MP2K1_DICDI
ID MP2K1_DICDI Reviewed; 660 AA.
AC Q55CL6; O00885;
DT 05-MAY-2009, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2005, sequence version 1.
DT 03-AUG-2022, entry version 119.
DE RecName: Full=Dual specificity mitogen-activated protein kinase kinase 1 {ECO:0000303|PubMed:12062087, ECO:0000303|PubMed:9250676};
DE Short=MAP kinase kinase 1 {ECO:0000303|PubMed:12062087, ECO:0000303|PubMed:9250676};
DE Short=MAPKK 1 {ECO:0000303|PubMed:12062087, ECO:0000303|PubMed:9250676};
DE EC=2.7.12.2 {ECO:0000250|UniProtKB:Q869N2};
DE AltName: Full=ERK activator kinase 1 {ECO:0000303|PubMed:12062087, ECO:0000303|PubMed:9250676};
DE AltName: Full=MAPK/ERK kinase 1 {ECO:0000303|PubMed:12062087, ECO:0000303|PubMed:9250676};
DE Short=DdMEK1 {ECO:0000303|PubMed:12062087, ECO:0000303|PubMed:9250676};
DE Short=MEK1 {ECO:0000303|PubMed:12062087, ECO:0000303|PubMed:9250676};
DE AltName: Full=MAPK/ERK kinase A {ECO:0000312|EMBL:EAL71926.1};
DE Short=MEKA {ECO:0000312|EMBL:EAL71926.1};
GN Name=mekA {ECO:0000312|EMBL:EAL71926.1};
GN Synonyms=MEK1 {ECO:0000303|PubMed:12062087, ECO:0000303|PubMed:9250676};
GN ORFNames=DDB_G0269152;
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:AAB58577.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS
RP OF LYS-321; SER-444; THR-448 AND PRO-458.
RC STRAIN=AX3-1 {ECO:0000312|EMBL:AAB58577.1};
RX PubMed=9250676; DOI=10.1093/emboj/16.14.4317;
RA Ma H., Gamper M., Parent C., Firtel R.A.;
RT "The Dictyostelium MAP kinase kinase DdMEK1 regulates chemotaxis and is
RT essential for chemoattractant-mediated activation of guanylyl cyclase.";
RL EMBO J. 16:4317-4332(1997).
RN [2] {ECO:0000312|EMBL:EAL71926.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4 {ECO:0000312|EMBL:EAL71926.1};
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).
RN [3] {ECO:0000305}
RP FUNCTION, INTERACTION WITH MIP1, SUBCELLULAR LOCATION, SUMOYLATION AT
RP LYS-105, UBIQUITINATION, AND MUTAGENESIS OF LYS-105; SER-444 AND THR-448.
RX PubMed=12062087; DOI=10.1016/s1534-5807(02)00186-7;
RA Sobko A., Ma H., Firtel R.A.;
RT "Regulated SUMOylation and ubiquitination of DdMEK1 is required for proper
RT chemotaxis.";
RL Dev. Cell 2:745-756(2002).
CC -!- FUNCTION: Required for cAMP-mediated activation of guanylyl cyclase
CC activity and plays an essential role in aggregation, morphogenesis, and
CC chemotaxis. Appears to act upstream of erk1 but not erk2.
CC {ECO:0000269|PubMed:12062087, ECO:0000269|PubMed:9250676}.
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 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=2.7.12.2; Evidence={ECO:0000250|UniProtKB:Q869N2};
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 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 mip1. {ECO:0000269|PubMed:12062087}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12062087}. Nucleus
CC {ECO:0000269|PubMed:12062087}. Note=Predominantly nuclear in
CC vegetatively growing cells. Translocates to the cell cortex in response
CC to chemoattractant stimulation and is present at the leading edge of
CC chemotaxing cells. {ECO:0000269|PubMed:12062087}.
CC -!- PTM: Sumoylated and ubiquitinated in response to chemoattractant
CC stimulation. Sumoylation is linked to kinase activation and results in
CC translocation. {ECO:0000269|PubMed:12062087}.
CC -!- DISRUPTION PHENOTYPE: Cells are unable to undergo chemotaxis properly
CC during aggregation in response to the chemoattractant cAMP or activate
CC guanylyl cyclase. Form extremely small aggregates resulting in the
CC development of slugs and terminal fruiting bodies that are
CC significantly smaller than those of wild-type cells. Transfer of the
CC temperature-sensitive mutants from a temperature of 18 degrees Celsius
CC to 27 degrees Celsius causes forming aggregates to split into multiple
CC small aggregates. {ECO:0000269|PubMed:9250676}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. MAP kinase kinase subfamily.
CC {ECO:0000250|UniProtKB:Q869N2}.
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DR EMBL; U87912; AAB58577.1; -; mRNA.
DR EMBL; AAFI02000005; EAL71926.1; -; Genomic_DNA.
DR RefSeq; XP_646465.1; XM_641373.1.
DR AlphaFoldDB; Q55CL6; -.
DR SMR; Q55CL6; -.
DR STRING; 44689.DDB0191164; -.
DR PaxDb; Q55CL6; -.
DR EnsemblProtists; EAL71926; EAL71926; DDB_G0269152.
DR GeneID; 8617426; -.
DR KEGG; ddi:DDB_G0269152; -.
DR dictyBase; DDB_G0269152; mekA.
DR eggNOG; KOG0581; Eukaryota.
DR HOGENOM; CLU_415880_0_0_1; -.
DR InParanoid; Q55CL6; -.
DR OMA; YERTETI; -.
DR PhylomeDB; Q55CL6; -.
DR PRO; PR:Q55CL6; -.
DR Proteomes; UP000002195; Chromosome 1.
DR GO; GO:0005938; C:cell cortex; IDA:dictyBase.
DR GO; GO:0031252; C:cell leading edge; IDA:dictyBase.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:dictyBase.
DR GO; GO:0016020; C:membrane; TAS:dictyBase.
DR GO; GO:0005634; C:nucleus; IDA:dictyBase.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004708; F:MAP kinase kinase activity; TAS:dictyBase.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0019887; F:protein kinase regulator activity; IMP:dictyBase.
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:0043130; F:ubiquitin binding; IPI:dictyBase.
DR GO; GO:0031152; P:aggregation involved in sorocarp development; TAS:dictyBase.
DR GO; GO:0043327; P:chemotaxis to cAMP; IMP:dictyBase.
DR GO; GO:0000165; P:MAPK cascade; IMP:dictyBase.
DR GO; GO:0072697; P:protein localization to cell cortex; IDA:dictyBase.
DR GO; GO:0030587; P:sorocarp development; HMP:dictyBase.
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; Chemotaxis; Cytoplasm; Isopeptide bond; Kinase; Magnesium;
KW Metal-binding; Nucleotide-binding; Nucleus; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Ubl conjugation.
FT CHAIN 1..660
FT /note="Dual specificity mitogen-activated protein kinase
FT kinase 1"
FT /id="PRO_0000371251"
FT DOMAIN 292..641
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..60
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 105..169
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 204..229
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 491..510
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 539..573
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 108..169
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 414
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P28523,
FT ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-
FT ProRule:PRU10027"
FT BINDING 298..306
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P28523,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 321
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P28523,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT CROSSLNK 105
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000269|PubMed:12062087"
FT MUTAGEN 105
FT /note="K->R: Loss of sumoylation, and translocation
FT ability."
FT /evidence="ECO:0000269|PubMed:12062087"
FT MUTAGEN 321
FT /note="K->A: Loss of aggregation ability."
FT /evidence="ECO:0000269|PubMed:9250676"
FT MUTAGEN 444
FT /note="S->A: Loss of aggregation ability, sumoylation and
FT translocation; when associated with A-448."
FT /evidence="ECO:0000269|PubMed:12062087,
FT ECO:0000269|PubMed:9250676"
FT MUTAGEN 444
FT /note="S->D: Loss of aggregation ability and defects in
FT cAMP-mediated signaling pathways; when associated with D-
FT 448."
FT /evidence="ECO:0000269|PubMed:12062087,
FT ECO:0000269|PubMed:9250676"
FT MUTAGEN 444
FT /note="S->E: Constitutively sumoylated and cytosolic; when
FT associated with E-448."
FT /evidence="ECO:0000269|PubMed:12062087,
FT ECO:0000269|PubMed:9250676"
FT MUTAGEN 448
FT /note="T->A: Loss of aggregation ability, sumoylation and
FT translocation; when associated with A-444."
FT /evidence="ECO:0000269|PubMed:12062087,
FT ECO:0000269|PubMed:9250676"
FT MUTAGEN 448
FT /note="T->D: Loss of aggregation ability and defects in
FT cAMP-mediated signaling pathways; when associated with D-
FT 444."
FT /evidence="ECO:0000269|PubMed:12062087,
FT ECO:0000269|PubMed:9250676"
FT MUTAGEN 448
FT /note="T->E: Constitutively sumoylated and cytosolic; when
FT associated with E-444."
FT /evidence="ECO:0000269|PubMed:12062087,
FT ECO:0000269|PubMed:9250676"
FT MUTAGEN 458
FT /note="P->S: Temperature-sensitive mutant."
FT /evidence="ECO:0000269|PubMed:9250676"
FT CONFLICT 471
FT /note="E -> D (in Ref. 1; AAB58577)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 660 AA; 74138 MW; 3B66637C4BA520FF CRC64;
MNTNTNTNTN ISSSGNNIIN TPTTNNNNKN NNNNNNNNNN SNNSNNNSSN NNNNNNNAVG
VKTGKKVNLK VETPVQNNEN SYSLTTSGTF KEGDLLINKK GLLIKGESPK NSSVNDRNKN
KSLHSNLNPQ LLASPTSSES MDFNQGFYNN NNNNNNNNNN NNLNNFNNLM NNGIDSPQLS
GISISTPTSS HSFNNTFTNY YNNNNNYNNY NNNNNSNNNN NNYNNSNNNF NNFNNYNNYG
NNNNFNNFNA LQSSSNSSFD ISSSGSSNNY LNNSANNHPH YDTNLSYDLK DLKIIRVLGR
GAGGVVKLAY HETSGTYIAL KVITLDIQEN IRKQIILELK TLHKTSYPYI VSFYDAFYTE
GSIFIALEFM ELGSLSDIMK KTSTIPEPVL GKIAFQVLQG LVYLHRKLHL IHRDIKPSNI
LVNNKGEAKI ADFGVSGQLQ HTLSKAVTWV GTVTYMSPER ISGRSYSFDS EIWSLGLTIL
ECAIGKFPYG SNLPHQQQQP LQQQQQQQQQ QQQPLQQQQQ QQQQQQQPLQ LQLQNLDINN
SNNNIRNSNN NNNNNNNNNN NNNNNNNNNV LDISNGGLVD SGSSVPEGMG FWVLLDCIVK
EEVPILPSTF SKEFRSFISE CLQKEPTERP TASNLLNHEF VKKYQNFNVE KWTANLKQQQ
