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P54646

- AAPK2_HUMAN

UniProt

P54646 - AAPK2_HUMAN

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Protein

5'-AMP-activated protein kinase catalytic subunit alpha-2

Gene

PRKAA2

Organism
Homo sapiens (Human)
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 phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1.12 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.
ATP + [hydroxymethylglutaryl-CoA reductase (NADPH)] = ADP + [hydroxymethylglutaryl-CoA reductase (NADPH)] phosphate.
ATP + [acetyl-CoA carboxylase] = ADP + [acetyl-CoA carboxylase] phosphate.

Cofactori

Mg2+By similarity

Enzyme regulationi

Activated by phosphorylation on Thr-172. Binding of AMP to non-catalytic gamma subunit (PRKAG1, PRKAG2 or PRKAG3) results in allosteric activation, inducing phosphorylation on Thr-172. AMP-binding to gamma subunit also sustains activity by preventing dephosphorylation of Thr-172. ADP also stimulates Thr-172 phosphorylation, without stimulating already phosphorylated AMPK. ATP promotes dephosphorylation of Thr-172, 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. Salicylate/aspirin directly activates kinase activity, primarily by inhibiting Thr-172 dephosphorylation.4 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei45 – 451ATPPROSITE-ProRule annotation
Active sitei139 – 1391Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi22 – 309ATPPROSITE-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. protein kinase activity Source: ProtInc
  9. protein serine/threonine/tyrosine kinase activity Source: MGI
  10. protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

  1. autophagy Source: UniProtKB-KW
  2. carnitine shuttle Source: Reactome
  3. cell cycle arrest Source: Reactome
  4. cellular lipid metabolic process Source: Reactome
  5. cellular response to glucose starvation Source: UniProtKB
  6. cellular response to nutrient levels Source: UniProtKB
  7. cholesterol biosynthetic process Source: UniProtKB-KW
  8. energy reserve metabolic process Source: Reactome
  9. fatty acid biosynthetic process Source: UniProtKB-KW
  10. fatty acid homeostasis Source: UniProtKB
  11. glucose homeostasis Source: UniProtKB
  12. insulin receptor signaling pathway Source: Reactome
  13. lipid biosynthetic process Source: UniProtKB
  14. membrane organization Source: Reactome
  15. negative regulation of apoptotic process Source: UniProtKB
  16. negative regulation of TOR signaling Source: UniProtKB
  17. positive regulation of autophagy Source: UniProtKB
  18. positive regulation of glycolytic process Source: UniProtKB
  19. protein phosphorylation Source: ProtInc
  20. regulation of circadian rhythm Source: UniProtKB
  21. regulation of energy homeostasis Source: UniProtKB
  22. regulation of fatty acid biosynthetic process Source: Reactome
  23. regulation of transcription, DNA-templated Source: UniProtKB-KW
  24. response to stress Source: UniProtKB
  25. rhythmic process Source: UniProtKB-KW
  26. signal transduction Source: ProtInc
  27. small molecule metabolic process Source: Reactome
  28. transcription, DNA-templated Source: UniProtKB-KW
  29. 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

Enzyme and pathway databases

BRENDAi2.7.11.1. 2681.
ReactomeiREACT_11082. Import of palmitoyl-CoA into the mitochondrial matrix.
REACT_147867. Translocation of GLUT4 to the plasma membrane.
REACT_1988. AMPK inhibits chREBP transcriptional activation activity.
REACT_200686. Activation of PPARGC1A (PGC-1alpha) by phosphorylation.
REACT_21285. Regulation of AMPK activity via LKB1.
REACT_21393. Regulation of Rheb GTPase activity by AMPK.
SignaLinkiP54646.

Names & Taxonomyi

Protein namesi
Recommended name:
5'-AMP-activated protein kinase catalytic subunit alpha-2 (EC:2.7.11.1)
Short name:
AMPK subunit alpha-2
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
Gene namesi
Name:PRKAA2
Synonyms:AMPK, AMPK2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 1

Organism-specific databases

HGNCiHGNC:9377. PRKAA2.

Subcellular locationi

Cytoplasm By similarity. Nucleus 1 Publication
Note: In response to stress, recruited by p53/TP53 to specific promoters.

GO - Cellular componenti

  1. cytosol Source: Reactome
  2. nucleoplasm Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi172 – 1721T → D: Phosphomimetic mutant.

Organism-specific databases

PharmGKBiPA33745.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 5525525'-AMP-activated protein kinase catalytic subunit alpha-2PRO_0000085594Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei172 – 1721Phosphothreonine; by LKB1 and CaMKK21 Publication
Modified residuei258 – 2581PhosphothreonineBy similarity
Modified residuei377 – 3771Phosphoserine2 Publications
Modified residuei491 – 4911PhosphoserineBy similarity

Post-translational modificationi

Ubiquitinated.By similarity
Phosphorylated at Thr-172 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Also phosphorylated at Thr-172 by CAMKK2; triggered by a rise in intracellular calcium ions, without detectable changes in the AMP/ATP ratio. CAMKK1 can also phosphorylate Thr-172, but at much lower level. Dephosphorylated by protein phosphatase 2A and 2C (PP2A and PP2C). Phosphorylated by ULK1; leading to negatively regulate AMPK activity and suggesting the existence of a regulatory feedback loop between ULK1 and AMPK. Dephosphorylated by PPM1A and PPM1B at Thr-172 (mediated by STK11/LKB1).4 Publications

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP54646.
PaxDbiP54646.
PRIDEiP54646.

PTM databases

PhosphoSiteiP54646.

Expressioni

Gene expression databases

BgeeiP54646.
CleanExiHS_PRKAA2.
GenevestigatoriP54646.

Organism-specific databases

HPAiCAB013043.

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 FNIP2.1 Publication

Protein-protein interaction databases

BioGridi111550. 47 interactions.
DIPiDIP-39796N.
IntActiP54646. 36 interactions.
MINTiMINT-2804161.
STRINGi9606.ENSP00000360290.

Structurei

Secondary structure

1
552
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi16 – 249Combined sources
Beta strandi26 – 3510Combined sources
Turni36 – 383Combined sources
Beta strandi41 – 488Combined sources
Helixi49 – 546Combined sources
Helixi58 – 6912Combined sources
Beta strandi79 – 846Combined sources
Beta strandi86 – 949Combined sources
Helixi101 – 1088Combined sources
Helixi113 – 13321Combined sources
Helixi142 – 1443Combined sources
Beta strandi145 – 1473Combined sources
Beta strandi153 – 1553Combined sources
Helixi160 – 1623Combined sources
Helixi183 – 1853Combined sources
Helixi192 – 20918Combined sources
Helixi219 – 22810Combined sources
Helixi239 – 24810Combined sources
Helixi253 – 2553Combined sources
Helixi259 – 2646Combined sources
Helixi266 – 2694Combined sources
Helixi274 – 2763Combined sources
Turni284 – 2863Combined sources
Helixi291 – 2944Combined sources
Helixi304 – 3129Combined sources
Helixi322 – 33514Combined sources
Helixi338 – 3414Combined sources
Beta strandi403 – 4086Combined sources
Helixi412 – 42413Combined sources
Turni425 – 4273Combined sources
Beta strandi429 – 4346Combined sources
Beta strandi437 – 4437Combined sources
Turni445 – 4473Combined sources
Beta strandi450 – 46011Combined sources
Turni461 – 4633Combined sources
Beta strandi464 – 4718Combined sources
Helixi535 – 54814Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2H6DX-ray1.85A6-279[»]
2LTUNMR-A282-339[»]
2YZAX-ray3.02A6-279[»]
3AQVX-ray2.08A6-279[»]
4CFEX-ray3.02A/C1-552[»]
4CFFX-ray3.92A/C1-552[»]
ProteinModelPortaliP54646.
SMRiP54646. Positions 7-549.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP54646.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini16 – 268253Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni291 – 37686AISBy similarityAdd
BLAST

Domaini

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

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000118892.
HOGENOMiHOG000233016.
HOVERGENiHBG050432.
KOiK07198.
OMAiTMHIPPG.
OrthoDBiEOG7RRF6K.
PhylomeDBiP54646.
TreeFamiTF314032.

Family and domain databases

InterProiIPR028375. KA1/Ssp2_C.
IPR011009. Kinase-like_dom.
IPR028783. PRKAA2.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERiPTHR24343:SF82. PTHR24343:SF82. 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: Complete.

P54646-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MAEKQKHDGR VKIGHYVLGD TLGVGTFGKV KIGEHQLTGH KVAVKILNRQ
60 70 80 90 100
KIRSLDVVGK IKREIQNLKL FRHPHIIKLY QVISTPTDFF MVMEYVSGGE
110 120 130 140 150
LFDYICKHGR VEEMEARRLF QQILSAVDYC HRHMVVHRDL KPENVLLDAH
160 170 180 190 200
MNAKIADFGL SNMMSDGEFL RTSCGSPNYA APEVISGRLY AGPEVDIWSC
210 220 230 240 250
GVILYALLCG TLPFDDEHVP TLFKKIRGGV FYIPEYLNRS VATLLMHMLQ
260 270 280 290 300
VDPLKRATIK DIREHEWFKQ DLPSYLFPED PSYDANVIDD EAVKEVCEKF
310 320 330 340 350
ECTESEVMNS LYSGDPQDQL AVAYHLIIDN RRIMNQASEF YLASSPPSGS
360 370 380 390 400
FMDDSAMHIP PGLKPHPERM PPLIADSPKA RCPLDALNTT KPKSLAVKKA
410 420 430 440 450
KWHLGIRSQS KPYDIMAEVY RAMKQLDFEW KVVNAYHLRV RRKNPVTGNY
460 470 480 490 500
VKMSLQLYLV DNRSYLLDFK SIDDEVVEQR SGSSTPQRSC SAAGLHRPRS
510 520 530 540 550
SFDSTTAESH SLSGSLTGSL TGSTLSSVSP RLGSHTMDFF EMCASLITTL

AR
Length:552
Mass (Da):62,320
Last modified:April 16, 2002 - v2
Checksum:iC46AAFC1D5104975
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti180 – 1801A → T in AAA64745. (PubMed:7959015)Curated
Sequence conflicti271 – 2711D → G in AAA64745. (PubMed:7959015)Curated
Sequence conflicti403 – 4042HL → RQ in AAA64745. (PubMed:7959015)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti371 – 3711P → T in breast cancer samples; infiltrating ductal carcinoma; somatic mutation. 2 Publications
VAR_035623
Natural varianti407 – 4071R → Q in a gastric adenocarcinoma sample; somatic mutation. 1 Publication
VAR_040355
Natural varianti523 – 5231S → G in a breast cancer sample; somatic mutation. 1 Publication
VAR_035624

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U06454 mRNA. Translation: AAA64745.1.
AL035705 Genomic DNA. Translation: CAC17574.2.
BC069680 mRNA. Translation: AAH69680.1.
BC069740 mRNA. Translation: AAH69740.1.
BC069823 mRNA. Translation: AAH69823.1.
CCDSiCCDS605.1.
PIRiS51025.
RefSeqiNP_006243.2. NM_006252.3.
UniGeneiHs.437039.

Genome annotation databases

EnsembliENST00000371244; ENSP00000360290; ENSG00000162409.
GeneIDi5563.
KEGGihsa:5563.
UCSCiuc001cyk.4. human.

Polymorphism databases

DMDMi20178276.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U06454 mRNA. Translation: AAA64745.1 .
AL035705 Genomic DNA. Translation: CAC17574.2 .
BC069680 mRNA. Translation: AAH69680.1 .
BC069740 mRNA. Translation: AAH69740.1 .
BC069823 mRNA. Translation: AAH69823.1 .
CCDSi CCDS605.1.
PIRi S51025.
RefSeqi NP_006243.2. NM_006252.3.
UniGenei Hs.437039.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2H6D X-ray 1.85 A 6-279 [» ]
2LTU NMR - A 282-339 [» ]
2YZA X-ray 3.02 A 6-279 [» ]
3AQV X-ray 2.08 A 6-279 [» ]
4CFE X-ray 3.02 A/C 1-552 [» ]
4CFF X-ray 3.92 A/C 1-552 [» ]
ProteinModelPortali P54646.
SMRi P54646. Positions 7-549.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 111550. 47 interactions.
DIPi DIP-39796N.
IntActi P54646. 36 interactions.
MINTi MINT-2804161.
STRINGi 9606.ENSP00000360290.

Chemistry

BindingDBi P54646.
ChEMBLi CHEMBL2116.
DrugBanki DB00945. Acetylsalicylic acid.
GuidetoPHARMACOLOGYi 1542.

PTM databases

PhosphoSitei P54646.

Polymorphism databases

DMDMi 20178276.

Proteomic databases

MaxQBi P54646.
PaxDbi P54646.
PRIDEi P54646.

Protocols and materials databases

DNASUi 5563.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000371244 ; ENSP00000360290 ; ENSG00000162409 .
GeneIDi 5563.
KEGGi hsa:5563.
UCSCi uc001cyk.4. human.

Organism-specific databases

CTDi 5563.
GeneCardsi GC01P057027.
HGNCi HGNC:9377. PRKAA2.
HPAi CAB013043.
MIMi 600497. gene.
neXtProti NX_P54646.
PharmGKBi PA33745.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00760000118892.
HOGENOMi HOG000233016.
HOVERGENi HBG050432.
KOi K07198.
OMAi TMHIPPG.
OrthoDBi EOG7RRF6K.
PhylomeDBi P54646.
TreeFami TF314032.

Enzyme and pathway databases

BRENDAi 2.7.11.1. 2681.
Reactomei REACT_11082. Import of palmitoyl-CoA into the mitochondrial matrix.
REACT_147867. Translocation of GLUT4 to the plasma membrane.
REACT_1988. AMPK inhibits chREBP transcriptional activation activity.
REACT_200686. Activation of PPARGC1A (PGC-1alpha) by phosphorylation.
REACT_21285. Regulation of AMPK activity via LKB1.
REACT_21393. Regulation of Rheb GTPase activity by AMPK.
SignaLinki P54646.

Miscellaneous databases

ChiTaRSi PRKAA2. human.
EvolutionaryTracei P54646.
GeneWikii PRKAA2.
GenomeRNAii 5563.
NextBioi 21552.
PROi P54646.
SOURCEi Search...

Gene expression databases

Bgeei P54646.
CleanExi HS_PRKAA2.
Genevestigatori P54646.

Family and domain databases

InterProi IPR028375. KA1/Ssp2_C.
IPR011009. Kinase-like_dom.
IPR028783. PRKAA2.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view ]
PANTHERi PTHR24343:SF82. PTHR24343:SF82. 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

« Hide 'large scale' publications
  1. "Characterization and chromosomal localization of the human homologue of a rat AMP-activated protein kinase-encoding gene: a major regulator of lipid metabolism in mammals."
    Aguan K., Scott J., See C.G., Sarkar N.H.
    Gene 149:345-350(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION.
    Tissue: Heart.
  2. "Molecular cloning, expression and chromosomal localisation of human AMP-activated protein kinase."
    Beri R.K., Marley A.E., See C.G., Sopwith W.F., Aguan K., Carling D., Scott J., Carey F.
    FEBS Lett. 356:117-121(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Skeletal muscle.
  3. "The DNA sequence and biological annotation of human chromosome 1."
    Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
    , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
    Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  5. "Cell cycle regulation via p53 phosphorylation by a 5'-AMP activated protein kinase activator, 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside, in a human hepatocellular carcinoma cell line."
    Imamura K., Ogura T., Kishimoto A., Kaminishi M., Esumi H.
    Biochem. Biophys. Res. Commun. 287:562-567(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  6. "Regulation of transcription by AMP-activated protein kinase: phosphorylation of p300 blocks its interaction with nuclear receptors."
    Yang W., Hong Y.H., Shen X.Q., Frankowski C., Camp H.S., Leff T.
    J. Biol. Chem. 276:38341-38344(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF EP300.
  7. Cited for: ENZYME REGULATION.
  8. "Physiological modulation of CFTR activity by AMP-activated protein kinase in polarized T84 cells."
    Hallows K.R., Kobinger G.P., Wilson J.M., Witters L.A., Foskett J.K.
    Am. J. Physiol. 284:C1297-C1308(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF CFTR.
  9. "TSC2 mediates cellular energy response to control cell growth and survival."
    Inoki K., Zhu T., Guan K.L.
    Cell 115:577-590(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF TSC2.
  10. "The Ca2+/calmodulin-dependent protein kinase kinases are AMP-activated protein kinase kinases."
    Hurley R.L., Anderson K.A., Franzone J.M., Kemp B.E., Means A.R., Witters L.A.
    J. Biol. Chem. 280:29060-29066(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT THR-172, ENZYME REGULATION.
  11. "AMP-activated protein kinase induces a p53-dependent metabolic checkpoint."
    Jones R.G., Plas D.R., Kubek S., Buzzai M., Mu J., Xu Y., Birnbaum M.J., Thompson C.B.
    Mol. Cell 18:283-293(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION.
  12. "The energy sensor AMP-activated protein kinase directly regulates the mammalian FOXO3 transcription factor."
    Greer E.L., Oskoui P.R., Banko M.R., Maniar J.M., Gygi M.P., Gygi S.P., Brunet A.
    J. Biol. Chem. 282:30107-30119(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF FOXO3.
  13. "Energy-dependent regulation of cell structure by AMP-activated protein kinase."
    Lee J.H., Koh H., Kim M., Kim Y., Lee S.Y., Karess R.E., Lee S.H., Shong M., Kim J.M., Kim J., Chung J.
    Nature 447:1017-1020(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN CELL POLARITY.
  14. "AMP-activated protein kinase regulates GLUT4 transcription by phosphorylating histone deacetylase 5."
    McGee S.L., van Denderen B.J., Howlett K.F., Mollica J., Schertzer J.D., Kemp B.E., Hargreaves M.
    Diabetes 57:860-867(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF HDAC5.
  15. "Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
    Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
    Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-377, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  16. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  17. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-377, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  18. "Cell-wide analysis of secretory granule dynamics in three dimensions in living pancreatic beta-cells: evidence against a role for AMPK-dependent phosphorylation of KLC1 at Ser517/Ser520 in glucose-stimulated insulin granule movement."
    McDonald A., Fogarty S., Leclerc I., Hill E.V., Hardie D.G., Rutter G.A.
    Biochem. Soc. Trans. 38:205-208(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF KLC1.
  19. Cited for: FUNCTION.
  20. "Ulk1-mediated phosphorylation of AMPK constitutes a negative regulatory feedback loop."
    Loffler A.S., Alers S., Dieterle A.M., Keppeler H., Franz-Wachtel M., Kundu M., Campbell D.G., Wesselborg S., Alessi D.R., Stork B.
    Autophagy 7:696-706(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION BY ULK1.
  21. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  22. Cited for: FUNCTION IN PHOSPHORYLATION OF ULK1.
  23. "AMP-activated protein kinase in metabolic control and insulin signaling."
    Towler M.C., Hardie D.G.
    Circ. Res. 100:328-341(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON FUNCTION.
  24. "AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy."
    Hardie D.G.
    Nat. Rev. Mol. Cell Biol. 8:774-785(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON FUNCTION.
  25. Cited for: ENZYME REGULATION BY SALICYLATE.
  26. "N-Myristoylation is essential for protein phosphatases PPM1A and PPM1B to dephosphorylate their physiological substrates in cells."
    Chida T., Ando M., Matsuki T., Masu Y., Nagaura Y., Takano-Yamamoto T., Tamura S., Kobayashi T.
    Biochem. J. 449:741-749(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: DEPHOSPHORYLATION AT THR-172.
  27. "A conserved mechanism of autoinhibition for the AMPK kinase domain: ATP-binding site and catalytic loop refolding as a means of regulation."
    Littler D.R., Walker J.R., Davis T., Wybenga-Groot L.E., Finerty P.J. Jr., Newman E., Mackenzie F., Dhe-Paganon S.
    Acta Crystallogr. F 66:143-151(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 6-279.
  28. "Structural basis for compound C inhibition of the human AMP-activated protein kinase alpha2 subunit kinase domain."
    Handa N., Takagi T., Saijo S., Kishishita S., Takaya D., Toyama M., Terada T., Shirouzu M., Suzuki A., Lee S., Yamauchi T., Okada-Iwabu M., Iwabu M., Kadowaki T., Minokoshi Y., Yokoyama S.
    Acta Crystallogr. D 67:480-487(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.08 ANGSTROMS) OF 6-279 OF MUTANT THR-172 IN COMPLEX WITH COMPOUND C, ENZYME REGULATION.
  29. Cited for: VARIANTS [LARGE SCALE ANALYSIS] THR-371 AND GLY-523.
  30. "Patterns of somatic mutation in human cancer genomes."
    Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.
    , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
    Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS [LARGE SCALE ANALYSIS] THR-371 AND GLN-407.

Entry informationi

Entry nameiAAPK2_HUMAN
AccessioniPrimary (citable) accession number: P54646
Secondary accession number(s): Q9H1E8, Q9UD43
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: April 16, 2002
Last modified: November 26, 2014
This is version 152 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3