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Protein

Serine/threonine-protein kinase ULK1

Gene

ULK1

Organism
Homo sapiens (Human)
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).4 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei46ATPPROSITE-ProRule annotation1
Active sitei138Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi22 – 30ATPPROSITE-ProRule annotation9

GO - Molecular functioni

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

GO - Biological processi

  • axon extension Source: GO_Central
  • cellular response to nutrient levels Source: UniProtKB
  • macroautophagy Source: Reactome
  • negative regulation of protein complex assembly Source: ParkinsonsUK-UCL
  • neuron projection development Source: UniProtKB
  • neuron projection regeneration Source: Ensembl
  • peptidyl-serine phosphorylation Source: ParkinsonsUK-UCL
  • positive regulation of autophagy Source: UniProtKB
  • positive regulation of macroautophagy Source: BHF-UCL
  • protein autophosphorylation Source: UniProtKB
  • protein localization Source: UniProtKB
  • protein phosphorylation Source: UniProtKB
  • regulation of autophagy Source: UniProtKB
  • response to starvation Source: UniProtKB
  • signal transduction Source: InterPro
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

BioCyciZFISH:HS11133-MONOMER.
BRENDAi2.7.11.1. 2681.
ReactomeiR-HSA-1632852. Macroautophagy.
R-HSA-8876198. RAB GEFs exchange GTP for GDP on RABs.
SignaLinkiO75385.
SIGNORiO75385.

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase ULK1 (EC:2.7.11.1)
Alternative name(s):
Autophagy-related protein 1 homolog
Short name:
ATG1
Short name:
hATG1
Unc-51-like kinase 1
Gene namesi
Name:ULK1
Synonyms:KIAA0722
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:12558. ULK1.

Subcellular locationi

  • Cytoplasmcytosol By similarity
  • Preautophagosomal structure By similarity

  • 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.By similarity

GO - Cellular componenti

  • ATG1/ULK1 kinase complex Source: UniProtKB
  • autophagosome Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • cytosol Source: UniProtKB
  • extrinsic component of autophagosome membrane Source: UniProtKB
  • extrinsic component of omegasome membrane Source: UniProtKB
  • extrinsic component of pre-autophagosomal structure membrane Source: UniProtKB
  • pre-autophagosomal structure membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Organism-specific databases

DisGeNETi8408.
OpenTargetsiENSG00000177169.
PharmGKBiPA37198.

Chemistry databases

ChEMBLiCHEMBL6006.
GuidetoPHARMACOLOGYi2271.

Polymorphism and mutation databases

BioMutaiULK1.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000867801 – 1050Serine/threonine-protein kinase ULK1Add BLAST1050

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei317Phosphoserine; by AMPKBy similarity1
Modified residuei403PhosphoserineCombined sources1
Modified residuei450PhosphoserineCombined sources1
Modified residuei456PhosphothreonineCombined sources1
Modified residuei467PhosphoserineCombined sources1
Modified residuei469PhosphoserineCombined sources1
Modified residuei477PhosphoserineCombined sources1
Modified residuei479PhosphoserineCombined sources1
Modified residuei522PhosphoserineBy similarity1
Modified residuei556PhosphoserineCombined sources1
Modified residuei575PhosphothreonineBy similarity1
Modified residuei636PhosphothreonineBy similarity1
Modified residuei638PhosphoserineCombined sources1
Modified residuei639PhosphoserineBy similarity1
Modified residuei758Phosphoserine; by MTORCombined sources1 Publication1
Modified residuei775PhosphoserineCombined sources1

Post-translational modificationi

Autophosphorylated. Phosphorylated under nutrient-rich conditions; dephosphorylated during starvation or following treatment with rapamycin. Under nutrient sufficiency, phosphorylated by MTOR/mTOR, disrupting the interaction with AMPK and preventing activation of ULK1 (By similarity). In response to nutrient limitation, phosphorylated and activated by AMPK, leading to activate autophagy.By similarity1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiO75385.
PaxDbiO75385.
PeptideAtlasiO75385.
PRIDEiO75385.

PTM databases

iPTMnetiO75385.
PhosphoSitePlusiO75385.
SwissPalmiO75385.

Expressioni

Tissue specificityi

Ubiquitously expressed. Detected in the following adult tissues: skeletal muscle, heart, pancreas, brain, placenta, liver, kidney, and lung.

Gene expression databases

BgeeiENSG00000177169.
CleanExiHS_ULK1.
GenevisibleiO75385. HS.

Organism-specific databases

HPAiHPA063990.

Interactioni

Subunit structurei

Interacts with GABARAP and GABARAPL2. Interacts (via C-terminus) with ATG13. 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. Interacts with FEZ1; SCOC interferes with FEZ1-binding. Interacts with TBC1D14. Interacts (phosphorylated form) with TRIM5 (PubMed:25127057). When phosphorylated at Ser-317, interacts with MEFV and BECN1 simultaneously. Interacts with TRIM21 and IRF3, in the presence of TRIM21 (PubMed:26347139). Interacts with SESN2 (PubMed:25040165). Interacts with SQSTM1 (PubMed:25040165).11 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ATG13O751434EBI-908831,EBI-2798775
GABARAPL1Q9H0R82EBI-908831,EBI-746969
GABARAPL2P605203EBI-908831,EBI-720116
MAP1LC3BQ9GZQ82EBI-908831,EBI-373144
MAP1LC3CQ9BXW42EBI-908831,EBI-2603996
RB1CC1Q8TDY27EBI-908831,EBI-1047793
TBC1D14Q9P2M44EBI-908831,EBI-2797718

GO - Molecular functioni

  • protein complex binding Source: UniProtKB
  • Rab GTPase binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi113996. 47 interactors.
DIPiDIP-35196N.
IntActiO75385. 29 interactors.
MINTiMINT-1892187.
STRINGi9606.ENSP00000324560.

Chemistry databases

BindingDBiO75385.

Structurei

Secondary structure

11050
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi9 – 11Combined sources3
Beta strandi14 – 24Combined sources11
Beta strandi29 – 37Combined sources9
Beta strandi42 – 47Combined sources6
Helixi50 – 52Combined sources3
Helixi53 – 67Combined sources15
Beta strandi78 – 83Combined sources6
Beta strandi88 – 93Combined sources6
Helixi100 – 106Combined sources7
Helixi112 – 132Combined sources21
Helixi141 – 143Combined sources3
Beta strandi144 – 147Combined sources4
Helixi151 – 153Combined sources3
Helixi156 – 158Combined sources3
Beta strandi160 – 163Combined sources4
Turni185 – 187Combined sources3
Helixi190 – 193Combined sources4
Helixi201 – 216Combined sources16
Helixi226 – 235Combined sources10
Helixi249 – 258Combined sources10
Turni263 – 265Combined sources3
Helixi269 – 273Combined sources5
Helixi276 – 278Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4WNOX-ray1.56A1-283[»]
4WNPX-ray1.88A/B/C/D1-283[»]
5CI7X-ray1.74A1-283[»]
ProteinModelPortaliO75385.
SMRiO75385.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini16 – 278Protein kinasePROSITE-ProRule annotationAdd BLAST263

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni287 – 416Interaction with GABARAP and GABARAPL21 PublicationAdd BLAST130
Regioni828 – 1050C-terminal domain; mediates interaction with SESN21 PublicationAdd BLAST223

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi297 – 310Poly-SerAdd BLAST14

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.
GeneTreeiENSGT00860000133711.
HOGENOMiHOG000044146.
HOVERGENiHBG000342.
InParanoidiO75385.
KOiK08269.
OMAiDTDDFVM.
OrthoDBiEOG091G14RD.
PhylomeDBiO75385.
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.

O75385-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEPGRGGTET VGKFEFSRKD LIGHGAFAVV FKGRHREKHD LEVAVKCINK
60 70 80 90 100
KNLAKSQTLL GKEIKILKEL KHENIVALYD FQEMANSVYL VMEYCNGGDL
110 120 130 140 150
ADYLHAMRTL SEDTIRLFLQ QIAGAMRLLH SKGIIHRDLK PQNILLSNPA
160 170 180 190 200
GRRANPNSIR VKIADFGFAR YLQSNMMAAT LCGSPMYMAP EVIMSQHYDG
210 220 230 240 250
KADLWSIGTI VYQCLTGKAP FQASSPQDLR LFYEKNKTLV PTIPRETSAP
260 270 280 290 300
LRQLLLALLQ RNHKDRMDFD EFFHHPFLDA SPSVRKSPPV PVPSYPSSGS
310 320 330 340 350
GSSSSSSSTS HLASPPSLGE MQQLQKTLAS PADTAGFLHS SRDSGGSKDS
360 370 380 390 400
SCDTDDFVMV PAQFPGDLVA EAPSAKPPPD SLMCSGSSLV ASAGLESHGR
410 420 430 440 450
TPSPSPPCSS SPSPSGRAGP FSSSRCGASV PIPVPTQVQN YQRIERNLQS
460 470 480 490 500
PTQFQTPRSS AIRRSGSTSP LGFARASPSP PAHAEHGGVL ARKMSLGGGR
510 520 530 540 550
PYTPSPQVGT IPERPGWSGT PSPQGAEMRG GRSPRPGSSA PEHSPRTSGL
560 570 580 590 600
GCRLHSAPNL SDLHVVRPKL PKPPTDPLGA VFSPPQASPP QPSHGLQSCR
610 620 630 640 650
NLRGSPKLPD FLQRNPLPPI LGSPTKAVPS FDFPKTPSSQ NLLALLARQG
660 670 680 690 700
VVMTPPRNRT LPDLSEVGPF HGQPLGPGLR PGEDPKGPFG RSFSTSRLTD
710 720 730 740 750
LLLKAAFGTQ APDPGSTESL QEKPMEIAPS AGFGGSLHPG ARAGGTSSPS
760 770 780 790 800
PVVFTVGSPP SGSTPPQGPR TRMFSAGPTG SASSSARHLV PGPCSEAPAP
810 820 830 840 850
ELPAPGHGCS FADPITANLE GAVTFEAPDL PEETLMEQEH TEILRGLRFT
860 870 880 890 900
LLFVQHVLEI AALKGSASEA AGGPEYQLQE SVVADQISLL SREWGFAEQL
910 920 930 940 950
VLYLKVAELL SSGLQSAIDQ IRAGKLCLSS TVKQVVRRLN ELYKASVVSC
960 970 980 990 1000
QGLSLRLQRF FLDKQRLLDR IHSITAERLI FSHAVQMVQS AALDEMFQHR
1010 1020 1030 1040 1050
EGCVPRYHKA LLLLEGLQHM LSDQADIENV TKCKLCIERR LSALLTGICA
Length:1,050
Mass (Da):112,631
Last modified:January 11, 2011 - v2
Checksum:iAED9BD5139F2DB92
GO

Sequence cautioni

The sequence BAA34442 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_041274290V → M in an ovarian mucinous carcinoma sample; somatic mutation. 1 PublicationCorresponds to variant rs370624303dbSNPEnsembl.1
Natural variantiVAR_041275298S → L.1 PublicationCorresponds to variant rs56364352dbSNPEnsembl.1
Natural variantiVAR_041276478P → L.1 PublicationCorresponds to variant rs12827141dbSNPEnsembl.1
Natural variantiVAR_041277503T → M.1 PublicationCorresponds to variant rs55824543dbSNPEnsembl.1
Natural variantiVAR_041278665S → L.1 PublicationCorresponds to variant rs55815560dbSNPEnsembl.1
Natural variantiVAR_041279714P → L.1 PublicationCorresponds to variant rs11546871dbSNPEnsembl.1
Natural variantiVAR_041280784S → C in a lung adenocarcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_054892816T → A.2 PublicationsCorresponds to variant rs11609348dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF045458 mRNA. Translation: AAC32326.1.
AB018265 mRNA. Translation: BAA34442.2. Different initiation.
AC131009 Genomic DNA. No translation available.
CCDSiCCDS9274.1.
RefSeqiNP_003556.1. NM_003565.2.
UniGeneiHs.47061.

Genome annotation databases

EnsembliENST00000321867; ENSP00000324560; ENSG00000177169.
GeneIDi8408.
KEGGihsa:8408.
UCSCiuc001uje.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF045458 mRNA. Translation: AAC32326.1.
AB018265 mRNA. Translation: BAA34442.2. Different initiation.
AC131009 Genomic DNA. No translation available.
CCDSiCCDS9274.1.
RefSeqiNP_003556.1. NM_003565.2.
UniGeneiHs.47061.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4WNOX-ray1.56A1-283[»]
4WNPX-ray1.88A/B/C/D1-283[»]
5CI7X-ray1.74A1-283[»]
ProteinModelPortaliO75385.
SMRiO75385.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113996. 47 interactors.
DIPiDIP-35196N.
IntActiO75385. 29 interactors.
MINTiMINT-1892187.
STRINGi9606.ENSP00000324560.

Chemistry databases

BindingDBiO75385.
ChEMBLiCHEMBL6006.
GuidetoPHARMACOLOGYi2271.

PTM databases

iPTMnetiO75385.
PhosphoSitePlusiO75385.
SwissPalmiO75385.

Polymorphism and mutation databases

BioMutaiULK1.

Proteomic databases

MaxQBiO75385.
PaxDbiO75385.
PeptideAtlasiO75385.
PRIDEiO75385.

Protocols and materials databases

DNASUi8408.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000321867; ENSP00000324560; ENSG00000177169.
GeneIDi8408.
KEGGihsa:8408.
UCSCiuc001uje.4. human.

Organism-specific databases

CTDi8408.
DisGeNETi8408.
GeneCardsiULK1.
HGNCiHGNC:12558. ULK1.
HPAiHPA063990.
MIMi603168. gene.
neXtProtiNX_O75385.
OpenTargetsiENSG00000177169.
PharmGKBiPA37198.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0595. Eukaryota.
ENOG410XR01. LUCA.
GeneTreeiENSGT00860000133711.
HOGENOMiHOG000044146.
HOVERGENiHBG000342.
InParanoidiO75385.
KOiK08269.
OMAiDTDDFVM.
OrthoDBiEOG091G14RD.
PhylomeDBiO75385.
TreeFamiTF324551.

Enzyme and pathway databases

BioCyciZFISH:HS11133-MONOMER.
BRENDAi2.7.11.1. 2681.
ReactomeiR-HSA-1632852. Macroautophagy.
R-HSA-8876198. RAB GEFs exchange GTP for GDP on RABs.
SignaLinkiO75385.
SIGNORiO75385.

Miscellaneous databases

ChiTaRSiULK1. human.
GeneWikiiULK1.
GenomeRNAii8408.
PROiO75385.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000177169.
CleanExiHS_ULK1.
GenevisibleiO75385. HS.

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_HUMAN
AccessioniPrimary (citable) accession number: O75385
Secondary accession number(s): Q9UQ28
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: January 11, 2011
Last modified: November 30, 2016
This is version 163 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. 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.