Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

P54646

- AAPK2_HUMAN

UniProt

P54646 - AAPK2_HUMAN

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
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 150 (01 Oct 2014)
      Sequence version 2 (16 Apr 2002)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    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

    Magnesium.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 binding Source: UniProtKB
    9. protein kinase activity Source: ProtInc
    10. protein serine/threonine/tyrosine kinase activity Source: MGI
    11. 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

    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

    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 CaMKK22 Publications
    Modified residuei258 – 2581PhosphothreonineBy similarity
    Modified residuei377 – 3771Phosphoserine3 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. 45 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 – 249
    Beta strandi26 – 3510
    Turni36 – 383
    Beta strandi41 – 488
    Helixi49 – 546
    Helixi58 – 6912
    Beta strandi79 – 846
    Beta strandi86 – 949
    Helixi101 – 1088
    Helixi113 – 13321
    Helixi142 – 1443
    Beta strandi145 – 1473
    Beta strandi153 – 1553
    Helixi160 – 1623
    Helixi183 – 1853
    Helixi192 – 20918
    Helixi219 – 22810
    Helixi239 – 24810
    Helixi253 – 2553
    Helixi259 – 2646
    Helixi266 – 2694
    Helixi274 – 2763
    Turni284 – 2863
    Helixi291 – 2944
    Helixi304 – 3129
    Helixi322 – 33514
    Helixi338 – 3414
    Beta strandi403 – 4086
    Helixi412 – 42413
    Turni425 – 4273
    Beta strandi429 – 4346
    Beta strandi437 – 4437
    Turni445 – 4473
    Beta strandi450 – 46011
    Turni461 – 4633
    Beta strandi464 – 4718
    Helixi535 – 54814

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    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 7-551.
    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.
    HOGENOMiHOG000233016.
    HOVERGENiHBG050432.
    InParanoidiP54646.
    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_dom.
    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

    MAEKQKHDGR VKIGHYVLGD TLGVGTFGKV KIGEHQLTGH KVAVKILNRQ    50
    KIRSLDVVGK IKREIQNLKL FRHPHIIKLY QVISTPTDFF MVMEYVSGGE 100
    LFDYICKHGR VEEMEARRLF QQILSAVDYC HRHMVVHRDL KPENVLLDAH 150
    MNAKIADFGL SNMMSDGEFL RTSCGSPNYA APEVISGRLY AGPEVDIWSC 200
    GVILYALLCG TLPFDDEHVP TLFKKIRGGV FYIPEYLNRS VATLLMHMLQ 250
    VDPLKRATIK DIREHEWFKQ DLPSYLFPED PSYDANVIDD EAVKEVCEKF 300
    ECTESEVMNS LYSGDPQDQL AVAYHLIIDN RRIMNQASEF YLASSPPSGS 350
    FMDDSAMHIP PGLKPHPERM PPLIADSPKA RCPLDALNTT KPKSLAVKKA 400
    KWHLGIRSQS KPYDIMAEVY RAMKQLDFEW KVVNAYHLRV RRKNPVTGNY 450
    VKMSLQLYLV DNRSYLLDFK SIDDEVVEQR SGSSTPQRSC SAAGLHRPRS 500
    SFDSTTAESH SLSGSLTGSL TGSTLSSVSP RLGSHTMDFF EMCASLITTL 550
    AR 552
    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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:
    PDBe
    RCSB PDB
    PDBj
    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 7-551.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 111550. 45 interactions.
    DIPi DIP-39796N.
    IntActi P54646. 36 interactions.
    MINTi MINT-2804161.
    STRINGi 9606.ENSP00000360290.

    Chemistry

    BindingDBi P54646.
    ChEMBLi CHEMBL3038455.
    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.
    HOGENOMi HOG000233016.
    HOVERGENi HBG050432.
    InParanoidi P54646.
    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

    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_dom.
    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

    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: October 1, 2014
    This is version 150 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