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Protein

Mitogen-activated protein kinase 4

Gene

MAPK4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Activity 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
  • cellular response to organic substance Source: GO_Central
  • protein phosphorylation Source: ProtInc
  • regulation of gene expression Source: GO_Central

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processCell cycle
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000141639.11
HGNCiHGNC:6878 MAPK4
MIMi176949 gene
neXtProtiNX_P31152

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi5596
OpenTargetsiENSG00000141639
PharmGKBiPA30623

Chemistry databases

ChEMBLiCHEMBL5759

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
ProteomicsDBi54762

PTM databases

iPTMnetiP31152
PhosphoSitePlusiP31152

Expressioni

Tissue specificityi

High expression in heart and brain.

Gene expression databases

BgeeiENSG00000141639 Expressed in 87 organ(s), highest expression level in caudate nucleus
CleanExiHS_MAPK4
ExpressionAtlasiP31152 baseline and differential
GenevisibleiP31152 HS

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, 24 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

Phylogenomic databases

eggNOGiKOG0660 Eukaryota
ENOG410XNY0 LUCA
GeneTreeiENSGT00910000144035
HOGENOMiHOG000233020
HOVERGENiHBG104376
InParanoidiP31152
KOiK06855
OMAiRCQDASE
OrthoDBiEOG091G03RQ
PhylomeDBiP31152
TreeFamiTF105098

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR008350 MAPK_ERK3/4
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
PRINTSiPR01771 ERK3ERK4MAPK
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
K7ELV1K7ELV1_HUMAN
Mitogen-activated protein kinase 4
MAPK4
233Annotation score:
K7EN18K7EN18_HUMAN
Mitogen-activated protein kinase 4
MAPK4
281Annotation score:
B4DEW2B4DEW2_HUMAN
Mitogen-activated protein kinase 4
MAPK4
376Annotation score:

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 → M2 PublicationsCorresponds to variant dbSNP:rs3752087Ensembl.1
Natural variantiVAR_042255371R → P1 PublicationCorresponds to variant dbSNP:rs3752089Ensembl.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

Similar proteinsi

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, 24 interactors
IntActiP31152, 11 interactors
STRINGi9606.ENSP00000383234

Chemistry databases

BindingDBiP31152
ChEMBLiCHEMBL5759

PTM databases

iPTMnetiP31152
PhosphoSitePlusiP31152

Polymorphism and mutation databases

BioMutaiMAPK4
DMDMi215274102

Proteomic databases

EPDiP31152
PaxDbiP31152
PeptideAtlasiP31152
PRIDEiP31152
ProteomicsDBi54762

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
EuPathDBiHostDB:ENSG00000141639.11
GeneCardsiMAPK4
H-InvDBiHIX0027373
HGNCiHGNC:6878 MAPK4
MIMi176949 gene
neXtProtiNX_P31152
OpenTargetsiENSG00000141639
PharmGKBiPA30623
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0660 Eukaryota
ENOG410XNY0 LUCA
GeneTreeiENSGT00910000144035
HOGENOMiHOG000233020
HOVERGENiHBG104376
InParanoidiP31152
KOiK06855
OMAiRCQDASE
OrthoDBiEOG091G03RQ
PhylomeDBiP31152
TreeFamiTF105098

Enzyme and pathway databases

BRENDAi2.7.11.24 2681
ReactomeiR-HSA-5687128 MAPK6/MAPK4 signaling
SignaLinkiP31152
SIGNORiP31152

Miscellaneous databases

GeneWikiiMAPK4
GenomeRNAii5596
PROiPR:P31152
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000141639 Expressed in 87 organ(s), highest expression level in caudate nucleus
CleanExiHS_MAPK4
ExpressionAtlasiP31152 baseline and differential
GenevisibleiP31152 HS

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR008350 MAPK_ERK3/4
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
PRINTSiPR01771 ERK3ERK4MAPK
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiMK04_HUMAN
AccessioniPrimary (citable) accession number: P31152
Secondary accession number(s): A1A4C4, Q0VG04
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: November 25, 2008
Last modified: September 12, 2018
This is version 170 of the entry and version 2 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 18
    Human chromosome 18: entries, gene names and cross-references to MIM
  3. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
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Main funding by: National Institutes of Health

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