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O70405

- ULK1_MOUSE

UniProt

O70405 - ULK1_MOUSE

Protein

Serine/threonine-protein kinase ULK1

Gene

Ulk1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 124 (01 Oct 2014)
      Sequence version 1 (01 Aug 1998)
      Previous versions | rss
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    Functioni

    Serine/threonine-protein kinase involved in autophagy in response to starvation. Acts upstream of phosphatidylinositol 3-kinase PIK3C3 to regulate the formation of autophagophores, the precursors of autophagosomes. Part of regulatory feedback loops in autophagy: acts both as a downstream effector and negative regulator of mammalian target of rapamycin complex 1 (mTORC1) via interaction with RPTOR. Activated via phosphorylation by AMPK and also acts as a regulator of AMPK by mediating phosphorylation of AMPK subunits PRKAA1, PRKAB2 and PRKAG1, leading to negatively regulate AMPK activity. May phosphorylate ATG13/KIAA0652 and RPTOR; however such data need additional evidences. Plays a role early in neuronal differentiation and is required for granule cell axon formation.5 Publications

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei46 – 461ATPCurated
    Active sitei138 – 1381Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi22 – 309ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. protein binding Source: UniProtKB
    3. protein kinase activity Source: MGI
    4. protein kinase binding Source: UniProtKB
    5. protein serine/threonine kinase activity Source: UniProtKB

    GO - Biological processi

    1. autophagic vacuole assembly Source: UniProtKB
    2. axon extension Source: MGI
    3. axonogenesis Source: MGI
    4. cellular response to nutrient levels Source: UniProtKB
    5. cerebellar granule cell differentiation Source: MGI
    6. negative regulation of collateral sprouting Source: MGI
    7. neuron projection development Source: UniProtKB
    8. neuron projection regeneration Source: Ensembl
    9. positive regulation of autophagy Source: UniProtKB
    10. positive regulation of macroautophagy Source: Ensembl
    11. protein autophosphorylation Source: MGI
    12. protein localization Source: UniProtKB
    13. radial glia guided migration of cerebellar granule cell Source: MGI
    14. Ras protein signal transduction Source: MGI
    15. receptor internalization Source: MGI
    16. regulation of autophagy Source: UniProtKB
    17. regulation of neurotrophin TRK receptor signaling pathway Source: MGI
    18. response to starvation Source: UniProtKB

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Biological processi

    Autophagy

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.11.1. 3474.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Serine/threonine-protein kinase ULK1 (EC:2.7.11.1)
    Alternative name(s):
    Serine/threonine-protein kinase Unc51.1
    Unc-51-like kinase 1
    Gene namesi
    Name:Ulk1
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 5

    Organism-specific databases

    MGIiMGI:1270126. Ulk1.

    Subcellular locationi

    Cytoplasmcytosol 1 Publication. Preautophagosomal structure 1 Publication
    Note: Under starvation conditions, is localized to puncate structures primarily representing the isolation membrane that sequesters a portion of the cytoplasm resulting in the formation of an autophagosome.

    GO - Cellular componenti

    1. ATG1/UKL1 signaling complex Source: RefGenome
    2. autophagic vacuole Source: Ensembl
    3. cytoplasm Source: MGI
    4. cytoplasmic vesicle membrane Source: MGI
    5. cytosol Source: UniProtKB
    6. membrane Source: MGI
    7. neuronal cell body Source: MGI
    8. neuron projection Source: MGI
    9. pre-autophagosomal structure Source: UniProtKB
    10. pre-autophagosomal structure membrane Source: UniProtKB
    11. ULK1-ATG13-FIP200 complex Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi46 – 461K → R: Loss of kinase activity and autophosphorylation. 2 Publications
    Mutagenesisi317 – 3171S → A: Impairs phosphorylation by AMPK and ability to promote autophagy; when associated with A-777. 1 Publication
    Mutagenesisi494 – 4941S → A: Does not affect phosphorylation by AMPK in vitro. 1 Publication
    Mutagenesisi555 – 5551S → A: Does not affect phosphorylation by AMPK in vitro. 1 Publication
    Mutagenesisi574 – 5741T → A: Does not affect phosphorylation by AMPK in vitro. 1 Publication
    Mutagenesisi622 – 6221S → A: Does not affect phosphorylation by AMPK in vitro. 1 Publication
    Mutagenesisi624 – 6241T → A: Does not affect phosphorylation by AMPK in vitro. 1 Publication
    Mutagenesisi693 – 6931S → A: Does not affect phosphorylation by AMPK in vitro. 1 Publication
    Mutagenesisi757 – 7571S → A or D: Impairs interaction with AMPK and subsequent phosphorylation by AMPK. 1 Publication
    Mutagenesisi777 – 7771S → A: Impairs phosphorylation by AMPK and ability to promote autophagy; when associated with A-317. 1 Publication
    Mutagenesisi811 – 8111S → A: Does not affect phosphorylation by AMPK in vitro. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 10511051Serine/threonine-protein kinase ULK1PRO_0000086781Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei317 – 3171Phosphoserine; by AMPK2 Publications
    Modified residuei450 – 4501PhosphoserineBy similarity
    Modified residuei456 – 4561PhosphothreonineBy similarity
    Modified residuei467 – 4671Phosphoserine2 Publications
    Modified residuei477 – 4771PhosphoserineBy similarity
    Modified residuei479 – 4791PhosphoserineBy similarity
    Modified residuei555 – 5551Phosphoserine; by AMPK2 Publications
    Modified residuei574 – 5741Phosphothreonine2 Publications
    Modified residuei637 – 6371Phosphoserine; by AMPK2 Publications
    Modified residuei757 – 7571Phosphoserine; by MTOR2 Publications
    Modified residuei777 – 7771Phosphoserine; by AMPK2 Publications

    Post-translational modificationi

    Autophosphorylated. Phosphorylated under nutrient-rich conditions; dephosphorylated during starvation or following treatment with rapamycin. In response to nutrient limitation, phosphorylated and activated by AMPK, leading to activate autophagy. Under nutrient sufficiency, phosphorylated by MTOR/mTOR, disrupting the interaction with AMPK and preventing activation of ULK1.3 Publications

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PaxDbiO70405.
    PRIDEiO70405.

    PTM databases

    PhosphoSiteiO70405.

    Expressioni

    Gene expression databases

    ArrayExpressiO70405.
    BgeeiO70405.
    CleanExiMM_ULK1.
    GenevestigatoriO70405.

    Interactioni

    Subunit structurei

    Interacts with GABARAP and GABARAPL2 By similarity. Interacts (via C-terminus) with ATG13 By similarity. Part of a complex consisting of ATG13, ATG101, ULK1 and RB1CC1. Associates with the mammalian target of rapamycin complex 1 (mTORC1) through an interaction with RPTOR; the association depends on nutrient conditions and is reduced during starvation By similarity. Interacts with FEZ1; SCOC interferes with FEZ1-binding By similarity. Interacts with TBC1D14 By similarity.By similarity

    Protein-protein interaction databases

    BioGridi204438. 4 interactions.
    DIPiDIP-60541N.
    IntActiO70405. 2 interactions.

    Structurei

    3D structure databases

    ProteinModelPortaliO70405.
    SMRiO70405. Positions 11-316.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini16 – 278263Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi297 – 31014Poly-SerAdd
    BLAST

    Sequence similaritiesi

    Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. APG1/unc-51/ULK1 subfamily.PROSITE-ProRule annotation
    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG0515.
    GeneTreeiENSGT00750000117559.
    HOGENOMiHOG000044146.
    HOVERGENiHBG000342.
    KOiK08269.
    OrthoDBiEOG7K0ZBF.
    PhylomeDBiO70405.
    TreeFamiTF324551.

    Family and domain databases

    InterProiIPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR002290. Ser/Thr_dual-sp_kinase_dom.
    IPR016237. Ser/Thr_kin_STPK_Ulk-1/2.
    IPR008271. Ser/Thr_kinase_AS.
    IPR022708. Ser/Thr_kinase_C.
    [Graphical view]
    PfamiPF12063. DUF3543. 1 hit.
    PF00069. Pkinase. 1 hit.
    [Graphical view]
    PIRSFiPIRSF000580. Ser/Thr_PK_STPK_ULK-1/2. 1 hit.
    SMARTiSM00220. S_TKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF56112. SSF56112. 1 hit.
    PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    O70405-1 [UniParc]FASTAAdd to Basket

    « Hide

    MEPGRGGVET VGKFEFSRKD LIGHGAFAVV FKGRHREKHD LEVAVKCINK     50
    KNLAKSQTLL GKEIKILKEL KHENIVALYD FQEMANSVYL VMEYCNGGDL 100
    ADYLHTMRTL SEDTVRLFLQ QIAGAMRLLH SKGIIHRDLK PQNILLSNPG 150
    GRRANPSNIR VKIADFGFAR YLQSNMMAAT LCGSPMYMAP EVIMSQHYDG 200
    KADLWSIGTI VYQCLTGKAP FQASSPQDLR LFYEKNKTLV PAIPRETSAP 250
    LRQLLLALLQ RNHKDRMDFD EFFHHPFLDA STPIKKSPPV PVPSYPSSGS 300
    GSSSSSSSAS HLASPPSLGE MPQLQKTLTS PADAAGFLQG SRDSGGSSKD 350
    SCDTDDFVMV PAQFPGDLVA EAASAKPPPD SLLCSGSSLV ASAGLESHGR 400
    TPSPSPTCSS SPSPSGRPGP FSSNRYGASV PIPVPTQVHN YQRIEQNLQS 450
    PTQQQTARSS AIRRSGSTTP LGFGRASPSP PSHTDGAMLA RKLSLGGGRP 500
    YTPSPQVGTI PERPSWSRVP SPQGADVRVG RSPRPGSSVP EHSPRTTGLG 550
    CRLHSAPNLS DFHVVRPKLP KPPTDPLGAT FSPPQTSAPQ PCPGLQSCRP 600
    LRGSPKLPDF LQRSPLPPIL GSPTKAGPSF DFPKTPSSQN LLTLLARQGV 650
    VMTPPRNRTL PDLSEASPFH GQQLGSGLRP AEDTRGPFGR SFSTSRITDL 700
    LLKAAFGTQA SDSGSTDSLQ EKPMEIAPSA GFGGTLHPGA RGGGASSPAP 750
    VVFTVGSPPS GATPPQSTRT RMFSVGSSSS LGSTGSSSAR HLVPGACGEA 800
    PELSAPGHCC SLADPLAANL EGAVTFEAPD LPEETLMEQE HTETLHSLRF 850
    TLAFAQQVLE IAALKGSASE AAGGPEYQLQ ESVVADQISQ LSREWGFAEQ 900
    LVLYLKVAEL LSSGLQTAID QIRAGKLCLS STVKQVVRRL NELYKASVVS 950
    CQGLSLRLQR FFLDKQRLLD GIHGVTAERL ILSHAVQMVQ SAALDEMFQH 1000
    REGCVPRYHK ALLLLEGLQH TLTDQADIEN IAKCKLCIER RLSALLSGVY 1050
    A 1051
    Length:1,051
    Mass (Da):112,463
    Last modified:August 1, 1998 - v1
    Checksum:i99B021985FB4E8A0
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti469 – 4691T → S in AAH57121. (PubMed:15489334)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF053756 mRNA. Translation: AAC40118.1.
    AF072370 mRNA. Translation: AAF23317.1.
    BC057121 mRNA. Translation: AAH57121.1.
    CCDSiCCDS19532.1.
    PIRiJW0051.
    RefSeqiNP_033495.2. NM_009469.3.
    UniGeneiMm.271898.

    Genome annotation databases

    EnsembliENSMUST00000031490; ENSMUSP00000031490; ENSMUSG00000029512.
    GeneIDi22241.
    KEGGimmu:22241.
    UCSCiuc008yrq.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF053756 mRNA. Translation: AAC40118.1 .
    AF072370 mRNA. Translation: AAF23317.1 .
    BC057121 mRNA. Translation: AAH57121.1 .
    CCDSi CCDS19532.1.
    PIRi JW0051.
    RefSeqi NP_033495.2. NM_009469.3.
    UniGenei Mm.271898.

    3D structure databases

    ProteinModelPortali O70405.
    SMRi O70405. Positions 11-316.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 204438. 4 interactions.
    DIPi DIP-60541N.
    IntActi O70405. 2 interactions.

    PTM databases

    PhosphoSitei O70405.

    Proteomic databases

    PaxDbi O70405.
    PRIDEi O70405.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000031490 ; ENSMUSP00000031490 ; ENSMUSG00000029512 .
    GeneIDi 22241.
    KEGGi mmu:22241.
    UCSCi uc008yrq.1. mouse.

    Organism-specific databases

    CTDi 8408.
    MGIi MGI:1270126. Ulk1.

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00750000117559.
    HOGENOMi HOG000044146.
    HOVERGENi HBG000342.
    KOi K08269.
    OrthoDBi EOG7K0ZBF.
    PhylomeDBi O70405.
    TreeFami TF324551.

    Enzyme and pathway databases

    BRENDAi 2.7.11.1. 3474.

    Miscellaneous databases

    NextBioi 302305.
    PROi O70405.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O70405.
    Bgeei O70405.
    CleanExi MM_ULK1.
    Genevestigatori O70405.

    Family and domain databases

    InterProi IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR002290. Ser/Thr_dual-sp_kinase_dom.
    IPR016237. Ser/Thr_kin_STPK_Ulk-1/2.
    IPR008271. Ser/Thr_kinase_AS.
    IPR022708. Ser/Thr_kinase_C.
    [Graphical view ]
    Pfami PF12063. DUF3543. 1 hit.
    PF00069. Pkinase. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF000580. Ser/Thr_PK_STPK_ULK-1/2. 1 hit.
    SMARTi SM00220. S_TKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56112. SSF56112. 1 hit.
    PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Identification of mouse ULK1, a novel protein kinase structurally related to C. elegans UNC-51."
      Yan J., Kuroyanagi H., Kuroiwa A., Matsuda Y., Tokumitsu H., Tomoda T., Shirasawa T., Muramatsu M.-A.
      Biochem. Biophys. Res. Commun. 246:222-227(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Brain.
    2. "A mouse serine/threonine kinase homologous to C. elegans UNC51 functions in parallel fiber formation of cerebellar granule neurons."
      Tomoda T., Bhatt R.S., Kuroyanagi H., Shirasawa T., Hatten M.E.
      Neuron 24:833-846(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION.
      Strain: C57BL/6J.
      Tissue: Brain.
    3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: C57BL/6.
      Tissue: Brain.
    4. "ULK1.ATG13.FIP200 complex mediates mTOR signaling and is essential for autophagy."
      Ganley I.G., Lam du H., Wang J., Ding X., Chen S., Jiang X.
      J. Biol. Chem. 284:12297-12305(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH ATG13 AND RB1CC1, PHOSPHORYLATION, SUBCELLULAR LOCATION.
    5. "Ulk1-mediated phosphorylation of AMPK constitutes a negative regulatory feedback loop."
      Loffler A.S., Alers S., Dieterle A.M., Keppeler H., Franz-Wachtel M., Kundu M., Campbell D.G., Wesselborg S., Alessi D.R., Stork B.
      Autophagy 7:696-706(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF AMPK.
    6. "AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1."
      Kim J., Kundu M., Viollet B., Guan K.L.
      Nat. Cell Biol. 13:132-141(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, AUTOPHOSPHORYLATION, PHOSPHORYLATION AT SER-317; SER-757 AND SER-777, MUTAGENESIS OF LYS-46; SER-317; SER-494; SER-555; THR-574; SER-622; THR-624; SER-693; SER-757; SER-777 AND SER-811.
    7. Cited for: FUNCTION, AUTOPHOSPHORYLATION, PHOSPHORYLATION AT SER-467; SER-555; THR-574 AND SER-637, MUTAGENESIS OF LYS-46.

    Entry informationi

    Entry nameiULK1_MOUSE
    AccessioniPrimary (citable) accession number: O70405
    Secondary accession number(s): Q6PGB2
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 15, 1999
    Last sequence update: August 1, 1998
    Last modified: October 1, 2014
    This is version 124 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3