Q13131 (AAPK1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	559 AA.
Sequence status	Complete.
Protein existence	Evidence 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: 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 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 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. Ref.14 Ref.15 Ref.16 Ref.35
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 process	Autophagy 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 component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Chromatin regulator Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Wnt receptor 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: Compara cellular response to glucose starvation Inferred from sequence or structural similarity. Source: UniProtKB cellular response to hydrogen peroxide Inferred from electronic annotation. Source: Compara cellular response to hypoxia Inferred from electronic annotation. Source: Compara cholesterol biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW cold acclimation Inferred from electronic annotation. Source: Compara 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: Compara glucose homeostasis Inferred from sequence or structural similarity. Source: UniProtKB glucose metabolic process Inferred from electronic annotation. Source: Compara 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 cascade 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: Compara 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: Compara 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: Compara 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-dependent Inferred from electronic annotation. Source: UniProtKB-KW regulation of vesicle-mediated transport Inferred from electronic annotation. Source: Compara response to activity Inferred from electronic annotation. Source: Compara response to caffeine Inferred from electronic annotation. Source: Compara response to hypoxia Non-traceable author statement Ref.7. Source: UniProtKB rhythmic process Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	AMP-activated protein kinase complex Inferred from sequence or structural similarity. Source: UniProtKB apical plasma membrane Inferred from electronic annotation. Source: Compara cytosol Traceable author statement. Source: Reactome nucleus Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	AMP-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: EC [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity Inferred from electronic annotation. Source: 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 tau-protein kinase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
HSP90AB1	P08238	2	EBI-1181405,EBI-352572
PRKAB2	O43741	6	EBI-1181405,EBI-1053424

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 559	559	5'-AMP-activated protein kinase catalytic subunit alpha-1		PRO_0000085589
Regions
	Domain	27 – 279	253	Protein kinase
	Nucleotide binding	33 – 41	9	ATP By similarity
	Region	302 – 381	80	AIS
Sites
	Active site	150	1	Proton acceptor By similarity
	Binding site	56	1	ATP By similarity
Amino acid modifications
	Modified residue	32	1	Phosphothreonine Ref.30
	Modified residue	183	1	Phosphothreonine; by LKB1 and CaMKK2 By similarity
	Modified residue	184	1	Phosphoserine By similarity
	Modified residue	269	1	Phosphothreonine By similarity
	Modified residue	356	1	Phosphoserine Ref.29
	Modified residue	360	1	Phosphoserine; by ULK1 By similarity
	Modified residue	368	1	Phosphothreonine; by ULK1 By similarity
	Modified residue	382	1	Phosphothreonine Ref.24 Ref.31
	Modified residue	397	1	Phosphoserine; by ULK1 Probable
	Modified residue	467	1	Phosphoserine Ref.30
	Modified residue	486	1	Phosphoserine Ref.29
	Modified residue	488	1	Phosphothreonine; by ULK1 Probable
	Modified residue	490	1	Phosphothreonine Ref.29
	Modified residue	496	1	Phosphoserine Ref.29
	Modified residue	508	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	121	1	R → RKSDVPGVVKTGSTKE in isoform 2.		VSP_035431
	Natural variant	10	1	M → L. Ref.2 Corresponds to variant rs17855679 [ dbSNP | Ensembl ].		VAR_058401
	Natural variant	16	1	Q → R in a breast cancer sample; somatic mutation. Ref.41		VAR_035622
Experimental info
	Mutagenesis	307	1	V → G or Q: Activates the kinase activity. Ref.19
	Sequence conflict	5	1	S → C in BAG35788. Ref.4
	Sequence conflict	9	1	K → S in AAD43027. Ref.5
	Sequence conflict	37	1	T → A in AAA64850. Ref.6
	Sequence conflict	202	1	A → V in AAA64850. Ref.6
	Sequence conflict	208	1	I → L in AAA64850. Ref.6
	Sequence conflict	269	1	T → S in BAA36547. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 28, 2009. Version 4. Checksum: ABAE71FBF912947A	FASTA	559	64,009
	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
	Isoform 2 [UniParc]. Checksum: 8EA8B85393F48DAA	FASTA	574	65,523
	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 RKSDVPGVVK TGSTKELDEK ESRRLFQQIL SGVDYCHRHM VVHRDLKPEN VLLDAHMNAK 190 200 210 220 230 240 IADFGLSNMM SDGEFLRTSC GSPNYAAPEV ISGRLYAGPE VDIWSSGVIL YALLCGTLPF 250 260 270 280 290 300 DDDHVPTLFK KICDGIFYTP QYLNPSVISL LKHMLQVDPM KRATIKDIRE HEWFKQDLPK 310 320 330 340 350 360 YLFPEDPSYS STMIDDEALK EVCEKFECSE EEVLSCLYNR NHQDPLAVAY HLIIDNRRIM 370 380 390 400 410 420 NEAKDFYLAT SPPDSFLDDH HLTRPHPERV PFLVAETPRA RHTLDELNPQ KSKHQGVRKA 430 440 450 460 470 480 KWHLGIRSQS RPNDIMAEVC RAIKQLDYEW KVVNPYYLRV RRKNPVTSTY SKMSLQLYQV 490 500 510 520 530 540 DSRTYLLDFR SIDDEITEAK SGTATPQRSG SVSNYRSCQR SDSDAEAQGK SSEVSLTSSV 550 560 570 TSLDSSPVDL TPRPGSHTIE FFEMCANLIK ILAQ

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY.
[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, MASS SPECTROMETRY. 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]	"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. , 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.
IPI	IPI00410287. IPI00792482.
PIR	G01743.
RefSeq	NP_006242.5. NM_006251.5. NP_996790.3. NM_206907.3.
UniGene	Hs.43322.
3D structure databases
ProteinModelPortal	Q13131.
SMR	Q13131. Positions 18-559.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-39973N.
IntAct	Q13131. 57 interactions.
MINT	MINT-6771251.
STRING	9606.ENSP00000346148.
PTM databases
PhosphoSite	Q13131.
Polymorphism databases
DMDM	254763436.
Proteomic databases
PaxDb	Q13131.
PRIDE	Q13131.
Protocols and materials databases
DNASU	5562.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000354209; ENSP00000346148; ENSG00000132356. ENST00000397128; ENSP00000380317; ENSG00000132356.
GeneID	5562.
KEGG	hsa:5562.
UCSC	uc003jmb.3. human. uc003jmc.3. human.
Organism-specific databases
CTD	5562.
GeneCards	GC05M040759.
H-InvDB	HIX0004832.
HGNC	HGNC:9376. PRKAA1.
HPA	CAB005050.
MIM	602739. gene.
neXtProt	NX_Q13131.
PharmGKB	PA33744.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000233016.
HOVERGEN	HBG050432.
KO	K07198.
OMA	ACQRNDS.
OrthoDB	EOG4BK53H.
Enzyme and pathway databases
BRENDA	2.7.11.1. 2681.
Reactome	REACT_111102. Signal Transduction. REACT_11163. Activated AMPK stimulates fatty-acid oxidation in muscle.
SignaLink	Q13131.
Gene expression databases
ArrayExpress	Q13131.
Bgee	Q13131.
CleanEx	HS_PRKAA1.
Genevestigator	Q13131.
GermOnline	ENSG00000132356. Homo sapiens.
Family and domain databases
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. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q13131.
ChEMBL	CHEMBL4045.
ChiTaRS	PRKAA1. human.
DrugBank	DB00131. Adenosine monophosphate. DB00171. Adenosine triphosphate. DB00914. Phenformin.
GenomeRNAi	5562.
NextBio	21546.
SOURCE	Search...

Entry information

Entry name

AAPK1_HUMAN

Accession

Primary (citable) accession number: Q13131
Secondary accession number(s): A8MTQ6 , B2R7E1, O00286, Q5D0E1, Q86VS1, Q9UNQ4

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	July 28, 2009
Last modified:	May 29, 2013
This is version 145 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.