 2.7.11.27
EC 2.7.11.31
HGNC (Hugo) PRKAA1
LocusID (NCBI) 5562
Atlas_Id 43428
Location 5p13.1  [Link to chromosome band 5p13]
Location_base_pair Starts at 40759379 and ends at 40798195 bp from pter ( according to hg19-Feb_2009)  [Mapping PRKAA1.png]
Local_order Starts at 40759379 and ends at 40798195 bp from pter (according to hg38-Dec_2013)
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)

DNA/RNA

Note Detailed genomic configuration of human PRKAA1 gene can be found in https://www.ncbi.nlm.nih.gov/gene/5562.
Description The human AMPK α1 gene is located on 5p13.1 and spans about 39 kb. It contains 12 exons and 2 promoters named as PRKAA1_1 and PRKAA1_2. The gene has 3 isoforms named as PRKAA1_001, PRKAA1_002 and PRKAA1_003.
Transcription The human AMPK α1 gene has 9 transcripts: PRKAA1-201 (1134 bp), PRKAA1-202 (1918 bp), PRKAA1-204 (5088 bp) that code for a protein. PRKAA1-203 (425 bp), PRKAA1-205 (919 bp), PRKAA1-206 (1082 bp), PRKAA1-207 (692 bp), PRKAA1-208 (668 bp) and PRKAA1-209 (436 bp) have retained introns. It also has 7 paralogues and 97 orthologues.
Pseudogene PRKAA1 has one hypothetical pseudogene titled as LOC363815 from Rattus norvegius and is located in 11q23.

Protein

Description AMPK α1 is the catalytic subunit of the heterotrimeric AMPK protein with a length of 548 amino acids. In response to an increase in the AMP/ATP ratio, AMPK gets activated. AMP binds to the non-catalytic gamma subunit of the AMPK protein and induces phosphorylation of Thr-183 (Lizcano et al., 2004). This residue is present in the T-loop region of the catalytic subunit, AMPK α1 (Bright et al., 2009).
There are several known AMPK kinases (AMPKKs). STK11 (LKB1), complexed with STRADA and CAB39 (MO25), is the major upstream regulator of the AMPK, which phosphorylates the AMP bound protein (Shackelford and Shaw, 2009). Ca2+/calmodulin-dependent protein kinase kinase β ( CAMKK2 or CaMKKβ) is also known to be an upstream kinase of AMPK (Sundararaman et al., 2016). TGF-beta-activated kinase-1 ( MAP3K7 or TAK1) may also phosphorylate AMPK α or at least play a role in its activation as loss of TAK1 leads to impaired AMPK activation (Xie et al., 2006).
The AMPK α1 protein consists of several domains (Figure 1). The N-terminal kinase domain carries out the serine/threonine kinase function. The C-terminus regulatory domain contains an α-RIM sensor loop and a β-subunit interaction domain (Crute et al., 1998). A UBA-like auto-inhibitory domain (AID) is present between the α-RIM sensor loop and the kinase domain. AID is required for allosteric regulation via AMP. Absence of this inhibitory region renders the protein independent of AMP but still requires phosphorylation of the activation loop (Crute et al., 1998).
 
  Figure 1. Domains of AMPK-α1. (AID: UBA-like Autoinhibitory Domain)
Expression AMPK α1 is widely expressed across many tissues such as brain, heart, kidney, liver and lung (Stapleton et al., 1996).
Localisation It is primarily localized in the cytoplasm, and with HUVEC cells it was shown that AMPK α1 localizes exclusively in the cytoskeleton (Pinter et al., 2012).
Function AMPK α1, in its active form, phosphorylates many downstream proteins. These phosphorylated target proteins of AMPK regulate metabolism, autophagy, cell growth and proliferation, and cell polarity (Hardie, 2011). AMPK exists as an obligate heterotrimer in cells (Mihaylova and Shaw, 2011), and all the functions that will be mentioned in this section are carried out by the α1 subunit in this obligate heterotrimer complex.
  • Cellular Metabolism
    AMPK is activated when there is energy stress in the cell manifested by an increase in the AMP/ATP ratio. In response to this stress, AMPK activates catabolic pathways while inhibiting anabolic pathways.
    • Glycolysis
      One of the key catabolic pathways for energy generation, glycolysis, is upregulated through AMPK signalling. In order increase glucose uptake to the cell, AMPK activates (induces translocation, short term response) and increases protein expression (longer term response) of SLC2A1 (GLUT1) and SLC2A4 (GLUT4) (Fryer et al., 2002). Also, 6-phosphofructo-2-kinase ( PFKFB3 or PFK-2) gets phosphorylated and activated by AMPK which enhances glycolysis (Marsin et al., 2000). Glycogen synthesis (anabolic pathway) is inhibited by the phosphorylation of glycogen synthase.
    • Gluconeogenesis
      Anabolic pathways such as gluconeogenesis that enhance glucose levels are inhibited by repression of transcripts that encode for gluconeogenesis enzymes. CRTC2, coactivator of the cyclic AMP response element-binding protein CREB, gets phosphorylated and inhibited (excluded from the nucleus) by AMPK. This leads to disruption of CREB-CRTC2 complex and inhibition of CREB-dependent gluconeogenesis (Lee et al., 2010). Transcription of mRNAs encoding glucose-6-phosphatase and phosphoenolpyruvate carboxykinase are inhibited via this mechanism. Also, class IIA histones, which can activate the FOXO family of transcription factors via HDAC3 recruitment, gets phosphorylated and excluded from the nucleus. This decrease in activity of FOXO family of transcription factors leads to reduced expression of gluconeogenesis genes (Mihaylova et al., 2011).
    • Lipid Metabolism
      In AMPK activated cells, fatty acid uptake is increased by translocation of fatty acid translocase, CD36 (FAT), to the cellular membrane (Bonen et al., 2007). Meanwhile, acetyl-CoA carboxylase ( ACACA ACC1), which catalyses the rate-limiting step of fatty acid synthesis (Hofbauer et al., 2014), gets phosphorylated and this phosphorylation inhibits the enzymatic activity of ACC1. Along with CD36 (FAT) translocation to the membrane, ACACB (ACC2) is also inhibited which leads to increased fatty acid uptake into mitochondria due to decreased amounts of malonyl-CoA in the cell (Merrill et al., 1997).
    • Protein Synthesis
      Synthesis of proteins is an enormous energy consuming process for the cells. MTOR, in its active form, promotes cell proliferation and protein synthesis. Activated AMPK inhibits mTOR via phosphorylation of upstream regulator TSC2 (Huang and Manning, 2008) and its subunit RPTOR (Raptor) (Gwinn et al., 2008). Also, eukaryotic elongation factor 2 ( EEF2) is required for the elongation of translation in eukaryotes. EEF2 kinase gets activated by AMPK which inhibits EEF2 via phosphorylation, resulting in inhibition of protein synthesis (Horman et al., 2002).
  • Autophagy
    Excess or dysfunctional organelles get "eaten up" by the cell over time, this process is called autophagy and it can give cells the advantage of recycling important nutrients, especially during starvation. It is known that mTORc1 inhibits autophagy via inhibition of ULK1 (Chan, 2009), and AMPK downregulates mTORc1 via phosphorylation of TSC2 and Raptor. This was thought to be the main mechanism by which AMPK activates autophagy. Recently, it was found that initiator of autophagy, the ULK1 protein kinase, directly interacts with AMPK, and gets phosphorylated and activated by AMPK (Roach, 2011).
  • Cell Growth and Proliferation
    AMPK can act as a metabolic checkpoint via inhibition of cellular growth when energy status in the cell is compromised (Mihaylova and Shaw, 2011). Processes of cellular growth and proliferation require many events to take place in the cell such as protein and lipid synthesis. As mentioned above, AMPK can decrease the synthesis of proteins and subsequently cell proliferation through the inhibition of mTORc1.
    mTORc1 also controls lipid biosynthesis via a transcription factor named as sterol regulatory element-binding protein-1, SREBF1 (SREBP-1) (Laplante and Sabatini, 2009). SREBP-1 targets lipogenic genes such as ACC (Brown et al., 2007); fatty acid synthase, FASN (Jung et al., 2012); and stearoyl-CoA desaturase 1, SCD (Mauvoisin et al., 2007). mTORc1 inhibition by AMPK along with the previously mentioned inhibition of ACC1 leads to decreased lipid synthesis in the cell.
    Other than metabolic effects, AMPK also activates checkpoint regulators such as TP53 via inactivation of SIRT1 (Sirtuin 1) (Lee et al., 2012) and phosphorylation at Ser-15 (Jones et al., 2005), as well as CDKN1B (cyclin-dependent kinase inhibitor p27(Kip1)) via phosphorylation at Thr198 (Liang et al., 2007).
  • Cell Polarity
    LKB1-null and AMPK-null Drosophila models show lethal phenotypes with severe defects in cell polarity and mitosis (Lee at al., 2007). AMPK activation was reported to rescue LKB1-null phenotype while non-muscle myosin regulatory light chain (MRLC) phopshomimetic mutants rescued AMPK-null models (Lee at al., 2007). However, another study reported that in mammalian MDCK cells, AMPK activation did not change phosphorylation of MRLC, rather AFDN (afadin) was identified as AMPK substrate for phosphorylation (Zhang et al., 2011). Activation via AMPK leads to deposition of junction components in the cellular membrane.
    The microtubule plus-end-tracking protein CLIP1 (CLIP-170) is activated via phosphorylation by AMPK. CLIP-170 phosphorylation is required for microtubule dynamics and the regulation of directional cell migration (Nakano et al., 2010). The same study reported that inhibition of AMPK leads to accumulation of CLIP-170 at microtubule tips and slower tubulin polymerization (Nakano et al., 2010). Thus, AMPK also controls microtubule dynamics through CLIP-170 phosphorylation.
 
  Figure 2. Functions of AMPK
Homology AMPK α1, with its kinase and regulatory domains, is a very well conserved protein.
Homologs of Human PRKAA1 (AMPK α1)
  Gene Name

  Organism

  NCBI RefSeq

  Protein

  Length (aa)

  PRKAA1

  H. sapiens

  NP_996790.3

  5'-AMP-activated protein kinase catalytic subunit alpha-1

  574

  PRKAA1

   P. troglodytes

  XP_009447514.1

  5'-AMP-activated protein kinase catalytic subunit alpha-1

  574

  PRKAA1

  M. mulatta

  XP_001086410.2

  5'-AMP-activated protein kinase catalytic subunit alpha-1

  559

  PRKAA1

  C. lupus

  XP_022273603.1

  5'-AMP-activated protein kinase catalytic subunit alpha-1

  573

  PRKAA1

  B. taurus

  NP_001103272

  5'-AMP-activated protein kinase catalytic subunit alpha-1

  458

  Prkaa1

  M. musculus

  NP_001013385.3

  5'-AMP-activated protein kinase catalytic subunit alpha-1

  559

  Prkaa1

  R. norvegicus

  NP_062015.2

  5'-AMP-activated protein kinase catalytic subunit alpha-1

  559

  PRKAA1

  G. gallus

  NP_001034692.1

  5'-AMP-activated protein kinase catalytic subunit alpha-1

  560

  prkaa1

  X. tropicalis

  NP_001120434.1

  5'-AMP-activated protein kinase catalytic subunit alpha-1

  551

  prkaa1

  D. rerio

  NP_001103756.1

  5'-AMP-activated protein kinase catalytic subunit alpha-1

  573

  KIN10

  A. thaliana

  NP_001118546.1

  SNF1 kinase homolog 10

  512

  KIN11

  A. thaliana

  NP_974374.1

  SNF1 kinase homolog 11

  512

  Os05g0530500

  O. sativa

  XP_015639849.1

  SNF1-related protein kinase catalytic subunit alpha KIN10

  505

Implicated in

Note AMPK, a central switch determining the AMP/ATP ratio, is dysregulated in several human diseases including diabetes and metabolic syndrome, cardiovascular diseases, neurodegenerative diseases and several different cancer types (Steinberg and Kemp, 2009). Both isoforms of AMPK: AMPK α1 and AMPK α2 may be involved in these diseases. AMPK was shown to negatively regulate the Warburg effect in genetically ablated AMPK- α1 cancer models in vivo (Faubert et al., 2013); therefore, AMPK can be classified as tumour suppressor although there is also evidence of negative regulation of AMPK by tumour suppressors or proto-oncogenes (Li et al., 2017; Yan et al., 2014).
  
Entity Huntington's Disease
Note Huntington's disease (HD) is a neurodegenerative disease where the AMPKα1 isoform is known to be activated in the caudate nucleus and frontal cortex of humans. Activated AMPKα1 was reported to accumulate in the nuclei in these specific regions of the brain of HD patients. Brain atrophy, facilitated neuronal loss and increased aggregation of huntingtin ( HTT) protein was observed in a transgenic mouse model with Huntington's disease, which had overactivated AMPKα1. Ameliorated cell death and down-regulation of BCL2 (by mutant Htt) was achieved by prevention of nuclear translocation or inactivation of AMPK- α1 (Ju et al., 2011).
  
  
Entity Prostate Cancer
Note In prostate cancer, the androgen receptor ( AR) plays a critical role in the regulation of cell proliferation and death. There is evidence that AR related progression of prostate cancer correlates with activated AMPK levels. Androgen-mediated AMPK activity was reported to increase the levels of intracellular ATP and PPARGC1A (peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α))-mediated mitochondrial biogenesis. siRNA-mediated knockdown of AMPKα1, the predominant isoform correlated with poor prognosis in prostate cancer patients, in LNCaP and YCaP human prostate cancer cells reduced the levels of PGC-1α, which is overexpressed in clinical cancer samples (Tennakoon et al., 2015).
5- ATIC (Aminoimidazole-4-carboxamide ribonucleotide (AICAR)), is an AMPK agonist that enhances phosphorylation of AMPK- α1 at Thr-172 and its downstream target ACC at Ser-79. Prostate cancer cell lines infected with lentiviral shRNA against AMPK- α1 were shown to almost block AICAR-induced AMPK phosphorylation. AICAR-induced cytotoxicity in prostate cancer cells was slightly more potent than other AMPK activators such as A-769662 and Compound 13. It has been suggested that AICAR-induced cytotoxicity was not dependent of AMPK activation but might play a pro-survival role in prostate cancer cells (Guo et al., 2016).
  
  
Entity Colorectal Cancer
Note The current literature suggests that activation of AMPK through natural compounds such as berberine, epigallocatechin gallate or quercetin can enhance apoptosis through the upregulation and phosphorylation of TP53 at Ser15, inhibition of COX-2 and mitigation of inflammation as well as delay in cell cycle progression (Sun and Xhu, 2017). AMPKα1 is expressed in almost all colorectal cancer cell lines; however, AMPKα2 expression is limited to some cell lines. Although siRNA-mediated AMPKα1 knock down has no effect on cell death, AMPKα2 depletion was shown to induce cell death in both HCT116 and SW480 cell lines. A competitive inhibitor of AMPK, 5'-hydroxy-staurosporine, was identified by FUSION (Functional Signature Ontology), a method to screen natural compounds for the identification of AMPK inhibitors. Colorectal cancer cell lines were reported to be more sensitive to 5'-hydroxy-staurosporine compared to non-transformed human colon epithelial cells (Das et al., 2018).
Another study suggests that Icaritin (a flavonoid with anti-tumorigenic activity) was reported to induce AMPK signaling in colorectal cancer (CRC) and it also activates autophagy. AMPK-α1 knockdown (shRNA or siRNA mediated) inhibited icaritin-activated autophagy but increased cell death in CRC both in vitro and in vivo (Zhou et al., 2017).
  
  
Entity Type 2 Diabetes
Note AMPK is known to be dysregulated in patients with metabolic syndrome or type 2 Diabetes. Activation of AMPK either through the alteration of the AMP/ATP ratio of by pharmacological agonists can improve insulin sensitivity and metabolic health. In the primary metabolic tissues such as skeletal muscles, cardiac muscle, liver and adipose tissue, activation of AMPK was reported to stimulate glucose uptake, fatty acid oxidation, glucose transporter type (GLUT)4 translocation (in skeletal muscles), mitochondrial biogenesis, while inhibiting gluconeogenesis (in the liver) as well as protein, fatty acid, cholesterol and glycogen synthesis. AMPK is also known to inhibit insulin secretion from pancreatic β-cells and can signals to enhance food intake in the hypothalamus. All of these are beneficial for Type 2 diabetes (Coughlan et al., 2014). In an animal model of type 2 diabetes established by the Otsuka Long-Evans Tokushima Fatty (OLETF) rat, which had chronic and slowly progressive hyperglycemia and hyperlipidemia, overexpression of adenoviral-mediated AMPK-α1 showed a modest decrease in blood glucose level although glucose tolerance was not recovered completely. Moreover, plasma triglyceride level and hepatic triglyceride contents were also slightly decreased (Seo et al., 2009).
  
  
Entity Aging
Note Dietary restriction (DR), a process of reduced food intake without inducing malnutrition, elicits a low-energy state in the organism, which in turn delays ageing in species ranging from yeast to primates through the activation of nutrient-sensing pathways such as AMPK (Burkewitz et al, 2014). For example, feeding C. elegans 2-deoxy-D glucose leading to the inhibition of glycolysis and glucose metabolism increased the lifespan of the worms in an aak-2 (catalytic subunit of AMPK in C. elegans) dependent manner (Schulz et al., 2007). In rat EDL (extensor digitorum longus) muscle, AMPK-α1 protein level was reported to be higher in older rats compared to younger rats. On the other hand, young rats showed higher expression of AMPK-α2 proteins than the older group. EDL cells treated with AICAR showed increased AMPK-α2 activity in both age groups, while AMPK-α1 activity was increased only in the young group. AMPK-α1 activity was not changed in the EDL muscles that were stimulated by high frequency electrical in the young group (Thompson et al., 2009).
  

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J Physiol 2009; 587(Pt 9): 2077-86
PMID 19273578
 
A pivotal role for endogenous TGF-beta-activated kinase-1 in the LKB1/AMP-activated protein kinase energy-sensor pathway.
Xie M, Zhang D, Dyck JR, Li Y, Zhang H, Morishima M, Mann DL, Taffet GE, Baldini A, Khoury DS, Schneider MD.
Proc Natl Acad Sci U S A 2006; 291(28): 14410-29.
PMID 27226623
 
The tumor suppressor folliculin regulates AMPK-dependent metabolic transformation.
Yan M, Gingras MC, Dunlop EA, Nouüt Y, Dupuy F, Jalali Z, Possik E, Coull BJ, Kharitidi D, Dydensborg AB, Faubert B, Kamps M, Sabourin S, Preston RS, Davies DM, Roughead T, Chotard L, van Steensel MA, Jones R, Tee AR, Pause A.
J Clin Invest 2014; 124(6): 2640-50.
PMID 24762438
 
AMP-activated protein kinase (AMPK) activation and glycogen synthase kinase-3? (GSK-3?) inhibition induce Ca2+-independent deposition of tight junction components at the plasma membrane.
Zhang L, Jouret F, Rinehart J, Sfakianos J, Mellman I, Lifton RP, Young LH, Caplan MJ.
J Biol Chem 2011; 286(19): 16879-90.
PMID 21383016
 
AMPK-autophagy inhibition sensitizes icaritin-induced anti-colorectal cancer cell activity.
Zhou C, Gu J, Zhang G, Dong D, Yang Q, Chen MB, Xu D.
Oncotarget 2017; 8(9): 14736-14747
PMID 28103582
 

Citation

This paper should be referenced as such :
Seza, E.G., Güderer, I., Ermis, C. Banerjee, S.
PRKAA1 (protein kinase AMP-activated catalytic subunit alpha 1);
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Genes/PRKAA1ID43428ch5p13.html


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ]
  t(5;5)(p13;p13) PRKAA1/TTC33


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 8 ]
  Lung: Translocations in Squamous Cell Carcinoma
PRKAA1/TTC33 (5p13)
PRKAA1/TTC33 (5p13)
PRKAA1/TTC33 (5p13)
PRKAA1/TTC33 (5p13)
PRKAA1/TTC33 (5p13)
PRKAA1/TTC33 (5p13)
t(5;8)(p13;p11) EIF4EBP1/PRKAA1


External links

Nomenclature
HGNC (Hugo)PRKAA1   9376
Cards
AtlasPRKAA1ID43428ch5p13
Entrez_Gene (NCBI)PRKAA1  5562  protein kinase AMP-activated catalytic subunit alpha 1
AliasesAMPK; AMPKa1
GeneCards (Weizmann)PRKAA1
Ensembl hg19 (Hinxton)ENSG00000132356 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000132356 [Gene_View]  ENSG00000132356 [Sequence]  chr5:40759379-40798195 [Contig_View]  PRKAA1 [Vega]
ICGC DataPortalENSG00000132356
TCGA cBioPortalPRKAA1
AceView (NCBI)PRKAA1
Genatlas (Paris)PRKAA1
WikiGenes5562
SOURCE (Princeton)PRKAA1
Genetics Home Reference (NIH)PRKAA1
Genomic and cartography
GoldenPath hg38 (UCSC)PRKAA1  -     chr5:40759379-40798195 -  5p13.1   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)PRKAA1  -     5p13.1   [Description]    (hg19-Feb_2009)
EnsemblPRKAA1 - 5p13.1 [CytoView hg19]  PRKAA1 - 5p13.1 [CytoView hg38]
Mapping of homologs : NCBIPRKAA1 [Mapview hg19]  PRKAA1 [Mapview hg38]
OMIM602739   
Gene and transcription
Genbank (Entrez)AB022017 AF100763 AK024252 AK307546 AK312947
RefSeq transcript (Entrez)NM_001355028 NM_001355029 NM_001355034 NM_001355035 NM_001355036 NM_001355037 NM_006251 NM_206907
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)PRKAA1
Cluster EST : UnigeneHs.43322 [ NCBI ]
CGAP (NCI)Hs.43322
Alternative Splicing GalleryENSG00000132356
Gene ExpressionPRKAA1 [ NCBI-GEO ]   PRKAA1 [ EBI - ARRAY_EXPRESS ]   PRKAA1 [ SEEK ]   PRKAA1 [ MEM ]
Gene Expression Viewer (FireBrowse)PRKAA1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)5562
GTEX Portal (Tissue expression)PRKAA1
Human Protein AtlasENSG00000132356-PRKAA1 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ13131   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ13131  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ13131
Splice isoforms : SwissVarQ13131
PhosPhoSitePlusQ13131
Domaine pattern : Prosite (Expaxy)PROTEIN_KINASE_ATP (PS00107)    PROTEIN_KINASE_DOM (PS50011)    PROTEIN_KINASE_ST (PS00108)   
Domains : Interpro (EBI)AMPK_C    KA1/Ssp2_C    Kinase-like_dom_sf    Prot_kinase_dom    Protein_kinase_ATP_BS    Ser/Thr_kinase_AS   
Domain families : Pfam (Sanger)AdenylateSensor (PF16579)    Pkinase (PF00069)   
Domain families : Pfam (NCBI)pfam16579    pfam00069   
Domain families : Smart (EMBL)S_TKc (SM00220)  
Conserved Domain (NCBI)PRKAA1
DMDM Disease mutations5562
Blocks (Seattle)PRKAA1
PDB (SRS)4RED    4RER    4REW    5EZV   
PDB (PDBSum)4RED    4RER    4REW    5EZV   
PDB (IMB)4RED    4RER    4REW    5EZV   
PDB (RSDB)4RED    4RER    4REW    5EZV   
Structural Biology KnowledgeBase4RED    4RER    4REW    5EZV   
SCOP (Structural Classification of Proteins)4RED    4RER    4REW    5EZV   
CATH (Classification of proteins structures)4RED    4RER    4REW    5EZV   
SuperfamilyQ13131
Human Protein Atlas [tissue]ENSG00000132356-PRKAA1 [tissue]
Peptide AtlasQ13131
HPRD04115
IPIIPI00792482   IPI00410287   IPI00061282   
Protein Interaction databases
DIP (DOE-UCLA)Q13131
IntAct (EBI)Q13131
FunCoupENSG00000132356
BioGRIDPRKAA1
STRING (EMBL)PRKAA1
ZODIACPRKAA1
Ontologies - Pathways
QuickGOQ13131
Ontology : AmiGOactivation of MAPK activity  response to hypoxia  chromatin binding  protein kinase activity  protein serine/threonine kinase activity  AMP-activated protein kinase activity  AMP-activated protein kinase activity  AMP-activated protein kinase activity  cAMP-dependent protein kinase activity  protein binding  ATP binding  intracellular  nucleus  nucleus  nucleoplasm  cytoplasm  cytoplasm  cytosol  cytosol  glucose metabolic process  transcription, DNA-templated  protein phosphorylation  protein phosphorylation  fatty acid biosynthetic process  cholesterol biosynthetic process  cell cycle arrest  signal transduction  protein C-terminus binding  positive regulation of cell proliferation  lipid biosynthetic process  response to UV  cold acclimation  response to gamma radiation  positive regulation of autophagy  positive regulation of autophagy  positive regulation of autophagy  positive regulation of gene expression  negative regulation of gene expression  response to activity  Wnt signaling pathway  macroautophagy  apical plasma membrane  nuclear speck  fatty acid oxidation  axon  dendrite  response to caffeine  nucleotide-activated protein kinase complex  nucleotide-activated protein kinase complex  nucleotide-activated protein kinase complex  cellular response to nutrient levels  negative regulation of TOR signaling  negative regulation of TOR signaling  regulation of peptidyl-serine phosphorylation  cellular response to oxidative stress  histone serine kinase activity  histone-serine phosphorylation  intracellular signal transduction  cellular response to glucose starvation  cellular response to glucose starvation  glucose homeostasis  regulation of circadian rhythm  neuronal cell body  negative regulation of apoptotic process  positive regulation of cholesterol biosynthetic process  positive regulation of glycolytic process  negative regulation of glucosylceramide biosynthetic process  metal ion binding  [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity  rhythmic process  positive regulation of skeletal muscle tissue development  tau-protein kinase activity  [acetyl-CoA carboxylase] kinase activity  negative regulation of lipid catabolic process  protein heterooligomerization  fatty acid homeostasis  regulation of vesicle-mediated transport  motor behavior  CAMKK-AMPK signaling cascade  CAMKK-AMPK signaling cascade  CAMKK-AMPK signaling cascade  neuron cellular homeostasis  cellular response to hydrogen peroxide  regulation of microtubule cytoskeleton organization  cellular response to calcium ion  cellular response to glucose stimulus  cellular response to ethanol  cellular response to prostaglandin E stimulus  cellular response to organonitrogen compound  cellular response to hypoxia  energy homeostasis  energy homeostasis  response to camptothecin  positive regulation of mitochondrial transcription  positive regulation of cellular protein localization  positive regulation of protein targeting to mitochondrion  negative regulation of tubulin deacetylation  positive regulation of peptidyl-lysine acetylation  negative regulation of glucose import in response to insulin stimulus  
Ontology : EGO-EBIactivation of MAPK activity  response to hypoxia  chromatin binding  protein kinase activity  protein serine/threonine kinase activity  AMP-activated protein kinase activity  AMP-activated protein kinase activity  AMP-activated protein kinase activity  cAMP-dependent protein kinase activity  protein binding  ATP binding  intracellular  nucleus  nucleus  nucleoplasm  cytoplasm  cytoplasm  cytosol  cytosol  glucose metabolic process  transcription, DNA-templated  protein phosphorylation  protein phosphorylation  fatty acid biosynthetic process  cholesterol biosynthetic process  cell cycle arrest  signal transduction  protein C-terminus binding  positive regulation of cell proliferation  lipid biosynthetic process  response to UV  cold acclimation  response to gamma radiation  positive regulation of autophagy  positive regulation of autophagy  positive regulation of autophagy  positive regulation of gene expression  negative regulation of gene expression  response to activity  Wnt signaling pathway  macroautophagy  apical plasma membrane  nuclear speck  fatty acid oxidation  axon  dendrite  response to caffeine  nucleotide-activated protein kinase complex  nucleotide-activated protein kinase complex  nucleotide-activated protein kinase complex  cellular response to nutrient levels  negative regulation of TOR signaling  negative regulation of TOR signaling  regulation of peptidyl-serine phosphorylation  cellular response to oxidative stress  histone serine kinase activity  histone-serine phosphorylation  intracellular signal transduction  cellular response to glucose starvation  cellular response to glucose starvation  glucose homeostasis  regulation of circadian rhythm  neuronal cell body  negative regulation of apoptotic process  positive regulation of cholesterol biosynthetic process  positive regulation of glycolytic process  negative regulation of glucosylceramide biosynthetic process  metal ion binding  [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity  rhythmic process  positive regulation of skeletal muscle tissue development  tau-protein kinase activity  [acetyl-CoA carboxylase] kinase activity  negative regulation of lipid catabolic process  protein heterooligomerization  fatty acid homeostasis  regulation of vesicle-mediated transport  motor behavior  CAMKK-AMPK signaling cascade  CAMKK-AMPK signaling cascade  CAMKK-AMPK signaling cascade  neuron cellular homeostasis  cellular response to hydrogen peroxide  regulation of microtubule cytoskeleton organization  cellular response to calcium ion  cellular response to glucose stimulus  cellular response to ethanol  cellular response to prostaglandin E stimulus  cellular response to organonitrogen compound  cellular response to hypoxia  energy homeostasis  energy homeostasis  response to camptothecin  positive regulation of mitochondrial transcription  positive regulation of cellular protein localization  positive regulation of protein targeting to mitochondrion  negative regulation of tubulin deacetylation  positive regulation of peptidyl-lysine acetylation  negative regulation of glucose import in response to insulin stimulus  
Pathways : KEGG   
REACTOMEQ13131 [protein]
REACTOME PathwaysR-HSA-6804756 [pathway]   
NDEx NetworkPRKAA1
Atlas of Cancer Signalling NetworkPRKAA1
Wikipedia pathwaysPRKAA1
Orthology - Evolution
OrthoDB5562
GeneTree (enSembl)ENSG00000132356
Phylogenetic Trees/Animal Genes : TreeFamPRKAA1
HOVERGENQ13131
HOGENOMQ13131
Homologs : HomoloGenePRKAA1
Homology/Alignments : Family Browser (UCSC)PRKAA1
Gene fusions - Rearrangements
Fusion : MitelmanEIF4EBP1/PRKAA1 [8p11.23/5p13.1]  [t(5;8)(p13;p11)]  
Fusion : QuiverPRKAA1
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerPRKAA1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)PRKAA1
dbVarPRKAA1
ClinVarPRKAA1
1000_GenomesPRKAA1 
Exome Variant ServerPRKAA1
ExAC (Exome Aggregation Consortium)ENSG00000132356
GNOMAD BrowserENSG00000132356
Varsome BrowserPRKAA1
Genetic variants : HAPMAP5562
Genomic Variants (DGV)PRKAA1 [DGVbeta]
DECIPHERPRKAA1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisPRKAA1 
Mutations
ICGC Data PortalPRKAA1 
TCGA Data PortalPRKAA1 
Broad Tumor PortalPRKAA1
OASIS PortalPRKAA1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICPRKAA1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDPRKAA1
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 PRKAA1
DgiDB (Drug Gene Interaction Database)PRKAA1
DoCM (Curated mutations)PRKAA1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)PRKAA1 (select a term)
intoGenPRKAA1
NCG5 (London)PRKAA1
Cancer3DPRKAA1(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM602739   
Orphanet
DisGeNETPRKAA1
MedgenPRKAA1
Genetic Testing Registry PRKAA1
NextProtQ13131 [Medical]
TSGene5562
GENETestsPRKAA1
Target ValidationPRKAA1
Huge Navigator PRKAA1 [HugePedia]
snp3D : Map Gene to Disease5562
BioCentury BCIQPRKAA1
ClinGenPRKAA1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD5562
Chemical/Pharm GKB GenePA33744
Clinical trialPRKAA1
Miscellaneous
canSAR (ICR)PRKAA1 (select the gene name)
Other databasehttps://www.genenames.org/cgi-bin/gene_symbol_report?hgnc_id=9376
Other databasehttps://www.ncbi.nlm.nih.gov/gene/5562
Other databasehttps://epd.vital-it.ch/cgi-bin/get_doc?db=hgEpdNew&format=genome&entry=PRKAA1_1
Other databaseDATABASES bin/get_doc?db=hgEpdNew&format=genome&entry=PRKAA1_2
Other databasehttps://www.proteinatlas.org/ENSG00000132356-PRKAA1/tissue#gene_information
Other databasehttps://www.ncbi.nlm.nih.gov/gene/?Term=related_functional_gene_65248%5Bgroup%5D
Other databasehttps://www.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000132356;r=5:40759379-40798374
Probes
Litterature
PubMed414 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMinePRKAA1
EVEXPRKAA1
GoPubMedPRKAA1
iHOPPRKAA1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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