M2K4_ARATH
ID M2K4_ARATH Reviewed; 366 AA.
AC O80397;
DT 11-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Mitogen-activated protein kinase kinase 4;
DE Short=AtMKK4;
DE Short=MAP kinase kinase 4;
DE EC=2.7.12.2;
GN Name=MKK4; OrderedLocusNames=At1g51660; ORFNames=F19C24.26;
OS Arabidopsis thaliana (Mouse-ear cress).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC rosids; malvids; Brassicales; Brassicaceae; Camelineae; Arabidopsis.
OX NCBI_TaxID=3702;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=cv. Columbia;
RX PubMed=10048483; DOI=10.1093/dnares/5.6.341;
RA Ichimura K., Mizoguchi T., Hayashida N., Seki M., Shinozaki K.;
RT "Molecular cloning and characterization of three cDNAs encoding putative
RT mitogen-activated protein kinase kinases (MAPKKs) in Arabidopsis
RT thaliana.";
RL DNA Res. 5:341-348(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=cv. Columbia;
RX PubMed=11130712; DOI=10.1038/35048500;
RA Theologis A., Ecker J.R., Palm C.J., Federspiel N.A., Kaul S., White O.,
RA Alonso J., Altafi H., Araujo R., Bowman C.L., Brooks S.Y., Buehler E.,
RA Chan A., Chao Q., Chen H., Cheuk R.F., Chin C.W., Chung M.K., Conn L.,
RA Conway A.B., Conway A.R., Creasy T.H., Dewar K., Dunn P., Etgu P.,
RA Feldblyum T.V., Feng J.-D., Fong B., Fujii C.Y., Gill J.E., Goldsmith A.D.,
RA Haas B., Hansen N.F., Hughes B., Huizar L., Hunter J.L., Jenkins J.,
RA Johnson-Hopson C., Khan S., Khaykin E., Kim C.J., Koo H.L.,
RA Kremenetskaia I., Kurtz D.B., Kwan A., Lam B., Langin-Hooper S., Lee A.,
RA Lee J.M., Lenz C.A., Li J.H., Li Y.-P., Lin X., Liu S.X., Liu Z.A.,
RA Luros J.S., Maiti R., Marziali A., Militscher J., Miranda M., Nguyen M.,
RA Nierman W.C., Osborne B.I., Pai G., Peterson J., Pham P.K., Rizzo M.,
RA Rooney T., Rowley D., Sakano H., Salzberg S.L., Schwartz J.R., Shinn P.,
RA Southwick A.M., Sun H., Tallon L.J., Tambunga G., Toriumi M.J., Town C.D.,
RA Utterback T., Van Aken S., Vaysberg M., Vysotskaia V.S., Walker M., Wu D.,
RA Yu G., Fraser C.M., Venter J.C., Davis R.W.;
RT "Sequence and analysis of chromosome 1 of the plant Arabidopsis thaliana.";
RL Nature 408:816-820(2000).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=cv. Columbia;
RX PubMed=27862469; DOI=10.1111/tpj.13415;
RA Cheng C.Y., Krishnakumar V., Chan A.P., Thibaud-Nissen F., Schobel S.,
RA Town C.D.;
RT "Araport11: a complete reannotation of the Arabidopsis thaliana reference
RT genome.";
RL Plant J. 89:789-804(2017).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=cv. Columbia;
RX PubMed=14593172; DOI=10.1126/science.1088305;
RA Yamada K., Lim J., Dale J.M., Chen H., Shinn P., Palm C.J., Southwick A.M.,
RA Wu H.C., Kim C.J., Nguyen M., Pham P.K., Cheuk R.F., Karlin-Newmann G.,
RA Liu S.X., Lam B., Sakano H., Wu T., Yu G., Miranda M., Quach H.L.,
RA Tripp M., Chang C.H., Lee J.M., Toriumi M.J., Chan M.M., Tang C.C.,
RA Onodera C.S., Deng J.M., Akiyama K., Ansari Y., Arakawa T., Banh J.,
RA Banno F., Bowser L., Brooks S.Y., Carninci P., Chao Q., Choy N., Enju A.,
RA Goldsmith A.D., Gurjal M., Hansen N.F., Hayashizaki Y., Johnson-Hopson C.,
RA Hsuan V.W., Iida K., Karnes M., Khan S., Koesema E., Ishida J., Jiang P.X.,
RA Jones T., Kawai J., Kamiya A., Meyers C., Nakajima M., Narusaka M.,
RA Seki M., Sakurai T., Satou M., Tamse R., Vaysberg M., Wallender E.K.,
RA Wong C., Yamamura Y., Yuan S., Shinozaki K., Davis R.W., Theologis A.,
RA Ecker J.R.;
RT "Empirical analysis of transcriptional activity in the Arabidopsis
RT genome.";
RL Science 302:842-846(2003).
RN [5]
RP FUNCTION, AND MUTAGENESIS OF LYS-108; THR-224 AND SER-230.
RX PubMed=11687590; DOI=10.1074/jbc.m109495200;
RA Ren D., Yang H., Zhang S.;
RT "Cell death mediated by MAPK is associated with hydrogen peroxide
RT production in Arabidopsis.";
RL J. Biol. Chem. 277:559-565(2002).
RN [6]
RP FUNCTION, ACTIVITY REGULATION, PHOSPHORYLATION AT THR-224 AND SER-230, AND
RP MUTAGENESIS OF LYS-108; THR-224 AND SER-230.
RX PubMed=11875555; DOI=10.1038/415977a;
RA Asai T., Tena G., Plotnikova J., Willmann M.R., Chiu W.-L., Gomez-Gomez L.,
RA Boller T., Ausubel F.M., Sheen J.;
RT "MAP kinase signalling cascade in Arabidopsis innate immunity.";
RL Nature 415:977-983(2002).
RN [7]
RP GENE FAMILY, AND NOMENCLATURE.
RX PubMed=12119167; DOI=10.1016/s1360-1385(02)02302-6;
RG MAPK group;
RT "Mitogen-activated protein kinase cascades in plants: a new nomenclature.";
RL Trends Plant Sci. 7:301-308(2002).
RN [8]
RP GENE FAMILY.
RX PubMed=16537113; DOI=10.1016/j.tplants.2006.02.007;
RA Hamel L.P., Nicole M.C., Sritubtim S., Morency M.J., Ellis M., Ehlting J.,
RA Beaudoin N., Barbazuk B., Klessig D., Lee J., Martin G., Mundy J.,
RA Ohashi Y., Scheel D., Sheen J., Xing T., Zhang S., Seguin A., Ellis B.E.;
RT "Ancient signals: comparative genomics of plant MAPK and MAPKK gene
RT families.";
RL Trends Plant Sci. 11:192-198(2006).
RN [9]
RP FUNCTION.
RX PubMed=17259259; DOI=10.1105/tpc.106.048298;
RA Wang H., Ngwenyama N., Liu Y., Walker J.C., Zhang S.;
RT "Stomatal development and patterning are regulated by environmentally
RT responsive mitogen-activated protein kinases in Arabidopsis.";
RL Plant Cell 19:63-73(2007).
RN [10]
RP SUBCELLULAR LOCATION.
RX PubMed=19516975; DOI=10.4161/psb.3.1.4856;
RA Samuel M.A., Chaal B.K., Lampard G., Green B.R., Ellis B.E.;
RT "Surviving the passage: Non-canonical stromal targeting of an Arabidopsis
RT mitogen-activated protein kinase kinase.";
RL Plant Signal. Behav. 3:6-12(2008).
RN [11]
RP INTERACTION WITH MPK6.
RX PubMed=19513235; DOI=10.4161/psb.3.12.6848;
RA Lee J.S., Huh K.W., Bhargava A., Ellis B.E.;
RT "Comprehensive analysis of protein-protein interactions between Arabidopsis
RT MAPKs and MAPK kinases helps define potential MAPK signalling modules.";
RL Plant Signal. Behav. 3:1037-1041(2008).
RN [12]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=18809915; DOI=10.1073/pnas.0805539105;
RA Cho S.K., Larue C.T., Chevalier D., Wang H., Jinn T.-L., Zhang S.,
RA Walker J.C.;
RT "Regulation of floral organ abscission in Arabidopsis thaliana.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:15629-15634(2008).
RN [13]
RP INTERACTION WITH P.SYRINGAE HOPF2.
RX PubMed=20571112; DOI=10.1105/tpc.110.075697;
RA Wang Y., Li J., Hou S., Wang X., Li Y., Ren D., Chen S., Tang X.,
RA Zhou J.M.;
RT "A Pseudomonas syringae ADP-ribosyltransferase inhibits Arabidopsis
RT mitogen-activated protein kinase kinases.";
RL Plant Cell 22:2033-2044(2010).
RN [14]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=21806969; DOI=10.1016/j.bbrc.2011.07.064;
RA Kim S.H., Woo D.H., Kim J.M., Lee S.Y., Chung W.S., Moon Y.H.;
RT "Arabidopsis MKK4 mediates osmotic-stress response via its regulation of
RT MPK3 activity.";
RL Biochem. Biophys. Res. Commun. 412:150-154(2011).
RN [15]
RP FUNCTION.
RX PubMed=23263767; DOI=10.1105/tpc.112.104695;
RA Meng X., Wang H., He Y., Liu Y., Walker J.C., Torii K.U., Zhang S.;
RT "A MAPK cascade downstream of ERECTA receptor-like protein kinase regulates
RT Arabidopsis inflorescence architecture by promoting localized cell
RT proliferation.";
RL Plant Cell 24:4948-4960(2012).
RN [16]
RP FUNCTION, ACTIVITY REGULATION, INTERACTION WITH ASK7/BIN2, MUTAGENESIS OF
RP SER-230 AND THR-234, IDENTIFICATION BY MASS SPECTROMETRY, PHOSPHORYLATION
RP AT SER-6; SER-230 AND THR-234, AND SUBCELLULAR LOCATION.
RX PubMed=23341468; DOI=10.1074/jbc.m112.384453;
RA Khan M., Rozhon W., Bigeard J., Pflieger D., Husar S., Pitzschke A.,
RA Teige M., Jonak C., Hirt H., Poppenberger B.;
RT "Brassinosteroid-regulated GSK3/Shaggy-like kinases phosphorylate mitogen-
RT activated protein (MAP) kinase kinases, which control stomata development
RT in Arabidopsis thaliana.";
RL J. Biol. Chem. 288:7519-7527(2013).
RN [17]
RP INTERACTION WITH RACK1A; RACK1B AND RACK1C.
RX PubMed=25731164; DOI=10.1038/nature14243;
RA Cheng Z., Li J.F., Niu Y., Zhang X.C., Woody O.Z., Xiong Y., Djonovic S.,
RA Millet Y., Bush J., McConkey B.J., Sheen J., Ausubel F.M.;
RT "Pathogen-secreted proteases activate a novel plant immune pathway.";
RL Nature 521:213-216(2015).
RN [18]
RP INTERACTION WITH MAPKKK5, PHOSPHORYLATION BY MAPKKK5, AND MUTAGENESIS OF
RP LYS-108; THR-224 AND SER-230.
RC STRAIN=cv. Columbia;
RX PubMed=27679653; DOI=10.15252/embj.201694248;
RA Yamada K., Yamaguchi K., Shirakawa T., Nakagami H., Mine A., Ishikawa K.,
RA Fujiwara M., Narusaka M., Narusaka Y., Ichimura K., Kobayashi Y.,
RA Matsui H., Nomura Y., Nomoto M., Tada Y., Fukao Y., Fukamizo T., Tsuda K.,
RA Shirasu K., Shibuya N., Kawasaki T.;
RT "The Arabidopsis CERK1-associated kinase PBL27 connects chitin perception
RT to MAPK activation.";
RL EMBO J. 35:2468-2483(2016).
CC -!- FUNCTION: Involved in the second phase of hydrogen peroxide generation
CC during hypersensitive response-like cell death. Involved in the innate
CC immune MAP kinase signaling cascade (MEKK1, MKK4/MKK5 and MPK3/MPK6)
CC downstream of bacterial flagellin receptor FLS2. Activates by
CC phosphorylation the downstream MPK3 and MPK6. YDA-MKK4/MKK5-MPK3/MPK6
CC module regulates stomatal cell fate before the guard mother cell (GMC)
CC is specified. This MAPK cascade also functions downstream of the ER
CC receptor in regulating coordinated local cell proliferation, which
CC shapes the morphology of plant organs. MKK4 and MKK5 participate in the
CC regulation of floral organ abscission. Mediates osmotic-stress response
CC via its regulation of MPK3 activity. Target of the Pseudomonas syringae
CC type III effector HopF2. {ECO:0000269|PubMed:11687590,
CC ECO:0000269|PubMed:11875555, ECO:0000269|PubMed:17259259,
CC ECO:0000269|PubMed:18809915, ECO:0000269|PubMed:21806969,
CC ECO:0000269|PubMed:23263767, ECO:0000269|PubMed:23341468}.
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=2.7.12.2;
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=2.7.12.2;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.12.2;
CC -!- ACTIVITY REGULATION: Activated through serine and threonine
CC phosphorylation by MEKK1. Inhibited through phosphorylation by
CC GSK3/Shaggy-like kinase ASKs. {ECO:0000269|PubMed:11875555,
CC ECO:0000269|PubMed:23341468}.
CC -!- SUBUNIT: Interacts with ASK7/BIN2 (PubMed:23341468). Interacts with
CC P.syringae type III effector HopF2 (PubMed:20571112). Interacts with
CC MPK6 (PubMed:19513235). Interacts with RACK1A, RACK1B and RACK1C
CC (PubMed:25731164). Interacts with MAPKKK5 mainly in the cytosol
CC (PubMed:27679653). {ECO:0000269|PubMed:19513235,
CC ECO:0000269|PubMed:20571112, ECO:0000269|PubMed:23341468,
CC ECO:0000269|PubMed:25731164, ECO:0000269|PubMed:27679653}.
CC -!- INTERACTION:
CC O80397; Q17TI5: BRX; NbExp=6; IntAct=EBI-2358409, EBI-4426649;
CC O80397; P46639: KNAT1; NbExp=3; IntAct=EBI-2358409, EBI-530486;
CC O80397; Q39023: MPK3; NbExp=9; IntAct=EBI-2358409, EBI-349526;
CC O80397; Q39026: MPK6; NbExp=7; IntAct=EBI-2358409, EBI-349548;
CC O80397; O23160: MYB73; NbExp=5; IntAct=EBI-2358409, EBI-25506855;
CC O80397; Q84MB2: TIFY8; NbExp=6; IntAct=EBI-2358409, EBI-4426557;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Plastid, chloroplast stroma.
CC -!- TISSUE SPECIFICITY: Expressed higher in stems and leaves than in
CC flowers and roots. {ECO:0000269|PubMed:10048483,
CC ECO:0000269|PubMed:21806969}.
CC -!- PTM: Phosphorylation at Thr-224 and Ser-230 by MAP kinase kinase
CC kinases positively regulates kinase activity. Phosphorylation at Ser-
CC 230 and Thr-234 by GSK3/Shaggy-like kinase ASKs negatively regulates
CC kinase activity. Phosphorylated by MAPKKK5 (PubMed:27679653).
CC {ECO:0000269|PubMed:11875555, ECO:0000269|PubMed:23341468,
CC ECO:0000269|PubMed:27679653}.
CC -!- DISRUPTION PHENOTYPE: RNAi double mutants MKK4 and MKK5 have a strong
CC abscission defect. Higher sensitivity to high salt and drought
CC stresses. {ECO:0000269|PubMed:18809915, ECO:0000269|PubMed:21806969}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. MAP kinase kinase subfamily. {ECO:0000305}.
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DR EMBL; AB015315; BAA28830.1; -; mRNA.
DR EMBL; AC025294; AAG50863.1; -; Genomic_DNA.
DR EMBL; CP002684; AEE32696.1; -; Genomic_DNA.
DR EMBL; AF324667; AAG40018.1; -; mRNA.
DR EMBL; AF326878; AAG41460.1; -; mRNA.
DR EMBL; AF349517; AAK15564.1; -; mRNA.
DR EMBL; AF375398; AAK52982.1; -; mRNA.
DR EMBL; AY129469; AAM91055.1; -; mRNA.
DR PIR; T51339; T51339.
DR RefSeq; NP_175577.1; NM_104044.3.
DR AlphaFoldDB; O80397; -.
DR SMR; O80397; -.
DR BioGRID; 26816; 19.
DR IntAct; O80397; 14.
DR STRING; 3702.AT1G51660.1; -.
DR iPTMnet; O80397; -.
DR PaxDb; O80397; -.
DR PRIDE; O80397; -.
DR ProteomicsDB; 238757; -.
DR EnsemblPlants; AT1G51660.1; AT1G51660.1; AT1G51660.
DR GeneID; 841591; -.
DR Gramene; AT1G51660.1; AT1G51660.1; AT1G51660.
DR KEGG; ath:AT1G51660; -.
DR Araport; AT1G51660; -.
DR TAIR; locus:2017662; AT1G51660.
DR eggNOG; KOG0581; Eukaryota.
DR HOGENOM; CLU_000288_63_23_1; -.
DR InParanoid; O80397; -.
DR OMA; NHEETVR; -.
DR OrthoDB; 688282at2759; -.
DR PhylomeDB; O80397; -.
DR PRO; PR:O80397; -.
DR Proteomes; UP000006548; Chromosome 1.
DR ExpressionAtlas; O80397; baseline and differential.
DR Genevisible; O80397; AT.
DR GO; GO:0009570; C:chloroplast stroma; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; HDA:TAIR.
DR GO; GO:0005634; C:nucleus; HDA:TAIR.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004708; F:MAP kinase kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IEA:RHEA.
DR GO; GO:0098542; P:defense response to other organism; IMP:TAIR.
DR GO; GO:0010227; P:floral organ abscission; IMP:TAIR.
DR GO; GO:0010229; P:inflorescence development; IGI:TAIR.
DR GO; GO:0009626; P:plant-type hypersensitive response; IEA:UniProtKB-KW.
DR GO; GO:0009875; P:pollen-pistil interaction; IGI:TAIR.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
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; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Chloroplast; Cytoplasm; Hypersensitive response; Kinase;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Plant defense; Plastid;
KW Reference proteome; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..366
FT /note="Mitogen-activated protein kinase kinase 4"
FT /id="PRO_0000245823"
FT DOMAIN 79..334
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..69
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 339..366
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 45..69
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 339..356
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 196
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 85..93
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 108
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 6
FT /note="Phosphoserine; by ASK7"
FT /evidence="ECO:0000269|PubMed:23341468"
FT MOD_RES 224
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:11875555"
FT MOD_RES 230
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:11875555,
FT ECO:0000269|PubMed:23341468"
FT MOD_RES 230
FT /note="Phosphoserine; by ASK7"
FT /evidence="ECO:0000269|PubMed:11875555,
FT ECO:0000269|PubMed:23341468"
FT MOD_RES 234
FT /note="Phosphothreonine; by ASK7"
FT /evidence="ECO:0000269|PubMed:23341468"
FT MUTAGEN 108
FT /note="K->M: Loss of activity."
FT /evidence="ECO:0000269|PubMed:11687590,
FT ECO:0000269|PubMed:11875555"
FT MUTAGEN 108
FT /note="K->R: Loss of activity. Phosphorylated by MAPKKK5."
FT /evidence="ECO:0000269|PubMed:11687590,
FT ECO:0000269|PubMed:11875555, ECO:0000269|PubMed:27679653"
FT MUTAGEN 224
FT /note="T->A: Impaired phosphorylation by MAPKKK5; when
FT associated with A-230."
FT /evidence="ECO:0000269|PubMed:27679653"
FT MUTAGEN 224
FT /note="T->D: Constitutively active; when associated with D-
FT 230 or E-230."
FT /evidence="ECO:0000269|PubMed:11687590,
FT ECO:0000269|PubMed:11875555"
FT MUTAGEN 230
FT /note="S->A: Abolishes phosphorylation by ASK7/BIN2.
FT Impaired phosphorylation by MAPKKK5; when associated with
FT A-224."
FT /evidence="ECO:0000269|PubMed:11687590,
FT ECO:0000269|PubMed:11875555, ECO:0000269|PubMed:23341468,
FT ECO:0000269|PubMed:27679653"
FT MUTAGEN 230
FT /note="S->D: Constitutively active; when associated with D-
FT 224."
FT /evidence="ECO:0000269|PubMed:11687590,
FT ECO:0000269|PubMed:11875555, ECO:0000269|PubMed:23341468"
FT MUTAGEN 230
FT /note="S->E: Constitutively active; when associated with D-
FT 224."
FT /evidence="ECO:0000269|PubMed:11687590,
FT ECO:0000269|PubMed:11875555, ECO:0000269|PubMed:23341468"
FT MUTAGEN 234
FT /note="T->A: Abolishes phosphorylation by ASK7/BIN2."
FT /evidence="ECO:0000269|PubMed:23341468"
FT MUTAGEN 234
FT /note="T->D,E: Abolishes activity of MKK4 against MPK6."
FT /evidence="ECO:0000269|PubMed:23341468"
SQ SEQUENCE 366 AA; 40117 MW; 34C1CA3EEA19D07C CRC64;
MRPIQSPPGV SVPVKSRPRR RPDLTLPLPQ RDVSLAVPLP LPPTSGGSGG SSGSAPSSGG
SASSTNTNSS IEAKNYSDLV RGNRIGSGAG GTVYKVIHRP SSRLYALKVI YGNHEETVRR
QICREIEILR DVNHPNVVKC HEMFDQNGEI QVLLEFMDKG SLEGAHVWKE QQLADLSRQI
LSGLAYLHSR HIVHRDIKPS NLLINSAKNV KIADFGVSRI LAQTMDPCNS SVGTIAYMSP
ERINTDLNQG KYDGYAGDIW SLGVSILEFY LGRFPFPVSR QGDWASLMCA ICMSQPPEAP
ATASPEFRHF ISCCLQREPG KRRSAMQLLQ HPFILRASPS QNRSPQNLHQ LLPPPRPLSS
SSSPTT
