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Q61532 (MK06_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 125. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Mitogen-activated protein kinase 6

Short name=MAP kinase 6
Short name=MAPK 6
EC=2.7.11.24
Alternative name(s):
Extracellular signal-regulated kinase 3
Short name=ERK-3
Gene names
Name:Mapk6
Synonyms:Erk3, Prkm4, Prkm6
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length720 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.5 Ref.6

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium By similarity.

Enzyme regulation

Activated by phosphorylation at Ser-189.

Subunit structure

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. Ref.5 Ref.6 Ref.7 Ref.8 Ref.9

Subcellular location

Cytoplasm. Nucleus. Note: Translocates to the cytoplasm following interaction with MAPKAPK5. Ref.5 Ref.6

Developmental stage

Expression increases markedly from days 9 to 11 in the developing embryo, followed by a gradual decrease up to birth. Ref.1

Domain

In contrast to classical MAPKs, the TXY motif within the activation loop is replaced by the SEG motif, whose phosphorylation activates the MAP kinases. Ref.9

Post-translational modification

Phosphorylated at Ser-189 by PAK1, PAK2 and PAK3 resulting in catalytic activation. Phosphorylated by MAPKAPK5 at other sites. Ref.8

Ubiquitination at Met-1 leads to degradation by the proteasome pathway By similarity.

Sequence similarities

Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.

Contains 1 protein kinase domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 720720Mitogen-activated protein kinase 6
PRO_0000186258

Regions

Domain20 – 316297Protein kinase
Nucleotide binding26 – 349ATP By similarity
Motif189 – 1913SEG motif
Motif332 – 3376FRIEDE motif

Sites

Active site1521Proton acceptor By similarity
Binding site491ATP By similarity

Amino acid modifications

Modified residue1891Phosphoserine; by PAK1, PAK2 and PAK3 Probable
Cross-link1Peptide (Met-Gly) (interchain with G-Cter in ubiquitin) By similarity

Experimental info

Mutagenesis1711D → A: Kinase defective mutant, abolishes activity. Ref.6
Mutagenesis1891S → A: Unable to activate MAPKAPK5 promote MAPKAPK5 localization to the cytoplasm. Ref.6 Ref.8
Mutagenesis1891S → E: Mimicks phosphorylation state and induces constitutive protein kinase activity. Ref.6 Ref.8
Mutagenesis3341I → K: Abolishes binding to MAPKAPK5. Ref.9
Sequence conflict191R → T in AAN64588. Ref.2
Sequence conflict40 – 412ND → KY in AAN64588. Ref.2
Sequence conflict631L → P in AAI00386. Ref.3
Sequence conflict1231P → S in AAF61348. Ref.1
Sequence conflict5741E → K in AAN64588. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q61532 [UniParc].

Last modified September 13, 2004. Version 3.
Checksum: D8BC667DEF6F62E2

FASTA72082,199
        10         20         30         40         50         60 
MAEKFESLMN IHGFDLGSRY MDLKPLGCGG NGLVFSAVDN DCDKRVAIKK IVLTDPQSVK 

        70         80         90        100        110        120 
HALREIKIIR RLDHDNIVKV FEILGPSGSQ LTDDVGSLTE LNSVYIVQEY METDLANVLE 

       130        140        150        160        170        180 
QGPLLEEHAR LFMYQLLRGL KYIHSANVLH RDLKPANLFI NTEDLVLKIG DFGLARIMDP 

       190        200        210        220        230        240 
HYSHKGHLSE GLVTKWYRSP RLLLSPNNYT KAIDMWAAGC IFAEMLTGKT LFAGAHELEQ 

       250        260        270        280        290        300 
MQLILDSIPV VHEEDRQELL SVIPVYIRND MTEPHRPLTQ LLPGISREAL DFLEQILTFS 

       310        320        330        340        350        360 
PMDRLTAEEA LSHPYMSIYS FPTDEPISSH PFHIEDEVDD ILLMDETHSH IYNWERYHDC 

       370        380        390        400        410        420 
QFSEHDWPIH NNFDIDEVQL DPRALSDVTD EEEVQVDPRK YLDGDREKYL EDPAFDTSYS 

       430        440        450        460        470        480 
AEPCWQYPDH HENKYCDLEC SHTCNYKTRS SPYLDNLVWR ESEVNHYYEP KLIIDLSNWK 

       490        500        510        520        530        540 
EQSKEKSDKR GKSKCERNGL VKAQIALEEA SQQLAERERG QGFDFDSFIA GTIQLSAQHQ 

       550        560        570        580        590        600 
SADVVDKLND LNSSVSQLEL KSLISKSVSR EKQEKGRANL AQLGALYQSS WDSQFVSGGE 

       610        620        630        640        650        660 
ECFLISQFCC EVRKDEHAEK ENTYTSYLDK FFSRKEDSEM LETEPVEEGK RGERGREAGL 

       670        680        690        700        710        720 
LSGGGEFLLS KQLESIGTPQ FHSPVGSPLK SIQATLTPSA MKSSPQIPHK TYSSILKHLN 

« Hide

References

« Hide 'large scale' references
[1]"Cloning and characterization of mouse extracellular-signal-regulated protein kinase 3 as a unique gene product of 100 kDa."
Turgeon B., Saba-El-Leil M.K., Meloche S.
Biochem. J. 346:169-175(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], DEVELOPMENTAL STAGE.
Tissue: Pituitary.
[2]"The protein kinase ERK3 is encoded by a single functional gene: genomic analysis of the ERK3 gene family."
Turgeon B., Lang B.F., Meloche S.
Genomics 80:673-680(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: 129/Sv.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6 and Czech II.
Tissue: Embryonic brain, Embryonic germ cell, Mammary tumor and Olfactory epithelium.
[4]"Novel CDC2-related protein kinases produced in murine hematopoietic stem cells."
Ershler M.A., Nagorskaya T.V., Visser J.W.M., Belyavsky A.V.
Gene 124:305-306(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 156-195.
Strain: CBA.
Tissue: Hematopoietic.
[5]"Scaffolding by ERK3 regulates MK5 in development."
Schumacher S., Laass K., Kant S., Shi Y., Visel A., Gruber A.D., Kotlyarov A., Gaestel M.
EMBO J. 23:4770-4779(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF MAPKAPK5, SUBCELLULAR LOCATION, INTERACTION WITH MAPKAPK5.
[6]"Activation of MK5/PRAK by the atypical MAP kinase ERK3 defines a novel signal transduction pathway."
Seternes O.M., Mikalsen T., Johansen B., Michaelsen E., Armstrong C.G., Morrice N.A., Turgeon B., Meloche S., Moens U., Keyse S.M.
EMBO J. 23:4780-4791(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF MAPKAPK5, SUBCELLULAR LOCATION, INTERACTION WITH MAPKAPK5, MUTAGENESIS OF ASP-171 AND SER-189.
[7]"Characterization of the atypical MAPK ERK4 and its activation of the MAPK-activated protein kinase MK5."
Kant S., Schumacher S., Singh M.K., Kispert A., Kotlyarov A., Gaestel M.
J. Biol. Chem. 281:35511-35519(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MAPK4.
[8]"Activation loop phosphorylation of the atypical MAP kinases ERK3 and ERK4 is required for binding, activation and cytoplasmic relocalization of MK5."
Deleris P., Rousseau J., Coulombe P., Rodier G., Tanguay P.L., Meloche S.
J. Cell. Physiol. 217:778-788(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MAPKAPK5, PHOSPHORYLATION AT SER-189, MUTAGENESIS OF SER-189.
[9]"Docking of PRAK/MK5 to the atypical MAPKs ERK3 and ERK4 defines a novel MAPK interaction motif."
Aberg E., Torgersen K.M., Johansen B., Keyse S.M., Perander M., Seternes O.M.
J. Biol. Chem. 284:19392-19401(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MAPKAPK5, DOMAIN FRIEDE MOTIF, MUTAGENESIS OF ILE-334.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF132850 mRNA. Translation: AAF61348.1.
AY134883 expand/collapse EMBL AC list , 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.
CCDSCCDS23342.1.
PIRPN0481.
RefSeqNP_056621.4. NM_015806.5.
NP_081694.1. NM_027418.2.
UniGeneMm.480076.

3D structure databases

ProteinModelPortalQ61532.
SMRQ61532. Positions 13-341.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid206104. 3 interactions.

PTM databases

PhosphoSiteQ61532.

Proteomic databases

PaxDbQ61532.
PRIDEQ61532.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000049355; ENSMUSP00000040315; ENSMUSG00000042688.
ENSMUST00000168937; ENSMUSP00000129024; ENSMUSG00000042688.
GeneID50772.
KEGGmmu:50772.
UCSCuc009qsd.1. mouse.

Organism-specific databases

CTD5597.
MGIMGI:1354946. Mapk6.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00550000074298.
HOVERGENHBG104376.
InParanoidQ61532.
KOK06855.
OMAEHDWPIH.
OrthoDBEOG780RKS.
PhylomeDBQ61532.
TreeFamTF105098.

Enzyme and pathway databases

BRENDA2.7.11.24. 3474.

Gene expression databases

ArrayExpressQ61532.
BgeeQ61532.
CleanExMM_MAPK6.
GenevestigatorQ61532.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR008350. MAPK_ERK3/4.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
PRINTSPR01771. ERK3ERK4MAPK.
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSMAPK6. mouse.
NextBio307695.
PROQ61532.
SOURCESearch...

Entry information

Entry nameMK06_MOUSE
AccessionPrimary (citable) accession number: Q61532
Secondary accession number(s): Q497T9 expand/collapse secondary AC list , Q6YKB0, Q7TT30, Q80XH5, Q922U4, Q9JLU6
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: September 13, 2004
Last modified: July 9, 2014
This is version 125 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

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