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Protein

Serine/threonine-protein kinase ULK2

Gene

Ulk2

Organism
Mus musculus (Mouse)
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.4 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: GO_Central
  2. axon extension Source: MGI
  3. negative regulation of collateral sprouting Source: MGI
  4. protein autophosphorylation Source: MGI
  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

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase ULK2 (EC:2.7.11.1)
Alternative name(s):
Serine/threonine-protein kinase Unc51.2
Unc-51-like kinase 2
Gene namesi
Name:Ulk2
Synonyms:Kiaa0623
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:1352758. 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: GO_Central
  2. cytoplasmic vesicle membrane Source: UniProtKB-SubCell
  3. cytosol Source: GO_Central
  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 → T: Decreased kinase activity. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 10371037Serine/threonine-protein kinase ULK2PRO_0000086783Add
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

MaxQBiQ9QY01.
PRIDEiQ9QY01.

PTM databases

PhosphoSiteiQ9QY01.

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Gene expression databases

BgeeiQ9QY01.
CleanExiMM_ULK2.
GenevestigatoriQ9QY01.

Interactioni

Subunit structurei

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 similarity). Interacts with SYNGAP1.By similarity2 Publications

Protein-protein interaction databases

BioGridi205934. 1 interaction.
DIPiDIP-60901N.

Structurei

3D structure databases

ProteinModelPortaliQ9QY01.
SMRiQ9QY01. Positions 9-317, 883-1027.
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
Regioni813 – 1037225CTD-like regionBy similarityAdd
BLAST

Domaini

The CTD-like region mediates membrane-binding and incorporation into large protein complexes.By similarity

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.
GeneTreeiENSGT00780000121891.
HOGENOMiHOG000044146.
HOVERGENiHBG000342.
InParanoidiQ9QY01.
KOiK08269.
OMAiGTIPEQF.
OrthoDBiEOG7K0ZBF.
PhylomeDBiQ9QY01.
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.

Q9QY01-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEVVGDFEYC KRDLVGHGAF AVVFRGRHRQ KTDWEVAIKS INKKNLSKSQ
60 70 80 90 100
ILLGKEIKIL KELQHENIVA LYDVQELPNS VFLVMEYCNG GDLADYLQAK
110 120 130 140 150
GTLSEDTIRV FLHQIAAAMR ILHSKGIIHR DLKPQNILLS YANRRKSNVS
160 170 180 190 200
GIRIKIADFG FARYLHSNTM AATLCGSPMY MAPEVIMSQH YDAKADLWSI
210 220 230 240 250
GTVIYQCLVG KPPFQANSPQ DLRMFYEKNR SLMPSIPRET SPYLANLLLG
260 270 280 290 300
LLQRNQKDRM DFEAFFSHPF LEQVPVKKSC PVPVPVYSGP VPGSSCSSSP
310 320 330 340 350
SCRFASPPSL PDMQHIQEEN LSSPPLGPPN YLQVSKDSAS NSSKNSSCDT
360 370 380 390 400
DDFVLVPHNI SSDHSYDMPM GTTARRASNE FFMCGGQCQP TVSPHSETAP
410 420 430 440 450
IPVPTQVRNY QRIEQNLIST ASSGTNPHGS PRSAVVRRSN TSPMGFLRVG
460 470 480 490 500
SCSPVPGDTV QTGGRRLSTG SSRPYSPSPL VGTIPEQFSQ CCCGHPQGHE
510 520 530 540 550
ARSRHSSGSP VPQTQAPQSL LLGARLQSAP TLTDIYQNKQ KLRKQHSDPV
560 570 580 590 600
CPSHAGAGYS YSPQPSRPGS LGTSPTKHTG SSPRNSDWFF KTPLPTIIGS
610 620 630 640 650
PTKTTAPFKI PKTQASSNLL ALVTRHGPAE SQSKDGNDPR ECSHCLSVQG
660 670 680 690 700
SERHRSEQQQ SKAVFGRSVS TGKLSEQQVK APLGGHQGST DSLNTERPMD
710 720 730 740 750
VAPAGACGVM LALPAGTAAS ARAVLFTVGS PPHSATAPTC THMVLRTRTT
760 770 780 790 800
SVGSSSSGGS LCSASGRVCV GSPPGPGLGS SPPGAEGAPS LRYVPYGASP
810 820 830 840 850
PSLEGLITFE APELPEETLM EREHTDTLRH LNMMLMFTEC VLDLTAVRGG
860 870 880 890 900
NPELCTSAVS LYQIQESVVV DQISQLSKDW GRVEQLVLYM KAAQLLAASL
910 920 930 940 950
HLAKAQVKSG KLSPSMAVKQ VVKNLNERYK FCITMCKKLT EKLNRFFSDK
960 970 980 990 1000
QRFIDEINSV TAEKLIYNCA VEMVQSAALD EMFQQTEDIV YRYHKAALLL
1010 1020 1030
EGLSKILQDP TDVENVHKYK CSIERRLSAL CCSTATV
Length:1,037
Mass (Da):112,877
Last modified:April 30, 2000 - v1
Checksum:i2E7DC3B0B87E9607
GO

Sequence cautioni

The sequence BAC65613.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti998 – 9981L → V in BAA77341 (PubMed:10557072).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF145922 mRNA. Translation: AAF18325.1.
AB019577 mRNA. Translation: BAA77341.1.
AK146620 mRNA. Translation: BAE27309.1.
AK122331 mRNA. Translation: BAC65613.2. Different initiation.
BC046778 mRNA. Translation: AAH46778.1.
BC053029 mRNA. Translation: AAH53029.1.
CCDSiCCDS24820.1.
RefSeqiNP_038909.3. NM_013881.4.
UniGeneiMm.162025.

Genome annotation databases

EnsembliENSMUST00000004920; ENSMUSP00000004920; ENSMUSG00000004798.
GeneIDi29869.
KEGGimmu:29869.
UCSCiuc007jih.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF145922 mRNA. Translation: AAF18325.1.
AB019577 mRNA. Translation: BAA77341.1.
AK146620 mRNA. Translation: BAE27309.1.
AK122331 mRNA. Translation: BAC65613.2. Different initiation.
BC046778 mRNA. Translation: AAH46778.1.
BC053029 mRNA. Translation: AAH53029.1.
CCDSiCCDS24820.1.
RefSeqiNP_038909.3. NM_013881.4.
UniGeneiMm.162025.

3D structure databases

ProteinModelPortaliQ9QY01.
SMRiQ9QY01. Positions 9-317, 883-1027.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi205934. 1 interaction.
DIPiDIP-60901N.

PTM databases

PhosphoSiteiQ9QY01.

Proteomic databases

MaxQBiQ9QY01.
PRIDEiQ9QY01.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000004920; ENSMUSP00000004920; ENSMUSG00000004798.
GeneIDi29869.
KEGGimmu:29869.
UCSCiuc007jih.2. mouse.

Organism-specific databases

CTDi9706.
MGIiMGI:1352758. Ulk2.
RougeiSearch...

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00780000121891.
HOGENOMiHOG000044146.
HOVERGENiHBG000342.
InParanoidiQ9QY01.
KOiK08269.
OMAiGTIPEQF.
OrthoDBiEOG7K0ZBF.
PhylomeDBiQ9QY01.
TreeFamiTF324551.

Miscellaneous databases

NextBioi307094.
PROiQ9QY01.
SOURCEiSearch...

Gene expression databases

BgeeiQ9QY01.
CleanExiMM_ULK2.
GenevestigatoriQ9QY01.

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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "A mouse serine/threonine kinase homologous to C. elegans UNC51 functions in parallel fiber formation of cerebellar granule neurons."
    Tomoda T., Bhatt R.S., Kuroyanagi H., Shirasawa T., Hatten M.E.
    Neuron 24:833-846(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION.
    Strain: C57BL/6J.
    Tissue: Brain.
  2. "Mouse ULK2, a novel member of the UNC-51-like protein kinases: unique features of functional domains."
    Yan J., Kuroyanagi H., Tomemori T., Okazaki N., Asato K., Matsuda Y., Suzuki Y., Ohshima Y., Mitani S., Masuho Y., Shirasawa T., Muramatsu M.
    Oncogene 18:5850-5859(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AUTOPHOSPHORYLATION.
  3. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Kidney.
  4. "Prediction of the coding sequences of mouse homologues of KIAA gene: II. The complete nucleotide sequences of 400 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries."
    Okazaki N., Kikuno R., Ohara R., Inamoto S., Aizawa H., Yuasa S., Nakajima D., Nagase T., Ohara O., Koga H.
    DNA Res. 10:35-48(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Brain.
  5. Okazaki N., Kikuno R., Nagase T., Ohara O., Koga H.
    Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: SEQUENCE REVISION.
  6. "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(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6.
    Tissue: Brain.
  7. "Role of Unc51.1 and its binding partners in CNS axon outgrowth."
    Tomoda T., Kim J.H., Zhan C., Hatten M.E.
    Genes Dev. 18:541-558(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SYNGAP1.
  8. "UNC-51-like kinase regulation of fibroblast growth factor receptor substrate 2/3."
    Avery A.W., Figueroa C., Vojtek A.B.
    Cell. Signal. 19:177-184(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF FRS2 AND FRS3.
  9. "FIP200, a ULK-interacting protein, is required for autophagosome formation in mammalian cells."
    Hara T., Takamura A., Kishi C., Iemura S., Natsume T., Guan J.L., Mizushima N.
    J. Cell Biol. 181:497-510(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH RB1CC1, MUTAGENESIS OF LYS-39.
  10. "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(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF AMPK.
  11. "AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1."
    Kim J., Kundu M., Viollet B., Guan K.L.
    Nat. Cell Biol. 13:132-141(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION BY AMPK.

Entry informationi

Entry nameiULK2_MOUSE
AccessioniPrimary (citable) accession number: Q9QY01
Secondary accession number(s): Q80TV7, Q9WTP4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 24, 2005
Last sequence update: April 30, 2000
Last modified: March 3, 2015
This is version 118 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.