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Q09136 (AAPK1_PIG) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 96. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·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):
AMPK 63 kDa subunit
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
OrganismSus scrofa (Pig) [Reference proteome]
Taxonomic identifier9823 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus

Protein attributes

Sequence length385 AA.
Sequence statusFragments.
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 By similarity. Ref.1

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 By similarity.

Enzyme regulation

Activated by phosphorylation on Thr-133. Binding of AMP to non-catalytic gamma subunit (PRKAG1, PRKAG2 or PRKAG3) results in allosteric activation, inducing phosphorylation on Thr-133. AMP-binding to gamma subunit also sustains activity by preventing dephosphorylation of Thr-133. ADP also stimulates Thr-133 phosphorylation, without stimulating already phosphorylated AMPK. ATP promotes dephosphorylation of Thr-133, 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. 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 By similarity.

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.

Subcellular location

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

Induction

By AMP.

Domain

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

Post-translational modification

Ubiquitinated By similarity.

Phosphorylated at Thr-133 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Also phosphorylated at Thr-133 by CAMKK2; triggered by a rise in intracellular calcium ions, without detectable changes in the AMP/ATP ratio. CAMKK1 can also phosphorylate Thr-133, 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 By similarity. Dephosphorylated by PPM1A and PPM1B By similarity.

Sequence similarities

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

Contains 1 protein kinase domain.

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
   LigandATP-binding
Magnesium
Metal-binding
Nucleotide-binding
   Molecular functionChromatin regulator
Kinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
Ubl conjugation
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processWnt signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

activation of MAPK activity

Inferred from electronic annotation. Source: InterPro

autophagy

Inferred from electronic annotation. Source: UniProtKB-KW

cellular response to glucose starvation

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to nutrient levels

Inferred from sequence or structural similarity. Source: UniProtKB

cholesterol biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-KW

fatty acid biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-KW

fatty acid homeostasis

Inferred from sequence or structural similarity. Source: UniProtKB

glucose homeostasis

Inferred from sequence or structural similarity. Source: UniProtKB

histone-serine phosphorylation

Inferred from sequence or structural similarity. Source: GOC

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 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 glycolysis

Inferred from sequence or structural similarity. 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

response to stress

Inferred from sequence or structural similarity. Source: UniProtKB

rhythmic process

Inferred from electronic annotation. Source: UniProtKB-KW

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentAMP-activated protein kinase complex

Inferred from sequence or structural similarity. Source: UniProtKB

cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionAMP-activated protein kinase activity

Inferred from sequence or structural similarity. 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

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: UniProtKB-EC

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain‹1 – ›385›3855'-AMP-activated protein kinase catalytic subunit alpha-1
PRO_0000085591

Regions

Domain‹1 – 229›229Protein kinase
Nucleotide binding15 – ›22›8ATP By similarity
Region252 – 29746AIS By similarity

Sites

Active site1001Proton acceptor By similarity

Amino acid modifications

Modified residue141Phosphothreonine By similarity
Modified residue1331Phosphothreonine; by LKB1 and CaMKK2 By similarity
Modified residue2191Phosphothreonine By similarity
Modified residue2771Phosphoserine By similarity
Modified residue2811Phosphoserine; by ULK1 By similarity
Modified residue2891Phosphothreonine; by ULK1 By similarity
Modified residue2981Phosphothreonine By similarity
Modified residue3531Phosphoserine By similarity

Experimental info

Non-adjacent residues22 – 232
Non-adjacent residues157 – 1582
Non-adjacent residues255 – 2562
Non-adjacent residues270 – 2712
Non-adjacent residues290 – 2912
Non-adjacent residues300 – 3012
Non-adjacent residues323 – 3242
Non-adjacent residues342 – 3432
Non-adjacent residues367 – 3682
Non-terminal residue11
Non-terminal residue3851

Sequences

Sequence LengthMass (Da)Tools
Q09136 [UniParc].

Last modified September 2, 2008. Version 2.
Checksum: A9B4BC0C935A85A6

FASTA38544,226
        10         20         30         40         50         60 
DGRVKIGHYI LGDTLGVGTF GKRREIQNLK LFRHPHIIKL YQVISTPSDI FMVMEYVSGG 

        70         80         90        100        110        120 
ELFDYICKNG RLDEKESRRL FQQILSGVDY CHRHMVVHRD LKPENVLLDA HMNAKIADFG 

       130        140        150        160        170        180 
LSNMMSDGEF LRTSCGSPNY AAPEVISGRL YAGPEVDIWS SGVILYALLC GTLPFDDDHV 

       190        200        210        220        230        240 
PTLFKKICDG IFYTPQYLNP SVISLLKHML QVDPMKRATI KDIREHEWFK QDLPKYLFPE 

       250        260        270        280        290        300 
DPSYSXTMID DEALKQDPLA VAYHLIIDNR DFYLATSPPD SFLDDHHLTR VPFLVAETPR 

       310        320        330        340        350        360 
DELNPQKXKH QGVRKAKXHL GIRQLDYEXK VVNPYYLRVR RKKMSLQLYQ VDSRTYLLDF 

       370        380 
RSIDDXIDAE AQGKSSEASL TXSVT 

« Hide

References

[1]"Mammalian AMP-activated protein kinase shares structural and functional homology with the catalytic domain of yeast Snf1 protein kinase."
Mitchelhill K.I., Stapleton D., Gao G., House C., Michell B., Katsis F., Witters L.A., Kemp B.E.
J. Biol. Chem. 269:2361-2364(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 1-22; 73-87; 100-157; 222-240 AND 344-361, FUNCTION.
Tissue: Liver.
[2]"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: PROTEIN SEQUENCE OF 1-22; 73-88; 100-132; 144-156; 209-216; 221-255; 256-270; 271-290; 291-300; 301-323; 324-342; 343-367 AND 368-385.
Tissue: Liver.
[3]"Effect of dietary hemicellulose on growth and energy metabolism of growing pigs."
Weber T.E.
Submitted (APR-2008) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 23-243.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
EU622639 mRNA. Translation: ACC78144.1.
PIRA49958.
UniGeneSsc.26892.

3D structure databases

ProteinModelPortalQ09136.
ModBaseSearch...
MobiDBSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Phylogenomic databases

HOVERGENHBG050432.

Family and domain databases

InterProIPR028375. KA1/Ssp2_C.
IPR011009. Kinase-like_dom.
IPR028797. PRKAA1.
IPR000719. Prot_kinase_dom.
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.
PROSITEPS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameAAPK1_PIG
AccessionPrimary (citable) accession number: Q09136
Secondary accession number(s): B2MV24
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: September 2, 2008
Last modified: April 16, 2014
This is version 96 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families