Q6P5G0 (MK04_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	583 AA.
Sequence status	Complete.
Protein existence	Evidence 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.

Ontologies

Keywords
Biological process	Cell cycle
Cellular component	Cytoplasm Nucleus
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	MAPK cascade Inferred from electronic annotation. Source: GOC cell cycle Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from direct assay Ref.2. Source: UniProtKB nucleus Inferred from direct assay Ref.2. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW MAP kinase activity Inferred from electronic annotation. Source: EC protein homodimerization activity Inferred from direct assay Ref.2. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 583	583	Mitogen-activated protein kinase 4		PRO_0000186255
Regions
	Domain	20 – 312	293	Protein kinase
	Nucleotide binding	26 – 34	9	ATP By similarity
	Motif	186 – 188	3	SEG motif
	Motif	328 – 333	6	FRIEDE motif
Sites
	Active site	149	1	Proton acceptor By similarity
	Binding site	49	1	ATP By similarity
Amino acid modifications
	Modified residue	186	1	Phosphoserine; by PAK1, PAK2 and PAK3 Ref.3 Ref.4
Experimental info
	Mutagenesis	49 – 50	2	KK → AA: ATP-binding site mutant; unable to activate MAPKAPK5. Ref.2
	Mutagenesis	168	1	D → A: Kinase defective mutant, abolishes activity. Ref.2 Ref.3
	Mutagenesis	186	1	S → A or D: Unable to activate MAPKAPK5 promote MAPKAPK5 localization to the cytoplasm. Ref.2 Ref.3 Ref.4
	Mutagenesis	328	1	F → A or Y: Impairs binding to MAPKAPK5. Ref.2 Ref.5
	Mutagenesis	330	1	I → K: Abolishes binding to MAPKAPK5. Ref.2 Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Q6P5G0 [UniParc]. Last modified July 5, 2004. Version 1. Checksum: 7CE7B2D5359CB52A	FASTA	583	65,574
	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

References

	« Hide 'large scale' referencesShow '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.
IPI	IPI00453690.
RefSeq	NP_766220.2. NM_172632.2.
UniGene	Mm.254517.
3D structure databases
ProteinModelPortal	Q6P5G0.
SMR	Q6P5G0. Positions 13-421.
ModBase	Search...
PTM databases
PhosphoSite	Q6P5G0.
Proteomic databases
PaxDb	Q6P5G0.
PRIDE	Q6P5G0.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000091851; ENSMUSP00000089462; ENSMUSG00000024558.
GeneID	225724.
KEGG	mmu:225724.
UCSC	uc008fpa.1. mouse.
Organism-specific databases
CTD	5596.
MGI	MGI:2444559. Mapk4.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00550000074298.
HOGENOM	HOG000233020.
HOVERGEN	HBG104376.
InParanoid	Q6P5G0.
KO	K06855.
OMA	RCQDASE.
OrthoDB	EOG4PG60R.
Gene expression databases
ArrayExpress	Q6P5G0.
Bgee	Q6P5G0.
CleanEx	MM_MAPK4.
Genevestigator	Q6P5G0.
GermOnline	ENSMUSG00000024558. Mus musculus.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR008350. MAPK_ERK3/4. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR002290. Ser/Thr_dual-sp_kinase_dom. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
PRINTS	PR01771. ERK3ERK4MAPK.
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	MAPK4. mouse.
NextBio	377772.
SOURCE	Search...

Entry information

Entry name

MK04_MOUSE

Accession

Primary (citable) accession number: Q6P5G0

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 13, 2004
Last sequence update:	July 5, 2004
Last modified:	May 1, 2013
This is version 79 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program