PRKAA1

Functionⁱ

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. In response to nutrient limitation, phosphorylates transcription factor FOXO3 promoting FOXO3 mitochondrial import (By similarity). 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.By similarity12 Publications

Catalytic activityⁱ

ATP + a protein = ADP + a phosphoprotein.By similarity

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

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

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

Cofactorⁱ

Mg²⁺

Activity regulationⁱ

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 (PubMed:11602624). 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.5 Publications

Sites

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Binding siteⁱ	56	ATPPROSITE-ProRule annotation		1
Active siteⁱ	150	Proton acceptorPROSITE-ProRule annotation		1

Regions

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Nucleotide bindingⁱ	33 – 41	ATPPROSITE-ProRule annotation		9

GO - Molecular functionⁱ

[acetyl-CoA carboxylase] kinase activity Source: UniProtKB-EC
[hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity Source: UniProtKB-EC
AMP-activated protein kinase activity
Source: UniProtKB
Inferred from direct assayⁱ
- 18439900
ATP binding Source: UniProtKB-KW
cAMP-dependent protein kinase activity
Source: UniProtKB
Non-traceable author statementⁱ
- 8557660
chromatin binding Source: UniProtKB
histone serine kinase activity Source: UniProtKB
metal ion binding Source: UniProtKB-KW
protein C-terminus binding Source: Ensembl
protein kinase activity
Source: UniProtKB
Inferred from direct assayⁱ
- 17028174
protein serine/threonine kinase activity
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
tau-protein kinase activity Source: UniProtKB-EC

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

activation of MAPK activity
Source: UniProtKB
Non-traceable author statementⁱ
- 11546797
CAMKK-AMPK signaling cascade
Source: ParkinsonsUK-UCL
Inferred from mutant phenotypeⁱ
- 26103054
cell cycle arrest Source: Reactome
cellular response to calcium ion Source: ARUK-UCL
cellular response to ethanol Source: Ensembl
cellular response to glucose starvation Source: UniProtKB
cellular response to glucose stimulus Source: ARUK-UCL
cellular response to hydrogen peroxide Source: Ensembl
cellular response to hypoxia Source: Ensembl
cellular response to nutrient levels Source: UniProtKB
cellular response to organonitrogen compound Source: Ensembl
cellular response to oxidative stress Source: ARUK-UCL
cellular response to prostaglandin E stimulus Source: Ensembl
cholesterol biosynthetic process Source: UniProtKB-KW
cold acclimation Source: Ensembl
energy homeostasis Source: UniProtKB
fatty acid biosynthetic process Source: UniProtKB-KW
fatty acid homeostasis Source: UniProtKB
fatty acid oxidation Source: Ensembl
glucose homeostasis Source: UniProtKB
glucose metabolic process Source: Ensembl
intracellular signal transduction
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
lipid biosynthetic process Source: UniProtKB
macroautophagy Source: Reactome
motor behavior
Source: ARUK-UCL
Inferred from genetic interactionⁱ
- 21768291
negative regulation of apoptotic process Source: UniProtKB
negative regulation of gene expression Source: ARUK-UCL
negative regulation of glucose import in response to insulin stimulus Source: Ensembl
negative regulation of glucosylceramide biosynthetic process
Source: UniProtKB
Non-traceable author statementⁱ
- 11165240
negative regulation of lipid catabolic process Source: UniProtKB
negative regulation of TOR signaling Source: UniProtKB
negative regulation of tubulin deacetylation Source: ARUK-UCL
neuron cellular homeostasis
Source: ARUK-UCL
Inferred from genetic interactionⁱ
- 21768291
positive regulation of autophagy
Source: ParkinsonsUK-UCL
Inferred from direct assayⁱ
- 22012985
positive regulation of cell proliferation Source: Ensembl
positive regulation of cellular protein localization Source: ARUK-UCL
positive regulation of cholesterol biosynthetic process
Source: UniProtKB
Non-traceable author statementⁱ
- 8557660
positive regulation of gene expression
Source: UniProtKB
Inferred from direct assayⁱ
- 17028174
positive regulation of glycolytic process Source: UniProtKB
positive regulation of mitochondrial transcription Source: Ensembl
positive regulation of peptidyl-lysine acetylation Source: ARUK-UCL
positive regulation of protein targeting to mitochondrion Source: Ensembl
positive regulation of skeletal muscle tissue development Source: Ensembl
protein heterooligomerization Source: Ensembl
protein phosphorylation
Source: UniProtKB
Inferred from direct assayⁱ
- 17028174
regulation of circadian rhythm Source: UniProtKB
regulation of microtubule cytoskeleton organization Source: ARUK-UCL
regulation of peptidyl-serine phosphorylation Source: Ensembl
regulation of stress granule assembly Source: Ensembl
regulation of vesicle-mediated transport Source: Ensembl
response to activity Source: Ensembl
response to caffeine Source: Ensembl
response to camptothecin Source: Ensembl
response to gamma radiation Source: UniProtKB
response to hypoxia
Source: UniProtKB
Non-traceable author statementⁱ
- 8557660
response to UV Source: Ensembl
rhythmic process Source: UniProtKB-KW
signal transduction
Source: ProtInc
Traceable author statementⁱ
- 8557660
Wnt signaling pathway Source: UniProtKB-KW

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Chromatin regulator, Kinase, Serine/threonine-protein kinase, Transferase
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
Ligand	ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAⁱ	2.7.11.1 2681
Reactomeⁱ	R-HSA-1632852 Macroautophagy R-HSA-380972 Energy dependent regulation of mTOR by LKB1-AMPK R-HSA-5628897 TP53 Regulates Metabolic Genes R-HSA-6804756 Regulation of TP53 Activity through Phosphorylation
SignaLinkⁱ	Q13131
SIGNORⁱ	Q13131

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: 5'-AMP-activated protein kinase catalytic subunit alpha-1 (EC:2.7.11.1By similarity) Short name: AMPK subunit alpha-1 Alternative name(s): Acetyl-CoA carboxylase kinase (EC:2.7.11.27By similarity) Short name: ACACA kinase Hydroxymethylglutaryl-CoA reductase kinase (EC:2.7.11.31By similarity) Short name: HMGCR kinase Tau-protein kinase PRKAA1 (EC:2.7.11.26)
Gene namesⁱ	Name:PRKAA1 Synonyms:AMPK1
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 5

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000132356.11
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:9376 PRKAA1
MIMⁱ	602739 gene
neXtProtⁱ	NX_Q13131

Keywords - Cellular componentⁱ

Cytoplasm, Nucleus

Pathology & Biotechⁱ

Mutagenesis

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Mutagenesisⁱ	307	V → G or Q: Activates the kinase activity. 1 Publication		1

Organism-specific databases

DisGeNET More...DisGeNETⁱ	5562
Open Targets More...OpenTargetsⁱ	ENSG00000132356
PharmGKBⁱ	PA33744

Chemistry databases

ChEMBLⁱ	CHEMBL4045
Drug and drug target database More...DrugBankⁱ	DB00945 Acetylsalicylic acid DB00131 Adenosine monophosphate DB00171 Adenosine triphosphate DB00914 Phenformin

Polymorphism and mutation databases

BioMutaⁱ	PRKAA1
DMDMⁱ	254763436

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
ChainⁱPRO_0000085589	1 – 559	5'-AMP-activated protein kinase catalytic subunit alpha-1Add BLAST		559

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Length
Modified residueⁱ	32	PhosphothreonineCombined sources	1
Modified residueⁱ	183	Phosphothreonine; by LKB1 and CaMKK2By similarity	1
Modified residueⁱ	269	PhosphothreonineBy similarity	1
Modified residueⁱ	355	PhosphothreonineCombined sources	1
Modified residueⁱ	356	PhosphoserineCombined sources	1
Modified residueⁱ	360	Phosphoserine; by ULK1By similarity	1
Modified residueⁱ	368	Phosphothreonine; by ULK1By similarity	1
Modified residueⁱ	382	PhosphothreonineCombined sources	1
Modified residueⁱ	397	PhosphoserineBy similarity	1
Modified residueⁱ	467	PhosphoserineCombined sources	1
Modified residueⁱ	486	PhosphoserineCombined sources	1
Modified residueⁱ	488	PhosphothreonineBy similarity	1
Modified residueⁱ	490	PhosphothreonineCombined sources	1
Modified residueⁱ	496	PhosphoserineCombined sources	1
Modified residueⁱ	508	PhosphoserineCombined sources	1
Modified residueⁱ	524	PhosphoserineCombined sources	1
Modified residueⁱ	527	PhosphoserineCombined sources	1

Post-translational modificationⁱ

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.4 Publications

Keywords - PTMⁱ

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDⁱ	Q13131
MaxQB - The MaxQuant DataBase More...MaxQBⁱ	Q13131
PaxDbⁱ	Q13131
PeptideAtlas More...PeptideAtlasⁱ	Q13131
PRIDEⁱ	Q13131
ProteomicsDBⁱ	59180 59181 [Q13131-2]

PTM databases

iPTMnetⁱ	Q13131
PhosphoSitePlusⁱ	Q13131

Expressionⁱ

Gene expression databases

Bgeeⁱ	ENSG00000132356 Expressed in 215 organ(s), highest expression level in intestine
CleanExⁱ	HS_PRKAA1
ExpressionAtlasⁱ	Q13131 baseline and differential
Genevisibleⁱ	Q13131 HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	CAB005050 HPA035409 HPA064946

HPAⁱ

CAB005050
HPA035409
HPA064946

Interactionⁱ

Subunit structureⁱ

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 FNIP2.4 Publications

Binary interactionsⁱ

With	Entry	#Exp.	IntAct
ABI2	Q9NYB9	3	EBI-1181405,EBI-743598
AES	Q08117	3	EBI-1181405,EBI-717810
BHLHE40	O14503	3	EBI-1181405,EBI-711810
CDX4	O14627	3	EBI-1181405,EBI-10181162
CTBP1	Q13363-2	3	EBI-1181405,EBI-10171858
FSBP	O95073	3	EBI-1181405,EBI-1059030
GOLGA2	Q08379	3	EBI-1181405,EBI-618309
HMBOX1	Q6NT76	3	EBI-1181405,EBI-2549423
HOMEZ	Q8IX15-3	3	EBI-1181405,EBI-10172004
HSP90AB1	P08238	2	EBI-1181405,EBI-352572
IKZF3	Q9UKT9	3	EBI-1181405,EBI-747204
INO80E	Q8NBZ0	3	EBI-1181405,EBI-769401
KRT40	Q6A162	3	EBI-1181405,EBI-10171697
L3MBTL3	Q96JM7	3	EBI-1181405,EBI-2686809
MTUS2	Q5JR59	3	EBI-1181405,EBI-742948
PHC2	Q8IXK0	3	EBI-1181405,EBI-713786
PNMA5	Q96PV4	3	EBI-1181405,EBI-10171633
PRKAB1	Q9Y478	8	EBI-1181405,EBI-719769
PRKAB2	O43741	13	EBI-1181405,EBI-1053424
PRKAG1	P54619	12	EBI-1181405,EBI-1181439
RBPMS	Q93062	3	EBI-1181405,EBI-740322
RFX6	Q8HWS3	3	EBI-1181405,EBI-746118
RIMBP3	Q9UFD9	3	EBI-1181405,EBI-10182375
ROPN1	Q9HAT0	3	EBI-1181405,EBI-1378139
SSX2IP	Q9Y2D8	3	EBI-1181405,EBI-2212028
THAP1	Q9NVV9	3	EBI-1181405,EBI-741515
TRIM27	P14373	3	EBI-1181405,EBI-719493
TRIP6	Q15654	3	EBI-1181405,EBI-742327
TSC22D4	Q9Y3Q8	3	EBI-1181405,EBI-739485
UBXN11	Q5T124	3	EBI-1181405,EBI-746004
VPS37B	Q9H9H4	3	EBI-1181405,EBI-4400866
VPS52	Q8N1B4	3	EBI-1181405,EBI-2799833
YAP1	P46937	3	EBI-1181405,EBI-1044059
ZBED1	O96006	3	EBI-1181405,EBI-740037

GO - Molecular functionⁱ

protein C-terminus binding Source: Ensembl

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridⁱ	111549, 161 interactors
CORUMⁱ	Q13131
Database of interacting proteins More...DIPⁱ	DIP-39973N
IntActⁱ	Q13131, 105 interactors
Molecular INTeraction database More...MINTⁱ	Q13131
STRINGⁱ	9606.ENSP00000346148

Chemistry databases

BindingDBⁱ

Q13131

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Feature key	Position(s)	DescriptionActions	Length
Beta strandⁱ	27 – 35	Combined sources	9
Beta strandⁱ	40 – 49	Combined sources	10
Beta strandⁱ	52 – 59	Combined sources	8
Helixⁱ	60 – 66	Combined sources	7
Beta strandⁱ	68 – 70	Combined sources	3
Helixⁱ	71 – 77	Combined sources	7
Beta strandⁱ	90 – 95	Combined sources	6
Beta strandⁱ	97 – 105	Combined sources	9
Helixⁱ	112 – 118	Combined sources	7
Helixⁱ	124 – 144	Combined sources	21
Helixⁱ	153 – 155	Combined sources	3
Beta strandⁱ	156 – 158	Combined sources	3
Beta strandⁱ	164 – 167	Combined sources	4
Beta strandⁱ	169 – 171	Combined sources	3
Helixⁱ	193 – 196	Combined sources	4
Helixⁱ	204 – 220	Combined sources	17
Beta strandⁱ	227 – 229	Combined sources	3
Helixⁱ	231 – 233	Combined sources	3
Helixⁱ	250 – 259	Combined sources	10
Helixⁱ	264 – 266	Combined sources	3
Helixⁱ	270 – 274	Combined sources	5
Helixⁱ	277 – 280	Combined sources	4
Turnⁱ	296 – 298	Combined sources	3
Helixⁱ	301 – 310	Combined sources	10
Helixⁱ	315 – 323	Combined sources	9
Helixⁱ	330 – 340	Combined sources	11
Turnⁱ	347 – 351	Combined sources	5
Helixⁱ	372 – 374	Combined sources	3

Show more details

3D structure databases

ProteinModelPortalⁱ	Q13131
SMRⁱ	Q13131
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Domainⁱ	27 – 279	Protein kinasePROSITE-ProRule annotationAdd BLAST		253

Region

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Regionⁱ	302 – 381	AISAdd BLAST		80

Domainⁱ

Sequence similaritiesⁱ

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

Phylogenomic databases

eggNOGⁱ	KOG0586 Eukaryota ENOG410XNQ0 LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00930000150880
HOGENOMⁱ	HOG000233016
HOVERGENⁱ	HBG050432
KEGG Orthology (KO) More...KOⁱ	K07198
OMAⁱ	QGVRRAK
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G03TG
PhylomeDBⁱ	Q13131
TreeFamⁱ	TF314032

Family and domain databases

Conserved Domains Database More...CDDⁱ	cd12199 AMPKA1_C, 1 hit
InterProⁱ	View protein in InterPro IPR032270 AMPK_C IPR039137 AMPKA1_C IPR028375 KA1/Ssp2_C IPR011009 Kinase-like_dom_sf IPR000719 Prot_kinase_dom IPR017441 Protein_kinase_ATP_BS IPR008271 Ser/Thr_kinase_AS
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF16579 AdenylateSensor, 1 hit PF00069 Pkinase, 1 hit
SMARTⁱ	View protein in SMART SM00220 S_TKc, 1 hit
SUPFAMⁱ	SSF103243 SSF103243, 1 hit SSF56112 SSF56112, 1 hit
PROSITEⁱ	View protein in PROSITE PS00107 PROTEIN_KINASE_ATP, 1 hit PS50011 PROTEIN_KINASE_DOM, 1 hit PS00108 PROTEIN_KINASE_ST, 1 hit

Sequences (2+)ⁱ

Sequence statusⁱ: Complete.

This entry describes 2 isoformsⁱ produced by alternative splicing. Align Add to basket

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show all Align All

Isoform 1 (identifier: Q13131-1) [UniParc]FASTA Add to basket

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.

« Hide

        10         20         30         40         50
MRRLSSWRKM ATAEKQKHDG RVKIGHYILG DTLGVGTFGK VKVGKHELTG 
        60         70         80         90        100
HKVAVKILNR QKIRSLDVVG KIRREIQNLK LFRHPHIIKL YQVISTPSDI 
       110        120        130        140        150
FMVMEYVSGG ELFDYICKNG RLDEKESRRL FQQILSGVDY CHRHMVVHRD 
       160        170        180        190        200
LKPENVLLDA HMNAKIADFG LSNMMSDGEF LRTSCGSPNY AAPEVISGRL 
       210        220        230        240        250
YAGPEVDIWS SGVILYALLC GTLPFDDDHV PTLFKKICDG IFYTPQYLNP 
       260        270        280        290        300
SVISLLKHML QVDPMKRATI KDIREHEWFK QDLPKYLFPE DPSYSSTMID 
       310        320        330        340        350
DEALKEVCEK FECSEEEVLS CLYNRNHQDP LAVAYHLIID NRRIMNEAKD 
       360        370        380        390        400
FYLATSPPDS FLDDHHLTRP HPERVPFLVA ETPRARHTLD ELNPQKSKHQ 
       410        420        430        440        450
GVRKAKWHLG IRSQSRPNDI MAEVCRAIKQ LDYEWKVVNP YYLRVRRKNP 
       460        470        480        490        500
VTSTYSKMSL QLYQVDSRTY LLDFRSIDDE ITEAKSGTAT PQRSGSVSNY 
       510        520        530        540        550
RSCQRSDSDA EAQGKSSEVS LTSSVTSLDS SPVDLTPRPG SHTIEFFEMC 

ANLIKILAQ

Length:559

Mass (Da):64,009

Last modified:July 28, 2009 - v4

Checksum:ⁱABAE71FBF912947A

GO

Isoform 2 (identifier: Q13131-2) [UniParc]FASTA Add to basket

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

« Hide

        10         20         30         40         50
MRRLSSWRKM ATAEKQKHDG RVKIGHYILG DTLGVGTFGK VKVGKHELTG 
        60         70         80         90        100
HKVAVKILNR QKIRSLDVVG KIRREIQNLK LFRHPHIIKL YQVISTPSDI 
       110        120        130        140        150
FMVMEYVSGG ELFDYICKNG RKSDVPGVVK TGSTKELDEK ESRRLFQQIL 
       160        170        180        190        200
SGVDYCHRHM VVHRDLKPEN VLLDAHMNAK IADFGLSNMM SDGEFLRTSC 
       210        220        230        240        250
GSPNYAAPEV ISGRLYAGPE VDIWSSGVIL YALLCGTLPF DDDHVPTLFK 
       260        270        280        290        300
KICDGIFYTP QYLNPSVISL LKHMLQVDPM KRATIKDIRE HEWFKQDLPK 
       310        320        330        340        350
YLFPEDPSYS STMIDDEALK EVCEKFECSE EEVLSCLYNR NHQDPLAVAY 
       360        370        380        390        400
HLIIDNRRIM NEAKDFYLAT SPPDSFLDDH HLTRPHPERV PFLVAETPRA 
       410        420        430        440        450
RHTLDELNPQ KSKHQGVRKA KWHLGIRSQS RPNDIMAEVC RAIKQLDYEW 
       460        470        480        490        500
KVVNPYYLRV RRKNPVTSTY SKMSLQLYQV DSRTYLLDFR SIDDEITEAK 
       510        520        530        540        550
SGTATPQRSG SVSNYRSCQR SDSDAEAQGK SSEVSLTSSV TSLDSSPVDL 
       560        570 
TPRPGSHTIE FFEMCANLIK ILAQ

Show »

Length:574

Mass (Da):65,523

Checksum:ⁱ8EA8B85393F48DAA

GO

Computationally mapped potential isoform sequencesⁱ

There is 1 potential isoform mapped to this entry.BLAST Align Show all Add to basket

	Entry	Entry name		Protein names	Gene names	Length	Annotation

	Q96E92	Q96E92_HUMAN		5'-AMP-activated protein kinase cat... 5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1 protein) (Protein kinase, AMP-activated, alpha 1 catalytic subunit, isoform CRA_b)	PRKAA1 hCG_37338	207	Annotation score:

Sequence cautionⁱ

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

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

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

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

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

Experimental Info

Feature key	Position(s)	DescriptionActions	Length
Sequence conflictⁱ	5	S → C in BAG35788 (PubMed:14702039).Curated	1
Sequence conflictⁱ	9	K → S in AAD43027 (PubMed:11042152).Curated	1
Sequence conflictⁱ	37	T → A in AAA64850 (Ref. 6) Curated	1
Sequence conflictⁱ	202	A → V in AAA64850 (Ref. 6) Curated	1
Sequence conflictⁱ	208	I → L in AAA64850 (Ref. 6) Curated	1
Sequence conflictⁱ	269	T → S in BAA36547 (Ref. 3) Curated	1

Natural variant

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Natural variantⁱVAR_058401	10	M → L1 PublicationCorresponds to variant dbSNP:rs17855679Ensembl.		1
Natural variantⁱVAR_035622	16	Q → R in a breast cancer sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs928784854Ensembl.		1

Alternative sequence

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Alternative sequenceⁱVSP_035431	121	R → RKSDVPGVVKTGSTKE in isoform 2. 1 Publication		1

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	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
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS3932.2 [Q13131-1] CCDS3933.2 [Q13131-2]
PIRⁱ	G01743
NCBI Reference Sequences More...RefSeqⁱ	NP_006242.5, NM_006251.5 [Q13131-1] NP_996790.3, NM_206907.3 [Q13131-2]
UniGeneⁱ	Hs.43322

Genome annotation databases

Ensemblⁱ	ENST00000354209; ENSP00000346148; ENSG00000132356 [Q13131-2] ENST00000397128; ENSP00000380317; ENSG00000132356 [Q13131-1]
GeneIDⁱ	5562
KEGGⁱ	hsa:5562
UCSC genome browser More...UCSCⁱ	uc003jmb.4 human [Q13131-1]

Keywords - Coding sequence diversityⁱ

Alternative splicing, Polymorphism

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
Q13131	Non-specific serine/threonine protein kinase		PANTR		559	UniRef100_Q13131
Non-specific serine/threonine protein kinase		PONAB		559
Non-specific serine/threonine protein kinase		Cebus capucinus imitator		559
Non-specific serine/threonine protein kinase		AOTNA		559
Non-specific serine/threonine protein kinase		PANPA		559
+2
Q13131-2	Non-specific serine/threonine protein kinase		PANTR		574	UniRef100_H2R5J1
Non-specific serine/threonine protein kinase		PONAB		574
Non-specific serine/threonine protein kinase		PANPA		574

Protein	Similar proteins		Species	Score	Length	Source
Q13131	Non-specific serine/threonine protein kinase		PANTR		559	UniRef90_Q13131
Non-specific serine/threonine protein kinase		PONAB		559
Non-specific serine/threonine protein kinase		Cebus capucinus imitator		559
Non-specific serine/threonine protein kinase		AOTNA		559
Non-specific serine/threonine protein kinase		PANPA		559
+66

Protein	Similar proteins		Species	Score	Length	Source
Q13131	5'-AMP-activated protein kinase catalytic subunit alpha-2		MOUSE		552	UniRef50_Q13131
5'-AMP-activated protein kinase catalytic subunit alpha-2		PONAB		552
5'-AMP-activated protein kinase catalytic subunit alpha-2		RAT		552
5'-AMP-activated protein kinase catalytic subunit alpha-2		PIG		552
Non-specific serine/threonine protein kinase		PANTR		559
+467

Cross-referencesⁱ

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	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
CCDSⁱ	CCDS3932.2 [Q13131-1] CCDS3933.2 [Q13131-2]
PIRⁱ	G01743
RefSeqⁱ	NP_006242.5, NM_006251.5 [Q13131-1] NP_996790.3, NM_206907.3 [Q13131-2]
UniGeneⁱ	Hs.43322

3D structure databases

Select the link destinations: Protein Data Bank Europe More...PDBeⁱ Protein Data Bank RCSB More...RCSB PDBⁱ Protein Data Bank Japan More...PDBjⁱ Links Updated	PDB entry	Method	Resolution (Å)	Chain	Positions	PDBsum
	4RED	X-ray	2.95	A/B	22-362	[»]
	4RER	X-ray	4.05	A	20-559	[»]
	4REW	X-ray	4.58	A	20-559	[»]
	5EZV	X-ray	2.99	A/C	359-401	[»]
ProteinModelPortalⁱ	Q13131
SMRⁱ	Q13131
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	111549, 161 interactors
CORUMⁱ	Q13131
DIPⁱ	DIP-39973N
IntActⁱ	Q13131, 105 interactors
MINTⁱ	Q13131
STRINGⁱ	9606.ENSP00000346148

Chemistry databases

BindingDBⁱ	Q13131
ChEMBLⁱ	CHEMBL4045
DrugBankⁱ	DB00945 Acetylsalicylic acid DB00131 Adenosine monophosphate DB00171 Adenosine triphosphate DB00914 Phenformin

PTM databases

iPTMnetⁱ	Q13131
PhosphoSitePlusⁱ	Q13131

Polymorphism and mutation databases

BioMutaⁱ	PRKAA1
DMDMⁱ	254763436

Proteomic databases

EPDⁱ	Q13131
MaxQBⁱ	Q13131
PaxDbⁱ	Q13131
PeptideAtlasⁱ	Q13131
PRIDEⁱ	Q13131
ProteomicsDBⁱ	59180 59181 [Q13131-2]

Protocols and materials databases

The DNASU plasmid repository More...DNASUⁱ	5562
Structural Biology Knowledgebase	Search...

Genome annotation databases

Ensemblⁱ	ENST00000354209; ENSP00000346148; ENSG00000132356 [Q13131-2] ENST00000397128; ENSP00000380317; ENSG00000132356 [Q13131-1]
GeneIDⁱ	5562
KEGGⁱ	hsa:5562
UCSCⁱ	uc003jmb.4 human [Q13131-1]

Organism-specific databases

CTDⁱ	5562
DisGeNETⁱ	5562
EuPathDBⁱ	HostDB:ENSG00000132356.11
GeneCardsⁱ	PRKAA1
H-InvDBⁱ	HIX0004832
HGNCⁱ	HGNC:9376 PRKAA1
HPAⁱ	CAB005050 HPA035409 HPA064946
MIMⁱ	602739 gene
neXtProtⁱ	NX_Q13131
OpenTargetsⁱ	ENSG00000132356
PharmGKBⁱ	PA33744
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	KOG0586 Eukaryota ENOG410XNQ0 LUCA
GeneTreeⁱ	ENSGT00930000150880
HOGENOMⁱ	HOG000233016
HOVERGENⁱ	HBG050432
KOⁱ	K07198
OMAⁱ	QGVRRAK
OrthoDBⁱ	EOG091G03TG
PhylomeDBⁱ	Q13131
TreeFamⁱ	TF314032

Enzyme and pathway databases

BRENDAⁱ	2.7.11.1 2681
Reactomeⁱ	R-HSA-1632852 Macroautophagy R-HSA-380972 Energy dependent regulation of mTOR by LKB1-AMPK R-HSA-5628897 TP53 Regulates Metabolic Genes R-HSA-6804756 Regulation of TP53 Activity through Phosphorylation
SignaLinkⁱ	Q13131
SIGNORⁱ	Q13131

Miscellaneous databases

ChiTaRSⁱ	PRKAA1 human
GeneWikiⁱ	Protein_kinase,_AMP-activated,_alpha_1
GenomeRNAiⁱ	5562
Protein Ontology More...PROⁱ	PR:Q13131
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000132356 Expressed in 215 organ(s), highest expression level in intestine
CleanExⁱ	HS_PRKAA1
ExpressionAtlasⁱ	Q13131 baseline and differential
Genevisibleⁱ	Q13131 HS

Family and domain databases

CDDⁱ	cd12199 AMPKA1_C, 1 hit
InterProⁱ	View protein in InterPro IPR032270 AMPK_C IPR039137 AMPKA1_C IPR028375 KA1/Ssp2_C IPR011009 Kinase-like_dom_sf IPR000719 Prot_kinase_dom IPR017441 Protein_kinase_ATP_BS IPR008271 Ser/Thr_kinase_AS
Pfamⁱ	View protein in Pfam PF16579 AdenylateSensor, 1 hit PF00069 Pkinase, 1 hit
SMARTⁱ	View protein in SMART SM00220 S_TKc, 1 hit
SUPFAMⁱ	SSF103243 SSF103243, 1 hit SSF56112 SSF56112, 1 hit
PROSITEⁱ	View protein in PROSITE PS00107 PROTEIN_KINASE_ATP, 1 hit PS50011 PROTEIN_KINASE_DOM, 1 hit PS00108 PROTEIN_KINASE_ST, 1 hit
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	AAPK1_HUMAN
Accessionⁱ	Q13131Primary (citable) accession number: Q13131 Secondary accession number(s): A8MTQ6 , B2R7E1, O00286, Q5D0E1, Q86VS1, Q9UNQ4
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
	Last sequence update:	July 28, 2009
	Last modified:	November 7, 2018
	This is version 204 of the entry and version 4 of the sequence. See complete history.
Entry statusⁱ	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.

Miscellaneousⁱ

Keywords - Technical termⁱ

3D-structure, Complete proteome, Reference proteome

Documents

SIMILARITY comments
Index of protein domains and families
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
PDB cross-references
Index of Protein Data Bank (PDB) cross-references
Human chromosome 5
Human chromosome 5: entries, gene names and cross-references to MIM
Human and mouse protein kinases
Human and mouse protein kinases: classification and index

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UniProtKB - Q13131 (AAPK1_HUMAN)

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

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Keywords - PTMi

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Keywords - Coding sequence diversityi

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Sequence cautionⁱ

Keywords - Coding sequence diversityⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ