ID MK06_PONAB Reviewed; 721 AA.
AC Q5R7U1;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 24-JAN-2024, entry version 99.
DE RecName: Full=Mitogen-activated protein kinase 6;
DE Short=MAP kinase 6;
DE Short=MAPK 6;
DE EC=2.7.11.24;
GN Name=MAPK6;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain cortex;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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 -!- 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}.
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DR EMBL; CR860018; CAH92169.1; -; mRNA.
DR RefSeq; NP_001126270.1; NM_001132798.1.
DR RefSeq; XP_009248112.1; XM_009249837.1.
DR AlphaFoldDB; Q5R7U1; -.
DR SMR; Q5R7U1; -.
DR STRING; 9601.ENSPPYP00000007346; -.
DR Ensembl; ENSPPYT00000007648.3; ENSPPYP00000007346.3; ENSPPYG00000006482.3.
DR GeneID; 100173242; -.
DR KEGG; pon:100173242; -.
DR CTD; 5597; -.
DR eggNOG; KOG0660; Eukaryota.
DR GeneTree; ENSGT00940000154351; -.
DR InParanoid; Q5R7U1; -.
DR OMA; EADWQLH; -.
DR OrthoDB; 5344491at2759; -.
DR Proteomes; UP000001595; Chromosome 15.
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; IEA:Ensembl.
DR GO; GO:0032156; C:septin cytoskeleton; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0060999; P:positive regulation of dendritic spine development; IEA:Ensembl.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR CDD; cd07854; STKc_MAPK4_6; 1.
DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
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 PANTHER; PTHR24055; MITOGEN-ACTIVATED PROTEIN KINASE; 1.
DR PANTHER; PTHR24055:SF171; MITOGEN-ACTIVATED PROTEIN KINASE 6; 1.
DR Pfam; PF00069; Pkinase; 1.
DR PRINTS; PR01771; ERK3ERK4MAPK.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 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..721
FT /note="Mitogen-activated protein kinase 6"
FT /id="PRO_0000249009"
FT DOMAIN 20..316
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 701..721
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: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 556
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q16659"
FT MOD_RES 558
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q16659"
FT MOD_RES 665
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q16659"
FT MOD_RES 684
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 721 AA; 82678 MW; CE43B75DADD726DF 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 FPMDEPISSH PFHIEDEVDD ILLMDETHSH IYNWERYHDC
QFSEHDWPVH NNFDIDEVQL DPRALSDVTD EEEVQVDPRK YLDGDREKYL EDPAFDTNYS
TEPCWQYSDH HENKYCDLEC GHTCNYKTRS SSYLDNLVWR ESEVNHYYEP KLIIDLSNWK
EQSKEKSDKK GKSKCERNGL VKAQIALEEA SQQLAGKERE KNQGFDFDSF IAGTIQLSSQ
HEPTDVVDKL NDLNSSVSQL ELKSLISKSV SQEKQEKGMA NLAQLEALYQ SSWDSQFVNG
GEDCFFINQF CEVRKDEQVE KENTYTSYLD KFFSRKEDTE MLETEPVEDG KLGERGHEEG
FLNNSGEFLF NKQLESIGIP QFHSPVGSPL KSIQATLTPS AMKSSPQIPH QTYSSILKHL
N
//
