MAP kinase-activated protein kinase 3 - Rattus norvegicus (Rat)

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Q66H84 (MAPK3_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 79. History...

Clusters with 100%, 90%, 50% identity |

Documents (1) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
MAP kinase-activated protein kinase 3
Short name=MAPK-activated protein kinase 3
Short name=MAPKAP kinase 3
Short name=MAPKAP-K3
Short name=MAPKAPK-3
Short name=MK-3
EC=2.7.11.1

Gene names

Name:

Mapkapk3

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	384 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	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.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	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.
Subunit structure	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.
Subcellular location	Nucleus By similarity. Cytoplasm By similarity. Note: Predominantly located in the nucleus, when activated it translocates to the cytoplasm By similarity.
Post-translational modification	Phosphorylated and activated by MAPK1/ERK2 and MAPK3/ERK1 By similarity. Phosphorylated and activated by MAP kinase p38-alpha/MAPK14 at Thr-203, Ser-253 and Thr-315 By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. Contains 1 protein kinase domain.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	macropinocytosis Inferred from sequence or structural similarity. Source: UniProtKB peptidyl-serine phosphorylation Inferred from electronic annotation. Source: Compara response to lipopolysaccharide Inferred from sequence or structural similarity. Source: UniProtKB response to stress Inferred from sequence or structural similarity. Source: UniProtKB toll-like receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine kinase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 384

384

MAP kinase-activated protein kinase 3

PRO_0000086295

Regions

Domain

46 – 306

261

Protein kinase

Nucleotide binding

52 – 60

ATP By similarity

Region

309 – 345

Autoinhibitory helix By similarity

Region

347 – 371

p38 MAPK-binding site By similarity

Motif

337 – 346

Nuclear export signal (NES) By similarity

Motif

352 – 355

Bipartite nuclear localization signal 1 By similarity

Motif

366 – 370

Bipartite nuclear localization signal 2 By similarity

Sites

Active site

168

Proton acceptor By similarity

Binding site

ATP By similarity

Amino acid modifications

Modified residue

203

Phosphothreonine; by MAPK14 By similarity

Modified residue

253

Phosphoserine; by MAPK14 By similarity

Modified residue

309

Phosphoserine; by autocatalysis By similarity

Modified residue

315

Phosphothreonine; by MAPK14 By similarity

Sequences

Sequence

Length

Mass (Da)

Tools

Q66H84 [UniParc].

Last modified October 11, 2004. Version 1.
Checksum: E094358C901F7E70
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FASTA

384

43,222

        10         20         30         40         50         60 
MDGETAGEKG SLVPQPGALG APALGGAPAP GVRREPKKYA VTDDYQLSKQ VLGLGVNGKV 

        70         80         90        100        110        120 
LECYHRRSGQ KCALKLLYDS PKARQEVDHH WQASGGPHIV RILDVYENMH HGKRCLLIVM 

       130        140        150        160        170        180 
ECMEGGELFS RIQERGDQAF TEREAAEIMR DIGTAIQFLH SQNIAHRDVK PENLLYTSKE 

       190        200        210        220        230        240 
KDAVLKLTDF GFAKETTQNA LQTPCYTPYY VAPEVLGPEK YDKSCDMWSL GVIMYILLCG 

       250        260        270        280        290        300 
FPPFYSNTGQ AISPGMKRRI RLGQYGFPKP EWADVSEDAK QLIRLLLKTD PTERLTIMQF 

       310        320        330        340        350        360 
MNHPWINQSM EVPQTPLHTA RVLEEDKDHW DDVKEEMTSA LATMRVDYDQ VKIKDLKTSN 

       370        380 
NRLLNKRRKK QGGSSSASPG CNNQ

« Hide

References

[1]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Kidney.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	BC081974 mRNA. Translation: AAH81974.1.
IPI	IPI00471813.
RefSeq	NP_001012127.1. NM_001012127.1.
UniGene	Rn.8789.
3D structure databases
ProteinModelPortal	Q66H84.
SMR	Q66H84. Positions 37-370.
ModBase	Search...
Protein-protein interaction databases
STRING	10116.ENSRNOP00000020065.
PTM databases
PhosphoSite	Q66H84.
Proteomic databases
PaxDb	Q66H84.
PRIDE	Q66H84.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000020065; ENSRNOP00000020065; ENSRNOG00000014832.
GeneID	315994.
KEGG	rno:315994.
UCSC	RGD:1304980. rat.
Organism-specific databases
CTD	7867.
RGD	1304980. Mapkapk3.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00550000074510.
HOGENOM	HOG000233031.
HOVERGEN	HBG106948.
InParanoid	Q66H84.
KO	K04444.
OMA	IRMGQYG.
OrthoDB	EOG4HQDJP.
Gene expression databases
ArrayExpress	Q66H84.
Genevestigator	Q66H84.
GermOnline	ENSRNOG00000014832. Rattus norvegicus.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR002290. Ser/Thr_dual-sp_kinase_dom. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	670215.

Entry information

Entry name

MAPK3_RAT

Accession

Primary (citable) accession number: Q66H84

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 6, 2005
Last sequence update:	October 11, 2004
Last modified:	April 3, 2013
This is version 79 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents