MAPK3_BOVIN
ID MAPK3_BOVIN Reviewed; 384 AA.
AC Q3SYZ2; Q0V8M1;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 122.
DE RecName: Full=MAP kinase-activated protein kinase 3;
DE Short=MAPK-activated protein kinase 3;
DE Short=MAPKAP kinase 3;
DE Short=MAPKAP-K3;
DE Short=MAPKAPK-3;
DE Short=MK-3;
DE EC=2.7.11.1;
GN Name=MAPKAPK3;
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].
RX PubMed=16305752; DOI=10.1186/1471-2164-6-166;
RA Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L.,
RA Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L.;
RT "Characterization of 954 bovine full-CDS cDNA sequences.";
RL BMC Genomics 6:166-166(2005).
RN [2]
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: Stress-activated serine/threonine-protein kinase involved in
CC cytokines production, endocytosis, cell migration, chromatin remodeling
CC and transcriptional regulation. Following stress, it is phosphorylated
CC and activated by MAP kinase p38-alpha/MAPK14, leading to
CC phosphorylation of substrates. Phosphorylates serine in the peptide
CC sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue.
CC MAPKAPK2 and MAPKAPK3, share the same function and substrate
CC specificity, but MAPKAPK3 kinase activity and level in protein
CC expression are lower compared to MAPKAPK2. Phosphorylates HSP27/HSPB1,
CC KRT18, KRT20, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Mediates
CC phosphorylation of HSP27/HSPB1 in response to stress, leading to
CC dissociate HSP27/HSPB1 from large small heat-shock protein (sHsps)
CC oligomers and impair their chaperone activities and ability to protect
CC against oxidative stress effectively. Involved in inflammatory response
CC by regulating tumor necrosis factor (TNF) and IL6 production post-
CC transcriptionally: acts by phosphorylating AU-rich elements (AREs)-
CC binding proteins, such as TTP/ZFP36, leading to regulate the stability
CC and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36, a
CC major post-transcriptional regulator of TNF, promotes its binding to
CC 14-3-3 proteins and reduces its ARE mRNA affinity leading to inhibition
CC of dependent degradation of ARE-containing transcript. Involved in
CC toll-like receptor signaling pathway (TLR) in dendritic cells: required
CC for acute TLR-induced macropinocytosis by phosphorylating and
CC activating RPS6KA3. Also acts as a modulator of Polycomb-mediated
CC repression (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=2.7.11.1;
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=2.7.11.1;
CC -!- ACTIVITY REGULATION: Activated following phosphorylation by p38-
CC alpha/MAPK14 following various stresses. Inhibited by ligand 5B (2'-[2-
CC (1,3-benzodioxol-5-yl)pyrimidin-4-yl]-5',6'-dihydrospiro[piperidine-
CC 4,7'-pyrrolo[3,2-c]pyridin]- 4'(1'h)-one) and ligand P4O (2-[2-(2-
CC fluorophenyl)pyridin-4-yl]-1,5,6,7-tetrahydro- 4h-pyrrolo[3,2-
CC c]pyridin-4-one), 2 ATP-competitive inhibitors (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: Heterodimer with p38-alpha/MAPK14. The heterodimer with p38-
CC alpha/MAPK14 forms a stable complex: molecules are positioned 'face to
CC face' so that the ATP-binding sites of both kinases are at the
CC heterodimer interface. Interacts with TCF3 and with polycomb proteins,
CC such as PCH2 and BMI1/PCGF4 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Cytoplasm {ECO:0000250}.
CC Note=Predominantly located in the nucleus, when activated it
CC translocates to the cytoplasm. {ECO:0000250}.
CC -!- PTM: Phosphorylated and activated by MAPK1/ERK2 and MAPK3/ERK1.
CC Phosphorylated and activated by MAP kinase p38-alpha/MAPK14 at Thr-203,
CC Ser-253 and Thr-315. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. {ECO:0000305}.
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DR EMBL; BT026197; ABG67036.1; -; mRNA.
DR EMBL; BC103321; AAI03322.1; -; mRNA.
DR RefSeq; NP_001029951.1; NM_001034779.2.
DR RefSeq; XP_005222977.1; XM_005222920.1.
DR AlphaFoldDB; Q3SYZ2; -.
DR SMR; Q3SYZ2; -.
DR STRING; 9913.ENSBTAP00000021983; -.
DR PaxDb; Q3SYZ2; -.
DR PRIDE; Q3SYZ2; -.
DR Ensembl; ENSBTAT00000021983; ENSBTAP00000021983; ENSBTAG00000016532.
DR GeneID; 615215; -.
DR KEGG; bta:615215; -.
DR CTD; 7867; -.
DR VEuPathDB; HostDB:ENSBTAG00000016532; -.
DR VGNC; VGNC:31229; MAPKAPK3.
DR eggNOG; KOG0604; Eukaryota.
DR GeneTree; ENSGT00940000154089; -.
DR HOGENOM; CLU_000288_63_0_1; -.
DR InParanoid; Q3SYZ2; -.
DR OMA; LTIMQFM; -.
DR OrthoDB; 843707at2759; -.
DR TreeFam; TF312891; -.
DR Proteomes; UP000009136; Chromosome 22.
DR Bgee; ENSBTAG00000016532; Expressed in cardiac ventricle and 104 other tissues.
DR ExpressionAtlas; Q3SYZ2; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0009931; F:calcium-dependent protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0005516; F:calmodulin binding; IBA:GO_Central.
DR GO; GO:0004683; F:calmodulin-dependent protein kinase activity; IBA:GO_Central.
DR GO; GO:0051019; F:mitogen-activated protein kinase binding; IBA:GO_Central.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0044351; P:macropinocytosis; ISS:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0046777; P:protein autophosphorylation; IBA:GO_Central.
DR GO; GO:0034097; P:response to cytokine; ISS:UniProtKB.
DR GO; GO:0032496; P:response to lipopolysaccharide; ISS:UniProtKB.
DR GO; GO:0002224; P:toll-like receptor signaling pathway; ISS:UniProtKB.
DR Gene3D; 4.10.1170.10; -; 1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR027442; MAPKAPK_C.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 2: Evidence at transcript level;
KW Acetylation; ATP-binding; Cytoplasm; Kinase; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transferase.
FT CHAIN 1..384
FT /note="MAP kinase-activated protein kinase 3"
FT /id="PRO_0000086292"
FT DOMAIN 46..306
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 309..345
FT /note="Autoinhibitory helix"
FT /evidence="ECO:0000250"
FT REGION 347..371
FT /note="p38 MAPK-binding site"
FT /evidence="ECO:0000250"
FT REGION 359..384
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 337..346
FT /note="Nuclear export signal (NES)"
FT /evidence="ECO:0000250"
FT MOTIF 352..355
FT /note="Bipartite nuclear localization signal 1"
FT /evidence="ECO:0000250"
FT MOTIF 366..370
FT /note="Bipartite nuclear localization signal 2"
FT /evidence="ECO:0000250"
FT COMPBIAS 370..384
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 168
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 52..60
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 75
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q16644"
FT MOD_RES 203
FT /note="Phosphothreonine; by MAPK14"
FT /evidence="ECO:0000250|UniProtKB:Q3UMW7"
FT MOD_RES 253
FT /note="Phosphoserine; by MAPK14"
FT /evidence="ECO:0000250"
FT MOD_RES 309
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 315
FT /note="Phosphothreonine; by MAPK14"
FT /evidence="ECO:0000250"
SQ SEQUENCE 384 AA; 43316 MW; C9D737DDCF8A0C06 CRC64;
MDVETAEEQG GPAPPSGVPC GPCSAGAPAL GGRREPKKYA VTDDYQLSKQ VLGLGVNGKV
LECFHRRTGQ KCALKLLYDS PKARQEVDHH WQASGGPHIV RILDVYENMH HSKRCLLIIM
ECMEGGELFS RIQERGDQAF TEREAAEIMR DIGTAIQFLH SRNIAHRDVK PENLLYTSKD
KDAVLKLTDF GFAKETTQNA LQTPCYTPYY VAPEVLGPEK YDKSCDMWSL GVIMYILLCG
FPPFYSNTGQ AISPGMKRRI RLGQYGFPSP EWSEVSEDAK QLIRLLLKTD PTERLTITQF
MNHPWINQSM VVPQTPLHTA RVLQEDRDHW DEVKEEMTSA LATMRVDYDQ VKIKDLKTSN
NRLLNKRRKK QAGSSSGSQG CNNQ
