Q8IYT8 (ULK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1036 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.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.

Ontologies

Keywords
Biological process	Autophagy Neurogenesis
Cellular component	Cytoplasmic vesicle Membrane
Coding sequence diversity	Polymorphism
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 electronic annotation. Source: Compara negative regulation of collateral sprouting Inferred from electronic annotation. Source: Compara protein autophosphorylation Inferred from direct assay Ref.4. Source: UniProtKB regulation of autophagy Inferred from direct assay Ref.4. Source: UniProtKB response to starvation Inferred from sequence or structural similarity. 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.4. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine kinase activity Inferred from direct assay Ref.4. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1036	1036	Serine/threonine-protein kinase ULK2		PRO_0000086782
Regions
	Domain	9 – 271	263	Protein kinase
	Nucleotide binding	15 – 23	9	ATP By similarity
	Region	812 – 1036	225	CTD-like region
Sites
	Active site	131	1	Proton acceptor By similarity
	Binding site	39	1	ATP Probable
Natural variations
	Natural variant	242	1	P → S. Ref.10 Corresponds to variant rs34670978 [ dbSNP | Ensembl ].		VAR_041281
	Natural variant	370	1	V → M. Ref.1 Ref.3 Corresponds to variant rs150122 [ dbSNP | Ensembl ].		VAR_055287
	Natural variant	533	1	T → I. Corresponds to variant rs4462660 [ dbSNP | Ensembl ].		VAR_055288
	Natural variant	627	1	G → E in a metastatic melanoma sample; somatic mutation. Ref.10		VAR_041282
	Natural variant	662	1	A → V in a metastatic melanoma sample; somatic mutation. Ref.10		VAR_041283
	Natural variant	752	1	G → R. Ref.10 Corresponds to variant rs55730189 [ dbSNP | Ensembl ].		VAR_041284
	Natural variant	842	1	D → E. Ref.10 Corresponds to variant rs35107651 [ dbSNP | Ensembl ].		VAR_041285
Experimental info
	Mutagenesis	39	1	K → R: Decreased kinase activity and decreased autophosphorylation. Ref.4
	Sequence conflict	935	1	C → R in BAA31598. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q8IYT8 [UniParc]. Last modified May 18, 2010. Version 3. Checksum: D311F01FA058CBBC	FASTA	1,036	112,694
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.
IPI	IPI00479399.
RefSeq	NP_001136082.1. NM_001142610.1. NP_055498.3. NM_014683.3.
UniGene	Hs.168762.
3D structure databases
ProteinModelPortal	Q8IYT8.
SMR	Q8IYT8. Positions 9-317.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8IYT8. 51 interactions.
MINT	MINT-1369789.
STRING	9606.ENSP00000354877.
PTM databases
PhosphoSite	Q8IYT8.
Polymorphism databases
DMDM	296453001.
Proteomic databases
PaxDb	Q8IYT8.
PRIDE	Q8IYT8.
Protocols and materials databases
DNASU	9706.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000361658; ENSP00000354877; ENSG00000083290. ENST00000395544; ENSP00000378914; ENSG00000083290.
GeneID	9706.
KEGG	hsa:9706.
UCSC	uc002gwm.4. human.
Organism-specific databases
CTD	9706.
GeneCards	GC17M019674.
H-InvDB	HIX0013624.
HGNC	HGNC:13480. ULK2.
HPA	HPA009027.
MIM	608650. gene.
neXtProt	NX_Q8IYT8.
PharmGKB	PA37780.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000044146.
HOVERGEN	HBG000342.
InParanoid	Q8IYT8.
KO	K08269.
OMA	RMFYEKN.
Enzyme and pathway databases
SignaLink	Q8IYT8.
Gene expression databases
Bgee	Q8IYT8.
CleanEx	HS_ULK2.
Genevestigator	Q8IYT8.
GermOnline	ENSG00000083290. Homo sapiens.
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
ChEMBL	CHEMBL5435.
ChiTaRS	ULK2. human.
GenomeRNAi	9706.
NextBio	36477.
SOURCE	Search...

Entry information

Entry name

ULK2_HUMAN

Accession

Primary (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:	May 29, 2013
This is version 107 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.