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Q09136

- AAPK1_PIG

UniProt

Q09136 - AAPK1_PIG

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Protein

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

Gene

PRKAA1

Organism
Sus scrofa (Pig)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

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. 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.By similarity

Catalytic activityi

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.

Cofactori

Magnesium.By similarity

Enzyme regulationi

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.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei100 – 1001Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi15 – ›22›8ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. [acetyl-CoA carboxylase] kinase activity Source: UniProtKB-EC
  2. [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity Source: UniProtKB-EC
  3. AMP-activated protein kinase activity Source: UniProtKB
  4. ATP binding Source: UniProtKB-KW
  5. chromatin binding Source: UniProtKB
  6. histone serine kinase activity Source: UniProtKB
  7. metal ion binding Source: UniProtKB-KW
  8. tau-protein kinase activity Source: UniProtKB-EC

GO - Biological processi

  1. activation of MAPK activity Source: InterPro
  2. autophagy Source: UniProtKB-KW
  3. cellular response to glucose starvation Source: UniProtKB
  4. cellular response to nutrient levels Source: UniProtKB
  5. cholesterol biosynthetic process Source: UniProtKB-KW
  6. fatty acid biosynthetic process Source: UniProtKB-KW
  7. fatty acid homeostasis Source: UniProtKB
  8. glucose homeostasis Source: UniProtKB
  9. histone-serine phosphorylation Source: GOC
  10. lipid biosynthetic process Source: UniProtKB
  11. negative regulation of apoptotic process Source: UniProtKB
  12. negative regulation of lipid catabolic process Source: UniProtKB
  13. negative regulation of TOR signaling Source: UniProtKB
  14. positive regulation of autophagy Source: UniProtKB
  15. positive regulation of glycolytic process Source: UniProtKB
  16. regulation of circadian rhythm Source: UniProtKB
  17. regulation of energy homeostasis Source: UniProtKB
  18. regulation of transcription, DNA-templated Source: UniProtKB-KW
  19. response to gamma radiation Source: UniProtKB
  20. rhythmic process Source: UniProtKB-KW
  21. transcription, DNA-templated Source: UniProtKB-KW
  22. Wnt signaling pathway Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

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

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
5'-AMP-activated protein kinase catalytic subunit alpha-1 (EC:2.7.11.1)
Short name:
AMPK subunit alpha-1
Alternative name(s):
AMPK 63 kDa subunit
Acetyl-CoA carboxylase kinase (EC:2.7.11.27)
Short name:
ACACA kinase
Hydroxymethylglutaryl-CoA reductase kinase (EC:2.7.11.31)
Short name:
HMGCR kinase
Tau-protein kinase PRKAA1 (EC:2.7.11.26)
Gene namesi
Name:PRKAA1
Synonyms:AMPK1
OrganismiSus scrofa (Pig)
Taxonomic identifieri9823 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus
ProteomesiUP000008227: Unplaced

Subcellular locationi

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

GO - Cellular componenti

  1. AMP-activated protein kinase complex Source: UniProtKB
  2. cytoplasm Source: UniProtKB-KW
  3. nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini‹1 – ›385›3855'-AMP-activated protein kinase catalytic subunit alpha-1PRO_0000085591Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei14 – 141PhosphothreonineBy similarity
Modified residuei133 – 1331Phosphothreonine; by LKB1 and CaMKK2By similarity
Modified residuei219 – 2191PhosphothreonineBy similarity
Modified residuei277 – 2771PhosphoserineBy similarity
Modified residuei281 – 2811Phosphoserine; by ULK1By similarity
Modified residuei289 – 2891Phosphothreonine; by ULK1By similarity
Modified residuei298 – 2981PhosphothreonineBy similarity
Modified residuei353 – 3531PhosphoserineBy similarity

Post-translational modificationi

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.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Expressioni

Inductioni

By AMP.

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.

Structurei

3D structure databases

ProteinModelPortaliQ09136.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini‹1 – 229›229Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni252 – 29746AISBy similarityAdd
BLAST

Domaini

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

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

HOVERGENiHBG050432.
InParanoidiQ09136.

Family and domain databases

InterProiIPR028375. KA1/Ssp2_C.
IPR011009. Kinase-like_dom.
IPR028797. PRKAA1.
IPR000719. Prot_kinase_dom.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERiPTHR24343:SF81. PTHR24343:SF81. 1 hit.
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF103243. SSF103243. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Fragments.

Q09136-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
DGRVKIGHYI LGDTLGVGTF GKRREIQNLK LFRHPHIIKL YQVISTPSDI
60 70 80 90 100
FMVMEYVSGG ELFDYICKNG RLDEKESRRL FQQILSGVDY CHRHMVVHRD
110 120 130 140 150
LKPENVLLDA HMNAKIADFG LSNMMSDGEF LRTSCGSPNY AAPEVISGRL
160 170 180 190 200
YAGPEVDIWS SGVILYALLC GTLPFDDDHV PTLFKKICDG IFYTPQYLNP
210 220 230 240 250
SVISLLKHML QVDPMKRATI KDIREHEWFK QDLPKYLFPE DPSYSXTMID
260 270 280 290 300
DEALKQDPLA VAYHLIIDNR DFYLATSPPD SFLDDHHLTR VPFLVAETPR
310 320 330 340 350
DELNPQKXKH QGVRKAKXHL GIRQLDYEXK VVNPYYLRVR RKKMSLQLYQ
360 370 380
VDSRTYLLDF RSIDDXIDAE AQGKSSEASL TXSVT
Length:385
Mass (Da):44,226
Last modified:September 2, 2008 - v2
Checksum:iA9B4BC0C935A85A6
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Non-terminal residuei1 – 11
Non-adjacent residuesi22 – 232Curated
Non-adjacent residuesi157 – 1582Curated
Non-adjacent residuesi255 – 2562Curated
Non-adjacent residuesi270 – 2712Curated
Non-adjacent residuesi290 – 2912Curated
Non-adjacent residuesi300 – 3012Curated
Non-adjacent residuesi323 – 3242Curated
Non-adjacent residuesi342 – 3432Curated
Non-adjacent residuesi367 – 3682Curated
Non-terminal residuei385 – 3851

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
EU622639 mRNA. Translation: ACC78144.1.
PIRiA49958.
UniGeneiSsc.26892.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
EU622639 mRNA. Translation: ACC78144.1 .
PIRi A49958.
UniGenei Ssc.26892.

3D structure databases

ProteinModelPortali Q09136.
ModBasei Search...
MobiDBi Search...

Protocols and materials databases

Structural Biology Knowledgebase Search...

Phylogenomic databases

HOVERGENi HBG050432.
InParanoidi Q09136.

Family and domain databases

InterProi IPR028375. KA1/Ssp2_C.
IPR011009. Kinase-like_dom.
IPR028797. PRKAA1.
IPR000719. Prot_kinase_dom.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view ]
PANTHERi PTHR24343:SF81. PTHR24343:SF81. 1 hit.
Pfami PF00069. Pkinase. 1 hit.
[Graphical view ]
SMARTi SM00220. S_TKc. 1 hit.
[Graphical view ]
SUPFAMi SSF103243. SSF103243. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEi PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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. 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.

Entry informationi

Entry nameiAAPK1_PIG
AccessioniPrimary (citable) accession number: Q09136
Secondary accession number(s): B2MV24
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: September 2, 2008
Last modified: October 29, 2014
This is version 100 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3