MK38A_DROME
ID MK38A_DROME Reviewed; 366 AA.
AC O62618; A4V3C0; O46216; Q9TXB4;
DT 02-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=Mitogen-activated protein kinase p38a {ECO:0000303|PubMed:9584193};
DE Short=MAP kinase p38a {ECO:0000303|PubMed:9584193};
DE Short=MAPK p38a {ECO:0000303|PubMed:9584193};
DE EC=2.7.11.24;
DE AltName: Full=MAP kinase 14A {ECO:0000312|FlyBase:FBgn0015765};
DE AltName: Full=p38 MAPK {ECO:0000303|PubMed:9417090};
GN Name=p38a {ECO:0000303|PubMed:9584193, ECO:0000312|FlyBase:FBgn0015765};
GN Synonyms=Mpk2 {ECO:0000312|FlyBase:FBgn0015765};
GN ORFNames=CG5475 {ECO:0000312|FlyBase:FBgn0015765};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PHOSPHORYLATION AT TYR-186, FUNCTION,
RP SUBCELLULAR LOCATION, AND ACTIVITY REGULATION.
RC TISSUE=Hemocyte;
RX PubMed=9417090; DOI=10.1074/jbc.273.1.369;
RA Han S.-J., Choi K.-Y., Brey P.T., Lee W.-J.;
RT "Molecular cloning and characterization of a Drosophila p38 mitogen-
RT activated protein kinase.";
RL J. Biol. Chem. 273:369-374(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], FUNCTION, DEVELOPMENTAL STAGE,
RP AND ACTIVITY REGULATION.
RC TISSUE=Embryo;
RX PubMed=9584193; DOI=10.1128/mcb.18.6.3527;
RA Han Z.S., Enslen H., Hu X., Meng X., Wu I.-H., Barrett T., Davis R.J.,
RA Ip Y.T.;
RT "A conserved p38 mitogen-activated protein kinase pathway regulates
RT Drosophila immunity gene expression.";
RL Mol. Cell. Biol. 18:3527-3539(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [4]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Head;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 38-188.
RC TISSUE=Imaginal disk;
RX PubMed=1378625; DOI=10.1073/pnas.89.14.6295;
RA Biggs W.H. III, Zipursky S.L.;
RT "Primary structure, expression, and signal-dependent tyrosine
RT phosphorylation of a Drosophila homolog of extracellular signal-regulated
RT kinase.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:6295-6299(1992).
CC -!- FUNCTION: Kinase involved in a signal transduction pathway. May down-
CC regulate insect immunity gene expression after prolonged infection.
CC {ECO:0000269|PubMed:9417090, ECO:0000269|PubMed:9584193}.
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 threonine and tyrosine
CC phosphorylation by Mkk3 in response to environmental stress.
CC {ECO:0000269|PubMed:9417090, ECO:0000269|PubMed:9584193}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:9417090}.
CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically. Levels
CC are highest at the preblastoderm stage but low levels are present
CC throughout development. {ECO:0000269|PubMed:9584193}.
CC -!- DOMAIN: The TXY motif contains the threonine and tyrosine residues
CC whose phosphorylation activates the MAP kinases.
CC -!- PTM: Dually phosphorylated on Thr-184 and Tyr-186, which activates the
CC enzyme. {ECO:0000269|PubMed:9417090}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. MAP kinase subfamily. {ECO:0000305}.
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; U86867; AAB97138.1; -; mRNA.
DR EMBL; AF035546; AAC39030.1; -; Genomic_DNA.
DR EMBL; AF035547; AAC39031.1; -; mRNA.
DR EMBL; AE014297; AAF56244.1; -; Genomic_DNA.
DR EMBL; AE014297; AAN13984.1; -; Genomic_DNA.
DR EMBL; AY071670; AAL49292.1; -; mRNA.
DR RefSeq; NP_001163711.1; NM_001170240.2.
DR RefSeq; NP_477163.1; NM_057815.5.
DR RefSeq; NP_732959.1; NM_170126.5.
DR AlphaFoldDB; O62618; -.
DR SMR; O62618; -.
DR BioGRID; 67799; 25.
DR IntAct; O62618; 3.
DR STRING; 7227.FBpp0083966; -.
DR iPTMnet; O62618; -.
DR PaxDb; O62618; -.
DR PRIDE; O62618; -.
DR DNASU; 42866; -.
DR EnsemblMetazoa; FBtr0084580; FBpp0083965; FBgn0015765.
DR EnsemblMetazoa; FBtr0084581; FBpp0083966; FBgn0015765.
DR EnsemblMetazoa; FBtr0300572; FBpp0289799; FBgn0015765.
DR GeneID; 42866; -.
DR KEGG; dme:Dmel_CG5475; -.
DR CTD; 42866; -.
DR FlyBase; FBgn0015765; p38a.
DR VEuPathDB; VectorBase:FBgn0015765; -.
DR eggNOG; KOG0660; Eukaryota.
DR GeneTree; ENSGT00940000160790; -.
DR HOGENOM; CLU_000288_181_1_1; -.
DR InParanoid; O62618; -.
DR OMA; IFHPHPP; -.
DR OrthoDB; 683132at2759; -.
DR PhylomeDB; O62618; -.
DR BRENDA; 2.7.11.24; 1994.
DR Reactome; R-DME-168638; NOD1/2 Signaling Pathway.
DR Reactome; R-DME-171007; p38MAPK events.
DR Reactome; R-DME-198753; ERK/MAPK targets.
DR Reactome; R-DME-2559580; Oxidative Stress Induced Senescence.
DR Reactome; R-DME-376172; DSCAM interactions.
DR Reactome; R-DME-418592; ADP signalling through P2Y purinoceptor 1.
DR Reactome; R-DME-432142; Platelet sensitization by LDL.
DR Reactome; R-DME-4420097; VEGFA-VEGFR2 Pathway.
DR Reactome; R-DME-450302; activated TAK1 mediates p38 MAPK activation.
DR Reactome; R-DME-450341; Activation of the AP-1 family of transcription factors.
DR Reactome; R-DME-525793; Myogenesis.
DR Reactome; R-DME-5675221; Negative regulation of MAPK pathway.
DR Reactome; R-DME-6798695; Neutrophil degranulation.
DR Reactome; R-DME-6804756; Regulation of TP53 Activity through Phosphorylation.
DR SignaLink; O62618; -.
DR BioGRID-ORCS; 42866; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 42866; -.
DR PRO; PR:O62618; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0015765; Expressed in adult midgut (Drosophila) and 28 other tissues.
DR ExpressionAtlas; O62618; baseline and differential.
DR Genevisible; O62618; DM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IDA:FlyBase.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004707; F:MAP kinase activity; IDA:FlyBase.
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:0071243; P:cellular response to arsenic-containing substance; IDA:FlyBase.
DR GO; GO:0071276; P:cellular response to cadmium ion; IDA:FlyBase.
DR GO; GO:0034614; P:cellular response to reactive oxygen species; IDA:FlyBase.
DR GO; GO:0042742; P:defense response to bacterium; IMP:FlyBase.
DR GO; GO:0050832; P:defense response to fungus; IMP:FlyBase.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:FlyBase.
DR GO; GO:0003007; P:heart morphogenesis; IGI:FlyBase.
DR GO; GO:0006955; P:immune response; IDA:FlyBase.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0000165; P:MAPK cascade; ISS:FlyBase.
DR GO; GO:0002385; P:mucosal immune response; IMP:FlyBase.
DR GO; GO:0008348; P:negative regulation of antimicrobial humoral response; IMP:FlyBase.
DR GO; GO:0038066; P:p38MAPK cascade; IDA:FlyBase.
DR GO; GO:0038001; P:paracrine signaling; IGI:FlyBase.
DR GO; GO:0045793; P:positive regulation of cell size; IGI:FlyBase.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0048082; P:regulation of adult chitin-containing cuticle pigmentation; IGI:FlyBase.
DR GO; GO:1900407; P:regulation of cellular response to oxidative stress; IMP:FlyBase.
DR GO; GO:0009408; P:response to heat; IMP:FlyBase.
DR GO; GO:0042542; P:response to hydrogen peroxide; IMP:FlyBase.
DR GO; GO:0006970; P:response to osmotic stress; IDA:FlyBase.
DR GO; GO:0006979; P:response to oxidative stress; IMP:FlyBase.
DR GO; GO:0042594; P:response to starvation; IMP:FlyBase.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR003527; MAP_kinase_CS.
DR InterPro; IPR008352; MAPK_p38-like.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR Pfam; PF00069; Pkinase; 1.
DR PRINTS; PR01773; P38MAPKINASE.
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.
PE 1: Evidence at protein level;
KW ATP-binding; Kinase; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..366
FT /note="Mitogen-activated protein kinase p38a"
FT /id="PRO_0000186300"
FT DOMAIN 25..312
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOTIF 184..186
FT /note="TXY"
FT ACT_SITE 154
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 31..39
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 54
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 184
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250"
FT MOD_RES 186
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:9417090"
FT CONFLICT 27
FT /note="D -> G (in Ref. 2; AAB97138)"
FT /evidence="ECO:0000305"
FT CONFLICT 77
FT /note="K -> R (in Ref. 6)"
FT /evidence="ECO:0000305"
FT CONFLICT 80
FT /note="D -> A (in Ref. 2; AAB97138)"
FT /evidence="ECO:0000305"
FT CONFLICT 108
FT /note="L -> LL (in Ref. 6)"
FT /evidence="ECO:0000305"
FT CONFLICT 124
FT /note="Q -> QQ (in Ref. 6)"
FT /evidence="ECO:0000305"
FT CONFLICT 149
FT /note="Missing (in Ref. 6)"
FT /evidence="ECO:0000305"
FT CONFLICT 163
FT /note="N -> NN (in Ref. 6)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 366 AA; 42256 MW; B3592B869F97990E CRC64;
MSVSITKKFY KLDINRTEWE IPDIYQDLQP VGSGAYGQVS KAVVRGTNMH VAIKKLARPF
QSAVHAKRTY RELRLLKHMD HENVIGLLDI FHPHPANGSL ENFQQVYLVT HLMDADLNNI
IRMQHLSDDH VQFLVYQILR GLKYIHSAGV IHRDLKPSNI AVNEDCELRI LDFGLARPTE
NEMTGYVATR WYRAPEIMLN WMHYDQTVDI WSVGCIMAEL ITRRTLFPGT DHIHQLNLIM
EMLGTPPAEF LKKISSESAR SYIQSLPPMK GRSFKNVFKN ANPLAIDLLE KMLELDAEKR
ITAEEALSHP YLEKYAEPSV EQTSPPYDHS FEDMDLPVDK WKELIYKEVT NFKPPPSYAQ
VLKDVK
