Serine/threonine-protein kinase ULK2

Details

Name
Serine/threonine-protein kinase ULK2
Synonyms
  • 2.7.11.1
  • KIAA0623
  • Unc-51-like kinase 2
Gene Name
ULK2
Organism
Humans
Amino acid sequence
>lcl|BSEQ0051690|Serine/threonine-protein kinase ULK2
MEVVGDFEYSKRDLVGHGAFAVVFRGRHRQKTDWEVAIKSINKKNLSKSQILLGKEIKIL
KELQHENIVALYDVQELPNSVFLVMEYCNGGDLADYLQAKGTLSEDTIRVFLHQIAAAMR
ILHSKGIIHRDLKPQNILLSYANRRKSSVSGIRIKIADFGFARYLHSNMMAATLCGSPMY
MAPEVIMSQHYDAKADLWSIGTVIYQCLVGKPPFQANSPQDLRMFYEKNRSLMPSIPRET
SPYLANLLLGLLQRNQKDRMDFEAFFSHPFLEQGPVKKSCPVPVPMYSGSVSGSSCGSSP
SCRFASPPSLPDMQHIQEENLSSPPLGPPNYLQVSKDSASTSSKNSSCDTDDFVLVPHNI
SSDHSCDMPVGTAGRRASNEFLVCGGQCQPTVSPHSETAPIPVPTQIRNYQRIEQNLTST
ASSGTNVHGSPRSAVVRRSNTSPMGFLRPGSCSPVPADTAQTVGRRLSTGSSRPYSPSPL
VGTIPEQFSQCCCGHPQGHDSRSRNSSGSPVPQAQSPQSLLSGARLQSAPTLTDIYQNKQ
KLRKQHSDPVCPSHTGAGYSYSPQPSRPGSLGTSPTKHLGSSPRSSDWFFKTPLPTIIGS
PTKTTAPFKIPKTQASSNLLALVTRHGPAEEQSKDGNEPRECAHCLLVQGSERQRAEQQS
KAVFGRSVSTGKLSDQQGKTPICRHQGSTDSLNTERPMDIAPAGACGGVLAPPAGTAASS
KAVLFTVGSPPHSAAAPTCTHMFLRTRTTSVGPSNSGGSLCAMSGRVCVGSPPGPGFGSS
PPGAEAAPSLRYVPYGASPPSLEGLITFEAPELPEETLMEREHTDTLRHLNVMLMFTECV
LDLTAMRGGNPELCTSAVSLYQIQESVVVDQISQLSKDWGRVEQLVLYMKAAQLLAASLH
LAKAQIKSGKLSPSTAVKQVVKNLNERYKFCITMCKKLTEKLNRFFSDKQRFIDEINSVT
AEKLIYNCAVEMVQSAALDEMFQQTEDIVYRYHKAALLLEGLSRILQDPADIENVHKYKC
SIERRLSALCHSTATV
Number of residues
1036
Molecular Weight
112693.175
Theoretical pI
Not Available
GO Classification
Functions
ATP binding / protein serine/threonine kinase activity
Processes
autophagy / autophagy of host cells involved in interaction with symbiont / axon extension / negative regulation of collateral sprouting / protein autophosphorylation / response to starvation / signal transduction
Components
cytoplasmic vesicle membrane / phagophore assembly site membrane
General 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.
Specific Function
Atp binding
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasmic vesicle membrane
Gene sequence
>lcl|BSEQ0051691|Serine/threonine-protein kinase ULK2 (ULK2)
ATGGAGGTGGTGGGTGACTTCGAGTACAGCAAGAGGGATCTCGTGGGACACGGGGCCTTC
GCCGTGGTCTTCCGGGGGCGGCACCGCCAGAAAACTGATTGGGAGGTAGCTATTAAAAGT
ATTAATAAAAAGAACTTGTCAAAATCACAAATACTGCTTGGAAAGGAAATTAAAATCTTA
AAGGAACTTCAGCATGAAAATATTGTAGCACTCTATGATGTTCAGGAATTACCCAACTCT
GTCTTTTTGGTGATGGAGTATTGCAATGGTGGAGACCTCGCAGATTATTTGCAAGCGAAA
GGGACTCTCAGTGAAGACACGATCAGAGTGTTTCTGCATCAGATTGCTGCTGCCATGCGA
ATCCTGCACAGCAAAGGAATCATCCACAGAGATCTCAAACCACAGAACATCTTGCTGTCC
TATGCCAATCGCAGAAAATCAAGTGTCAGTGGTATTCGCATCAAAATAGCGGATTTTGGT
TTTGCTCGTTACCTACATAGTAACATGATGGCTGCAACACTGTGTGGATCCCCGATGTAC
ATGGCTCCTGAGGTTATTATGTCTCAACATTATGATGCTAAGGCTGACTTGTGGAGCATA
GGAACAGTGATATACCAATGCCTAGTTGGAAAACCACCTTTTCAGGCCAATAGTCCTCAA
GACTTAAGGATGTTTTATGAAAAAAACAGGAGCTTAATGCCTAGTATTCCCAGAGAAACA
TCACCTTATTTGGCTAATCTCCTTTTGGGTTTGCTTCAGAGAAACCAAAAAGATAGAATG
GACTTTGAAGCATTTTTTAGCCATCCTTTTCTTGAGCAAGGTCCAGTAAAAAAATCTTGC
CCAGTTCCAGTGCCCATGTATTCTGGTTCTGTCTCTGGAAGCTCCTGTGGCAGCTCTCCA
TCTTGTCGTTTTGCTTCTCCACCATCCCTTCCAGATATGCAGCATATTCAGGAAGAAAAC
TTATCTTCCCCACCATTGGGTCCTCCCAACTATCTACAAGTTTCCAAAGATTCTGCCAGT
ACTAGTAGCAAGAACTCTTCTTGTGACACGGATGACTTTGTTTTGGTGCCACACAACATC
TCGTCAGACCACTCATGTGATATGCCAGTGGGGACTGCTGGCAGACGTGCTTCAAATGAA
TTCTTGGTGTGTGGAGGGCAGTGTCAGCCTACTGTGTCACCTCACAGCGAAACAGCACCA
ATTCCAGTTCCTACTCAAATAAGGAATTATCAGCGCATAGAGCAGAATCTTACATCTACT
GCCAGCTCAGGCACAAATGTACATGGTTCTCCAAGATCTGCAGTGGTACGAAGGTCCAAC
ACCAGCCCCATGGGCTTCCTCCGGCCGGGATCATGCTCCCCAGTACCAGCAGACACAGCA
CAGACAGTTGGACGAAGGCTCTCCACTGGGTCTTCTAGGCCTTACTCACCTTCCCCTTTG
GTTGGTACCATTCCTGAGCAATTCAGTCAGTGCTGCTGTGGGCATCCTCAGGGCCATGAC
TCCAGGAGTAGAAACTCCTCAGGTTCTCCAGTGCCACAAGCTCAGTCCCCACAGTCTCTC
TTATCGGGTGCTAGACTGCAGAGCGCCCCCACCCTCACTGACATCTATCAGAACAAGCAG
AAGCTCAGAAAACAGCACTCTGACCCCGTGTGCCCATCCCATACTGGGGCTGGGTACAGC
TACTCGCCTCAGCCCAGTCGGCCTGGCAGCCTTGGAACTTCTCCCACCAAGCACTTGGGG
TCCTCTCCACGGAGTTCTGACTGGTTCTTTAAAACTCCTTTGCCAACAATCATTGGCTCT
CCTACTAAGACCACAGCTCCTTTCAAAATCCCTAAAACTCAAGCATCTTCCAACCTGTTA
GCCTTGGTTACTCGTCATGGGCCTGCTGAAGAACAGTCGAAAGATGGGAATGAGCCACGG
GAATGTGCCCATTGCCTCTTAGTGCAAGGAAGTGAGAGGCAGCGGGCCGAGCAGCAGAGC
AAGGCAGTGTTTGGCAGATCTGTCAGTACCGGGAAGTTATCAGATCAACAAGGAAAGACT
CCTATATGTCGACATCAGGGCAGCACAGACAGTTTAAATACAGAACGACCAATGGATATA
GCTCCGGCAGGAGCCTGTGGTGGTGTTCTGGCACCTCCTGCAGGTACAGCAGCAAGTTCC
AAGGCTGTCCTCTTCACTGTAGGGTCTCCTCCACACAGTGCGGCAGCCCCCACTTGTACC
CACATGTTCCTTCGAACAAGAACAACCTCAGTGGGGCCCAGCAACTCCGGGGGCTCTCTT
TGTGCCATGAGTGGCCGCGTGTGCGTGGGGTCCCCGCCTGGCCCAGGCTTCGGCTCTTCC
CCTCCAGGAGCAGAGGCAGCTCCCAGCCTGAGATACGTGCCTTACGGTGCTTCACCCCCC
AGCCTAGAGGGGCTCATCACCTTTGAAGCCCCTGAACTGCCGGAGGAGACGCTGATGGAG
CGGGAACACACAGACACCTTACGCCATCTGAATGTGATGCTGATGTTCACTGAGTGTGTG
CTGGACCTGACAGCCATGAGGGGAGGAAACCCTGAGCTGTGCACATCTGCTGTGTCCTTG
TACCAGATCCAGGAGAGTGTGGTGGTGGACCAGATCAGTCAGCTGAGCAAAGACTGGGGG
CGGGTGGAGCAGCTGGTGTTGTACATGAAAGCAGCACAGCTGCTTGCGGCTTCTCTGCAT
CTTGCCAAAGCCCAGATCAAGTCCGGGAAACTGAGCCCATCCACAGCTGTGAAACAAGTT
GTCAAGAATCTGAACGAACGATATAAATTCTGCATCACCATGTGCAAGAAACTTACAGAA
AAGCTGAATCGATTCTTCTCTGACAAACAGAGGTTTATTGATGAAATCAACAGTGTGACT
GCAGAGAAACTCATCTATAATTGTGCTGTAGAAATGGTTCAGTCTGCAGCCCTGGATGAG
ATGTTTCAGCAGACCGAAGATATTGTTTATCGCTATCATAAGGCAGCCCTTCTTTTGGAA
GGCCTAAGTAGGATTCTACAGGACCCTGCAGATATTGAAAATGTGCATAAATATAAATGT
AGTATTGAGAGAAGACTGTCGGCGCTCTGCCATAGCACCGCAACCGTGTGA
Chromosome Location
17
Locus
17p11.2
External Identifiers
ResourceLink
UniProtKB IDQ8IYT8
UniProtKB Entry NameULK2_HUMAN
HGNC IDHGNC:13480
General References
  1. Ishikawa K, Nagase T, Suyama M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O: 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. DNA Res. 1998 Jun 30;5(3):169-76. [Article]
  2. Zody MC, Garber M, Adams DJ, Sharpe T, Harrow J, Lupski JR, Nicholson C, Searle SM, Wilming L, Young SK, Abouelleil A, Allen NR, Bi W, Bloom T, Borowsky ML, Bugalter BE, Butler J, Chang JL, Chen CK, Cook A, Corum B, Cuomo CA, de Jong PJ, DeCaprio D, Dewar K, FitzGerald M, Gilbert J, Gibson R, Gnerre S, Goldstein S, Grafham DV, Grocock R, Hafez N, Hagopian DS, Hart E, Norman CH, Humphray S, Jaffe DB, Jones M, Kamal M, Khodiyar VK, LaButti K, Laird G, Lehoczky J, Liu X, Lokyitsang T, Loveland J, Lui A, Macdonald P, Major JE, Matthews L, Mauceli E, McCarroll SA, Mihalev AH, Mudge J, Nguyen C, Nicol R, O'Leary SB, Osoegawa K, Schwartz DC, Shaw-Smith C, Stankiewicz P, Steward C, Swarbreck D, Venkataraman V, Whittaker CA, Yang X, Zimmer AR, Bradley A, Hubbard T, Birren BW, Rogers J, Lander ES, Nusbaum C: DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage. Nature. 2006 Apr 20;440(7087):1045-9. [Article]
  3. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  4. Chan EY, Longatti A, McKnight NC, Tooze SA: Kinase-inactivated ULK proteins inhibit autophagy via their conserved C-terminal domains using an Atg13-independent mechanism. Mol Cell Biol. 2009 Jan;29(1):157-71. doi: 10.1128/MCB.01082-08. Epub 2008 Oct 20. [Article]
  5. Lee EJ, Tournier C: The requirement of uncoordinated 51-like kinase 1 (ULK1) and ULK2 in the regulation of autophagy. Autophagy. 2011 Jul;7(7):689-95. Epub 2011 Jul 1. [Article]
  6. Loffler AS, Alers S, Dieterle AM, Keppeler H, Franz-Wachtel M, Kundu M, Campbell DG, Wesselborg S, Alessi DR, Stork B: Ulk1-mediated phosphorylation of AMPK constitutes a negative regulatory feedback loop. Autophagy. 2011 Jul;7(7):696-706. Epub 2011 Jul 1. [Article]
  7. Jung CH, Seo M, Otto NM, Kim DH: ULK1 inhibits the kinase activity of mTORC1 and cell proliferation. Autophagy. 2011 Oct;7(10):1212-21. doi: 10.4161/auto.7.10.16660. Epub 2011 Oct 1. [Article]
  8. Cheong H, Lindsten T, Wu J, Lu C, Thompson CB: Ammonia-induced autophagy is independent of ULK1/ULK2 kinases. Proc Natl Acad Sci U S A. 2011 Jul 5;108(27):11121-6. doi: 10.1073/pnas.1107969108. Epub 2011 Jun 20. [Article]
  9. Egan DF, Shackelford DB, Mihaylova MM, Gelino S, Kohnz RA, Mair W, Vasquez DS, Joshi A, Gwinn DM, Taylor R, Asara JM, Fitzpatrick J, Dillin A, Viollet B, Kundu M, Hansen M, Shaw RJ: Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science. 2011 Jan 28;331(6016):456-61. doi: 10.1126/science.1196371. Epub 2010 Dec 23. [Article]
  10. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, 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 DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails