ULK1_MOUSE
ID ULK1_MOUSE Reviewed; 1051 AA.
AC O70405; Q6PGB2;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=Serine/threonine-protein kinase ULK1;
DE EC=2.7.11.1 {ECO:0000305|PubMed:22539723};
DE AltName: Full=Serine/threonine-protein kinase Unc51.1;
DE AltName: Full=Unc-51-like kinase 1;
GN Name=Ulk1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=9600096; DOI=10.1006/bbrc.1998.8546;
RA Yan J., Kuroyanagi H., Kuroiwa A., Matsuda Y., Tokumitsu H., Tomoda T.,
RA Shirasawa T., Muramatsu M.-A.;
RT "Identification of mouse ULK1, a novel protein kinase structurally related
RT to C. elegans UNC-51.";
RL Biochem. Biophys. Res. Commun. 246:222-227(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=10624947; DOI=10.1016/s0896-6273(00)81031-4;
RA Tomoda T., Bhatt R.S., Kuroyanagi H., Shirasawa T., Hatten M.E.;
RT "A mouse serine/threonine kinase homologous to C. elegans UNC51 functions
RT in parallel fiber formation of cerebellar granule neurons.";
RL Neuron 24:833-846(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, INTERACTION WITH ATG13 AND RB1CC1, PHOSPHORYLATION, AND
RP SUBCELLULAR LOCATION.
RX PubMed=19258318; DOI=10.1074/jbc.m900573200;
RA Ganley I.G., Lam du H., Wang J., Ding X., Chen S., Jiang X.;
RT "ULK1.ATG13.FIP200 complex mediates mTOR signaling and is essential for
RT autophagy.";
RL J. Biol. Chem. 284:12297-12305(2009).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-450; SER-521; THR-635;
RP SER-637; SER-638 AND SER-757, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas, Spleen,
RC and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP FUNCTION IN PHOSPHORYLATION OF AMPK.
RX PubMed=21460634; DOI=10.4161/auto.7.7.15451;
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 regulatory
RT feedback loop.";
RL Autophagy 7:696-706(2011).
RN [7]
RP FUNCTION, AUTOPHOSPHORYLATION, PHOSPHORYLATION AT SER-317; SER-757 AND
RP SER-777, AND MUTAGENESIS OF LYS-46; SER-317; SER-494; SER-555; THR-574;
RP SER-622; THR-624; SER-693; SER-757; SER-777 AND SER-811.
RX PubMed=21258367; DOI=10.1038/ncb2152;
RA Kim J., Kundu M., Viollet B., Guan K.L.;
RT "AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1.";
RL Nat. Cell Biol. 13:132-141(2011).
RN [8]
RP FUNCTION, AUTOPHOSPHORYLATION, PHOSPHORYLATION AT SER-467; SER-555; THR-574
RP AND SER-637, AND MUTAGENESIS OF LYS-46.
RX PubMed=21205641; DOI=10.1126/science.1196371;
RA Egan D.F., Shackelford D.B., Mihaylova M.M., Gelino S., Kohnz R.A.,
RA Mair W., Vasquez D.S., Joshi A., Gwinn D.M., Taylor R., Asara J.M.,
RA Fitzpatrick J., Dillin A., Viollet B., Kundu M., Hansen M., Shaw R.J.;
RT "Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects
RT energy sensing to mitophagy.";
RL Science 331:456-461(2011).
RN [9]
RP FUNCTION, AND INTERACTION WITH SESN2 AND SQSTM1.
RX PubMed=25040165; DOI=10.1111/febs.12905;
RA Ro S.H., Semple I.A., Park H., Park H., Park H.W., Kim M., Kim J.S.,
RA Lee J.H.;
RT "Sestrin2 promotes Unc-51-like kinase 1 mediated phosphorylation of
RT p62/sequestosome-1.";
RL FEBS J. 281:3816-3827(2014).
RN [10]
RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, ACETYLATION AT LYS-162 AND
RP LYS-606, AND MUTAGENESIS OF LYS-162 AND LYS-606.
RX PubMed=22539723; DOI=10.1126/science.1217032;
RA Lin S.Y., Li T.Y., Liu Q., Zhang C., Li X., Chen Y., Zhang S.M., Lian G.,
RA Liu Q., Ruan K., Wang Z., Zhang C.S., Chien K.Y., Wu J., Li Q., Han J.,
RA Lin S.C.;
RT "GSK3-TIP60-ULK1 signaling pathway links growth factor deprivation to
RT autophagy.";
RL Science 336:477-481(2012).
CC -!- FUNCTION: Serine/threonine-protein kinase involved in autophagy in
CC response to starvation (PubMed:10624947, PubMed:19258318,
CC PubMed:21205641, PubMed:21258367, PubMed:21460634, PubMed:25040165).
CC Acts upstream of phosphatidylinositol 3-kinase PIK3C3 to regulate the
CC formation of autophagophores, the precursors of autophagosomes
CC (PubMed:10624947, PubMed:19258318, PubMed:21205641, PubMed:21258367,
CC PubMed:21460634, PubMed:25040165). Part of regulatory feedback loops in
CC autophagy: acts both as a downstream effector and negative regulator of
CC mammalian target of rapamycin complex 1 (mTORC1) via interaction with
CC RPTOR (PubMed:21205641, PubMed:21258367). Activated via phosphorylation
CC by AMPK and also acts as a regulator of AMPK by mediating
CC phosphorylation of AMPK subunits PRKAA1, PRKAB2 and PRKAG1, leading to
CC negatively regulate AMPK activity (PubMed:21460634). May phosphorylate
CC ATG13/KIAA0652 and RPTOR; however such data need additional evidences
CC (PubMed:19258318). Plays a role early in neuronal differentiation and
CC is required for granule cell axon formation (By similarity). May also
CC phosphorylate SESN2 and SQSTM1 to regulate autophagy (PubMed:25040165).
CC Phosphorylates FLCN, promoting autophagy (By similarity).
CC Phosphorylates AMBRA1 in response to autophagy induction, releasing
CC AMBRA1 from the cytoskeletal docking site to induce autophagosome
CC nucleation (By similarity). Phosphorylates ATG4B, leading to inhibit
CC autophagy by decreasing both proteolytic activation and delipidation
CC activities of ATG4B (By similarity). {ECO:0000250|UniProtKB:O75385,
CC ECO:0000269|PubMed:10624947, ECO:0000269|PubMed:19258318,
CC ECO:0000269|PubMed:21205641, ECO:0000269|PubMed:21258367,
CC ECO:0000269|PubMed:21460634, ECO:0000269|PubMed:25040165}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000305|PubMed:22539723};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000305|PubMed:22539723};
CC -!- ACTIVITY REGULATION: Acetylation by KAT5/TIP60 stimulates the protein
CC kinase activity (PubMed:22539723). The protein kinase activity is
CC activated by unanchored 'Lys-63'-linked polyubiquitin chains:
CC unanchored 'Lys-63'-linked polyubiquitin chains are catalyzed by TRIM32
CC in an AMBRA1-dependent manner (By similarity).
CC {ECO:0000250|UniProtKB:O75385, ECO:0000269|PubMed:22539723}.
CC -!- SUBUNIT: Interacts with GABARAP and GABARAPL2 (By similarity).
CC Interacts (via C-terminus) with ATG13 (PubMed:19258318). Part of a
CC complex consisting of ATG13, ATG101, ULK1 and RB1CC1 (PubMed:19258318).
CC Associates with the mammalian target of rapamycin complex 1 (mTORC1)
CC through an interaction with RPTOR; the association depends on nutrient
CC conditions and is reduced during starvation (By similarity). Interacts
CC with FEZ1; SCOC interferes with FEZ1-binding (By similarity). Interacts
CC with TBC1D14 (By similarity). Interacts (phosphorylated form) with
CC TRIM5 (By similarity). When phosphorylated at Ser-317, interacts with
CC MEFV and BECN1 simultaneously. Interacts with TRIM21 and IRF3, in the
CC presence of TRIM21 (By similarity). Interacts with SESN2
CC (PubMed:25040165). Interacts with SQSTM1 (PubMed:25040165). Interacts
CC with C9orf72 (By similarity). Interacts with WDR45 (By similarity).
CC Interacts with ATG13; this interaction is increased in the absence of
CC TMEM39A (By similarity). Interacts with WIPI2 (By similarity).
CC Interacts with ATP2A2 (By similarity). Interacts with AMBRA1 (By
CC similarity). {ECO:0000250|UniProtKB:O75385,
CC ECO:0000269|PubMed:19258318, ECO:0000269|PubMed:25040165}.
CC -!- INTERACTION:
CC O70405; Q9DB70: Fundc1; NbExp=2; IntAct=EBI-8390771, EBI-10106464;
CC O70405; P42859: Htt; NbExp=4; IntAct=EBI-8390771, EBI-5327353;
CC O70405; Q9JLN9: Mtor; NbExp=3; IntAct=EBI-8390771, EBI-1571628;
CC O70405; Q8IVP5: FUNDC1; Xeno; NbExp=3; IntAct=EBI-8390771, EBI-3059266;
CC O70405; P58004: SESN2; Xeno; NbExp=5; IntAct=EBI-8390771, EBI-3939642;
CC O70405; Q13501: SQSTM1; Xeno; NbExp=2; IntAct=EBI-8390771, EBI-307104;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:19258318}.
CC Preautophagosomal structure {ECO:0000269|PubMed:19258318}. Note=Under
CC starvation conditions, is localized to puncate structures primarily
CC representing the isolation membrane that sequesters a portion of the
CC cytoplasm resulting in the formation of an autophagosome.
CC -!- PTM: Autophosphorylated. Phosphorylated under nutrient-rich conditions;
CC dephosphorylated during starvation or following treatment with
CC rapamycin. In response to nutrient limitation, phosphorylated and
CC activated by AMPK, leading to activate autophagy. Under nutrient
CC sufficiency, phosphorylated by MTOR/mTOR, disrupting the interaction
CC with AMPK and preventing activation of ULK1.
CC {ECO:0000269|PubMed:19258318, ECO:0000269|PubMed:21205641,
CC ECO:0000269|PubMed:21258367}.
CC -!- PTM: Ubiquitinated via 'Lys-63'-linkage by a complex composed of AMBRA1
CC and TRAF6 following autophagy induction, promoting ULK1 stability and
CC kinase activity. {ECO:0000250|UniProtKB:O75385}.
CC -!- PTM: Acetylated by KAT5/TIP60 under autophagy induction, promoting
CC protein kinase activity. {ECO:0000269|PubMed:22539723}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. APG1/unc-51/ULK1 subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
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DR EMBL; AF053756; AAC40118.1; -; mRNA.
DR EMBL; AF072370; AAF23317.1; -; mRNA.
DR EMBL; BC057121; AAH57121.1; -; mRNA.
DR CCDS; CCDS19532.1; -.
DR PIR; JW0051; JW0051.
DR RefSeq; NP_033495.2; NM_009469.3.
DR AlphaFoldDB; O70405; -.
DR SMR; O70405; -.
DR BioGRID; 204438; 19.
DR ComplexPortal; CPX-380; ULK1-ATG13-RB1CC1-ATG101 autophagy initiation complex.
DR DIP; DIP-60541N; -.
DR IntAct; O70405; 29.
DR MINT; O70405; -.
DR STRING; 10090.ENSMUSP00000031490; -.
DR iPTMnet; O70405; -.
DR PhosphoSitePlus; O70405; -.
DR jPOST; O70405; -.
DR MaxQB; O70405; -.
DR PaxDb; O70405; -.
DR PeptideAtlas; O70405; -.
DR PRIDE; O70405; -.
DR ProteomicsDB; 298479; -.
DR DNASU; 22241; -.
DR GeneID; 22241; -.
DR KEGG; mmu:22241; -.
DR UCSC; uc008yrq.1; mouse.
DR CTD; 8408; -.
DR MGI; MGI:1270126; Ulk1.
DR eggNOG; KOG0595; Eukaryota.
DR InParanoid; O70405; -.
DR OrthoDB; 1084750at2759; -.
DR PhylomeDB; O70405; -.
DR TreeFam; TF324551; -.
DR BRENDA; 2.7.11.1; 3474.
DR Reactome; R-MMU-1632852; Macroautophagy.
DR Reactome; R-MMU-8854214; TBC/RABGAPs.
DR Reactome; R-MMU-8876198; RAB GEFs exchange GTP for GDP on RABs.
DR Reactome; R-MMU-8934903; Receptor Mediated Mitophagy.
DR BioGRID-ORCS; 22241; 4 hits in 76 CRISPR screens.
DR ChiTaRS; Ulk1; mouse.
DR PRO; PR:O70405; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; O70405; protein.
DR GO; GO:1990316; C:Atg1/ULK1 kinase complex; IDA:MGI.
DR GO; GO:0005776; C:autophagosome; ISO:MGI.
DR GO; GO:0030424; C:axon; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IDA:MGI.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0097635; C:extrinsic component of autophagosome membrane; ISO:MGI.
DR GO; GO:0097629; C:extrinsic component of omegasome membrane; ISO:MGI.
DR GO; GO:0097632; C:extrinsic component of phagophore assembly site membrane; ISO:MGI.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0043005; C:neuron projection; IDA:MGI.
DR GO; GO:0043025; C:neuronal cell body; IDA:MGI.
DR GO; GO:0000407; C:phagophore assembly site; IDA:UniProtKB.
DR GO; GO:0034045; C:phagophore assembly site membrane; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0051020; F:GTPase binding; ISO:MGI.
DR GO; GO:0051879; F:Hsp90 protein binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0004672; F:protein kinase activity; IDA:MGI.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0031267; F:small GTPase binding; ISO:MGI.
DR GO; GO:0000045; P:autophagosome assembly; IDA:ComplexPortal.
DR GO; GO:0006914; P:autophagy; IMP:UniProtKB.
DR GO; GO:0000422; P:autophagy of mitochondrion; IBA:GO_Central.
DR GO; GO:0048675; P:axon extension; IMP:MGI.
DR GO; GO:0007409; P:axonogenesis; IDA:MGI.
DR GO; GO:0034198; P:cellular response to amino acid starvation; IGI:ParkinsonsUK-UCL.
DR GO; GO:0031669; P:cellular response to nutrient levels; IDA:UniProtKB.
DR GO; GO:0021707; P:cerebellar granule cell differentiation; IMP:MGI.
DR GO; GO:0048668; P:collateral sprouting; IMP:MGI.
DR GO; GO:0051649; P:establishment of localization in cell; IMP:MGI.
DR GO; GO:0044805; P:late nucleophagy; IBA:GO_Central.
DR GO; GO:0016236; P:macroautophagy; IMP:MGI.
DR GO; GO:0000423; P:mitophagy; IMP:ParkinsonsUK-UCL.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:ComplexPortal.
DR GO; GO:0048671; P:negative regulation of collateral sprouting; IMP:MGI.
DR GO; GO:0031333; P:negative regulation of protein-containing complex assembly; ISO:MGI.
DR GO; GO:0001764; P:neuron migration; IMP:MGI.
DR GO; GO:0031175; P:neuron projection development; IMP:MGI.
DR GO; GO:0031102; P:neuron projection regeneration; ISO:MGI.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:ParkinsonsUK-UCL.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; ISO:MGI.
DR GO; GO:0034727; P:piecemeal microautophagy of the nucleus; IBA:GO_Central.
DR GO; GO:2000786; P:positive regulation of autophagosome assembly; ISO:MGI.
DR GO; GO:0010508; P:positive regulation of autophagy; IDA:ComplexPortal.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:MGI.
DR GO; GO:0008104; P:protein localization; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:ComplexPortal.
DR GO; GO:0021933; P:radial glia guided migration of cerebellar granule cell; IMP:MGI.
DR GO; GO:0007265; P:Ras protein signal transduction; IDA:MGI.
DR GO; GO:0031623; P:receptor internalization; IMP:MGI.
DR GO; GO:0010941; P:regulation of cell death; IGI:ParkinsonsUK-UCL.
DR GO; GO:0010468; P:regulation of gene expression; IGI:ParkinsonsUK-UCL.
DR GO; GO:0016241; P:regulation of macroautophagy; ISO:MGI.
DR GO; GO:0051386; P:regulation of neurotrophin TRK receptor signaling pathway; IMP:MGI.
DR GO; GO:1903059; P:regulation of protein lipidation; IDA:ComplexPortal.
DR GO; GO:0098780; P:response to mitochondrial depolarisation; IMP:BHF-UCL.
DR GO; GO:0042594; P:response to starvation; IDA:UniProtKB.
DR GO; GO:0061709; P:reticulophagy; IBA:GO_Central.
DR InterPro; IPR045269; Atg1-like.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR016237; Ser/Thr_kin_STPK_Ulk-1/2.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR022708; Ser/Thr_kinase_C.
DR PANTHER; PTHR24348; PTHR24348; 1.
DR Pfam; PF12063; DUF3543; 1.
DR Pfam; PF00069; Pkinase; 1.
DR PIRSF; PIRSF000580; Ser/Thr_PK_STPK_ULK-1/2; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 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 Acetylation; ATP-binding; Autophagy; Cytoplasm; Kinase; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transferase; Ubl conjugation.
FT CHAIN 1..1051
FT /note="Serine/threonine-protein kinase ULK1"
FT /id="PRO_0000086781"
FT DOMAIN 16..278
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 283..323
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 287..416
FT /note="Interaction with GABARAP and GABARAPL2"
FT /evidence="ECO:0000250|UniProtKB:O75385"
FT REGION 335..358
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 394..554
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 661..686
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 727..787
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 829..1051
FT /note="C-terminal domain; mediates interaction with SESN2"
FT /evidence="ECO:0000250|UniProtKB:O75385"
FT COMPBIAS 296..323
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 435..475
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 759..787
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 138
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 22..30
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 46
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000305"
FT MOD_RES 162
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:22539723"
FT MOD_RES 317
FT /note="Phosphoserine; by AMPK"
FT /evidence="ECO:0000269|PubMed:21258367"
FT MOD_RES 403
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75385"
FT MOD_RES 450
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 456
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O75385"
FT MOD_RES 467
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21205641"
FT MOD_RES 477
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75385"
FT MOD_RES 479
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75385"
FT MOD_RES 521
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 555
FT /note="Phosphoserine; by AMPK"
FT /evidence="ECO:0000269|PubMed:21205641"
FT MOD_RES 574
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:21205641"
FT MOD_RES 606
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:22539723"
FT MOD_RES 635
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 637
FT /note="Phosphoserine; by AMPK"
FT /evidence="ECO:0000269|PubMed:21205641,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 638
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 757
FT /note="Phosphoserine; by MTOR"
FT /evidence="ECO:0000269|PubMed:21258367,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 774
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75385"
FT MOD_RES 777
FT /note="Phosphoserine; by AMPK"
FT /evidence="ECO:0000269|PubMed:21258367"
FT MUTAGEN 46
FT /note="K->R: Loss of kinase activity and
FT autophosphorylation."
FT /evidence="ECO:0000269|PubMed:21205641,
FT ECO:0000269|PubMed:21258367"
FT MUTAGEN 162
FT /note="K->R: In K2R; abolished acetylation by KAT5/TIP60
FT and decreased kinase activity; when associated with R-606."
FT /evidence="ECO:0000269|PubMed:22539723"
FT MUTAGEN 317
FT /note="S->A: Impairs phosphorylation by AMPK and ability to
FT promote autophagy; when associated with A-777."
FT /evidence="ECO:0000269|PubMed:21258367"
FT MUTAGEN 494
FT /note="S->A: Does not affect phosphorylation by AMPK in
FT vitro."
FT /evidence="ECO:0000269|PubMed:21258367"
FT MUTAGEN 555
FT /note="S->A: Does not affect phosphorylation by AMPK in
FT vitro."
FT /evidence="ECO:0000269|PubMed:21258367"
FT MUTAGEN 574
FT /note="T->A: Does not affect phosphorylation by AMPK in
FT vitro."
FT /evidence="ECO:0000269|PubMed:21258367"
FT MUTAGEN 606
FT /note="K->R: In K2R; abolished acetylation by KAT5/TIP60
FT and decreased kinase activity; when associated with R-162."
FT /evidence="ECO:0000269|PubMed:22539723"
FT MUTAGEN 622
FT /note="S->A: Does not affect phosphorylation by AMPK in
FT vitro."
FT /evidence="ECO:0000269|PubMed:21258367"
FT MUTAGEN 624
FT /note="T->A: Does not affect phosphorylation by AMPK in
FT vitro."
FT /evidence="ECO:0000269|PubMed:21258367"
FT MUTAGEN 693
FT /note="S->A: Does not affect phosphorylation by AMPK in
FT vitro."
FT /evidence="ECO:0000269|PubMed:21258367"
FT MUTAGEN 757
FT /note="S->A,D: Impairs interaction with AMPK and subsequent
FT phosphorylation by AMPK."
FT /evidence="ECO:0000269|PubMed:21258367"
FT MUTAGEN 777
FT /note="S->A: Impairs phosphorylation by AMPK and ability to
FT promote autophagy; when associated with A-317."
FT /evidence="ECO:0000269|PubMed:21258367"
FT MUTAGEN 811
FT /note="S->A: Does not affect phosphorylation by AMPK in
FT vitro."
FT /evidence="ECO:0000269|PubMed:21258367"
FT CONFLICT 469
FT /note="T -> S (in Ref. 3; AAH57121)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1051 AA; 112463 MW; 99B021985FB4E8A0 CRC64;
MEPGRGGVET VGKFEFSRKD LIGHGAFAVV FKGRHREKHD LEVAVKCINK KNLAKSQTLL
GKEIKILKEL KHENIVALYD FQEMANSVYL VMEYCNGGDL ADYLHTMRTL SEDTVRLFLQ
QIAGAMRLLH SKGIIHRDLK PQNILLSNPG GRRANPSNIR VKIADFGFAR YLQSNMMAAT
LCGSPMYMAP EVIMSQHYDG KADLWSIGTI VYQCLTGKAP FQASSPQDLR LFYEKNKTLV
PAIPRETSAP LRQLLLALLQ RNHKDRMDFD EFFHHPFLDA STPIKKSPPV PVPSYPSSGS
GSSSSSSSAS HLASPPSLGE MPQLQKTLTS PADAAGFLQG SRDSGGSSKD SCDTDDFVMV
PAQFPGDLVA EAASAKPPPD SLLCSGSSLV ASAGLESHGR TPSPSPTCSS SPSPSGRPGP
FSSNRYGASV PIPVPTQVHN YQRIEQNLQS PTQQQTARSS AIRRSGSTTP LGFGRASPSP
PSHTDGAMLA RKLSLGGGRP YTPSPQVGTI PERPSWSRVP SPQGADVRVG RSPRPGSSVP
EHSPRTTGLG CRLHSAPNLS DFHVVRPKLP KPPTDPLGAT FSPPQTSAPQ PCPGLQSCRP
LRGSPKLPDF LQRSPLPPIL GSPTKAGPSF DFPKTPSSQN LLTLLARQGV VMTPPRNRTL
PDLSEASPFH GQQLGSGLRP AEDTRGPFGR SFSTSRITDL LLKAAFGTQA SDSGSTDSLQ
EKPMEIAPSA GFGGTLHPGA RGGGASSPAP VVFTVGSPPS GATPPQSTRT RMFSVGSSSS
LGSTGSSSAR HLVPGACGEA PELSAPGHCC SLADPLAANL EGAVTFEAPD LPEETLMEQE
HTETLHSLRF TLAFAQQVLE IAALKGSASE AAGGPEYQLQ ESVVADQISQ LSREWGFAEQ
LVLYLKVAEL LSSGLQTAID QIRAGKLCLS STVKQVVRRL NELYKASVVS CQGLSLRLQR
FFLDKQRLLD GIHGVTAERL ILSHAVQMVQ SAALDEMFQH REGCVPRYHK ALLLLEGLQH
TLTDQADIEN IAKCKLCIER RLSALLSGVY A
