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Protein

MAP kinase-activated protein kinase 3

Gene

MAPKAPK3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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-X(2)-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

Enzyme 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

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS03793-MONOMER.
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

HGNCiHGNC:6888. MAPKAPK3.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: GO_Central
  • cytosol Source: Reactome
  • nucleoplasm Source: HPA
  • nucleus Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

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

Organism-specific databases

DisGeNETi7867.
OpenTargetsiENSG00000114738.
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.

PTM databases

iPTMnetiQ16644.
PhosphoSitePlusiQ16644.

Expressioni

Tissue specificityi

Widely expressed, with a higher expression level observed in heart and skeletal muscle. No expression in brain.2 Publications

Gene expression databases

BgeeiENSG00000114738.
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

WithEntry#Exp.IntActNotes
P279585EBI-1384657,EBI-6377335From a different organism.
HSPB1P047923EBI-1384657,EBI-352682
MAPK14Q165395EBI-1384657,EBI-73946

GO - Molecular functioni

Protein-protein interaction databases

BioGridi113617. 21 interactors.
IntActiQ16644. 27 interactors.
MINTiMINT-3032958.
STRINGi9606.ENSP00000350639.

Chemistry databases

BindingDBiQ16644.

Structurei

Secondary structure

1382
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi39 – 41Combined sources3
Beta strandi43 – 53Combined sources11
Beta strandi56 – 63Combined sources8
Turni64 – 66Combined sources3
Beta strandi69 – 78Combined sources10
Helixi79 – 91Combined sources13
Beta strandi100 – 108Combined sources9
Beta strandi111 – 119Combined sources9
Helixi126 – 131Combined sources6
Helixi140 – 159Combined sources20
Helixi169 – 171Combined sources3
Beta strandi172 – 175Combined sources4
Beta strandi183 – 185Combined sources3
Helixi218 – 237Combined sources20
Turni267 – 269Combined sources3
Beta strandi271 – 273Combined sources3
Helixi275 – 284Combined sources10
Helixi289 – 291Combined sources3
Helixi295 – 300Combined sources6
Helixi302 – 305Combined sources4
Helixi307 – 309Combined sources3
Helixi317 – 323Combined sources7
Helixi325 – 327Combined sources3
Helixi328 – 343Combined sources16
Beta strandi344 – 346Combined sources3

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...

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

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0604. Eukaryota.
ENOG410XP8F. LUCA.
GeneTreeiENSGT00830000128274.
HOGENOMiHOG000233031.
HOVERGENiHBG106948.
InParanoidiQ16644.
KOiK04444.
OMAiSGCRHIV.
OrthoDBiEOG091G14PL.
PhylomeDBiQ16644.
TreeFamiTF312891.

Family and domain databases

Gene3Di4.10.1170.10. 1 hit.
InterProiIPR011009. Kinase-like_dom.
IPR027442. MAPKAPK_C.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
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.

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

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_040757276D → Y.1 PublicationCorresponds to variant rs56107897dbSNPEnsembl.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

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. 21 interactors.
IntActiQ16644. 27 interactors.
MINTiMINT-3032958.
STRINGi9606.ENSP00000350639.

Chemistry databases

BindingDBiQ16644.
ChEMBLiCHEMBL4670.
GuidetoPHARMACOLOGYi2095.

PTM databases

iPTMnetiQ16644.
PhosphoSitePlusiQ16644.

Polymorphism and mutation databases

BioMutaiMAPKAPK3.
DMDMi74762148.

Proteomic databases

EPDiQ16644.
MaxQBiQ16644.
PaxDbiQ16644.
PeptideAtlasiQ16644.
PRIDEiQ16644.

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.
GeneCardsiMAPKAPK3.
HGNCiHGNC:6888. MAPKAPK3.
HPAiHPA058275.
MIMi602130. gene.
neXtProtiNX_Q16644.
OpenTargetsiENSG00000114738.
PharmGKBiPA30632.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0604. Eukaryota.
ENOG410XP8F. LUCA.
GeneTreeiENSGT00830000128274.
HOGENOMiHOG000233031.
HOVERGENiHBG106948.
InParanoidiQ16644.
KOiK04444.
OMAiSGCRHIV.
OrthoDBiEOG091G14PL.
PhylomeDBiQ16644.
TreeFamiTF312891.

Enzyme and pathway databases

BioCyciZFISH:HS03793-MONOMER.
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.
PROiQ16644.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000114738.
CleanExiHS_MAPKAPK3.
ExpressionAtlasiQ16644. baseline and differential.
GenevisibleiQ16644. HS.

Family and domain databases

Gene3Di4.10.1170.10. 1 hit.
InterProiIPR011009. Kinase-like_dom.
IPR027442. MAPKAPK_C.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
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 nameiMAPK3_HUMAN
AccessioniPrimary (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: November 2, 2016
This is version 151 of the entry and version 1 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. 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.