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Q8IYT8 (ULK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 115. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | 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 ULK2

EC=2.7.11.1
Alternative name(s):
Unc-51-like kinase 2
Gene names
Name:ULK2
Synonyms:KIAA0623
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1036 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 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. Ref.4 Ref.5 Ref.6 Ref.7 Ref.8

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Subunit structure

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. Ref.4 Ref.7

Subcellular location

Cytoplasmic vesicle membrane; Peripheral membrane protein. Note: Localizes to pre-autophagosomal membrane. Ref.4

Domain

The CTD-like region mediates membrane-binding and incorporation into large protein complexes. Ref.4

Post-translational modification

Autophosphorylated. In response to nutrient limitation, probably phosphorylated and activated by AMPK, leading to activate autophagy. Ref.4 Ref.9

Sequence similarities

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

Contains 1 protein kinase domain.

Sequence caution

The sequence BAA31598.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10361036Serine/threonine-protein kinase ULK2
PRO_0000086782

Regions

Domain9 – 271263Protein kinase
Nucleotide binding15 – 239ATP By similarity
Region812 – 1036225CTD-like region

Sites

Active site1311Proton acceptor By similarity
Binding site391ATP Probable

Natural variations

Natural variant2421P → S. Ref.10
Corresponds to variant rs34670978 [ dbSNP | Ensembl ].
VAR_041281
Natural variant3701V → M. Ref.1 Ref.3
Corresponds to variant rs150122 [ dbSNP | Ensembl ].
VAR_055287
Natural variant5331T → I.
Corresponds to variant rs4462660 [ dbSNP | Ensembl ].
VAR_055288
Natural variant6271G → E in a metastatic melanoma sample; somatic mutation. Ref.10
VAR_041282
Natural variant6621A → V in a metastatic melanoma sample; somatic mutation. Ref.10
VAR_041283
Natural variant7521G → R. Ref.10
Corresponds to variant rs55730189 [ dbSNP | Ensembl ].
VAR_041284
Natural variant8421D → E. Ref.10
Corresponds to variant rs35107651 [ dbSNP | Ensembl ].
VAR_041285

Experimental info

Mutagenesis391K → R: Decreased kinase activity and decreased autophosphorylation. Ref.4
Sequence conflict9351C → R in BAA31598. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q8IYT8 [UniParc].

Last modified May 18, 2010. Version 3.
Checksum: D311F01FA058CBBC

FASTA1,036112,694
        10         20         30         40         50         60 
MEVVGDFEYS KRDLVGHGAF AVVFRGRHRQ KTDWEVAIKS INKKNLSKSQ ILLGKEIKIL 

        70         80         90        100        110        120 
KELQHENIVA LYDVQELPNS VFLVMEYCNG GDLADYLQAK GTLSEDTIRV FLHQIAAAMR 

       130        140        150        160        170        180 
ILHSKGIIHR DLKPQNILLS YANRRKSSVS GIRIKIADFG FARYLHSNMM AATLCGSPMY 

       190        200        210        220        230        240 
MAPEVIMSQH YDAKADLWSI GTVIYQCLVG KPPFQANSPQ DLRMFYEKNR SLMPSIPRET 

       250        260        270        280        290        300 
SPYLANLLLG LLQRNQKDRM DFEAFFSHPF LEQGPVKKSC PVPVPMYSGS VSGSSCGSSP 

       310        320        330        340        350        360 
SCRFASPPSL PDMQHIQEEN LSSPPLGPPN YLQVSKDSAS TSSKNSSCDT DDFVLVPHNI 

       370        380        390        400        410        420 
SSDHSCDMPV GTAGRRASNE FLVCGGQCQP TVSPHSETAP IPVPTQIRNY QRIEQNLTST 

       430        440        450        460        470        480 
ASSGTNVHGS PRSAVVRRSN TSPMGFLRPG SCSPVPADTA QTVGRRLSTG SSRPYSPSPL 

       490        500        510        520        530        540 
VGTIPEQFSQ CCCGHPQGHD SRSRNSSGSP VPQAQSPQSL LSGARLQSAP TLTDIYQNKQ 

       550        560        570        580        590        600 
KLRKQHSDPV CPSHTGAGYS YSPQPSRPGS LGTSPTKHLG SSPRSSDWFF KTPLPTIIGS 

       610        620        630        640        650        660 
PTKTTAPFKI PKTQASSNLL ALVTRHGPAE EQSKDGNEPR ECAHCLLVQG SERQRAEQQS 

       670        680        690        700        710        720 
KAVFGRSVST GKLSDQQGKT PICRHQGSTD SLNTERPMDI APAGACGGVL APPAGTAASS 

       730        740        750        760        770        780 
KAVLFTVGSP PHSAAAPTCT HMFLRTRTTS VGPSNSGGSL CAMSGRVCVG SPPGPGFGSS 

       790        800        810        820        830        840 
PPGAEAAPSL RYVPYGASPP SLEGLITFEA PELPEETLME REHTDTLRHL NVMLMFTECV 

       850        860        870        880        890        900 
LDLTAMRGGN PELCTSAVSL YQIQESVVVD QISQLSKDWG RVEQLVLYMK AAQLLAASLH 

       910        920        930        940        950        960 
LAKAQIKSGK LSPSTAVKQV VKNLNERYKF CITMCKKLTE KLNRFFSDKQ RFIDEINSVT 

       970        980        990       1000       1010       1020 
AEKLIYNCAV EMVQSAALDE MFQQTEDIVY RYHKAALLLE GLSRILQDPA DIENVHKYKC 

      1030 
SIERRLSALC HSTATV 

« Hide

References

« Hide 'large scale' references
[1]"Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro."
Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
DNA Res. 5:169-176(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT MET-370.
Tissue: Brain.
[2]"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. expand/collapse author list , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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], VARIANT MET-370.
Tissue: Testis.
[4]"Kinase-inactivated ULK proteins inhibit autophagy via their conserved C-terminal domains using an Atg13-independent mechanism."
Chan E.Y.W., Longatti A., McKnight N.C., Tooze S.A.
Mol. Cell. Biol. 29:157-171(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, AUTOPHOSPHORYLATION, INTERACTION WITH ATG13, DOMAIN, MUTAGENESIS OF LYS-39.
[5]"The requirement of uncoordinated 51-like kinase 1 (ULK1) and ULK2 in the regulation of autophagy."
Lee E.J., Tournier C.
Autophagy 7:689-695(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[6]"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.
[7]"ULK1 inhibits the kinase activity of mTORC1 and cell proliferation."
Jung C.H., Seo M., Otto N.M., Kim D.H.
Autophagy 7:1212-1221(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH RPTOR.
[8]"Ammonia-induced autophagy is independent of ULK1/ULK2 kinases."
Cheong H., Lindsten T., Wu J., Lu C., Thompson C.B.
Proc. Natl. Acad. Sci. U.S.A. 108:11121-11126(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[9]"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: PHOSPHORYLATION BY AMPK.
[10]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] SER-242; GLU-627; VAL-662; ARG-752 AND GLU-842.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB014523 mRNA. Translation: BAA31598.2. Different initiation.
AC005722 Genomic DNA. No translation available.
BC034988 mRNA. Translation: AAH34988.1.
RefSeqNP_001136082.1. NM_001142610.1.
NP_055498.3. NM_014683.3.
UniGeneHs.168762.

3D structure databases

ProteinModelPortalQ8IYT8.
SMRQ8IYT8. Positions 4-317.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115058. 14 interactions.
IntActQ8IYT8. 51 interactions.
MINTMINT-1369789.
STRING9606.ENSP00000354877.

Chemistry

ChEMBLCHEMBL5435.
GuidetoPHARMACOLOGY2272.

PTM databases

PhosphoSiteQ8IYT8.

Polymorphism databases

DMDM296453001.

Proteomic databases

PaxDbQ8IYT8.
PRIDEQ8IYT8.

Protocols and materials databases

DNASU9706.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000361658; ENSP00000354877; ENSG00000083290.
ENST00000395544; ENSP00000378914; ENSG00000083290.
GeneID9706.
KEGGhsa:9706.
UCSCuc002gwm.4. human.

Organism-specific databases

CTD9706.
GeneCardsGC17M019674.
H-InvDBHIX0013624.
HGNCHGNC:13480. ULK2.
HPACAB037021.
HPA009027.
MIM608650. gene.
neXtProtNX_Q8IYT8.
PharmGKBPA37780.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000044146.
HOVERGENHBG000342.
InParanoidQ8IYT8.
KOK08269.
OMAGTIPEQF.
OrthoDBEOG7K0ZBF.
PhylomeDBQ8IYT8.
TreeFamTF324551.

Enzyme and pathway databases

SignaLinkQ8IYT8.

Gene expression databases

BgeeQ8IYT8.
CleanExHS_ULK2.
GenevestigatorQ8IYT8.

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

ChiTaRSULK2. human.
GenomeRNAi9706.
NextBio36477.
PROQ8IYT8.
SOURCESearch...

Entry information

Entry nameULK2_HUMAN
AccessionPrimary (citable) accession number: Q8IYT8
Secondary accession number(s): A8MY69, O75119
Entry history
Integrated into UniProtKB/Swiss-Prot: October 25, 2005
Last sequence update: May 18, 2010
Last modified: April 16, 2014
This is version 115 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM