UniProtKB - Q16644 (MAPK3_HUMAN)
MAP kinase-activated protein kinase 3
MAPKAPK3
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 PublicationsCatalytic activityi
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 73 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 166 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 50 – 58 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- calcium-dependent protein serine/threonine kinase activity Source: GO_Central
- calmodulin binding 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
- protein serine kinase activity Source: RHEA
GO - Biological processi
- intracellular signal transduction Source: GO_Central
- macropinocytosis Source: UniProtKB
- peptidyl-serine phosphorylation Source: BHF-UCL
- protein autophosphorylation Source: GO_Central
- response to cytokine Source: UniProtKB
- response to lipopolysaccharide Source: UniProtKB
- signal transduction Source: ProtInc
- toll-like receptor signaling pathway Source: UniProtKB
- vascular endothelial growth factor receptor signaling pathway Source: Reactome
Keywordsi
Molecular function | Kinase, Serine/threonine-protein kinase, Transferase |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
PathwayCommonsi | Q16644 |
Reactomei | R-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 |
SignaLinki | Q16644 |
SIGNORi | Q16644 |
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 | Name:MAPKAPK3 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:6888, MAPKAPK3 |
MIMi | 602130, gene |
neXtProti | NX_Q16644 |
VEuPathDBi | HostDB:ENSG00000114738 |
Subcellular locationi
Cytosol
- cytosol Source: Reactome
Nucleus
- nucleoplasm Source: HPA
- nucleus Source: GO_Central
Other locations
- cytoplasm Source: GO_Central
Keywords - Cellular componenti
Cytoplasm, NucleusPathology & Biotechi
Involvement in diseasei
Macular dystrophy, patterned, 3 (MDPT3)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_077085 | 173 | L → P in MDPT3; decreased localization to the nucleus. 1 PublicationCorresponds to variant dbSNP:rs886037913EnsemblClinVar. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 73 | K → M: Higher affinity toward PCH2. 1 Publication | 1 |
Keywords - Diseasei
Disease variantOrganism-specific databases
DisGeNETi | 7867 |
MalaCardsi | MAPKAPK3 |
MIMi | 617111, phenotype |
OpenTargetsi | ENSG00000114738 |
Orphaneti | 466718, Martinique crinkled retinal pigment epitheliopathy |
PharmGKBi | PA30632 |
Miscellaneous databases
Pharosi | Q16644, Tchem |
Chemistry databases
ChEMBLi | CHEMBL4670 |
DrugBanki | DB08358, 2-(2-QUINOLIN-3-YLPYRIDIN-4-YL)-1,5,6,7-TETRAHYDRO-4H-PYRROLO[3,2-C]PYRIDIN-4-ONE DB07728, 2-[2-(2-FLUOROPHENYL)PYRIDIN-4-YL]-1,5,6,7-TETRAHYDRO-4H-PYRROLO[3,2-C]PYRIDIN-4-ONE |
GuidetoPHARMACOLOGYi | 2095 |
Genetic variation databases
BioMutai | MAPKAPK3 |
DMDMi | 74762148 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000086293 | 1 – 382 | MAP kinase-activated protein kinase 3Add BLAST | 382 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 1 | N-acetylmethionineCombined sources | 1 | |
Modified residuei | 201 | Phosphothreonine; by MAPK14By similarity | 1 | |
Modified residuei | 251 | Phosphoserine; by MAPK14By similarity | 1 | |
Modified residuei | 307 | Phosphoserine; by autocatalysisBy similarity | 1 | |
Modified residuei | 313 | Phosphothreonine; by MAPK14By similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
EPDi | Q16644 |
jPOSTi | Q16644 |
MassIVEi | Q16644 |
MaxQBi | Q16644 |
PaxDbi | Q16644 |
PeptideAtlasi | Q16644 |
PRIDEi | Q16644 |
ProteomicsDBi | 60998 |
PTM databases
iPTMneti | Q16644 |
PhosphoSitePlusi | Q16644 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000114738, Expressed in cardiac ventricle and 243 other tissues |
ExpressionAtlasi | Q16644, baseline and differential |
Genevisiblei | Q16644, HS |
Organism-specific databases
HPAi | ENSG00000114738, Tissue enhanced (heart muscle, skeletal muscle, tongue) |
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 PublicationsBinary interactionsi
Q16644
GO - Molecular functioni
- calmodulin binding Source: GO_Central
- mitogen-activated protein kinase binding Source: GO_Central
Protein-protein interaction databases
BioGRIDi | 113617, 31 interactors |
ELMi | Q16644 |
IntActi | Q16644, 28 interactors |
MINTi | Q16644 |
STRINGi | 9606.ENSP00000396467 |
Chemistry databases
BindingDBi | Q16644 |
Miscellaneous databases
RNActi | Q16644, protein |
Structurei
Secondary structure
3D structure databases
SMRi | Q16644 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q16644 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 44 – 304 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 261 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 34 | DisorderedSequence analysisAdd BLAST | 34 | |
Regioni | 307 – 343 | Autoinhibitory helixBy similarityAdd BLAST | 37 | |
Regioni | 345 – 369 | p38 MAPK-binding siteBy similarityAdd BLAST | 25 | |
Regioni | 357 – 382 | DisorderedSequence analysisAdd BLAST | 26 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 335 – 344 | Nuclear export signal (NES)By similarity | 10 | |
Motifi | 350 – 353 | Bipartite nuclear localization signal 1By similarity | 4 | |
Motifi | 364 – 368 | Bipartite nuclear localization signal 2By similarity | 5 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 368 – 382 | Polar residuesSequence analysisAdd BLAST | 15 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG0604, Eukaryota |
GeneTreei | ENSGT00940000154089 |
InParanoidi | Q16644 |
OMAi | TEDRAMW |
OrthoDBi | 843707at2759 |
PhylomeDBi | Q16644 |
TreeFami | TF312891 |
Family and domain databases
Gene3Di | 4.10.1170.10, 1 hit |
InterProi | View 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 |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All
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
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketH7C0G6 | H7C0G6_HUMAN | Non-specific serine/threonine prote... | MAPKAPK3 | 97 | Annotation score: | ||
C9J8E1 | C9J8E1_HUMAN | MAP kinase-activated protein kinase... | MAPKAPK3 | 332 | Annotation score: | ||
C9JPW3 | C9JPW3_HUMAN | MAP kinase-activated protein kinase... | MAPKAPK3 | 119 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_040755 | 28 | P → S in a glioblastoma multiforme sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs375412266Ensembl. | 1 | |
Natural variantiVAR_040756 | 105 | E → A in an ovarian endometrioid sample; somatic mutation. 1 Publication | 1 | |
Natural variantiVAR_077085 | 173 | L → P in MDPT3; decreased localization to the nucleus. 1 PublicationCorresponds to variant dbSNP:rs886037913EnsemblClinVar. | 1 | |
Natural variantiVAR_040757 | 276 | D → 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 |
CCDSi | CCDS2832.1 |
PIRi | JC6094 |
RefSeqi | NP_001230854.1, NM_001243925.1 NP_001230855.1, NM_001243926.1 NP_004626.1, NM_004635.4 |
Genome annotation databases
Ensembli | ENST00000357955; ENSP00000350639; ENSG00000114738 ENST00000446044; ENSP00000396467; ENSG00000114738 ENST00000621469; ENSP00000478922; ENSG00000114738 |
GeneIDi | 7867 |
KEGGi | hsa:7867 |
MANE-Selecti | ENST00000621469.5; ENSP00000478922.1; NM_001243925.2; NP_001230854.1 |
UCSCi | uc003day.3, human |
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 |
CCDSi | CCDS2832.1 |
PIRi | JC6094 |
RefSeqi | NP_001230854.1, NM_001243925.1 NP_001230855.1, NM_001243926.1 NP_004626.1, NM_004635.4 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
3FHR | X-ray | 1.90 | A | 33-349 | [»] | |
3FXW | X-ray | 2.00 | A | 33-349 | [»] | |
3R1N | X-ray | 2.09 | A | 33-349 | [»] | |
3SHE | X-ray | 2.25 | A | 33-349 | [»] | |
SMRi | Q16644 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 113617, 31 interactors |
ELMi | Q16644 |
IntActi | Q16644, 28 interactors |
MINTi | Q16644 |
STRINGi | 9606.ENSP00000396467 |
Chemistry databases
BindingDBi | Q16644 |
ChEMBLi | CHEMBL4670 |
DrugBanki | DB08358, 2-(2-QUINOLIN-3-YLPYRIDIN-4-YL)-1,5,6,7-TETRAHYDRO-4H-PYRROLO[3,2-C]PYRIDIN-4-ONE DB07728, 2-[2-(2-FLUOROPHENYL)PYRIDIN-4-YL]-1,5,6,7-TETRAHYDRO-4H-PYRROLO[3,2-C]PYRIDIN-4-ONE |
GuidetoPHARMACOLOGYi | 2095 |
PTM databases
iPTMneti | Q16644 |
PhosphoSitePlusi | Q16644 |
Genetic variation databases
BioMutai | MAPKAPK3 |
DMDMi | 74762148 |
Proteomic databases
EPDi | Q16644 |
jPOSTi | Q16644 |
MassIVEi | Q16644 |
MaxQBi | Q16644 |
PaxDbi | Q16644 |
PeptideAtlasi | Q16644 |
PRIDEi | Q16644 |
ProteomicsDBi | 60998 |
Protocols and materials databases
Antibodypediai | 30996, 335 antibodies from 33 providers |
DNASUi | 7867 |
Genome annotation databases
Ensembli | ENST00000357955; ENSP00000350639; ENSG00000114738 ENST00000446044; ENSP00000396467; ENSG00000114738 ENST00000621469; ENSP00000478922; ENSG00000114738 |
GeneIDi | 7867 |
KEGGi | hsa:7867 |
MANE-Selecti | ENST00000621469.5; ENSP00000478922.1; NM_001243925.2; NP_001230854.1 |
UCSCi | uc003day.3, human |
Organism-specific databases
CTDi | 7867 |
DisGeNETi | 7867 |
GeneCardsi | MAPKAPK3 |
HGNCi | HGNC:6888, MAPKAPK3 |
HPAi | ENSG00000114738, Tissue enhanced (heart muscle, skeletal muscle, tongue) |
MalaCardsi | MAPKAPK3 |
MIMi | 602130, gene 617111, phenotype |
neXtProti | NX_Q16644 |
OpenTargetsi | ENSG00000114738 |
Orphaneti | 466718, Martinique crinkled retinal pigment epitheliopathy |
PharmGKBi | PA30632 |
VEuPathDBi | HostDB:ENSG00000114738 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0604, Eukaryota |
GeneTreei | ENSGT00940000154089 |
InParanoidi | Q16644 |
OMAi | TEDRAMW |
OrthoDBi | 843707at2759 |
PhylomeDBi | Q16644 |
TreeFami | TF312891 |
Enzyme and pathway databases
PathwayCommonsi | Q16644 |
Reactomei | R-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 |
SignaLinki | Q16644 |
SIGNORi | Q16644 |
Miscellaneous databases
BioGRID-ORCSi | 7867, 11 hits in 1080 CRISPR screens |
ChiTaRSi | MAPKAPK3, human |
EvolutionaryTracei | Q16644 |
GeneWikii | MAPKAPK3 |
GenomeRNAii | 7867 |
Pharosi | Q16644, Tchem |
PROi | PR:Q16644 |
RNActi | Q16644, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000114738, Expressed in cardiac ventricle and 243 other tissues |
ExpressionAtlasi | Q16644, baseline and differential |
Genevisiblei | Q16644, HS |
Family and domain databases
Gene3Di | 4.10.1170.10, 1 hit |
InterProi | View 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 |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | MAPK3_HUMAN | |
Accessioni | Q16644Primary (citable) accession number: Q16644 Secondary accession number(s): B5BU67 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 6, 2005 |
Last sequence update: | November 1, 1996 | |
Last modified: | February 23, 2022 | |
This is version 185 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Reference proteomeDocuments
- Human and mouse protein kinases
Human and mouse protein kinases: classification and index - Human chromosome 3
Human chromosome 3: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families