ID AAKG2_MOUSE Reviewed; 566 AA. AC Q91WG5; E9QK80; Q6V7V5; DT 13-SEP-2005, integrated into UniProtKB/Swiss-Prot. DT 27-JUL-2011, sequence version 2. DT 03-OCT-2012, entry version 79. DE RecName: Full=5'-AMP-activated protein kinase subunit gamma-2; DE Short=AMPK gamma2; DE Short=AMPK subunit gamma-2; GN Name=Prkag2; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; OC Muroidea; Muridae; Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B). RC STRAIN=C57BL/6J; RA Zhou G., Jiang D., Zhang Y.; RT "Cloning of mouse protein kinase, AMP-activated, gamma 2 non-catalytic RT subunit."; RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., RA She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., RA Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., RA Zhou S., Teague B., Potamousis K., Churas C., Place M., Herschleb J., RA Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., RA Lindblad-Toh K., Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of RT the mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A). RC STRAIN=FVB/N; TISSUE=Kidney; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-196, AND MASS RP SPECTROMETRY. RC TISSUE=Brain cortex; RX PubMed=17114649; DOI=10.1074/mcp.M600046-MCP200; RA Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F., RA Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D., RA Gerrits B., Panse C., Schlapbach R., Mansuy I.M.; RT "Qualitative and quantitative analyses of protein phosphorylation in RT naive and stimulated mouse synaptosomal preparations."; RL Mol. Cell. Proteomics 6:283-293(2007). RN [5] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-65; SER-71; SER-73; RP SER-90; SER-138; SER-158; SER-161 AND SER-162, AND MASS SPECTROMETRY. RC TISSUE=Liver; RX PubMed=17242355; DOI=10.1073/pnas.0609836104; RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.; RT "Large-scale phosphorylation analysis of mouse liver."; RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007). RN [6] RP PHOSPHORYLATION BY ULK1. RX PubMed=21460634; RA Loffler A.S., Alers S., Dieterle A.M., Keppeler H., Franz-Wachtel M., RA Kundu M., Campbell D.G., Wesselborg S., Alessi D.R., Stork B.; RT "Ulk1-mediated phosphorylation of AMPK constitutes a negative RT regulatory feedback loop."; RL Autophagy 7:696-706(2011). CC -!- FUNCTION: AMP/ATP-binding subunit of AMP-activated protein kinase CC (AMPK), an energy sensor protein kinase that plays a key role in CC regulating cellular energy metabolism. In response to reduction of CC intracellular ATP levels, AMPK activates energy-producing pathways CC and inhibits energy-consuming processes: inhibits protein, CC carbohydrate and lipid biosynthesis, as well as cell growth and CC proliferation. AMPK acts via direct phosphorylation of metabolic CC enzymes, and by longer-term effects via phosphorylation of CC transcription regulators. Also acts as a regulator of cellular CC polarity by remodeling the actin cytoskeleton; probably by CC indirectly activating myosin. Gamma non-catalytic subunit mediates CC binding to AMP, ADP and ATP, leading to activate or inhibit AMPK: CC AMP-binding results in allosteric activation of alpha catalytic CC subunit (PRKAA1 or PRKAA2) both by inducing phosphorylation and CC preventing dephosphorylation of catalytic subunits. ADP also CC stimulates phosphorylation, without stimulating already CC phosphorylated catalytic subunit. ATP promotes dephosphorylation CC of catalytic subunit, rendering the AMPK enzyme inactive (By CC similarity). CC -!- SUBUNIT: AMPK is a heterotrimer of an alpha catalytic subunit CC (PRKAA1 or PRKAA2), a beta (PRKAB1 or PRKAB2) and a gamma non- CC catalytic subunits (PRKAG1, PRKAG2 or PRKAG3). Interacts with CC FNIP1 and FNIP2 (By similarity). CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=A; CC IsoId=Q91WG5-1; Sequence=Displayed; CC Name=B; CC IsoId=Q91WG5-2; Sequence=VSP_015586; CC -!- DOMAIN: The AMPK pseudosubstrate motif resembles the sequence CC around sites phosphorylated on target proteins of AMPK, except the CC presence of a non-phosphorylatable residue in place of Ser. In the CC absence of AMP this pseudosubstrate sequence may bind to the CC active site groove on the alpha subunit (PRKAA1 or PRKAA2), CC preventing phosphorylation by the upstream activating kinase CC STK11/LKB1 (By similarity). CC -!- DOMAIN: The CBS domains mediate binding to AMP, ADP and ATP. 2 CC sites bind either AMP or ATP, whereas a third site contains a CC tightly bound AMP that does not exchange. Under physiological CC conditions AMPK mainly exists in its inactive form in complex with CC ATP, which is much more abundant than AMP (By similarity). CC -!- PTM: Phosphorylated upon DNA damage, probably by ATM or ATR (By CC similarity). Phosphorylated by ULK1; leading to negatively CC regulate AMPK activity and suggesting the existence of a CC regulatory feedback loop between ULK1 and AMPK. CC -!- SIMILARITY: Belongs to the 5'-AMP-activated protein kinase gamma CC subunit family. CC -!- SIMILARITY: Contains 4 CBS domains. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AY348864; AAQ55224.1; -; mRNA. DR EMBL; AC116151; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC125270; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC015283; AAH15283.1; -; mRNA. DR IPI; IPI00128126; -. DR IPI; IPI00649331; -. DR RefSeq; NP_001164027.1; NM_001170556.1. DR RefSeq; NP_663376.2; NM_145401.2. DR UniGene; Mm.33649; -. DR ProteinModelPortal; Q91WG5; -. DR SMR; Q91WG5; 253-554. DR IntAct; Q91WG5; 1. DR STRING; Q91WG5; -. DR PhosphoSite; Q91WG5; -. DR PRIDE; Q91WG5; -. DR Ensembl; ENSMUST00000030784; ENSMUSP00000030784; ENSMUSG00000028944. DR Ensembl; ENSMUST00000114975; ENSMUSP00000110626; ENSMUSG00000028944. DR GeneID; 108099; -. DR KEGG; mmu:108099; -. DR CTD; 51422; -. DR MGI; MGI:1336153; Prkag2. DR eggNOG; COG0517; -. DR GeneTree; ENSGT00390000009849; -. DR HOGENOM; HOG000176880; -. DR HOVERGEN; HBG050431; -. DR InParanoid; Q91WG5; -. DR KO; K07200; -. DR OMA; TVFPFSY; -. DR OrthoDB; EOG45DWPQ; -. DR NextBio; 360062; -. DR ArrayExpress; Q91WG5; -. DR Bgee; Q91WG5; -. DR Genevestigator; Q91WG5; -. DR GermOnline; ENSMUSG00000028944; Mus musculus. DR GO; GO:0031588; C:AMP-activated protein kinase complex; IEA:Compara. DR GO; GO:0043531; F:ADP binding; IEA:Compara. DR GO; GO:0016208; F:AMP binding; IEA:Compara. DR GO; GO:0004679; F:AMP-activated protein kinase activity; TAS:MGI. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004862; F:cAMP-dependent protein kinase inhibitor activity; IEA:Compara. DR GO; GO:0008603; F:cAMP-dependent protein kinase regulator activity; IEA:Compara. DR GO; GO:0008607; F:phosphorylase kinase regulator activity; IEA:Compara. DR GO; GO:0030295; F:protein kinase activator activity; IEA:Compara. DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:UniProtKB-KW. DR GO; GO:0005977; P:glycogen metabolic process; IEA:Compara. DR GO; GO:0007243; P:intracellular protein kinase cascade; IEA:Compara. DR GO; GO:0010800; P:positive regulation of peptidyl-threonine phosphorylation; IEA:Compara. DR GO; GO:0019217; P:regulation of fatty acid metabolic process; IEA:Compara. DR GO; GO:0006110; P:regulation of glycolysis; IEA:Compara. DR GO; GO:0006950; P:response to stress; TAS:MGI. DR Gene3D; G3DSA:3.20.20.70; Aldolase_TIM; 2. DR InterPro; IPR013785; Aldolase_TIM. DR InterPro; IPR000644; Cysta_beta_synth_core. DR Pfam; PF00571; CBS; 3. DR SMART; SM00116; CBS; 4. DR PROSITE; PS51371; CBS; 4. PE 1: Evidence at protein level; KW Alternative splicing; ATP-binding; CBS domain; Complete proteome; KW Fatty acid biosynthesis; Fatty acid metabolism; Lipid biosynthesis; KW Lipid metabolism; Nucleotide-binding; Phosphoprotein; KW Reference proteome; Repeat. FT CHAIN 1 566 5'-AMP-activated protein kinase subunit FT gamma-2. FT /FTId=PRO_0000204382. FT DOMAIN 272 332 CBS 1. FT DOMAIN 354 412 CBS 2. FT DOMAIN 427 489 CBS 3. FT DOMAIN 501 559 CBS 4. FT MOTIF 367 388 AMPK pseudosubstrate. FT BINDING 299 299 AMP 1 (By similarity). FT BINDING 299 299 ATP 1 (By similarity). FT BINDING 380 380 AMP 2 (By similarity). FT BINDING 380 380 AMP 3 (By similarity). FT BINDING 380 380 ATP 2 (By similarity). FT BINDING 381 381 ATP 1 (By similarity). FT BINDING 381 381 ATP 2 (By similarity). FT BINDING 399 399 AMP 1 (By similarity). FT BINDING 399 399 ATP 1 (By similarity). FT BINDING 527 527 AMP 3 (By similarity). FT BINDING 528 528 AMP 1 (By similarity). FT BINDING 528 528 ATP 1 (By similarity). FT MOD_RES 65 65 Phosphoserine. FT MOD_RES 71 71 Phosphoserine. FT MOD_RES 73 73 Phosphoserine. FT MOD_RES 86 86 Phosphoserine (By similarity). FT MOD_RES 90 90 Phosphoserine. FT MOD_RES 129 129 Phosphoserine (By similarity). FT MOD_RES 130 130 Phosphoserine (By similarity). FT MOD_RES 131 131 Phosphoserine (By similarity). FT MOD_RES 134 134 Phosphoserine (By similarity). FT MOD_RES 135 135 Phosphoserine (By similarity). FT MOD_RES 138 138 Phosphoserine. FT MOD_RES 142 142 Phosphothreonine (By similarity). FT MOD_RES 143 143 Phosphoserine (By similarity). FT MOD_RES 156 156 Phosphothreonine (By similarity). FT MOD_RES 157 157 Phosphoserine (By similarity). FT MOD_RES 158 158 Phosphoserine. FT MOD_RES 160 160 Phosphoserine (By similarity). FT MOD_RES 161 161 Phosphoserine. FT MOD_RES 162 162 Phosphoserine. FT MOD_RES 164 164 Phosphoserine (By similarity). FT MOD_RES 165 165 Phosphothreonine (By similarity). FT MOD_RES 167 167 Phosphothreonine (By similarity). FT MOD_RES 195 195 Phosphoserine (By similarity). FT MOD_RES 196 196 Phosphoserine. FT MOD_RES 218 218 Phosphoserine (By similarity). FT VAR_SEQ 1 240 Missing (in isoform B). FT /FTId=VSP_015586. FT CONFLICT 257 257 V -> F (in Ref. 3; AAH15283). FT CONFLICT 516 516 T -> N (in Ref. 1; AAQ55224). SQ SEQUENCE 566 AA; 62949 MW; D112BFD69D1C5ACB CRC64; MGSAAMDTKK KKEVSSPGGS SGKKNPSLKR RSLRVHIPDL SSFAMPLLDG DVENSEKHSS RKVDSPFSSG SPSRGLFSRG PQPRPSSPVS APVRPKTSPG SPKTVFPFSY QESPPRSPRR MSFSGIFRSS SKESSPNSNP STSPGGIRFF SRSRKTSSVS SSPSTPTQVT KQHPFPLESY KQEPERPESR IYASSSPPDT GQRFCLAFQS PARPPLASPT YHAPLRTAVL AAAPGPAEAG MLEKLEFQEE EDSESGVYMR FMRSHKCYDI VPTSSKLVVF DTTLQVKKAF FALVANGVRA APLWESKKQS FVGMLTITDF INILHRYYKS PMVQIYELEE HKIETWRELY LQETFKPLVN ISPDASLFDA VYSLIKNKIH RLPVIDPISG NALYILTHKR ILKFLQLFMS DMPKPAFMKQ NLDELGIGTY HNIAFIHPDT PIIKALNIFV ERRISALPVV DESGKVVDIY SKFDVINLAA EKTYNNLDIT VTQALQHRSQ YFEGVVKCSK LETLETIVDR IVRAEVHRLV VVNEADSIVG IISLSDILQA LILTPAGAKQ KETETE //