UniProtKB - Q61532 (MK06_MOUSE)
Protein
Mitogen-activated protein kinase 6
Gene
Mapk6
Organism
Mus musculus (Mouse)
Status
Functioni
Atypical MAPK protein. Phosphorylates microtubule-associated protein 2 (MAP2) and MAPKAPK5. The precise role of the complex formed with MAPKAPK5 is still unclear, but the complex follows a complex set of phosphorylation events: upon interaction with atypical MAPKAPK5, ERK3/MAPK6 is phosphorylated at Ser-189 and then mediates phosphorylation and activation of MAPKAPK5, which in turn phosphorylates ERK3/MAPK6. May promote entry in the cell cycle.2 Publications
Catalytic activityi
Cofactori
Mg2+By similarity
Activity regulationi
Activated by phosphorylation at Ser-189.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 49 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 152 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 26 – 34 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- MAP kinase activity Source: UniProtKB
- protein heterodimerization activity Source: UniProtKB
- protein kinase activity Source: MGI
- protein kinase binding Source: UniProtKB
- protein serine kinase activity Source: RHEA
- protein threonine kinase activity Source: RHEA
GO - Biological processi
- cell cycle Source: UniProtKB-KW
- intracellular signal transduction Source: GO_Central
- positive regulation of dendritic spine development Source: MGI
- protein phosphorylation Source: UniProtKB
- regulation of gene expression Source: GO_Central
Keywordsi
Molecular function | Kinase, Serine/threonine-protein kinase, Transferase |
Biological process | Cell cycle |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 2.7.11.24, 3474 |
Reactomei | R-MMU-5687128, MAPK6/MAPK4 signaling |
Names & Taxonomyi
Protein namesi | Recommended name: Mitogen-activated protein kinase 6 (EC:2.7.11.24)Short name: MAP kinase 6 Short name: MAPK 6 Alternative name(s): Extracellular signal-regulated kinase 3 Short name: ERK-3 |
Gene namesi | Name:Mapk6 Synonyms:Erk3, Prkm4, Prkm6 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1354946, Mapk6 |
Subcellular locationi
Cytoskeleton
- septin cytoskeleton Source: MGI
Cytosol
- cytosol Source: MGI
Nucleus
- nucleus Source: UniProtKB
Other locations
- cytoplasm Source: UniProtKB
- protein-containing complex Source: MGI
Keywords - Cellular componenti
Cytoplasm, NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 171 | D → A: Kinase defective mutant, abolishes activity. 1 Publication | 1 | |
Mutagenesisi | 189 | S → A: Unable to activate MAPKAPK5 promote MAPKAPK5 localization to the cytoplasm. 2 Publications | 1 | |
Mutagenesisi | 189 | S → E: Mimicks phosphorylation state and induces constitutive protein kinase activity. 2 Publications | 1 | |
Mutagenesisi | 334 | I → K: Abolishes binding to MAPKAPK5. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000186258 | 1 – 720 | Mitogen-activated protein kinase 6Add BLAST | 720 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Cross-linki | 1 | Peptide (Met-Gly) (interchain with G-Cter in ubiquitin)By similarity | ||
Modified residuei | 189 | Phosphoserine; by PAK1, PAK2 and PAK31 Publication | 1 | |
Modified residuei | 386 | PhosphoserineBy similarity | 1 | |
Modified residuei | 554 | PhosphoserineBy similarity | 1 | |
Modified residuei | 556 | PhosphoserineBy similarity | 1 | |
Modified residuei | 683 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Phosphorylated at Ser-189 by PAK1, PAK2 and PAK3 resulting in catalytic activation. Phosphorylated by MAPKAPK5 at other sites.1 Publication
Ubiquitination at Met-1 leads to degradation by the proteasome pathway.By similarity
Keywords - PTMi
Phosphoprotein, Ubl conjugationProteomic databases
EPDi | Q61532 |
jPOSTi | Q61532 |
MaxQBi | Q61532 |
PaxDbi | Q61532 |
PeptideAtlasi | Q61532 |
PRIDEi | Q61532 |
ProteomicsDBi | 252571 |
PTM databases
iPTMneti | Q61532 |
PhosphoSitePlusi | Q61532 |
Expressioni
Developmental stagei
Expression increases markedly from days 9 to 11 in the developing embryo, followed by a gradual decrease up to birth.1 Publication
Gene expression databases
Bgeei | ENSMUSG00000042688, Expressed in blood and 328 other tissues |
Genevisiblei | Q61532, MM |
Interactioni
Subunit structurei
Heterodimer with ERK4/MAPK4.
Interacts with (via FRIEDE motif) MAPKAPK5.
Interacts with UBE3A; this interaction may be indirect and mediated by HERC2, possibly via HERC2 interaction with NEURL4 (By similarity).
By similarityGO - Molecular functioni
- protein heterodimerization activity Source: UniProtKB
- protein kinase binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 206104, 10 interactors |
STRINGi | 10090.ENSMUSP00000040315 |
Miscellaneous databases
RNActi | Q61532, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 20 – 316 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 297 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 189 – 191 | SEG motif | 3 | |
Motifi | 332 – 337 | FRIEDE motif | 6 |
Domaini
In contrast to classical MAPKs, the TXY motif within the activation loop is replaced by the SEG motif, whose phosphorylation activates the MAP kinases.1 Publication
Sequence similaritiesi
Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.Curated
Phylogenomic databases
eggNOGi | KOG0660, Eukaryota |
GeneTreei | ENSGT00940000154351 |
HOGENOMi | CLU_000288_181_15_1 |
InParanoidi | Q61532 |
OMAi | HESQFSE |
OrthoDBi | 741207at2759 |
PhylomeDBi | Q61532 |
TreeFami | TF105098 |
Family and domain databases
InterProi | View protein in InterPro IPR011009, Kinase-like_dom_sf IPR008350, MAPK_ERK3/4 IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit |
PRINTSi | PR01771, ERK3ERK4MAPK |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
i Sequence
Sequence statusi: Complete.
Q61532-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MAEKFESLMN IHGFDLGSRY MDLKPLGCGG NGLVFSAVDN DCDKRVAIKK
60 70 80 90 100
IVLTDPQSVK HALREIKIIR RLDHDNIVKV FEILGPSGSQ LTDDVGSLTE
110 120 130 140 150
LNSVYIVQEY METDLANVLE QGPLLEEHAR LFMYQLLRGL KYIHSANVLH
160 170 180 190 200
RDLKPANLFI NTEDLVLKIG DFGLARIMDP HYSHKGHLSE GLVTKWYRSP
210 220 230 240 250
RLLLSPNNYT KAIDMWAAGC IFAEMLTGKT LFAGAHELEQ MQLILDSIPV
260 270 280 290 300
VHEEDRQELL SVIPVYIRND MTEPHRPLTQ LLPGISREAL DFLEQILTFS
310 320 330 340 350
PMDRLTAEEA LSHPYMSIYS FPTDEPISSH PFHIEDEVDD ILLMDETHSH
360 370 380 390 400
IYNWERYHDC QFSEHDWPIH NNFDIDEVQL DPRALSDVTD EEEVQVDPRK
410 420 430 440 450
YLDGDREKYL EDPAFDTSYS AEPCWQYPDH HENKYCDLEC SHTCNYKTRS
460 470 480 490 500
SPYLDNLVWR ESEVNHYYEP KLIIDLSNWK EQSKEKSDKR GKSKCERNGL
510 520 530 540 550
VKAQIALEEA SQQLAERERG QGFDFDSFIA GTIQLSAQHQ SADVVDKLND
560 570 580 590 600
LNSSVSQLEL KSLISKSVSR EKQEKGRANL AQLGALYQSS WDSQFVSGGE
610 620 630 640 650
ECFLISQFCC EVRKDEHAEK ENTYTSYLDK FFSRKEDSEM LETEPVEEGK
660 670 680 690 700
RGERGREAGL LSGGGEFLLS KQLESIGTPQ FHSPVGSPLK SIQATLTPSA
710 720
MKSSPQIPHK TYSSILKHLN
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 19 | R → T in AAN64588 (PubMed:12504858).Curated | 1 | |
Sequence conflicti | 40 – 41 | ND → KY in AAN64588 (PubMed:12504858).Curated | 2 | |
Sequence conflicti | 63 | L → P in AAI00386 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 123 | P → S in AAF61348 (PubMed:10657254).Curated | 1 | |
Sequence conflicti | 574 | E → K in AAN64588 (PubMed:12504858).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF132850 mRNA Translation: AAF61348.1 AY134883 , AY134660, AY134880, AY134881, AY134882 Genomic DNA Translation: AAN64588.1 BC006778 mRNA Translation: AAH06778.1 BC048779 mRNA Translation: AAH48779.1 BC052420 mRNA Translation: AAH52420.2 BC100385 mRNA Translation: AAI00386.1 X64607 mRNA Translation: CAA45891.1 |
CCDSi | CCDS23342.1 |
PIRi | PN0481 |
RefSeqi | NP_056621.4, NM_015806.5 NP_081694.1, NM_027418.2 XP_011241069.1, XM_011242767.2 |
Genome annotation databases
Ensembli | ENSMUST00000049355; ENSMUSP00000040315; ENSMUSG00000042688 ENSMUST00000168937; ENSMUSP00000129024; ENSMUSG00000042688 |
GeneIDi | 50772 |
KEGGi | mmu:50772 |
UCSCi | uc009qsd.2, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF132850 mRNA Translation: AAF61348.1 AY134883 , AY134660, AY134880, AY134881, AY134882 Genomic DNA Translation: AAN64588.1 BC006778 mRNA Translation: AAH06778.1 BC048779 mRNA Translation: AAH48779.1 BC052420 mRNA Translation: AAH52420.2 BC100385 mRNA Translation: AAI00386.1 X64607 mRNA Translation: CAA45891.1 |
CCDSi | CCDS23342.1 |
PIRi | PN0481 |
RefSeqi | NP_056621.4, NM_015806.5 NP_081694.1, NM_027418.2 XP_011241069.1, XM_011242767.2 |
3D structure databases
SMRi | Q61532 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 206104, 10 interactors |
STRINGi | 10090.ENSMUSP00000040315 |
PTM databases
iPTMneti | Q61532 |
PhosphoSitePlusi | Q61532 |
Proteomic databases
EPDi | Q61532 |
jPOSTi | Q61532 |
MaxQBi | Q61532 |
PaxDbi | Q61532 |
PeptideAtlasi | Q61532 |
PRIDEi | Q61532 |
ProteomicsDBi | 252571 |
Protocols and materials databases
Antibodypediai | 3920, 546 antibodies |
Genome annotation databases
Ensembli | ENSMUST00000049355; ENSMUSP00000040315; ENSMUSG00000042688 ENSMUST00000168937; ENSMUSP00000129024; ENSMUSG00000042688 |
GeneIDi | 50772 |
KEGGi | mmu:50772 |
UCSCi | uc009qsd.2, mouse |
Organism-specific databases
CTDi | 5597 |
MGIi | MGI:1354946, Mapk6 |
Phylogenomic databases
eggNOGi | KOG0660, Eukaryota |
GeneTreei | ENSGT00940000154351 |
HOGENOMi | CLU_000288_181_15_1 |
InParanoidi | Q61532 |
OMAi | HESQFSE |
OrthoDBi | 741207at2759 |
PhylomeDBi | Q61532 |
TreeFami | TF105098 |
Enzyme and pathway databases
BRENDAi | 2.7.11.24, 3474 |
Reactomei | R-MMU-5687128, MAPK6/MAPK4 signaling |
Miscellaneous databases
BioGRID-ORCSi | 50772, 0 hits in 53 CRISPR screens |
ChiTaRSi | Mapk6, mouse |
PROi | PR:Q61532 |
RNActi | Q61532, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000042688, Expressed in blood and 328 other tissues |
Genevisiblei | Q61532, MM |
Family and domain databases
InterProi | View protein in InterPro IPR011009, Kinase-like_dom_sf IPR008350, MAPK_ERK3/4 IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit |
PRINTSi | PR01771, ERK3ERK4MAPK |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | MK06_MOUSE | |
Accessioni | Q61532Primary (citable) accession number: Q61532 Secondary accession number(s): Q497T9 Q9JLU6 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1997 |
Last sequence update: | September 13, 2004 | |
Last modified: | April 7, 2021 | |
This is version 166 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human and mouse protein kinases
Human and mouse protein kinases: classification and index - MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families