Wee1-like protein kinase

Details

Name
Wee1-like protein kinase
Synonyms
  • 2.7.10.2
  • Wee1A kinase
  • WEE1hu
Gene Name
WEE1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0006507|Wee1-like protein kinase
MSFLSRQQPPPPRRAGAACTLRQKLIFSPCSDCEEEEEEEEEEGSGHSTGEDSAFQEPDS
PLPPARSPTEPGPERRRSPGPAPGSPGELEEDLLLPGACPGADEAGGGAEGDSWEEEGFG
SSSPVKSPAAPYFLGSSFSPVRCGGPGDASPRGCGARRAGEGRRSPRPDHPGTPPHKTFR
KLRLFDTPHTPKSLLSKARGIDSSSVKLRGSSLFMDTEKSGKREFDVRQTPQVNINPFTP
DSLLLHSSGQCRRRKRTYWNDSCGEDMEASDYELEDETRPAKRITITESNMKSRYTTEFH
ELEKIGSGEFGSVFKCVKRLDGCIYAIKRSKKPLAGSVDEQNALREVYAHAVLGQHSHVV
RYFSAWAEDDHMLIQNEYCNGGSLADAISENYRIMSYFKEAELKDLLLQVGRGLRYIHSM
SLVHMDIKPSNIFISRTSIPNAASEEGDEDDWASNKVMFKIGDLGHVTRISSPQVEEGDS
RFLANEVLQENYTHLPKADIFALALTVVCAAGAEPLPRNGDQWHEIRQGRLPRIPQVLSQ
EFTELLKVMIHPDPERRPSAMALVKHSVLLSASRKSAEQLRIELNAEKFKNSLLQKELKK
AQMAKAAAEERALFTDRMATRSTTQSNRTSRLIGKKMNRSVSLTIY
Number of residues
646
Molecular Weight
71596.655
Theoretical pI
6.76
GO Classification
Functions
ATP binding / magnesium ion binding / non-membrane spanning protein tyrosine kinase activity / protein tyrosine kinase activity
Processes
blood coagulation / cell division / establishment of cell polarity / G1/S transition of mitotic cell cycle / G2/M transition of mitotic cell cycle / microtubule cytoskeleton organization / mitotic cell cycle / mitotic nuclear division / neuron projection morphogenesis / regulation of cell cycle
Components
cytoplasm / nucleolus / nucleoplasm / nucleus
General Function
Protein tyrosine kinase activity
Specific Function
Acts as a negative regulator of entry into mitosis (G2 to M transition) by protecting the nucleus from cytoplasmically activated cyclin B1-complexed CDK1 before the onset of mitosis by mediating phosphorylation of CDK1 on 'Tyr-15'. Specifically phosphorylates and inactivates cyclin B1-complexed CDK1 reaching a maximum during G2 phase and a minimum as cells enter M phase. Phosphorylation of cyclin B1-CDK1 occurs exclusively on 'Tyr-15' and phosphorylation of monomeric CDK1 does not occur. Its activity increases during S and G2 phases and decreases at M phase when it is hyperphosphorylated. A correlated decrease in protein level occurs at M/G1 phase, probably due to its degradation.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Nucleus
Gene sequence
>lcl|BSEQ0012333|Wee1-like protein kinase (WEE1)
ATGGATACAGAAAAATCAGGAAAAAGGGAATTTGATGTGCGACAGACTCCTCAAGTGAAT
ATTAATCCTTTTACTCCGGATTCTTTGTTGCTTCATTCCTCAGGACAGTGTCGTCGTAGA
AAGAGAACGTATTGGAATGATTCCTGTGGTGAAGACATGGAAGCCAGTGATTATGAGCTT
GAAGATGAAACAAGACCTGCTAAGAGAATTACAATTACTGAAAGCAATATGAAGTCCCGG
TATACAACAGAATTTCATGAGCTAGAGAAAATCGGCTCTGGAGAATTTGGTTCTGTATTT
AAGTGTGTGAAGAGGCTGGATGGATGCATTTATGCCATTAAGCGATCAAAAAAGCCATTG
GCGGGCTCTGTTGATGAGCAGAACGCTTTGAGAGAAGTATATGCTCATGCAGTGCTTGGA
CAGCATTCTCATGTAGTTCGATATTTCTCTGCGTGGGCAGAAGATGATCATATGCTTATA
CAGAATGAATATTGTAATGGTGGAAGTTTAGCTGATGCTATAAGTGAAAACTACAGAATC
ATGAGTTACTTTAAAGAAGCAGAGTTGAAGGATCTCCTTTTGCAAGTTGGCCGAGGCTTG
AGGTATATTCATTCAATGTCTTTGGTTCACATGGATATAAAACCTAGTAATATTTTCATA
TCTCGAACCTCAATCCCAAATGCTGCCTCTGAAGAAGGAGACGAAGATGATTGGGCATCC
AACAAAGTTATGTTTAAAATAGGTGATCTTGGGCATGTAACAAGGATCTCCAGTCCACAA
GTTGAAGAGGGCGATAGTCGTTTTCTTGCAAATGAAGTTTTACAGGAGAATTATACCCAT
CTACCAAAAGCAGATATTTTTGCGCTTGCCCTCACAGTGGTATGTGCTGCTGGTGCTGAA
CCTCTTCCGAGAAATGGAGATCAATGGCATGAAATCAGACAGGGTAGATTACCTCGGATA
CCACAAGTGCTTTCCCAAGAATTTACAGAGTTGCTAAAAGTTATGATTCATCCAGATCCA
GAGAGAAGACCTTCAGCAATGGCACTGGTAAAGCATTCAGTATTGCTGTCCGCTTCTAGA
AAGAGTGCAGAACAATTACGAATAGAATTGAATGCCGAAAAGTTCAAAAATTCACTTTTA
CAAAAAGAACTCAAGAAAGCACAGATGGCAAAAGCTGCAGCTGAGGAAAGAGCACTCTTC
ACTGACCGGATGGCCACTAGGTCCACCACCCAGAGTAATAGAACATCTCGACTTATTGGA
AAGAAAATGAACCGCTCTGTCAGCCTTACTATATACTGA
Chromosome Location
11
Locus
11p15.3-p15.1
External Identifiers
ResourceLink
UniProtKB IDP30291
UniProtKB Entry NameWEE1_HUMAN
GenBank Gene IDU10564
GenAtlas IDWEE1
HGNC IDHGNC:12761
General References
  1. Watanabe N, Broome M, Hunter T: Regulation of the human WEE1Hu CDK tyrosine 15-kinase during the cell cycle. EMBO J. 1995 May 1;14(9):1878-91. [Article]
  2. Cichutek A, Brueckmann T, Seipel B, Hauser H, Schlaubitz S, Prawitt D, Hankeln T, Schmidt ER, Winterpacht A, Zabel BU: Comparative architectural aspects of regions of conserved synteny on human chromosome 11p15.3 and mouse chromosome 7 (including genes WEE1 and LMO1). Cytogenet Cell Genet. 2001;93(3-4):277-83. [Article]
  3. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
  4. Taylor TD, Noguchi H, Totoki Y, Toyoda A, Kuroki Y, Dewar K, Lloyd C, Itoh T, Takeda T, Kim DW, She X, Barlow KF, Bloom T, Bruford E, Chang JL, Cuomo CA, Eichler E, FitzGerald MG, Jaffe DB, LaButti K, Nicol R, Park HS, Seaman C, Sougnez C, Yang X, Zimmer AR, Zody MC, Birren BW, Nusbaum C, Fujiyama A, Hattori M, Rogers J, Lander ES, Sakaki Y: Human chromosome 11 DNA sequence and analysis including novel gene identification. Nature. 2006 Mar 23;440(7083):497-500. [Article]
  5. Igarashi M, Nagata A, Jinno S, Suto K, Okayama H: Wee1(+)-like gene in human cells. Nature. 1991 Sep 5;353(6339):80-3. [Article]
  6. McGowan CH, Russell P: Human Wee1 kinase inhibits cell division by phosphorylating p34cdc2 exclusively on Tyr15. EMBO J. 1993 Jan;12(1):75-85. [Article]
  7. Lu R, Niida H, Nakanishi M: Human SAD1 kinase is involved in UV-induced DNA damage checkpoint function. J Biol Chem. 2004 Jul 23;279(30):31164-70. Epub 2004 May 18. [Article]
  8. Watanabe N, Arai H, Nishihara Y, Taniguchi M, Watanabe N, Hunter T, Osada H: M-phase kinases induce phospho-dependent ubiquitination of somatic Wee1 by SCFbeta-TrCP. Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4419-24. Epub 2004 Mar 22. [Article]
  9. Cantin GT, Yi W, Lu B, Park SK, Xu T, Lee JD, Yates JR 3rd: Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis. J Proteome Res. 2008 Mar;7(3):1346-51. doi: 10.1021/pr0705441. Epub 2008 Jan 26. [Article]
  10. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. [Article]
  11. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [Article]
  12. Muller M, Lutter D, Puschel AW: Persistence of the cell-cycle checkpoint kinase Wee1 in SadA- and SadB-deficient neurons disrupts neuronal polarity. J Cell Sci. 2010 Jan 15;123(Pt 2):286-94. doi: 10.1242/jcs.058230. Epub 2009 Dec 21. [Article]
  13. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. [Article]
  14. Visconti R, Palazzo L, Della Monica R, Grieco D: Fcp1-dependent dephosphorylation is required for M-phase-promoting factor inactivation at mitosis exit. Nat Commun. 2012 Jun 12;3:894. doi: 10.1038/ncomms1886. [Article]
  15. Squire CJ, Dickson JM, Ivanovic I, Baker EN: Structure and inhibition of the human cell cycle checkpoint kinase, Wee1A kinase: an atypical tyrosine kinase with a key role in CDK1 regulation. Structure. 2005 Apr;13(4):541-50. [Article]
  16. 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
DB046089-HYDROXY-4-PHENYL-6H-PYRROLO[3,4-C]CARBAZOLE-1,3-DIONEexperimentalunknownDetails
DB070069-HYDROXY-6-(3-HYDROXYPROPYL)-4-(2-METHOXYPHENYL)PYRROLO[3,4-C]CARBAZOLE-1,3(2H,6H)-DIONEexperimentalunknownDetails
DB07226N-[4-(2-CHLOROPHENYL)-1,3-DIOXO-1,2,3,6-TETRAHYDROPYRROLO[3,4-C]CARBAZOL-9-YL]FORMAMIDEexperimentalunknownDetails
DB072574-(2-chlorophenyl)-8-(2-hydroxyethyl)-6-methylpyrrolo[3,4-e]indole-1,3(2H,6H)-dioneexperimentalunknownDetails
DB072653-(9-HYDROXY-1,3-DIOXO-4-PHENYL-2,3-DIHYDROPYRROLO[3,4-C]CARBAZOL-6(1H)-YL)PROPANOIC ACIDexperimentalunknownDetails
DB083658-bromo-4-(2-chlorophenyl)-N-(2-hydroxyethyl)-6-methyl-1,3-dioxo-1,2,3,6-tetrahydropyrrolo[3,4-e]indole-7-carboxamideexperimentalunknownDetails
DB11740MK-1775investigationalyesinhibitorDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails