STK3_HUMAN
ID STK3_HUMAN Reviewed; 491 AA.
AC Q13188; A8K722; B3KYA7; Q15445; Q15801; Q96FM6;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2004, sequence version 2.
DT 03-AUG-2022, entry version 217.
DE RecName: Full=Serine/threonine-protein kinase 3;
DE EC=2.7.11.1;
DE AltName: Full=Mammalian STE20-like protein kinase 2;
DE Short=MST-2;
DE AltName: Full=STE20-like kinase MST2;
DE AltName: Full=Serine/threonine-protein kinase Krs-1;
DE Contains:
DE RecName: Full=Serine/threonine-protein kinase 3 36kDa subunit;
DE Short=MST2/N;
DE Contains:
DE RecName: Full=Serine/threonine-protein kinase 3 20kDa subunit;
DE Short=MST2/C;
GN Name=STK3; Synonyms=KRS1, MST2;
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), FUNCTION, AUTOPHOSPHORYLATION, AND
RP TISSUE SPECIFICITY.
RX PubMed=8566796; DOI=10.1016/0378-1119(95)00653-2;
RA Creasy C.L., Chernoff J.;
RT "Cloning and characterization of a member of the MST subfamily of Ste20-
RT like kinases.";
RL Gene 167:303-306(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] (ISOFORMS 1 AND 2).
RC TISSUE=Uterus;
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=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Eye;
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 1-8; 13-43; 57-69; 85-91; 115-128; 133-141; 149-178;
RP 229-256; 267-298; 329-338; 382-403; 423-451; 462-467 AND 474-485,
RP ACETYLATION AT 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 NUCLEOTIDE SEQUENCE [MRNA] OF 96-203.
RX PubMed=8274451;
RA Schultz S.J., Nigg E.A.;
RT "Identification of 21 novel human protein kinases, including 3 members of a
RT family related to the cell cycle regulator nimA of Aspergillus nidulans.";
RL Cell Growth Differ. 4:821-830(1993).
RN [9]
RP SUBCELLULAR LOCATION, PROTEOLYTIC PROCESSING, AND MUTAGENESIS OF ASP-322.
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 INTERACTION WITH RAF1, AND ACTIVITY REGULATION.
RX PubMed=15618521; DOI=10.1126/science.1103233;
RA O'Neill E., Rushworth L., Baccarini M., Kolch W.;
RT "Role of the kinase MST2 in suppression of apoptosis by the proto-oncogene
RT product Raf-1.";
RL Science 306:2267-2270(2004).
RN [11]
RP INTERACTION WITH SAV1, AND FUNCTION.
RX PubMed=15688006; DOI=10.1038/sj.onc.1208445;
RA Chan E.H.Y., Nousiainen M., Chalamalasetty R.B., Schaefer A., Nigg E.A.,
RA Sillje H.H.W.;
RT "The Ste20-like kinase Mst2 activates the human large tumor suppressor
RT kinase Lats1.";
RL Oncogene 24:2076-2086(2005).
RN [12]
RP 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 [13]
RP FUNCTION, INTERACTION WITH SAV1, AND MUTAGENESIS OF LYS-56.
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 [14]
RP FUNCTION, AND INDUCTION.
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 [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-316 AND SER-444, 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 [16]
RP FUNCTION, AND INTERACTION WITH STK38 AND MOBKL1B.
RX PubMed=18362890; DOI=10.1038/onc.2008.66;
RA Hirabayashi S., Nakagawa K., Sumita K., Hidaka S., Kawai T., Ikeda M.,
RA Kawata A., Ohno K., Hata Y.;
RT "Threonine 74 of MOB1 is a putative key phosphorylation site by MST2 to
RT form the scaffold to activate nuclear Dbf2-related kinase 1.";
RL Oncogene 27:4281-4292(2008).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-316, 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 [18]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [19]
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 [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-15; SER-316; THR-336 AND
RP SER-444, AND 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 [21]
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 [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-316, 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 [23]
RP PHOSPHORYLATION AT THR-117 AND THR-384, AND INTERACTION WITH PKB/AKT1.
RX PubMed=20086174; DOI=10.1158/0008-5472.can-09-3147;
RA Romano D., Matallanas D., Weitsman G., Preisinger C., Ng T., Kolch W.;
RT "Proapoptotic kinase MST2 coordinates signaling crosstalk between RASSF1A,
RT Raf-1, and Akt.";
RL Cancer Res. 70:1195-1203(2010).
RN [24]
RP SUBCELLULAR LOCATION.
RX PubMed=21145499; DOI=10.1016/j.devcel.2010.11.012;
RA Varelas X., Samavarchi-Tehrani P., Narimatsu M., Weiss A., Cockburn K.,
RA Larsen B.G., Rossant J., Wrana J.L.;
RT "The Crumbs complex couples cell density sensing to Hippo-dependent control
RT of the TGF-beta-SMAD pathway.";
RL Dev. Cell 19:831-844(2010).
RN [25]
RP FUNCTION.
RX PubMed=20212043; DOI=10.1074/jbc.m109.078915;
RA Kilili G.K., Kyriakis J.M.;
RT "Mammalian Ste20-like kinase (Mst2) indirectly supports Raf-1/ERK pathway
RT activity via maintenance of protein phosphatase-2A catalytic subunit levels
RT and consequent suppression of inhibitory Raf-1 phosphorylation.";
RL J. Biol. Chem. 285:15076-15087(2010).
RN [26]
RP FUNCTION, AND INTERACTION WITH NEK2.
RX PubMed=21076410; DOI=10.1038/ncb2120;
RA Mardin B.R., Lange C., Baxter J.E., Hardy T., Scholz S.R., Fry A.M.,
RA Schiebel E.;
RT "Components of the Hippo pathway cooperate with Nek2 kinase to regulate
RT centrosome disjunction.";
RL Nat. Cell Biol. 12:1166-1176(2010).
RN [27]
RP PHOSPHORYLATION AT THR-117, AND INTERACTION WITH PKB/AKT1.
RX PubMed=20231902; DOI=10.1371/journal.pone.0009616;
RA Kim D., Shu S., Coppola M.D., Kaneko S., Yuan Z.Q., Cheng J.Q.;
RT "Regulation of proapoptotic mammalian ste20-like kinase MST2 by the IGF1-
RT Akt pathway.";
RL PLoS ONE 5:E9616-E9616(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 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 [30]
RP FUNCTION, AND INTERACTION WITH ESR1.
RX PubMed=21104395; DOI=10.1007/s00109-010-0698-y;
RA Park Y., Park J., Lee Y., Lim W., Oh B.C., Shin C., Kim W., Lee Y.;
RT "Mammalian MST2 kinase and human Salvador activate and reduce estrogen
RT receptor alpha in the absence of ligand.";
RL J. Mol. Med. 89:181-191(2011).
RN [31]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-316, 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 [32]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-316; THR-336 AND SER-385, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and 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 [33]
RP FUNCTION, AND INTERACTION WITH LATS1; SAV1; 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 [34]
RP VARIANT [LARGE SCALE ANALYSIS] LEU-60.
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. Phosphorylates
CC NKX2-1 (By similarity). Phosphorylates NEK2 and plays a role in
CC centrosome disjunction by regulating the localization of NEK2 to
CC centrosome, and its ability to phosphorylate CROCC and CEP250. In
CC conjunction with SAV1, activates the transcriptional activity of ESR1
CC through the modulation of its phosphorylation. Positively regulates
CC RAF1 activation via suppression of the inhibitory phosphorylation of
CC RAF1 on 'Ser-259'. Phosphorylates MOBKL1A and RASSF2. Phosphorylates
CC MOBKL1B on 'Thr-74'. Acts cooperatively with MOBKL1B to activate STK38.
CC {ECO:0000250|UniProtKB:Q9JI10, ECO:0000269|PubMed:15688006,
CC ECO:0000269|PubMed:16930133, ECO:0000269|PubMed:18328708,
CC ECO:0000269|PubMed:18362890, ECO:0000269|PubMed:19525978,
CC ECO:0000269|PubMed:20212043, ECO:0000269|PubMed:21076410,
CC ECO:0000269|PubMed:21104395, ECO:0000269|PubMed:28087714,
CC ECO:0000269|PubMed:8566796, 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-180, which are
CC inhibited by the proto-oncogene product RAF1. Activated by RASSF1 which
CC acts by preventing its dephosphorylation. {ECO:0000269|PubMed:15618521,
CC ECO:0000269|PubMed:21199877}.
CC -!- SUBUNIT: Homodimer; mediated via the coiled-coil region. Interacts with
CC NORE1, which inhibits autoactivation (By similarity). Interacts with
CC and stabilizes SAV1 (PubMed:15688006, PubMed:16930133,
CC PubMed:28087714). Interacts with RAF1, which prevents dimerization and
CC phosphorylation. Interacts with RASSF1. Interacts (via SARAH domain)
CC with isoform 1 of NEK2. Interacts with ESR1 only in the presence of
CC SAV1. Interacts with PKB/AKT1. Forms a tripartite complex with MOBKL1B
CC and STK38. Interacts with RASSF2 (via SARAH domain). Interacts with
CC DLG5 (via PDZ domain 3) (PubMed:28087714). Interacts with LATS1; this
CC interaction is inhibited in the presence of DLG5 (PubMed:28087714).
CC Interacts with MARK3 in the presence of DLG5 (PubMed:28087714).
CC {ECO:0000250|UniProtKB:Q13043, ECO:0000269|PubMed:15618521,
CC ECO:0000269|PubMed:15688006, ECO:0000269|PubMed:16510573,
CC ECO:0000269|PubMed:16930133, ECO:0000269|PubMed:18362890,
CC ECO:0000269|PubMed:19525978, ECO:0000269|PubMed:20086174,
CC ECO:0000269|PubMed:20231902, ECO:0000269|PubMed:21076410,
CC ECO:0000269|PubMed:21104395, ECO:0000269|PubMed:21199877,
CC ECO:0000269|PubMed:28087714}.
CC -!- INTERACTION:
CC Q13188; Q8IZU0: FAM9B; NbExp=3; IntAct=EBI-992580, EBI-10175124;
CC Q13188; Q53SE7: FLJ13057; NbExp=3; IntAct=EBI-992580, EBI-10172181;
CC Q13188; O95166: GABARAP; NbExp=2; IntAct=EBI-992580, EBI-712001;
CC Q13188; Q9H0R8: GABARAPL1; NbExp=2; IntAct=EBI-992580, EBI-746969;
CC Q13188; P60520: GABARAPL2; NbExp=2; IntAct=EBI-992580, EBI-720116;
CC Q13188; Q99259: GAD1; NbExp=3; IntAct=EBI-992580, EBI-743184;
CC Q13188; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-992580, EBI-1055254;
CC Q13188; Q9GZQ8: MAP1LC3B; NbExp=5; IntAct=EBI-992580, EBI-373144;
CC Q13188; Q9BXW4: MAP1LC3C; NbExp=2; IntAct=EBI-992580, EBI-2603996;
CC Q13188; Q9H8S9: MOB1A; NbExp=7; IntAct=EBI-992580, EBI-748229;
CC Q13188; Q7L9L4: MOB1B; NbExp=9; IntAct=EBI-992580, EBI-2558745;
CC Q13188; Q86TA1: MOB3B; NbExp=3; IntAct=EBI-992580, EBI-751703;
CC Q13188; Q9H8W4: PLEKHF2; NbExp=3; IntAct=EBI-992580, EBI-742388;
CC Q13188; P04049: RAF1; NbExp=6; IntAct=EBI-992580, EBI-365996;
CC Q13188; Q9NS23-2: RASSF1; NbExp=7; IntAct=EBI-992580, EBI-438698;
CC Q13188; P50749: RASSF2; NbExp=19; IntAct=EBI-992580, EBI-960081;
CC Q13188; Q86WH2: RASSF3; NbExp=7; IntAct=EBI-992580, EBI-2845202;
CC Q13188; Q9H2L5: RASSF4; NbExp=11; IntAct=EBI-992580, EBI-2933362;
CC Q13188; Q8WWW0: RASSF5; NbExp=9; IntAct=EBI-992580, EBI-367390;
CC Q13188; Q8WWW0-1: RASSF5; NbExp=6; IntAct=EBI-992580, EBI-960496;
CC Q13188; Q9H4B6: SAV1; NbExp=26; IntAct=EBI-992580, EBI-1017775;
CC Q13188; Q14BN4: SLMAP; NbExp=7; IntAct=EBI-992580, EBI-1043216;
CC Q13188; Q8TAD8: SNIP1; NbExp=3; IntAct=EBI-992580, EBI-749336;
CC Q13188; Q13188: STK3; NbExp=13; IntAct=EBI-992580, EBI-992580;
CC Q13188; Q13043: STK4; NbExp=19; IntAct=EBI-992580, EBI-367376;
CC Q13188; P0C1Z6: TFPT; NbExp=3; IntAct=EBI-992580, EBI-1245626;
CC Q13188; P0C1Z6-2: TFPT; NbExp=3; IntAct=EBI-992580, EBI-10178002;
CC Q13188; Q13077: TRAF1; NbExp=6; IntAct=EBI-992580, EBI-359224;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21145499}. Nucleus
CC {ECO:0000269|PubMed:21145499}. Note=The caspase-cleaved form cycles
CC between nucleus and cytoplasm (PubMed:19525978, PubMed:11278283).
CC Phosphorylation at Thr-117 leads to inhibition of nuclear translocation
CC (PubMed:19525978). {ECO:0000269|PubMed:11278283,
CC ECO:0000269|PubMed:19525978}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q13188-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q13188-2; Sequence=VSP_054167;
CC -!- TISSUE SPECIFICITY: Expressed at high levels in adult kidney, skeletal
CC and placenta tissues and at very low levels in adult heart, lung and
CC brain tissues. {ECO:0000269|PubMed:8566796}.
CC -!- INDUCTION: Activity increases during mitosis.
CC {ECO:0000269|PubMed:18328708}.
CC -!- PTM: Phosphorylation at Thr-117 and Thr-384 by PKB/AKT1, leads to
CC inhibition of its: cleavage, kinase activity, autophosphorylation at
CC Thr-180, binding to RASSF1 and nuclear translocation, and increase in
CC its binding to RAF1. {ECO:0000269|PubMed:11278283,
CC ECO:0000269|PubMed:20086174, ECO:0000269|PubMed:20231902}.
CC -!- PTM: Proteolytically cleaved by caspase-3 during apoptosis. Proteolytic
CC cleavage results in kinase activation and nuclear translocation of the
CC truncated form (MST1/N). {ECO:0000269|PubMed:11278283}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. STE20 subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
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DR EMBL; U26424; AAC50386.1; -; mRNA.
DR EMBL; U60206; AAB17261.1; -; mRNA.
DR EMBL; AK131363; BAG54769.1; -; mRNA.
DR EMBL; AK291837; BAF84526.1; -; mRNA.
DR EMBL; AC016877; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP002087; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP003355; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP003467; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP003551; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471060; EAW91781.1; -; Genomic_DNA.
DR EMBL; BC010640; AAH10640.1; -; mRNA.
DR EMBL; Z25422; CAA80909.1; -; mRNA.
DR CCDS; CCDS47900.1; -. [Q13188-1]
DR CCDS; CCDS59108.1; -. [Q13188-2]
DR PIR; I38212; I38212.
DR RefSeq; NP_001243241.1; NM_001256312.1. [Q13188-2]
DR RefSeq; NP_006272.2; NM_006281.3. [Q13188-1]
DR PDB; 3WWS; X-ray; 2.01 A; A/B/C/D=436-484.
DR PDB; 4HKD; X-ray; 1.50 A; A/B/C/D=436-484.
DR PDB; 4L0N; X-ray; 1.40 A; A/B/C/D/E/F/G/H/I/J=436-484.
DR PDB; 4LG4; X-ray; 2.42 A; A/B/C/D/E/F=16-313.
DR PDB; 4LGD; X-ray; 3.05 A; A/B/C/D=9-491.
DR PDB; 4OH9; X-ray; 1.70 A; A/B=436-484.
DR PDB; 5BRM; X-ray; 2.65 A; G/H/I/J/K/L/M/N/O=371-401.
DR PDB; 5DH3; X-ray; 2.47 A; A/B=15-313.
DR PDB; 6AO5; X-ray; 2.96 A; A=16-491.
DR PDB; 6AR2; X-ray; 1.55 A; C/D=373-382.
DR PDBsum; 3WWS; -.
DR PDBsum; 4HKD; -.
DR PDBsum; 4L0N; -.
DR PDBsum; 4LG4; -.
DR PDBsum; 4LGD; -.
DR PDBsum; 4OH9; -.
DR PDBsum; 5BRM; -.
DR PDBsum; 5DH3; -.
DR PDBsum; 6AO5; -.
DR PDBsum; 6AR2; -.
DR AlphaFoldDB; Q13188; -.
DR SMR; Q13188; -.
DR BioGRID; 112664; 154.
DR CORUM; Q13188; -.
DR DIP; DIP-36128N; -.
DR ELM; Q13188; -.
DR IntAct; Q13188; 110.
DR MINT; Q13188; -.
DR STRING; 9606.ENSP00000429744; -.
DR BindingDB; Q13188; -.
DR ChEMBL; CHEMBL4708; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q13188; -.
DR GuidetoPHARMACOLOGY; 2219; -.
DR GlyGen; Q13188; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q13188; -.
DR MetOSite; Q13188; -.
DR PhosphoSitePlus; Q13188; -.
DR BioMuta; STK3; -.
DR DMDM; 46577700; -.
DR OGP; Q13188; -.
DR EPD; Q13188; -.
DR jPOST; Q13188; -.
DR MassIVE; Q13188; -.
DR MaxQB; Q13188; -.
DR PaxDb; Q13188; -.
DR PeptideAtlas; Q13188; -.
DR PRIDE; Q13188; -.
DR ProteomicsDB; 3835; -.
DR ProteomicsDB; 59211; -. [Q13188-1]
DR Antibodypedia; 26075; 489 antibodies from 42 providers.
DR DNASU; 6788; -.
DR Ensembl; ENST00000419617.7; ENSP00000390500.2; ENSG00000104375.17. [Q13188-1]
DR Ensembl; ENST00000523601.5; ENSP00000429744.1; ENSG00000104375.17. [Q13188-2]
DR GeneID; 6788; -.
DR KEGG; hsa:6788; -.
DR MANE-Select; ENST00000419617.7; ENSP00000390500.2; NM_006281.4; NP_006272.2.
DR UCSC; uc003yio.5; human. [Q13188-1]
DR CTD; 6788; -.
DR DisGeNET; 6788; -.
DR GeneCards; STK3; -.
DR HGNC; HGNC:11406; STK3.
DR HPA; ENSG00000104375; Low tissue specificity.
DR MIM; 605030; gene.
DR neXtProt; NX_Q13188; -.
DR OpenTargets; ENSG00000104375; -.
DR PharmGKB; PA36213; -.
DR VEuPathDB; HostDB:ENSG00000104375; -.
DR eggNOG; KOG0574; Eukaryota.
DR GeneTree; ENSGT00940000154984; -.
DR HOGENOM; CLU_000288_63_23_1; -.
DR InParanoid; Q13188; -.
DR OMA; QRMANLD; -.
DR OrthoDB; 967913at2759; -.
DR PhylomeDB; Q13188; -.
DR TreeFam; TF354217; -.
DR BRENDA; 2.7.11.1; 2681.
DR PathwayCommons; Q13188; -.
DR Reactome; R-HSA-2028269; Signaling by Hippo.
DR SignaLink; Q13188; -.
DR SIGNOR; Q13188; -.
DR BioGRID-ORCS; 6788; 50 hits in 1111 CRISPR screens.
DR ChiTaRS; STK3; human.
DR GeneWiki; STK3; -.
DR GenomeRNAi; 6788; -.
DR Pharos; Q13188; Tchem.
DR PRO; PR:Q13188; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q13188; protein.
DR Bgee; ENSG00000104375; Expressed in calcaneal tendon and 200 other tissues.
DR ExpressionAtlas; Q13188; baseline and differential.
DR Genevisible; Q13188; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
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:0004672; F:protein kinase activity; IDA:UniProtKB.
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:0006915; P:apoptotic process; TAS:UniProtKB.
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: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:0007254; P:JNK cascade; 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:0043065; P:positive regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IGI:MGI.
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:0046330; P:positive regulation of JNK cascade; IEA:Ensembl.
DR GO; GO:0032092; P:positive regulation of protein binding; IDA:MGI.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IEA:Ensembl.
DR GO; GO:0060215; P:primitive hemopoiesis; IEA:Ensembl.
DR GO; GO:0006606; P:protein import into nucleus; IGI:UniProtKB.
DR GO; GO:0043491; P:protein kinase B signaling; IEA:Ensembl.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; IMP: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 DisProt; DP01461; -.
DR Gene3D; 4.10.170.10; -; 1.
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..491
FT /note="Serine/threonine-protein kinase 3"
FT /id="PRO_0000086689"
FT CHAIN 1..322
FT /note="Serine/threonine-protein kinase 3 36kDa subunit"
FT /id="PRO_0000413713"
FT CHAIN 323..491
FT /note="Serine/threonine-protein kinase 3 20kDa subunit"
FT /id="PRO_0000413714"
FT DOMAIN 27..278
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 437..484
FT /note="SARAH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00310"
FT REGION 301..327
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 370..392
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 287..328
FT /evidence="ECO:0000255"
FT COILED 442..475
FT /evidence="ECO:0000255"
FT ACT_SITE 146
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 33..41
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 56
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT SITE 322..323
FT /note="Cleavage; by caspase-3"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000269|Ref.7, ECO:0007744|PubMed:19413330"
FT MOD_RES 15
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 117
FT /note="Phosphothreonine; by PKB/AKT1"
FT /evidence="ECO:0000269|PubMed:20086174,
FT ECO:0000269|PubMed:20231902"
FT MOD_RES 180
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:O54748, ECO:0000305"
FT MOD_RES 316
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:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 336
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 384
FT /note="Phosphothreonine; by PKB/AKT1"
FT /evidence="ECO:0000269|PubMed:20086174"
FT MOD_RES 385
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 444
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
FT VAR_SEQ 1..8
FT /note="MEQPPAPK -> MLQLMDSGITICLRNGAASVFKKKEWSTQGEENKQD (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054167"
FT VARIANT 60
FT /note="V -> L (in an ovarian clear cell carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041122"
FT VARIANT 418
FT /note="F -> C (in dbSNP:rs36047674)"
FT /id="VAR_051670"
FT MUTAGEN 56
FT /note="K->R: Loss of activity."
FT /evidence="ECO:0000269|PubMed:16930133"
FT MUTAGEN 322
FT /note="D->N: Resistant to proteolytic cleavage."
FT /evidence="ECO:0000269|PubMed:11278283"
FT CONFLICT 96..98
FT /note="WIV -> YLY (in Ref. 8; CAA80909)"
FT /evidence="ECO:0000305"
FT CONFLICT 121
FT /note="D -> Y (in Ref. 8; CAA80909)"
FT /evidence="ECO:0000305"
FT CONFLICT 203
FT /note="D -> G (in Ref. 8; CAA80909)"
FT /evidence="ECO:0000305"
FT CONFLICT 303
FT /note="E -> D (in Ref. 1; AAC50386)"
FT /evidence="ECO:0000305"
FT CONFLICT 332..334
FT /note="ESV -> GEC (in Ref. 1; AAC50386)"
FT /evidence="ECO:0000305"
FT HELIX 17..20
FT /evidence="ECO:0007829|PDB:4LGD"
FT HELIX 23..26
FT /evidence="ECO:0007829|PDB:4LG4"
FT STRAND 27..34
FT /evidence="ECO:0007829|PDB:4LG4"
FT STRAND 36..39
FT /evidence="ECO:0007829|PDB:6AO5"
FT STRAND 40..46
FT /evidence="ECO:0007829|PDB:4LG4"
FT TURN 47..49
FT /evidence="ECO:0007829|PDB:4LG4"
FT STRAND 52..58
FT /evidence="ECO:0007829|PDB:4LG4"
FT HELIX 64..76
FT /evidence="ECO:0007829|PDB:4LG4"
FT STRAND 85..91
FT /evidence="ECO:0007829|PDB:4LG4"
FT STRAND 94..100
FT /evidence="ECO:0007829|PDB:4LG4"
FT STRAND 103..106
FT /evidence="ECO:0007829|PDB:5DH3"
FT HELIX 107..114
FT /evidence="ECO:0007829|PDB:4LG4"
FT HELIX 120..139
FT /evidence="ECO:0007829|PDB:4LG4"
FT HELIX 149..151
FT /evidence="ECO:0007829|PDB:4LG4"
FT STRAND 152..154
FT /evidence="ECO:0007829|PDB:4LG4"
FT STRAND 160..162
FT /evidence="ECO:0007829|PDB:4LG4"
FT HELIX 170..172
FT /evidence="ECO:0007829|PDB:4LG4"
FT HELIX 175..182
FT /evidence="ECO:0007829|PDB:4LG4"
FT HELIX 185..187
FT /evidence="ECO:0007829|PDB:5DH3"
FT HELIX 190..195
FT /evidence="ECO:0007829|PDB:4LG4"
FT HELIX 201..216
FT /evidence="ECO:0007829|PDB:4LG4"
FT TURN 220..223
FT /evidence="ECO:0007829|PDB:4LG4"
FT HELIX 226..235
FT /evidence="ECO:0007829|PDB:4LG4"
FT HELIX 244..246
FT /evidence="ECO:0007829|PDB:4LG4"
FT HELIX 249..258
FT /evidence="ECO:0007829|PDB:4LG4"
FT HELIX 263..265
FT /evidence="ECO:0007829|PDB:4LG4"
FT HELIX 269..272
FT /evidence="ECO:0007829|PDB:4LG4"
FT HELIX 276..279
FT /evidence="ECO:0007829|PDB:4LG4"
FT HELIX 284..287
FT /evidence="ECO:0007829|PDB:4LG4"
FT HELIX 288..306
FT /evidence="ECO:0007829|PDB:4LG4"
FT TURN 308..311
FT /evidence="ECO:0007829|PDB:6AO5"
FT STRAND 379..381
FT /evidence="ECO:0007829|PDB:5BRM"
FT HELIX 392..394
FT /evidence="ECO:0007829|PDB:5BRM"
FT TURN 395..397
FT /evidence="ECO:0007829|PDB:5BRM"
FT HELIX 436..440
FT /evidence="ECO:0007829|PDB:4L0N"
FT HELIX 445..483
FT /evidence="ECO:0007829|PDB:4L0N"
SQ SEQUENCE 491 AA; 56301 MW; 84F598ED3617292C CRC64;
MEQPPAPKSK LKKLSEDSLT KQPEEVFDVL EKLGEGSYGS VFKAIHKESG QVVAIKQVPV
ESDLQEIIKE ISIMQQCDSP YVVKYYGSYF KNTDLWIVME YCGAGSVSDI IRLRNKTLIE
DEIATILKST LKGLEYLHFM RKIHRDIKAG NILLNTEGHA KLADFGVAGQ LTDTMAKRNT
VIGTPFWMAP EVIQEIGYNC VADIWSLGIT SIEMAEGKPP YADIHPMRAI FMIPTNPPPT
FRKPELWSDD FTDFVKKCLV KNPEQRATAT QLLQHPFIKN AKPVSILRDL ITEAMEIKAK
RHEEQQRELE EEEENSDEDE LDSHTMVKTS VESVGTMRAT STMSEGAQTM IEHNSTMLES
DLGTMVINSE DEEEEDGTMK RNATSPQVQR PSFMDYFDKQ DFKNKSHENC NQNMHEPFPM
SKNVFPDNWK VPQDGDFDFL KNLSLEELQM RLKALDPMME REIEELRQRY TAKRQPILDA
MDAKKRRQQN F
