STK4

Serine/threonine kinase 4

PDB rendering based on 2jo8.

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
2JO8, 3COM, 4NR2, 4OH8

Identifiers

Symbols

STK4 ; KRS2; MST1; TIIAC; YSK3

External IDs

OMIM: 604965 MGI: 1929004 HomoloGene: 55965 ChEMBL: 4598 GeneCards: STK4 Gene

EC number

2.7.11.1

Gene ontology
Molecular function	• magnesium ion binding • protein serine/threonine kinase activity • MAP kinase kinase kinase activity • protein binding • ATP binding • transcription factor binding • identical protein binding • protein homodimerization activity • protein serine/threonine kinase activator activity • protein dimerization activity
Cellular component	• nucleus • nucleoplasm • cytoplasm • cytosol • protein complex
Biological process	• MAPK cascade • activation of MAPKK activity • cell morphogenesis • patterning of blood vessels • neural tube formation • positive regulation of protein phosphorylation • endocardium development • protein phosphorylation • apoptotic process • signal transduction • regulation of mitotic cell cycle • central nervous system development • negative regulation of cell proliferation • peptidyl-serine phosphorylation • signal transduction by protein phosphorylation • keratinocyte differentiation • stress-activated protein kinase signaling cascade • positive regulation of protein binding • positive regulation of peptidyl-serine phosphorylation • hippo signaling • intracellular signal transduction • positive regulation of apoptotic process • positive regulation of fat cell differentiation • negative regulation of organ growth • protein autophosphorylation • protein stabilization • primitive hemopoiesis • cell differentiation involved in embryonic placenta development • regulation of cell differentiation involved in embryonic placenta development • positive regulation of protein serine/threonine kinase activity • negative regulation of canonical Wnt signaling pathway • hepatocyte apoptotic process • positive regulation of extrinsic apoptotic signaling pathway via death domain receptors
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 20:
44.97 – 45.08 Mb

Chr 2:
164.07 – 164.16 Mb

PubMed search

Serine/threonine-protein kinase 4 is an enzyme that in humans is encoded by the STK4 gene.^[1]^[2]^[3]

Function

The protein encoded by this gene is a cytoplasmic kinase that is structurally similar to the yeast Ste20p kinase, which acts upstream of the stress-induced mitogen-activated protein kinase cascade. The encoded protein can phosphorylate myelin basic protein and undergoes autophosphorylation. A caspase-cleaved fragment of the encoded protein has been shown to be capable of phosphorylating histone H2B. The particular phosphorylation catalyzed by this protein has been correlated with apoptosis, and it's possible that this protein induces the chromatin condensation observed in this process.^[4]

Interactions

STK4 has been shown to interact with PRKRIR.^[5]

STK4 has also been shown to prevent, through Yap1 coactivator modulation, haematological tumor cell apoptosis. Cottini F, Hideshima T, Xu C, Sattler M, Dori M, Agnelli L, ten Hacken E, Bertilaccio MT, Antonini E, Neri A, Ponzoni M, Marcatti M, Richardson PG, Carrasco R, Kimmelman AC, Wong KK, Caligaris-Cappio F, Blandino G, Kuehl WM, Anderson KC, Tonon G (2014). "Rescue of Hippo coactivator YAP1 triggers DNA damage-induced apoptosis in hematological cancers". Nat. Med. 20 (6): 599–606. doi:10.1038/nm.3562. PMID 24813251.

References

↑ Taylor LK, Wang HC, Erikson RL (November 1996). "Newly identified stress-responsive protein kinases, Krs-1 and Krs-2". Proc. Natl. Acad. Sci. U.S.A. 93 (19): 10099–104. doi:10.1073/pnas.93.19.10099. PMC 38343. PMID 8816758.
↑ Graves JD, Gotoh Y, Draves KE, Ambrose D, Han DK, Wright M, Chernoff J, Clark EA, Krebs EG (June 1998). "Caspase-mediated activation and induction of apoptosis by the mammalian Ste20-like kinase Mst1". EMBO J. 17 (8): 2224–34. doi:10.1093/emboj/17.8.2224. PMC 1170567. PMID 9545236.
↑ Ura S, Masuyama N, Graves JD, Gotoh Y (August 2001). "Caspase cleavage of MST1 promotes nuclear translocation and chromatin condensation". Proc. Natl. Acad. Sci. U.S.A. 98 (18): 10148–53. doi:10.1073/pnas.181161698. PMC 56930. PMID 11517310.
↑ "Entrez Gene: STK4 serine/threonine kinase 4".
↑ Lin Y, Khokhlatchev A, Figeys D, Avruch J (December 2002). "Death-associated protein 4 binds MST1 and augments MST1-induced apoptosis". J. Biol. Chem. 277 (50): 47991–8001. doi:10.1074/jbc.M202630200. PMID 12384512.

Choi J, Oh S, Lee D, Oh HJ, Park JY, Lee SB, Lim DS (2009). Kaeberlein M, ed. "Mst1-FoxO signaling protects Naïve T lymphocytes from cellular oxidative stress in mice". PLoS ONE 4 (11): e8011. doi:10.1371/journal.pone.0008011. PMC 2776980. PMID 19956688.
de Souza PM, Lindsay MA (2004). "Mammalian Sterile20-like kinase 1 and the regulation of apoptosis". Biochem. Soc. Trans. 32 (Pt3): 485–8. doi:10.1042/BST0320485. PMID 15157167.
Han S, Stuart LA, Degen SJ (1991). "Characterization of the DNF15S2 locus on human chromosome 3: identification of a gene coding for four kringle domains with homology to hepatocyte growth factor". Biochemistry 30 (40): 9768–80. doi:10.1021/bi00104a029. PMID 1655021.
Gerber MJ, Drabkin HA, Firnhaber C, Miller YE, Scoggin CH, Smith DI (1988). "Regional localization of chromosome 3-specific DNA fragments by using a hybrid cell deletion mapping panel". Am. J. Hum. Genet. 43 (4): 442–51. PMC 1715492. PMID 2902784.
Creasy CL, Chernoff J (1995). "Cloning and characterization of a human protein kinase with homology to Ste20". J. Biol. Chem. 270 (37): 21695–700. doi:10.1074/jbc.270.37.21695. PMID 7665586.
Schultz SJ, Nigg EA (1993). "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. 4 (10): 821–30. PMID 8274451.
Creasy CL, Chernoff J (1995). "Cloning and characterization of a member of the MST subfamily of Ste20-like kinases". Gene 167 (1-2): 303–6. doi:10.1016/0378-1119(95)00653-2. PMID 8566796.
Creasy CL, Ambrose DM, Chernoff J (1996). "The Ste20-like protein kinase, Mst1, dimerizes and contains an inhibitory domain". J. Biol. Chem. 271 (35): 21049–53. doi:10.1074/jbc.271.35.21049. PMID 8702870.
Bonaldo MF, Lennon G, Soares MB (1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
Lee KK, Ohyama T, Yajima N, Tsubuki S, Yonehara S (2001). "MST, a physiological caspase substrate, highly sensitizes apoptosis both upstream and downstream of caspase activation". J. Biol. Chem. 276 (22): 19276–85. doi:10.1074/jbc.M005109200. PMID 11278283.
Graves JD, Draves KE, Gotoh Y, Krebs EG, Clark EA (2001). "Both phosphorylation and caspase-mediated cleavage contribute to regulation of the Ste20-like protein kinase Mst1 during CD95/Fas-induced apoptosis". J. Biol. Chem. 276 (18): 14909–15. doi:10.1074/jbc.M010905200. PMID 11278782.
Lee KK, Yonehara S (2002). "Phosphorylation and dimerization regulate nucleocytoplasmic shuttling of mammalian STE20-like kinase (MST)". J. Biol. Chem. 277 (14): 12351–8. doi:10.1074/jbc.M108138200. PMID 11805089.
Khokhlatchev A, Rabizadeh S, Xavier R, Nedwidek M, Chen T, Zhang XF, Seed B, Avruch J (2002). "Identification of a novel Ras-regulated proapoptotic pathway". Curr. Biol. 12 (4): 253–65. doi:10.1016/S0960-9822(02)00683-8. PMID 11864565.
De Souza PM, Kankaanranta H, Michael A, Barnes PJ, Giembycz MA, Lindsay MA (2002). "Caspase-catalyzed cleavage and activation of Mst1 correlates with eosinophil but not neutrophil apoptosis". Blood 99 (9): 3432–8. doi:10.1182/blood.V99.9.3432. PMID 11964314.
Glantschnig H, Rodan GA, Reszka AA (2002). "Mapping of MST1 kinase sites of phosphorylation. Activation and autophosphorylation". J. Biol. Chem. 277 (45): 42987–96. doi:10.1074/jbc.M208538200. PMID 12223493.
Lin Y, Khokhlatchev A, Figeys D, Avruch J (2002). "Death-associated protein 4 binds MST1 and augments MST1-induced apoptosis". J. Biol. Chem. 277 (50): 47991–8001. doi:10.1074/jbc.M202630200. PMID 12384512.

PDB gallery

2jo8: Solution structure of C-terminal domain of human mammalian sterile 20-like kinase 1 (MST1)

Kinases: Serine/threonine-specific protein kinases (EC 2.7.11-12)

Serine/threonine-specific protein kinases (EC 2.7.11.1-EC 2.7.11.20)

Non-specific serine/threonine protein kinases (EC 2.7.11.1)	LATS1 LATS2 MAST1 MAST2 STK38 STK38L CIT ROCK1 SGK SGK2 SGK3 Protein kinase B AKT1 AKT2 AKT3 Ataxia telangiectasia mutated Mammalian target of rapamycin EIF-2 kinases PKR HRI EIF2AK3 EIF2AK4 Wee1 WEE1

Pyruvate dehydrogenase kinase (EC 2.7.11.2)	PDK1 PDK2 PDK3

Dephospho-(reductase kinase) kinase (EC 2.7.11.3)	AMP-activated protein kinase α PRKAA1 PRKAA2 β PRKAB1 PRKAB2 γ PRKAG1 PRKAG2 PRKAG3

(3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)) (EC 2.7.11.4)	BCKDK BCKDHA BCKDHB

(isocitrate dehydrogenase (NADP+)) kinase (EC 2.7.11.5)	IDH2 IDH3A IDH3B IDH3G

(tyrosine 3-monooxygenase) kinase (EC 2.7.11.6)	STK4

Myosin-heavy-chain kinase (EC 2.7.11.7)	Aurora kinase Aurora A kinase Aurora B kinase

Fas-activated serine/threonine kinase (EC 2.7.11.8)	FASTK STK10

Goodpasture-antigen-binding protein kinase (EC 2.7.11.9)	-

IκB kinase (EC 2.7.11.10)	CHUK IKK2 TBK1 IKBKE IKBKG IKBKAP

cAMP-dependent protein kinase (EC 2.7.11.11)	Protein kinase A PRKACG PRKACB PRKACA PRKY

cGMP-dependent protein kinase (EC 2.7.11.12)	Protein kinase G PRKG1

Protein kinase C (EC 2.7.11.13)	Protein kinase C Protein kinase Cζ PKC alpha PRKCB1 PRKCD PRKCE PRKCH PRKCG PRKCI PRKCQ Protein kinase N1 PKN2 PKN3

Rhodopsin kinase (EC 2.7.11.14)	Rhodopsin kinase

Beta adrenergic receptor kinase (EC 2.7.11.15)	Beta adrenergic receptor kinase Beta adrenergic receptor kinase-2

G-protein coupled receptor kinases (EC 2.7.11.16)	GRK4 GRK5 GRK6

Ca2+/calmodulin-dependent (EC 2.7.11.17)	BRSK2 CAMK1 CAMK2A CAMK2B CAMK2D CAMK2G CAMK4 MLCK CASK CHEK1 CHEK2 DAPK1 DAPK2 DAPK3 STK11 MAPKAPK2 MAPKAPK3 MAPKAPK5 MARK1 MARK2 MARK3 MARK4 MELK MKNK1 MKNK2 NUAK1 NUAK2 OBSCN PASK PHKG1 PHKG2 PIM1 PIM2 PKD1 PRKD2 PRKD3 PSKH1 SNF1LK2 KIAA0999 STK40 SNF1LK SNRK SPEG TSSK2 Kalirin TRIB1 TRIB2 TRIB3 TRIO Titin DCLK1

Myosin light-chain kinase (EC 2.7.11.18)	MYLK MYLK2 MYLK3 MYLK4

Phosphorylase kinase (EC 2.7.11.19)	PHKA1 PHKA2 PHKB PHKG1 PHKG2

Elongation factor 2 kinase (EC 2.7.11.20)	EEF2K STK19

Polo kinase (EC 2.7.11.21)	PLK1 PLK2 PLK3 PLK4

Serine/threonine-specific protein kinases (EC 2.7.11.21-EC 2.7.11.30)

Polo kinase (EC 2.7.11.21)	PLK1 PLK2 PLK3 PLK4

Cyclin-dependent kinase (EC 2.7.11.22)	CDK1 CDK2 CDKL2 CDK3 CDK4 CDK5 CDKL5 CDK6 CDK7 CDK8 CDK9 CDK10 CDK12 CDC2L5 PCTK1 PCTK2 PCTK3 PFTK1 CDC2L1

(RNA-polymerase)-subunit kinase (EC 2.7.11.23)	RPS6KA5 RPS6KA4 P70S6 kinase P70-S6 Kinase 1 RPS6KB2 RPS6KA2 RPS6KA3 RPS6KA1 RPS6KC1

Mitogen-activated protein kinase (EC 2.7.11.24)	Extracellular signal-regulated MAPK1 MAPK3 MAPK4 MAPK6 MAPK7 MAPK12 MAPK15 C-Jun N-terminal MAPK8 MAPK9 MAPK10 P38 mitogen-activated protein MAPK11 MAPK13 MAPK14

MAP3K (EC 2.7.11.25)	MAP kinase kinase kinases MAP3K1 MAP3K2 MAP3K3 MAP3K4 MAP3K5 MAP3K6 MAP3K7 MAP3K8 RAFs ARAF BRAF KSR1 KSR2 MLKs MAP3K12 MAP3K13 MAP3K9 MAP3K10 MAP3K11 MAP3K7 ZAK CDC7 MAP3K14

Tau-protein kinase (EC 2.7.11.26)	TPK1 TTK GSK-3

(acetyl-CoA carboxylase) kinase (EC 2.7.11.27)	-

Tropomyosin kinase (EC 2.7.11.28)	-

Low-density-lipoprotein receptor kinase (EC 2.7.11.29)	-

Receptor protein serine/threonine kinase (EC 2.7.11.30)	Bone morphogenetic protein receptors BMPR1 BMPR1A BMPR1B BMPR2 ACVR1 ACVR1B ACVR1C ACVR2A ACVR2B ACVRL1 Anti-Müllerian hormone receptor

Dual-specificity kinases (EC 2.7.12)

MAP2K	MAP2K1 MAP2K2 MAP2K3 MAP2K4 MAP2K5 MAP2K6 MAP2K7

Proteins: enzymes

Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis Enzyme kinetics Lineweaver–Burk plot Michaelis–Menten kinetics

Regulation	Allosteric regulation Cooperativity Enzyme inhibitor

Classification	EC number Enzyme superfamily Enzyme family List of enzymes

Types	EC1 Oxidoreductases(list) EC2 Transferases(list) EC3 Hydrolases(list) EC4 Lyases(list) EC5 Isomerases(list) EC6 Ligases(list)

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STK4

Function

Interactions

References

Further reading