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Mitogen-activated protein kinase kinase 4 (AtMKK4) (MAP kinase kinase 4) (EC 2.7.12.2)

 M2K4_ARATH              Reviewed;         366 AA.
O80397;
11-JUL-2006, integrated into UniProtKB/Swiss-Prot.
01-NOV-1998, sequence version 1.
07-NOV-2018, entry version 139.
RecName: Full=Mitogen-activated protein kinase kinase 4;
Short=AtMKK4;
Short=MAP kinase kinase 4;
EC=2.7.12.2;
Name=MKK4; OrderedLocusNames=At1g51660; ORFNames=F19C24.26;
Arabidopsis thaliana (Mouse-ear cress).
Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
Spermatophyta; Magnoliophyta; eudicotyledons; Gunneridae;
Pentapetalae; rosids; malvids; Brassicales; Brassicaceae; Camelineae;
Arabidopsis.
NCBI_TaxID=3702;
[1]
NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
STRAIN=cv. Columbia;
PubMed=10048483; DOI=10.1093/dnares/5.6.341;
Ichimura K., Mizoguchi T., Hayashida N., Seki M., Shinozaki K.;
"Molecular cloning and characterization of three cDNAs encoding
putative mitogen-activated protein kinase kinases (MAPKKs) in
Arabidopsis thaliana.";
DNA Res. 5:341-348(1998).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
STRAIN=cv. Columbia;
PubMed=11130712; DOI=10.1038/35048500;
Theologis A., Ecker J.R., Palm C.J., Federspiel N.A., Kaul S.,
White O., Alonso J., Altafi H., Araujo R., Bowman C.L., Brooks S.Y.,
Buehler E., Chan A., Chao Q., Chen H., Cheuk R.F., Chin C.W.,
Chung M.K., Conn L., Conway A.B., Conway A.R., Creasy T.H., Dewar K.,
Dunn P., Etgu P., Feldblyum T.V., Feng J.-D., Fong B., Fujii C.Y.,
Gill J.E., Goldsmith A.D., Haas B., Hansen N.F., Hughes B., Huizar L.,
Hunter J.L., Jenkins J., Johnson-Hopson C., Khan S., Khaykin E.,
Kim C.J., Koo H.L., Kremenetskaia I., Kurtz D.B., Kwan A., Lam B.,
Langin-Hooper S., Lee A., Lee J.M., Lenz C.A., Li J.H., Li Y.-P.,
Lin X., Liu S.X., Liu Z.A., Luros J.S., Maiti R., Marziali A.,
Militscher J., Miranda M., Nguyen M., Nierman W.C., Osborne B.I.,
Pai G., Peterson J., Pham P.K., Rizzo M., Rooney T., Rowley D.,
Sakano H., Salzberg S.L., Schwartz J.R., Shinn P., Southwick A.M.,
Sun H., Tallon L.J., Tambunga G., Toriumi M.J., Town C.D.,
Utterback T., Van Aken S., Vaysberg M., Vysotskaia V.S., Walker M.,
Wu D., Yu G., Fraser C.M., Venter J.C., Davis R.W.;
"Sequence and analysis of chromosome 1 of the plant Arabidopsis
thaliana.";
Nature 408:816-820(2000).
[3]
GENOME REANNOTATION.
STRAIN=cv. Columbia;
PubMed=27862469; DOI=10.1111/tpj.13415;
Cheng C.Y., Krishnakumar V., Chan A.P., Thibaud-Nissen F., Schobel S.,
Town C.D.;
"Araport11: a complete reannotation of the Arabidopsis thaliana
reference genome.";
Plant J. 89:789-804(2017).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
STRAIN=cv. Columbia;
PubMed=14593172; DOI=10.1126/science.1088305;
Yamada K., Lim J., Dale J.M., Chen H., Shinn P., Palm C.J.,
Southwick A.M., Wu H.C., Kim C.J., Nguyen M., Pham P.K., Cheuk R.F.,
Karlin-Newmann G., Liu S.X., Lam B., Sakano H., Wu T., Yu G.,
Miranda M., Quach H.L., Tripp M., Chang C.H., Lee J.M., Toriumi M.J.,
Chan M.M., Tang C.C., Onodera C.S., Deng J.M., Akiyama K., Ansari Y.,
Arakawa T., Banh J., Banno F., Bowser L., Brooks S.Y., Carninci P.,
Chao Q., Choy N., Enju A., Goldsmith A.D., Gurjal M., Hansen N.F.,
Hayashizaki Y., Johnson-Hopson C., Hsuan V.W., Iida K., Karnes M.,
Khan S., Koesema E., Ishida J., Jiang P.X., Jones T., Kawai J.,
Kamiya A., Meyers C., Nakajima M., Narusaka M., Seki M., Sakurai T.,
Satou M., Tamse R., Vaysberg M., Wallender E.K., Wong C., Yamamura Y.,
Yuan S., Shinozaki K., Davis R.W., Theologis A., Ecker J.R.;
"Empirical analysis of transcriptional activity in the Arabidopsis
genome.";
Science 302:842-846(2003).
[5]
FUNCTION, AND MUTAGENESIS OF LYS-108; THR-224 AND SER-230.
PubMed=11687590; DOI=10.1074/jbc.M109495200;
Ren D., Yang H., Zhang S.;
"Cell death mediated by MAPK is associated with hydrogen peroxide
production in Arabidopsis.";
J. Biol. Chem. 277:559-565(2002).
[6]
FUNCTION, ACTIVITY REGULATION, PHOSPHORYLATION AT THR-224 AND SER-230,
AND MUTAGENESIS OF LYS-108; THR-224 AND SER-230.
PubMed=11875555; DOI=10.1038/415977a;
Asai T., Tena G., Plotnikova J., Willmann M.R., Chiu W.-L.,
Gomez-Gomez L., Boller T., Ausubel F.M., Sheen J.;
"MAP kinase signalling cascade in Arabidopsis innate immunity.";
Nature 415:977-983(2002).
[7]
GENE FAMILY, AND NOMENCLATURE.
PubMed=12119167; DOI=10.1016/S1360-1385(02)02302-6;
MAPK group;
"Mitogen-activated protein kinase cascades in plants: a new
nomenclature.";
Trends Plant Sci. 7:301-308(2002).
[8]
GENE FAMILY.
PubMed=16537113; DOI=10.1016/j.tplants.2006.02.007;
Hamel L.P., Nicole M.C., Sritubtim S., Morency M.J., Ellis M.,
Ehlting J., Beaudoin N., Barbazuk B., Klessig D., Lee J., Martin G.,
Mundy J., Ohashi Y., Scheel D., Sheen J., Xing T., Zhang S.,
Seguin A., Ellis B.E.;
"Ancient signals: comparative genomics of plant MAPK and MAPKK gene
families.";
Trends Plant Sci. 11:192-198(2006).
[9]
FUNCTION.
PubMed=17259259; DOI=10.1105/tpc.106.048298;
Wang H., Ngwenyama N., Liu Y., Walker J.C., Zhang S.;
"Stomatal development and patterning are regulated by environmentally
responsive mitogen-activated protein kinases in Arabidopsis.";
Plant Cell 19:63-73(2007).
[10]
SUBCELLULAR LOCATION.
PubMed=19516975; DOI=10.4161/psb.3.1.4856;
Samuel M.A., Chaal B.K., Lampard G., Green B.R., Ellis B.E.;
"Surviving the passage: Non-canonical stromal targeting of an
Arabidopsis mitogen-activated protein kinase kinase.";
Plant Signal. Behav. 3:6-12(2008).
[11]
INTERACTION WITH MPK6.
PubMed=19513235; DOI=10.4161/psb.3.12.6848;
Lee J.S., Huh K.W., Bhargava A., Ellis B.E.;
"Comprehensive analysis of protein-protein interactions between
Arabidopsis MAPKs and MAPK kinases helps define potential MAPK
signalling modules.";
Plant Signal. Behav. 3:1037-1041(2008).
[12]
DISRUPTION PHENOTYPE, AND FUNCTION.
PubMed=18809915; DOI=10.1073/pnas.0805539105;
Cho S.K., Larue C.T., Chevalier D., Wang H., Jinn T.-L., Zhang S.,
Walker J.C.;
"Regulation of floral organ abscission in Arabidopsis thaliana.";
Proc. Natl. Acad. Sci. U.S.A. 105:15629-15634(2008).
[13]
INTERACTION WITH P.SYRINGAE HOPF2.
PubMed=20571112; DOI=10.1105/tpc.110.075697;
Wang Y., Li J., Hou S., Wang X., Li Y., Ren D., Chen S., Tang X.,
Zhou J.M.;
"A Pseudomonas syringae ADP-ribosyltransferase inhibits Arabidopsis
mitogen-activated protein kinase kinases.";
Plant Cell 22:2033-2044(2010).
[14]
FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
PubMed=21806969; DOI=10.1016/j.bbrc.2011.07.064;
Kim S.H., Woo D.H., Kim J.M., Lee S.Y., Chung W.S., Moon Y.H.;
"Arabidopsis MKK4 mediates osmotic-stress response via its regulation
of MPK3 activity.";
Biochem. Biophys. Res. Commun. 412:150-154(2011).
[15]
FUNCTION.
PubMed=23263767; DOI=10.1105/tpc.112.104695;
Meng X., Wang H., He Y., Liu Y., Walker J.C., Torii K.U., Zhang S.;
"A MAPK cascade downstream of ERECTA receptor-like protein kinase
regulates Arabidopsis inflorescence architecture by promoting
localized cell proliferation.";
Plant Cell 24:4948-4960(2012).
[16]
FUNCTION, ACTIVITY REGULATION, INTERACTION WITH ASK7/BIN2, MUTAGENESIS
OF SER-230 AND THR-234, IDENTIFICATION BY MASS SPECTROMETRY,
PHOSPHORYLATION AT SER-6; SER-230 AND THR-234, AND SUBCELLULAR
LOCATION.
PubMed=23341468; DOI=10.1074/jbc.M112.384453;
Khan M., Rozhon W., Bigeard J., Pflieger D., Husar S., Pitzschke A.,
Teige M., Jonak C., Hirt H., Poppenberger B.;
"Brassinosteroid-regulated GSK3/Shaggy-like kinases phosphorylate
mitogen-activated protein (MAP) kinase kinases, which control stomata
development in Arabidopsis thaliana.";
J. Biol. Chem. 288:7519-7527(2013).
[17]
INTERACTION WITH RACK1A; RACK1B AND RACK1C.
PubMed=25731164; DOI=10.1038/nature14243;
Cheng Z., Li J.F., Niu Y., Zhang X.C., Woody O.Z., Xiong Y.,
Djonovic S., Millet Y., Bush J., McConkey B.J., Sheen J.,
Ausubel F.M.;
"Pathogen-secreted proteases activate a novel plant immune pathway.";
Nature 521:213-216(2015).
[18]
INTERACTION WITH MAPKKK5, PHOSPHORYLATION BY MAPKKK5, AND MUTAGENESIS
OF LYS-108; THR-224 AND SER-230.
STRAIN=cv. Columbia;
PubMed=27679653; DOI=10.15252/embj.201694248;
Yamada K., Yamaguchi K., Shirakawa T., Nakagami H., Mine A.,
Ishikawa K., Fujiwara M., Narusaka M., Narusaka Y., Ichimura K.,
Kobayashi Y., Matsui H., Nomura Y., Nomoto M., Tada Y., Fukao Y.,
Fukamizo T., Tsuda K., Shirasu K., Shibuya N., Kawasaki T.;
"The Arabidopsis CERK1-associated kinase PBL27 connects chitin
perception to MAPK activation.";
EMBO J. 35:2468-2483(2016).
-!- FUNCTION: Involved in the second phase of hydrogen peroxide
generation during hypersensitive response-like cell death.
Involved in the innate immune MAP kinase signaling cascade (MEKK1,
MKK4/MKK5 and MPK3/MPK6) downstream of bacterial flagellin
receptor FLS2. Activates by phosphorylation the downstream MPK3
and MPK6. YDA-MKK4/MKK5-MPK3/MPK6 module regulates stomatal cell
fate before the guard mother cell (GMC) is specified. This MAPK
cascade also functions downstream of the ER receptor in regulating
coordinated local cell proliferation, which shapes the morphology
of plant organs. MKK4 and MKK5 participate in the regulation of
floral organ abscission. Mediates osmotic-stress response via its
regulation of MPK3 activity. Target of the Pseudomonas syringae
type III effector HopF2. {ECO:0000269|PubMed:11687590,
ECO:0000269|PubMed:11875555, ECO:0000269|PubMed:17259259,
ECO:0000269|PubMed:18809915, ECO:0000269|PubMed:21806969,
ECO:0000269|PubMed:23263767, ECO:0000269|PubMed:23341468}.
-!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
-!- ACTIVITY REGULATION: Activated through serine and threonine
phosphorylation by MEKK1. Inhibited through phosphorylation by
GSK3/Shaggy-like kinase ASKs. {ECO:0000269|PubMed:11875555,
ECO:0000269|PubMed:23341468}.
-!- SUBUNIT: Interacts with ASK7/BIN2 (PubMed:23341468). Interacts
with P.syringae type III effector HopF2 (PubMed:20571112).
Interacts with MPK6 (PubMed:19513235). Interacts with RACK1A,
RACK1B and RACK1C (PubMed:25731164). Interacts with MAPKKK5 mainly
in the cytosol (PubMed:27679653). {ECO:0000269|PubMed:19513235,
ECO:0000269|PubMed:20571112, ECO:0000269|PubMed:23341468,
ECO:0000269|PubMed:25731164, ECO:0000269|PubMed:27679653}.
-!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Plastid, chloroplast
stroma.
-!- TISSUE SPECIFICITY: Expressed higher in stems and leaves than in
flowers and roots. {ECO:0000269|PubMed:10048483,
ECO:0000269|PubMed:21806969}.
-!- PTM: Phosphorylation at Thr-224 and Ser-230 by MAP kinase kinase
kinases positively regulates kinase activity. Phosphorylation at
Ser-230 and Thr-234 by GSK3/Shaggy-like kinase ASKs negatively
regulates kinase activity. Phosphorylated by MAPKKK5
(PubMed:27679653). {ECO:0000269|PubMed:11875555,
ECO:0000269|PubMed:23341468, ECO:0000269|PubMed:27679653}.
-!- DISRUPTION PHENOTYPE: RNAi double mutants MKK4 and MKK5 have a
strong abscission defect. Higher sensitivity to high salt and
drought stresses. {ECO:0000269|PubMed:18809915,
ECO:0000269|PubMed:21806969}.
-!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
protein kinase family. MAP kinase kinase subfamily. {ECO:0000305}.
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EMBL; AB015315; BAA28830.1; -; mRNA.
EMBL; AC025294; AAG50863.1; -; Genomic_DNA.
EMBL; CP002684; AEE32696.1; -; Genomic_DNA.
EMBL; AF324667; AAG40018.1; -; mRNA.
EMBL; AF326878; AAG41460.1; -; mRNA.
EMBL; AF349517; AAK15564.1; -; mRNA.
EMBL; AF375398; AAK52982.1; -; mRNA.
EMBL; AY129469; AAM91055.1; -; mRNA.
PIR; T51339; T51339.
RefSeq; NP_175577.1; NM_104044.3.
UniGene; At.351; -.
ProteinModelPortal; O80397; -.
SMR; O80397; -.
BioGrid; 26816; 14.
IntAct; O80397; 9.
STRING; 3702.AT1G51660.1; -.
iPTMnet; O80397; -.
PaxDb; O80397; -.
PRIDE; O80397; -.
EnsemblPlants; AT1G51660.1; AT1G51660.1; AT1G51660.
GeneID; 841591; -.
Gramene; AT1G51660.1; AT1G51660.1; AT1G51660.
KEGG; ath:AT1G51660; -.
Araport; AT1G51660; -.
TAIR; locus:2017662; AT1G51660.
eggNOG; KOG0581; Eukaryota.
eggNOG; ENOG410XQ5A; LUCA.
HOGENOM; HOG000234206; -.
InParanoid; O80397; -.
KO; K13413; -.
OMA; CHDMYER; -.
OrthoDB; EOG09360HJ2; -.
PhylomeDB; O80397; -.
PRO; PR:O80397; -.
Proteomes; UP000006548; Chromosome 1.
ExpressionAtlas; O80397; baseline and differential.
Genevisible; O80397; AT.
GO; GO:0009570; C:chloroplast stroma; IDA:UniProtKB.
GO; GO:0005737; C:cytoplasm; IDA:TAIR.
GO; GO:0005634; C:nucleus; IDA:TAIR.
GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
GO; GO:0004708; F:MAP kinase kinase activity; IBA:GO_Central.
GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
GO; GO:0000187; P:activation of MAPK activity; IBA:GO_Central.
GO; GO:0032147; P:activation of protein kinase activity; IBA:GO_Central.
GO; GO:0009814; P:defense response, incompatible interaction; IMP:TAIR.
GO; GO:0010227; P:floral organ abscission; IMP:TAIR.
GO; GO:0010229; P:inflorescence development; IGI:TAIR.
GO; GO:0009626; P:plant-type hypersensitive response; IEA:UniProtKB-KW.
GO; GO:0023014; P:signal transduction by protein phosphorylation; IBA:GO_Central.
GO; GO:0031098; P:stress-activated protein kinase signaling cascade; IBA:GO_Central.
InterPro; IPR011009; Kinase-like_dom_sf.
InterPro; IPR000719; Prot_kinase_dom.
InterPro; IPR017441; Protein_kinase_ATP_BS.
InterPro; IPR008271; Ser/Thr_kinase_AS.
Pfam; PF00069; Pkinase; 1.
SMART; SM00220; S_TKc; 1.
SUPFAM; SSF56112; SSF56112; 1.
PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
1: Evidence at protein level;
ATP-binding; Chloroplast; Complete proteome; Cytoplasm;
Hypersensitive response; Kinase; Nucleotide-binding; Nucleus;
Phosphoprotein; Plant defense; Plastid; Reference proteome;
Serine/threonine-protein kinase; Transferase.
CHAIN 1 366 Mitogen-activated protein kinase kinase
4.
/FTId=PRO_0000245823.
DOMAIN 79 334 Protein kinase. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
NP_BIND 85 93 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
ACT_SITE 196 196 Proton acceptor. {ECO:0000255|PROSITE-
ProRule:PRU00159, ECO:0000255|PROSITE-
ProRule:PRU10027}.
BINDING 108 108 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
MOD_RES 6 6 Phosphoserine; by ASK7.
{ECO:0000269|PubMed:23341468}.
MOD_RES 224 224 Phosphothreonine.
{ECO:0000269|PubMed:11875555}.
MOD_RES 230 230 Phosphoserine.
{ECO:0000269|PubMed:11875555,
ECO:0000269|PubMed:23341468}.
MOD_RES 230 230 Phosphoserine; by ASK7.
{ECO:0000269|PubMed:11875555,
ECO:0000269|PubMed:23341468}.
MOD_RES 234 234 Phosphothreonine; by ASK7.
{ECO:0000269|PubMed:23341468}.
MUTAGEN 108 108 K->M: Loss of activity.
{ECO:0000269|PubMed:11687590,
ECO:0000269|PubMed:11875555}.
MUTAGEN 108 108 K->R: Loss of activity. Phopshorylated by
MAPKKK5. {ECO:0000269|PubMed:11687590,
ECO:0000269|PubMed:11875555,
ECO:0000269|PubMed:27679653}.
MUTAGEN 224 224 T->A: Impaired phosphorylation by
MAPKKK5; when associated with A-230.
{ECO:0000269|PubMed:27679653}.
MUTAGEN 224 224 T->D: Constitutively active; when
associated with D-230 or E-230.
{ECO:0000269|PubMed:11687590,
ECO:0000269|PubMed:11875555}.
MUTAGEN 230 230 S->A: Abolishes phosphorylation by
ASK7/BIN2. Impaired phosphorylation by
MAPKKK5; when associated with A-224.
{ECO:0000269|PubMed:11687590,
ECO:0000269|PubMed:11875555,
ECO:0000269|PubMed:23341468,
ECO:0000269|PubMed:27679653}.
MUTAGEN 230 230 S->D: Constitutively active; when
associated with D-224.
{ECO:0000269|PubMed:11687590,
ECO:0000269|PubMed:11875555,
ECO:0000269|PubMed:23341468}.
MUTAGEN 230 230 S->E: Constitutively active; when
associated with D-224.
{ECO:0000269|PubMed:11687590,
ECO:0000269|PubMed:11875555,
ECO:0000269|PubMed:23341468}.
MUTAGEN 234 234 T->A: Abolishes phosphorylation by
ASK7/BIN2. {ECO:0000269|PubMed:23341468}.
MUTAGEN 234 234 T->D,E: Abolishes activity of MKK4
against MPK6.
{ECO:0000269|PubMed:23341468}.
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


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10-782-55048 Dual specificity mitogen-activated protein kinase kinase 1 - EC 2.7.12.2; MAP kinase kinase 1; MAPKK 1; ERK activator kinase 1; MAPK_ERK kinase 1; MEK1 N_A 0.02 mg
10-782-55048 Dual specificity mitogen-activated protein kinase kinase 1 - EC 2.7.12.2; MAP kinase kinase 1; MAPKK 1; ERK activator kinase 1; MAPK_ERK kinase 1; MEK1 N_A 0.05 mg
10-782-55047 Dual specificity mitogen-activated protein kinase kinase 1 - EC 2.7.12.2; MAP kinase kinase 1; MAPKK 1; ERK activator kinase 1; MAPK_ERK kinase 1; MEK1 N_A 0.05 mg
10-782-55047 Dual specificity mitogen-activated protein kinase kinase 1 - EC 2.7.12.2; MAP kinase kinase 1; MAPKK 1; ERK activator kinase 1; MAPK_ERK kinase 1; MEK1 N_A 0.02 mg
EIAAB25228 Dual specificity mitogen-activated protein kinase kinase 1,ERK activator kinase 1,MAP kinase kinase 1,Map2k1,MAPK_ERK kinase 1,MAPKK 1,MEK 1,Mek1,Prkmk1,Rat,Rattus norvegicus
EIAAB25230 Dual specificity mitogen-activated protein kinase kinase 1,ERK activator kinase 1,MAP kinase kinase 1,Map2k1,MAPK_ERK kinase 1,MAPKK 1,MEK 1,Mek1,Mouse,Mus musculus,Prkmk1


 

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