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

MAP kinase-activated protein kinase 3

Gene

MAPKAPK3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Stress-activated serine/threonine-protein kinase involved in cytokines production, endocytosis, cell migration, chromatin remodeling and transcriptional regulation. Following stress, it is phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to phosphorylation of substrates. Phosphorylates serine in the peptide sequence, Hyd-X-R-X2-S, where Hyd is a large hydrophobic residue. MAPKAPK2 and MAPKAPK3, share the same function and substrate specificity, but MAPKAPK3 kinase activity and level in protein expression are lower compared to MAPKAPK2. Phosphorylates HSP27/HSPB1, KRT18, KRT20, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to dissociate HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impair their chaperone activities and ability to protect against oxidative stress effectively. Involved in inflammatory response by regulating tumor necrosis factor (TNF) and IL6 production post-transcriptionally: acts by phosphorylating AU-rich elements (AREs)-binding proteins, such as TTP/ZFP36, leading to regulate the stability and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36, a major post-transcriptional regulator of TNF, promotes its binding to 14-3-3 proteins and reduces its ARE mRNA affinity leading to inhibition of dependent degradation of ARE-containing transcript. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3. Also acts as a modulator of Polycomb-mediated repression.6 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.1 Publication

Activity regulationi

Activated following phosphorylation by p38-alpha/MAPK14 following various stresses. Inhibited by ligand 5B (2'-[2-(1,3-benzodioxol-5-yl)pyrimidin-4-yl]-5',6'-dihydrospiro[piperidine-4,7'-pyrrolo[3,2-c]pyridin]- 4'(1'h)-one) and ligand P4O (2-[2-(2-fluorophenyl)pyridin-4-yl]-1,5,6,7-tetrahydro- 4h-pyrrolo[3,2-c]pyridin-4-one), 2 ATP-competitive inhibitors.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei73ATPPROSITE-ProRule annotation1
Active sitei166Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi50 – 58ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • calcium-dependent protein serine/threonine kinase activity Source: GO_Central
  • calmodulin-dependent protein kinase activity Source: GO_Central
  • MAP kinase kinase activity Source: ProtInc
  • mitogen-activated protein kinase binding Source: GO_Central
  • protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-HSA-171007 p38MAPK events
R-HSA-2559580 Oxidative Stress Induced Senescence
R-HSA-4420097 VEGFA-VEGFR2 Pathway
R-HSA-450302 activated TAK1 mediates p38 MAPK activation
SignaLinkiQ16644
SIGNORiQ16644

Names & Taxonomyi

Protein namesi
Recommended name:
MAP kinase-activated protein kinase 3 (EC:2.7.11.1)
Short name:
MAPK-activated protein kinase 3
Short name:
MAPKAP kinase 3
Short name:
MAPKAP-K3
Short name:
MAPKAPK-3
Short name:
MK-3
Alternative name(s):
Chromosome 3p kinase
Short name:
3pK
Gene namesi
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000114738.10
HGNCiHGNC:6888 MAPKAPK3
MIMi602130 gene
neXtProtiNX_Q16644

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

Involvement in diseasei

Macular dystrophy, patterned, 3 (MDPT3)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of retinal patterned dystrophy, characterized by retinal pigment epithelium and Bruch's membrane changes resembling a 'dry desert land'. It begins around the age of 30 and progresses to retinitis pigmentosa. MDPT3 inheritance is autosomal dominant.
See also OMIM:617111
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_077085173L → P in MDPT3; decreased localization to the nucleus. 1 PublicationCorresponds to variant dbSNP:rs886037913EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi73K → M: Higher affinity toward PCH2. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi7867
MalaCardsiMAPKAPK3
MIMi617111 phenotype
OpenTargetsiENSG00000114738
Orphaneti466718 Martinique crinkled retinal pigment epitheliopathy
PharmGKBiPA30632

Chemistry databases

ChEMBLiCHEMBL4670
GuidetoPHARMACOLOGYi2095

Polymorphism and mutation databases

BioMutaiMAPKAPK3
DMDMi74762148

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000862931 – 382MAP kinase-activated protein kinase 3Add BLAST382

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei201Phosphothreonine; by MAPK14By similarity1
Modified residuei251Phosphoserine; by MAPK14By similarity1
Modified residuei307Phosphoserine; by autocatalysisBy similarity1
Modified residuei313Phosphothreonine; by MAPK14By similarity1

Post-translational modificationi

Phosphorylated and activated by MAPK1/ERK2 and MAPK3/ERK1. Phosphorylated and activated by MAP kinase p38-alpha/MAPK14 at Thr-201, Ser-251 and Thr-313 (By similarity).By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ16644
MaxQBiQ16644
PaxDbiQ16644
PeptideAtlasiQ16644
PRIDEiQ16644
ProteomicsDBi60998

PTM databases

iPTMnetiQ16644
PhosphoSitePlusiQ16644

Expressioni

Tissue specificityi

Widely expressed, with a higher expression level observed in heart and skeletal muscle. No expression in brain. Expressed in the retinal pigment epithelium (PubMed:26744326).3 Publications

Gene expression databases

BgeeiENSG00000114738 Expressed in 232 organ(s), highest expression level in cardiac ventricle
CleanExiHS_MAPKAPK3
ExpressionAtlasiQ16644 baseline and differential
GenevisibleiQ16644 HS

Organism-specific databases

HPAiHPA058275

Interactioni

Subunit structurei

Heterodimer with p38-alpha/MAPK14. The heterodimer with p38-alpha/MAPK14 forms a stable complex: molecules are positioned 'face to face' so that the ATP-binding sites of both kinases are at the heterodimer interface (By similarity). Interacts with TCF3 and with polycomb proteins, such as PCH2 and BMI1/PCGF4.By similarity4 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi113617, 30 interactors
ELMiQ16644
IntActiQ16644, 27 interactors
MINTiQ16644
STRINGi9606.ENSP00000350639

Chemistry databases

BindingDBiQ16644

Structurei

Secondary structure

1382
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ16644
SMRiQ16644
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ16644

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini44 – 304Protein kinasePROSITE-ProRule annotationAdd BLAST261

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni307 – 343Autoinhibitory helixBy similarityAdd BLAST37
Regioni345 – 369p38 MAPK-binding siteBy similarityAdd BLAST25

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi335 – 344Nuclear export signal (NES)By similarity10
Motifi350 – 353Bipartite nuclear localization signal 1By similarity4
Motifi364 – 368Bipartite nuclear localization signal 2By similarity5

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0604 Eukaryota
ENOG410XP8F LUCA
GeneTreeiENSGT00930000150819
HOGENOMiHOG000233031
HOVERGENiHBG106948
InParanoidiQ16644
KOiK04444
OMAiRMGQYGF
OrthoDBiEOG091G14PL
PhylomeDBiQ16644
TreeFamiTF312891

Family and domain databases

Gene3Di4.10.1170.10, 1 hit
InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR027442 MAPKAPK_C
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
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

Q16644-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MDGETAEEQG GPVPPPVAPG GPGLGGAPGG RREPKKYAVT DDYQLSKQVL
60 70 80 90 100
GLGVNGKVLE CFHRRTGQKC ALKLLYDSPK ARQEVDHHWQ ASGGPHIVCI
110 120 130 140 150
LDVYENMHHG KRCLLIIMEC MEGGELFSRI QERGDQAFTE REAAEIMRDI
160 170 180 190 200
GTAIQFLHSH NIAHRDVKPE NLLYTSKEKD AVLKLTDFGF AKETTQNALQ
210 220 230 240 250
TPCYTPYYVA PEVLGPEKYD KSCDMWSLGV IMYILLCGFP PFYSNTGQAI
260 270 280 290 300
SPGMKRRIRL GQYGFPNPEW SEVSEDAKQL IRLLLKTDPT ERLTITQFMN
310 320 330 340 350
HPWINQSMVV PQTPLHTARV LQEDKDHWDE VKEEMTSALA TMRVDYDQVK
360 370 380
IKDLKTSNNR LLNKRRKKQA GSSSASQGCN NQ
Length:382
Mass (Da):42,987
Last modified:November 1, 1996 - v1
Checksum:i405F958B7F54E6F3
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H7C0G6H7C0G6_HUMAN
MAP kinase-activated protein kinase...
MAPKAPK3
97Annotation score:
C9J8E1C9J8E1_HUMAN
MAP kinase-activated protein kinase...
MAPKAPK3
332Annotation score:
C9JPW3C9JPW3_HUMAN
MAP kinase-activated protein kinase...
MAPKAPK3
119Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04075528P → S in a glioblastoma multiforme sample; somatic mutation. 1 Publication1
Natural variantiVAR_040756105E → A in an ovarian endometrioid sample; somatic mutation. 1 Publication1
Natural variantiVAR_077085173L → P in MDPT3; decreased localization to the nucleus. 1 PublicationCorresponds to variant dbSNP:rs886037913EnsemblClinVar.1
Natural variantiVAR_040757276D → Y1 PublicationCorresponds to variant dbSNP:rs56107897Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U43784 mRNA Translation: AAC50428.1
U09578 mRNA Translation: AAD09136.1
AB451303 mRNA Translation: BAG70117.1
CH471055 Genomic DNA Translation: EAW65131.1
BC001662 mRNA Translation: AAH01662.1
BC007591 mRNA Translation: AAH07591.1
BC010407 mRNA Translation: AAH10407.1
CCDSiCCDS2832.1
PIRiJC6094
RefSeqiNP_001230854.1, NM_001243925.1
NP_001230855.1, NM_001243926.1
NP_004626.1, NM_004635.4
UniGeneiHs.234521
Hs.735013

Genome annotation databases

EnsembliENST00000357955; ENSP00000350639; ENSG00000114738
ENST00000446044; ENSP00000396467; ENSG00000114738
ENST00000621469; ENSP00000478922; ENSG00000114738
GeneIDi7867
KEGGihsa:7867
UCSCiuc003day.3 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U43784 mRNA Translation: AAC50428.1
U09578 mRNA Translation: AAD09136.1
AB451303 mRNA Translation: BAG70117.1
CH471055 Genomic DNA Translation: EAW65131.1
BC001662 mRNA Translation: AAH01662.1
BC007591 mRNA Translation: AAH07591.1
BC010407 mRNA Translation: AAH10407.1
CCDSiCCDS2832.1
PIRiJC6094
RefSeqiNP_001230854.1, NM_001243925.1
NP_001230855.1, NM_001243926.1
NP_004626.1, NM_004635.4
UniGeneiHs.234521
Hs.735013

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3FHRX-ray1.90A33-349[»]
3FXWX-ray2.00A33-349[»]
3R1NX-ray2.09A33-349[»]
3SHEX-ray2.25A33-349[»]
ProteinModelPortaliQ16644
SMRiQ16644
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113617, 30 interactors
ELMiQ16644
IntActiQ16644, 27 interactors
MINTiQ16644
STRINGi9606.ENSP00000350639

Chemistry databases

BindingDBiQ16644
ChEMBLiCHEMBL4670
GuidetoPHARMACOLOGYi2095

PTM databases

iPTMnetiQ16644
PhosphoSitePlusiQ16644

Polymorphism and mutation databases

BioMutaiMAPKAPK3
DMDMi74762148

Proteomic databases

EPDiQ16644
MaxQBiQ16644
PaxDbiQ16644
PeptideAtlasiQ16644
PRIDEiQ16644
ProteomicsDBi60998

Protocols and materials databases

DNASUi7867
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000357955; ENSP00000350639; ENSG00000114738
ENST00000446044; ENSP00000396467; ENSG00000114738
ENST00000621469; ENSP00000478922; ENSG00000114738
GeneIDi7867
KEGGihsa:7867
UCSCiuc003day.3 human

Organism-specific databases

CTDi7867
DisGeNETi7867
EuPathDBiHostDB:ENSG00000114738.10
GeneCardsiMAPKAPK3
HGNCiHGNC:6888 MAPKAPK3
HPAiHPA058275
MalaCardsiMAPKAPK3
MIMi602130 gene
617111 phenotype
neXtProtiNX_Q16644
OpenTargetsiENSG00000114738
Orphaneti466718 Martinique crinkled retinal pigment epitheliopathy
PharmGKBiPA30632
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0604 Eukaryota
ENOG410XP8F LUCA
GeneTreeiENSGT00930000150819
HOGENOMiHOG000233031
HOVERGENiHBG106948
InParanoidiQ16644
KOiK04444
OMAiRMGQYGF
OrthoDBiEOG091G14PL
PhylomeDBiQ16644
TreeFamiTF312891

Enzyme and pathway databases

ReactomeiR-HSA-171007 p38MAPK events
R-HSA-2559580 Oxidative Stress Induced Senescence
R-HSA-4420097 VEGFA-VEGFR2 Pathway
R-HSA-450302 activated TAK1 mediates p38 MAPK activation
SignaLinkiQ16644
SIGNORiQ16644

Miscellaneous databases

ChiTaRSiMAPKAPK3 human
EvolutionaryTraceiQ16644
GeneWikiiMAPKAPK3
GenomeRNAii7867
PROiPR:Q16644
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000114738 Expressed in 232 organ(s), highest expression level in cardiac ventricle
CleanExiHS_MAPKAPK3
ExpressionAtlasiQ16644 baseline and differential
GenevisibleiQ16644 HS

Family and domain databases

Gene3Di4.10.1170.10, 1 hit
InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR027442 MAPKAPK_C
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
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 nameiMAPK3_HUMAN
AccessioniPrimary (citable) accession number: Q16644
Secondary accession number(s): B5BU67
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 6, 2005
Last sequence update: November 1, 1996
Last modified: November 7, 2018
This is version 167 of the entry and version 1 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again