MK06_RAT
ID MK06_RAT Reviewed; 720 AA.
AC P27704; Q32LY4;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 03-AUG-2022, entry version 165.
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;
DE AltName: Full=p55-MAPK;
GN Name=Mapk6; Synonyms=Erk3, Prkm6;
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=Sprague-Dawley; TISSUE=Brain, and Liver;
RX PubMed=2032290; DOI=10.1016/0092-8674(91)90098-j;
RA Boulton T.G., Nye S.H., Robbins D.J., Ip N.Y., Radziejewska E.,
RA Morgenbesser S.D., DePinho R.A., Panayotatos N., Cobb M.H.,
RA Yancopoulos G.D.;
RT "ERKs: a family of protein-serine/threonine kinases that are activated and
RT tyrosine phosphorylated in response to insulin and NGF.";
RL Cell 65:663-675(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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).
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 (By
CC 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 at Ser-189.
CC {ECO:0000250}.
CC -!- SUBUNIT: Heterodimer with ERK4/MAPK4. Interacts with (via FRIEDE motif)
CC MAPKAPK5 (By similarity). Interacts with UBE3A; this interaction may be
CC indirect and mediated by HERC2, possibly via HERC2 interaction with
CC NEURL4 (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: Highest levels within the nervous system, expressed
CC in different tissues, mostly in skeletal muscle.
CC -!- DEVELOPMENTAL STAGE: Expressed at highest levels early in development.
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 at Ser-189 by PAK1, PAK2 and PAK3 resulting in
CC catalytic activation. Phosphorylated by MAPKAPK5 at other sites (By
CC similarity). {ECO:0000250}.
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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA41125.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; M64301; AAA41125.1; ALT_FRAME; mRNA.
DR EMBL; BC109380; AAI09381.1; -; mRNA.
DR PIR; B40033; B40033.
DR RefSeq; NP_113810.2; NM_031622.2.
DR RefSeq; XP_006243471.1; XM_006243409.3.
DR AlphaFoldDB; P27704; -.
DR SMR; P27704; -.
DR STRING; 10116.ENSRNOP00000013053; -.
DR iPTMnet; P27704; -.
DR PhosphoSitePlus; P27704; -.
DR PaxDb; P27704; -.
DR PRIDE; P27704; -.
DR Ensembl; ENSRNOT00000013053; ENSRNOP00000013053; ENSRNOG00000009381.
DR GeneID; 58840; -.
DR KEGG; rno:58840; -.
DR UCSC; RGD:62087; rat.
DR CTD; 5597; -.
DR RGD; 62087; Mapk6.
DR eggNOG; KOG0660; Eukaryota.
DR GeneTree; ENSGT00940000154351; -.
DR InParanoid; P27704; -.
DR OMA; EADWQLH; -.
DR OrthoDB; 741207at2759; -.
DR PhylomeDB; P27704; -.
DR TreeFam; TF105098; -.
DR BRENDA; 2.7.11.24; 5301.
DR Reactome; R-RNO-5687128; MAPK6/MAPK4 signaling.
DR PRO; PR:P27704; -.
DR Proteomes; UP000002494; Chromosome 8.
DR Bgee; ENSRNOG00000009381; Expressed in testis and 19 other tissues.
DR ExpressionAtlas; P27704; baseline and differential.
DR Genevisible; P27704; RN.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISO:RGD.
DR GO; GO:0032156; C:septin cytoskeleton; ISO:RGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004707; F:MAP kinase activity; ISS:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:RGD.
DR GO; GO:0004672; F:protein kinase activity; ISO:RGD.
DR GO; GO:0019901; F:protein kinase binding; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0006468; P:protein phosphorylation; ISS: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 2: Evidence at transcript 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_0000186259"
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 698..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 COMPBIAS 698..713
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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:0000250|UniProtKB:Q16659"
FT MOD_RES 386
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q16659"
FT MOD_RES 452
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"
SQ SEQUENCE 720 AA; 82275 MW; B200B215574AB84D 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
MQLILESIPV VHEEDRQELL SVIPVYIRND MTEPHKPLTQ LLPGISREAL DFLEQILTFS
PMDRLTAEEA LSHPYMSIYS FPTDEPISSH PFHIEDEVDD ILLMDETHSH IYNWERYHDC
QFSEHDWPIH NNFDIDEVQL DPRALSDVTD EEEVQVDPRK YLDGDREKYL EDPAFDTSYS
AEPCWQYPDH HENKYCDLEC SHTCNYKTRS PSYLDNLVWR ESEVNHYYEP KLIIDLSNWK
EQSKDKSDKR GKSKCERNGL VKAQIALEEA SQQLAERERG QGFDFDAFIA GTVQLSAQRE
SADVVDKLND LNSSVSQLEM KSLISKSVSR EKQEKGRANL AQLGALYQPS WESQFVSGGE
ECFLISQFCC EVRKDEHVEK ENTYTSYLDK FFSRKEDSEM LETEPVEEGK RGERGREAGL
LSSGGEFLLS RQLESIGTPQ FHSPGGSPLK SIQATLTPSA MKSSPQIPHK TYSNILKHLN
