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Identification
HMDB Protein ID HMDBP01454
Secondary Accession Numbers
  • 6750
Name Serine/threonine-protein kinase 3
Synonyms
  1. MST-2
  2. Mammalian STE20-like protein kinase 2
  3. STE20-like kinase MST2
  4. Serine/threonine-protein kinase Krs-1
Gene Name STK3
Protein Type Unknown
Biological Properties
General Function Involved in protein kinase activity
Specific Function Stress-activated, pro-apoptotic kinase which, following caspase-cleavage, enters the nucleus and induces chromatin condensation followed by internucleosomal DNA fragmentation. Key component of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein MST1/MST2, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. MST1/MST2 are required to repress proliferation of mature hepatocytes, to prevent activation of facultative adult liver stem cells (oval cells), and to inhibit tumor formation. Phosphorylates NKX2-1
Pathways Not Available
Reactions Not Available
GO Classification
Function
binding
catalytic activity
transferase activity
transferase activity, transferring phosphorus-containing groups
kinase activity
nucleoside binding
purine nucleoside binding
adenyl nucleotide binding
adenyl ribonucleotide binding
atp binding
protein binding
protein kinase activity
protein serine/threonine kinase activity
Process
phosphorus metabolic process
phosphate metabolic process
metabolic process
biological regulation
regulation of biological process
cellular metabolic process
regulation of cellular process
signal transduction
protein amino acid phosphorylation
phosphorylation
Cellular Location
  1. Nucleus
  2. Cytoplasm
Gene Properties
Chromosome Location Chromosome:8
Locus 8q22.2
SNPs STK3
Gene Sequence
>1476 bp
ATGGAGCAGCCGCCGGCGCCTAAGAGTAAACTAAAAAAGCTGAGTGAAGACAGTTTGACT
AAGCAGCCTGAAGAAGTTTTTGATGTATTAGAGAAGCTTGGAGAAGGGTCTTATGGAAGT
GTATTTAAAGCAATACACAAGGAATCCGGTCAAGTTGTCGCAATTAAACAAGTACCTGTT
GAATCAGATCTTCAGGAAATAATCAAAGAAATTTCCATAATGCAGCAATGTGACAGCCCA
TATGTTGTAAAGTACTATGGCAGTTATTTTAAGAATACAGACCTCTGGATTGTTATGGAG
TACTGTGGCGCTGGCTCTGTCTCAGACATAATTAGATTACGAAACAAGACATTAATAGAA
GATGAAATTGCAACCATTCTTAAATCTACATTGAAAGGACTAGAATATTTGCACTTTATG
AGAAAAATACACAGAGATATAAAAGCTGGAAATATTCTCCTCAATACAGAAGGACATGCA
AAATTGGCAGATTTTGGAGTGGCTGGTCAGTTAACAGATACAATGGCAAAACGCAATACT
GTAATAGGAACTCCATTTTGGATGGCTCCTGAGGTGATTCAAGAAATAGGCTATAACTGT
GTGGCCGACATCTGGTCCCTTGGCATTACTTCTATAGAAATGGCTGAAGGAAAACCTCCT
TATGCTGATATACATCCAATGAGGGCTATTTTTATGATTCCCACAAATCCACCACCAACA
TTCAGAAAGCCAGAACTTTGGTCCGATGATTTCACCGATTTTGTTAAAAAGTGTTTGGTG
AAGAATCCTGAGCAGAGAGCTACTGCAACACAACTTTTACAGCACCCTTTTATCAAGAAT
GCCAAACCTGTATCAATATTAAGAGACCTGATCACAGAAGCTATGGAGATCAAAGCTAAA
AGACATGAGGAACAGCAACGAGAATTGGAAGAGGAAGAAGAAAATTCGGATGAAGATGAG
CTGGATTCCCACACCATGGTGAAGACTAGTGTGGAGAGTGTGGGCACCATGCGGGCCACA
AGCACGATGAGTGAAGGGGCCCAGACCATGATTGAACATAATAGCACGATGTTGGAATCC
GACTTGGGGACCATGGTGATAAACAGTGAGGATGAGGAAGAAGAAGATGGAACTATGAAA
AGAAATGCAACCTCACCACAAGTACAAAGACCATCTTTCATGGACTACTTTGATAAGCAA
GACTTCAAGAATAAGAGTCACGAAAACTGTAATCAGAACATGCATGAACCCTTCCCTATG
TCCAAAAACGTTTTTCCTGATAACTGGAAAGTTCCTCAAGATGGAGACTTTGACTTTTTG
AAAAATCTAAGTTTAGAAGAACTACAGATGCGGTTAAAAGCACTGGACCCCATGATGGAA
CGGGAGATAGAAGAACTTCGTCAGAGATACACTGCGAAAAGACAGCCCATTCTGGATGCG
ATGGATGCAAAGAAAAGAAGGCAGCAAAACTTTTGA
Protein Properties
Number of Residues 491
Molecular Weight 56300.7
Theoretical pI 4.88
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence
>Serine/threonine-protein kinase 3
MEQPPAPKSKLKKLSEDSLTKQPEEVFDVLEKLGEGSYGSVFKAIHKESGQVVAIKQVPV
ESDLQEIIKEISIMQQCDSPYVVKYYGSYFKNTDLWIVMEYCGAGSVSDIIRLRNKTLIE
DEIATILKSTLKGLEYLHFMRKIHRDIKAGNILLNTEGHAKLADFGVAGQLTDTMAKRNT
VIGTPFWMAPEVIQEIGYNCVADIWSLGITSIEMAEGKPPYADIHPMRAIFMIPTNPPPT
FRKPELWSDDFTDFVKKCLVKNPEQRATATQLLQHPFIKNAKPVSILRDLITEAMEIKAK
RHEEQQRELEEEEENSDEDELDSHTMVKTSVESVGTMRATSTMSEGAQTMIEHNSTMLES
DLGTMVINSEDEEEEDGTMKRNATSPQVQRPSFMDYFDKQDFKNKSHENCNQNMHEPFPM
SKNVFPDNWKVPQDGDFDFLKNLSLEELQMRLKALDPMMEREIEELRQRYTAKRQPILDA
MDAKKRRQQNF
GenBank ID Protein 158257106
UniProtKB/Swiss-Prot ID Q13188
UniProtKB/Swiss-Prot Entry Name STK3_HUMAN
PDB IDs Not Available
GenBank Gene ID AK291837
GeneCard ID STK3
GenAtlas ID STK3
HGNC ID HGNC:11406
References
General References
  1. 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. [PubMed:14702039 ]
  2. 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. [PubMed:15489334 ]
  3. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [PubMed:18669648 ]
  4. 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. [PubMed:19690332 ]
  5. 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. [PubMed:18691976 ]
  6. Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H: Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics. 2009 Jul;8(7):1751-64. doi: 10.1074/mcp.M800588-MCP200. Epub 2009 Apr 15. [PubMed:19369195 ]
  7. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell. 2006 Nov 3;127(3):635-48. [PubMed:17081983 ]
  8. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [PubMed:19413330 ]
  9. Nusbaum C, Mikkelsen TS, Zody MC, Asakawa S, Taudien S, Garber M, Kodira CD, Schueler MG, Shimizu A, Whittaker CA, Chang JL, Cuomo CA, Dewar K, FitzGerald MG, Yang X, Allen NR, Anderson S, Asakawa T, Blechschmidt K, Bloom T, Borowsky ML, Butler J, Cook A, Corum B, DeArellano K, DeCaprio D, Dooley KT, Dorris L 3rd, Engels R, Glockner G, Hafez N, Hagopian DS, Hall JL, Ishikawa SK, Jaffe DB, Kamat A, Kudoh J, Lehmann R, Lokitsang T, Macdonald P, Major JE, Matthews CD, Mauceli E, Menzel U, Mihalev AH, Minoshima S, Murayama Y, Naylor JW, Nicol R, Nguyen C, O'Leary SB, O'Neill K, Parker SC, Polley A, Raymond CK, Reichwald K, Rodriguez J, Sasaki T, Schilhabel M, Siddiqui R, Smith CL, Sneddon TP, Talamas JA, Tenzin P, Topham K, Venkataraman V, Wen G, Yamazaki S, Young SK, Zeng Q, Zimmer AR, Rosenthal A, Birren BW, Platzer M, Shimizu N, Lander ES: DNA sequence and analysis of human chromosome 8. Nature. 2006 Jan 19;439(7074):331-5. [PubMed:16421571 ]
  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. [PubMed:17344846 ]
  11. O'Neill E, Rushworth L, Baccarini M, Kolch W: Role of the kinase MST2 in suppression of apoptosis by the proto-oncogene product Raf-1. Science. 2004 Dec 24;306(5705):2267-70. [PubMed:15618521 ]
  12. Schultz SJ, Nigg EA: Identification of 21 novel human protein kinases, including 3 members of a family related to the cell cycle regulator nimA of Aspergillus nidulans. Cell Growth Differ. 1993 Oct;4(10):821-30. [PubMed:8274451 ]
  13. Chan EH, Nousiainen M, Chalamalasetty RB, Schafer A, Nigg EA, Sillje HH: The Ste20-like kinase Mst2 activates the human large tumor suppressor kinase Lats1. Oncogene. 2005 Mar 17;24(12):2076-86. [PubMed:15688006 ]
  14. Creasy CL, Chernoff J: Cloning and characterization of a member of the MST subfamily of Ste20-like kinases. Gene. 1995 Dec 29;167(1-2):303-6. [PubMed:8566796 ]
  15. Taylor LK, Wang HC, Erikson RL: Newly identified stress-responsive protein kinases, Krs-1 and Krs-2. Proc Natl Acad Sci U S A. 1996 Sep 17;93(19):10099-104. [PubMed:8816758 ]
  16. Oh HJ, Lee KK, Song SJ, Jin MS, Song MS, Lee JH, Im CR, Lee JO, Yonehara S, Lim DS: Role of the tumor suppressor RASSF1A in Mst1-mediated apoptosis. Cancer Res. 2006 Mar 1;66(5):2562-9. [PubMed:16510573 ]
  17. Callus BA, Verhagen AM, Vaux DL: Association of mammalian sterile twenty kinases, Mst1 and Mst2, with hSalvador via C-terminal coiled-coil domains, leads to its stabilization and phosphorylation. FEBS J. 2006 Sep;273(18):4264-76. Epub 2006 Aug 23. [PubMed:16930133 ]