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Q6P5G0

- MK04_MOUSE

UniProt

Q6P5G0 - MK04_MOUSE

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Protein

Mitogen-activated protein kinase 4

Gene

Mapk4

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

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, 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.1 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Magnesium.By similarity

Enzyme regulationi

Activated by phosphorylation at Ser-186.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei49 – 491ATPPROSITE-ProRule annotation
Active sitei149 – 1491Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi26 – 349ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. MAP kinase activity Source: UniProtKB-EC
  3. protein heterodimerization activity Source: UniProtKB
  4. protein homodimerization activity Source: UniProtKB
  5. protein kinase binding Source: UniProtKB

GO - Biological processi

  1. cell cycle Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Cell cycle

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Mitogen-activated protein kinase 4 (EC:2.7.11.24)
Short name:
MAP kinase 4
Short name:
MAPK 4
Alternative name(s):
Extracellular signal-regulated kinase 4
Short name:
ERK-4
Gene namesi
Name:Mapk4
Synonyms:Erk4, Prkm4
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 18

Organism-specific databases

MGIiMGI:2444559. Mapk4.

Subcellular locationi

Cytoplasm 1 Publication. Nucleus 1 Publication
Note: Translocates to the cytoplasm following interaction with MAPKAPK5.

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi49 – 502KK → AA: ATP-binding site mutant; unable to activate MAPKAPK5. 1 Publication
Mutagenesisi168 – 1681D → A: Kinase defective mutant, abolishes activity. 1 Publication
Mutagenesisi186 – 1861S → A or D: Unable to activate MAPKAPK5 promote MAPKAPK5 localization to the cytoplasm. 2 Publications
Mutagenesisi328 – 3281F → A or Y: Impairs binding to MAPKAPK5. 1 Publication
Mutagenesisi330 – 3301I → K: Abolishes binding to MAPKAPK5. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 583583Mitogen-activated protein kinase 4PRO_0000186255Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei186 – 1861Phosphoserine; by PAK1, PAK2 and PAK32 Publications

Post-translational modificationi

Phosphorylated at Ser-186 by PAK1, PAK2 and PAK3 resulting in catalytic activation. Phosphorylated by MAPKAPK5 at other sites.2 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ6P5G0.
PaxDbiQ6P5G0.
PRIDEiQ6P5G0.

PTM databases

PhosphoSiteiQ6P5G0.

Expressioni

Gene expression databases

BgeeiQ6P5G0.
CleanExiMM_MAPK4.
ExpressionAtlasiQ6P5G0. baseline and differential.
GenevestigatoriQ6P5G0.

Interactioni

Subunit structurei

Homodimer. Heterodimer with ERK3/MAPK6. Interacts with (via FRIEDE motif) MAPKAPK5.4 Publications

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000089462.

Structurei

3D structure databases

ProteinModelPortaliQ6P5G0.
SMRiQ6P5G0. Positions 13-421.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini20 – 312293Protein kinasePROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi186 – 1883SEG motif
Motifi328 – 3336FRIEDE motif

Domaini

The FRIEDE motif is required for docking MAPKAPK5.1 Publication
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

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00550000074298.
HOGENOMiHOG000233020.
HOVERGENiHBG104376.
InParanoidiQ6P5G0.
KOiK06855.
OMAiRCQDASE.
OrthoDBiEOG780RKS.
PhylomeDBiQ6P5G0.
TreeFamiTF105098.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR008350. MAPK_ERK3/4.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
PRINTSiPR01771. ERK3ERK4MAPK.
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q6P5G0-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MAEKGDCIAS VYGYDLGGRF IDFQPLGFGV NGLVLSATDS RACRKVAVKK
60 70 80 90 100
IVLSDARSMK HALREIKIIR RLDHDNIVKV YEVLGPKGSD LQGELFKFSV
110 120 130 140 150
AYIVQEYMET DLACLLEQGT LTEDHAKLFM YQLLRGLKYI HSANVLHRDL
160 170 180 190 200
KPANIFISTE DLVLKIGDFG LARIVDQHYS HKGYLSEGLV TKWYRSPRLL
210 220 230 240 250
LSPNNYTKAI DMWAAGCILA EMLTGKMLFA GAHELEQMQL ILDTIPVVRE
260 270 280 290 300
EDKEELLRVM PSFVSSTWEV KRPLRKLLPD VNSEAIDFLE KILTFNPMDR
310 320 330 340 350
LTAEMGLQHP YMSPYSCPED EPTSQHPFRI EDEIDDIVLM AASQSQLSNW
360 370 380 390 400
DRYPVSLSSD LEWRPDRCQD ASEVQRDPRA GSTPLAEDVQ VDPRKDSQSS
410 420 430 440 450
SERFLEQSHS SMERAFEADY GRSCDYKVGS PSYLDKLLWR DNKPHHYSEP
460 470 480 490 500
KLILDLSHWK QAASAPPRAA VAADPVSRED EPASLFLEIA QWVKSTQSGS
510 520 530 540 550
ERASPPPDAP EPRLSASPPG HPTPIDGGAS PQFDLDVFIS RALKLCTKPE
560 570 580
DLPENKLGDL NGACISEHPG DLVQTEAFSK ERW
Length:583
Mass (Da):65,574
Last modified:July 5, 2004 - v1
Checksum:i7CE7B2D5359CB52A
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
BC058942 mRNA. Translation: AAH58942.1.
BC062911 mRNA. Translation: AAH62911.1.
CCDSiCCDS37856.1.
RefSeqiNP_766220.2. NM_172632.2.
XP_006525963.1. XM_006525900.1.
XP_006525964.1. XM_006525901.1.
UniGeneiMm.254517.

Genome annotation databases

EnsembliENSMUST00000091851; ENSMUSP00000089462; ENSMUSG00000024558.
GeneIDi225724.
KEGGimmu:225724.
UCSCiuc008fpa.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
BC058942 mRNA. Translation: AAH58942.1 .
BC062911 mRNA. Translation: AAH62911.1 .
CCDSi CCDS37856.1.
RefSeqi NP_766220.2. NM_172632.2.
XP_006525963.1. XM_006525900.1.
XP_006525964.1. XM_006525901.1.
UniGenei Mm.254517.

3D structure databases

ProteinModelPortali Q6P5G0.
SMRi Q6P5G0. Positions 13-421.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 10090.ENSMUSP00000089462.

PTM databases

PhosphoSitei Q6P5G0.

Proteomic databases

MaxQBi Q6P5G0.
PaxDbi Q6P5G0.
PRIDEi Q6P5G0.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000091851 ; ENSMUSP00000089462 ; ENSMUSG00000024558 .
GeneIDi 225724.
KEGGi mmu:225724.
UCSCi uc008fpa.2. mouse.

Organism-specific databases

CTDi 5596.
MGIi MGI:2444559. Mapk4.

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00550000074298.
HOGENOMi HOG000233020.
HOVERGENi HBG104376.
InParanoidi Q6P5G0.
KOi K06855.
OMAi RCQDASE.
OrthoDBi EOG780RKS.
PhylomeDBi Q6P5G0.
TreeFami TF105098.

Miscellaneous databases

ChiTaRSi MAPK4. mouse.
NextBioi 377772.
PROi Q6P5G0.
SOURCEi Search...

Gene expression databases

Bgeei Q6P5G0.
CleanExi MM_MAPK4.
ExpressionAtlasi Q6P5G0. baseline and differential.
Genevestigatori Q6P5G0.

Family and domain databases

InterProi IPR011009. Kinase-like_dom.
IPR008350. MAPK_ERK3/4.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view ]
Pfami PF00069. Pkinase. 1 hit.
[Graphical view ]
PRINTSi PR01771. ERK3ERK4MAPK.
SMARTi SM00220. S_TKc. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 1 hit.
PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.

Entry informationi

Entry nameiMK04_MOUSE
AccessioniPrimary (citable) accession number: Q6P5G0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 13, 2004
Last sequence update: July 5, 2004
Last modified: October 29, 2014
This is version 91 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3