MK13_PANTR
ID MK13_PANTR Reviewed; 365 AA.
AC Q9N272;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=Mitogen-activated protein kinase 13;
DE Short=MAP kinase 13;
DE Short=MAPK 13;
DE EC=2.7.11.24;
DE AltName: Full=Stress-activated protein kinase 4;
GN Name=MAPK13; Synonyms=SAPK4;
OS Pan troglodytes (Chimpanzee).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pan.
OX NCBI_TaxID=9598;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10727080; DOI=10.3109/10425179909033952;
RA Herbison C.E., Sayer D.C., Bellgard M., Allcock R.J.N., Christiansen F.T.,
RA Price P.;
RT "Structure and polymorphism of two stress-activated protein kinase genes
RT centromeric of the MHC: SAPK2a and SAPK4.";
RL DNA Seq. 10:229-243(1999).
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; AF100547; AAF36773.1; -; mRNA.
DR RefSeq; NP_001029261.2; NM_001034089.2.
DR STRING; 9598.ENSPTRP00000030916; -.
DR PaxDb; Q9N272; -.
DR GeneID; 462644; -.
DR KEGG; ptr:462644; -.
DR CTD; 5603; -.
DR eggNOG; KOG0660; Eukaryota.
DR InParanoid; Q9N272; -.
DR OrthoDB; 683132at2759; -.
DR BRENDA; 2.7.11.24; 4497.
DR Proteomes; UP000002277; 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; ISS: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:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0051403; P:stress-activated MAPK cascade; ISS:UniProtKB.
DR CDD; cd07879; STKc_p38delta; 1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR003527; MAP_kinase_CS.
DR InterPro; IPR008352; MAPK_p38-like.
DR InterPro; IPR038785; p38delta.
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; Cell cycle; Kinase; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Stress response;
KW Transcription; Transcription regulation; Transferase.
FT CHAIN 1..365
FT /note="Mitogen-activated protein kinase 13"
FT /id="PRO_0000186288"
FT DOMAIN 25..308
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 309..328
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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 365 AA; 42109 MW; 03E4CB40A51C71D9 CRC64;
MSLIRKKGFY KQDVNKXXXE LXKTYVSPTH VGSGAYGSVC SAIDKRSGEK VAIKKLSRPF
QSEIFAKRAY RELLLLKHMQ HENVIGLLDV FTPASSLRNF HDFYLVMXFM QTDLQKIMXM
EFSEEKIQYL VYQMLKGLKY IHSAGVVHRD LKPGNLAVNE DCELKILDFG LARHADAEMT
GYVVTRWYRA PEVILSWMHY NQTVDIWSVG CIMAEMLTGK TLFKGKDYLD QLTQILKVTG
VPGTEFVQKL NDXAAKSYIQ SLPQTPRKDF TQLFPRASPQ AADLLEKMLE LDVDKRLTAA
QALTHPFFEP FRDPEEETEA QQPFDDSLEH EKLTVDEWKQ HIYKEIVNFS PIARKDSRRR
XGXKL
