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 27-MAR-2024, entry version 216.
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:28821708, ECO:0000269|PubMed:31123703, ECO:0000269|PubMed:37306101};
DE AltName: Full=Autophagy-related protein 1 homolog;
DE Short=ATG1;
DE Short=hATG1 {ECO:0000303|PubMed:21205641};
DE AltName: Full=Unc-51-like kinase 1 {ECO:0000303|PubMed:9693035};
GN Name=ULK1 {ECO:0000303|PubMed:9693035, ECO:0000312|HGNC:HGNC:12558};
GN Synonyms=KIAA0722 {ECO:0000303|PubMed:9872452};
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 IRGM, AND PHOSPHORYLATION AT SER-317 AND SER-556.
RX PubMed=25891078; DOI=10.1016/j.molcel.2015.03.020;
RA Chauhan S., Mandell M.A., Deretic V.;
RT "IRGM governs the core autophagy machinery to conduct antimicrobial
RT defense.";
RL Mol. Cell 58:507-521(2015).
RN [31]
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 [32]
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 [33]
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 [34]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF LYS-46.
RX PubMed=28821708; DOI=10.1038/s41467-017-00303-2;
RA Pengo N., Agrotis A., Prak K., Jones J., Ketteler R.;
RT "A reversible phospho-switch mediated by ULK1 regulates the activity of
RT autophagy protease ATG4B.";
RL Nat. Commun. 8:294-294(2017).
RN [35]
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 [36]
RP FUNCTION, AND DEUBIQUITINATION BY USP20.
RX PubMed=29487085; DOI=10.15252/embr.201744378;
RA Kim J.H., Seo D., Kim S.J., Choi D.W., Park J.S., Ha J., Choi J., Lee J.H.,
RA Jung S.M., Seo K.W., Lee E.W., Lee Y.S., Cheong H., Choi C.Y., Park S.H.;
RT "The deubiquitinating enzyme USP20 stabilizes ULK1 and promotes autophagy
RT initiation.";
RL EMBO Rep. 19:0-0(2018).
RN [37]
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 [38]
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 [39]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=37306101; DOI=10.15252/embj.2022113349;
RA Ikeda R., Noshiro D., Morishita H., Takada S., Kageyama S., Fujioka Y.,
RA Funakoshi T., Komatsu-Hirota S., Arai R., Ryzhii E., Abe M., Koga T.,
RA Motohashi H., Nakao M., Sakimura K., Horii A., Waguri S., Ichimura Y.,
RA Noda N.N., Komatsu M.;
RT "Phosphorylation of phase-separated p62 bodies by ULK1 activates a redox-
RT independent stress response.";
RL EMBO J. 42:e113349-e113349(2023).
RN [40]
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 PubMed:29487085). Acts upstream of phosphatidylinositol 3-kinase PIK3C3
CC to regulate the formation of autophagophores, the precursors of
CC autophagosomes (PubMed:18936157, PubMed:21460634, PubMed:21795849,
CC PubMed:25040165). Part of regulatory feedback loops in autophagy: acts
CC both as a downstream effector and negative regulator of mammalian
CC target of 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). Also phosphorylates SESN2 and SQSTM1 to
CC regulate autophagy (PubMed:25040165, PubMed:37306101). Phosphorylates
CC FLCN, promoting autophagy (PubMed:25126726). Phosphorylates AMBRA1 in
CC response to autophagy induction, releasing AMBRA1 from the cytoskeletal
CC docking site to induce autophagosome nucleation (PubMed:20921139).
CC Phosphorylates ATG4B, leading to inhibit autophagy by decreasing both
CC proteolytic activation and delipidation activities of ATG4B
CC (PubMed:28821708). {ECO:0000269|PubMed:11146101,
CC ECO:0000269|PubMed:18936157, ECO:0000269|PubMed:20921139,
CC ECO:0000269|PubMed:21460634, ECO:0000269|PubMed:21795849,
CC ECO:0000269|PubMed:23524951, ECO:0000269|PubMed:25040165,
CC ECO:0000269|PubMed:25126726, ECO:0000269|PubMed:28821708,
CC ECO:0000269|PubMed:29487085, ECO:0000269|PubMed:31123703,
CC ECO:0000269|PubMed:37306101}.
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:28821708, ECO:0000269|PubMed:31123703,
CC ECO:0000269|PubMed:37306101};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17990;
CC Evidence={ECO:0000269|PubMed:18936157, ECO:0000269|PubMed:25126726,
CC ECO:0000269|PubMed:31123703, ECO:0000269|PubMed:37306101};
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). Interacts with IRGM; promoting the coassembly of ULK1
CC and BECN1 (PubMed:25891078). {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:25891078, ECO:0000269|PubMed:26347139,
CC ECO:0000269|PubMed:27334615, ECO:0000269|PubMed:28561066,
CC ECO:0000269|PubMed:28890335, ECO:0000269|PubMed:31123703,
CC 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=13; 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=11; 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 (PubMed:21205641,
CC PubMed:25891078). {ECO:0000250|UniProtKB:O70405,
CC ECO:0000269|PubMed:21205641, ECO:0000269|PubMed:25891078}.
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. Deubiquitinated by USP20; leading to ULK1 stability
CC and autophagy initiation (PubMed:29487085).
CC {ECO:0000269|PubMed:23524951, ECO:0000269|PubMed:29487085}.
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 PDB; 8SOI; EM; 4.20 A; C=840-1044.
DR PDB; 8SQZ; EM; 5.85 A; C/D=836-1050.
DR PDB; 8SRM; EM; 4.46 A; C/D=836-1050.
DR PDB; 8SRQ; EM; 6.20 A; C=840-1044.
DR PDBsum; 4WNO; -.
DR PDBsum; 4WNP; -.
DR PDBsum; 5CI7; -.
DR PDBsum; 6HYO; -.
DR PDBsum; 6MNH; -.
DR PDBsum; 6QAS; -.
DR PDBsum; 8SOI; -.
DR PDBsum; 8SQZ; -.
DR PDBsum; 8SRM; -.
DR PDBsum; 8SRQ; -.
DR AlphaFoldDB; O75385; -.
DR EMDB; EMD-40658; -.
DR EMDB; EMD-40715; -.
DR EMDB; EMD-40735; -.
DR EMDB; EMD-40738; -.
DR SMR; O75385; -.
DR BioGRID; 113996; 141.
DR ComplexPortal; CPX-373; ULK1-ATG13-RB1CC1-ATG101 autophagy initiation complex.
DR CORUM; O75385; -.
DR DIP; DIP-35196N; -.
DR IntAct; O75385; 70.
DR MINT; O75385; -.
DR STRING; 9606.ENSP00000324560; -.
DR BindingDB; O75385; -.
DR ChEMBL; CHEMBL6006; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; O75385; -.
DR GuidetoPHARMACOLOGY; 2271; -.
DR GlyCosmos; O75385; 1 site, 1 glycan.
DR GlyGen; O75385; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; O75385; -.
DR PhosphoSitePlus; O75385; -.
DR SwissPalm; O75385; -.
DR BioMuta; ULK1; -.
DR CPTAC; CPTAC-3098; -.
DR CPTAC; CPTAC-3099; -.
DR EPD; O75385; -.
DR jPOST; O75385; -.
DR MassIVE; O75385; -.
DR MaxQB; O75385; -.
DR PaxDb; 9606-ENSP00000324560; -.
DR PeptideAtlas; O75385; -.
DR ProteomicsDB; 49958; -.
DR Pumba; O75385; -.
DR Antibodypedia; 31999; 1044 antibodies from 39 providers.
DR DNASU; 8408; -.
DR Ensembl; ENST00000321867.6; ENSP00000324560.3; ENSG00000177169.10.
DR GeneID; 8408; -.
DR KEGG; hsa:8408; -.
DR MANE-Select; ENST00000321867.6; ENSP00000324560.3; NM_003565.4; NP_003556.2.
DR UCSC; uc001uje.4; human.
DR AGR; HGNC:12558; -.
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; CVCEVAR; -.
DR OrthoDB; 8335at2759; -.
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-5357905; Regulation of TNFR1 signaling.
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; 18 hits in 1202 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 body of pancreas and 161 other cell types or 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:0000421; C:autophagosome membrane; IDA:UniProtKB.
DR GO; GO:0030424; C:axon; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProt.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0005741; C:mitochondrial outer membrane; TAS:Reactome.
DR GO; GO:1903349; C:omegasome membrane; IDA:UniProtKB.
DR GO; GO:0000407; C:phagophore assembly site; IDA:ComplexPortal.
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:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
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:0048675; P:axon extension; IBA:GO_Central.
DR GO; GO:0031669; P:cellular response to nutrient levels; ISS:UniProtKB.
DR GO; GO:0016236; P:macroautophagy; IMP:BHF-UCL.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:ComplexPortal.
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:0044804; P:nucleophagy; IBA:GO_Central.
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: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:0016241; P:regulation of macroautophagy; IDA:UniProtKB.
DR GO; GO:1903059; P:regulation of protein lipidation; IDA:ComplexPortal.
DR GO; GO:0010803; P:regulation of tumor necrosis factor-mediated signaling pathway; TAS:Reactome.
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 CDD; cd14202; STKc_ULK1; 1.
DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR InterPro; IPR045269; Atg1-like.
DR InterPro; IPR048941; ATG1-like_MIT2.
DR InterPro; IPR022708; Atg1-like_tMIT.
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 PANTHER; PTHR24348; SERINE/THREONINE-PROTEIN KINASE UNC-51-RELATED; 1.
DR PANTHER; PTHR24348:SF19; SERINE_THREONINE-PROTEIN KINASE ULK1; 1.
DR Pfam; PF12063; ATG1-like_MIT1; 1.
DR Pfam; PF21127; ATG1-like_MIT2; 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; Protein kinase-like (PK-like); 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 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 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: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:0000269|PubMed:25891078"
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:0000269|PubMed:25891078, ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:21406692, 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 ECO:0000269|PubMed:28821708"
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
//
