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Mitogen-activated protein kinase 13 (MAP kinase 13) (MAPK 13) (EC 2.7.11.24) (Mitogen-activated protein kinase p38 delta) (MAP kinase p38 delta) (Stress-activated protein kinase 4)

 MK13_RAT                Reviewed;         366 AA.
Q9WTY9;
21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
01-NOV-1999, sequence version 1.
26-FEB-2020, entry version 140.
RecName: Full=Mitogen-activated protein kinase 13;
Short=MAP kinase 13;
Short=MAPK 13;
EC=2.7.11.24;
AltName: Full=Mitogen-activated protein kinase p38 delta;
Short=MAP kinase p38 delta;
AltName: Full=Stress-activated protein kinase 4;
Name=Mapk13;
Rattus norvegicus (Rat).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
Murinae; Rattus.
NCBI_TaxID=10116;
[1]
NUCLEOTIDE SEQUENCE [MRNA].
PubMed=10066767; DOI=10.1074/jbc.274.11.7095;
Hu M.C.-T., Wang Y.-P., Mikhail A., Qiu W.R., Tan T.-H.;
"Murine p38-delta mitogen-activated protein kinase, a developmentally
regulated protein kinase that is activated by stress and proinflammatory
cytokines.";
J. Biol. Chem. 274:7095-7102(1999).
[2]
PHOSPHORYLATION, AND FUNCTION.
PubMed=20826544; DOI=10.1096/fj.10-164277;
Leong D.J., Li Y.H., Gu X.I., Sun L., Zhou Z., Nasser P., Laudier D.M.,
Iqbal J., Majeska R.J., Schaffler M.B., Goldring M.B., Cardoso L.,
Zaidi M., Sun H.B.;
"Physiological loading of joints prevents cartilage degradation through
CITED2.";
FASEB J. 25:182-191(2011).
[3]
REVIEW ON FUNCTION.
PubMed=20090411; DOI=10.4161/cc.9.3.10541;
Efimova T.;
"p38delta mitogen-activated protein kinase regulates skin homeostasis and
tumorigenesis.";
Cell Cycle 9:498-505(2010).
[4]
REVIEW ON ACTIVITY REGULATION, AND REVIEW ON FUNCTION.
PubMed=20626350; DOI=10.1042/bj20100323;
Cuadrado A., Nebreda A.R.;
"Mechanisms and functions of p38 MAPK signalling.";
Biochem. J. 429:403-417(2010).
-!- FUNCTION: Serine/threonine kinase which acts as an essential component
of the MAP kinase signal transduction pathway. MAPK13 is one of the
four p38 MAPKs which play an important role in the cascades of cellular
responses evoked by extracellular stimuli such as proinflammatory
cytokines or physical stress leading to direct activation of
transcription factors such as ELK1 and ATF2. Accordingly, p38 MAPKs
phosphorylate a broad range of proteins and it has been estimated that
they may have approximately 200 to 300 substrates each. MAPK13 is one
of the less studied p38 MAPK isoforms. Some of the targets are
downstream kinases such as MAPKAPK2, which are activated through
phosphorylation and further phosphorylate additional targets. Plays a
role in the regulation of protein translation by phosphorylating and
inactivating EEF2K. Involved in cytoskeletal remodeling through
phosphorylation of MAPT and STMN1. Mediates UV irradiation induced up-
regulation of the gene expression of CXCL14. Plays an important role in
the regulation of epidermal keratinocyte differentiation, apoptosis and
skin tumor development. Phosphorylates the transcriptional activator
MYB in response to stress which leads to rapid MYB degradation via a
proteasome-dependent pathway. MAPK13 also phosphorylates and down-
regulates PRKD1 during regulation of insulin secretion in pancreatic
beta cells. {ECO:0000269|PubMed:20826544}.
-!- CATALYTIC ACTIVITY:
Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
[protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.24;
-!- CATALYTIC ACTIVITY:
Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
EC=2.7.11.24;
-!- COFACTOR:
Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
-!- ACTIVITY REGULATION: Activated by phosphorylation on threonine and
tyrosine by dual specificity kinases, MAP2K3/MKK3, MAP2K6/MKK6,
MAP2K4/MKK4 and MAP2K7/MKK7. Activation by ultraviolet radiation,
hyperosmotic shock, anisomycin or by TNF-alpha is mediated by
MAP2K3/MKK3. Inhibited by dual specificity phosphatase DUSP1.
-!- SUBUNIT: Interacts with MAPK8IP2. {ECO:0000250}.
-!- DOMAIN: The TXY motif contains the threonine and tyrosine residues
whose phosphorylation activates the MAP kinases.
-!- PTM: Dually phosphorylated on Thr-180 and Tyr-182 by MAP2K3/MKK3,
MAP2K4/MKK4, MAP2K6/MKK6 and MAP2K7/MKK7, which activates the enzyme.
Dephosphorylated by dual specificity phosphatase DUSP1 (By similarity).
{ECO:0000250}.
-!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
protein kinase family. MAP kinase subfamily. {ECO:0000305}.
---------------------------------------------------------------------------
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---------------------------------------------------------------------------
EMBL; AF092534; AAD23376.1; -; mRNA.
SMR; Q9WTY9; -.
STRING; 10116.ENSRNOP00000000621; -.
iPTMnet; Q9WTY9; -.
PhosphoSitePlus; Q9WTY9; -.
jPOST; Q9WTY9; -.
PaxDb; Q9WTY9; -.
PRIDE; Q9WTY9; -.
UCSC; RGD:3045; rat.
RGD; 3045; Mapk13.
eggNOG; KOG0660; Eukaryota.
eggNOG; ENOG410XNY0; LUCA.
InParanoid; Q9WTY9; -.
PhylomeDB; Q9WTY9; -.
BRENDA; 2.7.11.24; 5301.
Reactome; R-RNO-168638; NOD1/2 Signaling Pathway.
Reactome; R-RNO-376172; DSCAM interactions.
Reactome; R-RNO-4420097; VEGFA-VEGFR2 Pathway.
PRO; PR:Q9WTY9; -.
Proteomes; UP000002494; Unplaced.
GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
GO; GO:0005634; C:nucleus; IBA:GO_Central.
GO; GO:0005524; F:ATP binding; IDA:RGD.
GO; GO:0004707; F:MAP kinase activity; IDA:RGD.
GO; GO:0004674; F:protein serine/threonine kinase activity; ISO:RGD.
GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
GO; GO:0072740; P:cellular response to anisomycin; ISO:RGD.
GO; GO:0070301; P:cellular response to hydrogen peroxide; ISO:RGD.
GO; GO:0071347; P:cellular response to interleukin-1; ISO:RGD.
GO; GO:1903936; P:cellular response to sodium arsenite; ISO:RGD.
GO; GO:0072709; P:cellular response to sorbitol; ISO:RGD.
GO; GO:0034644; P:cellular response to UV; ISO:RGD.
GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
GO; GO:0018105; P:peptidyl-serine phosphorylation; ISO:RGD.
GO; GO:0032755; P:positive regulation of interleukin-6 production; ISO:RGD.
GO; GO:0006468; P:protein phosphorylation; IDA:RGD.
GO; GO:0010468; P:regulation of gene expression; IBA:GO_Central.
GO; GO:0006970; P:response to osmotic stress; ISO:RGD.
GO; GO:0051403; P:stress-activated MAPK cascade; ISS:UniProtKB.
CDD; cd07879; STKc_p38delta; 1.
InterPro; IPR011009; Kinase-like_dom_sf.
InterPro; IPR003527; MAP_kinase_CS.
InterPro; IPR008352; MAPK_p38-like.
InterPro; IPR038785; p38delta.
InterPro; IPR000719; Prot_kinase_dom.
InterPro; IPR017441; Protein_kinase_ATP_BS.
Pfam; PF00069; Pkinase; 1.
PRINTS; PR01773; P38MAPKINASE.
SMART; SM00220; S_TKc; 1.
SUPFAM; SSF56112; SSF56112; 1.
PROSITE; PS01351; MAPK; 1.
PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
1: Evidence at protein level;
ATP-binding; Cell cycle; Kinase; Nucleotide-binding; Phosphoprotein;
Reference proteome; Serine/threonine-protein kinase; Stress response;
Transcription; Transcription regulation; Transferase.
CHAIN 1..366
/note="Mitogen-activated protein kinase 13"
/id="PRO_0000186289"
DOMAIN 25..308
/note="Protein kinase"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
NP_BIND 31..39
/note="ATP"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
MOTIF 180..182
/note="TXY"
ACT_SITE 150
/note="Proton acceptor"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
BINDING 54
/note="ATP"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
MOD_RES 180
/note="Phosphothreonine; by MAP2K3, MAP2K4, MAP2K6 and
MAP2K7"
/evidence="ECO:0000250|UniProtKB:O15264"
MOD_RES 182
/note="Phosphotyrosine; by MAP2K3, MAP2K4, MAP2K6 and
MAP2K7"
/evidence="ECO:0000250|UniProtKB:O15264"
MOD_RES 350
/note="Phosphoserine"
/evidence="ECO:0000250|UniProtKB:O15264"
SEQUENCE 366 AA; 42051 MW; 09F6E65092F2E8D8 CRC64;
MSLIRKRGFY KQDINKTAWE LPKTYLAPAH VGSGAYGAVC SAIDKRTGEK VAIKKLSRPF
QSEIFAKRAY RELLLLKHMH HENVIGLLDV YTPATSVRNF QDFYLVMPFM QTDLQKIMGM
EFSEEKVQYL VYQMLKGLKY IHSAGIVHRD LKPGNLAVNE DCELKILDFG LARHTDAEMT
GYVVTRWYRA PEVILSWMHY NQTVDIWSVG CIMAEMLTGK TLFKGKDYLD QLTQILKVTG
VPGAEFVQKL KDKAAKSYIQ SLPQSPKKDF TQLFPRASPQ AVDLLDKMLE LDVDKRLTAA
QALAHPLFEP LRDPEEETEA QQPFDDALER ENLSVDEWKQ HIYKEIANFS PIARKDSRRR
SGMKLQ


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Pathways :
WP1493: Carbon assimilation C4 pathway
WP32: Translation Factors
WP1653: Galactose metabolism
WP1946: Cori Cycle
WP2341: vitamin B1 (thiamin) biosynthesis and salvage pathway
WP1844: MAP kinase cascade
WP253: Glycolysis
WP1681: Pantothenate and CoA biosynthesis
WP1694: Pyrimidine metabolism
WP2340: Thiamine (vitamin B1) biosynthesis and salvage
WP1703: Streptomycin biosynthesis
WP1663: Homologous recombination
WP1567: Glycolysis and Gluconeogenesis
WP1619: Amino sugar and nucleotide sugar metabolism
WP1644: DNA replication
WP1693: Purine metabolism
WP1701: Starch and sucrose metabolism
WP1672: Mismatch repair
WP2292: Chemokine signaling pathway
WP2199: Seed Development
WP1438: Influenza A virus infection
WP1692: Protein export
WP232: G Protein Signaling Pathways
WP525: Mitochondrial Unfolded-Protein Response
WP346: Protein Modifications

Related Genes :
[MAPK13 PRKM13 SAPK4] Mitogen-activated protein kinase 13 (MAP kinase 13) (MAPK 13) (EC 2.7.11.24) (Mitogen-activated protein kinase p38 delta) (MAP kinase p38 delta) (Stress-activated protein kinase 4)
[Mapk13] Mitogen-activated protein kinase 13 (MAP kinase 13) (MAPK 13) (EC 2.7.11.24) (Mitogen-activated protein kinase p38 delta) (MAP kinase p38 delta) (Stress-activated protein kinase 4)
[Mapk13 Serk4] Mitogen-activated protein kinase 13 (MAP kinase 13) (MAPK 13) (EC 2.7.11.24) (Mitogen-activated protein kinase p38 delta) (MAP kinase p38 delta) (Stress-activated protein kinase 4)
[MAPK14 CSBP CSBP1 CSBP2 CSPB1 MXI2 SAPK2A] Mitogen-activated protein kinase 14 (MAP kinase 14) (MAPK 14) (EC 2.7.11.24) (Cytokine suppressive anti-inflammatory drug-binding protein) (CSAID-binding protein) (CSBP) (MAP kinase MXI2) (MAX-interacting protein 2) (Mitogen-activated protein kinase p38 alpha) (MAP kinase p38 alpha) (Stress-activated protein kinase 2a) (SAPK2a)
[Mapk12 Sapk3] Mitogen-activated protein kinase 12 (MAP kinase 12) (MAPK 12) (EC 2.7.11.24) (Extracellular signal-regulated kinase 6) (ERK-6) (Mitogen-activated protein kinase p38 gamma) (MAP kinase p38 gamma) (Stress-activated protein kinase 3)
[MAPK12 ERK6 SAPK3] Mitogen-activated protein kinase 12 (MAP kinase 12) (MAPK 12) (EC 2.7.11.24) (Extracellular signal-regulated kinase 6) (ERK-6) (Mitogen-activated protein kinase p38 gamma) (MAP kinase p38 gamma) (Stress-activated protein kinase 3)
[MAPK11 PRKM11 SAPK2 SAPK2B] Mitogen-activated protein kinase 11 (MAP kinase 11) (MAPK 11) (EC 2.7.11.24) (Mitogen-activated protein kinase p38 beta) (MAP kinase p38 beta) (p38b) (Stress-activated protein kinase 2b) (SAPK2b) (p38-2)
[Mapk12 Sapk3] Mitogen-activated protein kinase 12 (MAP kinase 12) (MAPK 12) (EC 2.7.11.24) (Extracellular signal-regulated kinase 6) (ERK-6) (Mitogen-activated protein kinase p38 gamma) (MAP kinase p38 gamma) (Stress-activated protein kinase 3)
[Mapk14 Crk1 Csbp1 Csbp2] Mitogen-activated protein kinase 14 (MAP kinase 14) (MAPK 14) (EC 2.7.11.24) (CRK1) (Mitogen-activated protein kinase p38 alpha) (MAP kinase p38 alpha)
[Mapk14 Csbp1 Csbp2] Mitogen-activated protein kinase 14 (MAP kinase 14) (MAPK 14) (EC 2.7.11.24) (CRK1) (Mitogen-activated protein kinase p38 alpha) (MAP kinase p38 alpha)
[Mapk11 Prkm11] Mitogen-activated protein kinase 11 (MAP kinase 11) (MAPK 11) (EC 2.7.11.24) (Mitogen-activated protein kinase p38 beta) (MAP kinase p38 beta) (p38B)
[MAPK14 CSBP1 CSBP2] Mitogen-activated protein kinase 14 (MAP kinase 14) (MAPK 14) (EC 2.7.11.24) (Mitogen-activated protein kinase p38 alpha) (MAP kinase p38 alpha)
[mapk14a mapk14] Mitogen-activated protein kinase 14A (MAP kinase 14A) (MAPK 14A) (EC 2.7.11.24) (Mitogen-activated protein kinase p38a) (MAP kinase p38a) (zp38a)
[mapk14b mapk14] Mitogen-activated protein kinase 14B (MAP kinase 14B) (MAPK 14B) (EC 2.7.11.24) (Mitogen-activated protein kinase p38b) (MAP kinase p38b) (zp38b)
[pmk-1 B0218.3] Mitogen-activated protein kinase pmk-1 (EC 2.7.11.24) (Stress-activated protein kinase pmk-1) (p38 MAP kinase 1)
[mapk14b] Mitogen-activated protein kinase 14B (MAP kinase 14B) (MAPK 14B) (EC 2.7.11.24) (Mitogen-activated protein kinase p38b) (MAP kinase p38b) (cp38b)
[pmk-3 F42G8.4] Mitogen-activated protein kinase pmk-3 (EC 2.7.11.24) (Stress-activated protein kinase pmk-3) (p38 MAP kinase 3)
[mapk14a] Mitogen-activated protein kinase 14A (MAP kinase 14A) (MAPK 14A) (EC 2.7.11.24) (Mitogen-activated protein kinase p38a) (MAP kinase p38a) (cp38a)
[p38b CG7393] Mitogen-activated protein kinase p38b (MAP kinase p38b) (MAPK p38b) (EC 2.7.11.24)
[MAPK14 CSBP1] Mitogen-activated protein kinase 14 (MAP kinase 14) (MAPK 14) (EC 2.7.11.24) (Mitogen-activated protein kinase p38 alpha) (MAP kinase p38 alpha) (Stress-activated protein kinase 2a)
[MAPKAPK5 PRAK] MAP kinase-activated protein kinase 5 (MAPK-activated protein kinase 5) (MAPKAP kinase 5) (MAPKAP-K5) (MAPKAPK-5) (MK-5) (MK5) (EC 2.7.11.1) (p38-regulated/activated protein kinase) (PRAK)
[MAPK1 ERK2 PRKM1 PRKM2] Mitogen-activated protein kinase 1 (MAP kinase 1) (MAPK 1) (EC 2.7.11.24) (ERT1) (Extracellular signal-regulated kinase 2) (ERK-2) (MAP kinase isoform p42) (p42-MAPK) (Mitogen-activated protein kinase 2) (MAP kinase 2) (MAPK 2)
[Mapk8 Jnk1 Prkm8] Mitogen-activated protein kinase 8 (MAP kinase 8) (MAPK 8) (EC 2.7.11.24) (Stress-activated protein kinase JNK1) (c-Jun N-terminal kinase 1)
[MAPK3 ERK1 PRKM3] Mitogen-activated protein kinase 3 (MAP kinase 3) (MAPK 3) (EC 2.7.11.24) (ERT2) (Extracellular signal-regulated kinase 1) (ERK-1) (Insulin-stimulated MAP2 kinase) (MAP kinase isoform p44) (p44-MAPK) (Microtubule-associated protein 2 kinase) (p44-ERK1)
[MAP2K6 MEK6 MKK6 PRKMK6 SKK3] Dual specificity mitogen-activated protein kinase kinase 6 (MAP kinase kinase 6) (MAPKK 6) (EC 2.7.12.2) (MAPK/ERK kinase 6) (MEK 6) (Stress-activated protein kinase kinase 3) (SAPK kinase 3) (SAPKK-3) (SAPKK3)
[Mapk8 Jnk1 Prkm8] Mitogen-activated protein kinase 8 (MAP kinase 8) (MAPK 8) (EC 2.7.11.24) (SAPK gamma) (Stress-activated protein kinase JNK1) (c-Jun N-terminal kinase 1) (p54 gamma)
[MAP3K5 ASK1 MAPKKK5 MEKK5] Mitogen-activated protein kinase kinase kinase 5 (EC 2.7.11.25) (Apoptosis signal-regulating kinase 1) (ASK-1) (MAPK/ERK kinase kinase 5) (MEK kinase 5) (MEKK 5)
[MAP3K20 MLTK ZAK HCCS4] Mitogen-activated protein kinase kinase kinase 20 (EC 2.7.11.25) (Human cervical cancer suppressor gene 4 protein) (HCCS-4) (Leucine zipper- and sterile alpha motif-containing kinase) (MLK-like mitogen-activated protein triple kinase) (Mitogen-activated protein kinase kinase kinase MLT) (Mixed lineage kinase-related kinase) (MLK-related kinase) (MRK) (Sterile alpha motif- and leucine zipper-containing kinase AZK)
[MAP4K2 GCK RAB8IP] Mitogen-activated protein kinase kinase kinase kinase 2 (EC 2.7.11.1) (B lymphocyte serine/threonine-protein kinase) (Germinal center kinase) (GC kinase) (MAPK/ERK kinase kinase kinase 2) (MEK kinase kinase 2) (MEKKK 2) (Rab8-interacting protein)
[MAPK10 JNK3 JNK3A PRKM10 SAPK1B] Mitogen-activated protein kinase 10 (MAP kinase 10) (MAPK 10) (EC 2.7.11.24) (MAP kinase p49 3F12) (Stress-activated protein kinase 1b) (SAPK1b) (Stress-activated protein kinase JNK3) (c-Jun N-terminal kinase 3)

Bibliography :
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