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O70405 (ULK1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 121. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Ulk1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1051 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.2 Ref.4 Ref.5 Ref.6 Ref.7

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Subunit structure

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. Ref.4

Subcellular location

Cytoplasmcytosol. Preautophagosomal structure. 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. Ref.4

Post-translational modification

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. Ref.4 Ref.6 Ref.7

Sequence similarities

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. APG1/unc-51/ULK1 subfamily.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processAutophagy
   Cellular componentCytoplasm
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processRas protein signal transduction

Inferred from direct assay PubMed 15014045. Source: MGI

autophagic vacuole assembly

Inferred from mutant phenotype Ref.4. Source: UniProtKB

axon extension

Inferred from mutant phenotype PubMed 17389358. Source: MGI

axonogenesis

Inferred from direct assay PubMed 15014045. Source: MGI

cellular response to nutrient levels

Inferred from direct assay Ref.6. Source: UniProtKB

cerebellar granule cell differentiation

Inferred from mutant phenotype Ref.2. Source: MGI

negative regulation of collateral sprouting

Inferred from mutant phenotype PubMed 17389358. Source: MGI

neuron projection development

Inferred from sequence or structural similarity. Source: UniProtKB

neuron projection regeneration

Inferred from electronic annotation. Source: Ensembl

positive regulation of autophagy

Inferred from mutant phenotype Ref.6. Source: UniProtKB

positive regulation of macroautophagy

Inferred from electronic annotation. Source: Ensembl

protein autophosphorylation

Inferred from direct assay Ref.2Ref.1. Source: MGI

protein localization

Inferred from sequence or structural similarity. Source: UniProtKB

radial glia guided migration of cerebellar granule cell

Inferred from mutant phenotype Ref.2. Source: MGI

receptor internalization

Inferred from mutant phenotype PubMed 17389358. Source: MGI

regulation of autophagy

Inferred from mutant phenotype PubMed 18443221. Source: UniProtKB

regulation of neurotrophin TRK receptor signaling pathway

Inferred from mutant phenotype PubMed 17389358. Source: MGI

response to starvation

Inferred from direct assay PubMed 18443221. Source: UniProtKB

   Cellular_componentULK1-ATG13-FIP200 complex

Inferred from physical interaction Ref.4. Source: UniProtKB

autophagic vacuole

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from direct assay Ref.2. Source: MGI

cytoplasmic vesicle membrane

Inferred from direct assay PubMed 15014045. Source: MGI

cytosol

Inferred from direct assay Ref.4. Source: UniProtKB

membrane

Inferred from direct assay PubMed 15014045. Source: MGI

neuron projection

Inferred from direct assay Ref.2PubMed 15014045. Source: MGI

neuronal cell body

Inferred from direct assay Ref.2. Source: MGI

pre-autophagosomal structure

Inferred from direct assay Ref.4. Source: UniProtKB

pre-autophagosomal structure membrane

Inferred from direct assay PubMed 18443221. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein kinase activity

Inferred from direct assay Ref.2Ref.1. Source: MGI

protein kinase binding

Inferred from physical interaction Ref.6. Source: UniProtKB

protein serine/threonine kinase activity

Inferred from direct assay PubMed 18443221. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10511051Serine/threonine-protein kinase ULK1
PRO_0000086781

Regions

Domain16 – 278263Protein kinase
Nucleotide binding22 – 309ATP By similarity
Compositional bias297 – 31014Poly-Ser

Sites

Active site1381Proton acceptor By similarity
Binding site461ATP Probable

Amino acid modifications

Modified residue3171Phosphoserine; by AMPK Ref.6
Modified residue4501Phosphoserine By similarity
Modified residue4561Phosphothreonine By similarity
Modified residue4671Phosphoserine Ref.7
Modified residue4771Phosphoserine By similarity
Modified residue4791Phosphoserine By similarity
Modified residue5551Phosphoserine; by AMPK Ref.7
Modified residue5741Phosphothreonine Ref.7
Modified residue6371Phosphoserine; by AMPK Ref.7
Modified residue7571Phosphoserine; by MTOR Ref.6
Modified residue7771Phosphoserine; by AMPK Ref.6

Experimental info

Mutagenesis461K → R: Loss of kinase activity and autophosphorylation. Ref.6 Ref.7
Mutagenesis3171S → A: Impairs phosphorylation by AMPK and ability to promote autophagy; when associated with A-777. Ref.6
Mutagenesis4941S → A: Does not affect phosphorylation by AMPK in vitro. Ref.6
Mutagenesis5551S → A: Does not affect phosphorylation by AMPK in vitro. Ref.6
Mutagenesis5741T → A: Does not affect phosphorylation by AMPK in vitro. Ref.6
Mutagenesis6221S → A: Does not affect phosphorylation by AMPK in vitro. Ref.6
Mutagenesis6241T → A: Does not affect phosphorylation by AMPK in vitro. Ref.6
Mutagenesis6931S → A: Does not affect phosphorylation by AMPK in vitro. Ref.6
Mutagenesis7571S → A or D: Impairs interaction with AMPK and subsequent phosphorylation by AMPK. Ref.6
Mutagenesis7771S → A: Impairs phosphorylation by AMPK and ability to promote autophagy; when associated with A-317. Ref.6
Mutagenesis8111S → A: Does not affect phosphorylation by AMPK in vitro. Ref.6
Sequence conflict4691T → S in AAH57121. Ref.3

Sequences

Sequence LengthMass (Da)Tools
O70405 [UniParc].

Last modified August 1, 1998. Version 1.
Checksum: 99B021985FB4E8A0

FASTA1,051112,463
        10         20         30         40         50         60 
MEPGRGGVET VGKFEFSRKD LIGHGAFAVV FKGRHREKHD LEVAVKCINK KNLAKSQTLL 

        70         80         90        100        110        120 
GKEIKILKEL KHENIVALYD FQEMANSVYL VMEYCNGGDL ADYLHTMRTL SEDTVRLFLQ 

       130        140        150        160        170        180 
QIAGAMRLLH SKGIIHRDLK PQNILLSNPG GRRANPSNIR VKIADFGFAR YLQSNMMAAT 

       190        200        210        220        230        240 
LCGSPMYMAP EVIMSQHYDG KADLWSIGTI VYQCLTGKAP FQASSPQDLR LFYEKNKTLV 

       250        260        270        280        290        300 
PAIPRETSAP LRQLLLALLQ RNHKDRMDFD EFFHHPFLDA STPIKKSPPV PVPSYPSSGS 

       310        320        330        340        350        360 
GSSSSSSSAS HLASPPSLGE MPQLQKTLTS PADAAGFLQG SRDSGGSSKD SCDTDDFVMV 

       370        380        390        400        410        420 
PAQFPGDLVA EAASAKPPPD SLLCSGSSLV ASAGLESHGR TPSPSPTCSS SPSPSGRPGP 

       430        440        450        460        470        480 
FSSNRYGASV PIPVPTQVHN YQRIEQNLQS PTQQQTARSS AIRRSGSTTP LGFGRASPSP 

       490        500        510        520        530        540 
PSHTDGAMLA RKLSLGGGRP YTPSPQVGTI PERPSWSRVP SPQGADVRVG RSPRPGSSVP 

       550        560        570        580        590        600 
EHSPRTTGLG CRLHSAPNLS DFHVVRPKLP KPPTDPLGAT FSPPQTSAPQ PCPGLQSCRP 

       610        620        630        640        650        660 
LRGSPKLPDF LQRSPLPPIL GSPTKAGPSF DFPKTPSSQN LLTLLARQGV VMTPPRNRTL 

       670        680        690        700        710        720 
PDLSEASPFH GQQLGSGLRP AEDTRGPFGR SFSTSRITDL LLKAAFGTQA SDSGSTDSLQ 

       730        740        750        760        770        780 
EKPMEIAPSA GFGGTLHPGA RGGGASSPAP VVFTVGSPPS GATPPQSTRT RMFSVGSSSS 

       790        800        810        820        830        840 
LGSTGSSSAR HLVPGACGEA PELSAPGHCC SLADPLAANL EGAVTFEAPD LPEETLMEQE 

       850        860        870        880        890        900 
HTETLHSLRF TLAFAQQVLE IAALKGSASE AAGGPEYQLQ ESVVADQISQ LSREWGFAEQ 

       910        920        930        940        950        960 
LVLYLKVAEL LSSGLQTAID QIRAGKLCLS STVKQVVRRL NELYKASVVS CQGLSLRLQR 

       970        980        990       1000       1010       1020 
FFLDKQRLLD GIHGVTAERL ILSHAVQMVQ SAALDEMFQH REGCVPRYHK ALLLLEGLQH 

      1030       1040       1050 
TLTDQADIEN IAKCKLCIER RLSALLSGVY A 

« Hide

References

« Hide 'large scale' references
[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]"Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy."
Egan D.F., Shackelford D.B., Mihaylova M.M., Gelino S., Kohnz R.A., Mair W., Vasquez D.S., Joshi A., Gwinn D.M., Taylor R., Asara J.M., Fitzpatrick J., Dillin A., Viollet B., Kundu M., Hansen M., Shaw R.J.
Science 331:456-461(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, AUTOPHOSPHORYLATION, PHOSPHORYLATION AT SER-467; SER-555; THR-574 AND SER-637, MUTAGENESIS OF LYS-46.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF053756 mRNA. Translation: AAC40118.1.
AF072370 mRNA. Translation: AAF23317.1.
BC057121 mRNA. Translation: AAH57121.1.
PIRJW0051.
RefSeqNP_033495.2. NM_009469.3.
UniGeneMm.271898.

3D structure databases

ProteinModelPortalO70405.
SMRO70405. Positions 11-278.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid204438. 4 interactions.
DIPDIP-60541N.
IntActO70405. 2 interactions.

PTM databases

PhosphoSiteO70405.

Proteomic databases

PaxDbO70405.
PRIDEO70405.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000031490; ENSMUSP00000031490; ENSMUSG00000029512.
GeneID22241.
KEGGmmu:22241.
UCSCuc008yrq.1. mouse.

Organism-specific databases

CTD8408.
MGIMGI:1270126. Ulk1.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00750000117559.
HOGENOMHOG000044146.
HOVERGENHBG000342.
KOK08269.
OrthoDBEOG7K0ZBF.
PhylomeDBO70405.
TreeFamTF324551.

Enzyme and pathway databases

BRENDA2.7.11.1. 3474.

Gene expression databases

ArrayExpressO70405.
BgeeO70405.
CleanExMM_ULK1.
GenevestigatorO70405.

Family and domain databases

InterProIPR011009. 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]
PfamPF12063. DUF3543. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
PIRSFPIRSF000580. Ser/Thr_PK_STPK_ULK-1/2. 1 hit.
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio302305.
PROO70405.
SOURCESearch...

Entry information

Entry nameULK1_MOUSE
AccessionPrimary (citable) accession number: O70405
Secondary accession number(s): Q6PGB2
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: August 1, 1998
Last modified: April 16, 2014
This is version 121 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot