ERK2_DICDI
ID ERK2_DICDI Reviewed; 369 AA.
AC Q54QB1; Q7M445;
DT 04-DEC-2007, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2005, sequence version 1.
DT 03-AUG-2022, entry version 120.
DE RecName: Full=Extracellular signal-regulated kinase 2;
DE Short=ERK2;
DE EC=2.7.11.24;
DE AltName: Full=Defective in aggregation protein C;
DE AltName: Full=MAP kinase 2;
GN Name=erkB; Synonyms=dagC, erk2; ORFNames=DDB_G0283903;
OS Dictyostelium discoideum (Slime mold).
OC Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC Dictyosteliaceae; Dictyostelium.
OX NCBI_TaxID=44689;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC STRAIN=AX4;
RX PubMed=7844154; DOI=10.1083/jcb.128.3.405;
RA Segall J.E., Kuspa A., Shaulsky G., Ecke M., Maeda M., Gaskins C.,
RA Firtel R.A., Loomis W.F.;
RT "A MAP kinase necessary for receptor-mediated activation of adenylyl
RT cyclase in Dictyostelium.";
RL J. Cell Biol. 128:405-413(1995).
RN [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).
RN [3]
RP DISRUPTION PHENOTYPE.
RX PubMed=9427685; DOI=10.1242/jcs.111.3.373;
RA Wang Y., Liu J., Segall J.E.;
RT "MAP kinase function in amoeboid chemotaxis.";
RL J. Cell Sci. 111:373-383(1998).
RN [4]
RP DISRUPTION PHENOTYPE.
RX PubMed=18408056; DOI=10.1128/ec.00442-07;
RA Rodriguez M., Kim B., Lee N.-S., Veeranki S., Kim L.;
RT "MPL1, a novel phosphatase with leucine-rich repeats, is essential for
RT proper ERK2 phosphorylation and cell motility.";
RL Eukaryot. Cell 7:958-966(2008).
CC -!- FUNCTION: Implicated in the relay of the cAMP chemotactic signal and
CC cell differentiation. Important for receptor-mediated activation of
CC adenylyl cyclase. {ECO:0000269|PubMed:7844154}.
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=2.7.11.24;
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=2.7.11.24;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC -!- ACTIVITY REGULATION: Activated by tyrosine and threonine
CC phosphorylation. {ECO:0000250}.
CC -!- INTERACTION:
CC Q54QB1; P34042: gpaD; NbExp=2; IntAct=EBI-2905550, EBI-2905587;
CC -!- DOMAIN: The TXY motif contains the threonine and tyrosine residues
CC whose phosphorylation activates the MAP kinases. {ECO:0000250}.
CC -!- PTM: Dually phosphorylated on Thr-176 and Tyr-178, which activates the
CC enzyme. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Cells, starved for 8 hours, exhibited a decrease
CC in motility and a severe chemotaxis defect toward a cAMP gradient.
CC Aberrancy in chemotaxis was aggravated in the presence of a strong cAMP
CC gradient. Cells also display defective cytoskeletal remodeling in
CC response to chemoattractant stimulation. Cells are defective in
CC aggregation and display multiple crown-like membranous protrusions,
CC which were enriched not only in F-actin but also in myosin II. This
CC aberrant structure, which was proposed to be less stable and unable to
CC provide necessary traction force for cells to move, is believed to be
CC the reason why cells are less motile than wild-type cells.
CC {ECO:0000269|PubMed:18408056, ECO:0000269|PubMed:9427685}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. MAP kinase subfamily. {ECO:0000305}.
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DR EMBL; L33043; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AAFI02000058; EAL65439.1; -; Genomic_DNA.
DR PIR; A56492; A56492.
DR RefSeq; XP_638833.1; XM_633741.1.
DR AlphaFoldDB; Q54QB1; -.
DR SMR; Q54QB1; -.
DR IntAct; Q54QB1; 1.
DR STRING; 44689.DDB0191457; -.
DR PaxDb; Q54QB1; -.
DR PRIDE; Q54QB1; -.
DR EnsemblProtists; EAL65439; EAL65439; DDB_G0283903.
DR GeneID; 8624357; -.
DR KEGG; ddi:DDB_G0283903; -.
DR dictyBase; DDB_G0283903; erkB.
DR eggNOG; KOG0660; Eukaryota.
DR HOGENOM; CLU_000288_181_1_1; -.
DR InParanoid; Q54QB1; -.
DR OMA; MDIPRPE; -.
DR PhylomeDB; Q54QB1; -.
DR PRO; PR:Q54QB1; -.
DR Proteomes; UP000002195; Chromosome 4.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:dictyBase.
DR GO; GO:0005634; C:nucleus; IDA:dictyBase.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016301; F:kinase activity; IMP:dictyBase.
DR GO; GO:0004707; F:MAP kinase activity; IDA:dictyBase.
DR GO; GO:0004672; F:protein kinase activity; IDA: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:0007190; P:activation of adenylate cyclase activity; IMP:dictyBase.
DR GO; GO:0140582; P:adenylate cyclase-activating G protein-coupled cAMP receptor signaling pathway; IDA:dictyBase.
DR GO; GO:0031152; P:aggregation involved in sorocarp development; IMP:dictyBase.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IMP:dictyBase.
DR GO; GO:0043327; P:chemotaxis to cAMP; IMP:dictyBase.
DR GO; GO:0043326; P:chemotaxis to folate; IMP:dictyBase.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IMP:dictyBase.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0000165; P:MAPK cascade; IMP:dictyBase.
DR GO; GO:0051344; P:negative regulation of cyclic-nucleotide phosphodiesterase activity; IGI:dictyBase.
DR GO; GO:1990443; P:peptidyl-threonine autophosphorylation; IDA:dictyBase.
DR GO; GO:0038083; P:peptidyl-tyrosine autophosphorylation; IDA:dictyBase.
DR GO; GO:0050921; P:positive regulation of chemotaxis; IDA:dictyBase.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:dictyBase.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:dictyBase.
DR GO; GO:1905301; P:regulation of macropinocytosis; IMP:dictyBase.
DR GO; GO:0072718; P:response to cisplatin; IMP:dictyBase.
DR GO; GO:1903013; P:response to differentiation-inducing factor 1; HDA:dictyBase.
DR GO; GO:0032496; P:response to lipopolysaccharide; IMP:dictyBase.
DR GO; GO:0044671; P:sorocarp spore cell differentiation; IMP:dictyBase.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR003527; MAP_kinase_CS.
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; PS01351; MAPK; 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; Cell cycle; Cell division; Chemotaxis; Kinase; Mitosis;
KW Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..369
FT /note="Extracellular signal-regulated kinase 2"
FT /id="PRO_0000312369"
FT DOMAIN 14..304
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 346..369
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 176..178
FT /note="TXY"
FT ACT_SITE 137
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 20..28
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 43
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 176
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250"
FT MOD_RES 178
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250"
FT CONFLICT 17..18
FT /note="LQ -> FH (in Ref. 1; L33043)"
FT /evidence="ECO:0000305"
FT CONFLICT 30
FT /note="K -> E (in Ref. 1; L33043)"
FT /evidence="ECO:0000305"
FT CONFLICT 36..38
FT /note="TKQ -> PHH (in Ref. 1; L33043)"
FT /evidence="ECO:0000305"
FT CONFLICT 285
FT /note="L -> S (in Ref. 1; L33043)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 369 AA; 41978 MW; 3AB5C85E6F10722B CRC64;
MSSEDIDKHV LRKYEVLQKI GKGAYGIVWK AIDKKTKQTV ALKKIFDAFQ NATDAQRTFR
EIMFLQELHG HENIIKLLNV IKADNDRDIY LVFEHMETDL HAVIRAKILE EIHKQYTIYQ
LLKALKYMHS ANVLHRDIKP SNLLLNSECL VKVADFGLAR SITSLESIAE ANPVLTEYVA
TRWYRAPEIL LGSTKYTKGV DMWSIGCILG ELLGEKAMFP GNSTMNQLDL IIEVTGRPSA
EDIEAIKSPF AGTMLESLPP SNPRSLSDMY PSASVDALDL LKKLLQFNPD KRITAEEALA
HPFVTQFHNP AEEPHFDRII KISIDDGQKF PIAEYRNRLY NDIIKKKKEE RKKQTNPTKP
DTTAPTLST
