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Q5RDH5 (AAPK1_PONAB) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 73. 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):
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
OrganismPongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii) [Reference proteome]
Taxonomic identifier9601 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaePongo

Protein attributes

Sequence length554 AA.
Sequence statusFragment.
Protein existenceEvidence at transcript 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.

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-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.

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.

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-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.

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

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
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 – 554›5545'-AMP-activated protein kinase catalytic subunit alpha-1
PRO_0000085592

Regions

Domain22 – 274253Protein kinase
Nucleotide binding28 – 369ATP By similarity
Region297 – 37680AIS By similarity

Sites

Active site1451Proton acceptor By similarity
Binding site511ATP By similarity

Amino acid modifications

Modified residue271Phosphothreonine By similarity
Modified residue1781Phosphothreonine; by LKB1 and CaMKK2 By similarity
Modified residue2641Phosphothreonine By similarity
Modified residue3511Phosphoserine By similarity
Modified residue3551Phosphoserine; by ULK1 By similarity
Modified residue3631Phosphothreonine; by ULK1 By similarity
Modified residue3771Phosphothreonine By similarity
Modified residue3921Phosphoserine; by ULK1 By similarity
Modified residue4621Phosphoserine By similarity
Modified residue4811Phosphoserine; by ULK1 By similarity
Modified residue4831Phosphothreonine; by ULK1 By similarity
Modified residue4851Phosphothreonine By similarity
Modified residue4911Phosphoserine By similarity

Experimental info

Non-terminal residue11

Sequences

Sequence LengthMass (Da)Tools
Q5RDH5 [UniParc].

Last modified July 28, 2009. Version 2.
Checksum: D33AA742EA2FAEE7

FASTA55463,393
        10         20         30         40         50         60 
SWRKMATAEK QKHDGRVRIG HYILGDTLGV GTFGKVKVGK HELTGHKVAV KILNRQKIRS 

        70         80         90        100        110        120 
LDVVGKIRRE IQNLKLFRHP HIIKLYQVIS TPSDIFMVME YVSGGELFDY ICKNGRLDEK 

       130        140        150        160        170        180 
ESRRLFQQIL SGVDYCHRHM VVHRDLKPEN VLLDAHMNAK IADFGLSNMM SDGEFLRTSC 

       190        200        210        220        230        240 
GSPNYAAPEV ISGRLYAGPE VDIWSSGVIL YALLCGTLPF DDDHVPTLFK KICDGIFYTP 

       250        260        270        280        290        300 
QYLNPSVISL LKHMLQVDPM KRATIKDIRE HEWFKQDLPK YLFPEDPSYS STMIDDEALK 

       310        320        330        340        350        360 
EVCEKFECSE EEVLSCLYNR NHQDPLAVAY HLIIDNRRIM NEAKDFYLAT SPPDSFLDDH 

       370        380        390        400        410        420 
HLTRPHPERV PFLVAETPRA RHTLDELNPQ KSKHQGVRKA KWHLGIRSQS RPNDIMAEVC 

       430        440        450        460        470        480 
RAIKQLDYEW KVVNPYYLRV RRKNPVTSTY SKMSLQLYQV DSRTYLLDFR SIDDEITEAK 

       490        500        510        520        530        540 
SGTATPQRSG SVSNYRSCQR SDSDAEAQGK SSEVSLTSSV TSLDSSPVDL TPRPGSHTIE 

       550 
FFEMCANLIK ILAQ 

« Hide

References

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

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
CR857935 mRNA. Translation: CAH90182.1. Different initiation.
RefSeqNP_001127249.1. NM_001133777.1.
UniGenePab.8607.

3D structure databases

ProteinModelPortalQ5RDH5.
ModBaseSearch...
MobiDBSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID100174304.
KEGGpon:100174304.

Organism-specific databases

CTD5562.

Phylogenomic databases

HOVERGENHBG050432.
KOK07198.

Family and domain databases

InterProIPR028375. 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]
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.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameAAPK1_PONAB
AccessionPrimary (citable) accession number: Q5RDH5
Entry history
Integrated into UniProtKB/Swiss-Prot: September 13, 2005
Last sequence update: July 28, 2009
Last modified: April 16, 2014
This is version 73 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