ID MK14A_DANRE Reviewed; 361 AA.
AC Q9DGE2;
DT 30-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 27-MAR-2024, entry version 161.
DE RecName: Full=Mitogen-activated protein kinase 14A;
DE Short=MAP kinase 14A;
DE Short=MAPK 14A;
DE EC=2.7.11.24;
DE AltName: Full=Mitogen-activated protein kinase p38a;
DE Short=MAP kinase p38a;
DE Short=zp38a;
GN Name=mapk14a; Synonyms=mapk14;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955 {ECO:0000312|EMBL:BAB11807.1};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, ACTIVITY REGULATION, PHOSPHORYLATION
RP AT THR-181 AND TYR-183, DEVELOPMENTAL STAGE, AND MUTAGENESIS OF THR-181 AND
RP TYR-183.
RX PubMed=10995439; DOI=10.1083/jcb.150.6.1335;
RA Fujii R., Yamashita S., Hibi M., Hirano T.;
RT "Asymmetric p38 activation in zebrafish: its possible role in symmetric and
RT synchronous cleavage.";
RL J. Cell Biol. 150:1335-1348(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=AB;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Serine/threonine kinase which acts as an essential component
CC of the MAP kinase signal transduction pathway. Mapk14a is one of the
CC four p38 MAPKs which play an important role in the cascades of cellular
CC responses evoked by extracellular stimuli such as pro-inflammatory
CC cytokines or physical stress leading to direct activation of
CC transcription factors. Accordingly, p38 MAPKs phosphorylate a broad
CC range of proteins and it has been estimated that they may have
CC approximately 200 to 300 substrates each. Some of the targets are
CC downstream kinases which are activated through phosphorylation and
CC further phosphorylate additional targets. Required for cytokinesis on
CC the future dorsal side of the blastodisc, suggesting a role in
CC symmetrical and synchronous blastomere cleavage.
CC {ECO:0000269|PubMed:10995439}.
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 Evidence={ECO:0000250|UniProtKB:Q90336};
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; Evidence={ECO:0000250|UniProtKB:Q90336};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q90336};
CC -!- ACTIVITY REGULATION: Activated by threonine and tyrosine
CC phosphorylation by the dual specificity kinase, MKK3.
CC {ECO:0000269|PubMed:10995439}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC -!- DEVELOPMENTAL STAGE: Expressed as the predominant form of mapk14 both
CC maternally and zygotically throughout development.
CC {ECO:0000269|PubMed:10995439}.
CC -!- DOMAIN: The TXY motif contains the threonine and tyrosine residues
CC whose phosphorylation activates the MAP kinases.
CC -!- PTM: Dually phosphorylated on Thr-181 and Tyr-183, which activates the
CC enzyme. {ECO:0000269|PubMed:10995439}.
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; AB030897; BAB11807.1; -; mRNA.
DR EMBL; BC044128; AAH44128.2; -; mRNA.
DR RefSeq; NP_571797.1; NM_131722.1.
DR AlphaFoldDB; Q9DGE2; -.
DR SMR; Q9DGE2; -.
DR STRING; 7955.ENSDARP00000040361; -.
DR iPTMnet; Q9DGE2; -.
DR PaxDb; 7955-ENSDARP00000040361; -.
DR GeneID; 65237; -.
DR KEGG; dre:65237; -.
DR AGR; ZFIN:ZDB-GENE-010202-2; -.
DR CTD; 65237; -.
DR ZFIN; ZDB-GENE-010202-2; mapk14a.
DR eggNOG; KOG0660; Eukaryota.
DR HOGENOM; CLU_000288_181_1_1; -.
DR InParanoid; Q9DGE2; -.
DR OrthoDB; 158564at2759; -.
DR PhylomeDB; Q9DGE2; -.
DR TreeFam; TF105100; -.
DR BRENDA; 2.7.11.24; 928.
DR Reactome; R-DRE-168638; NOD1/2 Signaling Pathway.
DR Reactome; R-DRE-171007; p38MAPK events.
DR Reactome; R-DRE-198753; ERK/MAPK targets.
DR Reactome; R-DRE-2559580; Oxidative Stress Induced Senescence.
DR Reactome; R-DRE-376172; DSCAM interactions.
DR Reactome; R-DRE-418592; ADP signalling through P2Y purinoceptor 1.
DR Reactome; R-DRE-432142; Platelet sensitization by LDL.
DR Reactome; R-DRE-4420097; VEGFA-VEGFR2 Pathway.
DR Reactome; R-DRE-450302; activated TAK1 mediates p38 MAPK activation.
DR Reactome; R-DRE-450341; Activation of the AP-1 family of transcription factors.
DR Reactome; R-DRE-525793; Myogenesis.
DR Reactome; R-DRE-5668599; RHO GTPases Activate NADPH Oxidases.
DR Reactome; R-DRE-6798695; Neutrophil degranulation.
DR Reactome; R-DRE-6804756; Regulation of TP53 Activity through Phosphorylation.
DR SignaLink; Q9DGE2; -.
DR PRO; PR:Q9DGE2; -.
DR Proteomes; UP000000437; Alternate scaffold 8.
DR Proteomes; UP000000437; Chromosome 8.
DR Bgee; ENSDARG00000000857; Expressed in cleaving embryo and 27 other cell types or tissues.
DR ExpressionAtlas; Q9DGE2; baseline.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004707; F:MAP kinase activity; IDA:UniProtKB.
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:0034644; P:cellular response to UV; IDA:UniProtKB.
DR GO; GO:0040016; P:embryonic cleavage; IDA:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0038066; P:p38MAPK cascade; IDA:UniProtKB.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0045663; P:positive regulation of myoblast differentiation; ISS:UniProtKB.
DR GO; GO:1901741; P:positive regulation of myoblast fusion; ISS:UniProtKB.
DR GO; GO:0010831; P:positive regulation of myotube differentiation; ISS:UniProtKB.
DR GO; GO:0048696; P:regulation of collateral sprouting in absence of injury; IMP:ZFIN.
DR GO; GO:0031647; P:regulation of protein stability; IMP:ZFIN.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0001756; P:somitogenesis; IMP:ZFIN.
DR CDD; cd07877; STKc_p38alpha; 1.
DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR003527; MAP_kinase_CS.
DR InterPro; IPR038784; MAPK14.
DR InterPro; IPR008352; MAPK_p38-like.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR PANTHER; PTHR24055; MITOGEN-ACTIVATED PROTEIN KINASE; 1.
DR PANTHER; PTHR24055:SF110; MITOGEN-ACTIVATED PROTEIN KINASE 14; 1.
DR Pfam; PF00069; Pkinase; 1.
DR PRINTS; PR01773; P38MAPKINASE.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 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; Cytoplasm; Developmental protein; Kinase; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Stress response; Transcription;
KW Transcription regulation; Transferase.
FT CHAIN 1..361
FT /note="Mitogen-activated protein kinase 14A"
FT /id="PRO_0000186295"
FT DOMAIN 25..309
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOTIF 181..183
FT /note="TXY"
FT ACT_SITE 169
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 181
FT /note="Phosphothreonine; by MAP2K3"
FT /evidence="ECO:0000269|PubMed:10995439"
FT MOD_RES 183
FT /note="Phosphotyrosine; by MAP2K3"
FT /evidence="ECO:0000269|PubMed:10995439"
FT MUTAGEN 181
FT /note="T->A: Loss of enzyme activation."
FT /evidence="ECO:0000269|PubMed:10995439"
FT MUTAGEN 183
FT /note="Y->F: Loss of enzyme activation."
FT /evidence="ECO:0000269|PubMed:10995439"
SQ SEQUENCE 361 AA; 41633 MW; B3FD9577831718C0 CRC64;
MSQKERPTFY RQEVNKTIWE VPVQYQNLSP VGSGAYGSVC SAFDAKTGFK VAVKKLSRPF
QSIIHAKRTY RELRLLKHMR HENVIGLLDV FTPATSLKEF NDVYLVTHLM GADLNNIVKC
QKLTDDHVQF LIYQILRGLK YIHSADIIHR DLKPSNLAVN EDCELKILDF GLARHTDDEM
TGYVATRWYR APEIMLNWMH YNVTVDIWSV GCIMAELLTG RTLFPGTDHI NQLQQIMRLT
GTPPSSLISR MPSHEARTYI SSLPQMPKRN FADVFIGANP QAVDLLEKML VLDTDKRITA
AEALAHPYFA QYHDPDDEPE AEPFDQSFES RELDIEEWKR QTYEEMISFE PPVFDVDEME
S
//
