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

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

Alternative products

Sequence annotation (Features)

Sequences

References

Cross-references

Entry information

Relevant documents

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

Alternative products

Sequence annotation (Features)

Sequences

References

Cross-references

Entry information

Relevant documents

Molecule processing

Regions

Sites

Amino acid modifications

Natural variations

Experimental info

Keywords

Gene Ontology (GO)

With

Entry

#Exp.

IntAct

Notes

Molecule processing

Regions

Sites

Amino acid modifications

Natural variations

Experimental info

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other Resources

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Reviewed, UniProtKB/Swiss-Prot Q13131 (AAPK1_HUMAN)

Last modified November 25, 2008. Version 93. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Protein names

Recommended name:
    5'-AMP-activated protein kinase catalytic subunit alpha-1
      Short name=AMPK alpha-1 chain
    EC=2.7.11.1

Gene names

Name:	PRKAA1
Synonyms:	AMPK1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Sequence length	550 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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Function	Responsible for the regulation of fatty acid synthesis by phosphorylation of acetyl-CoA carboxylase. It also regulates cholesterol synthesis via phosphorylation and inactivation of hormone-sensitive lipase and hydroxymethylglutaryl-CoA reductase. Appears to act as a metabolic stress-sensing protein kinase switching off biosynthetic pathways when cellular ATP levels are depleted and when 5'-AMP rises in response to fuel limitation and/or hypoxia. This is a catalytic subunit.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium.
Enzyme regulation	Binding of AMP results in allosteric activation, inducing phosphorylation on Thr-174 by STK11 in complex with STE20-related adapter-alpha (STRAD alpha) pseudo kinase and CAB39. Also activated by phosphorylation by CAMKK2 triggered by a rise in intracellular calcium ions, without detectable changes in the AMP/ATP ratio.
Subunit structure	Heterotrimer of an alpha catalytic subunit, a beta and a gamma non-catalytic subunits. Interacts with FNIP1 and FNIP2.
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 AAH48980.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

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Keywords
Biological process	Cholesterol biosynthesis Fatty acid biosynthesis Lipid synthesis Steroid biosynthesis Sterol biosynthesis
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	activation of MAPK activity Non-traceable author statement. Source: UniProtKB fatty acid biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of glucosylceramide biosynthetic process Non-traceable author statement. Source: UniProtKB positive regulation of anti-apoptosis Non-traceable author statement. Source: UniProtKB positive regulation of cholesterol biosynthetic process Ref.5 Non-traceable author statement. Source: UniProtKB response to hypoxia Ref.5 Non-traceable author statement. Source: UniProtKB
Cellular component	intracellular Ref.5 Inferred by curator. Source: UniProtKB
Molecular function	ATP binding Inferred from electronic annotation. Source: InterPro cAMP-dependent protein kinase activity Ref.5 Non-traceable author statement. Source: UniProtKB magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Ref.13 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

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With	Entry	#Exp.	IntAct	Notes
Ppard	P35396	1	EBI-1181405,EBI-1809541	From a different organism.

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Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Chain

1 – 550

550

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

PRO_0000085589

Domain

18 – 270

253

Protein kinase

Nucleotide binding

24 – 32

ATP By similarity

Active site

141

Proton acceptor By similarity

Binding site

ATP By similarity

Modified residue

174

Phosphothreonine; by STK11 By similarity

Modified residue

175

Phosphoserine By similarity

Modified residue

260

Phosphothreonine By similarity

Modified residue

347

Phosphoserine

Modified residue

373

Phosphothreonine

Modified residue

433

Phosphotyrosine

Modified residue

477

Phosphoserine

Modified residue

481

Phosphothreonine

Modified residue

487

Phosphoserine

Modified residue

499

Phosphoserine By similarity

Alternative sequence

112

R → RKSDVPGVVKTGSTKE in isoform 2.

VSP_035431

Natural variant

Q → R in a breast cancer sample; somatic mutation.

VAR_035622

Sequence conflict

M → L in AAH48980. Ref.3

Sequence conflict

T → A in AAA64850. Ref.4

Sequence conflict

193

A → V in AAA64850. Ref.4

Sequence conflict

199

I → L in AAA64850. Ref.4

Sequence conflict

260

T → S in BAA36547. Ref.1

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Sequence		Length	Mass (Da)
Isoform 1 [UniParc]. Last modified September 13, 2005. Version 3. Checksum: F878493C3158B1C2 Show »	FASTA	550	62,808
10 20 30 40 50 60 MATAEKQKHD GRVKIGHYIL GDTLGVGTFG KVKVGKHELT GHKVAVKILN RQKIRSLDVV 70 80 90 100 110 120 GKIRREIQNL KLFRHPHIIK LYQVISTPSD IFMVMEYVSG GELFDYICKN GRLDEKESRR 130 140 150 160 170 180 LFQQILSGVD YCHRHMVVHR DLKPENVLLD AHMNAKIADF GLSNMMSDGE FLRTSCGSPN 190 200 210 220 230 240 YAAPEVISGR LYAGPEVDIW SSGVILYALL CGTLPFDDDH VPTLFKKICD GIFYTPQYLN 250 260 270 280 290 300 PSVISLLKHM LQVDPMKRAT IKDIREHEWF KQDLPKYLFP EDPSYSSTMI DDEALKEVCE 310 320 330 340 350 360 KFECSEEEVL SCLYNRNHQD PLAVAYHLII DNRRIMNEAK DFYLATSPPD SFLDDHHLTR 370 380 390 400 410 420 PHPERVPFLV AETPRARHTL DELNPQKSKH QGVRKAKWHL GIRSQSRPND IMAEVCRAIK 430 440 450 460 470 480 QLDYEWKVVN PYYLRVRRKN PVTSTYSKMS LQLYQVDSRT YLLDFRSIDD EITEAKSGTA 490 500 510 520 530 540 TPQRSGSVSN YRSCQRSDSD AEAQGKSSEV SLTSSVTSLD SSPVDLTPRP GSHTIEFFEM 550 CANLIKILAQ « Hide
Isoform 2 [UniParc]. Checksum: C19095B1223AE887 Show »		565	64,321
10 20 30 40 50 60 MATAEKQKHD GRVKIGHYIL GDTLGVGTFG KVKVGKHELT GHKVAVKILN RQKIRSLDVV 70 80 90 100 110 120 GKIRREIQNL KLFRHPHIIK LYQVISTPSD IFMVMEYVSG GELFDYICKN GRKSDVPGVV 130 140 150 160 170 180 KTGSTKELDE KESRRLFQQI LSGVDYCHRH MVVHRDLKPE NVLLDAHMNA KIADFGLSNM 190 200 210 220 230 240 MSDGEFLRTS CGSPNYAAPE VISGRLYAGP EVDIWSSGVI LYALLCGTLP FDDDHVPTLF 250 260 270 280 290 300 KKICDGIFYT PQYLNPSVIS LLKHMLQVDP MKRATIKDIR EHEWFKQDLP KYLFPEDPSY 310 320 330 340 350 360 SSTMIDDEAL KEVCEKFECS EEEVLSCLYN RNHQDPLAVA YHLIIDNRRI MNEAKDFYLA 370 380 390 400 410 420 TSPPDSFLDD HHLTRPHPER VPFLVAETPR ARHTLDELNP QKSKHQGVRK AKWHLGIRSQ 430 440 450 460 470 480 SRPNDIMAEV CRAIKQLDYE WKVVNPYYLR VRRKNPVTST YSKMSLQLYQ VDSRTYLLDF 490 500 510 520 530 540 RSIDDEITEA KSGTATPQRS GSVSNYRSCQ RSDSDAEAQG KSSEVSLTSS VTSLDSSPVD 550 560 LTPRPGSHTI EFFEMCANLI KILAQ « Hide

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	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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] (ISOFORM 1). Tissue: Mammary gland.
[2]	"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: 11042152] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Umbilical cord blood.
[3]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Brain and Testis.
[4]	Taboada E.N., Hickey D.A. Submitted (APR-1995) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 27-200. Tissue: Intestine.
[5]	"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: 8557660] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 294-550. Tissue: Liver.
[6]	"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: 14976552] [Abstract] Cited for: FUNCTION, ENZYME REGULATION.
[7]	"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: 16054095] [Abstract] Cited for: FUNCTION, ENZYME REGULATION.
[8]	"Global phosphoproteome of HT-29 human colon adenocarcinoma cells." Kim J.-E., Tannenbaum S.R., White F.M. J. Proteome Res. 4:1339-1346(2005) [PubMed: 16083285] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-487, MASS SPECTROMETRY.
[9]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-433, MASS SPECTROMETRY.
[10]	"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: 18088087] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-487, MASS SPECTROMETRY. Tissue: Platelet.
[11]	"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: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-373, MASS SPECTROMETRY.
[12]	"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: 17028174] [Abstract] Cited for: INTERACTION WITH FNIP1.
[13]	"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: 18403135] [Abstract] Cited for: INTERACTION WITH FNIP2.
[14]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-347; THR-373; SER-477; THR-481 AND SER-487, MASS SPECTROMETRY.
[15]	"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. Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] ARG-7.
+	Additional computationally mapped references.

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Sequence databases
	AB022017 mRNA. Translation: BAA36547.1. AF100763 mRNA. Translation: AAD43027.1. BC037303 mRNA. Translation: AAH37303.1. BC048980 mRNA. Translation: AAH48980.1. U22456 mRNA. Translation: AAA64850.1. Y12856 mRNA. Translation: CAA73361.1.
PIR	G01743.
RefSeq	NP_006242.5. NP_996790.3.
UniGene	Hs.43322
3D structure databases
HSSP	HSSP built from PDB template 1A06 based on UniProtKB Q63450.
SMR	Q13131. Positions 12-280.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q13131.
PTM databases
PhosphoSite	Q13131.
Genome annotation databases
Ensembl	ENSG00000132356. Homo sapiens. [Contig view]
GeneID	5562.
KEGG	hsa:5562.
Organism-specific databases
H-InvDB	HIX0004832.
HGNC	HGNC:9376. PRKAA1.
HPA	CAB005050.
MIM	602739. gene.
PharmGKB	PA33744.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOVERGEN	Q13131.
Gene expression databases
ArrayExpress	Q13131.
CleanEx	HS_PRKAA1.
GermOnline	ENSG00000132356. Homo sapiens.
Family and domain databases
InterPro	IPR015741. AMPK. IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_bd_CS. IPR017442. Se/Thr_pkinase-rel. IPR008271. Ser_thr_pkin_AS. IPR002290. Ser_thr_pkinase. [Graphical view]
PANTHER	PTHR22982:SF61. AMPK. 1 hit.
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
ProDom	PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB00131. Adenosine monophosphate. DB00171. Adenosine triphosphate. DB00914. Phenformin.
SOURCE	Search...

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Entry name

AAPK1_HUMAN

Accession

Primary (citable) accession number: Q13131
Secondary accession number(s): O00286

Q9UNQ4

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	September 13, 2005
Last modified:	November 25, 2008
This is version 93 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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Human chromosome 5

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

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

SIMILARITY comments

Index of protein domains and families

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:
112-112: R → RKSDVPGVVKTGSTKE