Hmdb loader
Survey
You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Human Metabolome Database.
Identification
HMDB Protein ID HMDBP01490
Secondary Accession Numbers
  • 6786
Name Serine/threonine-protein kinase 4
Synonyms
  1. MST-1
  2. Mammalian STE20-like protein kinase 1
  3. STE20-like kinase MST1
  4. Serine/threonine-protein kinase Krs-2
Gene Name STK4
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 'Ser-14' of histone H2B (H2BS14ph) during apoptosis. Phosphorylates FOXO3 upon oxidative stress, which results in its nuclear translocation and cell death initiation
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:2
Locus 20q11.2-q13.2
SNPs STK4
Gene Sequence
>1464 bp
ATGGAGACGGTACAGCTGAGGAACCCGCCGCGCCGGCAGCTGAAAAAGTTGGATGAAGAT
AGTTTAACCAAACAACCAGAAGAAGTATTTGATGTCTTAGAGAAACTTGGAGAAGGGTCC
TATGGCAGCGTATACAAAGCTATTCATAAAGAGACCGGCCAGATTGTTGCTATTAAGCAA
GTTCCTGTGGAATCAGACCTCCAGGAGATAATCAAAGAAATCTCTATAATGCAGCAATGT
GACAGCCCTCATGTAGTCAAATATTATGGCAGTTATTTTAAGAACACAGACTTATGGATC
GTTATGGAGTACTGTGGGGCTGGTTCTGTATCTGATATCATTCGATTACGAAATAAAACG
TTAACAGAAGATGAAATAGCTACAATATTACAATCAACTCTTAAGGGACTTGAATACCTT
CATTTTATGAGAAAAATACACCGAGATATCAAGGCAGGAAATATTTTGCTAAATACAGAA
GGACATGCAAAACTTGCAGATTTTGGGGTAGCAGGTCAACTTACAGATACCATGGCCAAG
CGGAATACAGTGATAGGAACACCATTTTGGATGGCTCCAGAAGTGATTCAGGAAATTGGA
TACAACTGTGTAGCAGACATCTGGTCCCTGGGAATAACTGCCATAGAAATGGCTGAAGGA
AAGCCCCCTTATGCTGATATCCATCCAATGAGGGCAATCTTCATGATTCCTACAAATCCT
CCTCCCACATTCCGAAAACCAGAGCTATGGTCAGATAACTTTACAGATTTTGTGAAACAG
TGTCTTGTAAAGAGCCCTGAGCAGAGGGCCACAGCCACTCAGCTCCTGCAGCACCCATTT
GTCAGGAGTGCCAAAGGAGTGTCAATACTGCGAGACTTAATTAATGAAGCCATGGATGTG
AAACTGAAACGCCAGGAATCCCAGCAGCGGGAAGTGGACCAGGACGATGAAGAAAACTCA
GAAGAGGATGAAATGGATTCTGGCACGATGGTTCGAGCAGTGGGTGATGAGATGGGCACT
GTCCGAGTAGCCAGCACCATGACTGATGGAGCCAATACTATGATTGAGCACGATGACACG
TTGCCATCACAACTGGGCACCATGGTGATCAATGCAGAGGATGAGGAAGAGGAAGGAACT
ATGAAAAGAAGGGATGAGACCATGCAGCCTGCGAAACCATCCTTTCTTGAATATTTTGAA
CAAAAAGAAAAGGAAAACCAGATCAACAGCTTTGGCAAGAGTGTACCTGGTCCACTGAAA
AATTCTTCAGATTGGAAAATACCACAGGATGGAGACTACGAGTTTCTTAAGAGTTGGACA
GTGGAGGACCTTCAGAAGAGGCTCTTGGCCCTGGACCCCATGATGGAGCAGGAGATTGAA
GAGATCCGGCAGAAGTACCAGTCCAAGCGGCAGCCCATCCTGGATGCCATAGAGGCTAAG
AAGAGACGGCAACAAAACTTCTGA
Protein Properties
Number of Residues 487
Molecular Weight 55629.8
Theoretical pI 4.71
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence
>Serine/threonine-protein kinase 4
METVQLRNPPRRQLKKLDEDSLTKQPEEVFDVLEKLGEGSYGSVYKAIHKETGQIVAIKQ
VPVESDLQEIIKEISIMQQCDSPHVVKYYGSYFKNTDLWIVMEYCGAGSVSDIIRLRNKT
LTEDEIATILQSTLKGLEYLHFMRKIHRDIKAGNILLNTEGHAKLADFGVAGQLTDTMAK
RNTVIGTPFWMAPEVIQEIGYNCVADIWSLGITAIEMAEGKPPYADIHPMRAIFMIPTNP
PPTFRKPELWSDNFTDFVKQCLVKSPEQRATATQLLQHPFVRSAKGVSILRDLINEAMDV
KLKRQESQQREVDQDDEENSEEDEMDSGTMVRAVGDEMGTVRVASTMTDGANTMIEHDDT
LPSQLGTMVINAEDEEEEGTMKRRDETMQPAKPSFLEYFEQKEKENQINSFGKSVPGPLK
NSSDWKIPQDGDYEFLKSWTVEDLQKRLLALDPMMEQEIEEIRQKYQSKRQPILDAIEAK
KRRQQNF
GenBank ID Protein 189054830
UniProtKB/Swiss-Prot ID Q13043
UniProtKB/Swiss-Prot Entry Name STK4_HUMAN
PDB IDs Not Available
GenBank Gene ID AK315238
GeneCard ID STK4
GenAtlas ID STK4
HGNC ID HGNC:11408
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. Deloukas P, Matthews LH, Ashurst J, Burton J, Gilbert JG, Jones M, Stavrides G, Almeida JP, Babbage AK, Bagguley CL, Bailey J, Barlow KF, Bates KN, Beard LM, Beare DM, Beasley OP, Bird CP, Blakey SE, Bridgeman AM, Brown AJ, Buck D, Burrill W, Butler AP, Carder C, Carter NP, Chapman JC, Clamp M, Clark G, Clark LN, Clark SY, Clee CM, Clegg S, Cobley VE, Collier RE, Connor R, Corby NR, Coulson A, Coville GJ, Deadman R, Dhami P, Dunn M, Ellington AG, Frankland JA, Fraser A, French L, Garner P, Grafham DV, Griffiths C, Griffiths MN, Gwilliam R, Hall RE, Hammond S, Harley JL, Heath PD, Ho S, Holden JL, Howden PJ, Huckle E, Hunt AR, Hunt SE, Jekosch K, Johnson CM, Johnson D, Kay MP, Kimberley AM, King A, Knights A, Laird GK, Lawlor S, Lehvaslaiho MH, Leversha M, Lloyd C, Lloyd DM, Lovell JD, Marsh VL, Martin SL, McConnachie LJ, McLay K, McMurray AA, Milne S, Mistry D, Moore MJ, Mullikin JC, Nickerson T, Oliver K, Parker A, Patel R, Pearce TA, Peck AI, Phillimore BJ, Prathalingam SR, Plumb RW, Ramsay H, Rice CM, Ross MT, Scott CE, Sehra HK, Shownkeen R, Sims S, Skuce CD, Smith ML, Soderlund C, Steward CA, Sulston JE, Swann M, Sycamore N, Taylor R, Tee L, Thomas DW, Thorpe A, Tracey A, Tromans AC, Vaudin M, Wall M, Wallis JM, Whitehead SL, Whittaker P, Willey DL, Williams L, Williams SA, Wilming L, Wray PW, Hubbard T, Durbin RM, Bentley DR, Beck S, Rogers J: The DNA sequence and comparative analysis of human chromosome 20. Nature. 2001 Dec 20-27;414(6866):865-71. [PubMed:11780052 ]
  8. 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 ]
  9. Wissing J, Jansch L, Nimtz M, Dieterich G, Hornberger R, Keri G, Wehland J, Daub H: Proteomics analysis of protein kinases by target class-selective prefractionation and tandem mass spectrometry. Mol Cell Proteomics. 2007 Mar;6(3):537-47. Epub 2006 Dec 27. [PubMed:17192257 ]
  10. 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 ]
  11. 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 ]
  12. 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 ]
  13. Creasy CL, Chernoff J: Cloning and characterization of a human protein kinase with homology to Ste20. J Biol Chem. 1995 Sep 15;270(37):21695-700. [PubMed:7665586 ]
  14. Creasy CL, Ambrose DM, Chernoff J: The Ste20-like protein kinase, Mst1, dimerizes and contains an inhibitory domain. J Biol Chem. 1996 Aug 30;271(35):21049-53. [PubMed:8702870 ]
  15. Lee KK, Ohyama T, Yajima N, Tsubuki S, Yonehara S: MST, a physiological caspase substrate, highly sensitizes apoptosis both upstream and downstream of caspase activation. J Biol Chem. 2001 Jun 1;276(22):19276-85. Epub 2001 Mar 7. [PubMed:11278283 ]
  16. Ura S, Masuyama N, Graves JD, Gotoh Y: Caspase cleavage of MST1 promotes nuclear translocation and chromatin condensation. Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10148-53. Epub 2001 Aug 21. [PubMed:11517310 ]
  17. Cheung WL, Ajiro K, Samejima K, Kloc M, Cheung P, Mizzen CA, Beeser A, Etkin LD, Chernoff J, Earnshaw WC, Allis CD: Apoptotic phosphorylation of histone H2B is mediated by mammalian sterile twenty kinase. Cell. 2003 May 16;113(4):507-17. [PubMed:12757711 ]
  18. Praskova M, Khoklatchev A, Ortiz-Vega S, Avruch J: Regulation of the MST1 kinase by autophosphorylation, by the growth inhibitory proteins, RASSF1 and NORE1, and by Ras. Biochem J. 2004 Jul 15;381(Pt 2):453-62. [PubMed:15109305 ]
  19. Lehtinen MK, Yuan Z, Boag PR, Yang Y, Villen J, Becker EB, DiBacco S, de la Iglesia N, Gygi S, Blackwell TK, Bonni A: A conserved MST-FOXO signaling pathway mediates oxidative-stress responses and extends life span. Cell. 2006 Jun 2;125(5):987-1001. [PubMed:16751106 ]