ID   MK13_BOVIN              Reviewed;         366 AA.
AC   Q3T0N5;
DT   25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT   11-OCT-2005, sequence version 1.
DT   08-NOV-2023, entry version 106.
DE   RecName: Full=Mitogen-activated protein kinase 13;
DE            Short=MAP kinase 13;
DE            Short=MAPK 13;
DE            EC=2.7.11.24;
GN   Name=MAPK13;
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Crossbred X Angus; TISSUE=Ileum;
RG   NIH - Mammalian Gene Collection (MGC) project;
RL   Submitted (AUG-2005) 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. MAPK13 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 such as ELK1 and ATF2. Accordingly, p38 MAPKs
CC       phosphorylate a broad range of proteins and it has been estimated that
CC       they may have approximately 200 to 300 substrates each. MAPK13 is one
CC       of the less studied p38 MAPK isoforms. Some of the targets are
CC       downstream kinases such as MAPKAPK2, which are activated through
CC       phosphorylation and further phosphorylate additional targets. Plays a
CC       role in the regulation of protein translation by phosphorylating and
CC       inactivating EEF2K. Involved in cytoskeletal remodeling through
CC       phosphorylation of MAPT and STMN1. Mediates UV irradiation induced up-
CC       regulation of the gene expression of CXCL14. Plays an important role in
CC       the regulation of epidermal keratinocyte differentiation, apoptosis and
CC       skin tumor development. Phosphorylates the transcriptional activator
CC       MYB in response to stress which leads to rapid MYB degradation via a
CC       proteasome-dependent pathway. MAPK13 also phosphorylates and down-
CC       regulates PRKD1 during regulation of insulin secretion in pancreatic
CC       beta cells (By 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   -!- 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 phosphorylation on threonine and
CC       tyrosine by dual specificity kinases, MAP2K3/MKK3 MAP2K6/MKK6,
CC       MAP2K4/MKK4 and MAP2K7/MKK7. Activation by ultraviolet radiation,
CC       hyperosmotic shock, anisomycin or by TNF-alpha is mediated by
CC       MAP2K3/MKK3. Inhibited by dual specificity phosphatase DUSP1 (By
CC       similarity). {ECO:0000250}.
CC   -!- SUBUNIT: Interacts with MAPK8IP2. {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-180 and Tyr-182 by MAP2K3/MKK3,
CC       MAP2K4/MKK4, MAP2K6/MKK6 and MAP2K7/MKK7, which activates the enzyme.
CC       Dephosphorylated by dual specificity phosphatase DUSP1 (By similarity).
CC       {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; BC102319; AAI02320.1; -; mRNA.
DR   AlphaFoldDB; Q3T0N5; -.
DR   SMR; Q3T0N5; -.
DR   STRING; 9913.ENSBTAP00000013198; -.
DR   PaxDb; 9913-ENSBTAP00000013198; -.
DR   eggNOG; KOG0660; Eukaryota.
DR   InParanoid; Q3T0N5; -.
DR   Proteomes; UP000009136; Unplaced.
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; IEA:UniProtKB-EC.
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:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR   GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR   CDD; cd07879; STKc_p38delta; 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; IPR038785; MAPK13.
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:SF107; MITOGEN-ACTIVATED PROTEIN KINASE 13; 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   2: Evidence at transcript level;
KW   ATP-binding; Cell cycle; Kinase; Nucleotide-binding; Phosphoprotein;
KW   Reference proteome; Serine/threonine-protein kinase; Stress response;
KW   Transcription; Transcription regulation; Transferase.
FT   CHAIN           1..366
FT                   /note="Mitogen-activated protein kinase 13"
FT                   /id="PRO_0000246181"
FT   DOMAIN          25..308
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   MOTIF           180..182
FT                   /note="TXY"
FT   ACT_SITE        150
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         47
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:O15264"
FT   MOD_RES         180
FT                   /note="Phosphothreonine; by MAP2K3, MAP2K4, MAP2K6 and
FT                   MAP2K7"
FT                   /evidence="ECO:0000250|UniProtKB:O15264"
FT   MOD_RES         182
FT                   /note="Phosphotyrosine; by MAP2K3, MAP2K4, MAP2K6 and
FT                   MAP2K7"
FT                   /evidence="ECO:0000250|UniProtKB:O15264"
FT   MOD_RES         350
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:O15264"
SQ   SEQUENCE   366 AA;  42229 MW;  C35CF0064C4BE83E CRC64;
     MSFTRKKGFY KQDVNKTAWE LPKTYVSLTH IGSGAYGSVC SAIDKRSGEK VAIKKLSRPF
     QSEIFAKRAY RELLLLKHMQ HENVIGLLDV FTPASSLRNF HDFYLVMPFM QTDLQKIMGM
     EFSEDKIQYL VYQMLKGLKY IHSAGVVHRD LKPGNLAVNE DCELKILDFG LARHTDVEMT
     GYVVTRWYRA PEVILSWMHY NQTVDIWSVG CIMAEMLTGK TLFKGKDYLD QLTQILKVTG
     VPGAEFVQKL NDKAAKSYIQ SLPQSPKKDF SQLFPRASPQ ATDLLEKMLE LDVDKRLTAS
     QALAHPFFEP FRDPEEETEA QQPLEDSLER EKLIVDEWKQ HIYKEIVNFS PIARKDSRRR
     SGMKLQ
//