GenomeNet

Database: UniProt/SWISS-PROT
Entry: MK06_MOUSE
LinkDB: MK06_MOUSE
Original site: 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   13-FEB-2019, entry version 155.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
OC   Muroidea; Muridae; 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:
RT   genomic 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
RT   project: 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
RT   stem 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,
RP   INTERACTION 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.,
RA   Armstrong C.G., Morrice N.A., Turgeon B., Meloche S., Moens U.,
RA   Keyse S.M.;
RT   "Activation of MK5/PRAK by the atypical MAP kinase ERK3 defines a
RT   novel 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.,
RA   Gaestel M.;
RT   "Characterization of the atypical MAPK ERK4 and its activation of the
RT   MAPK-activated protein kinase MK5.";
RL   J. Biol. Chem. 281:35511-35519(2006).
RN   [8]
RP   INTERACTION WITH MAPKAPK5, PHOSPHORYLATION AT SER-189, AND MUTAGENESIS
RP   OF SER-189.
RX   PubMed=18720373; DOI=10.1002/jcp.21560;
RA   Deleris P., Rousseau J., Coulombe P., Rodier G., Tanguay P.L.,
RA   Meloche S.;
RT   "Activation loop phosphorylation of the atypical MAP kinases ERK3 and
RT   ERK4 is required for binding, activation and cytoplasmic
RT   relocalization of MK5.";
RL   J. Cell. Physiol. 217:778-788(2008).
RN   [9]
RP   INTERACTION WITH MAPKAPK5, DOMAIN FRIEDE MOTIF, AND MUTAGENESIS OF
RP   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
RT   novel MAPK interaction motif.";
RL   J. Biol. Chem. 284:19392-19401(2009).
CC   -!- FUNCTION: Atypical MAPK protein. Phosphorylates microtubule-
CC       associated protein 2 (MAP2) and MAPKAPK5. The precise role of the
CC       complex formed with MAPKAPK5 is still unclear, but the complex
CC       follows a complex set of phosphorylation events: upon interaction
CC       with atypical MAPKAPK5, ERK3/MAPK6 is phosphorylated at Ser-189
CC       and then mediates phosphorylation and activation of MAPKAPK5,
CC       which in turn phosphorylates ERK3/MAPK6. May promote entry in the
CC       cell cycle. {ECO:0000269|PubMed:15538386,
CC       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,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216;
CC         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
CC       motif) MAPKAPK5. Interacts with UBE3A; this interaction may be
CC       indirect and mediated by HERC2, possibly via HERC2 interaction
CC       with NEURL4 (By 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
CC       11 in the developing embryo, followed by a gradual decrease up to
CC       birth. {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
CC       phosphorylation activates the MAP kinases.
CC       {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
CC       proteasome pathway. {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC
CC       Ser/Thr protein kinase family. MAP kinase subfamily.
CC       {ECO:0000305}.
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   UniGene; Mm.480076; -.
DR   ProteinModelPortal; Q61532; -.
DR   SMR; Q61532; -.
DR   BioGrid; 206104; 4.
DR   STRING; 10090.ENSMUSP00000040315; -.
DR   iPTMnet; Q61532; -.
DR   PhosphoSitePlus; Q61532; -.
DR   jPOST; Q61532; -.
DR   MaxQB; Q61532; -.
DR   PaxDb; Q61532; -.
DR   PeptideAtlas; Q61532; -.
DR   PRIDE; Q61532; -.
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   eggNOG; KOG0660; Eukaryota.
DR   eggNOG; ENOG410XNY0; LUCA.
DR   GeneTree; ENSGT00940000154351; -.
DR   HOVERGEN; HBG104376; -.
DR   InParanoid; Q61532; -.
DR   KO; K06855; -.
DR   OMA; RDSEVNH; -.
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   ChiTaRS; Mapk6; mouse.
DR   PRO; PR:Q61532; -.
DR   Proteomes; UP000000589; Chromosome 9.
DR   Bgee; ENSMUSG00000042688; Expressed in 315 organ(s), highest expression level in blood.
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:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR   GO; GO:0071310; P:cellular response to organic substance; IBA:GO_Central.
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   GO; GO:0010468; P:regulation of gene expression; IBA:GO_Central.
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; Complete proteome; Cytoplasm; Kinase;
KW   Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW   Serine/threonine-protein kinase; Transferase; Ubl conjugation.
FT   CHAIN         1    720       Mitogen-activated protein kinase 6.
FT                                /FTId=PRO_0000186258.
FT   DOMAIN       20    316       Protein kinase. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00159}.
FT   NP_BIND      26     34       ATP. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00159}.
FT   MOTIF       189    191       SEG motif.
FT   MOTIF       332    337       FRIEDE motif.
FT   ACT_SITE    152    152       Proton acceptor. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00159, ECO:0000255|PROSITE-
FT                                ProRule:PRU10027}.
FT   BINDING      49     49       ATP. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00159}.
FT   MOD_RES     189    189       Phosphoserine; by PAK1, PAK2 and PAK3.
FT                                {ECO:0000305|PubMed:18720373}.
FT   MOD_RES     386    386       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q16659}.
FT   MOD_RES     554    554       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q16659}.
FT   MOD_RES     556    556       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q16659}.
FT   MOD_RES     683    683       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q16659}.
FT   CROSSLNK      1      1       Peptide (Met-Gly) (interchain with G-Cter
FT                                in ubiquitin). {ECO:0000250}.
FT   MUTAGEN     171    171       D->A: Kinase defective mutant, abolishes
FT                                activity. {ECO:0000269|PubMed:15577943}.
FT   MUTAGEN     189    189       S->A: Unable to activate MAPKAPK5 promote
FT                                MAPKAPK5 localization to the cytoplasm.
FT                                {ECO:0000269|PubMed:15577943,
FT                                ECO:0000269|PubMed:18720373}.
FT   MUTAGEN     189    189       S->E: Mimicks phosphorylation state and
FT                                induces constitutive protein kinase
FT                                activity. {ECO:0000269|PubMed:15577943,
FT                                ECO:0000269|PubMed:18720373}.
FT   MUTAGEN     334    334       I->K: Abolishes binding to MAPKAPK5.
FT                                {ECO:0000269|PubMed:19473979}.
FT   CONFLICT     19     19       R -> T (in Ref. 2; AAN64588).
FT                                {ECO:0000305}.
FT   CONFLICT     40     41       ND -> KY (in Ref. 2; AAN64588).
FT                                {ECO:0000305}.
FT   CONFLICT     63     63       L -> P (in Ref. 3; AAI00386).
FT                                {ECO:0000305}.
FT   CONFLICT    123    123       P -> S (in Ref. 1; AAF61348).
FT                                {ECO:0000305}.
FT   CONFLICT    574    574       E -> K (in Ref. 2; AAN64588).
FT                                {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
//
DBGET integrated database retrieval system