MKKA_DICDI
ID MKKA_DICDI Reviewed; 942 AA.
AC Q54R82; O96611;
DT 05-MAY-2009, integrated into UniProtKB/Swiss-Prot.
DT 05-MAY-2009, sequence version 2.
DT 03-AUG-2022, entry version 109.
DE RecName: Full=Mitogen-activated protein kinase kinase kinase A {ECO:0000303|PubMed:9832508};
DE EC=2.7.11.25;
DE AltName: Full=MAPK/ERK kinase 1;
DE Short=MEK kinase 1 {ECO:0000312|EMBL:AAC97114.1};
DE Short=MEKK 1 {ECO:0000312|EMBL:AAC97114.1};
DE AltName: Full=MAPK/ERK kinase A;
DE Short=MEK kinase A {ECO:0000303|PubMed:9832508};
DE Short=MEKK A {ECO:0000303|PubMed:9832508};
DE Short=MEKKalpha {ECO:0000303|PubMed:9832508};
GN Name=mkkA {ECO:0000312|EMBL:EAL65773.2}; ORFNames=DDB_G0283265;
OS Dictyostelium discoideum (Slime mold).
OC Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC Dictyosteliaceae; Dictyostelium.
OX NCBI_TaxID=44689;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAC97114.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH UBC AND UPC,
RP SUBCELLULAR LOCATION, UBIQUITINATION, AND DISRUPTION PHENOTYPE.
RC STRAIN=AX3-1 {ECO:0000312|EMBL:AAC97114.1};
RX PubMed=9832508; DOI=10.1101/gad.12.22.3564;
RA Chung C.Y., Reddy T.B.K., Zhou K., Firtel R.A.;
RT "A novel, putative MEK kinase controls developmental timing and spatial
RT patterning in Dictyostelium and is regulated by ubiquitin-mediated protein
RT degradation.";
RL Genes Dev. 12:3564-3578(1998).
RN [2] {ECO:0000312|EMBL:EAL65773.2}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=15875012; DOI=10.1038/nature03481;
RA Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT "The genome of the social amoeba Dictyostelium discoideum.";
RL Nature 435:43-57(2005).
CC -!- FUNCTION: Regulates cell-type differentiation and spatial patterning,
CC required for the proper induction and maintenance of prespore cell
CC differentiation. {ECO:0000269|PubMed:9832508}.
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=2.7.11.25;
CC Evidence={ECO:0000250|UniProtKB:Q869N2};
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=2.7.11.25; Evidence={ECO:0000250|UniProtKB:Q869N2};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q869N2};
CC -!- SUBUNIT: Interacts with ubcB and ubpB. {ECO:0000269|PubMed:9832508}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}. Note=Localized predominantly at the periphery of
CC the cells, possibly in the cortex or the plasma membrane. {ECO:0000255,
CC ECO:0000269|PubMed:9832508}.
CC -!- PTM: ubcB and ubpB differentially control
CC ubiquitination/deubiquitination and degradation in a cell-type-specific
CC and temporally regulated manner. {ECO:0000269|PubMed:9832508}.
CC -!- DISRUPTION PHENOTYPE: Cells develop precociously and exhibit abnormal
CC cell-type patterning with an increase in the pstO prestalk compartment,
CC a concomitant reduction in the prespore domain, and a loss of the sharp
CC compartment boundaries, resulting in overlapping prestalk and prespore
CC domains. {ECO:0000269|PubMed:9832508}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. MAP kinase kinase kinase subfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=EAL65773.2; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AF093689; AAC97114.1; -; mRNA.
DR EMBL; AAFI02000052; EAL65773.2; ALT_SEQ; Genomic_DNA.
DR RefSeq; XP_639165.2; XM_634073.2.
DR AlphaFoldDB; Q54R82; -.
DR SMR; Q54R82; -.
DR PaxDb; Q54R82; -.
DR EnsemblProtists; EAL65773; EAL65773; DDB_G0283265.
DR GeneID; 8624035; -.
DR KEGG; ddi:DDB_G0283265; -.
DR dictyBase; DDB_G0283265; mkkA.
DR eggNOG; KOG0198; Eukaryota.
DR eggNOG; KOG0274; Eukaryota.
DR InParanoid; Q54R82; -.
DR PRO; PR:Q54R82; -.
DR Proteomes; UP000002195; Chromosome 4.
DR GO; GO:0005938; C:cell cortex; IDA:dictyBase.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004709; F:MAP kinase kinase kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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:0009653; P:anatomical structure morphogenesis; IMP:dictyBase.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0030587; P:sorocarp development; IMP:dictyBase.
DR GO; GO:0030435; P:sporulation resulting in formation of a cellular spore; IEA:UniProtKB-KW.
DR Gene3D; 2.130.10.10; -; 3.
DR InterPro; IPR036047; F-box-like_dom_sf.
DR InterPro; IPR001810; F-box_dom.
DR InterPro; IPR020472; G-protein_beta_WD-40_rep.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000270; PB1_dom.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR019775; WD40_repeat_CS.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR Pfam; PF12937; F-box-like; 1.
DR Pfam; PF00564; PB1; 1.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00400; WD40; 5.
DR PRINTS; PR00320; GPROTEINBRPT.
DR SMART; SM00256; FBOX; 1.
DR SMART; SM00666; PB1; 1.
DR SMART; SM00220; S_TKc; 1.
DR SMART; SM00320; WD40; 7.
DR SUPFAM; SSF50978; SSF50978; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF81383; SSF81383; 1.
DR PROSITE; PS50181; FBOX; 1.
DR PROSITE; PS51745; PB1; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 4.
DR PROSITE; PS50082; WD_REPEATS_2; 5.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Kinase; Magnesium; Membrane; Metal-binding;
KW Nucleotide-binding; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; Sporulation; Transferase; Transmembrane;
KW Transmembrane helix; Ubl conjugation; WD repeat.
FT CHAIN 1..942
FT /note="Mitogen-activated protein kinase kinase kinase A"
FT /id="PRO_0000371250"
FT TRANSMEM 513..533
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 15..96
FT /note="PB1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01081"
FT DOMAIN 170..429
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 518..564
FT /note="F-box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00080"
FT REPEAT 607..646
FT /note="WD 1"
FT /evidence="ECO:0000255"
FT REPEAT 690..733
FT /note="WD 2"
FT /evidence="ECO:0000255"
FT REPEAT 736..778
FT /note="WD 3"
FT /evidence="ECO:0000255"
FT REPEAT 780..825
FT /note="WD 4"
FT /evidence="ECO:0000255"
FT REPEAT 828..865
FT /note="WD 5"
FT /evidence="ECO:0000255"
FT REPEAT 872..909
FT /note="WD 6"
FT /evidence="ECO:0000255"
FT REPEAT 912..942
FT /note="WD 7"
FT /evidence="ECO:0000255"
FT REGION 107..144
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 441..512
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 297
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P28523,
FT ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-
FT ProRule:PRU10027"
FT BINDING 176..184
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P28523,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 199
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P28523,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
SQ 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
