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O70405

- ULK1_MOUSE

UniProt

O70405 - ULK1_MOUSE

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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

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 kinase activity Source: MGI
  3. protein kinase binding Source: UniProtKB
  4. 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
Complete GO annotation...

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
Complete GO annotation...

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 AMPK1 Publication
Modified residuei450 – 4501PhosphoserineBy similarity
Modified residuei456 – 4561PhosphothreonineBy similarity
Modified residuei467 – 4671Phosphoserine1 Publication
Modified residuei477 – 4771PhosphoserineBy similarity
Modified residuei479 – 4791PhosphoserineBy similarity
Modified residuei555 – 5551Phosphoserine; by AMPK1 Publication
Modified residuei574 – 5741Phosphothreonine1 Publication
Modified residuei637 – 6371Phosphoserine; by AMPK1 Publication
Modified residuei757 – 7571Phosphoserine; by MTOR1 Publication
Modified residuei777 – 7771Phosphoserine; by AMPK1 Publication

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

MaxQBiO70405.
PaxDbiO70405.
PRIDEiO70405.

PTM databases

PhosphoSiteiO70405.

Expressioni

Gene expression databases

BgeeiO70405.
CleanExiMM_ULK1.
ExpressionAtlasiO70405. baseline and differential.
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

Binary interactionsi

WithEntry#Exp.IntActNotes
SESN2P580045EBI-8390771,EBI-3939642From a different organism.
SQSTM1Q135012EBI-8390771,EBI-307104From a different organism.

Protein-protein interaction databases

BioGridi204438. 5 interactions.
DIPiDIP-60541N.
IntActiO70405. 5 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.
GeneTreeiENSGT00770000120504.
HOGENOMiHOG000044146.
HOVERGENiHBG000342.
InParanoidiO70405.
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.
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

        10         20         30         40         50
MEPGRGGVET VGKFEFSRKD LIGHGAFAVV FKGRHREKHD LEVAVKCINK
60 70 80 90 100
KNLAKSQTLL GKEIKILKEL KHENIVALYD FQEMANSVYL VMEYCNGGDL
110 120 130 140 150
ADYLHTMRTL SEDTVRLFLQ QIAGAMRLLH SKGIIHRDLK PQNILLSNPG
160 170 180 190 200
GRRANPSNIR VKIADFGFAR YLQSNMMAAT LCGSPMYMAP EVIMSQHYDG
210 220 230 240 250
KADLWSIGTI VYQCLTGKAP FQASSPQDLR LFYEKNKTLV PAIPRETSAP
260 270 280 290 300
LRQLLLALLQ RNHKDRMDFD EFFHHPFLDA STPIKKSPPV PVPSYPSSGS
310 320 330 340 350
GSSSSSSSAS HLASPPSLGE MPQLQKTLTS PADAAGFLQG SRDSGGSSKD
360 370 380 390 400
SCDTDDFVMV PAQFPGDLVA EAASAKPPPD SLLCSGSSLV ASAGLESHGR
410 420 430 440 450
TPSPSPTCSS SPSPSGRPGP FSSNRYGASV PIPVPTQVHN YQRIEQNLQS
460 470 480 490 500
PTQQQTARSS AIRRSGSTTP LGFGRASPSP PSHTDGAMLA RKLSLGGGRP
510 520 530 540 550
YTPSPQVGTI PERPSWSRVP SPQGADVRVG RSPRPGSSVP EHSPRTTGLG
560 570 580 590 600
CRLHSAPNLS DFHVVRPKLP KPPTDPLGAT FSPPQTSAPQ PCPGLQSCRP
610 620 630 640 650
LRGSPKLPDF LQRSPLPPIL GSPTKAGPSF DFPKTPSSQN LLTLLARQGV
660 670 680 690 700
VMTPPRNRTL PDLSEASPFH GQQLGSGLRP AEDTRGPFGR SFSTSRITDL
710 720 730 740 750
LLKAAFGTQA SDSGSTDSLQ EKPMEIAPSA GFGGTLHPGA RGGGASSPAP
760 770 780 790 800
VVFTVGSPPS GATPPQSTRT RMFSVGSSSS LGSTGSSSAR HLVPGACGEA
810 820 830 840 850
PELSAPGHCC SLADPLAANL EGAVTFEAPD LPEETLMEQE HTETLHSLRF
860 870 880 890 900
TLAFAQQVLE IAALKGSASE AAGGPEYQLQ ESVVADQISQ LSREWGFAEQ
910 920 930 940 950
LVLYLKVAEL LSSGLQTAID QIRAGKLCLS STVKQVVRRL NELYKASVVS
960 970 980 990 1000
CQGLSLRLQR FFLDKQRLLD GIHGVTAERL ILSHAVQMVQ SAALDEMFQH
1010 1020 1030 1040 1050
REGCVPRYHK ALLLLEGLQH TLTDQADIEN IAKCKLCIER RLSALLSGVY

A
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:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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. 5 interactions.
DIPi DIP-60541N.
IntActi O70405. 5 interactions.

PTM databases

PhosphoSitei O70405.

Proteomic databases

MaxQBi O70405.
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 ENSGT00770000120504.
HOGENOMi HOG000044146.
HOVERGENi HBG000342.
InParanoidi O70405.
KOi K08269.
OrthoDBi EOG7K0ZBF.
PhylomeDBi O70405.
TreeFami TF324551.

Enzyme and pathway databases

BRENDAi 2.7.11.1. 3474.

Miscellaneous databases

ChiTaRSi Ulk1. mouse.
NextBioi 302305.
PROi O70405.
SOURCEi Search...

Gene expression databases

Bgeei O70405.
CleanExi MM_ULK1.
ExpressionAtlasi O70405. baseline and differential.
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.
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

« Hide 'large scale' publications
  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: November 26, 2014
This is version 126 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