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Q6P5G0 (MK04_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 89. 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 4

Short name=MAP kinase 4
Short name=MAPK 4
EC=2.7.11.24
Alternative name(s):
Extracellular signal-regulated kinase 4
Short name=ERK-4
Gene names
Name:Mapk4
Synonyms:Erk4, Prkm4
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length583 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, ERK4/MAPK4 is phosphorylated at Ser-186 and then mediates phosphorylation and activation of MAPKAPK5, which in turn phosphorylates ERK4/MAPK4. May promote entry in the cell cycle. Ref.2

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium By similarity.

Enzyme regulation

Activated by phosphorylation at Ser-186.

Subunit structure

Homodimer. Heterodimer with ERK3/MAPK6. Interacts with (via FRIEDE motif) MAPKAPK5. Ref.2 Ref.3 Ref.4 Ref.5

Subcellular location

Cytoplasm. Nucleus. Note: Translocates to the cytoplasm following interaction with MAPKAPK5. Ref.2

Domain

The FRIEDE motif is required for docking MAPKAPK5. Ref.5

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.5

Post-translational modification

Phosphorylated at Ser-186 by PAK1, PAK2 and PAK3 resulting in catalytic activation. Phosphorylated by MAPKAPK5 at other sites. Ref.3 Ref.4

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 – 583583Mitogen-activated protein kinase 4
PRO_0000186255

Regions

Domain20 – 312293Protein kinase
Nucleotide binding26 – 349ATP By similarity
Motif186 – 1883SEG motif
Motif328 – 3336FRIEDE motif

Sites

Active site1491Proton acceptor By similarity
Binding site491ATP By similarity

Amino acid modifications

Modified residue1861Phosphoserine; by PAK1, PAK2 and PAK3 Ref.3 Ref.4

Experimental info

Mutagenesis49 – 502KK → AA: ATP-binding site mutant; unable to activate MAPKAPK5. Ref.2
Mutagenesis1681D → A: Kinase defective mutant, abolishes activity. Ref.2 Ref.3
Mutagenesis1861S → A or D: Unable to activate MAPKAPK5 promote MAPKAPK5 localization to the cytoplasm. Ref.2 Ref.3 Ref.4
Mutagenesis3281F → A or Y: Impairs binding to MAPKAPK5. Ref.2 Ref.5
Mutagenesis3301I → K: Abolishes binding to MAPKAPK5. Ref.2 Ref.5

Sequences

Sequence LengthMass (Da)Tools
Q6P5G0 [UniParc].

Last modified July 5, 2004. Version 1.
Checksum: 7CE7B2D5359CB52A

FASTA58365,574
        10         20         30         40         50         60 
MAEKGDCIAS VYGYDLGGRF IDFQPLGFGV NGLVLSATDS RACRKVAVKK IVLSDARSMK 

        70         80         90        100        110        120 
HALREIKIIR RLDHDNIVKV YEVLGPKGSD LQGELFKFSV AYIVQEYMET DLACLLEQGT 

       130        140        150        160        170        180 
LTEDHAKLFM YQLLRGLKYI HSANVLHRDL KPANIFISTE DLVLKIGDFG LARIVDQHYS 

       190        200        210        220        230        240 
HKGYLSEGLV TKWYRSPRLL LSPNNYTKAI DMWAAGCILA EMLTGKMLFA GAHELEQMQL 

       250        260        270        280        290        300 
ILDTIPVVRE EDKEELLRVM PSFVSSTWEV KRPLRKLLPD VNSEAIDFLE KILTFNPMDR 

       310        320        330        340        350        360 
LTAEMGLQHP YMSPYSCPED EPTSQHPFRI EDEIDDIVLM AASQSQLSNW DRYPVSLSSD 

       370        380        390        400        410        420 
LEWRPDRCQD ASEVQRDPRA GSTPLAEDVQ VDPRKDSQSS SERFLEQSHS SMERAFEADY 

       430        440        450        460        470        480 
GRSCDYKVGS PSYLDKLLWR DNKPHHYSEP KLILDLSHWK QAASAPPRAA VAADPVSRED 

       490        500        510        520        530        540 
EPASLFLEIA QWVKSTQSGS ERASPPPDAP EPRLSASPPG HPTPIDGGAS PQFDLDVFIS 

       550        560        570        580 
RALKLCTKPE DLPENKLGDL NGACISEHPG DLVQTEAFSK ERW 

« Hide

References

« Hide 'large scale' references
[1]"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.
Tissue: Brain.
[2]"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: FUNCTION IN PHOSPHORYLATION OF MAPKAPK5, SUBCELLULAR LOCATION, INTERACTION WITH MAPKAPK5 AND MAPK6, SUBUNIT, MUTAGENESIS OF 49-LYS-LYS-50.
[3]"The Ser(186) phospho-acceptor site within ERK4 is essential for its ability to interact with and activate PRAK/MK5."
Perander M., Aberg E., Johansen B., Dreyer B., Guldvik I.J., Outzen H., Keyse S.M., Seternes O.M.
Biochem. J. 411:613-622(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MAPKAPK5, PHOSPHORYLATION AT SER-186, MUTAGENESIS OF ASP-168 AND SER-186.
[4]"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-186, MUTAGENESIS OF SER-186.
[5]"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 PHE-328 AND ILE-330.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
BC058942 mRNA. Translation: AAH58942.1.
BC062911 mRNA. Translation: AAH62911.1.
CCDSCCDS37856.1.
RefSeqNP_766220.2. NM_172632.2.
XP_006525963.1. XM_006525900.1.
XP_006525964.1. XM_006525901.1.
UniGeneMm.254517.

3D structure databases

ProteinModelPortalQ6P5G0.
SMRQ6P5G0. Positions 13-421.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING10090.ENSMUSP00000089462.

PTM databases

PhosphoSiteQ6P5G0.

Proteomic databases

PaxDbQ6P5G0.
PRIDEQ6P5G0.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000091851; ENSMUSP00000089462; ENSMUSG00000024558.
GeneID225724.
KEGGmmu:225724.
UCSCuc008fpa.2. mouse.

Organism-specific databases

CTD5596.
MGIMGI:2444559. Mapk4.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00550000074298.
HOGENOMHOG000233020.
HOVERGENHBG104376.
InParanoidQ6P5G0.
KOK06855.
OMARCQDASE.
OrthoDBEOG780RKS.
PhylomeDBQ6P5G0.
TreeFamTF105098.

Gene expression databases

BgeeQ6P5G0.
CleanExMM_MAPK4.
GenevestigatorQ6P5G0.

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

ChiTaRSMAPK4. mouse.
NextBio377772.
PROQ6P5G0.
SOURCESearch...

Entry information

Entry nameMK04_MOUSE
AccessionPrimary (citable) accession number: Q6P5G0
Entry history
Integrated into UniProtKB/Swiss-Prot: September 13, 2004
Last sequence update: July 5, 2004
Last modified: July 9, 2014
This is version 89 of the entry and version 1 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