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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 //