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Q8IYT8

- ULK2_HUMAN

UniProt

Q8IYT8 - ULK2_HUMAN

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
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    • History
      Entry version 119 (01 Oct 2014)
      Sequence version 3 (18 May 2010)
      Previous versions | rss
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    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 binding Source: UniProtKB
    3. 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

    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 membrane Source: UniProtKB-SubCell
    3. cytosol Source: RefGenome
    4. pre-autophagosomal structure membrane Source: UniProtKB

    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.
    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.
    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_dom.
    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

    MEVVGDFEYS KRDLVGHGAF AVVFRGRHRQ KTDWEVAIKS INKKNLSKSQ     50
    ILLGKEIKIL KELQHENIVA LYDVQELPNS VFLVMEYCNG GDLADYLQAK 100
    GTLSEDTIRV FLHQIAAAMR ILHSKGIIHR DLKPQNILLS YANRRKSSVS 150
    GIRIKIADFG FARYLHSNMM AATLCGSPMY MAPEVIMSQH YDAKADLWSI 200
    GTVIYQCLVG KPPFQANSPQ DLRMFYEKNR SLMPSIPRET SPYLANLLLG 250
    LLQRNQKDRM DFEAFFSHPF LEQGPVKKSC PVPVPMYSGS VSGSSCGSSP 300
    SCRFASPPSL PDMQHIQEEN LSSPPLGPPN YLQVSKDSAS TSSKNSSCDT 350
    DDFVLVPHNI SSDHSCDMPV GTAGRRASNE FLVCGGQCQP TVSPHSETAP 400
    IPVPTQIRNY QRIEQNLTST ASSGTNVHGS PRSAVVRRSN TSPMGFLRPG 450
    SCSPVPADTA QTVGRRLSTG SSRPYSPSPL VGTIPEQFSQ CCCGHPQGHD 500
    SRSRNSSGSP VPQAQSPQSL LSGARLQSAP TLTDIYQNKQ KLRKQHSDPV 550
    CPSHTGAGYS YSPQPSRPGS LGTSPTKHLG SSPRSSDWFF KTPLPTIIGS 600
    PTKTTAPFKI PKTQASSNLL ALVTRHGPAE EQSKDGNEPR ECAHCLLVQG 650
    SERQRAEQQS KAVFGRSVST GKLSDQQGKT PICRHQGSTD SLNTERPMDI 700
    APAGACGGVL APPAGTAASS KAVLFTVGSP PHSAAAPTCT HMFLRTRTTS 750
    VGPSNSGGSL CAMSGRVCVG SPPGPGFGSS PPGAEAAPSL RYVPYGASPP 800
    SLEGLITFEA PELPEETLME REHTDTLRHL NVMLMFTECV LDLTAMRGGN 850
    PELCTSAVSL YQIQESVVVD QISQLSKDWG RVEQLVLYMK AAQLLAASLH 900
    LAKAQIKSGK LSPSTAVKQV VKNLNERYKF CITMCKKLTE KLNRFFSDKQ 950
    RFIDEINSVT AEKLIYNCAV EMVQSAALDE MFQQTEDIVY RYHKAALLLE 1000
    GLSRILQDPA DIENVHKYKC SIERRLSALC HSTATV 1036
    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.
    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.
    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_dom.
    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

    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 1, 2014
    This is version 119 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