Q9QY01 (ULK2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	Ulk2
Synonyms:	Kiaa0623

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1037 AA.
Sequence status	Complete.
Protein existence	Evidence 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.1 Ref.8 Ref.9 Ref.10
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Subunit structure	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. Ref.7 Ref.9
Subcellular location	Cytoplasmic vesicle membrane; Peripheral membrane protein. Note: Localizes to pre-autophagosomal membrane. Ref.9
Tissue specificity	Widely expressed. Ref.2
Domain	The CTD-like region mediates membrane-binding and incorporation into large protein complexes By similarity.
Post-translational modification	Autophosphorylated. In response to nutrient limitation, probably phosphorylated and activated by AMPK, leading to activate autophagy. Ref.2 Ref.11
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 BAC65613.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Biological process	Autophagy Neurogenesis
Cellular component	Cytoplasmic vesicle Membrane
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	autophagy Inferred from electronic annotation. Source: UniProtKB-KW axon extension Inferred from mutant phenotype PubMed 17389358. Source: MGI negative regulation of collateral sprouting Inferred from mutant phenotype PubMed 17389358. Source: MGI protein autophosphorylation Inferred from electronic annotation. Source: Compara regulation of autophagy Inferred from mutant phenotype Ref.9. Source: UniProtKB response to starvation Inferred from direct assay Ref.9. Source: UniProtKB signal transduction Inferred from electronic annotation. Source: InterPro
Cellular_component	cytoplasmic vesicle membrane Inferred from electronic annotation. Source: UniProtKB-SubCell pre-autophagosomal structure membrane Inferred from direct assay Ref.9. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine kinase activity Inferred from direct assay Ref.9. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1037	1037	Serine/threonine-protein kinase ULK2		PRO_0000086783
Regions
	Domain	9 – 271	263	Protein kinase
	Nucleotide binding	15 – 23	9	ATP By similarity
	Region	813 – 1037	225	CTD-like region By similarity
Sites
	Active site	131	1	Proton acceptor By similarity
	Binding site	39	1	ATP Probable
Experimental info
	Mutagenesis	39	1	K → T: Decreased kinase activity. Ref.9
	Sequence conflict	998	1	L → V in BAA77341. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q9QY01 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: 2E7DC3B0B87E9607	FASTA	1,037	112,877
	10 20 30 40 50 60 MEVVGDFEYC 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 YANRRKSNVS GIRIKIADFG FARYLHSNTM AATLCGSPMY 190 200 210 220 230 240 MAPEVIMSQH YDAKADLWSI GTVIYQCLVG KPPFQANSPQ DLRMFYEKNR SLMPSIPRET 250 260 270 280 290 300 SPYLANLLLG LLQRNQKDRM DFEAFFSHPF LEQVPVKKSC PVPVPVYSGP VPGSSCSSSP 310 320 330 340 350 360 SCRFASPPSL PDMQHIQEEN LSSPPLGPPN YLQVSKDSAS NSSKNSSCDT DDFVLVPHNI 370 380 390 400 410 420 SSDHSYDMPM GTTARRASNE FFMCGGQCQP TVSPHSETAP IPVPTQVRNY QRIEQNLIST 430 440 450 460 470 480 ASSGTNPHGS PRSAVVRRSN TSPMGFLRVG SCSPVPGDTV QTGGRRLSTG SSRPYSPSPL 490 500 510 520 530 540 VGTIPEQFSQ CCCGHPQGHE ARSRHSSGSP VPQTQAPQSL LLGARLQSAP TLTDIYQNKQ 550 560 570 580 590 600 KLRKQHSDPV CPSHAGAGYS YSPQPSRPGS LGTSPTKHTG SSPRNSDWFF KTPLPTIIGS 610 620 630 640 650 660 PTKTTAPFKI PKTQASSNLL ALVTRHGPAE SQSKDGNDPR ECSHCLSVQG SERHRSEQQQ 670 680 690 700 710 720 SKAVFGRSVS TGKLSEQQVK APLGGHQGST DSLNTERPMD VAPAGACGVM LALPAGTAAS 730 740 750 760 770 780 ARAVLFTVGS PPHSATAPTC THMVLRTRTT SVGSSSSGGS LCSASGRVCV GSPPGPGLGS 790 800 810 820 830 840 SPPGAEGAPS LRYVPYGASP PSLEGLITFE APELPEETLM EREHTDTLRH LNMMLMFTEC 850 860 870 880 890 900 VLDLTAVRGG NPELCTSAVS LYQIQESVVV DQISQLSKDW GRVEQLVLYM KAAQLLAASL 910 920 930 940 950 960 HLAKAQVKSG KLSPSMAVKQ VVKNLNERYK FCITMCKKLT EKLNRFFSDK QRFIDEINSV 970 980 990 1000 1010 1020 TAEKLIYNCA VEMVQSAALD EMFQQTEDIV YRYHKAALLL EGLSKILQDP TDVENVHKYK 1030 CSIERRLSAL CCSTATV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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(1999) [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(1999) [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(2005) [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(2003) [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 (JUN-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(2004) [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(2004) [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(2007) [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(2008) [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(2011) [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(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION BY AMPK.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00336256.
RefSeq	NP_038909.3. NM_013881.4.
UniGene	Mm.162025.
3D structure databases
ProteinModelPortal	Q9QY01.
SMR	Q9QY01. Positions 9-317.
ModBase	Search...
PTM databases
PhosphoSite	Q9QY01.
Proteomic databases
PRIDE	Q9QY01.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000004920; ENSMUSP00000004920; ENSMUSG00000004798.
GeneID	29869.
KEGG	mmu:29869.
Organism-specific databases
CTD	9706.
MGI	MGI:1352758. Ulk2.
Rouge	Search...
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00700000104114.
HOGENOM	HOG000044146.
HOVERGEN	HBG000342.
InParanoid	Q9QY01.
KO	K08269.
OMA	RMFYEKN.
OrthoDB	EOG4F1X2B.
Gene expression databases
ArrayExpress	Q9QY01.
Bgee	Q9QY01.
CleanEx	MM_ULK2.
Genevestigator	Q9QY01.
GermOnline	ENSMUSG00000004798. Mus musculus.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_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]
Pfam	PF12063. DUF3543. 1 hit. PF00069. Pkinase. 1 hit. [Graphical view]
PIRSF	PIRSF000580. Ser/Thr_PK_STPK_ULK-1/2. 1 hit.
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	307094.
SOURCE	Search...

Entry information

Entry name

ULK2_MOUSE

Accession

Primary (citable) accession number: Q9QY01
Secondary accession number(s): Q80TV7, Q9WTP4

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 25, 2005
Last sequence update:	May 1, 2000
Last modified:	May 1, 2013
This is version 102 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program