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Protein

Serine/threonine-protein kinase ULK1

Gene

Ulk1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: 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. May also phosphorylate SESN2 and SQSTM1 to regulate autophagy (PubMed:25040165).6 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

  • ATP binding Source: UniProtKB-KW
  • Hsp90 protein binding Source: ParkinsonsUK-UCL
  • protein complex binding Source: MGI
  • protein kinase activity Source: MGI
  • protein kinase binding Source: UniProtKB
  • protein serine/threonine kinase activity Source: UniProtKB
  • Rab GTPase binding Source: MGI

GO - Biological processi

  • autophagosome assembly Source: UniProtKB
  • axon extension Source: MGI
  • axonogenesis Source: MGI
  • cellular response to amino acid starvation Source: ParkinsonsUK-UCL
  • cellular response to nutrient levels Source: UniProtKB
  • cerebellar granule cell differentiation Source: MGI
  • macroautophagy Source: ParkinsonsUK-UCL
  • mitophagy in response to mitochondrial depolarization Source: ParkinsonsUK-UCL
  • negative regulation of collateral sprouting Source: MGI
  • negative regulation of protein complex assembly Source: MGI
  • neuron projection development Source: UniProtKB
  • peptidyl-serine phosphorylation Source: ParkinsonsUK-UCL
  • positive regulation of autophagy Source: UniProtKB
  • positive regulation of macroautophagy Source: MGI
  • protein autophosphorylation Source: MGI
  • protein localization Source: UniProtKB
  • radial glia guided migration of cerebellar granule cell Source: MGI
  • Ras protein signal transduction Source: MGI
  • receptor internalization Source: MGI
  • regulation of autophagy Source: UniProtKB
  • regulation of cell death Source: ParkinsonsUK-UCL
  • regulation of gene expression Source: ParkinsonsUK-UCL
  • regulation of neurotrophin TRK receptor signaling pathway Source: MGI
  • 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
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:1270126. Ulk1.

Subcellular locationi

GO - Cellular componenti

  • ATG1/ULK1 kinase complex Source: UniProtKB
  • autophagosome Source: MGI
  • cytoplasm Source: MGI
  • cytoplasmic vesicle membrane Source: MGI
  • cytosol Source: UniProtKB
  • extrinsic component of autophagosome membrane Source: MGI
  • extrinsic component of omegasome membrane Source: MGI
  • extrinsic component of pre-autophagosomal structure membrane Source: MGI
  • membrane Source: MGI
  • neuronal cell body Source: MGI
  • neuron projection Source: MGI
  • pre-autophagosomal structure Source: UniProtKB
  • pre-autophagosomal structure membrane 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 residuei403 – 4031PhosphoserineBy similarity
Modified residuei450 – 4501PhosphoserineCombined sources
Modified residuei456 – 4561PhosphothreonineBy similarity
Modified residuei467 – 4671Phosphoserine1 Publication
Modified residuei477 – 4771PhosphoserineBy similarity
Modified residuei479 – 4791PhosphoserineBy similarity
Modified residuei521 – 5211PhosphoserineCombined sources
Modified residuei555 – 5551Phosphoserine; by AMPK1 Publication
Modified residuei574 – 5741Phosphothreonine1 Publication
Modified residuei635 – 6351PhosphothreonineCombined sources
Modified residuei637 – 6371Phosphoserine; by AMPKCombined sources1 Publication
Modified residuei638 – 6381PhosphoserineCombined sources
Modified residuei757 – 7571Phosphoserine; by MTORCombined sources1 Publication
Modified residuei774 – 7741PhosphoserineBy similarity
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.
PeptideAtlasiO70405.
PRIDEiO70405.

PTM databases

iPTMnetiO70405.
PhosphoSiteiO70405.

Expressioni

Gene expression databases

BgeeiENSMUSG00000029512.
CleanExiMM_ULK1.

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). Interacts (phosphorylated form) with TRIM5 (By similarity). When phosphorylated at Ser-317, interacts with MEFV and BECN1 simultaneously. Interacts with TRIM21 and IRF3, in the presence of TRIM21 (By similarity). Interacts with SESN2 (PubMed:25040165). Interacts with SQSTM1 (PubMed:25040165).By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
FUNDC1Q8IVP53EBI-8390771,EBI-3059266From a different organism.
Fundc1Q9DB702EBI-8390771,EBI-10106464
SESN2P580045EBI-8390771,EBI-3939642From a different organism.
SQSTM1Q135012EBI-8390771,EBI-307104From a different organism.

GO - Molecular functioni

  • Hsp90 protein binding Source: ParkinsonsUK-UCL
  • protein complex binding Source: MGI
  • protein kinase binding Source: UniProtKB
  • Rab GTPase binding Source: MGI

Protein-protein interaction databases

BioGridi204438. 7 interactions.
DIPiDIP-60541N.
IntActiO70405. 12 interactions.
STRINGi10090.ENSMUSP00000031490.

Structurei

3D structure databases

ProteinModelPortaliO70405.
SMRiO70405. Positions 9-280.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

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

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni287 – 416130Interaction with GABARAP and GABARAPL2By similarityAdd
BLAST
Regioni829 – 1051223C-terminal domain; mediates interaction with SESN2By similarityAdd
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

eggNOGiKOG0595. Eukaryota.
ENOG410XR01. LUCA.
HOGENOMiHOG000044146.
HOVERGENiHBG000342.
InParanoidiO70405.
KOiK08269.
PhylomeDBiO70405.
TreeFamiTF324551.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
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

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.
CCDSiCCDS19532.1.
PIRiJW0051.
RefSeqiNP_033495.2. NM_009469.3.
UniGeneiMm.271898.

3D structure databases

ProteinModelPortaliO70405.
SMRiO70405. Positions 9-280.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204438. 7 interactions.
DIPiDIP-60541N.
IntActiO70405. 12 interactions.
STRINGi10090.ENSMUSP00000031490.

PTM databases

iPTMnetiO70405.
PhosphoSiteiO70405.

Proteomic databases

MaxQBiO70405.
PaxDbiO70405.
PeptideAtlasiO70405.
PRIDEiO70405.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi22241.
KEGGimmu:22241.
UCSCiuc008yrq.1. mouse.

Organism-specific databases

CTDi8408.
MGIiMGI:1270126. Ulk1.

Phylogenomic databases

eggNOGiKOG0595. Eukaryota.
ENOG410XR01. LUCA.
HOGENOMiHOG000044146.
HOVERGENiHBG000342.
InParanoidiO70405.
KOiK08269.
PhylomeDBiO70405.
TreeFamiTF324551.

Enzyme and pathway databases

BRENDAi2.7.11.1. 3474.

Miscellaneous databases

ChiTaRSiUlk1. mouse.
PROiO70405.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000029512.
CleanExiMM_ULK1.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
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]
ProtoNetiSearch...

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: September 7, 2016
This is version 144 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.