UniProt Accession

 AAPK1_HUMAN; Q13131; A8MTQ6; B2R7E1; O00286; Q5D0E1; Q86VS1; Q9UNQ4 

Genbank Protein ID

 AC008810; BC048980; AB022017; AK312947; BC037303; AF100763; U22456; Y12856 

Genbank Nucleotide ID

 AAH48980.1; BAA36547.1; BAG35788.1; AAH37303.1; AAD43027.1; AAA64850.1; CAA73361.1 

Protein Name

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

Protein Synonyms/Alias

 AMPK subunit alpha-1; Acetyl-CoA carboxylase kinase; ACACA kinase; Hydroxymethylglutaryl-CoA reductase kinase; HMGCR kinase; Tau-protein kinase PRKAA1 

Gene Name

 PRKAA1 

Gene Synonyms/Alias

 AMPK1 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
40	LGVGTFGKVKVGKHE	acetylation	[1]
40	LGVGTFGKVKVGKHE	ubiquitination	[2]
266	MLQVDPMKRATIKDI	ubiquitination	[2]
280	IREHEWFKQDLPKYL	ubiquitination	[2]
285	WFKQDLPKYLFPEDP	ubiquitination	[3]
396	LDELNPQKSKHQGVR	ubiquitination	[2, 3, 4, 5]
429	AEVCRAIKQLDYEWK	ubiquitination	[2]
457	PVTSTYSKMSLQLYQ	ubiquitination	[4]
485	DDEITEAKSGTATPQ	ubiquitination	[2, 3, 4]

Reference

 [1] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [3] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [4] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [5] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302] 

Functional Description

 Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Regulates lipid synthesis by phosphorylating and inactivating lipid metabolic enzymes such as ACACA, ACACB, GYS1, HMGCR and LIPE; regulates fatty acid and cholesterol synthesis by phosphorylating acetyl-CoA carboxylase (ACACA and ACACB) and hormone-sensitive lipase (LIPE) enzymes, respectively. Regulates insulin-signaling and glycolysis by phosphorylating IRS1, PFKFB2 and PFKFB3. AMPK stimulates glucose uptake in muscle by increasing the translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane, possibly by mediating phosphorylation of TBC1D4/AS160. Regulates transcription and chromatin structure by phosphorylating transcription regulators involved in energy metabolism such as CRTC2/TORC2, FOXO3, histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A, p53/TP53, SREBF1, SREBF2 and PPARGC1A. Acts as a key regulator of glucose homeostasis in liver by phosphorylating CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm. In response to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), leading to promote transcription. Acts as a key regulator of cell growth and proliferation by phosphorylating TSC2, RPTOR and ATG1/ULK1: in response to nutrient limitation, negatively regulates the mTORC1 complex by phosphorylating RPTOR component of the mTORC1 complex and by phosphorylating and activating TSC2. In response to nutrient limitation, promotes autophagy by phosphorylating and activating ATG1/ULK1. AMPK also acts as a regulator of circadian rhythm by mediating phosphorylation of CRY1, leading to destabilize it. May regulate the Wnt signaling pathway by phosphorylating CTNNB1, leading to stabilize it. Also has tau-protein kinase activity: in response to amyloid beta A4 protein (APP) exposure, activated by CAMKK2, leading to phosphorylation of MAPT/TAU; however the relevance of such data remains unclear in vivo. Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1. 

Sequence Annotation

 DOMAIN 27 279 Protein kinase.
 NP_BIND 33 41 ATP (By similarity).
 REGION 302 381 AIS.
 ACT_SITE 150 150 Proton acceptor (By similarity).
 BINDING 56 56 ATP (By similarity).
 MOD_RES 32 32 Phosphothreonine.
 MOD_RES 183 183 Phosphothreonine; by LKB1 and CaMKK2 (By
 MOD_RES 184 184 Phosphoserine (By similarity).
 MOD_RES 269 269 Phosphothreonine (By similarity).
 MOD_RES 356 356 Phosphoserine.
 MOD_RES 360 360 Phosphoserine; by ULK1 (By similarity).
 MOD_RES 368 368 Phosphothreonine; by ULK1 (By
 MOD_RES 382 382 Phosphothreonine.
 MOD_RES 397 397 Phosphoserine; by ULK1 (Probable).
 MOD_RES 467 467 Phosphoserine.
 MOD_RES 486 486 Phosphoserine.
 MOD_RES 488 488 Phosphothreonine; by ULK1 (Probable).
 MOD_RES 490 490 Phosphothreonine.
 MOD_RES 496 496 Phosphoserine.
 MOD_RES 508 508 Phosphoserine (By similarity).  

Keyword

 Alternative splicing; ATP-binding; Autophagy; Biological rhythms; Cholesterol biosynthesis; Cholesterol metabolism; Chromatin regulator; Complete proteome; Cytoplasm; Fatty acid biosynthesis; Fatty acid metabolism; Kinase; Lipid biosynthesis; Lipid metabolism; Magnesium; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Serine/threonine-protein kinase; Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transcription; Transcription regulation; Transferase; Ubl conjugation; Wnt signaling pathway. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 559 AA 

Protein Sequence

Gene Ontology

 GO:0031588; C:AMP-activated protein kinase complex; ISS:UniProtKB.
 GO:0016324; C:apical plasma membrane; IEA:Compara.
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005634; C:nucleus; ISS:UniProtKB.
 GO:0050405; F:[acetyl-CoA carboxylase] kinase activity; IEA:EC.
 GO:0047322; F:[hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity; IEA:EC.
 GO:0004679; F:AMP-activated protein kinase activity; IDA:UniProtKB.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004691; F:cAMP-dependent protein kinase activity; NAS:UniProtKB.
 GO:0003682; F:chromatin binding; ISS:UniProtKB.
 GO:0035174; F:histone serine kinase activity; ISS:UniProtKB.
 GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
 GO:0050321; F:tau-protein kinase activity; IEA:EC.
 GO:0000187; P:activation of MAPK activity; NAS:UniProtKB.
 GO:0006914; P:autophagy; IEA:UniProtKB-KW.
 GO:0007050; P:cell cycle arrest; TAS:Reactome.
 GO:0071361; P:cellular response to ethanol; IEA:Compara.
 GO:0042149; P:cellular response to glucose starvation; ISS:UniProtKB.
 GO:0070301; P:cellular response to hydrogen peroxide; IEA:Compara.
 GO:0071456; P:cellular response to hypoxia; IEA:Compara.
 GO:0006695; P:cholesterol biosynthetic process; IEA:UniProtKB-KW.
 GO:0009631; P:cold acclimation; IEA:Compara.
 GO:0006633; P:fatty acid biosynthetic process; IEA:UniProtKB-KW.
 GO:0055089; P:fatty acid homeostasis; ISS:UniProtKB.
 GO:0019395; P:fatty acid oxidation; IEA:Compara.
 GO:0042593; P:glucose homeostasis; ISS:UniProtKB.
 GO:0006006; P:glucose metabolic process; IEA:Compara.
 GO:0008286; P:insulin receptor signaling pathway; TAS:Reactome.
 GO:0008610; P:lipid biosynthetic process; ISS:UniProtKB.
 GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
 GO:2001274; P:negative regulation of glucose import in response to insulin stimulus; IEA:Compara.
 GO:0046318; P:negative regulation of glucosylceramide biosynthetic process; NAS:UniProtKB.
 GO:0050995; P:negative regulation of lipid catabolic process; ISS:UniProtKB.
 GO:0032007; P:negative regulation of TOR signaling cascade; ISS:UniProtKB.
 GO:0010508; P:positive regulation of autophagy; ISS:UniProtKB.
 GO:0008284; P:positive regulation of cell proliferation; IEA:Compara.
 GO:0045542; P:positive regulation of cholesterol biosynthetic process; NAS:UniProtKB.
 GO:0010628; P:positive regulation of gene expression; IDA:UniProtKB.
 GO:0045821; P:positive regulation of glycolysis; ISS:UniProtKB.
 GO:0051291; P:protein heterooligomerization; IEA:Compara.
 GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
 GO:2000505; P:regulation of energy homeostasis; ISS:UniProtKB.
 GO:0006355; P:regulation of transcription, DNA-dependent; IEA:UniProtKB-KW.
 GO:0060627; P:regulation of vesicle-mediated transport; IEA:Compara.
 GO:0014823; P:response to activity; IEA:Compara.
 GO:0031000; P:response to caffeine; IEA:Compara.
 GO:0001666; P:response to hypoxia; NAS:UniProtKB.
 GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
 GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
 GO:0016055; P:Wnt receptor signaling pathway; IEA:UniProtKB-KW. 

Interpro

 IPR011009; Kinase-like_dom.
 IPR000719; Prot_kinase_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR002290; Ser/Thr_dual-sp_kinase_dom.
 IPR008271; Ser/Thr_kinase_AS. 

Pfam

 PF00069; Pkinase 

SMART

 SM00220; S_TKc 

PROSITE

 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST 

PRINTS