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Protein

Mitogen-activated protein kinase 4

Gene

Mapk4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: 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

Mg2+By similarity

Enzyme regulationi

Activated by phosphorylation at Ser-186.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei49ATPPROSITE-ProRule annotation1
Active sitei149Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi26 – 34ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • MAP kinase activity Source: UniProtKB-EC
  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • protein kinase binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Cell cycle

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-5687128. MAPK6/MAPK4 signaling.

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
Proteomesi
  • UP000000589 Componenti: Chromosome 18

Organism-specific databases

MGIiMGI:2444559. Mapk4.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi49 – 50KK → AA: ATP-binding site mutant; unable to activate MAPKAPK5. 1 Publication2
Mutagenesisi168D → A: Kinase defective mutant, abolishes activity. 1 Publication1
Mutagenesisi186S → A or D: Unable to activate MAPKAPK5 promote MAPKAPK5 localization to the cytoplasm. 2 Publications1
Mutagenesisi328F → A or Y: Impairs binding to MAPKAPK5. 1 Publication1
Mutagenesisi330I → K: Abolishes binding to MAPKAPK5. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001862551 – 583Mitogen-activated protein kinase 4Add BLAST583

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei186Phosphoserine; by PAK1, PAK2 and PAK3Combined sources2 Publications1
Modified residuei430PhosphoserineCombined sources1

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

iPTMnetiQ6P5G0.
PhosphoSitePlusiQ6P5G0.

Expressioni

Gene expression databases

BgeeiENSMUSG00000024558.
CleanExiMM_MAPK4.
ExpressionAtlasiQ6P5G0. baseline and differential.
GenevisibleiQ6P5G0. MM.

Interactioni

Subunit structurei

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

GO - Molecular functioni

  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • protein kinase binding Source: UniProtKB

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000089462.

Structurei

3D structure databases

ProteinModelPortaliQ6P5G0.
SMRiQ6P5G0.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini20 – 312Protein kinasePROSITE-ProRule annotationAdd BLAST293

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi186 – 188SEG motif3
Motifi328 – 333FRIEDE motif6

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

eggNOGiKOG0660. Eukaryota.
ENOG410XNY0. LUCA.
GeneTreeiENSGT00550000074298.
HOGENOMiHOG000233020.
HOVERGENiHBG104376.
InParanoidiQ6P5G0.
KOiK06855.
OMAiRCQDASE.
OrthoDBiEOG091G03RQ.
PhylomeDBiQ6P5G0.
TreeFamiTF105098.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR008350. MAPK_ERK3/4.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
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:
EMBLi
GenBanki
DDBJi
Links Updated
BC058942 mRNA. Translation: AAH58942.1.
BC062911 mRNA. Translation: AAH62911.1.
CCDSiCCDS37856.1.
RefSeqiNP_766220.2. NM_172632.2.
XP_006525963.1. XM_006525900.3.
XP_006525964.1. XM_006525901.3.
UniGeneiMm.254517.

Genome annotation databases

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

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC058942 mRNA. Translation: AAH58942.1.
BC062911 mRNA. Translation: AAH62911.1.
CCDSiCCDS37856.1.
RefSeqiNP_766220.2. NM_172632.2.
XP_006525963.1. XM_006525900.3.
XP_006525964.1. XM_006525901.3.
UniGeneiMm.254517.

3D structure databases

ProteinModelPortaliQ6P5G0.
SMRiQ6P5G0.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000089462.

PTM databases

iPTMnetiQ6P5G0.
PhosphoSitePlusiQ6P5G0.

Proteomic databases

MaxQBiQ6P5G0.
PaxDbiQ6P5G0.
PRIDEiQ6P5G0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi5596.
MGIiMGI:2444559. Mapk4.

Phylogenomic databases

eggNOGiKOG0660. Eukaryota.
ENOG410XNY0. LUCA.
GeneTreeiENSGT00550000074298.
HOGENOMiHOG000233020.
HOVERGENiHBG104376.
InParanoidiQ6P5G0.
KOiK06855.
OMAiRCQDASE.
OrthoDBiEOG091G03RQ.
PhylomeDBiQ6P5G0.
TreeFamiTF105098.

Enzyme and pathway databases

ReactomeiR-MMU-5687128. MAPK6/MAPK4 signaling.

Miscellaneous databases

ChiTaRSiMapk4. mouse.
PROiQ6P5G0.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000024558.
CleanExiMM_MAPK4.
ExpressionAtlasiQ6P5G0. baseline and differential.
GenevisibleiQ6P5G0. MM.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR008350. MAPK_ERK3/4.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
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]
ProtoNetiSearch...

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: November 2, 2016
This is version 104 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.