MK12_DANRE
ID MK12_DANRE Reviewed; 363 AA.
AC O42376;
DT 30-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Mitogen-activated protein kinase 12;
DE Short=MAP kinase 12;
DE Short=MAPK 12;
DE EC=2.7.11.24;
DE AltName: Full=Stress-activated protein kinase 3;
GN Name=mapk12; Synonyms=sapk3;
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:CAA75355.1};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Somatic embryo;
RA Goedert M.;
RL Submitted (OCT-1997) 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. MAPK12 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 such as MAPKAPK2, which are activated through
CC phosphorylation and further phosphorylate additional targets (By
CC similarity). {ECO:0000250}.
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:Q63538};
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:Q63538};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q63538};
CC -!- ACTIVITY REGULATION: Activated by threonine and tyrosine
CC phosphorylation. {ECO:0000250|UniProtKB:Q63538}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
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:0000250}.
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; Y15075; CAA75355.1; -; mRNA.
DR AlphaFoldDB; O42376; -.
DR SMR; O42376; -.
DR STRING; 7955.ENSDARP00000011298; -.
DR PaxDb; O42376; -.
DR Ensembl; ENSDART00000018502; ENSDARP00000011298; ENSDARG00000042021.
DR ZFIN; ZDB-GENE-990415-257; mapk12a.
DR eggNOG; KOG0660; Eukaryota.
DR GeneTree; ENSGT00940000156189; -.
DR HOGENOM; CLU_000288_181_1_1; -.
DR InParanoid; O42376; -.
DR OMA; PYVAAYH; -.
DR PhylomeDB; O42376; -.
DR TreeFam; TF105100; -.
DR Reactome; R-DRE-168638; NOD1/2 Signaling Pathway.
DR Reactome; R-DRE-376172; DSCAM interactions.
DR Reactome; R-DRE-4420097; VEGFA-VEGFR2 Pathway.
DR Reactome; R-DRE-525793; Myogenesis.
DR Reactome; R-DRE-5675221; Negative regulation of MAPK pathway.
DR PRO; PR:O42376; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 18.
DR Bgee; ENSDARG00000042021; Expressed in zone of skin and 36 other tissues.
DR ExpressionAtlas; O42376; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004707; F:MAP kinase activity; IBA:GO_Central.
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:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
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 2: Evidence at transcript level;
KW ATP-binding; Cytoplasm; Kinase; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Stress response;
KW Transcription; Transcription regulation; Transferase.
FT CHAIN 1..363
FT /note="Mitogen-activated protein kinase 12"
FT /id="PRO_0000186285"
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 151
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"
FT /evidence="ECO:0000250"
FT MOD_RES 183
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250"
SQ SEQUENCE 363 AA; 41971 MW; 81B06D414254EFBF CRC64;
MTARSRPGYF RQEINKTIWE VPDRYKDLKQ VGTGAYGTVC YALDRRTGAK VAIKKLHRPF
QSDLFAKRAY RELRLLKHMK HDNVIGLVDV FTADLSLDRF HDFYLVMPFM GTDLGKLMKM
ERLSEERVQY LVYQMLKGLK YIHAAGIIHR DLKPGNLAIN EECELKILDF GLARQTDSEM
TGYVVTRWYR APEVILSWMH YTQTVDIWSV GCIMAEMLLG KPLFKGHDHL DQLMEIMKVT
GTPSKEFTAK LQSEDARNYV TKLPRFRKKD LRILLPNVNP QAIKVLDGML LLDPESRITA
AEALAFPFFS EFREPEEETE APPYDHSLDE ADQSLEQWKR LTFTEILTFQ PAPAVAESKE
TAL
