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Protein

Serine/threonine-protein kinase ULK2

Gene

ULK2

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 a negative regulator of mammalian target of rapamycin complex 1 (mTORC1) via interaction with RPTOR. Activated via phosphorylation by AMPK, also acts as a negative regulator of AMPK through phosphorylation of the AMPK subunits PRKAA1, PRKAB2 and PRKAG1. May phosphorylate ATG13/KIAA0652, FRS2, FRS3 and RPTOR; however such data need additional evidences. Not involved in ammonia-induced autophagy or in autophagic response of cerebellar granule neurons (CGN) to low potassium concentration. Plays a role early in neuronal differentiation and is required for granule cell axon formation: may govern axon formation via Ras-like GTPase signaling and through regulation of the Rab5-mediated endocytic pathways within developing axons.5 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei39ATPCurated1
Active sitei131Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi15 – 23ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

  • autophagy Source: UniProtKB-KW
  • axon extension Source: GO_Central
  • negative regulation of collateral sprouting Source: Ensembl
  • protein autophosphorylation 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, Neurogenesis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS01437-MONOMER.
SignaLinkiQ8IYT8.
SIGNORiQ8IYT8.

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase ULK2 (EC:2.7.11.1)
Alternative name(s):
Unc-51-like kinase 2
Gene namesi
Name:ULK2
Synonyms:KIAA0623
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:13480. ULK2.

Subcellular locationi

GO - Cellular componenti

  • cytoplasmic vesicle membrane Source: UniProtKB-SubCell
  • pre-autophagosomal structure membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasmic vesicle, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi39K → R: Decreased kinase activity and decreased autophosphorylation. 1 Publication1

Organism-specific databases

DisGeNETi9706.
OpenTargetsiENSG00000083290.
PharmGKBiPA37780.

Chemistry databases

ChEMBLiCHEMBL5435.
GuidetoPHARMACOLOGYi2272.

Polymorphism and mutation databases

BioMutaiULK2.
DMDMi296453001.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000867821 – 1036Serine/threonine-protein kinase ULK2Add BLAST1036

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei430PhosphoserineBy similarity1
Modified residuei771PhosphoserineBy similarity1
Modified residuei780PhosphoserineBy similarity1

Post-translational modificationi

Autophosphorylated. In response to nutrient limitation, probably phosphorylated and activated by AMPK, leading to activate autophagy.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ8IYT8.
PaxDbiQ8IYT8.
PeptideAtlasiQ8IYT8.
PRIDEiQ8IYT8.

PTM databases

iPTMnetiQ8IYT8.
PhosphoSitePlusiQ8IYT8.

Expressioni

Gene expression databases

BgeeiENSG00000083290.
CleanExiHS_ULK2.
ExpressionAtlasiQ8IYT8. baseline and differential.
GenevisibleiQ8IYT8. HS.

Organism-specific databases

HPAiCAB037021.
HPA009027.

Interactioni

Subunit structurei

Interacts with SYNGAP1 (By similarity). Component of a complex consisting of ATG13/KIAA0652, ULK1 and RB1CC1/FIP200. Interacts (via C-terminus) with ATG13/KIAA0652. Associates with the mammalian target of rapamycin complex 1 (mTORC1) through an interaction with RPTOR.By similarity2 Publications

Protein-protein interaction databases

BioGridi115058. 13 interactors.
IntActiQ8IYT8. 51 interactors.
MINTiMINT-1369789.
STRINGi9606.ENSP00000354877.

Chemistry databases

BindingDBiQ8IYT8.

Structurei

3D structure databases

ProteinModelPortaliQ8IYT8.
SMRiQ8IYT8.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini9 – 271Protein kinasePROSITE-ProRule annotationAdd BLAST263

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni812 – 1036CTD-like regionAdd BLAST225

Domaini

The CTD-like region mediates membrane-binding and incorporation into large protein complexes.1 Publication

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.
InParanoidiQ8IYT8.
KOiK08269.
OMAiRIKIVCE.
OrthoDBiEOG091G018I.
PhylomeDBiQ8IYT8.
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.

Q8IYT8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEVVGDFEYS KRDLVGHGAF AVVFRGRHRQ KTDWEVAIKS INKKNLSKSQ
60 70 80 90 100
ILLGKEIKIL KELQHENIVA LYDVQELPNS VFLVMEYCNG GDLADYLQAK
110 120 130 140 150
GTLSEDTIRV FLHQIAAAMR ILHSKGIIHR DLKPQNILLS YANRRKSSVS
160 170 180 190 200
GIRIKIADFG FARYLHSNMM AATLCGSPMY MAPEVIMSQH YDAKADLWSI
210 220 230 240 250
GTVIYQCLVG KPPFQANSPQ DLRMFYEKNR SLMPSIPRET SPYLANLLLG
260 270 280 290 300
LLQRNQKDRM DFEAFFSHPF LEQGPVKKSC PVPVPMYSGS VSGSSCGSSP
310 320 330 340 350
SCRFASPPSL PDMQHIQEEN LSSPPLGPPN YLQVSKDSAS TSSKNSSCDT
360 370 380 390 400
DDFVLVPHNI SSDHSCDMPV GTAGRRASNE FLVCGGQCQP TVSPHSETAP
410 420 430 440 450
IPVPTQIRNY QRIEQNLTST ASSGTNVHGS PRSAVVRRSN TSPMGFLRPG
460 470 480 490 500
SCSPVPADTA QTVGRRLSTG SSRPYSPSPL VGTIPEQFSQ CCCGHPQGHD
510 520 530 540 550
SRSRNSSGSP VPQAQSPQSL LSGARLQSAP TLTDIYQNKQ KLRKQHSDPV
560 570 580 590 600
CPSHTGAGYS YSPQPSRPGS LGTSPTKHLG SSPRSSDWFF KTPLPTIIGS
610 620 630 640 650
PTKTTAPFKI PKTQASSNLL ALVTRHGPAE EQSKDGNEPR ECAHCLLVQG
660 670 680 690 700
SERQRAEQQS KAVFGRSVST GKLSDQQGKT PICRHQGSTD SLNTERPMDI
710 720 730 740 750
APAGACGGVL APPAGTAASS KAVLFTVGSP PHSAAAPTCT HMFLRTRTTS
760 770 780 790 800
VGPSNSGGSL CAMSGRVCVG SPPGPGFGSS PPGAEAAPSL RYVPYGASPP
810 820 830 840 850
SLEGLITFEA PELPEETLME REHTDTLRHL NVMLMFTECV LDLTAMRGGN
860 870 880 890 900
PELCTSAVSL YQIQESVVVD QISQLSKDWG RVEQLVLYMK AAQLLAASLH
910 920 930 940 950
LAKAQIKSGK LSPSTAVKQV VKNLNERYKF CITMCKKLTE KLNRFFSDKQ
960 970 980 990 1000
RFIDEINSVT AEKLIYNCAV EMVQSAALDE MFQQTEDIVY RYHKAALLLE
1010 1020 1030
GLSRILQDPA DIENVHKYKC SIERRLSALC HSTATV
Length:1,036
Mass (Da):112,694
Last modified:May 18, 2010 - v3
Checksum:iD311F01FA058CBBC
GO

Sequence cautioni

The sequence BAA31598 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti935C → R in BAA31598 (PubMed:9734811).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_041281242P → S.1 PublicationCorresponds to variant rs34670978dbSNPEnsembl.1
Natural variantiVAR_055287370V → M.2 PublicationsCorresponds to variant rs150122dbSNPEnsembl.1
Natural variantiVAR_055288533T → I.Corresponds to variant rs4462660dbSNPEnsembl.1
Natural variantiVAR_041282627G → E in a metastatic melanoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_041283662A → V in a metastatic melanoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_041284752G → R.1 PublicationCorresponds to variant rs55730189dbSNPEnsembl.1
Natural variantiVAR_041285842D → E.1 PublicationCorresponds to variant rs35107651dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB014523 mRNA. Translation: BAA31598.2. Different initiation.
AC005722 Genomic DNA. No translation available.
BC034988 mRNA. Translation: AAH34988.1.
CCDSiCCDS11213.1.
RefSeqiNP_001136082.1. NM_001142610.1.
NP_055498.3. NM_014683.3.
UniGeneiHs.168762.

Genome annotation databases

EnsembliENST00000361658; ENSP00000354877; ENSG00000083290.
ENST00000395544; ENSP00000378914; ENSG00000083290.
GeneIDi9706.
KEGGihsa:9706.
UCSCiuc002gwm.5. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB014523 mRNA. Translation: BAA31598.2. Different initiation.
AC005722 Genomic DNA. No translation available.
BC034988 mRNA. Translation: AAH34988.1.
CCDSiCCDS11213.1.
RefSeqiNP_001136082.1. NM_001142610.1.
NP_055498.3. NM_014683.3.
UniGeneiHs.168762.

3D structure databases

ProteinModelPortaliQ8IYT8.
SMRiQ8IYT8.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115058. 13 interactors.
IntActiQ8IYT8. 51 interactors.
MINTiMINT-1369789.
STRINGi9606.ENSP00000354877.

Chemistry databases

BindingDBiQ8IYT8.
ChEMBLiCHEMBL5435.
GuidetoPHARMACOLOGYi2272.

PTM databases

iPTMnetiQ8IYT8.
PhosphoSitePlusiQ8IYT8.

Polymorphism and mutation databases

BioMutaiULK2.
DMDMi296453001.

Proteomic databases

MaxQBiQ8IYT8.
PaxDbiQ8IYT8.
PeptideAtlasiQ8IYT8.
PRIDEiQ8IYT8.

Protocols and materials databases

DNASUi9706.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000361658; ENSP00000354877; ENSG00000083290.
ENST00000395544; ENSP00000378914; ENSG00000083290.
GeneIDi9706.
KEGGihsa:9706.
UCSCiuc002gwm.5. human.

Organism-specific databases

CTDi9706.
DisGeNETi9706.
GeneCardsiULK2.
H-InvDBHIX0013624.
HGNCiHGNC:13480. ULK2.
HPAiCAB037021.
HPA009027.
MIMi608650. gene.
neXtProtiNX_Q8IYT8.
OpenTargetsiENSG00000083290.
PharmGKBiPA37780.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0595. Eukaryota.
ENOG410XR01. LUCA.
GeneTreeiENSGT00860000133711.
HOGENOMiHOG000044146.
HOVERGENiHBG000342.
InParanoidiQ8IYT8.
KOiK08269.
OMAiRIKIVCE.
OrthoDBiEOG091G018I.
PhylomeDBiQ8IYT8.
TreeFamiTF324551.

Enzyme and pathway databases

BioCyciZFISH:HS01437-MONOMER.
SignaLinkiQ8IYT8.
SIGNORiQ8IYT8.

Miscellaneous databases

ChiTaRSiULK2. human.
GenomeRNAii9706.
PROiQ8IYT8.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000083290.
CleanExiHS_ULK2.
ExpressionAtlasiQ8IYT8. baseline and differential.
GenevisibleiQ8IYT8. 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 nameiULK2_HUMAN
AccessioniPrimary (citable) accession number: Q8IYT8
Secondary accession number(s): A8MY69, O75119
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 25, 2005
Last sequence update: May 18, 2010
Last modified: November 30, 2016
This is version 142 of the entry and version 3 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: 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. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  6. 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.