Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Mitogen-activated protein kinase 4

Gene

MAPK4

Organism
Homo sapiens (Human)
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 (By similarity).By similarity

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

GO - Biological processi

  • cell cycle Source: UniProtKB-KW
  • protein phosphorylation Source: ProtInc
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

BioCyciZFISH:HS06857-MONOMER.
BRENDAi2.7.11.24. 2681.
ReactomeiR-HSA-5687128. MAPK6/MAPK4 signaling.
SignaLinkiP31152.
SIGNORiP31152.

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
MAP kinase isoform p63
Short name:
p63-MAPK
Gene namesi
Name:MAPK4
Synonyms:ERK4, PRKM4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 18

Organism-specific databases

HGNCiHGNC:6878. MAPK4.

Subcellular locationi

  • Cytoplasm By similarity
  • Nucleus By similarity

  • Note: Translocates to the cytoplasm following interaction with MAPKAPK5.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi5596.
OpenTargetsiENSG00000141639.
PharmGKBiPA30623.

Chemistry databases

ChEMBLiCHEMBL5759.
GuidetoPHARMACOLOGYi2091.

Polymorphism and mutation databases

BioMutaiMAPK4.
DMDMi215274102.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001862541 – 587Mitogen-activated protein kinase 4Add BLAST587

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei186Phosphoserine; by PAK1, PAK2 and PAK3Combined sources1 Publication1
Modified residuei434PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated at Ser-186 by PAK1, PAK2 and PAK3 resulting in catalytic activation. Phosphorylated by MAPKAPK5 at other sites.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP31152.
PaxDbiP31152.
PeptideAtlasiP31152.
PRIDEiP31152.

PTM databases

iPTMnetiP31152.
PhosphoSitePlusiP31152.

Expressioni

Tissue specificityi

High expression in heart and brain.

Gene expression databases

BgeeiENSG00000141639.
CleanExiHS_MAPK4.
ExpressionAtlasiP31152. baseline and differential.
GenevisibleiP31152. HS.

Organism-specific databases

HPAiCAB025868.
HPA007461.

Interactioni

Subunit structurei

Homodimer. Heterodimer with ERK3/MAPK6. Interacts with (via FRIEDE motif) MAPKAPK5 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
HSP90AB1P082382EBI-3906061,EBI-352572

GO - Molecular functioni

Protein-protein interaction databases

BioGridi111582. 13 interactors.
IntActiP31152. 11 interactors.
STRINGi9606.ENSP00000383234.

Chemistry databases

BindingDBiP31152.

Structurei

3D structure databases

ProteinModelPortaliP31152.
SMRiP31152.
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.By similarity
In contrast to classical MAPKs, the TXY motif within the activation loop is replaced by the SEG motif, whose phosphorylation activates the MAP kinases.

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0660. Eukaryota.
ENOG410XNY0. LUCA.
GeneTreeiENSGT00550000074298.
HOGENOMiHOG000233020.
HOVERGENiHBG104376.
InParanoidiP31152.
KOiK06855.
OMAiRCQDASE.
OrthoDBiEOG091G03RQ.
PhylomeDBiP31152.
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.

P31152-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAEKGDCIAS VYGYDLGGRF VDFQPLGFGV NGLVLSAVDS RACRKVAVKK
60 70 80 90 100
IALSDARSMK HALREIKIIR RLDHDNIVKV YEVLGPKGTD LQGELFKFSV
110 120 130 140 150
AYIVQEYMET DLARLLEQGT LAEEHAKLFM YQLLRGLKYI HSANVLHRDL
160 170 180 190 200
KPANIFISTE DLVLKIGDFG LARIVDQHYS HKGYLSEGLV TKWYRSPRLL
210 220 230 240 250
LSPNNYTKAI DMWAAGCILA EMLTGRMLFA GAHELEQMQL ILETIPVIRE
260 270 280 290 300
EDKDELLRVM PSFVSSTWEV KRPLRKLLPE VNSEAIDFLE KILTFNPMDR
310 320 330 340 350
LTAEMGLQHP YMSPYSCPED EPTSQHPFRI EDEIDDIVLM AANQSQLSNW
360 370 380 390 400
DTCSSRYPVS LSSDLEWRPD RCQDASEVQR DPRAGSAPLA EDVQVDPRKD
410 420 430 440 450
SHSSSERFLE QSHSSMERAF EADYGRSCDY KVGSPSYLDK LLWRDNKPHH
460 470 480 490 500
YSEPKLILDL SHWKQAAGAP PTATGLADTG AREDEPASLF LEIAQWVKST
510 520 530 540 550
QGGPEHASPP ADDPERRLSA SPPGRPAPVD GGASPQFDLD VFISRALKLC
560 570 580
TKPEDLPDNK LGDLNGACIP EHPGDLVQTE AFSKERW
Length:587
Mass (Da):65,922
Last modified:November 25, 2008 - v2
Checksum:i71DB32D1E63EF8EE
GO

Sequence cautioni

The sequence CAA42411 differs from that shown. Reason: Frameshift at several positions.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti220A → S in AAH50299 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04225438V → M.2 PublicationsCorresponds to variant rs3752087dbSNPEnsembl.1
Natural variantiVAR_042255371R → P.1 PublicationCorresponds to variant rs3752089dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X59727 mRNA. Translation: CAA42411.1. Frameshift.
AK295058 mRNA. Translation: BAG58107.1.
AC012433 Genomic DNA. No translation available.
AC090395 Genomic DNA. No translation available.
CH471096 Genomic DNA. Translation: EAW62976.1.
CH471096 Genomic DNA. Translation: EAW62977.1.
BC050299 mRNA. Translation: AAH50299.1.
BC117216 mRNA. Translation: AAI17217.1.
CCDSiCCDS42437.1.
PIRiS23429.
RefSeqiNP_001278968.1. NM_001292039.1.
NP_001278969.1. NM_001292040.1.
NP_002738.2. NM_002747.3.
XP_005258356.1. XM_005258299.3.
XP_011524376.1. XM_011526074.2.
XP_011524377.1. XM_011526075.2.
XP_011524378.1. XM_011526076.2.
XP_016881328.1. XM_017025839.1.
UniGeneiHs.433728.

Genome annotation databases

EnsembliENST00000400384; ENSP00000383234; ENSG00000141639.
GeneIDi5596.
KEGGihsa:5596.
UCSCiuc002lev.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X59727 mRNA. Translation: CAA42411.1. Frameshift.
AK295058 mRNA. Translation: BAG58107.1.
AC012433 Genomic DNA. No translation available.
AC090395 Genomic DNA. No translation available.
CH471096 Genomic DNA. Translation: EAW62976.1.
CH471096 Genomic DNA. Translation: EAW62977.1.
BC050299 mRNA. Translation: AAH50299.1.
BC117216 mRNA. Translation: AAI17217.1.
CCDSiCCDS42437.1.
PIRiS23429.
RefSeqiNP_001278968.1. NM_001292039.1.
NP_001278969.1. NM_001292040.1.
NP_002738.2. NM_002747.3.
XP_005258356.1. XM_005258299.3.
XP_011524376.1. XM_011526074.2.
XP_011524377.1. XM_011526075.2.
XP_011524378.1. XM_011526076.2.
XP_016881328.1. XM_017025839.1.
UniGeneiHs.433728.

3D structure databases

ProteinModelPortaliP31152.
SMRiP31152.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111582. 13 interactors.
IntActiP31152. 11 interactors.
STRINGi9606.ENSP00000383234.

Chemistry databases

BindingDBiP31152.
ChEMBLiCHEMBL5759.
GuidetoPHARMACOLOGYi2091.

PTM databases

iPTMnetiP31152.
PhosphoSitePlusiP31152.

Polymorphism and mutation databases

BioMutaiMAPK4.
DMDMi215274102.

Proteomic databases

EPDiP31152.
PaxDbiP31152.
PeptideAtlasiP31152.
PRIDEiP31152.

Protocols and materials databases

DNASUi5596.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000400384; ENSP00000383234; ENSG00000141639.
GeneIDi5596.
KEGGihsa:5596.
UCSCiuc002lev.4. human.

Organism-specific databases

CTDi5596.
DisGeNETi5596.
GeneCardsiMAPK4.
H-InvDBHIX0027373.
HGNCiHGNC:6878. MAPK4.
HPAiCAB025868.
HPA007461.
MIMi176949. gene.
neXtProtiNX_P31152.
OpenTargetsiENSG00000141639.
PharmGKBiPA30623.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0660. Eukaryota.
ENOG410XNY0. LUCA.
GeneTreeiENSGT00550000074298.
HOGENOMiHOG000233020.
HOVERGENiHBG104376.
InParanoidiP31152.
KOiK06855.
OMAiRCQDASE.
OrthoDBiEOG091G03RQ.
PhylomeDBiP31152.
TreeFamiTF105098.

Enzyme and pathway databases

BioCyciZFISH:HS06857-MONOMER.
BRENDAi2.7.11.24. 2681.
ReactomeiR-HSA-5687128. MAPK6/MAPK4 signaling.
SignaLinkiP31152.
SIGNORiP31152.

Miscellaneous databases

GeneWikiiMAPK4.
GenomeRNAii5596.
PROiP31152.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000141639.
CleanExiHS_MAPK4.
ExpressionAtlasiP31152. baseline and differential.
GenevisibleiP31152. HS.

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_HUMAN
AccessioniPrimary (citable) accession number: P31152
Secondary accession number(s): A1A4C4, Q0VG04
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: November 25, 2008
Last modified: November 2, 2016
This is version 159 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 18
    Human chromosome 18: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  6. 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.