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Q8IYT8

- ULK2_HUMAN

UniProt

Q8IYT8 - ULK2_HUMAN

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Protein

Serine/threonine-protein kinase ULK2

Gene

ULK2

Organism
Homo sapiens (Human)
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 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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei39 – 391ATPCurated
Active sitei131 – 1311Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi15 – 239ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

  1. autophagic vacuole assembly Source: RefGenome
  2. axon extension Source: RefGenome
  3. negative regulation of collateral sprouting Source: Ensembl
  4. protein autophosphorylation Source: UniProtKB
  5. regulation of autophagy Source: UniProtKB
  6. response to starvation Source: UniProtKB
  7. 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

SignaLinkiQ8IYT8.

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
ProteomesiUP000005640: Chromosome 17

Organism-specific databases

HGNCiHGNC:13480. ULK2.

Subcellular locationi

Cytoplasmic vesicle membrane 1 Publication; Peripheral membrane protein 1 Publication
Note: Localizes to pre-autophagosomal membrane.

GO - Cellular componenti

  1. ATG1/UKL1 signaling complex Source: RefGenome
  2. cytoplasmic vesicle Source: UniProtKB-KW
  3. cytosol Source: RefGenome
  4. pre-autophagosomal structure membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasmic vesicle, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi39 – 391K → R: Decreased kinase activity and decreased autophosphorylation. 1 Publication

Organism-specific databases

PharmGKBiPA37780.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 10361036Serine/threonine-protein kinase ULK2PRO_0000086782Add
BLAST

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

PaxDbiQ8IYT8.
PRIDEiQ8IYT8.

PTM databases

PhosphoSiteiQ8IYT8.

Expressioni

Gene expression databases

BgeeiQ8IYT8.
CleanExiHS_ULK2.
GenevestigatoriQ8IYT8.

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. 14 interactions.
IntActiQ8IYT8. 51 interactions.
MINTiMINT-1369789.
STRINGi9606.ENSP00000354877.

Structurei

3D structure databases

ProteinModelPortaliQ8IYT8.
SMRiQ8IYT8. Positions 9-317, 882-1026.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini9 – 271263Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni812 – 1036225CTD-like regionAdd
BLAST

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

eggNOGiCOG0515.
GeneTreeiENSGT00760000119118.
HOGENOMiHOG000044146.
HOVERGENiHBG000342.
InParanoidiQ8IYT8.
KOiK08269.
OMAiGTIPEQF.
OrthoDBiEOG7K0ZBF.
PhylomeDBiQ8IYT8.
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.

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

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti935 – 9351C → R in BAA31598. (PubMed:9734811)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti242 – 2421P → S.1 Publication
Corresponds to variant rs34670978 [ dbSNP | Ensembl ].
VAR_041281
Natural varianti370 – 3701V → M.2 Publications
Corresponds to variant rs150122 [ dbSNP | Ensembl ].
VAR_055287
Natural varianti533 – 5331T → I.
Corresponds to variant rs4462660 [ dbSNP | Ensembl ].
VAR_055288
Natural varianti627 – 6271G → E in a metastatic melanoma sample; somatic mutation. 1 Publication
VAR_041282
Natural varianti662 – 6621A → V in a metastatic melanoma sample; somatic mutation. 1 Publication
VAR_041283
Natural varianti752 – 7521G → R.1 Publication
Corresponds to variant rs55730189 [ dbSNP | Ensembl ].
VAR_041284
Natural varianti842 – 8421D → E.1 Publication
Corresponds to variant rs35107651 [ dbSNP | Ensembl ].
VAR_041285

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.4. human.

Polymorphism databases

DMDMi296453001.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AB014523 mRNA. Translation: BAA31598.2 . Different initiation.
AC005722 Genomic DNA. No translation available.
BC034988 mRNA. Translation: AAH34988.1 .
CCDSi CCDS11213.1.
RefSeqi NP_001136082.1. NM_001142610.1.
NP_055498.3. NM_014683.3.
UniGenei Hs.168762.

3D structure databases

ProteinModelPortali Q8IYT8.
SMRi Q8IYT8. Positions 9-317, 882-1026.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 115058. 14 interactions.
IntActi Q8IYT8. 51 interactions.
MINTi MINT-1369789.
STRINGi 9606.ENSP00000354877.

Chemistry

ChEMBLi CHEMBL5435.
GuidetoPHARMACOLOGYi 2272.

PTM databases

PhosphoSitei Q8IYT8.

Polymorphism databases

DMDMi 296453001.

Proteomic databases

PaxDbi Q8IYT8.
PRIDEi Q8IYT8.

Protocols and materials databases

DNASUi 9706.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000361658 ; ENSP00000354877 ; ENSG00000083290 .
ENST00000395544 ; ENSP00000378914 ; ENSG00000083290 .
GeneIDi 9706.
KEGGi hsa:9706.
UCSCi uc002gwm.4. human.

Organism-specific databases

CTDi 9706.
GeneCardsi GC17M019674.
H-InvDB HIX0013624.
HGNCi HGNC:13480. ULK2.
HPAi CAB037021.
HPA009027.
MIMi 608650. gene.
neXtProti NX_Q8IYT8.
PharmGKBi PA37780.
HUGEi Search...
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00760000119118.
HOGENOMi HOG000044146.
HOVERGENi HBG000342.
InParanoidi Q8IYT8.
KOi K08269.
OMAi GTIPEQF.
OrthoDBi EOG7K0ZBF.
PhylomeDBi Q8IYT8.
TreeFami TF324551.

Enzyme and pathway databases

SignaLinki Q8IYT8.

Miscellaneous databases

ChiTaRSi ULK2. human.
GenomeRNAii 9706.
NextBioi 36477.
PROi Q8IYT8.
SOURCEi Search...

Gene expression databases

Bgeei Q8IYT8.
CleanExi HS_ULK2.
Genevestigatori Q8IYT8.

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. "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.
    , 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. 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.
    , 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.

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: October 29, 2014
This is version 120 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

External Data

Dasty 3