STK24_HUMAN
ID STK24_HUMAN Reviewed; 443 AA.
AC Q9Y6E0; O14840; Q5JV92;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 203.
DE RecName: Full=Serine/threonine-protein kinase 24;
DE EC=2.7.11.1;
DE AltName: Full=Mammalian STE20-like protein kinase 3;
DE Short=MST-3;
DE AltName: Full=STE20-like kinase MST3;
DE Contains:
DE RecName: Full=Serine/threonine-protein kinase 24 36 kDa subunit;
DE AltName: Full=Mammalian STE20-like protein kinase 3 N-terminal;
DE Short=MST3/N;
DE Contains:
DE RecName: Full=Serine/threonine-protein kinase 24 12 kDa subunit;
DE AltName: Full=Mammalian STE20-like protein kinase 3 C-terminal;
DE Short=MST3/C;
GN Name=STK24; Synonyms=MST3, STK3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
RX PubMed=9353338; DOI=10.1074/jbc.272.45.28695;
RA Schinkmann K., Blenis J.;
RT "Cloning and characterization of a human STE20-like protein kinase with
RT unusual cofactor requirements.";
RL J. Biol. Chem. 272:28695-28703(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B), PHOSPHORYLATION AT THR-18,
RP MUTAGENESIS OF THR-18, AND VARIANT VAL-414.
RC TISSUE=Brain;
RX PubMed=10644707; DOI=10.1074/jbc.275.4.2513;
RA Zhou T.-H., Ling K., Guo J., Zhou H., Wu Y.-L., Jing Q., Ma L., Pei G.;
RT "Identification of a human brain-specific isoform of mammalian STE20-like
RT kinase 3 that is regulated by cAMP-dependent protein kinase.";
RL J. Biol. Chem. 275:2513-2519(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
RC TISSUE=Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PROTEOLYTIC PROCESSING, SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-65 AND
RP ASP-321.
RX PubMed=12107159; DOI=10.1074/jbc.m202468200;
RA Huang C.Y., Wu Y.M., Hsu C.Y., Lee W.S., Lai M.D., Lu T.J., Huang C.L.,
RA Leu T.H., Shih H.M., Fang H.I., Robinson D.R., Kung H.J., Yuan C.J.;
RT "Caspase activation of mammalian sterile 20-like kinase 3 (Mst3).";
RL J. Biol. Chem. 277:34367-34374(2002).
RN [7]
RP SUBCELLULAR LOCATION, NUCLEAR LOCALIZATION SIGNAL, AND NUCLEAR EXPORT
RP SIGNAL.
RX PubMed=15304321; DOI=10.1016/j.febslet.2004.07.007;
RA Lee W.S., Hsu C.Y., Wang P.L., Huang C.Y., Chang C.H., Yuan C.J.;
RT "Identification and characterization of the nuclear import and export
RT signals of the mammalian Ste20-like protein kinase 3.";
RL FEBS Lett. 572:41-45(2004).
RN [8]
RP COFACTOR, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=15917084; DOI=10.1016/j.jinorgbio.2005.03.003;
RA Lu T.J., Huang C.Y., Yuan C.J., Lee Y.C., Leu T.H., Chang W.C., Lu T.L.,
RA Jeng W.Y., Lai M.D.;
RT "Zinc ion acts as a cofactor for serine/threonine kinase MST3 and has a
RT distinct role in autophosphorylation of MST3.";
RL J. Inorg. Biochem. 99:1306-1313(2005).
RN [9]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=16314523; DOI=10.1128/mcb.25.24.11019-11029.2005;
RA Stegert M.R., Hergovich A., Tamaskovic R., Bichsel S.J., Hemmings B.A.;
RT "Regulation of NDR protein kinase by hydrophobic motif phosphorylation
RT mediated by the mammalian Ste20-like kinase MST3.";
RL Mol. Cell. Biol. 25:11019-11029(2005).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-320, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [11]
RP FUNCTION, PHOSPHORYLATION AT THR-190, AND MUTAGENESIS OF THR-190.
RX PubMed=17046825; DOI=10.1074/jbc.m605035200;
RA Lu T.J., Lai W.Y., Huang C.Y., Hsieh W.J., Yu J.S., Hsieh Y.J., Chang W.T.,
RA Leu T.H., Chang W.C., Chuang W.J., Tang M.J., Chen T.Y., Lu T.L., Lai M.D.;
RT "Inhibition of cell migration by autophosphorylated mammalian sterile 20-
RT like kinase 3 (MST3) involves paxillin and protein-tyrosine phosphatase-
RT PEST.";
RL J. Biol. Chem. 281:38405-38417(2006).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-4 (ISOFORM A), AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [13]
RP FUNCTION, AND PHOSPHORYLATION AT THR-190.
RX PubMed=19604147; DOI=10.1042/bsr20090096;
RA Chen C.B., Ng J.K., Choo P.H., Wu W., Porter A.G.;
RT "Mammalian sterile 20-like kinase 3 (MST3) mediates oxidative-stress-
RT induced cell death by modulating JNK activation.";
RL Biosci. Rep. 29:405-415(2009).
RN [14]
RP INTERACTION WITH CTTNBP2NL.
RX PubMed=18782753; DOI=10.1074/mcp.m800266-mcp200;
RA Goudreault M., D'Ambrosio L.M., Kean M.J., Mullin M.J., Larsen B.G.,
RA Sanchez A., Chaudhry S., Chen G.I., Sicheri F., Nesvizhskii A.I.,
RA Aebersold R., Raught B., Gingras A.C.;
RT "A PP2A phosphatase high density interaction network identifies a novel
RT striatin-interacting phosphatase and kinase complex linked to the cerebral
RT cavernous malformation 3 (CCM3) protein.";
RL Mol. Cell. Proteomics 8:157-171(2009).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2 (ISOFORM A), PHOSPHORYLATION
RP [LARGE SCALE ANALYSIS] AT SER-4 (ISOFORM A), CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS] (ISOFORM A), AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [16]
RP FUNCTION.
RX PubMed=19855390; DOI=10.1038/nn.2414;
RA Lorber B., Howe M.L., Benowitz L.I., Irwin N.;
RT "Mst3b, an Ste20-like kinase, regulates axon regeneration in mature CNS and
RT PNS pathways.";
RL Nat. Neurosci. 12:1407-1414(2009).
RN [17]
RP FUNCTION.
RX PubMed=19782762; DOI=10.1016/j.biocel.2009.09.012;
RA Lin C.Y., Wu H.Y., Wang P.L., Yuan C.J.;
RT "Mammalian Ste20-like protein kinase 3 induces a caspase-independent
RT apoptotic pathway.";
RL Int. J. Biochem. Cell Biol. 42:98-105(2010).
RN [18]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2 (ISOFORM A), PHOSPHORYLATION
RP [LARGE SCALE ANALYSIS] AT SER-4 (ISOFORM A), CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS] (ISOFORM A), AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [20]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2 (ISOFORM A), PHOSPHORYLATION
RP [LARGE SCALE ANALYSIS] AT SER-4 (ISOFORM A), CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS] (ISOFORM A), AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-190, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [22]
RP FUNCTION, AND INTERACTION WITH PDCD10 AND RIPOR1.
RX PubMed=27807006; DOI=10.1242/jcs.198614;
RA Mardakheh F.K., Self A., Marshall C.J.;
RT "RHO binding to FAM65A regulates Golgi reorientation during cell
RT migration.";
RL J. Cell Sci. 129:4466-4479(2016).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 27-315 IN COMPLEX WITH ADENINE;
RP ADP AND MANGANESE IONS, SUBUNIT, AND PHOSPHORYLATION AT THR-190.
RX PubMed=20124694; DOI=10.1107/s0907444909047507;
RA Ko T.P., Jeng W.Y., Liu C.I., Lai M.D., Wu C.L., Chang W.J., Shr H.L.,
RA Lu T.J., Wang A.H.;
RT "Structures of human MST3 kinase in complex with adenine, ADP and Mn2+.";
RL Acta Crystallogr. D 66:145-154(2010).
RN [24]
RP VARIANTS [LARGE SCALE ANALYSIS] VAL-414 AND ILE-426.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Serine/threonine-protein kinase that acts on both serine and
CC threonine residues and promotes apoptosis in response to stress stimuli
CC and caspase activation. Mediates oxidative-stress-induced cell death by
CC modulating phosphorylation of JNK1-JNK2 (MAPK8 and MAPK9), p38 (MAPK11,
CC MAPK12, MAPK13 and MAPK14) during oxidative stress. Plays a role in a
CC staurosporine-induced caspase-independent apoptotic pathway by
CC regulating the nuclear translocation of AIFM1 and ENDOG and the DNase
CC activity associated with ENDOG. Phosphorylates STK38L on 'Thr-442' and
CC stimulates its kinase activity. In association with STK26 negatively
CC regulates Golgi reorientation in polarized cell migration upon RHO
CC activation (PubMed:27807006). Regulates also cellular migration with
CC alteration of PTPN12 activity and PXN phosphorylation: phosphorylates
CC PTPN12 and inhibits its activity and may regulate PXN phosphorylation
CC through PTPN12. May act as a key regulator of axon regeneration in the
CC optic nerve and radial nerve. {ECO:0000269|PubMed:16314523,
CC ECO:0000269|PubMed:17046825, ECO:0000269|PubMed:19604147,
CC ECO:0000269|PubMed:19782762, ECO:0000269|PubMed:19855390,
CC ECO:0000269|PubMed:27807006}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:15917084};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:15917084};
CC Name=Co(2+); Xref=ChEBI:CHEBI:48828;
CC Evidence={ECO:0000269|PubMed:15917084};
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:15917084};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=12.8 uM for manganese ions {ECO:0000269|PubMed:15917084};
CC KM=34.9 uM for cobalt ions {ECO:0000269|PubMed:15917084};
CC KM=22.7 uM for magnesium ions {ECO:0000269|PubMed:15917084};
CC KM=4.1 uM for zinc ions {ECO:0000269|PubMed:15917084};
CC Vmax=2623.1 pmol/min/mg enzyme for manganese ions
CC {ECO:0000269|PubMed:15917084};
CC Vmax=1746.1 pmol/min/mg enzyme for cobalt ions
CC {ECO:0000269|PubMed:15917084};
CC Vmax=129.1 pmol/min/mg enzyme for magnesium ions
CC {ECO:0000269|PubMed:15917084};
CC Vmax=22.3 pmol/min/mg enzyme for zinc ions
CC {ECO:0000269|PubMed:15917084};
CC -!- SUBUNIT: Monomer (PubMed:20124694). Interacts with CTTNBP2NL
CC (PubMed:18782753). Interacts with RIPOR1 (via C-terminus); this
CC interaction occurs in a PDCD10-dependent and Rho-independent manner
CC (PubMed:27807006). Interacts with PDCD10; this interaction is required
CC for the association of STK24 with RIPOR1 (PubMed:27807006).
CC {ECO:0000269|PubMed:18782753, ECO:0000269|PubMed:20124694,
CC ECO:0000269|PubMed:27807006}.
CC -!- INTERACTION:
CC Q9Y6E0; Q9P2B4: CTTNBP2NL; NbExp=5; IntAct=EBI-740175, EBI-1774273;
CC Q9Y6E0; Q9BUL8: PDCD10; NbExp=11; IntAct=EBI-740175, EBI-740195;
CC Q9Y6E0; Q5VSL9: STRIP1; NbExp=4; IntAct=EBI-740175, EBI-1773588;
CC Q9Y6E0; O43815: STRN; NbExp=4; IntAct=EBI-740175, EBI-1046642;
CC Q9Y6E0; Q9Y228: TRAF3IP3; NbExp=2; IntAct=EBI-740175, EBI-765817;
CC Q9Y6E0-2; Q9Y376: CAB39; NbExp=3; IntAct=EBI-10299018, EBI-306905;
CC Q9Y6E0-2; Q9BUL8: PDCD10; NbExp=9; IntAct=EBI-10299018, EBI-740195;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Membrane. Note=The truncated
CC form (MST3/N) translocates to the nucleus. Colocalizes with STK38L in
CC the membrane.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=B;
CC IsoId=Q9Y6E0-1; Sequence=Displayed;
CC Name=A;
CC IsoId=Q9Y6E0-2; Sequence=VSP_004874;
CC -!- TISSUE SPECIFICITY: Isoform A is ubiquitous. Isoform B is expressed in
CC brain with high expression in hippocampus and cerebral cortex.
CC -!- PTM: Proteolytically processed by caspases during apoptosis.
CC Proteolytic cleavage results in kinase activation, nuclear
CC translocation of the truncated form (MST3/N) and the induction of
CC apoptosis. {ECO:0000269|PubMed:12107159}.
CC -!- PTM: Isoform B is activated by phosphorylation by PKA. Oxidative stress
CC induces phosphorylation. Activated by autophosphorylation at Thr-190
CC and phosphorylation at this site is essential for its function.
CC Manganese, magnesium and cobalt-dependent autophosphorylation is mainly
CC on threonine residues while zinc-dependent autophosphorylation is on
CC both serine and threonine residues. {ECO:0000269|PubMed:10644707,
CC ECO:0000269|PubMed:17046825, ECO:0000269|PubMed:19604147,
CC ECO:0000269|PubMed:20124694}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. STE20 subfamily. {ECO:0000305}.
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DR EMBL; AF024636; AAB82560.1; -; mRNA.
DR EMBL; AF083420; AAD42039.1; -; mRNA.
DR EMBL; AL356423; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL137249; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471085; EAX08986.1; -; Genomic_DNA.
DR EMBL; BC035578; AAH35578.1; -; mRNA.
DR CCDS; CCDS32001.1; -. [Q9Y6E0-2]
DR CCDS; CCDS9488.1; -. [Q9Y6E0-1]
DR RefSeq; NP_001027467.2; NM_001032296.3. [Q9Y6E0-2]
DR RefSeq; NP_003567.2; NM_003576.4. [Q9Y6E0-1]
DR PDB; 3A7F; X-ray; 1.55 A; A=27-315.
DR PDB; 3A7G; X-ray; 2.00 A; A/B=27-315.
DR PDB; 3A7H; X-ray; 1.96 A; A/B=27-315.
DR PDB; 3A7I; X-ray; 1.45 A; A=27-315.
DR PDB; 3A7J; X-ray; 1.50 A; A=27-315.
DR PDB; 3CKW; X-ray; 1.96 A; A=31-323.
DR PDB; 3CKX; X-ray; 2.70 A; A=31-323.
DR PDB; 3ZHP; X-ray; 2.90 A; C/D=31-301.
DR PDB; 4O27; X-ray; 3.19 A; B=30-309.
DR PDB; 4QML; X-ray; 1.88 A; A=24-315.
DR PDB; 4QMM; X-ray; 1.85 A; A=24-315.
DR PDB; 4QMN; X-ray; 2.09 A; A=27-315.
DR PDB; 4QMO; X-ray; 1.90 A; A=24-315.
DR PDB; 4QMP; X-ray; 2.00 A; A=24-315.
DR PDB; 4QMQ; X-ray; 1.77 A; A=24-315.
DR PDB; 4QMS; X-ray; 1.88 A; A=24-315.
DR PDB; 4QMT; X-ray; 1.50 A; A=24-315.
DR PDB; 4QMU; X-ray; 1.55 A; A=24-315.
DR PDB; 4QMV; X-ray; 2.40 A; A=24-315.
DR PDB; 4QMW; X-ray; 1.60 A; A=24-315.
DR PDB; 4QMX; X-ray; 1.88 A; A=24-315.
DR PDB; 4QMY; X-ray; 1.88 A; A=24-315.
DR PDB; 4QMZ; X-ray; 1.88 A; A=24-315.
DR PDB; 4QNA; X-ray; 1.85 A; A=27-315.
DR PDB; 4QO9; X-ray; 2.20 A; A/B=24-315.
DR PDB; 4U8Z; X-ray; 1.63 A; A=24-310.
DR PDB; 4W8D; X-ray; 1.77 A; A=24-310.
DR PDB; 4W8E; X-ray; 1.79 A; A=24-311.
DR PDB; 7B30; X-ray; 2.10 A; A=4-301.
DR PDB; 7B31; X-ray; 1.80 A; A=4-301.
DR PDB; 7B32; X-ray; 1.75 A; A=4-301.
DR PDB; 7B33; X-ray; 1.90 A; A=4-301.
DR PDB; 7B34; X-ray; 2.10 A; A=4-301.
DR PDB; 7B35; X-ray; 2.40 A; A/B=4-301.
DR PDBsum; 3A7F; -.
DR PDBsum; 3A7G; -.
DR PDBsum; 3A7H; -.
DR PDBsum; 3A7I; -.
DR PDBsum; 3A7J; -.
DR PDBsum; 3CKW; -.
DR PDBsum; 3CKX; -.
DR PDBsum; 3ZHP; -.
DR PDBsum; 4O27; -.
DR PDBsum; 4QML; -.
DR PDBsum; 4QMM; -.
DR PDBsum; 4QMN; -.
DR PDBsum; 4QMO; -.
DR PDBsum; 4QMP; -.
DR PDBsum; 4QMQ; -.
DR PDBsum; 4QMS; -.
DR PDBsum; 4QMT; -.
DR PDBsum; 4QMU; -.
DR PDBsum; 4QMV; -.
DR PDBsum; 4QMW; -.
DR PDBsum; 4QMX; -.
DR PDBsum; 4QMY; -.
DR PDBsum; 4QMZ; -.
DR PDBsum; 4QNA; -.
DR PDBsum; 4QO9; -.
DR PDBsum; 4U8Z; -.
DR PDBsum; 4W8D; -.
DR PDBsum; 4W8E; -.
DR PDBsum; 7B30; -.
DR PDBsum; 7B31; -.
DR PDBsum; 7B32; -.
DR PDBsum; 7B33; -.
DR PDBsum; 7B34; -.
DR PDBsum; 7B35; -.
DR AlphaFoldDB; Q9Y6E0; -.
DR SMR; Q9Y6E0; -.
DR BioGRID; 114011; 134.
DR DIP; DIP-40608N; -.
DR IntAct; Q9Y6E0; 61.
DR MINT; Q9Y6E0; -.
DR STRING; 9606.ENSP00000365730; -.
DR BindingDB; Q9Y6E0; -.
DR ChEMBL; CHEMBL5082; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q9Y6E0; -.
DR GuidetoPHARMACOLOGY; 2217; -.
DR GlyGen; Q9Y6E0; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9Y6E0; -.
DR MetOSite; Q9Y6E0; -.
DR PhosphoSitePlus; Q9Y6E0; -.
DR SwissPalm; Q9Y6E0; -.
DR BioMuta; STK24; -.
DR DMDM; 13626607; -.
DR EPD; Q9Y6E0; -.
DR jPOST; Q9Y6E0; -.
DR MassIVE; Q9Y6E0; -.
DR MaxQB; Q9Y6E0; -.
DR PaxDb; Q9Y6E0; -.
DR PeptideAtlas; Q9Y6E0; -.
DR PRIDE; Q9Y6E0; -.
DR ProteomicsDB; 86657; -. [Q9Y6E0-1]
DR ProteomicsDB; 86658; -. [Q9Y6E0-2]
DR Antibodypedia; 10785; 355 antibodies from 33 providers.
DR DNASU; 8428; -.
DR Ensembl; ENST00000376547.7; ENSP00000365730.3; ENSG00000102572.15. [Q9Y6E0-1]
DR Ensembl; ENST00000539966.6; ENSP00000442539.2; ENSG00000102572.15. [Q9Y6E0-2]
DR GeneID; 8428; -.
DR KEGG; hsa:8428; -.
DR MANE-Select; ENST00000539966.6; ENSP00000442539.2; NM_001032296.4; NP_001027467.2. [Q9Y6E0-2]
DR UCSC; uc001vnm.3; human. [Q9Y6E0-1]
DR CTD; 8428; -.
DR DisGeNET; 8428; -.
DR GeneCards; STK24; -.
DR HGNC; HGNC:11403; STK24.
DR HPA; ENSG00000102572; Low tissue specificity.
DR MIM; 604984; gene.
DR neXtProt; NX_Q9Y6E0; -.
DR OpenTargets; ENSG00000102572; -.
DR PharmGKB; PA36210; -.
DR VEuPathDB; HostDB:ENSG00000102572; -.
DR eggNOG; KOG0201; Eukaryota.
DR GeneTree; ENSGT00940000153476; -.
DR InParanoid; Q9Y6E0; -.
DR OMA; YGCFLDG; -.
DR OrthoDB; 967913at2759; -.
DR PhylomeDB; Q9Y6E0; -.
DR TreeFam; TF354217; -.
DR PathwayCommons; Q9Y6E0; -.
DR Reactome; R-HSA-111465; Apoptotic cleavage of cellular proteins.
DR Reactome; R-HSA-75153; Apoptotic execution phase.
DR SABIO-RK; Q9Y6E0; -.
DR SignaLink; Q9Y6E0; -.
DR SIGNOR; Q9Y6E0; -.
DR BioGRID-ORCS; 8428; 18 hits in 1112 CRISPR screens.
DR ChiTaRS; STK24; human.
DR EvolutionaryTrace; Q9Y6E0; -.
DR GeneWiki; STK24; -.
DR GenomeRNAi; 8428; -.
DR Pharos; Q9Y6E0; Tchem.
DR PRO; PR:Q9Y6E0; -.
DR Proteomes; UP000005640; Chromosome 13.
DR RNAct; Q9Y6E0; protein.
DR Bgee; ENSG00000102572; Expressed in secondary oocyte and 208 other tissues.
DR ExpressionAtlas; Q9Y6E0; baseline and differential.
DR Genevisible; Q9Y6E0; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IBA:GO_Central.
DR GO; GO:0000139; C:Golgi membrane; IEA:Ensembl.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004672; F:protein kinase activity; TAS:ProtInc.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0009267; P:cellular response to starvation; IMP:UniProtKB.
DR GO; GO:0097194; P:execution phase of apoptosis; IMP:UniProtKB.
DR GO; GO:0008631; P:intrinsic apoptotic signaling pathway in response to oxidative stress; IMP:UniProtKB.
DR GO; GO:0030336; P:negative regulation of cell migration; IMP:UniProtKB.
DR GO; GO:0048680; P:positive regulation of axon regeneration; IEA:Ensembl.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0048679; P:regulation of axon regeneration; IMP:UniProtKB.
DR GO; GO:0042542; P:response to hydrogen peroxide; IDA:UniProtKB.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR Gene3D; 1.10.12.70; -; 1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR046409; PDC10_dimerisation_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Apoptosis; ATP-binding;
KW Cytoplasm; Kinase; Magnesium; Membrane; Metal-binding; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..443
FT /note="Serine/threonine-protein kinase 24"
FT /id="PRO_0000086711"
FT CHAIN 1..325
FT /note="Serine/threonine-protein kinase 24 36 kDa subunit"
FT /id="PRO_0000413618"
FT CHAIN 326..443
FT /note="Serine/threonine-protein kinase 24 12 kDa subunit"
FT /id="PRO_0000413619"
FT DOMAIN 36..286
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 309..337
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 278..292
FT /note="Bipartite nuclear localization signal"
FT MOTIF 335..386
FT /note="Nuclear export signal (NES)"
FT ACT_SITE 156
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 42..50
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 65
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 112..114
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 161
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT BINDING 174
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT SITE 325..326
FT /note="Cleavage; by caspase-3, caspase-7 and caspase-8"
FT MOD_RES 18
FT /note="Phosphothreonine; by PKA"
FT /evidence="ECO:0000269|PubMed:10644707"
FT MOD_RES 190
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:17046825,
FT ECO:0000269|PubMed:19604147, ECO:0000269|PubMed:20124694,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 320
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983"
FT VAR_SEQ 1..26
FT /note="MDSRAQLWGLALNKRRATLPHPGGST -> MAHSPVQSGLPGMQ (in
FT isoform A)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:9353338"
FT /id="VSP_004874"
FT VARIANT 414
FT /note="A -> V (in dbSNP:rs55953606)"
FT /evidence="ECO:0000269|PubMed:10644707,
FT ECO:0000269|PubMed:17344846"
FT /id="VAR_041148"
FT VARIANT 426
FT /note="L -> I (in dbSNP:rs55897869)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041149"
FT MUTAGEN 18
FT /note="T->A: Loss of phosphorylation by PKA."
FT /evidence="ECO:0000269|PubMed:10644707"
FT MUTAGEN 65
FT /note="K->A: Loss of activity and autophosphorylation."
FT /evidence="ECO:0000269|PubMed:12107159"
FT MUTAGEN 190
FT /note="T->A: Loss of activity and autophosphorylation."
FT /evidence="ECO:0000269|PubMed:17046825"
FT MUTAGEN 321
FT /note="D->N: Loss of proteolytic cleavage by caspases."
FT /evidence="ECO:0000269|PubMed:12107159"
FT STRAND 27..30
FT /evidence="ECO:0007829|PDB:7B32"
FT HELIX 32..34
FT /evidence="ECO:0007829|PDB:3A7I"
FT STRAND 36..44
FT /evidence="ECO:0007829|PDB:3A7I"
FT STRAND 46..55
FT /evidence="ECO:0007829|PDB:3A7I"
FT TURN 56..58
FT /evidence="ECO:0007829|PDB:3A7I"
FT STRAND 61..68
FT /evidence="ECO:0007829|PDB:3A7I"
FT TURN 69..71
FT /evidence="ECO:0007829|PDB:3A7I"
FT TURN 73..75
FT /evidence="ECO:0007829|PDB:4QMT"
FT HELIX 76..88
FT /evidence="ECO:0007829|PDB:3A7I"
FT STRAND 97..103
FT /evidence="ECO:0007829|PDB:3A7I"
FT STRAND 106..112
FT /evidence="ECO:0007829|PDB:3A7I"
FT STRAND 116..118
FT /evidence="ECO:0007829|PDB:3A7J"
FT HELIX 119..123
FT /evidence="ECO:0007829|PDB:3A7I"
FT STRAND 124..126
FT /evidence="ECO:0007829|PDB:3A7H"
FT HELIX 130..149
FT /evidence="ECO:0007829|PDB:3A7I"
FT HELIX 159..161
FT /evidence="ECO:0007829|PDB:3A7I"
FT STRAND 162..164
FT /evidence="ECO:0007829|PDB:3A7I"
FT STRAND 166..168
FT /evidence="ECO:0007829|PDB:3ZHP"
FT STRAND 170..172
FT /evidence="ECO:0007829|PDB:3A7I"
FT STRAND 183..185
FT /evidence="ECO:0007829|PDB:4QO9"
FT STRAND 186..188
FT /evidence="ECO:0007829|PDB:4QMQ"
FT HELIX 195..197
FT /evidence="ECO:0007829|PDB:3A7I"
FT HELIX 200..203
FT /evidence="ECO:0007829|PDB:3A7I"
FT HELIX 211..226
FT /evidence="ECO:0007829|PDB:3A7I"
FT TURN 230..233
FT /evidence="ECO:0007829|PDB:3A7I"
FT HELIX 236..245
FT /evidence="ECO:0007829|PDB:3A7I"
FT STRAND 253..255
FT /evidence="ECO:0007829|PDB:4QML"
FT HELIX 257..266
FT /evidence="ECO:0007829|PDB:3A7I"
FT HELIX 271..273
FT /evidence="ECO:0007829|PDB:3A7I"
FT HELIX 277..280
FT /evidence="ECO:0007829|PDB:3A7I"
FT HELIX 284..289
FT /evidence="ECO:0007829|PDB:3A7I"
FT HELIX 293..296
FT /evidence="ECO:0007829|PDB:3A7I"
FT HELIX 297..309
FT /evidence="ECO:0007829|PDB:3A7I"
FT INIT_MET Q9Y6E0-2:1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692"
FT MOD_RES Q9Y6E0-2:2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692"
FT MOD_RES Q9Y6E0-2:4
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692"
SQ SEQUENCE 443 AA; 49308 MW; 4A9FF1F6B6A88A97 CRC64;
MDSRAQLWGL ALNKRRATLP HPGGSTNLKA DPEELFTKLE KIGKGSFGEV FKGIDNRTQK
VVAIKIIDLE EAEDEIEDIQ QEITVLSQCD SPYVTKYYGS YLKDTKLWII MEYLGGGSAL
DLLEPGPLDE TQIATILREI LKGLDYLHSE KKIHRDIKAA NVLLSEHGEV KLADFGVAGQ
LTDTQIKRNT FVGTPFWMAP EVIKQSAYDS KADIWSLGIT AIELARGEPP HSELHPMKVL
FLIPKNNPPT LEGNYSKPLK EFVEACLNKE PSFRPTAKEL LKHKFILRNA KKTSYLTELI
DRYKRWKAEQ SHDDSSSEDS DAETDGQASG GSDSGDWIFT IREKDPKNLE NGALQPSDLD
RNKMKDIPKR PFSQCLSTII SPLFAELKEK SQACGGNLGS IEELRGAIYL AEEACPGISD
TMVAQLVQRL QRYSLSGGGT SSH
