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Protein

MAP kinase-activated protein kinase 3

Gene

MAPKAPK3

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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 (By similarity).By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

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 (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei75ATPPROSITE-ProRule annotation1
Active sitei168Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi52 – 60ATPPROSITE-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

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

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
Gene namesi
Name:MAPKAPK3
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 22

Subcellular locationi

  • Nucleus By similarity
  • Cytoplasm By similarity

  • Note: Predominantly located in the nucleus, when activated it translocates to the cytoplasm.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000862921 – 384MAP kinase-activated protein kinase 3Add BLAST384

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineBy similarity1
Modified residuei203Phosphothreonine; by MAPK14By similarity1
Modified residuei253Phosphoserine; by MAPK14By similarity1
Modified residuei309Phosphoserine; by autocatalysisBy similarity1
Modified residuei315Phosphothreonine; 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-203, Ser-253 and Thr-315.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiQ3SYZ2.
PRIDEiQ3SYZ2.

Expressioni

Gene expression databases

BgeeiENSBTAG00000016532.

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. Interacts with TCF3 and with polycomb proteins, such as PCH2 and BMI1/PCGF4 (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000021983.

Structurei

3D structure databases

ProteinModelPortaliQ3SYZ2.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini46 – 306Protein kinasePROSITE-ProRule annotationAdd BLAST261

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni309 – 345Autoinhibitory helixBy similarityAdd BLAST37
Regioni347 – 371p38 MAPK-binding siteBy similarityAdd BLAST25

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi337 – 346Nuclear export signal (NES)By similarity10
Motifi352 – 355Bipartite nuclear localization signal 1By similarity4
Motifi366 – 370Bipartite nuclear localization signal 2By similarity5

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0604. Eukaryota.
ENOG410XP8F. LUCA.
GeneTreeiENSGT00830000128274.
HOGENOMiHOG000233031.
HOVERGENiHBG106948.
InParanoidiQ3SYZ2.
KOiK04444.
OMAiSGCRHIV.
OrthoDBiEOG091G14PL.
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.

Q3SYZ2-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDVETAEEQG GPAPPSGVPC GPCSAGAPAL GGRREPKKYA VTDDYQLSKQ
60 70 80 90 100
VLGLGVNGKV LECFHRRTGQ KCALKLLYDS PKARQEVDHH WQASGGPHIV
110 120 130 140 150
RILDVYENMH HSKRCLLIIM ECMEGGELFS RIQERGDQAF TEREAAEIMR
160 170 180 190 200
DIGTAIQFLH SRNIAHRDVK PENLLYTSKD KDAVLKLTDF GFAKETTQNA
210 220 230 240 250
LQTPCYTPYY VAPEVLGPEK YDKSCDMWSL GVIMYILLCG FPPFYSNTGQ
260 270 280 290 300
AISPGMKRRI RLGQYGFPSP EWSEVSEDAK QLIRLLLKTD PTERLTITQF
310 320 330 340 350
MNHPWINQSM VVPQTPLHTA RVLQEDRDHW DEVKEEMTSA LATMRVDYDQ
360 370 380
VKIKDLKTSN NRLLNKRRKK QAGSSSGSQG CNNQ
Length:384
Mass (Da):43,316
Last modified:October 11, 2005 - v1
Checksum:iC9D737DDCF8A0C06
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BT026197 mRNA. Translation: ABG67036.1.
BC103321 mRNA. Translation: AAI03322.1.
RefSeqiNP_001029951.1. NM_001034779.2.
XP_005222977.1. XM_005222920.1.
UniGeneiBt.43984.

Genome annotation databases

EnsembliENSBTAT00000021983; ENSBTAP00000021983; ENSBTAG00000016532.
GeneIDi615215.
KEGGibta:615215.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BT026197 mRNA. Translation: ABG67036.1.
BC103321 mRNA. Translation: AAI03322.1.
RefSeqiNP_001029951.1. NM_001034779.2.
XP_005222977.1. XM_005222920.1.
UniGeneiBt.43984.

3D structure databases

ProteinModelPortaliQ3SYZ2.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000021983.

Proteomic databases

PaxDbiQ3SYZ2.
PRIDEiQ3SYZ2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000021983; ENSBTAP00000021983; ENSBTAG00000016532.
GeneIDi615215.
KEGGibta:615215.

Organism-specific databases

CTDi7867.

Phylogenomic databases

eggNOGiKOG0604. Eukaryota.
ENOG410XP8F. LUCA.
GeneTreeiENSGT00830000128274.
HOGENOMiHOG000233031.
HOVERGENiHBG106948.
InParanoidiQ3SYZ2.
KOiK04444.
OMAiSGCRHIV.
OrthoDBiEOG091G14PL.
TreeFamiTF312891.

Enzyme and pathway databases

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

Gene expression databases

BgeeiENSBTAG00000016532.

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_BOVIN
AccessioniPrimary (citable) accession number: Q3SYZ2
Secondary accession number(s): Q0V8M1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 6, 2005
Last sequence update: October 11, 2005
Last modified: October 5, 2016
This is version 96 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 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.