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Mitogen-activated protein kinase kinase kinase A (EC 2.7.11.25) (MAPK/ERK kinase 1) (MEK kinase 1) (MEKK 1) (MAPK/ERK kinase A) (MEK kinase A) (MEKK A) (MEKKalpha)

 MKKA_DICDI              Reviewed;         942 AA.
Q54R82; O96611;
05-MAY-2009, integrated into UniProtKB/Swiss-Prot.
05-MAY-2009, sequence version 2.
03-JUL-2019, entry version 97.
RecName: Full=Mitogen-activated protein kinase kinase kinase A {ECO:0000303|PubMed:9832508};
EC=2.7.11.25;
AltName: Full=MAPK/ERK kinase 1;
Short=MEK kinase 1 {ECO:0000312|EMBL:AAC97114.1};
Short=MEKK 1 {ECO:0000312|EMBL:AAC97114.1};
AltName: Full=MAPK/ERK kinase A;
Short=MEK kinase A {ECO:0000303|PubMed:9832508};
Short=MEKK A {ECO:0000303|PubMed:9832508};
Short=MEKKalpha {ECO:0000303|PubMed:9832508};
Name=mkkA {ECO:0000312|EMBL:EAL65773.2}; ORFNames=DDB_G0283265;
Dictyostelium discoideum (Slime mold).
Eukaryota; Amoebozoa; Mycetozoa; Dictyostelids; Dictyosteliales;
Dictyosteliaceae; Dictyostelium.
NCBI_TaxID=44689;
[1] {ECO:0000305, ECO:0000312|EMBL:AAC97114.1}
NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH UBC AND UPC,
SUBCELLULAR LOCATION, UBIQUITINATION, AND DISRUPTION PHENOTYPE.
STRAIN=AX3-1 {ECO:0000312|EMBL:AAC97114.1};
PubMed=9832508; DOI=10.1101/gad.12.22.3564;
Chung C.Y., Reddy T.B.K., Zhou K., Firtel R.A.;
"A novel, putative MEK kinase controls developmental timing and
spatial patterning in Dictyostelium and is regulated by ubiquitin-
mediated protein degradation.";
Genes Dev. 12:3564-3578(1998).
[2] {ECO:0000312|EMBL:EAL65773.2}
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
STRAIN=AX4;
PubMed=15875012; DOI=10.1038/nature03481;
Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A.,
Sucgang R., Berriman M., Song J., Olsen R., Szafranski K., Xu Q.,
Tunggal B., Kummerfeld S., Madera M., Konfortov B.A., Rivero F.,
Bankier A.T., Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P.,
Pilcher K., Chen G., Saunders D., Sodergren E.J., Davis P.,
Kerhornou A., Nie X., Hall N., Anjard C., Hemphill L., Bason N.,
Farbrother P., Desany B., Just E., Morio T., Rost R., Churcher C.M.,
Cooper J., Haydock S., van Driessche N., Cronin A., Goodhead I.,
Muzny D.M., Mourier T., Pain A., Lu M., Harper D., Lindsay R.,
Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
Knights A., Loulseged H., Mungall K.L., Oliver K., Price C.,
Quail M.A., Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D.,
Sanders M., Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S.,
Tivey A., Sugano S., White B., Walker D., Woodward J.R., Winckler T.,
Tanaka Y., Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A.,
Cox E.C., Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M.,
Kay R.R., Williams J.G., Dear P.H., Noegel A.A., Barrell B.G.,
Kuspa A.;
"The genome of the social amoeba Dictyostelium discoideum.";
Nature 435:43-57(2005).
-!- FUNCTION: Regulates cell-type differentiation and spatial
patterning, required for the proper induction and maintenance of
prespore cell differentiation. {ECO:0000269|PubMed:9832508}.
-!- CATALYTIC ACTIVITY:
Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
[protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999,
ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216;
EC=2.7.11.25; Evidence={ECO:0000250|UniProtKB:Q869N2};
-!- CATALYTIC ACTIVITY:
Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
EC=2.7.11.25; Evidence={ECO:0000250|UniProtKB:Q869N2};
-!- COFACTOR:
Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
Evidence={ECO:0000250|UniProtKB:Q869N2};
-!- SUBUNIT: Interacts with ubcB and ubpB.
{ECO:0000269|PubMed:9832508}.
-!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
protein {ECO:0000255}. Note=Localized predominantly at the
periphery of the cells, possibly in the cortex or the plasma
membrane. {ECO:0000255, ECO:0000269|PubMed:9832508}.
-!- PTM: ubcB and ubpB differentially control
ubiquitination/deubiquitination and degradation in a cell-type-
specific and temporally regulated manner.
{ECO:0000269|PubMed:9832508}.
-!- DISRUPTION PHENOTYPE: Cells develop precociously and exhibit
abnormal cell-type patterning with an increase in the pstO
prestalk compartment, a concomitant reduction in the prespore
domain, and a loss of the sharp compartment boundaries, resulting
in overlapping prestalk and prespore domains.
{ECO:0000269|PubMed:9832508}.
-!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
protein kinase family. MAP kinase kinase kinase subfamily.
{ECO:0000305}.
-!- SEQUENCE CAUTION:
Sequence=EAL65773.2; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
-----------------------------------------------------------------------
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Distributed under the Creative Commons Attribution (CC BY 4.0) License
-----------------------------------------------------------------------
EMBL; AF093689; AAC97114.1; -; mRNA.
EMBL; AAFI02000052; EAL65773.2; ALT_SEQ; Genomic_DNA.
RefSeq; XP_639165.2; XM_634073.2.
STRING; 44689.DDB0220118; -.
PaxDb; Q54R82; -.
PRIDE; Q54R82; -.
EnsemblProtists; EAL65773; EAL65773; DDB_G0283265.
GeneID; 8624035; -.
KEGG; ddi:DDB_G0283265; -.
dictyBase; DDB_G0283265; mkkA.
eggNOG; KOG0198; Eukaryota.
eggNOG; ENOG410XQGS; LUCA.
InParanoid; Q54R82; -.
Reactome; R-DDI-6798695; Neutrophil degranulation.
Reactome; R-DDI-75153; Apoptotic execution phase.
PRO; PR:Q54R82; -.
Proteomes; UP000002195; Chromosome 4.
Proteomes; UP000002195; Unassembled WGS sequence.
GO; GO:0005938; C:cell cortex; IDA:dictyBase.
GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
GO; GO:0004709; F:MAP kinase kinase kinase activity; IEA:UniProtKB-EC.
GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
GO; GO:0032147; P:activation of protein kinase activity; IBA:GO_Central.
GO; GO:0009653; P:anatomical structure morphogenesis; IMP:dictyBase.
GO; GO:0023014; P:signal transduction by protein phosphorylation; IBA:GO_Central.
GO; GO:0030587; P:sorocarp development; IMP:dictyBase.
GO; GO:0030435; P:sporulation resulting in formation of a cellular spore; IEA:UniProtKB-KW.
GO; GO:0031098; P:stress-activated protein kinase signaling cascade; IBA:GO_Central.
Gene3D; 2.130.10.10; -; 3.
InterPro; IPR036047; F-box-like_dom_sf.
InterPro; IPR001810; F-box_dom.
InterPro; IPR020472; G-protein_beta_WD-40_rep.
InterPro; IPR011009; Kinase-like_dom_sf.
InterPro; IPR000270; PB1_dom.
InterPro; IPR000719; Prot_kinase_dom.
InterPro; IPR017441; Protein_kinase_ATP_BS.
InterPro; IPR008271; Ser/Thr_kinase_AS.
InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
InterPro; IPR001680; WD40_repeat.
InterPro; IPR019775; WD40_repeat_CS.
InterPro; IPR017986; WD40_repeat_dom.
InterPro; IPR036322; WD40_repeat_dom_sf.
Pfam; PF12937; F-box-like; 1.
Pfam; PF00564; PB1; 1.
Pfam; PF00069; Pkinase; 1.
Pfam; PF00400; WD40; 5.
PRINTS; PR00320; GPROTEINBRPT.
SMART; SM00256; FBOX; 1.
SMART; SM00666; PB1; 1.
SMART; SM00220; S_TKc; 1.
SMART; SM00320; WD40; 7.
SUPFAM; SSF50978; SSF50978; 1.
SUPFAM; SSF56112; SSF56112; 1.
SUPFAM; SSF81383; SSF81383; 1.
PROSITE; PS50181; FBOX; 1.
PROSITE; PS51745; PB1; 1.
PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PROSITE; PS00678; WD_REPEATS_1; 4.
PROSITE; PS50082; WD_REPEATS_2; 5.
PROSITE; PS50294; WD_REPEATS_REGION; 1.
1: Evidence at protein level;
ATP-binding; Complete proteome; Kinase; Magnesium; Membrane;
Metal-binding; Nucleotide-binding; Reference proteome; Repeat;
Serine/threonine-protein kinase; Sporulation; Transferase;
Transmembrane; Transmembrane helix; Ubl conjugation; WD repeat.
CHAIN 1 942 Mitogen-activated protein kinase kinase
kinase A.
/FTId=PRO_0000371250.
TRANSMEM 513 533 Helical. {ECO:0000255}.
DOMAIN 15 96 PB1. {ECO:0000255|PROSITE-
ProRule:PRU01081}.
DOMAIN 170 429 Protein kinase. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
DOMAIN 518 564 F-box. {ECO:0000255|PROSITE-
ProRule:PRU00080}.
REPEAT 607 646 WD 1. {ECO:0000255}.
REPEAT 690 733 WD 2. {ECO:0000255}.
REPEAT 736 778 WD 3. {ECO:0000255}.
REPEAT 780 825 WD 4. {ECO:0000255}.
REPEAT 828 865 WD 5. {ECO:0000255}.
REPEAT 872 909 WD 6. {ECO:0000255}.
REPEAT 912 942 WD 7. {ECO:0000255}.
NP_BIND 176 184 ATP. {ECO:0000250|UniProtKB:P28523,
ECO:0000255|PROSITE-ProRule:PRU00159}.
COMPBIAS 121 144 Poly-Asn. {ECO:0000255}.
COMPBIAS 449 461 Poly-Thr. {ECO:0000255}.
COMPBIAS 471 479 Poly-Gln. {ECO:0000255}.
COMPBIAS 504 513 Poly-Ser. {ECO:0000255}.
ACT_SITE 297 297 Proton acceptor.
{ECO:0000250|UniProtKB:P28523,
ECO:0000255|PROSITE-ProRule:PRU00159,
ECO:0000255|PROSITE-ProRule:PRU10027}.
BINDING 199 199 ATP. {ECO:0000250|UniProtKB:P28523,
ECO:0000255|PROSITE-ProRule:PRU00159}.
SEQUENCE 942 AA; 105796 MW; C9E4928A8C7C68F7 CRC64;
MSWLNNPSQN FVDPFIRIKC ILGDDIRIIK FNSNISYGGL MNQLEQDFQC PISIHQYEDY
EGDKVTVKSK DDIMEALTMY FELKALNPTK IISTKFFLKQ LPPQSQPLSS SLSPTQSLIL
NNNNNNNNNN NNNNNNNNNN NNNNIIQHTD FPSLIINEHE ELISNHNIKW QKGQILGRGG
YGSVYLGLNK DTGELFAVKQ LEIVDINSDP KLKNMILSFS KEIEVMRSLR HDNIVRYLGT
SLDQSFLSVF LEYIPGGSIS SLLGKFGAFS ENVIKVYTKQ ILQGLSFLHA NSIIHRDIKG
ANILIDTKGI VKLSDFGCSK SFSGIVSQFK SMQGTPYWMA PEVIKQTGHG RSSDIWSLGC
VIVEMATAQP PWSNITELAA VMYHIASSNS IPNIPSHMSQ EAFDFLNLCF KRDPKERPDA
NQLLKHPFIM NLDDNIQLPT ISPTTTLSTN TTNTTATTTT TNNATNSNIN QQQQQQQQQP
PTRTQRVSIS AGSSNNKRYT PPISTSTSSS SSSILNNFSI NIILPINLII LIFREIKPNF
VNTLSRVCKH WKQIIDDDEL WNKYCSDRLI NKSKFEESIT WKSNYIKIYK QQKVWFHNKL
NHSTLKGHDK GVFCVKLIDD QGMVLSGGED KKLKVWDISG NHHHNHHSGI VGSISKKSGL
NIINNNNSNN SNSSSNSSSS NSRYLFSLKG HSGCIKSVDY QRQSGSDVSR VFTASADFTC
KIFSLKTKKT LFTYTNHQEA VTCINYLGDV ENKCITSSLD KTIQLWDAET GSCLSTLRGH
TGGIYCVKTD QVATHGNGYN HLVVSASVDK TSNVWDTRSS SKVRSFTQHT EDVLCCYVFD
QKVVTGSCDG TIKLWDIGTG KTISTFIPSE TRQKNYVWTV QFDQSKIISS GKTGIIRIWD
IYNERDSRSI GGHHETIFSL QFNNQKLITG SLDKLVKIWS ID


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Related Genes :
[mkkA DDB_G0283265] Mitogen-activated protein kinase kinase kinase A (EC 2.7.11.25) (MAPK/ERK kinase 1) (MEK kinase 1) (MEKK 1) (MAPK/ERK kinase A) (MEK kinase A) (MEKK A) (MEKKalpha)
[Map3k1 Mekk Mekk1] Mitogen-activated protein kinase kinase kinase 1 (EC 2.7.11.25) (MAPK/ERK kinase kinase 1) (MEK kinase 1) (MEKK 1)
[MAP3K1 MAPKKK1 MEKK MEKK1] Mitogen-activated protein kinase kinase kinase 1 (EC 2.7.11.25) (MAPK/ERK kinase kinase 1) (MEK kinase 1) (MEKK 1)
[Map3k1 Mekk Mekk1] Mitogen-activated protein kinase kinase kinase 1 (EC 2.7.11.25) (MAPK/ERK kinase kinase 1) (MEK kinase 1) (MEKK 1)
[Map3k2 Mekk2] Mitogen-activated protein kinase kinase kinase 2 (EC 2.7.11.25) (MAPK/ERK kinase kinase 2) (MEK kinase 2) (MEKK 2)
[MAP3K5 ASK1 MAPKKK5 MEKK5] Mitogen-activated protein kinase kinase kinase 5 (EC 2.7.11.25) (Apoptosis signal-regulating kinase 1) (ASK-1) (MAPK/ERK kinase kinase 5) (MEK kinase 5) (MEKK 5)
[MAP2K1 MEK1 PRKMK1] Dual specificity mitogen-activated protein kinase kinase 1 (MAP kinase kinase 1) (MAPKK 1) (MKK1) (EC 2.7.12.2) (ERK activator kinase 1) (MAPK/ERK kinase 1) (MEK 1)
[Map2k1 Mek1 Prkmk1] Dual specificity mitogen-activated protein kinase kinase 1 (MAP kinase kinase 1) (MAPKK 1) (EC 2.7.12.2) (ERK activator kinase 1) (MAPK/ERK kinase 1) (MEK 1)
[MAP2K1 MEK1 PRKMK1] Dual specificity mitogen-activated protein kinase kinase 1 (MAP kinase kinase 1) (MAPKK 1) (EC 2.7.12.2) (ERK activator kinase 1) (MAPK/ERK kinase 1) (MEK 1)
[Map2k1 Mek1 Prkmk1] Dual specificity mitogen-activated protein kinase kinase 1 (MAP kinase kinase 1) (MAPKK 1) (EC 2.7.12.2) (ERK activator kinase 1) (MAPK/ERK kinase 1) (MEK 1)
[MAP2K1 MEK1 PRKMK1] Dual specificity mitogen-activated protein kinase kinase 1 (MAP kinase kinase 1) (MAPKK 1) (EC 2.7.12.2) (ERK activator kinase 1) (MAPK/ERK kinase 1) (MEK 1)
[Map3k5 Ask1 Mekk5] Mitogen-activated protein kinase kinase kinase 5 (EC 2.7.11.25) (Apoptosis signal-regulating kinase 1) (ASK-1) (MAPK/ERK kinase kinase 5) (MEK kinase 5) (MEKK 5)
[MAP2K2 MEK2 MKK2 PRKMK2] Dual specificity mitogen-activated protein kinase kinase 2 (MAP kinase kinase 2) (MAPKK 2) (EC 2.7.12.2) (ERK activator kinase 2) (MAPK/ERK kinase 2) (MEK 2)
[Map2k2 Mek2 Mkk2 Prkmk2] Dual specificity mitogen-activated protein kinase kinase 2 (MAP kinase kinase 2) (MAPKK 2) (EC 2.7.12.2) (ERK activator kinase 2) (MAPK/ERK kinase 2) (MEK 2)
[MAP2K1 MEK1 PRKMK1] Dual specificity mitogen-activated protein kinase kinase 1 (MAP kinase kinase 1) (MAPKK 1) (EC 2.7.12.2) (ERK activator kinase 1) (MAPK/ERK kinase 1) (MEK 1)
[Map2k2 Mek2 Mkk2 Prkmk2] Dual specificity mitogen-activated protein kinase kinase 2 (MAP kinase kinase 2) (MAPKK 2) (EC 2.7.12.2) (ERK activator kinase 2) (MAPK/ERK kinase 2) (MEK 2)
[mekA MEK1 DDB_G0269152] Dual specificity mitogen-activated protein kinase kinase 1 (MAP kinase kinase 1) (MAPKK 1) (EC 2.7.12.2) (ERK activator kinase 1) (MAPK/ERK kinase 1) (DdMEK1) (MEK1) (MAPK/ERK kinase A) (MEKA)
[MAP2K2 MEK2] Dual specificity mitogen-activated protein kinase kinase 2 (MAP kinase kinase 2) (MAPKK 2) (EC 2.7.12.2) (ERK activator kinase 2) (MAPK/ERK kinase 2) (MEK 2)
[MAP2K6 MEK6 MKK6 PRKMK6 SKK3] Dual specificity mitogen-activated protein kinase kinase 6 (MAP kinase kinase 6) (MAPKK 6) (EC 2.7.12.2) (MAPK/ERK kinase 6) (MEK 6) (Stress-activated protein kinase kinase 3) (SAPK kinase 3) (SAPKK-3) (SAPKK3)
[MAP4K2 GCK RAB8IP] Mitogen-activated protein kinase kinase kinase kinase 2 (EC 2.7.11.1) (B lymphocyte serine/threonine-protein kinase) (Germinal center kinase) (GC kinase) (MAPK/ERK kinase kinase kinase 2) (MEK kinase kinase 2) (MEKKK 2) (Rab8-interacting protein)
[Mapk1 Erk2 Mapk Prkm1] Mitogen-activated protein kinase 1 (MAP kinase 1) (MAPK 1) (EC 2.7.11.24) (ERT1) (Extracellular signal-regulated kinase 2) (ERK-2) (MAP kinase isoform p42) (p42-MAPK) (Mitogen-activated protein kinase 2) (MAP kinase 2) (MAPK 2)
[MAPK1 ERK2 PRKM1 PRKM2] Mitogen-activated protein kinase 1 (MAP kinase 1) (MAPK 1) (EC 2.7.11.24) (ERT1) (Extracellular signal-regulated kinase 2) (ERK-2) (MAP kinase isoform p42) (p42-MAPK) (Mitogen-activated protein kinase 2) (MAP kinase 2) (MAPK 2)
[Mapk1 Erk2 Mapk Prkm1] Mitogen-activated protein kinase 1 (MAP kinase 1) (MAPK 1) (EC 2.7.11.24) (ERT1) (Extracellular signal-regulated kinase 2) (ERK-2) (MAP kinase isoform p42) (p42-MAPK) (Mitogen-activated protein kinase 2) (MAP kinase 2) (MAPK 2)
[Map2k5 Mek5 Mkk5 Prkmk5] Dual specificity mitogen-activated protein kinase kinase 5 (MAP kinase kinase 5) (MAPKK 5) (EC 2.7.12.2) (MAPK/ERK kinase 5) (MEK 5)
[MAPK3 ERK1 PRKM3] Mitogen-activated protein kinase 3 (MAP kinase 3) (MAPK 3) (EC 2.7.11.24) (ERT2) (Extracellular signal-regulated kinase 1) (ERK-1) (Insulin-stimulated MAP2 kinase) (MAP kinase isoform p44) (p44-MAPK) (Microtubule-associated protein 2 kinase) (p44-ERK1)
[MAPK1 ERK2 PRKM1] Mitogen-activated protein kinase 1 (MAP kinase 1) (MAPK 1) (EC 2.7.11.24) (ERT1) (Extracellular signal-regulated kinase 2) (ERK-2) (Mitogen-activated protein kinase 2) (MAP kinase 2) (MAPK 2)
[Mapk3 Erk1 Prkm3] Mitogen-activated protein kinase 3 (MAP kinase 3) (MAPK 3) (EC 2.7.11.24) (ERT2) (Extracellular signal-regulated kinase 1) (ERK-1) (Insulin-stimulated MAP2 kinase) (MAP kinase isoform p44) (p44-MAPK) (MNK1) (Microtubule-associated protein 2 kinase) (p44-ERK1)
[Mapk3 Erk1 Prkm3] Mitogen-activated protein kinase 3 (MAP kinase 3) (MAPK 3) (EC 2.7.11.24) (ERT2) (Extracellular signal-regulated kinase 1) (ERK-1) (Insulin-stimulated MAP2 kinase) (MAP kinase isoform p44) (p44-MAPK) (MNK1) (Microtubule-associated protein 2 kinase) (p44-ERK1)
[Map4k2 Rab8ip] Mitogen-activated protein kinase kinase kinase kinase 2 (EC 2.7.11.1) (Germinal center kinase) (GCK) (MAPK/ERK kinase kinase kinase 2) (MEK kinase kinase 2) (MEKKK 2) (Rab8-interacting protein)
[MAPK7 BMK1 ERK5 PRKM7] Mitogen-activated protein kinase 7 (MAP kinase 7) (MAPK 7) (EC 2.7.11.24) (Big MAP kinase 1) (BMK-1) (Extracellular signal-regulated kinase 5) (ERK-5)

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