GenomeNet

Database: UniProt
Entry: O75385
LinkDB: O75385
Original site: O75385 
ID   ULK1_HUMAN              Reviewed;        1050 AA.
AC   O75385; Q9UQ28;
DT   15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT   11-JAN-2011, sequence version 2.
DT   29-SEP-2021, entry version 204.
DE   RecName: Full=Serine/threonine-protein kinase ULK1 {ECO:0000305};
DE            EC=2.7.11.1 {ECO:0000269|PubMed:18936157, ECO:0000269|PubMed:25126726, ECO:0000269|PubMed:31123703};
DE   AltName: Full=Autophagy-related protein 1 homolog;
DE            Short=ATG1;
DE            Short=hATG1;
DE   AltName: Full=Unc-51-like kinase 1;
GN   Name=ULK1 {ECO:0000312|HGNC:HGNC:12558}; Synonyms=KIAA0722;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ALA-816.
RX   PubMed=9693035; DOI=10.1006/geno.1998.5340;
RA   Kuroyanagi H., Yan J., Seki N., Yamanouchi Y., Suzuki Y., Takano T.,
RA   Muramatsu M., Shirasawa T.;
RT   "Human ULK1, a novel serine/threonine kinase related to UNC-51 kinase of
RT   Caenorhabditis elegans: cDNA cloning, expression, and chromosomal
RT   assignment.";
RL   Genomics 51:76-85(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-816.
RC   TISSUE=Brain;
RX   PubMed=9872452; DOI=10.1093/dnares/5.5.277;
RA   Nagase T., Ishikawa K., Suyama M., Kikuno R., Miyajima N., Tanaka A.,
RA   Kotani H., Nomura N., Ohara O.;
RT   "Prediction of the coding sequences of unidentified human genes. XI. The
RT   complete sequences of 100 new cDNA clones from brain which code for large
RT   proteins in vitro.";
RL   DNA Res. 5:277-286(1998).
RN   [3]
RP   SEQUENCE REVISION.
RX   PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA   Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT   "Construction of expression-ready cDNA clones for KIAA genes: manual
RT   curation of 330 KIAA cDNA clones.";
RL   DNA Res. 9:99-106(2002).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16541075; DOI=10.1038/nature04569;
RA   Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA   Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA   Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA   Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA   Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA   Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA   Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA   Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA   Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA   Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA   Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA   Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA   Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA   Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA   Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA   Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA   Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA   David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA   D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA   Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA   Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA   Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA   LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA   Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA   Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA   Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA   Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA   Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA   Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA   Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA   Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA   Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA   Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA   Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA   Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA   Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA   Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA   Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA   Gibbs R.A.;
RT   "The finished DNA sequence of human chromosome 12.";
RL   Nature 440:346-351(2006).
RN   [5]
RP   FUNCTION, INTERACTION WITH GABARAP AND GABARAPL2, AND REGION.
RX   PubMed=11146101; DOI=10.1016/s0169-328x(00)00218-7;
RA   Okazaki N., Yan J., Yuasa S., Ueno T., Kominami E., Masuho Y., Koga H.,
RA   Muramatsu M.-A.;
RT   "Interaction of the Unc-51-like kinase and microtubule-associated protein
RT   light chain 3 related proteins in the brain: possible role of vesicular
RT   transport in axonal elongation.";
RL   Brain Res. Mol. Brain Res. 85:1-12(2000).
RN   [6]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-477 AND SER-479, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA   Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA   Greff Z., Keri G., Stemmann O., Mann M.;
RT   "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT   kinome across the cell cycle.";
RL   Mol. Cell 31:438-448(2008).
RN   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-450; THR-456 AND SER-556, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA   Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA   Elledge S.J., Gygi S.P.;
RT   "A quantitative atlas of mitotic phosphorylation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN   [8]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19413330; DOI=10.1021/ac9004309;
RA   Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT   "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT   refined SCX-based approach.";
RL   Anal. Chem. 81:4493-4501(2009).
RN   [9]
RP   SUBUNIT, AND COMPLEX FORMATION WITH ATG13; ATG101 AND RB1CC1.
RX   PubMed=19287211; DOI=10.4161/auto.5.5.8249;
RA   Mercer C.A., Kaliappan A., Dennis P.B.;
RT   "A novel, human Atg13 binding protein, Atg101, interacts with ULK1 and is
RT   essential for macroautophagy.";
RL   Autophagy 5:649-662(2009).
RN   [10]
RP   SUBUNIT.
RX   PubMed=19597335; DOI=10.4161/auto.5.7.9296;
RA   Hosokawa N., Sasaki T., Iemura S.I., Natsume T., Hara T., Mizushima N.;
RT   "Atg101, a novel mammalian autophagy protein interacting with Atg13.";
RL   Autophagy 5:973-979(2009).
RN   [11]
RP   SUBUNIT, AND INTERACTION WITH RPTOR AND TORC1 COMPLEX.
RX   PubMed=19211835; DOI=10.1091/mbc.e08-12-1248;
RA   Hosokawa N., Hara T., Kaizuka T., Kishi C., Takamura A., Miura Y.,
RA   Iemura S., Natsume T., Takehana K., Yamada N., Guan J.L., Oshiro N.,
RA   Mizushima N.;
RT   "Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex
RT   required for autophagy.";
RL   Mol. Biol. Cell 20:1981-1991(2009).
RN   [12]
RP   FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH ATG13.
RX   PubMed=18936157; DOI=10.1128/mcb.01082-08;
RA   Chan E.Y.W., Longatti A., McKnight N.C., Tooze S.A.;
RT   "Kinase-inactivated ULK proteins inhibit autophagy via their conserved C-
RT   terminal domains using an Atg13-independent mechanism.";
RL   Mol. Cell. Biol. 29:157-171(2009).
RN   [13]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA   Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA   Mann M., Daub H.;
RT   "Large-scale proteomics analysis of the human kinome.";
RL   Mol. Cell. Proteomics 8:1751-1764(2009).
RN   [14]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-450 AND SER-638, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Leukemic T-cell;
RX   PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA   Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA   Rodionov V., Han D.K.;
RT   "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT   reveals system-wide modulation of protein-protein interactions.";
RL   Sci. Signal. 2:RA46-RA46(2009).
RN   [15]
RP   FUNCTION, AND MUTAGENESIS OF LYS-46.
RX   PubMed=20921139; DOI=10.1083/jcb.201002100;
RA   Di Bartolomeo S., Corazzari M., Nazio F., Oliverio S., Lisi G.,
RA   Antonioli M., Pagliarini V., Matteoni S., Fuoco C., Giunta L., D'Amelio M.,
RA   Nardacci R., Romagnoli A., Piacentini M., Cecconi F., Fimia G.M.;
RT   "The dynamic interaction of AMBRA1 with the dynein motor complex regulates
RT   mammalian autophagy.";
RL   J. Cell Biol. 191:155-168(2010).
RN   [16]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-450; THR-456 AND SER-638, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA   Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA   Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT   "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT   site occupancy during mitosis.";
RL   Sci. Signal. 3:RA3-RA3(2010).
RN   [17]
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   [18]
RP   FUNCTION, AND INTERACTION WITH RPTOR.
RX   PubMed=21795849; DOI=10.4161/auto.7.10.16660;
RA   Jung C.H., Seo M., Otto N.M., Kim D.H.;
RT   "ULK1 inhibits the kinase activity of mTORC1 and cell proliferation.";
RL   Autophagy 7:1212-1221(2011).
RN   [19]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-450; SER-469; SER-556 AND
RP   SER-638, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA   Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA   Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT   "System-wide temporal characterization of the proteome and phosphoproteome
RT   of human embryonic stem cell differentiation.";
RL   Sci. Signal. 4:RS3-RS3(2011).
RN   [20]
RP   PHOSPHORYLATION BY AMPK.
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   [21]
RP   INTERACTION WITH FEZ1.
RX   PubMed=22354037; DOI=10.1038/emboj.2012.36;
RA   McKnight N.C., Jefferies H.B., Alemu E.A., Saunders R.E., Howell M.,
RA   Johansen T., Tooze S.A.;
RT   "Genome-wide siRNA screen reveals amino acid starvation-induced autophagy
RT   requires SCOC and WAC.";
RL   EMBO J. 31:1931-1946(2012).
RN   [22]
RP   INTERACTION WITH TBC1D14.
RX   PubMed=22613832; DOI=10.1083/jcb.201111079;
RA   Longatti A., Lamb C.A., Razi M., Yoshimura S., Barr F.A., Tooze S.A.;
RT   "TBC1D14 regulates autophagosome formation via Rab11- and ULK1-positive
RT   recycling endosomes.";
RL   J. Cell Biol. 197:659-675(2012).
RN   [23]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-403; SER-450; SER-467;
RP   SER-469; SER-477; SER-479; SER-556; SER-638; SER-758 AND SER-775, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma, and Erythroleukemia;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
RN   [24]
RP   FUNCTION, AND UBIQUITINATION.
RX   PubMed=23524951; DOI=10.1038/ncb2708;
RA   Nazio F., Strappazzon F., Antonioli M., Bielli P., Cianfanelli V.,
RA   Bordi M., Gretzmeier C., Dengjel J., Piacentini M., Fimia G.M., Cecconi F.;
RT   "mTOR inhibits autophagy by controlling ULK1 ubiquitylation, self-
RT   association and function through AMBRA1 and TRAF6.";
RL   Nat. Cell Biol. 15:406-416(2013).
RN   [25]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=25126726; DOI=10.4161/auto.29640;
RA   Dunlop E.A., Seifan S., Claessens T., Behrends C., Kamps M.A., Rozycka E.,
RA   Kemp A.J., Nookala R.K., Blenis J., Coull B.J., Murray J.T.,
RA   van Steensel M.A., Wilkinson S., Tee A.R.;
RT   "FLCN, a novel autophagy component, interacts with GABARAP and is regulated
RT   by ULK1 phosphorylation.";
RL   Autophagy 10:1749-1760(2014).
RN   [26]
RP   PHOSPHORYLATION AT SER-556.
RX   PubMed=24767988; DOI=10.1016/j.celrep.2014.03.065;
RA   Lanning N.J., Looyenga B.D., Kauffman A.L., Niemi N.M., Sudderth J.,
RA   DeBerardinis R.J., MacKeigan J.P.;
RT   "A mitochondrial RNAi screen defines cellular bioenergetic determinants and
RT   identifies an adenylate kinase as a key regulator of ATP levels.";
RL   Cell Rep. 7:907-917(2014).
RN   [27]
RP   FUNCTION, INTERACTION WITH SESN2 AND SQSTM1, AND REGION.
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   [28]
RP   INTERACTION WITH TRIM5.
RX   PubMed=25127057; DOI=10.1016/j.devcel.2014.06.013;
RA   Mandell M.A., Jain A., Arko-Mensah J., Chauhan S., Kimura T., Dinkins C.,
RA   Silvestri G., Munch J., Kirchhoff F., Simonsen A., Wei Y., Levine B.,
RA   Johansen T., Deretic V.;
RT   "TRIM proteins regulate autophagy and can target autophagic substrates by
RT   direct recognition.";
RL   Dev. Cell 30:394-409(2014).
RN   [29]
RP   INTERACTION WITH BECN1; IRF3; MEFV AND TRIM21.
RX   PubMed=26347139; DOI=10.1083/jcb.201503023;
RA   Kimura T., Jain A., Choi S.W., Mandell M.A., Schroder K., Johansen T.,
RA   Deretic V.;
RT   "TRIM-mediated precision autophagy targets cytoplasmic regulators of innate
RT   immunity.";
RL   J. Cell Biol. 210:973-989(2015).
RN   [30]
RP   INTERACTION WITH AMBRA1.
RX   PubMed=25438055; DOI=10.1038/ncb3072;
RA   Cianfanelli V., Fuoco C., Lorente M., Salazar M., Quondamatteo F.,
RA   Gherardini P.F., De Zio D., Nazio F., Antonioli M., D'Orazio M., Skobo T.,
RA   Bordi M., Rohde M., Dalla Valle L., Helmer-Citterich M., Gretzmeier C.,
RA   Dengjel J., Fimia G.M., Piacentini M., Di Bartolomeo S., Velasco G.,
RA   Cecconi F.;
RT   "AMBRA1 links autophagy to cell proliferation and tumorigenesis by
RT   promoting c-Myc dephosphorylation and degradation.";
RL   Nat. Cell Biol. 17:20-30(2015).
RN   [31]
RP   INTERACTION WITH C9ORF72.
RX   PubMed=27334615; DOI=10.15252/embj.201694401;
RA   Webster C.P., Smith E.F., Bauer C.S., Moller A., Hautbergue G.M.,
RA   Ferraiuolo L., Myszczynska M.A., Higginbottom A., Walsh M.J.,
RA   Whitworth A.J., Kaspar B.K., Meyer K., Shaw P.J., Grierson A.J.,
RA   De Vos K.J.;
RT   "The C9orf72 protein interacts with Rab1a and the ULK1 complex to regulate
RT   initiation of autophagy.";
RL   EMBO J. 35:1656-1676(2016).
RN   [32]
RP   INTERACTION WITH ATP2A2 AND WIPI2.
RX   PubMed=28890335; DOI=10.1016/j.molcel.2017.08.005;
RA   Zhao Y.G., Chen Y., Miao G., Zhao H., Qu W., Li D., Wang Z., Liu N., Li L.,
RA   Chen S., Liu P., Feng D., Zhang H.;
RT   "The ER-Localized Transmembrane Protein EPG-3/VMP1 Regulates SERCA Activity
RT   to Control ER-Isolation Membrane Contacts for Autophagosome Formation.";
RL   Mol. Cell 67:974.e6-989.e6(2017).
RN   [33]
RP   INTERACTION WITH WDR45.
RX   PubMed=28561066; DOI=10.1038/ncomms15637;
RA   Bakula D., Mueller A.J., Zuleger T., Takacs Z., Franz-Wachtel M.,
RA   Thost A.K., Brigger D., Tschan M.P., Frickey T., Robenek H., Macek B.,
RA   Proikas-Cezanne T.;
RT   "WIPI3 and WIPI4 beta-propellers are scaffolds for LKB1-AMPK-TSC signalling
RT   circuits in the control of autophagy.";
RL   Nat. Commun. 8:15637-15637(2017).
RN   [34]
RP   INTERACTION WITH ATG13.
RX   PubMed=31806350; DOI=10.1016/j.molcel.2019.10.035;
RA   Miao G., Zhang Y., Chen D., Zhang H.;
RT   "The ER-Localized Transmembrane Protein TMEM39A/SUSR2 Regulates Autophagy
RT   by Controlling the Trafficking of the PtdIns(4)P Phosphatase SAC1.";
RL   Mol. Cell 0:0-0(2019).
RN   [35]
RP   FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND INTERACTION WITH
RP   AMBRA1.
RX   PubMed=31123703; DOI=10.1126/sciadv.aau8857;
RA   Di Rienzo M., Antonioli M., Fusco C., Liu Y., Mari M., Orhon I., Refolo G.,
RA   Germani F., Corazzari M., Romagnoli A., Ciccosanti F., Mandriani B.,
RA   Pellico M.T., De La Torre R., Ding H., Dentice M., Neri M., Ferlini A.,
RA   Reggiori F., Kulesz-Martin M., Piacentini M., Merla G., Fimia G.M.;
RT   "Autophagy induction in atrophic muscle cells requires ULK1 activation by
RT   TRIM32 through unanchored K63-linked polyubiquitin chains.";
RL   Sci. Adv. 5:eaau8857-eaau8857(2019).
RN   [36]
RP   VARIANTS [LARGE SCALE ANALYSIS] MET-290; LEU-298; LEU-478; MET-503;
RP   LEU-665; LEU-714 AND CYS-784.
RX   PubMed=17344846; DOI=10.1038/nature05610;
RA   Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA   Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA   Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA   Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA   Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA   Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA   Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA   Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA   Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA   Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA   Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA   Futreal P.A., Stratton M.R.;
RT   "Patterns of somatic mutation in human cancer genomes.";
RL   Nature 446:153-158(2007).
CC   -!- FUNCTION: Serine/threonine-protein kinase involved in autophagy in
CC       response to starvation (PubMed:18936157, PubMed:21460634,
CC       PubMed:21795849, PubMed:23524951, PubMed:25040165, PubMed:31123703).
CC       Acts upstream of phosphatidylinositol 3-kinase PIK3C3 to regulate the
CC       formation of autophagophores, the precursors of autophagosomes
CC       (PubMed:18936157, PubMed:21460634, PubMed:21795849, PubMed:25040165).
CC       Part of regulatory feedback loops in autophagy: acts both as a
CC       downstream effector and negative regulator of mammalian target of
CC       rapamycin complex 1 (mTORC1) via interaction with RPTOR
CC       (PubMed:21795849). Activated via phosphorylation by AMPK and also acts
CC       as a regulator of AMPK by mediating phosphorylation of AMPK subunits
CC       PRKAA1, PRKAB2 and PRKAG1, leading to negatively regulate AMPK activity
CC       (PubMed:21460634). May phosphorylate ATG13/KIAA0652 and RPTOR; however
CC       such data need additional evidences (PubMed:18936157). Plays a role
CC       early in neuronal differentiation and is required for granule cell axon
CC       formation (PubMed:11146101). May also phosphorylate SESN2 and SQSTM1 to
CC       regulate autophagy (PubMed:25040165). Phosphorylates FLCN, promoting
CC       autophagy (PubMed:25126726). Phosphorylates AMBRA1 in response to
CC       autophagy induction, releasing AMBRA1 from the cytoskeletal docking
CC       site to induce autophagosome nucleation (PubMed:20921139).
CC       {ECO:0000269|PubMed:11146101, ECO:0000269|PubMed:18936157,
CC       ECO:0000269|PubMed:20921139, ECO:0000269|PubMed:21460634,
CC       ECO:0000269|PubMed:21795849, ECO:0000269|PubMed:23524951,
CC       ECO:0000269|PubMed:25040165, ECO:0000269|PubMed:25126726,
CC       ECO:0000269|PubMed:31123703}.
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:0000269|PubMed:18936157, ECO:0000269|PubMed:25126726,
CC         ECO:0000269|PubMed:31123703};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17990;
CC         Evidence={ECO:0000269|PubMed:18936157, ECO:0000269|PubMed:25126726,
CC         ECO:0000269|PubMed:31123703};
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:0000269|PubMed:18936157};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46609;
CC         Evidence={ECO:0000269|PubMed:18936157};
CC   -!- ACTIVITY REGULATION: Acetylation by KAT5/TIP60 stimulates the protein
CC       kinase activity (By similarity). 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 (PubMed:31123703).
CC       {ECO:0000250|UniProtKB:O70405, ECO:0000269|PubMed:31123703}.
CC   -!- SUBUNIT: Interacts with GABARAP and GABARAPL2 (PubMed:11146101).
CC       Interacts (via C-terminus) with ATG13 (PubMed:18936157). Part of a
CC       complex consisting of ATG13, ATG101, ULK1 and RB1CC1 (PubMed:19287211).
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 (PubMed:19211835,
CC       PubMed:21795849). Interacts with FEZ1; SCOC interferes with FEZ1-
CC       binding (PubMed:22354037). Interacts with TBC1D14 (PubMed:22613832).
CC       Interacts (phosphorylated form) with TRIM5 (PubMed:25127057). When
CC       phosphorylated at Ser-317, interacts with MEFV and BECN1 simultaneously
CC       (PubMed:26347139). Interacts with TRIM21 and IRF3, in the presence of
CC       TRIM21 (PubMed:26347139). Interacts with SESN2 (PubMed:25040165).
CC       Interacts with SQSTM1 (PubMed:25040165). Interacts with C9orf72
CC       (PubMed:27334615). Interacts with WDR45 (PubMed:28561066). Interacts
CC       with ATG13; this interaction is increased in the absence of TMEM39A
CC       (PubMed:31806350). Interacts with WIPI2 (PubMed:28890335). Interacts
CC       with ATP2A2 (PubMed:28890335). Interacts with AMBRA1 (PubMed:25438055,
CC       PubMed:31123703). {ECO:0000269|PubMed:11146101,
CC       ECO:0000269|PubMed:18936157, ECO:0000269|PubMed:19211835,
CC       ECO:0000269|PubMed:19287211, ECO:0000269|PubMed:19597335,
CC       ECO:0000269|PubMed:21795849, ECO:0000269|PubMed:22354037,
CC       ECO:0000269|PubMed:22613832, ECO:0000269|PubMed:25040165,
CC       ECO:0000269|PubMed:25127057, ECO:0000269|PubMed:25438055,
CC       ECO:0000269|PubMed:26347139, ECO:0000269|PubMed:27334615,
CC       ECO:0000269|PubMed:28561066, ECO:0000269|PubMed:28890335,
CC       ECO:0000269|PubMed:31123703, ECO:0000269|PubMed:31806350}.
CC   -!- INTERACTION:
CC       O75385; Q9C0C7: AMBRA1; NbExp=3; IntAct=EBI-908831, EBI-2512975;
CC       O75385; Q9C0C7-3: AMBRA1; NbExp=4; IntAct=EBI-908831, EBI-16042318;
CC       O75385; O75143: ATG13; NbExp=12; IntAct=EBI-908831, EBI-2798775;
CC       O75385; Q96LT7-1: C9orf72; NbExp=5; IntAct=EBI-908831, EBI-16693635;
CC       O75385; Q96LT7-2: C9orf72; NbExp=4; IntAct=EBI-908831, EBI-16693673;
CC       O75385; Q9H0R8: GABARAPL1; NbExp=2; IntAct=EBI-908831, EBI-746969;
CC       O75385; P60520: GABARAPL2; NbExp=3; IntAct=EBI-908831, EBI-720116;
CC       O75385; P42858: HTT; NbExp=8; IntAct=EBI-908831, EBI-466029;
CC       O75385; Q9GZQ8: MAP1LC3B; NbExp=3; IntAct=EBI-908831, EBI-373144;
CC       O75385; Q9BXW4: MAP1LC3C; NbExp=3; IntAct=EBI-908831, EBI-2603996;
CC       O75385; P42345: MTOR; NbExp=7; IntAct=EBI-908831, EBI-359260;
CC       O75385; P04629: NTRK1; NbExp=2; IntAct=EBI-908831, EBI-1028226;
CC       O75385; O15530: PDPK1; NbExp=2; IntAct=EBI-908831, EBI-717097;
CC       O75385; P54646: PRKAA2; NbExp=2; IntAct=EBI-908831, EBI-1383852;
CC       O75385; Q9Y478: PRKAB1; NbExp=3; IntAct=EBI-908831, EBI-719769;
CC       O75385; Q8TDY2: RB1CC1; NbExp=10; IntAct=EBI-908831, EBI-1047793;
CC       O75385; Q8N122: RPTOR; NbExp=3; IntAct=EBI-908831, EBI-1567928;
CC       O75385; Q9P2M4: TBC1D14; NbExp=4; IntAct=EBI-908831, EBI-2797718;
CC       O75385; Q9Y4K3: TRAF6; NbExp=2; IntAct=EBI-908831, EBI-359276;
CC       O75385; O75385: ULK1; NbExp=3; IntAct=EBI-908831, EBI-908831;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000250}.
CC       Preautophagosomal structure {ECO:0000250}. Note=Under starvation
CC       conditions, is localized to puncate structures primarily representing
CC       the isolation membrane that sequesters a portion of the cytoplasm
CC       resulting in the formation of an autophagosome. {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: Ubiquitously expressed. Detected in the following
CC       adult tissues: skeletal muscle, heart, pancreas, brain, placenta,
CC       liver, kidney, and lung.
CC   -!- PTM: Autophosphorylated. Phosphorylated under nutrient-rich conditions;
CC       dephosphorylated during starvation or following treatment with
CC       rapamycin. Under nutrient sufficiency, phosphorylated by MTOR/mTOR,
CC       disrupting the interaction with AMPK and preventing activation of ULK1
CC       (By similarity). In response to nutrient limitation, phosphorylated and
CC       activated by AMPK, leading to activate autophagy. {ECO:0000250,
CC       ECO:0000269|PubMed:21205641}.
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:0000269|PubMed:23524951}.
CC   -!- PTM: Acetylated by KAT5/TIP60 under autophagy induction, promoting
CC       protein kinase activity. {ECO:0000250|UniProtKB:O70405}.
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}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAA34442.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; AF045458; AAC32326.1; -; mRNA.
DR   EMBL; AB018265; BAA34442.2; ALT_INIT; mRNA.
DR   EMBL; AC131009; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   CCDS; CCDS9274.1; -.
DR   RefSeq; NP_003556.1; NM_003565.2.
DR   PDB; 4WNO; X-ray; 1.56 A; A=1-283.
DR   PDB; 4WNP; X-ray; 1.88 A; A/B/C/D=1-283.
DR   PDB; 5CI7; X-ray; 1.74 A; A=1-283.
DR   PDB; 6HYO; X-ray; 1.07 A; A=354-366.
DR   PDB; 6MNH; X-ray; 1.73 A; A=6-290.
DR   PDB; 6QAS; X-ray; 1.75 A; A/B=1-283.
DR   PDBsum; 4WNO; -.
DR   PDBsum; 4WNP; -.
DR   PDBsum; 5CI7; -.
DR   PDBsum; 6HYO; -.
DR   PDBsum; 6MNH; -.
DR   PDBsum; 6QAS; -.
DR   SMR; O75385; -.
DR   BioGRID; 113996; 94.
DR   ComplexPortal; CPX-373; ULK1-ATG13-RB1CC1-ATG101 autophagy initiation complex.
DR   CORUM; O75385; -.
DR   DIP; DIP-35196N; -.
DR   IntAct; O75385; 47.
DR   MINT; O75385; -.
DR   STRING; 9606.ENSP00000324560; -.
DR   BindingDB; O75385; -.
DR   ChEMBL; CHEMBL6006; -.
DR   DrugBank; DB12010; Fostamatinib.
DR   DrugCentral; O75385; -.
DR   GuidetoPHARMACOLOGY; 2271; -.
DR   GlyGen; O75385; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; O75385; -.
DR   PhosphoSitePlus; O75385; -.
DR   SwissPalm; O75385; -.
DR   BioMuta; ULK1; -.
DR   EPD; O75385; -.
DR   jPOST; O75385; -.
DR   MassIVE; O75385; -.
DR   MaxQB; O75385; -.
DR   PaxDb; O75385; -.
DR   PeptideAtlas; O75385; -.
DR   PRIDE; O75385; -.
DR   ProteomicsDB; 49958; -.
DR   Antibodypedia; 31999; 910 antibodies.
DR   DNASU; 8408; -.
DR   Ensembl; ENST00000321867; ENSP00000324560; ENSG00000177169.
DR   GeneID; 8408; -.
DR   KEGG; hsa:8408; -.
DR   UCSC; uc001uje.4; human.
DR   CTD; 8408; -.
DR   DisGeNET; 8408; -.
DR   GeneCards; ULK1; -.
DR   HGNC; HGNC:12558; ULK1.
DR   HPA; ENSG00000177169; Low tissue specificity.
DR   MIM; 603168; gene.
DR   neXtProt; NX_O75385; -.
DR   OpenTargets; ENSG00000177169; -.
DR   PharmGKB; PA37198; -.
DR   VEuPathDB; HostDB:ENSG00000177169; -.
DR   eggNOG; KOG0595; Eukaryota.
DR   GeneTree; ENSGT00940000156664; -.
DR   HOGENOM; CLU_011264_0_0_1; -.
DR   InParanoid; O75385; -.
DR   OMA; VTMTCLP; -.
DR   OrthoDB; 1084750at2759; -.
DR   PhylomeDB; O75385; -.
DR   TreeFam; TF324551; -.
DR   BRENDA; 2.7.11.1; 2681.
DR   PathwayCommons; O75385; -.
DR   Reactome; R-HSA-1632852; Macroautophagy.
DR   Reactome; R-HSA-8854214; TBC/RABGAPs.
DR   Reactome; R-HSA-8876198; RAB GEFs exchange GTP for GDP on RABs.
DR   Reactome; R-HSA-8934903; Receptor Mediated Mitophagy.
DR   SignaLink; O75385; -.
DR   SIGNOR; O75385; -.
DR   BioGRID-ORCS; 8408; 9 hits in 1056 CRISPR screens.
DR   ChiTaRS; ULK1; human.
DR   GeneWiki; ULK1; -.
DR   GenomeRNAi; 8408; -.
DR   Pharos; O75385; Tchem.
DR   PRO; PR:O75385; -.
DR   Proteomes; UP000005640; Chromosome 12.
DR   RNAct; O75385; protein.
DR   Bgee; ENSG00000177169; Expressed in esophagogastric junction muscularis propria and 212 other tissues.
DR   Genevisible; O75385; HS.
DR   GO; GO:1990316; C:Atg1/ULK1 kinase complex; IPI:UniProtKB.
DR   GO; GO:0005776; C:autophagosome; IDA:UniProtKB.
DR   GO; GO:0030424; C:axon; IEA:Ensembl.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR   GO; GO:0097635; C:extrinsic component of autophagosome membrane; IDA:UniProtKB.
DR   GO; GO:0097629; C:extrinsic component of omegasome membrane; IDA:UniProtKB.
DR   GO; GO:0097632; C:extrinsic component of phagophore assembly site membrane; IDA:UniProtKB.
DR   GO; GO:0005741; C:mitochondrial outer membrane; TAS:Reactome.
DR   GO; GO:0034045; C:phagophore assembly site membrane; IDA:UniProtKB.
DR   GO; GO:0055037; C:recycling endosome; TAS:Reactome.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0051020; F:GTPase binding; IPI:UniProtKB.
DR   GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR   GO; GO:0106310; F:protein serine kinase activity; IEA:UniProtKB-EC.
DR   GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR   GO; GO:0106311; F:protein threonine kinase activity; IEA:UniProtKB-EC.
DR   GO; GO:0044877; F:protein-containing complex binding; IPI:UniProtKB.
DR   GO; GO:0031267; F:small GTPase binding; IPI:BHF-UCL.
DR   GO; GO:0000045; P:autophagosome assembly; IDA:UniProtKB.
DR   GO; GO:0006914; P:autophagy; IDA:UniProtKB.
DR   GO; GO:0000422; P:autophagy of mitochondrion; IBA:GO_Central.
DR   GO; GO:0048675; P:axon extension; IBA:GO_Central.
DR   GO; GO:0031669; P:cellular response to nutrient levels; ISS:UniProtKB.
DR   GO; GO:0044805; P:late nucleophagy; IBA:GO_Central.
DR   GO; GO:0016236; P:macroautophagy; IMP:BHF-UCL.
DR   GO; GO:0048671; P:negative regulation of collateral sprouting; IBA:GO_Central.
DR   GO; GO:0031333; P:negative regulation of protein-containing complex assembly; IDA:ParkinsonsUK-UCL.
DR   GO; GO:0031175; P:neuron projection development; IMP:UniProtKB.
DR   GO; GO:0031102; P:neuron projection regeneration; IEA:Ensembl.
DR   GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:UniProtKB.
DR   GO; GO:0018107; P:peptidyl-threonine phosphorylation; IDA:HGNC.
DR   GO; GO:0034727; P:piecemeal microautophagy of the nucleus; IBA:GO_Central.
DR   GO; GO:0075044; P:positive regulation by symbiont of host autophagy; IGI:UniProtKB.
DR   GO; GO:2000786; P:positive regulation of autophagosome assembly; IEA:Ensembl.
DR   GO; GO:0010508; P:positive regulation of autophagy; IDA:UniProtKB.
DR   GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR   GO; GO:0008104; P:protein localization; IMP:UniProtKB.
DR   GO; GO:0006468; P:protein phosphorylation; NAS:UniProtKB.
DR   GO; GO:0042594; P:response to starvation; ISS:UniProtKB.
DR   GO; GO:0061709; P:reticulophagy; IBA:GO_Central.
DR   GO; GO:0007165; P:signal transduction; IEA:InterPro.
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   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   3D-structure; Acetylation; ATP-binding; Autophagy; Cytoplasm; Kinase;
KW   Nucleotide-binding; Phosphoprotein; Reference proteome;
KW   Serine/threonine-protein kinase; Transferase; Ubl conjugation.
FT   CHAIN           1..1050
FT                   /note="Serine/threonine-protein kinase ULK1"
FT                   /id="PRO_0000086780"
FT   DOMAIN          16..278
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   NP_BIND         22..30
FT                   /note="ATP"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   REGION          283..358
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          287..416
FT                   /note="Interaction with GABARAP and GABARAPL2"
FT                   /evidence="ECO:0000269|PubMed:11146101"
FT   REGION          393..608
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          728..791
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          828..1050
FT                   /note="C-terminal domain; mediates interaction with SESN2"
FT                   /evidence="ECO:0000269|PubMed:25040165"
FT   COMPBIAS        296..330
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        429..474
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        570..591
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        748..788
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         46
FT                   /note="ATP"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT                   ECO:0000305|PubMed:20921139"
FT   MOD_RES         162
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:O70405"
FT   MOD_RES         317
FT                   /note="Phosphoserine; by AMPK"
FT                   /evidence="ECO:0000250|UniProtKB:O70405"
FT   MOD_RES         403
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         450
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18669648,
FT                   ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT                   ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT   MOD_RES         456
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:18669648,
FT                   ECO:0007744|PubMed:20068231"
FT   MOD_RES         467
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         469
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21406692,
FT                   ECO:0007744|PubMed:23186163"
FT   MOD_RES         477
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18691976,
FT                   ECO:0007744|PubMed:23186163"
FT   MOD_RES         479
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18691976,
FT                   ECO:0007744|PubMed:23186163"
FT   MOD_RES         522
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:O70405"
FT   MOD_RES         556
FT                   /note="Phosphoserine; by AMPK"
FT                   /evidence="ECO:0000269|PubMed:24767988,
FT                   ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:21406692,
FT                   ECO:0007744|PubMed:23186163"
FT   MOD_RES         575
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:O70405"
FT   MOD_RES         607
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:O70405"
FT   MOD_RES         636
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:O70405"
FT   MOD_RES         638
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:19690332,
FT                   ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT                   ECO:0007744|PubMed:23186163"
FT   MOD_RES         639
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:O70405"
FT   MOD_RES         758
FT                   /note="Phosphoserine; by MTOR"
FT                   /evidence="ECO:0000305|PubMed:21205641,
FT                   ECO:0007744|PubMed:23186163"
FT   MOD_RES         775
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   VARIANT         290
FT                   /note="V -> M (in an ovarian mucinous carcinoma sample;
FT                   somatic mutation; dbSNP:rs370624303)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041274"
FT   VARIANT         298
FT                   /note="S -> L (in dbSNP:rs56364352)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041275"
FT   VARIANT         478
FT                   /note="P -> L (in dbSNP:rs12827141)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041276"
FT   VARIANT         503
FT                   /note="T -> M (in dbSNP:rs55824543)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041277"
FT   VARIANT         665
FT                   /note="S -> L (in dbSNP:rs55815560)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041278"
FT   VARIANT         714
FT                   /note="P -> L (in dbSNP:rs11546871)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041279"
FT   VARIANT         784
FT                   /note="S -> C (in a lung adenocarcinoma sample; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041280"
FT   VARIANT         816
FT                   /note="T -> A (in dbSNP:rs11609348)"
FT                   /evidence="ECO:0000269|PubMed:9693035,
FT                   ECO:0000269|PubMed:9872452"
FT                   /id="VAR_054892"
FT   MUTAGEN         46
FT                   /note="K->I: Abolished serine/threonine-protein kinase
FT                   activity."
FT                   /evidence="ECO:0000269|PubMed:20921139"
FT   STRAND          9..11
FT                   /evidence="ECO:0007829|PDB:4WNO"
FT   STRAND          14..24
FT                   /evidence="ECO:0007829|PDB:4WNO"
FT   STRAND          29..37
FT                   /evidence="ECO:0007829|PDB:4WNO"
FT   STRAND          42..47
FT                   /evidence="ECO:0007829|PDB:4WNO"
FT   HELIX           50..52
FT                   /evidence="ECO:0007829|PDB:4WNO"
FT   HELIX           53..67
FT                   /evidence="ECO:0007829|PDB:4WNO"
FT   STRAND          78..83
FT                   /evidence="ECO:0007829|PDB:4WNO"
FT   STRAND          88..93
FT                   /evidence="ECO:0007829|PDB:4WNO"
FT   HELIX           100..106
FT                   /evidence="ECO:0007829|PDB:4WNO"
FT   HELIX           112..132
FT                   /evidence="ECO:0007829|PDB:4WNO"
FT   HELIX           141..143
FT                   /evidence="ECO:0007829|PDB:4WNO"
FT   STRAND          144..147
FT                   /evidence="ECO:0007829|PDB:4WNO"
FT   HELIX           151..153
FT                   /evidence="ECO:0007829|PDB:4WNP"
FT   HELIX           156..158
FT                   /evidence="ECO:0007829|PDB:4WNO"
FT   STRAND          160..163
FT                   /evidence="ECO:0007829|PDB:4WNO"
FT   TURN            185..187
FT                   /evidence="ECO:0007829|PDB:4WNO"
FT   HELIX           190..193
FT                   /evidence="ECO:0007829|PDB:4WNO"
FT   HELIX           201..216
FT                   /evidence="ECO:0007829|PDB:4WNO"
FT   HELIX           226..235
FT                   /evidence="ECO:0007829|PDB:4WNO"
FT   HELIX           249..258
FT                   /evidence="ECO:0007829|PDB:4WNO"
FT   TURN            263..265
FT                   /evidence="ECO:0007829|PDB:4WNO"
FT   HELIX           269..273
FT                   /evidence="ECO:0007829|PDB:4WNO"
FT   HELIX           276..278
FT                   /evidence="ECO:0007829|PDB:4WNO"
FT   STRAND          281..284
FT                   /evidence="ECO:0007829|PDB:6MNH"
SQ   SEQUENCE   1050 AA;  112631 MW;  AED9BD5139F2DB92 CRC64;
     MEPGRGGTET VGKFEFSRKD LIGHGAFAVV FKGRHREKHD LEVAVKCINK KNLAKSQTLL
     GKEIKILKEL KHENIVALYD FQEMANSVYL VMEYCNGGDL ADYLHAMRTL SEDTIRLFLQ
     QIAGAMRLLH SKGIIHRDLK PQNILLSNPA GRRANPNSIR VKIADFGFAR YLQSNMMAAT
     LCGSPMYMAP EVIMSQHYDG KADLWSIGTI VYQCLTGKAP FQASSPQDLR LFYEKNKTLV
     PTIPRETSAP LRQLLLALLQ RNHKDRMDFD EFFHHPFLDA SPSVRKSPPV PVPSYPSSGS
     GSSSSSSSTS HLASPPSLGE MQQLQKTLAS PADTAGFLHS SRDSGGSKDS SCDTDDFVMV
     PAQFPGDLVA EAPSAKPPPD SLMCSGSSLV ASAGLESHGR TPSPSPPCSS SPSPSGRAGP
     FSSSRCGASV PIPVPTQVQN YQRIERNLQS PTQFQTPRSS AIRRSGSTSP LGFARASPSP
     PAHAEHGGVL ARKMSLGGGR PYTPSPQVGT IPERPGWSGT PSPQGAEMRG GRSPRPGSSA
     PEHSPRTSGL GCRLHSAPNL SDLHVVRPKL PKPPTDPLGA VFSPPQASPP QPSHGLQSCR
     NLRGSPKLPD FLQRNPLPPI LGSPTKAVPS FDFPKTPSSQ NLLALLARQG VVMTPPRNRT
     LPDLSEVGPF HGQPLGPGLR PGEDPKGPFG RSFSTSRLTD LLLKAAFGTQ APDPGSTESL
     QEKPMEIAPS AGFGGSLHPG ARAGGTSSPS PVVFTVGSPP SGSTPPQGPR TRMFSAGPTG
     SASSSARHLV PGPCSEAPAP ELPAPGHGCS FADPITANLE GAVTFEAPDL PEETLMEQEH
     TEILRGLRFT LLFVQHVLEI AALKGSASEA AGGPEYQLQE SVVADQISLL SREWGFAEQL
     VLYLKVAELL SSGLQSAIDQ IRAGKLCLSS TVKQVVRRLN ELYKASVVSC QGLSLRLQRF
     FLDKQRLLDR IHSITAERLI FSHAVQMVQS AALDEMFQHR EGCVPRYHKA LLLLEGLQHM
     LSDQADIENV TKCKLCIERR LSALLTGICA
//
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