MK06_MOUSE
ID MK06_MOUSE Reviewed; 720 AA.
AC Q61532; Q497T9; Q6YKB0; Q7TT30; Q80XH5; Q922U4; Q9JLU6;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 13-SEP-2004, sequence version 3.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Mitogen-activated protein kinase 6;
DE Short=MAP kinase 6;
DE Short=MAPK 6;
DE EC=2.7.11.24;
DE AltName: Full=Extracellular signal-regulated kinase 3;
DE Short=ERK-3;
GN Name=Mapk6; Synonyms=Erk3, Prkm4, Prkm6;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND DEVELOPMENTAL STAGE.
RC TISSUE=Pituitary;
RX PubMed=10657254; DOI=10.1042/bj3460169;
RA Turgeon B., Saba-El-Leil M.K., Meloche S.;
RT "Cloning and characterization of mouse extracellular-signal-regulated
RT protein kinase 3 as a unique gene product of 100 kDa.";
RL Biochem. J. 346:169-175(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=129/Sv;
RX PubMed=12504858; DOI=10.1006/geno.2002.7013;
RA Turgeon B., Lang B.F., Meloche S.;
RT "The protein kinase ERK3 is encoded by a single functional gene: genomic
RT analysis of the ERK3 gene family.";
RL Genomics 80:673-680(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and Czech II;
RC TISSUE=Embryonic brain, Embryonic germ cell, Mammary tumor, and
RC Olfactory epithelium;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 156-195.
RC STRAIN=CBA/J; TISSUE=Hematopoietic;
RX PubMed=8444355; DOI=10.1016/0378-1119(93)90411-u;
RA Ershler M.A., Nagorskaya T.V., Visser J.W.M., Belyavsky A.V.;
RT "Novel CDC2-related protein kinases produced in murine hematopoietic stem
RT cells.";
RL Gene 124:305-306(1993).
RN [5]
RP FUNCTION IN PHOSPHORYLATION OF MAPKAPK5, SUBCELLULAR LOCATION, AND
RP INTERACTION WITH MAPKAPK5.
RX PubMed=15538386; DOI=10.1038/sj.emboj.7600467;
RA Schumacher S., Laass K., Kant S., Shi Y., Visel A., Gruber A.D.,
RA Kotlyarov A., Gaestel M.;
RT "Scaffolding by ERK3 regulates MK5 in development.";
RL EMBO J. 23:4770-4779(2004).
RN [6]
RP FUNCTION IN PHOSPHORYLATION OF MAPKAPK5, SUBCELLULAR LOCATION, INTERACTION
RP WITH MAPKAPK5, AND MUTAGENESIS OF ASP-171 AND SER-189.
RX PubMed=15577943; DOI=10.1038/sj.emboj.7600489;
RA Seternes O.M., Mikalsen T., Johansen B., Michaelsen E., Armstrong C.G.,
RA Morrice N.A., Turgeon B., Meloche S., Moens U., Keyse S.M.;
RT "Activation of MK5/PRAK by the atypical MAP kinase ERK3 defines a novel
RT signal transduction pathway.";
RL EMBO J. 23:4780-4791(2004).
RN [7]
RP INTERACTION WITH MAPK4.
RX PubMed=16973613; DOI=10.1074/jbc.m606693200;
RA Kant S., Schumacher S., Singh M.K., Kispert A., Kotlyarov A., Gaestel M.;
RT "Characterization of the atypical MAPK ERK4 and its activation of the MAPK-
RT activated protein kinase MK5.";
RL J. Biol. Chem. 281:35511-35519(2006).
RN [8]
RP INTERACTION WITH MAPKAPK5, PHOSPHORYLATION AT SER-189, AND MUTAGENESIS OF
RP SER-189.
RX PubMed=18720373; DOI=10.1002/jcp.21560;
RA Deleris P., Rousseau J., Coulombe P., Rodier G., Tanguay P.L., Meloche S.;
RT "Activation loop phosphorylation of the atypical MAP kinases ERK3 and ERK4
RT is required for binding, activation and cytoplasmic relocalization of
RT MK5.";
RL J. Cell. Physiol. 217:778-788(2008).
RN [9]
RP INTERACTION WITH MAPKAPK5, DOMAIN FRIEDE MOTIF, AND MUTAGENESIS OF ILE-334.
RX PubMed=19473979; DOI=10.1074/jbc.m109.023283;
RA Aberg E., Torgersen K.M., Johansen B., Keyse S.M., Perander M.,
RA Seternes O.M.;
RT "Docking of PRAK/MK5 to the atypical MAPKs ERK3 and ERK4 defines a novel
RT MAPK interaction motif.";
RL J. Biol. Chem. 284:19392-19401(2009).
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 ERK3/MAPK6 is phosphorylated at Ser-189 and then mediates
CC phosphorylation and activation of MAPKAPK5, which in turn
CC phosphorylates ERK3/MAPK6. May promote entry in the cell cycle.
CC {ECO:0000269|PubMed:15538386, ECO:0000269|PubMed:15577943}.
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 at Ser-189.
CC -!- SUBUNIT: Heterodimer with ERK4/MAPK4. Interacts with (via FRIEDE motif)
CC MAPKAPK5. Interacts with UBE3A; this interaction may be indirect and
CC mediated by HERC2, possibly via HERC2 interaction with NEURL4 (By
CC similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Translocates to the
CC cytoplasm following interaction with MAPKAPK5.
CC -!- DEVELOPMENTAL STAGE: Expression increases markedly from days 9 to 11 in
CC the developing embryo, followed by a gradual decrease up to birth.
CC {ECO:0000269|PubMed:10657254}.
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:0000269|PubMed:19473979}.
CC -!- PTM: Phosphorylated at Ser-189 by PAK1, PAK2 and PAK3 resulting in
CC catalytic activation. Phosphorylated by MAPKAPK5 at other sites.
CC {ECO:0000269|PubMed:18720373}.
CC -!- PTM: Ubiquitination at Met-1 leads to degradation by the proteasome
CC pathway. {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; AF132850; AAF61348.1; -; mRNA.
DR EMBL; AY134883; AAN64588.1; -; Genomic_DNA.
DR EMBL; AY134660; AAN64588.1; JOINED; Genomic_DNA.
DR EMBL; AY134880; AAN64588.1; JOINED; Genomic_DNA.
DR EMBL; AY134881; AAN64588.1; JOINED; Genomic_DNA.
DR EMBL; AY134882; AAN64588.1; JOINED; Genomic_DNA.
DR EMBL; BC006778; AAH06778.1; -; mRNA.
DR EMBL; BC048779; AAH48779.1; -; mRNA.
DR EMBL; BC052420; AAH52420.2; -; mRNA.
DR EMBL; BC100385; AAI00386.1; -; mRNA.
DR EMBL; X64607; CAA45891.1; -; mRNA.
DR CCDS; CCDS23342.1; -.
DR PIR; PN0481; PN0481.
DR RefSeq; NP_056621.4; NM_015806.5.
DR RefSeq; NP_081694.1; NM_027418.2.
DR RefSeq; XP_011241069.1; XM_011242767.2.
DR AlphaFoldDB; Q61532; -.
DR SMR; Q61532; -.
DR BioGRID; 206104; 10.
DR STRING; 10090.ENSMUSP00000040315; -.
DR iPTMnet; Q61532; -.
DR PhosphoSitePlus; Q61532; -.
DR EPD; Q61532; -.
DR jPOST; Q61532; -.
DR MaxQB; Q61532; -.
DR PaxDb; Q61532; -.
DR PeptideAtlas; Q61532; -.
DR PRIDE; Q61532; -.
DR ProteomicsDB; 252571; -.
DR Antibodypedia; 3920; 572 antibodies from 39 providers.
DR DNASU; 50772; -.
DR Ensembl; ENSMUST00000049355; ENSMUSP00000040315; ENSMUSG00000042688.
DR Ensembl; ENSMUST00000168937; ENSMUSP00000129024; ENSMUSG00000042688.
DR GeneID; 50772; -.
DR KEGG; mmu:50772; -.
DR UCSC; uc009qsd.2; mouse.
DR CTD; 5597; -.
DR MGI; MGI:1354946; Mapk6.
DR VEuPathDB; HostDB:ENSMUSG00000042688; -.
DR eggNOG; KOG0660; Eukaryota.
DR GeneTree; ENSGT00940000154351; -.
DR HOGENOM; CLU_000288_181_15_1; -.
DR InParanoid; Q61532; -.
DR OMA; EADWQLH; -.
DR OrthoDB; 741207at2759; -.
DR PhylomeDB; Q61532; -.
DR TreeFam; TF105098; -.
DR BRENDA; 2.7.11.24; 3474.
DR Reactome; R-MMU-5687128; MAPK6/MAPK4 signaling.
DR BioGRID-ORCS; 50772; 0 hits in 76 CRISPR screens.
DR ChiTaRS; Mapk6; mouse.
DR PRO; PR:Q61532; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q61532; protein.
DR Bgee; ENSMUSG00000042688; Expressed in spermatocyte and 265 other tissues.
DR Genevisible; Q61532; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:MGI.
DR GO; GO:0032156; C:septin cytoskeleton; IDA:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004707; F:MAP kinase activity; IDA:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:UniProtKB.
DR GO; GO:0004672; F:protein kinase activity; IDA:MGI.
DR GO; GO:0019901; F:protein kinase binding; IPI: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:0060999; P:positive regulation of dendritic spine development; IGI:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR008350; MAPK_ERK3/4.
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 PRINTS; PR01771; ERK3ERK4MAPK.
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 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; Ubl conjugation.
FT CHAIN 1..720
FT /note="Mitogen-activated protein kinase 6"
FT /id="PRO_0000186258"
FT DOMAIN 20..316
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 638..657
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 700..720
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 189..191
FT /note="SEG motif"
FT MOTIF 332..337
FT /note="FRIEDE motif"
FT ACT_SITE 152
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 26..34
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 49
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 189
FT /note="Phosphoserine; by PAK1, PAK2 and PAK3"
FT /evidence="ECO:0000305|PubMed:18720373"
FT MOD_RES 386
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q16659"
FT MOD_RES 554
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q16659"
FT MOD_RES 556
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q16659"
FT MOD_RES 683
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q16659"
FT CROSSLNK 1
FT /note="Peptide (Met-Gly) (interchain with G-Cter in
FT ubiquitin)"
FT /evidence="ECO:0000250"
FT MUTAGEN 171
FT /note="D->A: Kinase defective mutant, abolishes activity."
FT /evidence="ECO:0000269|PubMed:15577943"
FT MUTAGEN 189
FT /note="S->A: Unable to activate MAPKAPK5 promote MAPKAPK5
FT localization to the cytoplasm."
FT /evidence="ECO:0000269|PubMed:15577943,
FT ECO:0000269|PubMed:18720373"
FT MUTAGEN 189
FT /note="S->E: Mimicks phosphorylation state and induces
FT constitutive protein kinase activity."
FT /evidence="ECO:0000269|PubMed:15577943,
FT ECO:0000269|PubMed:18720373"
FT MUTAGEN 334
FT /note="I->K: Abolishes binding to MAPKAPK5."
FT /evidence="ECO:0000269|PubMed:19473979"
FT CONFLICT 19
FT /note="R -> T (in Ref. 2; AAN64588)"
FT /evidence="ECO:0000305"
FT CONFLICT 40..41
FT /note="ND -> KY (in Ref. 2; AAN64588)"
FT /evidence="ECO:0000305"
FT CONFLICT 63
FT /note="L -> P (in Ref. 3; AAI00386)"
FT /evidence="ECO:0000305"
FT CONFLICT 123
FT /note="P -> S (in Ref. 1; AAF61348)"
FT /evidence="ECO:0000305"
FT CONFLICT 574
FT /note="E -> K (in Ref. 2; AAN64588)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 720 AA; 82199 MW; D8BC667DEF6F62E2 CRC64;
MAEKFESLMN IHGFDLGSRY MDLKPLGCGG NGLVFSAVDN DCDKRVAIKK IVLTDPQSVK
HALREIKIIR RLDHDNIVKV FEILGPSGSQ LTDDVGSLTE LNSVYIVQEY METDLANVLE
QGPLLEEHAR LFMYQLLRGL KYIHSANVLH RDLKPANLFI NTEDLVLKIG DFGLARIMDP
HYSHKGHLSE GLVTKWYRSP RLLLSPNNYT KAIDMWAAGC IFAEMLTGKT LFAGAHELEQ
MQLILDSIPV VHEEDRQELL SVIPVYIRND MTEPHRPLTQ LLPGISREAL DFLEQILTFS
PMDRLTAEEA LSHPYMSIYS FPTDEPISSH PFHIEDEVDD ILLMDETHSH IYNWERYHDC
QFSEHDWPIH NNFDIDEVQL DPRALSDVTD EEEVQVDPRK YLDGDREKYL EDPAFDTSYS
AEPCWQYPDH HENKYCDLEC SHTCNYKTRS SPYLDNLVWR ESEVNHYYEP KLIIDLSNWK
EQSKEKSDKR GKSKCERNGL VKAQIALEEA SQQLAERERG QGFDFDSFIA GTIQLSAQHQ
SADVVDKLND LNSSVSQLEL KSLISKSVSR EKQEKGRANL AQLGALYQSS WDSQFVSGGE
ECFLISQFCC EVRKDEHAEK ENTYTSYLDK FFSRKEDSEM LETEPVEEGK RGERGREAGL
LSGGGEFLLS KQLESIGTPQ FHSPVGSPLK SIQATLTPSA MKSSPQIPHK TYSSILKHLN
