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Q5RDH5

- AAPK1_PONAB

UniProt

Q5RDH5 - AAPK1_PONAB

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Protein
5'-AMP-activated protein kinase catalytic subunit alpha-1
Gene
PRKAA1
Organism
Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at transcript 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.

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-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. 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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei51 – 511ATP By similarity
Active sitei145 – 1451Proton acceptor By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi28 – 369ATP By similarity

GO - Molecular functioni

  1. AMP-activated protein kinase activity Source: UniProtKB
  2. ATP binding Source: UniProtKB-KW
  3. [acetyl-CoA carboxylase] kinase activity Source: UniProtKB-EC
  4. [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity Source: UniProtKB-EC
  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
Complete GO annotation...

GO - Biological processi

  1. Wnt signaling pathway Source: UniProtKB-KW
  2. activation of MAPK activity Source: InterPro
  3. autophagy Source: UniProtKB-KW
  4. cellular response to glucose starvation Source: UniProtKB
  5. cellular response to nutrient levels Source: UniProtKB
  6. cholesterol biosynthetic process Source: UniProtKB-KW
  7. fatty acid biosynthetic process Source: UniProtKB-KW
  8. fatty acid homeostasis Source: UniProtKB
  9. glucose homeostasis Source: UniProtKB
  10. histone-serine phosphorylation Source: GOC
  11. lipid biosynthetic process Source: UniProtKB
  12. negative regulation of TOR signaling Source: UniProtKB
  13. negative regulation of apoptotic process Source: UniProtKB
  14. negative regulation of lipid catabolic process Source: UniProtKB
  15. positive regulation of autophagy Source: UniProtKB
  16. positive regulation of glycolytic process Source: UniProtKB
  17. regulation of circadian rhythm Source: UniProtKB
  18. regulation of energy homeostasis Source: UniProtKB
  19. regulation of transcription, DNA-templated Source: UniProtKB-KW
  20. response to gamma radiation Source: UniProtKB
  21. rhythmic process Source: UniProtKB-KW
  22. transcription, DNA-templated 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):
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
OrganismiPongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii)
Taxonomic identifieri9601 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaePongo
ProteomesiUP000001595: 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-SubCell
  3. nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini‹1 – 554›5545'-AMP-activated protein kinase catalytic subunit alpha-1
PRO_0000085592Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei27 – 271Phosphothreonine By similarity
Modified residuei178 – 1781Phosphothreonine; by LKB1 and CaMKK2 By similarity
Modified residuei264 – 2641Phosphothreonine By similarity
Modified residuei351 – 3511Phosphoserine By similarity
Modified residuei355 – 3551Phosphoserine; by ULK1 By similarity
Modified residuei363 – 3631Phosphothreonine; by ULK1 By similarity
Modified residuei377 – 3771Phosphothreonine By similarity
Modified residuei392 – 3921Phosphoserine; by ULK1 By similarity
Modified residuei462 – 4621Phosphoserine By similarity
Modified residuei481 – 4811Phosphoserine; by ULK1 By similarity
Modified residuei483 – 4831Phosphothreonine; by ULK1 By similarity
Modified residuei485 – 4851Phosphothreonine By similarity
Modified residuei491 – 4911Phosphoserine By similarity

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 By similarity. Dephosphorylated by PPM1A and PPM1B By similarity.

Keywords - PTMi

Phosphoprotein, Ubl conjugation

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

ProteinModelPortaliQ5RDH5.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini22 – 274253Protein kinase
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni297 – 37680AIS By similarity
Add
BLAST

Domaini

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

Sequence similaritiesi

Phylogenomic databases

HOVERGENiHBG050432.
KOiK07198.

Family and domain databases

InterProiIPR028375. KA1/Ssp2_C.
IPR011009. Kinase-like_dom.
IPR028797. PRKAA1.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
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.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Fragment.

Q5RDH5-1 [UniParc]FASTAAdd to Basket

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SWRKMATAEK QKHDGRVRIG HYILGDTLGV GTFGKVKVGK HELTGHKVAV    50
KILNRQKIRS LDVVGKIRRE IQNLKLFRHP HIIKLYQVIS TPSDIFMVME 100
YVSGGELFDY ICKNGRLDEK ESRRLFQQIL SGVDYCHRHM VVHRDLKPEN 150
VLLDAHMNAK IADFGLSNMM SDGEFLRTSC GSPNYAAPEV ISGRLYAGPE 200
VDIWSSGVIL YALLCGTLPF DDDHVPTLFK KICDGIFYTP QYLNPSVISL 250
LKHMLQVDPM KRATIKDIRE HEWFKQDLPK YLFPEDPSYS STMIDDEALK 300
EVCEKFECSE EEVLSCLYNR NHQDPLAVAY HLIIDNRRIM NEAKDFYLAT 350
SPPDSFLDDH HLTRPHPERV PFLVAETPRA RHTLDELNPQ KSKHQGVRKA 400
KWHLGIRSQS RPNDIMAEVC RAIKQLDYEW KVVNPYYLRV RRKNPVTSTY 450
SKMSLQLYQV DSRTYLLDFR SIDDEITEAK SGTATPQRSG SVSNYRSCQR 500
SDSDAEAQGK SSEVSLTSSV TSLDSSPVDL TPRPGSHTIE FFEMCANLIK 550
ILAQ 554
Length:554
Mass (Da):63,393
Last modified:July 28, 2009 - v2
Checksum:iD33AA742EA2FAEE7
GO

Sequence cautioni

The sequence CAH90182.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Non-terminal residue

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Non-terminal residuei1 – 11

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
CR857935 mRNA. Translation: CAH90182.1. Different initiation.
RefSeqiNP_001127249.1. NM_001133777.1.
UniGeneiPab.8607.

Genome annotation databases

GeneIDi100174304.
KEGGipon:100174304.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
CR857935 mRNA. Translation: CAH90182.1 . Different initiation.
RefSeqi NP_001127249.1. NM_001133777.1.
UniGenei Pab.8607.

3D structure databases

ProteinModelPortali Q5RDH5.
ModBasei Search...

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 100174304.
KEGGi pon:100174304.

Organism-specific databases

CTDi 5562.

Phylogenomic databases

HOVERGENi HBG050432.
KOi K07198.

Family and domain databases

InterProi IPR028375. KA1/Ssp2_C.
IPR011009. Kinase-like_dom.
IPR028797. PRKAA1.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
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 PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  1. The German cDNA consortium
    Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Kidney.

Entry informationi

Entry nameiAAPK1_PONAB
AccessioniPrimary (citable) accession number: Q5RDH5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 13, 2005
Last sequence update: July 28, 2009
Last modified: June 11, 2014
This is version 75 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, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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