STK4_HUMAN
ID STK4_HUMAN Reviewed; 487 AA.
AC Q13043; B2RCR8; Q15802; Q4G156; Q5H982; Q6PD60; Q9BR32; Q9NTZ4;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 21-FEB-2001, sequence version 2.
DT 03-AUG-2022, entry version 220.
DE RecName: Full=Serine/threonine-protein kinase 4;
DE EC=2.7.11.1;
DE AltName: Full=Mammalian STE20-like protein kinase 1;
DE Short=MST-1;
DE AltName: Full=STE20-like kinase MST1;
DE AltName: Full=Serine/threonine-protein kinase Krs-2;
DE Contains:
DE RecName: Full=Serine/threonine-protein kinase 4 37kDa subunit;
DE Short=MST1/N;
DE Contains:
DE RecName: Full=Serine/threonine-protein kinase 4 18kDa subunit;
DE Short=MST1/C;
GN Name=STK4; Synonyms=KRS2, MST1;
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 1), AND VARIANT MET-312.
RX PubMed=7665586; DOI=10.1074/jbc.270.37.21695;
RA Creasy C.L., Chernoff J.;
RT "Cloning and characterization of a human protein kinase with homology to
RT Ste20.";
RL J. Biol. Chem. 270:21695-21700(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION.
RX PubMed=8816758; DOI=10.1073/pnas.93.19.10099;
RA Taylor L.K., Wang H.C., Erikson R.L.;
RT "Newly identified stress-responsive protein kinases, Krs-1 and Krs-2.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:10099-10104(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [5]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Bone, Brain, and Liver;
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 [7]
RP PROTEIN SEQUENCE OF 1-7; 16-94; 118-144; 152-181; 232-259; 270-282;
RP 292-301; 333-342; 384-402; 405-413; 421-465 AND 470-481, ACETYLATION AT
RP MET-1, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Mammary carcinoma;
RA Bienvenut W.V., Matallanas D., Cooper W.N., Kolch W.;
RL Submitted (JUL-2007) to UniProtKB.
RN [8]
RP FUNCTION, HOMODIMERIZATION, AND ACTIVITY REGULATION.
RX PubMed=8702870; DOI=10.1074/jbc.271.35.21049;
RA Creasy C.L., Ambrose D.M., Chernoff J.;
RT "The Ste20-like protein kinase, Mst1, dimerizes and contains an inhibitory
RT domain.";
RL J. Biol. Chem. 271:21049-21053(1996).
RN [9]
RP FUNCTION, PROTEOLYTIC PROCESSING, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP ASP-326 AND ASP-349.
RX PubMed=11278283; DOI=10.1074/jbc.m005109200;
RA Lee K.-K., Ohyama T., Yajima N., Tsubuki S., Yonehara S.;
RT "MST, a physiological caspase substrate, highly sensitizes apoptosis both
RT upstream and downstream of caspase activation.";
RL J. Biol. Chem. 276:19276-19285(2001).
RN [10]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=11517310; DOI=10.1073/pnas.181161698;
RA Ura S., Masuyama N., Graves J.D., Gotoh Y.;
RT "Caspase cleavage of MST1 promotes nuclear translocation and chromatin
RT condensation.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:10148-10153(2001).
RN [11]
RP FUNCTION IN PHOSPHORYLATION OF HISTONE H2B.
RX PubMed=12757711; DOI=10.1016/s0092-8674(03)00355-6;
RA Cheung W.L., Ajiro K., Samejima K., Kloc M., Cheung P., Mizzen C.A.,
RA Beeser A., Etkin L.D., Chernoff J., Earnshaw W.C., Allis C.D.;
RT "Apoptotic phosphorylation of histone H2B is mediated by mammalian sterile
RT twenty kinase.";
RL Cell 113:507-517(2003).
RN [12]
RP FUNCTION, ACTIVITY REGULATION, HOMODIMERIZATION, PHOSPHORYLATION AT
RP THR-183, MUTAGENESIS OF LYS-59; THR-175; THR-177; THR-183 AND LEU-444, AND
RP INTERACTION WITH RASSF1 AND NORE1.
RX PubMed=15109305; DOI=10.1042/bj20040025;
RA Praskova M., Khoklatchev A., Ortiz-Vega S., Avruch J.;
RT "Regulation of the MST1 kinase by autophosphorylation, by the growth
RT inhibitory proteins, RASSF1 and NORE1, and by Ras.";
RL Biochem. J. 381:453-462(2004).
RN [13]
RP FUNCTION, AND INTERACTION WITH RASSF1.
RX PubMed=16510573; DOI=10.1158/0008-5472.can-05-2951;
RA Oh H.J., Lee K.-K., Song S.J., Jin M.S., Song M.S., Lee J.H., Im C.R.,
RA Lee J.-O., Yonehara S., Lim D.-S.;
RT "Role of the tumor suppressor RASSF1A in Mst1-mediated apoptosis.";
RL Cancer Res. 66:2562-2569(2006).
RN [14]
RP FUNCTION, AND INTERACTION WITH FOXO3.
RX PubMed=16751106; DOI=10.1016/j.cell.2006.03.046;
RA Lehtinen M.K., Yuan Z., Boag P.R., Yang Y., Villen J., Becker E.B.E.,
RA DiBacco S., de la Iglesia N., Gygi S.P., Blackwell T.K., Bonni A.;
RT "A conserved MST-FOXO signaling pathway mediates oxidative-stress responses
RT and extends life span.";
RL Cell 125:987-1001(2006).
RN [15]
RP INTERACTION WITH SAV1, FUNCTION, AND MUTAGENESIS OF LYS-59.
RX PubMed=16930133; DOI=10.1111/j.1742-4658.2006.05427.x;
RA Callus B.A., Verhagen A.M., Vaux D.L.;
RT "Association of mammalian sterile twenty kinases, Mst1 and Mst2, with
RT hSalvador via C-terminal coiled-coil domains, leads to its stabilization
RT and phosphorylation.";
RL FEBS J. 273:4264-4276(2006).
RN [16]
RP FUNCTION, INTERACTION WITH PKB/AKT1, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=17932490; DOI=10.1038/sj.emboj.7601872;
RA Cinar B., Fang P.K., Lutchman M., Di Vizio D., Adam R.M., Pavlova N.,
RA Rubin M.A., Yelick P.C., Freeman M.R.;
RT "The pro-apoptotic kinase Mst1 and its caspase cleavage products are direct
RT inhibitors of Akt1.";
RL EMBO J. 26:4523-4534(2007).
RN [17]
RP PHOSPHORYLATION AT THR-387, AND INTERACTION WITH PKB/AKT1.
RX PubMed=17726016; DOI=10.1074/jbc.m704542200;
RA Jang S.W., Yang S.J., Srinivasan S., Ye K.;
RT "Akt phosphorylates MstI and prevents its proteolytic activation, blocking
RT FOXO3 phosphorylation and nuclear translocation.";
RL J. Biol. Chem. 282:30836-30844(2007).
RN [18]
RP FUNCTION.
RX PubMed=18328708; DOI=10.1016/j.cub.2008.02.006;
RA Praskova M., Xia F., Avruch J.;
RT "MOBKL1A/MOBKL1B phosphorylation by MST1 and MST2 inhibits cell
RT proliferation.";
RL Curr. Biol. 18:311-321(2008).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-265; SER-320 AND THR-340, 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 [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-320, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [21]
RP REVIEW.
RX PubMed=19484742; DOI=10.1002/biof.47;
RA Hergovich A., Hemmings B.A.;
RT "Mammalian NDR/LATS protein kinases in hippo tumor suppressor signaling.";
RL BioFactors 35:338-345(2009).
RN [22]
RP FUNCTION, AND INTERACTION WITH TNNI3.
RX PubMed=18986304; DOI=10.1042/bj20081340;
RA You B., Yan G., Zhang Z., Yan L., Li J., Ge Q., Jin J.P., Sun J.;
RT "Phosphorylation of cardiac troponin I by mammalian sterile 20-like kinase
RT 1.";
RL Biochem. J. 418:93-101(2009).
RN [23]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT THR-3; SER-320; THR-340; THR-367; SER-410 AND SER-414, AND
RP IDENTIFICATION BY MASS 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 [24]
RP FUNCTION, INTERACTION WITH RASSF2, AND SUBCELLULAR LOCATION.
RX PubMed=19525978; DOI=10.1038/onc.2009.152;
RA Cooper W.N., Hesson L.B., Matallanas D., Dallol A., von Kriegsheim A.,
RA Ward R., Kolch W., Latif F.;
RT "RASSF2 associates with and stabilizes the proapoptotic kinase MST2.";
RL Oncogene 28:2988-2998(2009).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-320, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [26]
RP CAUTION.
RX PubMed=19940129; DOI=10.1074/jbc.m109.059675;
RA Yuan Z., Kim D., Shu S., Wu J., Guo J., Xiao L., Kaneko S., Coppola D.,
RA Cheng J.Q.;
RT "Phosphoinositide 3-kinase/Akt inhibits MST1-mediated pro-apoptotic
RT signaling through phosphorylation of threonine 120.";
RL J. Biol. Chem. 285:3815-3824(2010).
RN [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-320, AND IDENTIFICATION BY
RP MASS 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 [28]
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 [29]
RP FUNCTION.
RX PubMed=21245099; DOI=10.1158/0008-5472.can-10-2203;
RA Valis K., Prochazka L., Boura E., Chladova J., Obsil T., Rohlena J.,
RA Truksa J., Dong L.F., Ralph S.J., Neuzil J.;
RT "Hippo/Mst1 stimulates transcription of the proapoptotic mediator NOXA in a
RT FoxO1-dependent manner.";
RL Cancer Res. 71:946-954(2011).
RN [30]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH AR.
RX PubMed=21512132; DOI=10.1158/0008-5472.can-10-4532;
RA Cinar B., Collak F.K., Lopez D., Akgul S., Mukhopadhyay N.K.,
RA Kilicarslan M., Gioeli D.G., Freeman M.R.;
RT "MST1 is a multifunctional caspase-independent inhibitor of androgenic
RT signaling.";
RL Cancer Res. 71:4303-4313(2011).
RN [31]
RP INTERACTION WITH RASSF1, AND ACTIVITY REGULATION.
RX PubMed=21199877; DOI=10.1074/jbc.m110.178210;
RA Guo C., Zhang X., Pfeifer G.P.;
RT "The tumor suppressor RASSF1A prevents dephosphorylation of the mammalian
RT STE20-like kinases MST1 and MST2.";
RL J. Biol. Chem. 286:6253-6261(2011).
RN [32]
RP FUNCTION, AND INTERACTION WITH SIRT1.
RX PubMed=21212262; DOI=10.1074/jbc.m110.182543;
RA Yuan F., Xie Q., Wu J., Bai Y., Mao B., Dong Y., Bi W., Ji G., Tao W.,
RA Wang Y., Yuan Z.;
RT "MST1 promotes apoptosis through regulating Sirt1-dependent p53
RT deacetylation.";
RL J. Biol. Chem. 286:6940-6945(2011).
RN [33]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-320, AND IDENTIFICATION BY
RP MASS 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 [34]
RP INVOLVEMENT IN TIIAC.
RX PubMed=22294732; DOI=10.1182/blood-2011-09-378158;
RA Abdollahpour H., Appaswamy G., Kotlarz D., Diestelhorst J., Beier R.,
RA Schaffer A.A., Gertz E.M., Schambach A., Kreipe H.H., Pfeifer D.,
RA Engelhardt K.R., Rezaei N., Grimbacher B., Lohrmann S., Sherkat R.,
RA Klein C.;
RT "The phenotype of human STK4 deficiency.";
RL Blood 119:3450-3457(2012).
RN [35]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [36]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [37]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-340; THR-387; SER-410 AND
RP SER-414, AND IDENTIFICATION BY 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 [38]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-320, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [39]
RP INTERACTION WITH MARK3 AND DLG5.
RX PubMed=28087714; DOI=10.1101/gad.284539.116;
RA Kwan J., Sczaniecka A., Arash E.H., Nguyen L., Chen C.C., Ratkovic S.,
RA Klezovitch O., Attisano L., McNeill H., Emili A., Vasioukhin V.;
RT "DLG5 connects cell polarity and Hippo signaling protein networks by
RT linking PAR-1 with MST1/2.";
RL Genes Dev. 30:2696-2709(2016).
RN [40]
RP CAUTION, AND RETRACTION NOTICE OF PUBMED:28087714.
RX PubMed=27825096; DOI=10.1074/jbc.a109.059675;
RA Yuan Z., Kim D., Shu S., Wu J., Guo J., Xiao L., Kaneko S., Coppola D.,
RA Cheng J.Q.;
RL J. Biol. Chem. 291:22858-22858(2016).
RN [41]
RP INTERACTION WITH SCRIB.
RX PubMed=28169360; DOI=10.1038/srep42125;
RA Liu J., Li J., Li P., Wang Y., Liang Z., Jiang Y., Li J., Feng C., Wang R.,
RA Chen H., Zhou C., Zhang J., Yang J., Liu P.;
RT "Loss of DLG5 promotes breast cancer malignancy by inhibiting the Hippo
RT signaling pathway.";
RL Sci. Rep. 7:42125-42125(2017).
RN [42]
RP VARIANTS [LARGE SCALE ANALYSIS] ASN-162; GLN-310; MET-312; THR-355 AND
RP LEU-416.
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: Stress-activated, pro-apoptotic kinase which, following
CC caspase-cleavage, enters the nucleus and induces chromatin condensation
CC followed by internucleosomal DNA fragmentation. Key component of the
CC Hippo signaling pathway which plays a pivotal role in organ size
CC control and tumor suppression by restricting proliferation and
CC promoting apoptosis. The core of this pathway is composed of a kinase
CC cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory
CC protein SAV1, phosphorylates and activates LATS1/2 in complex with its
CC regulatory protein MOB1, which in turn phosphorylates and inactivates
CC YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS2
CC inhibits its translocation into the nucleus to regulate cellular genes
CC important for cell proliferation, cell death, and cell migration.
CC STK3/MST2 and STK4/MST1 are required to repress proliferation of mature
CC hepatocytes, to prevent activation of facultative adult liver stem
CC cells (oval cells), and to inhibit tumor formation (By similarity).
CC Phosphorylates 'Ser-14' of histone H2B (H2BS14ph) during apoptosis.
CC Phosphorylates FOXO3 upon oxidative stress, which results in its
CC nuclear translocation and cell death initiation. Phosphorylates
CC MOBKL1A, MOBKL1B and RASSF2. Phosphorylates TNNI3 (cardiac Tn-I) and
CC alters its binding affinity to TNNC1 (cardiac Tn-C) and TNNT2 (cardiac
CC Tn-T). Phosphorylates FOXO1 on 'Ser-212' and regulates its activation
CC and stimulates transcription of PMAIP1 in a FOXO1-dependent manner.
CC Phosphorylates SIRT1 and inhibits SIRT1-mediated p53/TP53
CC deacetylation, thereby promoting p53/TP53 dependent transcription and
CC apoptosis upon DNA damage. Acts as an inhibitor of PKB/AKT1.
CC Phosphorylates AR on 'Ser-650' and suppresses its activity by
CC intersecting with PKB/AKT1 signaling and antagonizing formation of AR-
CC chromatin complexes. {ECO:0000250|UniProtKB:Q9JI11,
CC ECO:0000269|PubMed:11278283, ECO:0000269|PubMed:11517310,
CC ECO:0000269|PubMed:12757711, ECO:0000269|PubMed:15109305,
CC ECO:0000269|PubMed:16510573, ECO:0000269|PubMed:16751106,
CC ECO:0000269|PubMed:16930133, ECO:0000269|PubMed:17932490,
CC ECO:0000269|PubMed:18328708, ECO:0000269|PubMed:18986304,
CC ECO:0000269|PubMed:19525978, ECO:0000269|PubMed:21212262,
CC ECO:0000269|PubMed:21245099, ECO:0000269|PubMed:21512132,
CC ECO:0000269|PubMed:8702870, ECO:0000269|PubMed:8816758}.
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 -!- ACTIVITY REGULATION: Inhibited by the C-terminal non-catalytic region.
CC Activated by caspase-cleavage. Full activation also requires
CC homodimerization and autophosphorylation of Thr-183. Activated by
CC RASSF1 which acts by preventing its dephosphorylation.
CC {ECO:0000269|PubMed:15109305, ECO:0000269|PubMed:21199877,
CC ECO:0000269|PubMed:8702870}.
CC -!- SUBUNIT: Homodimer; mediated via the coiled-coil region. Interacts with
CC NORE1, which inhibits autoactivation. Interacts with and stabilizes
CC SAV1. Interacts with RASSF1. Interacts with FOXO3. Interacts with
CC RASSF2 (via SARAH domain). Interacts with AR, PKB/AKT1, TNNI3 and
CC SIRT1. Interacts with DLG5 (via PDZ domain 3). Interacts with MARK3 in
CC the presence of DLG5 (PubMed:28087714). Interacts with SCRIB in the
CC presence of DLG5 (PubMed:28169360). {ECO:0000250|UniProtKB:Q13188,
CC ECO:0000269|PubMed:15109305, ECO:0000269|PubMed:16510573,
CC ECO:0000269|PubMed:16751106, ECO:0000269|PubMed:16930133,
CC ECO:0000269|PubMed:17726016, ECO:0000269|PubMed:17932490,
CC ECO:0000269|PubMed:18986304, ECO:0000269|PubMed:19525978,
CC ECO:0000269|PubMed:21199877, ECO:0000269|PubMed:21212262,
CC ECO:0000269|PubMed:21512132, ECO:0000269|PubMed:28087714,
CC ECO:0000269|PubMed:28169360}.
CC -!- INTERACTION:
CC Q13043; P31749: AKT1; NbExp=13; IntAct=EBI-367376, EBI-296087;
CC Q13043; O95166: GABARAP; NbExp=2; IntAct=EBI-367376, EBI-712001;
CC Q13043; Q9H0R8: GABARAPL1; NbExp=2; IntAct=EBI-367376, EBI-746969;
CC Q13043; P60520: GABARAPL2; NbExp=2; IntAct=EBI-367376, EBI-720116;
CC Q13043; Q9GZQ8: MAP1LC3B; NbExp=7; IntAct=EBI-367376, EBI-373144;
CC Q13043; Q9H8S9: MOB1A; NbExp=9; IntAct=EBI-367376, EBI-748229;
CC Q13043; Q7L9L4: MOB1B; NbExp=4; IntAct=EBI-367376, EBI-2558745;
CC Q13043; Q06830: PRDX1; NbExp=11; IntAct=EBI-367376, EBI-353193;
CC Q13043; Q9NS23-2: RASSF1; NbExp=4; IntAct=EBI-367376, EBI-438698;
CC Q13043; P50749: RASSF2; NbExp=16; IntAct=EBI-367376, EBI-960081;
CC Q13043; Q86WH2: RASSF3; NbExp=6; IntAct=EBI-367376, EBI-2845202;
CC Q13043; Q9H2L5: RASSF4; NbExp=6; IntAct=EBI-367376, EBI-2933362;
CC Q13043; Q8WWW0: RASSF5; NbExp=8; IntAct=EBI-367376, EBI-367390;
CC Q13043; Q8WWW0-2: RASSF5; NbExp=4; IntAct=EBI-367376, EBI-960502;
CC Q13043; Q8WWW0-3: RASSF5; NbExp=2; IntAct=EBI-367376, EBI-960507;
CC Q13043; Q6ZTQ3: RASSF6; NbExp=4; IntAct=EBI-367376, EBI-2933412;
CC Q13043; Q9H4B6: SAV1; NbExp=19; IntAct=EBI-367376, EBI-1017775;
CC Q13043; Q14BN4: SLMAP; NbExp=7; IntAct=EBI-367376, EBI-1043216;
CC Q13043; Q13188: STK3; NbExp=19; IntAct=EBI-367376, EBI-992580;
CC Q13043; Q13043: STK4; NbExp=4; IntAct=EBI-367376, EBI-367376;
CC Q13043; P35700: Prdx1; Xeno; NbExp=3; IntAct=EBI-367376, EBI-444948;
CC Q13043; Q91VJ4: Stk38; Xeno; NbExp=2; IntAct=EBI-367376, EBI-2527046;
CC Q13043-1; Q8WWW0-1: RASSF5; NbExp=3; IntAct=EBI-15638366, EBI-960496;
CC Q13043-1; Q9H4B6: SAV1; NbExp=2; IntAct=EBI-15638366, EBI-1017775;
CC Q13043-1; Q13043-1: STK4; NbExp=4; IntAct=EBI-15638366, EBI-15638366;
CC Q13043-2; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-14280485, EBI-742054;
CC Q13043-2; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-14280485, EBI-79165;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=The caspase-cleaved form
CC cycles between the nucleus and cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q13043-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q13043-2; Sequence=VSP_019851, VSP_019852;
CC -!- TISSUE SPECIFICITY: Expressed in prostate cancer and levels increase
CC from the normal to the malignant state (at protein level). Ubiquitously
CC expressed. {ECO:0000269|PubMed:17932490}.
CC -!- INDUCTION: Activity increases during mitosis.
CC -!- PTM: Autophosphorylated on serine and threonine residues.
CC Phosphorylation at Thr-387 by PKB/AKT1, leads to inhibition of its:
CC kinase activity, nuclear translocation and autophosphorylation at Thr-
CC 183. It also diminishes its cleavage by caspases and its ability to
CC phosphorylate FOXO3. {ECO:0000269|PubMed:11278283,
CC ECO:0000269|PubMed:15109305, ECO:0000269|PubMed:17726016,
CC ECO:0000269|PubMed:19940129}.
CC -!- PTM: Proteolytically cleaved by caspase-3 during apoptosis at Asp-326
CC and Asp-349 resulting in a 37 kDa or a 39 kDa subunit respectively. The
CC 39 kDa subunit is further cleaved into the 37 kDa form. Proteolytic
CC cleavage results in kinase activation and nuclear translocation of the
CC truncated form (MST1/N). It is less likely that cleavage at Asp-349 is
CC a prerequisite for activation as this site is not conserved in the
CC murine ortholog. {ECO:0000269|PubMed:11278283}.
CC -!- DISEASE: T-cell immunodeficiency, recurrent infections, and
CC autoimmunity with or without cardiac malformations (TIIAC)
CC [MIM:614868]: A primary T-cell immunodeficiency syndrome characterized
CC by progressive loss of naive T-cells, recurrent bacterial, viral, and
CC fungal infections, warts, and abscesses, autoimmune manifestations, and
CC cardiac malformations, including atrial septal defect.
CC {ECO:0000269|PubMed:22294732}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. STE20 subfamily. {ECO:0000305}.
CC -!- CAUTION: Was originally thought to be phosphorylated at Thr-120
CC (PubMed:19940129). However, this work has been retracted
CC (PubMed:27825096). {ECO:0000269|PubMed:19940129,
CC ECO:0000305|PubMed:27825096}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH29511.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
CC Sequence=AAH58916.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/STK4ID42440ch20q11.html";
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DR EMBL; U18297; AAA83254.1; -; mRNA.
DR EMBL; U60207; AAB17262.1; -; mRNA.
DR EMBL; AK315238; BAG37665.1; -; mRNA.
DR EMBL; Z93016; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL109839; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471077; EAW75882.1; -; Genomic_DNA.
DR EMBL; BC029511; AAH29511.1; ALT_SEQ; mRNA.
DR EMBL; BC058916; AAH58916.1; ALT_SEQ; mRNA.
DR EMBL; BC093768; AAH93768.1; -; mRNA.
DR CCDS; CCDS13341.1; -. [Q13043-1]
DR CCDS; CCDS86957.1; -. [Q13043-2]
DR RefSeq; NP_006273.1; NM_006282.3. [Q13043-1]
DR RefSeq; XP_005260590.1; XM_005260533.2.
DR PDB; 2JO8; NMR; -; A/B=432-480.
DR PDB; 3COM; X-ray; 2.20 A; A/B=2-311.
DR PDB; 4NR2; X-ray; 2.00 A; A/B/C/D/E/F/G/H=432-480.
DR PDB; 4OH8; X-ray; 2.28 A; A=432-480.
DR PDB; 5TWG; X-ray; 2.30 A; E=343-356.
DR PDB; 5TWH; X-ray; 2.50 A; E=358-374.
DR PDB; 6YAT; X-ray; 2.58 A; A/B=1-311.
DR PDBsum; 2JO8; -.
DR PDBsum; 3COM; -.
DR PDBsum; 4NR2; -.
DR PDBsum; 4OH8; -.
DR PDBsum; 5TWG; -.
DR PDBsum; 5TWH; -.
DR PDBsum; 6YAT; -.
DR AlphaFoldDB; Q13043; -.
DR SMR; Q13043; -.
DR BioGRID; 112665; 120.
DR CORUM; Q13043; -.
DR DIP; DIP-32491N; -.
DR ELM; Q13043; -.
DR IntAct; Q13043; 186.
DR MINT; Q13043; -.
DR STRING; 9606.ENSP00000361892; -.
DR BindingDB; Q13043; -.
DR ChEMBL; CHEMBL4598; -.
DR DrugCentral; Q13043; -.
DR GuidetoPHARMACOLOGY; 2225; -.
DR iPTMnet; Q13043; -.
DR MetOSite; Q13043; -.
DR PhosphoSitePlus; Q13043; -.
DR BioMuta; STK4; -.
DR DMDM; 13124559; -.
DR EPD; Q13043; -.
DR jPOST; Q13043; -.
DR MassIVE; Q13043; -.
DR MaxQB; Q13043; -.
DR PaxDb; Q13043; -.
DR PeptideAtlas; Q13043; -.
DR PRIDE; Q13043; -.
DR ProteomicsDB; 59119; -. [Q13043-1]
DR ProteomicsDB; 59120; -. [Q13043-2]
DR Antibodypedia; 3325; 508 antibodies from 42 providers.
DR DNASU; 6789; -.
DR Ensembl; ENST00000372801.5; ENSP00000361887.1; ENSG00000101109.12. [Q13043-2]
DR Ensembl; ENST00000372806.8; ENSP00000361892.3; ENSG00000101109.12. [Q13043-1]
DR GeneID; 6789; -.
DR KEGG; hsa:6789; -.
DR MANE-Select; ENST00000372806.8; ENSP00000361892.3; NM_006282.5; NP_006273.1.
DR UCSC; uc002xnb.4; human. [Q13043-1]
DR CTD; 6789; -.
DR DisGeNET; 6789; -.
DR GeneCards; STK4; -.
DR HGNC; HGNC:11408; STK4.
DR HPA; ENSG00000101109; Tissue enhanced (bone).
DR MalaCards; STK4; -.
DR MIM; 604965; gene.
DR MIM; 614868; phenotype.
DR neXtProt; NX_Q13043; -.
DR OpenTargets; ENSG00000101109; -.
DR Orphanet; 314689; Combined immunodeficiency due to STK4 deficiency.
DR PharmGKB; PA36215; -.
DR VEuPathDB; HostDB:ENSG00000101109; -.
DR eggNOG; KOG0574; Eukaryota.
DR GeneTree; ENSGT00940000159787; -.
DR InParanoid; Q13043; -.
DR OMA; FLKSWSV; -.
DR OrthoDB; 967913at2759; -.
DR PhylomeDB; Q13043; -.
DR TreeFam; TF354217; -.
DR BRENDA; 2.7.11.1; 2681.
DR PathwayCommons; Q13043; -.
DR Reactome; R-HSA-2028269; Signaling by Hippo.
DR SignaLink; Q13043; -.
DR SIGNOR; Q13043; -.
DR BioGRID-ORCS; 6789; 11 hits in 1111 CRISPR screens.
DR ChiTaRS; STK4; human.
DR EvolutionaryTrace; Q13043; -.
DR GeneWiki; STK4; -.
DR GenomeRNAi; 6789; -.
DR Pharos; Q13043; Tchem.
DR PRO; PR:Q13043; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q13043; protein.
DR Bgee; ENSG00000101109; Expressed in colonic epithelium and 188 other tissues.
DR ExpressionAtlas; Q13043; baseline and differential.
DR Genevisible; Q13043; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:MGI.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:MGI.
DR GO; GO:0004672; F:protein kinase activity; IGI:MGI.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0043539; F:protein serine/threonine kinase activator activity; TAS:BHF-UCL.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IDA:UniProtKB.
DR GO; GO:0001569; P:branching involved in blood vessel morphogenesis; IEA:Ensembl.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; IEA:Ensembl.
DR GO; GO:0060706; P:cell differentiation involved in embryonic placenta development; IEA:Ensembl.
DR GO; GO:0000902; P:cell morphogenesis; IDA:MGI.
DR GO; GO:0007417; P:central nervous system development; IEA:Ensembl.
DR GO; GO:0003157; P:endocardium development; IEA:Ensembl.
DR GO; GO:0050673; P:epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; IEA:Ensembl.
DR GO; GO:0097284; P:hepatocyte apoptotic process; IEA:Ensembl.
DR GO; GO:0035329; P:hippo signaling; IDA:BHF-UCL.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:UniProtKB.
DR GO; GO:0030216; P:keratinocyte differentiation; IEA:Ensembl.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IMP:BHF-UCL.
DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:0046621; P:negative regulation of organ growth; IEA:Ensembl.
DR GO; GO:0001841; P:neural tube formation; IEA:Ensembl.
DR GO; GO:0035265; P:organ growth; IEA:Ensembl.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:1902043; P:positive regulation of extrinsic apoptotic signaling pathway via death domain receptors; IEA:Ensembl.
DR GO; GO:0045600; P:positive regulation of fat cell differentiation; IEA:Ensembl.
DR GO; GO:1903945; P:positive regulation of hepatocyte apoptotic process; IEA:Ensembl.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IDA:MGI.
DR GO; GO:0032092; P:positive regulation of protein binding; IDA:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:MGI.
DR GO; GO:1904237; P:positive regulation of substrate-dependent cell migration, cell attachment to substrate; IEA:Ensembl.
DR GO; GO:0060215; P:primitive hemopoiesis; IEA:Ensembl.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:MGI.
DR GO; GO:0006606; P:protein import into nucleus; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; IDA:MGI.
DR GO; GO:0051262; P:protein tetramerization; IEA:InterPro.
DR GO; GO:0060800; P:regulation of cell differentiation involved in embryonic placenta development; IEA:Ensembl.
DR GO; GO:0043408; P:regulation of MAPK cascade; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR Gene3D; 4.10.170.10; -; 1.
DR IDEAL; IID00168; -.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR024205; Mst1_SARAH_domain.
DR InterPro; IPR036674; p53_tetramer_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR011524; SARAH_dom.
DR Pfam; PF11629; Mst1_SARAH; 1.
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.
DR PROSITE; PS50951; SARAH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Apoptosis; ATP-binding;
KW Coiled coil; Cytoplasm; Direct protein sequencing; Kinase; Magnesium;
KW Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..487
FT /note="Serine/threonine-protein kinase 4"
FT /id="PRO_0000086691"
FT CHAIN 1..326
FT /note="Serine/threonine-protein kinase 4 37kDa subunit"
FT /id="PRO_0000413735"
FT CHAIN 327..487
FT /note="Serine/threonine-protein kinase 4 18kDa subunit"
FT /id="PRO_0000413736"
FT DOMAIN 30..281
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 433..480
FT /note="SARAH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00310"
FT REGION 303..332
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 290..310
FT /evidence="ECO:0000255"
FT ACT_SITE 149
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 36..44
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 59
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT SITE 326..327
FT /note="Cleavage; by caspase-3"
FT SITE 349..350
FT /note="Cleavage; by caspase-3"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000269|Ref.7, ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378"
FT MOD_RES 3
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 183
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:15109305"
FT MOD_RES 265
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 320
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:24275569"
FT MOD_RES 340
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:23186163"
FT MOD_RES 367
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 387
FT /note="Phosphothreonine; by PKB/AKT1"
FT /evidence="ECO:0000269|PubMed:17726016,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 410
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 414
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 433
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9JI11"
FT VAR_SEQ 436..462
FT /note="LKSWTVEDLQKRLLALDPMMEQEIEEI -> KTSQEQQSGKDICIQNCQGNL
FT LCRYAF (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_019851"
FT VAR_SEQ 463..487
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_019852"
FT VARIANT 162
FT /note="H -> N (in dbSNP:rs55850759)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041123"
FT VARIANT 310
FT /note="R -> Q (in dbSNP:rs35447878)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041124"
FT VARIANT 312
FT /note="V -> M (in dbSNP:rs17420378)"
FT /evidence="ECO:0000269|PubMed:17344846,
FT ECO:0000269|PubMed:7665586"
FT /id="VAR_027040"
FT VARIANT 355
FT /note="I -> T (in dbSNP:rs35944046)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041125"
FT VARIANT 416
FT /note="P -> L (in dbSNP:rs33963346)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041126"
FT MUTAGEN 59
FT /note="K->R: Loss of activity."
FT /evidence="ECO:0000269|PubMed:15109305,
FT ECO:0000269|PubMed:16930133"
FT MUTAGEN 175
FT /note="T->A: No effect on activity."
FT /evidence="ECO:0000269|PubMed:15109305"
FT MUTAGEN 177
FT /note="T->A: No effect on activity."
FT /evidence="ECO:0000269|PubMed:15109305"
FT MUTAGEN 183
FT /note="T->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:15109305"
FT MUTAGEN 326
FT /note="D->N: Resistant to proteolytic cleavage by caspase
FT during apoptosis; when associated with N-349."
FT /evidence="ECO:0000269|PubMed:11278283"
FT MUTAGEN 349
FT /note="D->N: Resistant to proteolytic cleavage by caspase
FT during apoptosis; when associated with N-326."
FT /evidence="ECO:0000269|PubMed:11278283"
FT MUTAGEN 444
FT /note="L->P: Loss of homodimerization, activation, and
FT autophosphorylation."
FT /evidence="ECO:0000269|PubMed:15109305"
FT CONFLICT 222
FT /note="P -> R (in Ref. 1; AAA83254)"
FT /evidence="ECO:0000305"
FT HELIX 19..22
FT /evidence="ECO:0007829|PDB:3COM"
FT HELIX 26..29
FT /evidence="ECO:0007829|PDB:6YAT"
FT STRAND 30..35
FT /evidence="ECO:0007829|PDB:3COM"
FT STRAND 43..49
FT /evidence="ECO:0007829|PDB:3COM"
FT TURN 50..52
FT /evidence="ECO:0007829|PDB:3COM"
FT STRAND 55..62
FT /evidence="ECO:0007829|PDB:3COM"
FT HELIX 68..78
FT /evidence="ECO:0007829|PDB:3COM"
FT STRAND 88..94
FT /evidence="ECO:0007829|PDB:3COM"
FT STRAND 97..103
FT /evidence="ECO:0007829|PDB:3COM"
FT HELIX 110..117
FT /evidence="ECO:0007829|PDB:3COM"
FT HELIX 123..142
FT /evidence="ECO:0007829|PDB:3COM"
FT HELIX 152..154
FT /evidence="ECO:0007829|PDB:3COM"
FT STRAND 155..157
FT /evidence="ECO:0007829|PDB:3COM"
FT STRAND 163..165
FT /evidence="ECO:0007829|PDB:3COM"
FT HELIX 188..190
FT /evidence="ECO:0007829|PDB:3COM"
FT HELIX 193..196
FT /evidence="ECO:0007829|PDB:3COM"
FT STRAND 197..199
FT /evidence="ECO:0007829|PDB:3COM"
FT HELIX 205..219
FT /evidence="ECO:0007829|PDB:3COM"
FT TURN 223..226
FT /evidence="ECO:0007829|PDB:3COM"
FT HELIX 229..238
FT /evidence="ECO:0007829|PDB:3COM"
FT HELIX 247..249
FT /evidence="ECO:0007829|PDB:3COM"
FT HELIX 252..261
FT /evidence="ECO:0007829|PDB:3COM"
FT TURN 266..268
FT /evidence="ECO:0007829|PDB:3COM"
FT HELIX 272..275
FT /evidence="ECO:0007829|PDB:3COM"
FT HELIX 279..282
FT /evidence="ECO:0007829|PDB:3COM"
FT HELIX 287..290
FT /evidence="ECO:0007829|PDB:3COM"
FT HELIX 291..297
FT /evidence="ECO:0007829|PDB:3COM"
FT HELIX 433..436
FT /evidence="ECO:0007829|PDB:4NR2"
FT HELIX 441..478
FT /evidence="ECO:0007829|PDB:4NR2"
SQ SEQUENCE 487 AA; 55630 MW; 150758EBC5F77D5C CRC64;
METVQLRNPP RRQLKKLDED SLTKQPEEVF DVLEKLGEGS YGSVYKAIHK ETGQIVAIKQ
VPVESDLQEI IKEISIMQQC DSPHVVKYYG SYFKNTDLWI VMEYCGAGSV SDIIRLRNKT
LTEDEIATIL QSTLKGLEYL HFMRKIHRDI KAGNILLNTE GHAKLADFGV AGQLTDTMAK
RNTVIGTPFW MAPEVIQEIG YNCVADIWSL GITAIEMAEG KPPYADIHPM RAIFMIPTNP
PPTFRKPELW SDNFTDFVKQ CLVKSPEQRA TATQLLQHPF VRSAKGVSIL RDLINEAMDV
KLKRQESQQR EVDQDDEENS EEDEMDSGTM VRAVGDEMGT VRVASTMTDG ANTMIEHDDT
LPSQLGTMVI NAEDEEEEGT MKRRDETMQP AKPSFLEYFE QKEKENQINS FGKSVPGPLK
NSSDWKIPQD GDYEFLKSWT VEDLQKRLLA LDPMMEQEIE EIRQKYQSKR QPILDAIEAK
KRRQQNF
