2yza

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[2yza]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YZA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2YZA FirstGlance]. <br>
<table><tr><td colspan='2'>[[2yza]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YZA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2YZA FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2h6d|2h6d]]</td></tr>
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</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2h6d|2h6d]]</td></tr>
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<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PRKAA2, AMPK, AMPK2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PRKAA2, AMPK, AMPK2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2yza FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yza OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2yza RCSB], [http://www.ebi.ac.uk/pdbsum/2yza PDBsum]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2yza FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yza OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2yza RCSB], [http://www.ebi.ac.uk/pdbsum/2yza PDBsum]</span></td></tr>
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<table>
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</table>
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== Function ==
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[[http://www.uniprot.org/uniprot/AAPK2_HUMAN AAPK2_HUMAN]] 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: 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 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.<ref>PMID:7959015</ref> <ref>PMID:11554766</ref> <ref>PMID:11518699</ref> <ref>PMID:12519745</ref> <ref>PMID:14651849</ref> <ref>PMID:15866171</ref> <ref>PMID:17711846</ref> <ref>PMID:17486097</ref> <ref>PMID:18184930</ref> <ref>PMID:20074060</ref> <ref>PMID:20160076</ref> <ref>PMID:21205641</ref>
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Non-specific serine/threonine protein kinase]]
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[[Category: Kishishita, S.]]
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[[Category: Kishishita, S]]
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[[Category: RSGI, RIKEN Structural Genomics/Proteomics Initiative.]]
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[[Category: Structural genomic]]
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[[Category: Saijo, S.]]
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[[Category: Saijo, S]]
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[[Category: Shirouzu, M.]]
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[[Category: Shirouzu, M]]
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[[Category: Takagi, T.]]
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[[Category: Takagi, T]]
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[[Category: Yokoyama, S.]]
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[[Category: Yokoyama, S]]
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[[Category: Yoshikawa, S.]]
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[[Category: Yoshikawa, S]]
[[Category: Atp-binding]]
[[Category: Atp-binding]]
[[Category: Cholesterol biosynthesis]]
[[Category: Cholesterol biosynthesis]]
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[[Category: Nucleotide-binding]]
[[Category: Nucleotide-binding]]
[[Category: Phosphorylation]]
[[Category: Phosphorylation]]
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[[Category: Riken structural genomics/proteomics initiative]]
 
[[Category: Rsgi]]
[[Category: Rsgi]]
[[Category: Serine/threonine protein kinase]]
[[Category: Serine/threonine protein kinase]]
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[[Category: Signaling protein]]
[[Category: Signaling protein]]
[[Category: Steroid biosynthesis]]
[[Category: Steroid biosynthesis]]
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[[Category: Structural genomic]]
 
[[Category: Transferase]]
[[Category: Transferase]]

Revision as of 19:10, 25 December 2014

Crystal structure of kinase domain of Human 5'-AMP-activated protein kinase alpha-2 subunit mutant (T172D)

2yza, resolution 3.02Å

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