ID   AAPK2_MOUSE             Reviewed;         552 AA.
AC   Q8BRK8; Q3UYM4;
DT   28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT   28-NOV-2006, sequence version 2.
DT   16-JUN-2009, entry version 52.
DE   RecName: Full=5'-AMP-activated protein kinase catalytic subunit alpha-2;
DE            Short=AMPK alpha-2 chain;
DE            EC=2.7.11.1;
GN   Name=Prkaa2;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi;
OC   Muroidea; Muridae; Murinae; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RG   The mouse genome sequencing consortium;
RL   Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 15-552.
RC   STRAIN=C57BL/6J; TISSUE=Brain cortex, and Medulla oblongata;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M.,
RA   Davis M.J., Wilming L.G., Aidinis V., Allen J.E.,
RA   Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L.,
RA   Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M.,
RA   Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R.,
RA   Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G.,
RA   di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G.,
RA   Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M.,
RA   Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N.,
RA   Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T.,
RA   Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H.,
RA   Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K.,
RA   Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J.,
RA   Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L.,
RA   Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K.,
RA   Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P.,
RA   Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O.,
RA   Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G.,
RA   Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M.,
RA   Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B.,
RA   Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K.,
RA   Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A.,
RA   Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K.,
RA   Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C.,
RA   Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J.,
RA   Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y.,
RA   Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T.,
RA   Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N.,
RA   Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N.,
RA   Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S.,
RA   Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J.,
RA   Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [3]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=15331533;
RA   Villena J.A., Viollet B., Andreelli F., Kahn A., Vaulont S., Sul H.S.;
RT   "Induced adiposity and adipocyte hypertrophy in mice lacking the AMP-
RT   activated protein kinase-alpha2 subunit.";
RL   Diabetes 53:2242-2249(2004).
RN   [4]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-173 AND SER-500, AND
RP   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).
CC   -!- FUNCTION: Responsible for the regulation of fatty acid synthesis
CC       by phosphorylation of acetyl-CoA carboxylase. It also regulates
CC       cholesterol synthesis via phosphorylation and inactivation of
CC       hormone-sensitive lipase and hydroxymethylglutaryl-CoA reductase.
CC       Appears to act as a metabolic stress-sensing protein kinase
CC       switching off biosynthetic pathways when cellular ATP levels are
CC       depleted and when 5'-AMP rises in response to fuel limitation
CC       and/or hypoxia. This is a catalytic subunit.
CC   -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
CC   -!- COFACTOR: Magnesium (By similarity).
CC   -!- ENZYME REGULATION: Binding of AMP results in allosteric
CC       activation, inducing phosphorylation on Thr-172 by STK11 in
CC       complex with STE20-related adapter-alpha (STRAD alpha) pseudo
CC       kinase and CAB39. Also activated by phosphorylation by CAMKK2
CC       triggered by a rise in intracellular calcium ions, without
CC       detectable changes in the AMP/ATP ratio (By similarity).
CC   -!- SUBUNIT: Heterotrimer of a catalytic subunit, a beta and a gamma
CC       non-catalytic subunits (By similarity).
CC   -!- DISRUPTION PHENOTYPE: Mice develop obesity when animals are fed a
CC       high-fat diet, as a result of an enhanced lipid accumulation in
CC       pre-existing adipocytes but not in other tissues.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK
CC       Ser/Thr protein kinase family. SNF1 subfamily.
CC   -!- SIMILARITY: Contains 1 protein kinase domain.
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DR   EMBL; AL627307; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AK044030; BAC31746.1; -; mRNA.
DR   EMBL; AK134573; BAE22188.1; -; mRNA.
DR   IPI; IPI00123445; -.
DR   RefSeq; NP_835279.1; -.
DR   UniGene; Mm.48638; -.
DR   HSSP; P49137; 1NXK.
DR   SMR; Q8BRK8; 10-278.
DR   PhosphoSite; Q8BRK8; -.
DR   Ensembl; ENSMUSG00000028518; Mus musculus.
DR   GeneID; 108079; -.
DR   KEGG; mmu:108079; -.
DR   MGI; MGI:1336173; Prkaa2.
DR   HOVERGEN; Q8BRK8; -.
DR   BRENDA; 2.7.11.1; 244.
DR   NextBio; 360016; -.
DR   ArrayExpress; Q8BRK8; -.
DR   Bgee; Q8BRK8; -.
DR   GermOnline; ENSMUSG00000028518; Mus musculus.
DR   GO; GO:0005634; C:nucleus; IDA:MGI.
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:0000287; F:magnesium ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0006695; P:cholesterol biosynthetic process; IEA:UniProtKB-KW.
DR   GO; GO:0006633; P:fatty acid biosynthetic process; IEA:UniProtKB-KW.
DR   GO; GO:0006468; P:protein amino acid phosphorylation; IEA:InterPro.
DR   GO; GO:0006950; P:response to stress; TAS:MGI.
DR   InterPro; IPR015741; AMPK.
DR   InterPro; IPR000719; Prot_kinase_core.
DR   InterPro; IPR017441; Protein_kinase_ATP_BS.
DR   InterPro; IPR017442; Se/Thr_pkinase-rel.
DR   InterPro; IPR008271; Ser_thr_pkin_AS.
DR   InterPro; IPR002290; Ser_thr_pkinase.
DR   PANTHER; PTHR22982:SF61; AMPK; 1.
DR   Pfam; PF00069; Pkinase; 1.
DR   ProDom; PD000001; Prot_kinase; 1.
DR   SMART; SM00220; S_TKc; 1.
DR   PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE   1: Evidence at protein level;
KW   ATP-binding; Cholesterol biosynthesis; Fatty acid biosynthesis;
KW   Kinase; Lipid synthesis; Magnesium; Metal-binding; Nucleotide-binding;
KW   Phosphoprotein; Serine/threonine-protein kinase; Steroid biosynthesis;
KW   Sterol biosynthesis; Transferase.
FT   CHAIN         1    552       5'-AMP-activated protein kinase catalytic
FT                                subunit alpha-2.
FT                                /FTId=PRO_0000262957.
FT   DOMAIN       16    268       Protein kinase.
FT   NP_BIND      22     30       ATP (By similarity).
FT   ACT_SITE    139    139       Proton acceptor (By similarity).
FT   BINDING      45     45       ATP (By similarity).
FT   MOD_RES     172    172       Phosphothreonine; by STK11 (By
FT                                similarity).
FT   MOD_RES     173    173       Phosphoserine.
FT   MOD_RES     176    176       Phosphoserine (By similarity).
FT   MOD_RES     377    377       Phosphoserine (By similarity).
FT   MOD_RES     500    500       Phosphoserine.
FT   CONFLICT     15     15       H -> D (in Ref. 2; BAE22188).
FT   CONFLICT    289    289       V -> D (in Ref. 2; BAE22188).
FT   CONFLICT    380    380       A -> E (in Ref. 2; BAE22188).
FT   CONFLICT    502    502       F -> Y (in Ref. 2; BAE22188).
FT   CONFLICT    506    506       T -> K (in Ref. 2; BAE22188).
SQ   SEQUENCE   552 AA;  62006 MW;  593911EAB3BBFE3F CRC64;
     MAEKQKHDGR VKIGHYVLGD TLGVGTFGKV KIGEHQLTGH KVAVKILNRQ KIRSLDVVGK
     IKREIQNLKL FRHPHIIKLY QVISTPTDFF MVMEYVSGGE LFDYICKHGR VEEVEARRLF
     QQILSAVDYC HRHMVVHRDL KPENVLLDAQ MNAKIADFGL SNMMSDGEFL RTSCGSPNYA
     APEVISGRLY AGPEVDIWSC GVILYALLCG TLPFDDEHVP TLFKKIRGGV FYIPDYLNRS
     VATLLMHMLQ VDPLKRATIK DIREHEWFKQ DLPSYLFPED PSYDANVIVD EAVKEVCEKF
     ECTESEVMNS LYSGDPQDQL AVAYHLIIDN RRIMNQASEF YLASSPPSGS FMDDSAMHIP
     PGLKPHPERM PPLIADSPKA RCPLDALNTT KPKSLAVKKA KWHLGIRSQS KACDIMAEVY
     RAMKQLGFEW KVVNAYHLRV RRKNPVTGNY VKMSLQLYLV DSRSYLLDFK SIDDEVVEQR
     SGSSTPQRSC SAAGLHRARS SFDSSTAENH SLSGSLTGSL TGSTLSSASP RLGSHTMDFF
     EMCASLITAL AR
//