MK04_RAT
ID MK04_RAT Reviewed; 274 AA.
AC Q63454;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=Mitogen-activated protein kinase 4;
DE Short=MAP kinase 4;
DE Short=MAPK 4;
DE EC=2.7.11.24;
DE AltName: Full=Extracellular signal-regulated kinase 4;
DE Short=ERK-4;
DE AltName: Full=MAP kinase isoform p63;
DE Short=p63-MAPK;
DE AltName: Full=MNK2;
DE Flags: Fragment;
GN Name=Mapk4; Synonyms=Prkm4;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Wistar; TISSUE=Corpus striatum;
RX PubMed=8875888; DOI=10.1007/s003359900242;
RA Garcia J.I., Zalba G., Detera-Wadleigh S.D., de Miguel C.;
RT "Isolation of a cDNA encoding the rat MAP-kinase homolog of human
RT p63mapk.";
RL Mamm. Genome 7:810-814(1996).
RN [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-160, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Atypical MAPK protein. Phosphorylates microtubule-associated
CC protein 2 (MAP2) and MAPKAPK5. The precise role of the complex formed
CC with MAPKAPK5 is still unclear, but the complex follows a complex set
CC of phosphorylation events: upon interaction with atypical MAPKAPK5,
CC ERK4/MAPK4 is phosphorylated and then mediates phosphorylation and
CC activation of MAPKAPK5, which in turn phosphorylates ERK4/MAPK4. May
CC promote entry in the cell cycle (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 in the activation
CC loop. {ECO:0000250}.
CC -!- SUBUNIT: Homodimer. Heterodimer with ERK3/MAPK6. Interacts with
CC MAPKAPK5 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC Note=Translocates to the cytoplasm following interaction with MAPKAPK5.
CC {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Exclusively detected in the brain, where expression
CC is restricted to the choroid plexus and hippocampus, and to a lesser
CC extent in lung.
CC -!- DOMAIN: In contrast to classical MAPKs, the TXY motif within the
CC activation loop is replaced by the SEG motif, whose phosphorylation
CC activates the MAP kinases. {ECO:0000250}.
CC -!- PTM: Phosphorylated by PAK1, PAK2 and PAK3 in the activation loop
CC resulting in catalytic activation. Phosphorylated by MAPKAPK5 at other
CC sites (By similarity). {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; Z21935; CAA79929.1; -; mRNA.
DR PIR; S33178; S33178.
DR AlphaFoldDB; Q63454; -.
DR SMR; Q63454; -.
DR IntAct; Q63454; 1.
DR MINT; Q63454; -.
DR STRING; 10116.ENSRNOP00000050164; -.
DR iPTMnet; Q63454; -.
DR PaxDb; Q63454; -.
DR RGD; 3047; Mapk4.
DR eggNOG; KOG0660; Eukaryota.
DR InParanoid; Q63454; -.
DR PhylomeDB; Q63454; -.
DR Reactome; R-RNO-5687128; MAPK6/MAPK4 signaling.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004707; F:MAP kinase activity; IBA:GO_Central.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; 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 InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR008350; MAPK_ERK3/4.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR PRINTS; PR01771; ERK3ERK4MAPK.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cell cycle; Cytoplasm; Kinase; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transferase.
FT CHAIN <1..>274
FT /note="Mitogen-activated protein kinase 4"
FT /id="PRO_0000186256"
FT DOMAIN <1..>274
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOTIF 160..162
FT /note="SEG motif"
FT ACT_SITE 123
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING <1..8
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 23
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 160
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT NON_TER 1
FT NON_TER 274
SQ SEQUENCE 274 AA; 31162 MW; D98E3079487AB51F CRC64;
GCGGNGLVLS ATDSRACRKV AVKKIVLSDA RSMKHALREI KIIRRLDHDN IVKVYEVLGP
KGSDLQGELF KFSVAYIVQE YMETDLACLL EQGTLTEEHA KLFMYQLLRG LKYIHSANVL
HRDLKPANIF ISTEDLVLKI GDFGLARIAD QHYSHKGYLS EGLVTKWYRS PRLLLSPNNY
TKAIDMWAAG CILAEMLTGK MLFAGAHELE QMQLILDTIP VVREEDKEEL LRVMPSFVSS
TWEVKRPLRK LLPDVNREAI DFLEKILTFS PMDR
