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Q13131 (AAPK1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 155. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
5'-AMP-activated protein kinase catalytic subunit alpha-1

Short name=AMPK subunit alpha-1
EC=2.7.11.1
Alternative name(s):
Acetyl-CoA carboxylase kinase
Short name=ACACA kinase
EC=2.7.11.27
Hydroxymethylglutaryl-CoA reductase kinase
Short name=HMGCR kinase
EC=2.7.11.31
Tau-protein kinase PRKAA1
EC=2.7.11.26
Gene names
Name:PRKAA1
Synonyms:AMPK1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length559 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.9 Ref.10 Ref.12 Ref.13 Ref.17 Ref.20 Ref.21 Ref.22 Ref.26 Ref.32 Ref.33 Ref.37

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

ATP + [tau protein] = ADP + [tau protein] phosphate.

ATP + [hydroxymethylglutaryl-CoA reductase (NADPH)] = ADP + [hydroxymethylglutaryl-CoA reductase (NADPH)] phosphate.

ATP + [acetyl-CoA carboxylase] = ADP + [acetyl-CoA carboxylase] phosphate.

Cofactor

Magnesium.

Enzyme regulation

Activated by phosphorylation on Thr-183. Binding of AMP to non-catalytic gamma subunit (PRKAG1, PRKAG2 or PRKAG3) results in allosteric activation, inducing phosphorylation on Thr-183. AMP-binding to gamma subunit also sustains activity by preventing dephosphorylation of Thr-183. ADP also stimulates Thr-183 phosphorylation, without stimulating already phosphorylated AMPK. ATP promotes dephosphorylation of Thr-183, rendering the enzyme inactive. Under physiological conditions AMPK mainly exists in its inactive form in complex with ATP, which is much more abundant than AMP. AMPK is activated by antihyperglycemic drug metformin, a drug prescribed to patients with type 2 diabetes: in vivo, metformin seems to mainly inhibit liver gluconeogenesis. However, metformin can be used to activate AMPK in muscle and other cells in culture or ex vivo (Ref.11). Selectively inhibited by compound C (6-[4-(2-Piperidin-1-yl-ethoxy)-phenyl)]-3-pyridin-4-yl-pyyrazolo[1,5-a] pyrimidine. Activated by resveratrol, a natural polyphenol present in red wine, and S17834, a synthetic polyphenol. Ref.11 Ref.14 Ref.15 Ref.16 Ref.38

Subunit structure

AMPK is a heterotrimer of an alpha catalytic subunit (PRKAA1 or PRKAA2), a beta (PRKAB1 or PRKAB2) and a gamma non-catalytic subunits (PRKAG1, PRKAG2 or PRKAG3). Interacts with FNIP1 and FNIP2. Ref.18 Ref.23 Ref.28 Ref.38

Subcellular location

Cytoplasm. Nucleus. Note: In response to stress, recruited by p53/TP53 to specific promoters. Ref.17

Domain

The AIS (autoinhibitory sequence) region shows some sequence similarity with the ubiquitin-associated domains and represses kinase activity. Ref.8 Ref.19

Post-translational modification

Ubiquitinated By similarity.

Phosphorylated at Thr-183 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Also phosphorylated at Thr-183 by CAMKK2; triggered by a rise in intracellular calcium ions, without detectable changes in the AMP/ATP ratio. CAMKK1 can also phosphorylate Thr-183, but at a much lower level. Dephosphorylated by protein phosphatase 2A and 2C (PP2A and PP2C). Phosphorylated by ULK1 and ULK2; leading to negatively regulate AMPK activity and suggesting the existence of a regulatory feedback loop between ULK1, ULK2 and AMPK. Dephosphorylated by PPM1A and PPM1B. Ref.14 Ref.15 Ref.16 Ref.35 Ref.41

Sequence similarities

Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.

Contains 1 protein kinase domain.

Sequence caution

The sequence AAA64850.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence AAD43027.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence AAH37303.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence BAA36547.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence BAG35788.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
   Biological processAutophagy
Biological rhythms
Cholesterol biosynthesis
Cholesterol metabolism
Fatty acid biosynthesis
Fatty acid metabolism
Lipid biosynthesis
Lipid metabolism
Steroid biosynthesis
Steroid metabolism
Sterol biosynthesis
Sterol metabolism
Transcription
Transcription regulation
Wnt signaling pathway
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandATP-binding
Magnesium
Metal-binding
Nucleotide-binding
   Molecular functionChromatin regulator
Kinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processWnt signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

activation of MAPK activity

Non-traceable author statement PubMed 11546797. Source: UniProtKB

autophagy

Inferred from electronic annotation. Source: UniProtKB-KW

cell cycle arrest

Traceable author statement. Source: Reactome

cellular response to ethanol

Inferred from electronic annotation. Source: Ensembl

cellular response to glucose starvation

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to hydrogen peroxide

Inferred from electronic annotation. Source: Ensembl

cellular response to hypoxia

Inferred from electronic annotation. Source: Ensembl

cellular response to nutrient levels

Inferred from sequence or structural similarity. Source: UniProtKB

cholesterol biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-KW

cold acclimation

Inferred from electronic annotation. Source: Ensembl

fatty acid biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-KW

fatty acid homeostasis

Inferred from sequence or structural similarity. Source: UniProtKB

fatty acid oxidation

Inferred from electronic annotation. Source: Ensembl

glucose homeostasis

Inferred from sequence or structural similarity. Source: UniProtKB

glucose metabolic process

Inferred from electronic annotation. Source: Ensembl

insulin receptor signaling pathway

Traceable author statement. Source: Reactome

lipid biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of TOR signaling

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of glucose import in response to insulin stimulus

Inferred from electronic annotation. Source: Ensembl

negative regulation of glucosylceramide biosynthetic process

Non-traceable author statement PubMed 11165240. Source: UniProtKB

negative regulation of lipid catabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of autophagy

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of cholesterol biosynthetic process

Non-traceable author statement Ref.7. Source: UniProtKB

positive regulation of gene expression

Inferred from direct assay Ref.18. Source: UniProtKB

positive regulation of glycolysis

Inferred from sequence or structural similarity. Source: UniProtKB

protein heterooligomerization

Inferred from electronic annotation. Source: Ensembl

protein phosphorylation

Inferred from direct assay Ref.18. Source: UniProtKB

regulation of circadian rhythm

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of energy homeostasis

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

regulation of vesicle-mediated transport

Inferred from electronic annotation. Source: Ensembl

response to activity

Inferred from electronic annotation. Source: Ensembl

response to caffeine

Inferred from electronic annotation. Source: Ensembl

response to hypoxia

Non-traceable author statement Ref.7. Source: UniProtKB

response to stress

Inferred from sequence or structural similarity. Source: UniProtKB

rhythmic process

Inferred from electronic annotation. Source: UniProtKB-KW

signal transduction

Traceable author statement Ref.7. Source: ProtInc

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentAMP-activated protein kinase complex

Inferred from sequence or structural similarity. Source: UniProtKB

apical plasma membrane

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from direct assay. Source: HPA

cytosol

Traceable author statement. Source: Reactome

intracellular

Inferred by curator Ref.7. Source: UniProtKB

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionAMP-activated protein kinase activity

Inferred from direct assay Ref.26. Source: UniProtKB

ATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

[acetyl-CoA carboxylase] kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

[hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

cAMP-dependent protein kinase activity

Non-traceable author statement Ref.7. Source: UniProtKB

chromatin binding

Inferred from sequence or structural similarity. Source: UniProtKB

histone serine kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein kinase activity

Inferred from direct assay Ref.18. Source: UniProtKB

tau-protein kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q13131-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q13131-2)

The sequence of this isoform differs from the canonical sequence as follows:
     121-121: R → RKSDVPGVVKTGSTKE

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 5595595'-AMP-activated protein kinase catalytic subunit alpha-1
PRO_0000085589

Regions

Domain27 – 279253Protein kinase
Nucleotide binding33 – 419ATP By similarity
Region302 – 38180AIS

Sites

Active site1501Proton acceptor By similarity
Binding site561ATP By similarity

Amino acid modifications

Modified residue321Phosphothreonine Ref.30
Modified residue1831Phosphothreonine; by LKB1 and CaMKK2 By similarity
Modified residue2691Phosphothreonine By similarity
Modified residue3561Phosphoserine Ref.29
Modified residue3601Phosphoserine; by ULK1 By similarity
Modified residue3681Phosphothreonine; by ULK1 By similarity
Modified residue3821Phosphothreonine Ref.24 Ref.31
Modified residue3971Phosphoserine; by ULK1 Probable
Modified residue4671Phosphoserine Ref.30
Modified residue4861Phosphoserine Ref.29
Modified residue4881Phosphothreonine; by ULK1 Probable
Modified residue4901Phosphothreonine Ref.29
Modified residue4961Phosphoserine Ref.29

Natural variations

Alternative sequence1211R → RKSDVPGVVKTGSTKE in isoform 2.
VSP_035431
Natural variant101M → L. Ref.2
Corresponds to variant rs17855679 [ dbSNP | Ensembl ].
VAR_058401
Natural variant161Q → R in a breast cancer sample; somatic mutation. Ref.42
VAR_035622

Experimental info

Mutagenesis3071V → G or Q: Activates the kinase activity. Ref.19
Sequence conflict51S → C in BAG35788. Ref.4
Sequence conflict91K → S in AAD43027. Ref.5
Sequence conflict371T → A in AAA64850. Ref.6
Sequence conflict2021A → V in AAA64850. Ref.6
Sequence conflict2081I → L in AAA64850. Ref.6
Sequence conflict2691T → S in BAA36547. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified July 28, 2009. Version 4.
Checksum: ABAE71FBF912947A

FASTA55964,009
        10         20         30         40         50         60 
MRRLSSWRKM ATAEKQKHDG RVKIGHYILG DTLGVGTFGK VKVGKHELTG HKVAVKILNR 

        70         80         90        100        110        120 
QKIRSLDVVG KIRREIQNLK LFRHPHIIKL YQVISTPSDI FMVMEYVSGG ELFDYICKNG 

       130        140        150        160        170        180 
RLDEKESRRL FQQILSGVDY CHRHMVVHRD LKPENVLLDA HMNAKIADFG LSNMMSDGEF 

       190        200        210        220        230        240 
LRTSCGSPNY AAPEVISGRL YAGPEVDIWS SGVILYALLC GTLPFDDDHV PTLFKKICDG 

       250        260        270        280        290        300 
IFYTPQYLNP SVISLLKHML QVDPMKRATI KDIREHEWFK QDLPKYLFPE DPSYSSTMID 

       310        320        330        340        350        360 
DEALKEVCEK FECSEEEVLS CLYNRNHQDP LAVAYHLIID NRRIMNEAKD FYLATSPPDS 

       370        380        390        400        410        420 
FLDDHHLTRP HPERVPFLVA ETPRARHTLD ELNPQKSKHQ GVRKAKWHLG IRSQSRPNDI 

       430        440        450        460        470        480 
MAEVCRAIKQ LDYEWKVVNP YYLRVRRKNP VTSTYSKMSL QLYQVDSRTY LLDFRSIDDE 

       490        500        510        520        530        540 
ITEAKSGTAT PQRSGSVSNY RSCQRSDSDA EAQGKSSEVS LTSSVTSLDS SPVDLTPRPG 

       550 
SHTIEFFEMC ANLIKILAQ 

« Hide

Isoform 2 [UniParc].

Checksum: 8EA8B85393F48DAA
Show »

FASTA57465,523

References

« Hide 'large scale' references
[1]"The DNA sequence and comparative analysis of human chromosome 5."
Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. expand/collapse author list , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANT LEU-10.
Tissue: Brain and Testis.
[3]"Nucleotide sequence of cDNA for human AMP-activated protein kinase alpha-1."
Yano K.
Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 3-559 (ISOFORM 1).
Tissue: Mammary gland.
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 5-559 (ISOFORM 1).
Tissue: Trachea.
[5]"Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells."
Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., Tao J., Huang Q.-H., Zhou J., Hu G.-X. expand/collapse author list , Gu J., Chen S.-J., Chen Z.
Genome Res. 10:1546-1560(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 9-559 (ISOFORM 1).
Tissue: Umbilical cord blood.
[6]Taboada E.N., Hickey D.A.
Submitted (APR-1995) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 36-209 (ISOFORM 1).
Tissue: Intestine.
[7]"Mammalian AMP-activated protein kinase subfamily."
Stapleton D., Mitchelhill K.I., Gao G., Widmer J., Michell B.J., Teh T., House C.M., Fernandez C.S., Cox T., Witters L.A., Kemp B.E.
J. Biol. Chem. 271:611-614(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 303-559 (ISOFORMS 1/2).
Tissue: Liver.
[8]"Functional domains of the alpha1 catalytic subunit of the AMP-activated protein kinase."
Crute B.E., Seefeld K., Gamble J., Kemp B.E., Witters L.A.
J. Biol. Chem. 273:35347-35354(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: DOMAIN AIS.
[9]"Cell cycle regulation via p53 phosphorylation by a 5'-AMP activated protein kinase activator, 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside, in a human hepatocellular carcinoma cell line."
Imamura K., Ogura T., Kishimoto A., Kaminishi M., Esumi H.
Biochem. Biophys. Res. Commun. 287:562-567(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[10]"Regulation of transcription by AMP-activated protein kinase: phosphorylation of p300 blocks its interaction with nuclear receptors."
Yang W., Hong Y.H., Shen X.Q., Frankowski C., Camp H.S., Leff T.
J. Biol. Chem. 276:38341-38344(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF EP300.
[11]"Role of AMP-activated protein kinase in mechanism of metformin action."
Zhou G., Myers R., Li Y., Chen Y., Shen X., Fenyk-Melody J., Wu M., Ventre J., Doebber T., Fujii N., Musi N., Hirshman M.F., Goodyear L.J., Moller D.E.
J. Clin. Invest. 108:1167-1174(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION.
[12]"Physiological modulation of CFTR activity by AMP-activated protein kinase in polarized T84 cells."
Hallows K.R., Kobinger G.P., Wilson J.M., Witters L.A., Foskett J.K.
Am. J. Physiol. 284:C1297-C1308(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF CFTR.
[13]"TSC2 mediates cellular energy response to control cell growth and survival."
Inoki K., Zhu T., Guan K.L.
Cell 115:577-590(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF TSC2.
[14]"LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1."
Lizcano J.M., Goeransson O., Toth R., Deak M., Morrice N.A., Boudeau J., Hawley S.A., Udd L., Maekelae T.P., Hardie D.G., Alessi D.R.
EMBO J. 23:833-843(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-183, ENZYME REGULATION.
[15]"Calmodulin-dependent protein kinase kinase-beta is an alternative upstream kinase for AMP-activated protein kinase."
Hawley S.A., Pan D.A., Mustard K.J., Ross L., Bain J., Edelman A.M., Frenguelli B.G., Hardie D.G.
Cell Metab. 2:9-19(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-183, ENZYME REGULATION.
[16]"The Ca2+/calmodulin-dependent protein kinase kinases are AMP-activated protein kinase kinases."
Hurley R.L., Anderson K.A., Franzone J.M., Kemp B.E., Means A.R., Witters L.A.
J. Biol. Chem. 280:29060-29066(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-183, ENZYME REGULATION.
[17]"AMP-activated protein kinase induces a p53-dependent metabolic checkpoint."
Jones R.G., Plas D.R., Kubek S., Buzzai M., Mu J., Xu Y., Birnbaum M.J., Thompson C.B.
Mol. Cell 18:283-293(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[18]"Folliculin encoded by the BHD gene interacts with a binding protein, FNIP1, and AMPK, and is involved in AMPK and mTOR signaling."
Baba M., Hong S.-B., Sharma N., Warren M.B., Nickerson M.L., Iwamatsu A., Esposito D., Gillette W.K., Hopkins R.F. III, Hartley J.L., Furihata M., Oishi S., Zhen W., Burke T.R. Jr., Linehan W.M., Schmidt L.S., Zbar B.
Proc. Natl. Acad. Sci. U.S.A. 103:15552-15557(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FNIP1.
[19]"Conserved alpha-helix acts as autoinhibitory sequence in AMP-activated protein kinase alpha subunits."
Pang T., Xiong B., Li J.Y., Qiu B.Y., Jin G.Z., Shen J.K., Li J.
J. Biol. Chem. 282:495-506(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: DOMAIN AIS, MUTAGENESIS OF VAL-307.
[20]"The energy sensor AMP-activated protein kinase directly regulates the mammalian FOXO3 transcription factor."
Greer E.L., Oskoui P.R., Banko M.R., Maniar J.M., Gygi M.P., Gygi S.P., Brunet A.
J. Biol. Chem. 282:30107-30119(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF FOXO3.
[21]"Energy-dependent regulation of cell structure by AMP-activated protein kinase."
Lee J.H., Koh H., Kim M., Kim Y., Lee S.Y., Karess R.E., Lee S.H., Shong M., Kim J.M., Kim J., Chung J.
Nature 447:1017-1020(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CELL POLARITY.
[22]"AMP-activated protein kinase regulates GLUT4 transcription by phosphorylating histone deacetylase 5."
McGee S.L., van Denderen B.J., Howlett K.F., Mollica J., Schertzer J.D., Kemp B.E., Hargreaves M.
Diabetes 57:860-867(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF HDAC5.
[23]"Identification and characterization of a novel folliculin-interacting protein FNIP2."
Hasumi H., Baba M., Hong S.-B., Hasumi Y., Huang Y., Yao M., Valera V.A., Linehan W.M., Schmidt L.S.
Gene 415:60-67(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FNIP2.
[24]"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis."
Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III
J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-382, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[25]"Phosphoproteome of resting human platelets."
Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A.
J. Proteome Res. 7:526-534(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Platelet.
[26]"AMPK phosphorylation of raptor mediates a metabolic checkpoint."
Gwinn D.M., Shackelford D.B., Egan D.F., Mihaylova M.M., Mery A., Vasquez D.S., Turk B.E., Shaw R.J.
Mol. Cell 30:214-226(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF RPTOR.
[27]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[28]"Interaction of folliculin (Birt-Hogg-Dube gene product) with a novel Fnip1-like (FnipL/Fnip2) protein."
Takagi Y., Kobayashi T., Shiono M., Wang L., Piao X., Sun G., Zhang D., Abe M., Hagiwara Y., Takahashi K., Hino O.
Oncogene 27:5339-5347(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FNIP2.
[29]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-356; SER-486; THR-490 AND SER-496, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[30]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-32 AND SER-467, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[31]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-382, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[32]"Cell-wide analysis of secretory granule dynamics in three dimensions in living pancreatic beta-cells: evidence against a role for AMPK-dependent phosphorylation of KLC1 at Ser517/Ser520 in glucose-stimulated insulin granule movement."
McDonald A., Fogarty S., Leclerc I., Hill E.V., Hardie D.G., Rutter G.A.
Biochem. Soc. Trans. 38:205-208(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF KLC1.
[33]"ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response to ROS."
Alexander A., Cai S.L., Kim J., Nanez A., Sahin M., MacLean K.H., Inoki K., Guan K.L., Shen J., Person M.D., Kusewitt D., Mills G.B., Kastan M.B., Walker C.L.
Proc. Natl. Acad. Sci. U.S.A. 107:4153-4158(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[34]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[35]"Ulk1-mediated phosphorylation of AMPK constitutes a negative regulatory feedback loop."
Loffler A.S., Alers S., Dieterle A.M., Keppeler H., Franz-Wachtel M., Kundu M., Campbell D.G., Wesselborg S., Alessi D.R., Stork B.
Autophagy 7:696-706(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION BY ULK1 AND ULK2.
[36]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[37]"Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy."
Egan D.F., Shackelford D.B., Mihaylova M.M., Gelino S., Kohnz R.A., Mair W., Vasquez D.S., Joshi A., Gwinn D.M., Taylor R., Asara J.M., Fitzpatrick J., Dillin A., Viollet B., Kundu M., Hansen M., Shaw R.J.
Science 331:456-461(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF ULK1.
[38]"AMPK is a direct adenylate charge-regulated protein kinase."
Oakhill J.S., Steel R., Chen Z.P., Scott J.W., Ling N., Tam S., Kemp B.E.
Science 332:1433-1435(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PRKAB1 AND PRKAG1, ENZYME REGULATION.
[39]"AMP-activated protein kinase in metabolic control and insulin signaling."
Towler M.C., Hardie D.G.
Circ. Res. 100:328-341(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[40]"AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy."
Hardie D.G.
Nat. Rev. Mol. Cell Biol. 8:774-785(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[41]"N-Myristoylation is essential for protein phosphatases PPM1A and PPM1B to dephosphorylate their physiological substrates in cells."
Chida T., Ando M., Matsuki T., Masu Y., Nagaura Y., Takano-Yamamoto T., Tamura S., Kobayashi T.
Biochem. J. 449:741-749(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: DEPHOSPHORYLATION.
[42]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] ARG-16.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AC008810 Genomic DNA. No translation available.
BC048980 mRNA. Translation: AAH48980.1.
AB022017 mRNA. Translation: BAA36547.1. Different initiation.
AK312947 mRNA. Translation: BAG35788.1. Different initiation.
BC037303 mRNA. Translation: AAH37303.1. Different initiation.
AF100763 mRNA. Translation: AAD43027.1. Different initiation.
U22456 mRNA. Translation: AAA64850.1. Different initiation.
Y12856 mRNA. Translation: CAA73361.1.
PIRG01743.
RefSeqNP_006242.5. NM_006251.5.
NP_996790.3. NM_206907.3.
UniGeneHs.43322.

3D structure databases

ProteinModelPortalQ13131.
SMRQ13131. Positions 18-559.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111549. 251 interactions.
DIPDIP-39973N.
IntActQ13131. 62 interactions.
MINTMINT-6771251.
STRING9606.ENSP00000346148.

Chemistry

BindingDBQ13131.
ChEMBLCHEMBL2096907.
DrugBankDB00131. Adenosine monophosphate.
DB00171. Adenosine triphosphate.
DB00914. Phenformin.
GuidetoPHARMACOLOGY1541.

PTM databases

PhosphoSiteQ13131.

Polymorphism databases

DMDM254763436.

Proteomic databases

PaxDbQ13131.
PRIDEQ13131.

Protocols and materials databases

DNASU5562.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000354209; ENSP00000346148; ENSG00000132356. [Q13131-2]
ENST00000397128; ENSP00000380317; ENSG00000132356. [Q13131-1]
GeneID5562.
KEGGhsa:5562.
UCSCuc003jmb.3. human. [Q13131-2]
uc003jmc.3. human. [Q13131-1]

Organism-specific databases

CTD5562.
GeneCardsGC05M040759.
H-InvDBHIX0004832.
HGNCHGNC:9376. PRKAA1.
HPACAB005050.
HPA035409.
MIM602739. gene.
neXtProtNX_Q13131.
PharmGKBPA33744.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233016.
HOVERGENHBG050432.
KOK07198.
OMAMKRATIR.
OrthoDBEOG7RRF6K.
PhylomeDBQ13131.
TreeFamTF314032.

Enzyme and pathway databases

BRENDA2.7.11.1. 2681.
ReactomeREACT_111102. Signal Transduction.
SignaLinkQ13131.

Gene expression databases

ArrayExpressQ13131.
BgeeQ13131.
CleanExHS_PRKAA1.
GenevestigatorQ13131.

Family and domain databases

InterProIPR028375. KA1/Ssp2_C.
IPR011009. Kinase-like_dom.
IPR028797. PRKAA1.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERPTHR24343:SF81. PTHR24343:SF81. 1 hit.
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF103243. SSF103243. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPRKAA1. human.
GeneWikiProtein_kinase,_AMP-activated,_alpha_1.
GenomeRNAi5562.
NextBio21546.
PROQ13131.
SOURCESearch...

Entry information

Entry nameAAPK1_HUMAN
AccessionPrimary (citable) accession number: Q13131
Secondary accession number(s): A8MTQ6 expand/collapse secondary AC list , B2R7E1, O00286, Q5D0E1, Q86VS1, Q9UNQ4
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: July 28, 2009
Last modified: April 16, 2014
This is version 155 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM