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 02-SEP-2026, entry version 135. 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, GN ECO:0000303|PubMed:9250676}; ORFNames=DDB_G0269152; OS Dictyostelium discoideum (Social amoeba). 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=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + CC H(+); 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=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + CC ADP + H(+); Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA- CC COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.12.2; CC Evidence={ECO:0000250|UniProtKB:Q869N2}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + CC ADP + H(+); Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA- CC COMP:20101, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, CC ChEBI:CHEBI:61978, 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 FunCoup; Q55CL6; 259. DR STRING; 44689.Q55CL6; -. DR PaxDb; 44689-Q55CL6; -. DR GeneID; 8617426; -. DR KEGG; ddi:DDB_G0269152; -. DR dictyBase; DDB_G0269152; mekA. DR VEuPathDB; AmoebaDB:DDB_G0269152; -. DR eggNOG; KOG0581; Eukaryota. DR HOGENOM; CLU_415880_0_0_1; -. DR InParanoid; Q55CL6; -. DR OMA; LECAIGK; -. 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; EXP:UniProtKB. 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:InterPro. DR GO; GO:0004708; F:MAP kinase kinase activity; TAS:dictyBase. DR GO; GO:0019887; F:protein kinase regulator activity; IMP:dictyBase. DR GO; GO:0106310; F:protein serine kinase activity; ISS:UniProtKB. DR GO; GO:0004713; F:protein tyrosine kinase activity; ISS:UniProtKB. 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 CDD; cd06623; PKc_MAPKK_plant_like; 1. DR FunFam; 3.30.200.20:FF:000716; Mitogen-activated protein kinase kinase 1; 1. DR FunFam; 1.10.510.10:FF:000432; mitogen-activated protein kinase kinase 3; 1. DR Gene3D; 3.30.200.20; Phosphorylase Kinase, domain 1; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. 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 PANTHER; PTHR48013:SF9; DUAL SPECIFICITY MITOGEN-ACTIVATED PROTEIN KINASE KINASE 5; 1. DR PANTHER; PTHR48013; DUAL SPECIFICITY MITOGEN-ACTIVATED PROTEIN KINASE KINASE 5-RELATED; 1. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 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 1..57 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 123..148 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 149..169 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 496..510 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 539..569 FT /note="Low complexity" 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 FT D-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 FT D-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 //