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Protein

Mitogen-activated protein kinase 6

Gene

Mapk6

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Atypical MAPK protein. Phosphorylates microtubule-associated protein 2 (MAP2) and MAPKAPK5. The precise role of the complex formed with MAPKAPK5 is still unclear, but the complex follows a complex set of phosphorylation events: upon interaction with atypical MAPKAPK5, ERK3/MAPK6 is phosphorylated at Ser-189 and then mediates phosphorylation and activation of MAPKAPK5, which in turn phosphorylates ERK3/MAPK6. May promote entry in the cell cycle (By similarity).By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mg2+By similarity

Enzyme regulationi

Activated by phosphorylation at Ser-189.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei49ATPPROSITE-ProRule annotation1
Active sitei152Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi26 – 34ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Cell cycle

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.24. 5301.
ReactomeiR-RNO-5687128. MAPK6/MAPK4 signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Mitogen-activated protein kinase 6 (EC:2.7.11.24)
Short name:
MAP kinase 6
Short name:
MAPK 6
Alternative name(s):
Extracellular signal-regulated kinase 3
Short name:
ERK-3
p55-MAPK
Gene namesi
Name:Mapk6
Synonyms:Erk3, Prkm6
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 8

Organism-specific databases

RGDi62087. Mapk6.

Subcellular locationi

  • Cytoplasm By similarity
  • Nucleus By similarity

  • Note: Translocates to the cytoplasm following interaction with MAPKAPK5.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001862591 – 720Mitogen-activated protein kinase 6Add BLAST720

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki1Peptide (Met-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei189Phosphoserine; by PAK1, PAK2 and PAK3By similarity1
Modified residuei386PhosphoserineBy similarity1
Modified residuei452PhosphoserineBy similarity1
Modified residuei554PhosphoserineBy similarity1
Modified residuei556PhosphoserineBy similarity1
Modified residuei683PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylated at Ser-189 by PAK1, PAK2 and PAK3 resulting in catalytic activation. Phosphorylated by MAPKAPK5 at other sites (By similarity).By similarity
Ubiquitination at Met-1 leads to degradation by the proteasome pathway.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP27704.
PRIDEiP27704.

PTM databases

iPTMnetiP27704.
PhosphoSitePlusiP27704.

Expressioni

Tissue specificityi

Highest levels within the nervous system, expressed in different tissues, mostly in skeletal muscle.

Developmental stagei

Expressed at highest levels early in development.

Gene expression databases

BgeeiENSRNOG00000009381.
ExpressionAtlasiP27704. baseline and differential.
GenevisibleiP27704. RN.

Interactioni

Subunit structurei

Heterodimer with ERK4/MAPK4. Interacts with (via FRIEDE motif) MAPKAPK5 (By similarity). Interacts with UBE3A; this interaction may be indirect and mediated by HERC2, possibly via HERC2 interaction with NEURL4 (By similarity).By similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000013053.

Structurei

3D structure databases

ProteinModelPortaliP27704.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini20 – 316Protein kinasePROSITE-ProRule annotationAdd BLAST297

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi189 – 191SEG motif3
Motifi332 – 337FRIEDE motif6

Domaini

In contrast to classical MAPKs, the TXY motif within the activation loop is replaced by the SEG motif, whose phosphorylation activates the MAP kinases.By similarity

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0660. Eukaryota.
ENOG410XNY0. LUCA.
GeneTreeiENSGT00550000074298.
HOGENOMiHOG000233020.
HOVERGENiHBG104376.
InParanoidiP27704.
KOiK06855.
OMAiSEHDWPI.
OrthoDBiEOG091G03RQ.
PhylomeDBiP27704.
TreeFamiTF105098.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR008350. MAPK_ERK3/4.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
PRINTSiPR01771. ERK3ERK4MAPK.
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.

P27704-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAEKFESLMN IHGFDLGSRY MDLKPLGCGG NGLVFSAVDN DCDKRVAIKK
60 70 80 90 100
IVLTDPQSVK HALREIKIIR RLDHDNIVKV FEILGPSGSQ LTDDVGSLTE
110 120 130 140 150
LNSVYIVQEY METDLANVLE QGPLLEEHAR LFMYQLLRGL KYIHSANVLH
160 170 180 190 200
RDLKPANLFI NTEDLVLKIG DFGLARIMDP HYSHKGHLSE GLVTKWYRSP
210 220 230 240 250
RLLLSPNNYT KAIDMWAAGC IFAEMLTGKT LFAGAHELEQ MQLILESIPV
260 270 280 290 300
VHEEDRQELL SVIPVYIRND MTEPHKPLTQ LLPGISREAL DFLEQILTFS
310 320 330 340 350
PMDRLTAEEA LSHPYMSIYS FPTDEPISSH PFHIEDEVDD ILLMDETHSH
360 370 380 390 400
IYNWERYHDC QFSEHDWPIH NNFDIDEVQL DPRALSDVTD EEEVQVDPRK
410 420 430 440 450
YLDGDREKYL EDPAFDTSYS AEPCWQYPDH HENKYCDLEC SHTCNYKTRS
460 470 480 490 500
PSYLDNLVWR ESEVNHYYEP KLIIDLSNWK EQSKDKSDKR GKSKCERNGL
510 520 530 540 550
VKAQIALEEA SQQLAERERG QGFDFDAFIA GTVQLSAQRE SADVVDKLND
560 570 580 590 600
LNSSVSQLEM KSLISKSVSR EKQEKGRANL AQLGALYQPS WESQFVSGGE
610 620 630 640 650
ECFLISQFCC EVRKDEHVEK ENTYTSYLDK FFSRKEDSEM LETEPVEEGK
660 670 680 690 700
RGERGREAGL LSSGGEFLLS RQLESIGTPQ FHSPGGSPLK SIQATLTPSA
710 720
MKSSPQIPHK TYSNILKHLN
Length:720
Mass (Da):82,275
Last modified:November 1, 1997 - v2
Checksum:iB200B215574AB84D
GO

Sequence cautioni

The sequence AAA41125 differs from that shown. Reason: Frameshift at position 503.Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M64301 mRNA. Translation: AAA41125.1. Frameshift.
BC109380 mRNA. Translation: AAI09381.1.
PIRiB40033.
RefSeqiNP_113810.2. NM_031622.2.
XP_006243471.1. XM_006243409.3.
UniGeneiRn.88457.

Genome annotation databases

EnsembliENSRNOT00000013053; ENSRNOP00000013053; ENSRNOG00000009381.
GeneIDi58840.
KEGGirno:58840.
UCSCiRGD:62087. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M64301 mRNA. Translation: AAA41125.1. Frameshift.
BC109380 mRNA. Translation: AAI09381.1.
PIRiB40033.
RefSeqiNP_113810.2. NM_031622.2.
XP_006243471.1. XM_006243409.3.
UniGeneiRn.88457.

3D structure databases

ProteinModelPortaliP27704.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000013053.

PTM databases

iPTMnetiP27704.
PhosphoSitePlusiP27704.

Proteomic databases

PaxDbiP27704.
PRIDEiP27704.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000013053; ENSRNOP00000013053; ENSRNOG00000009381.
GeneIDi58840.
KEGGirno:58840.
UCSCiRGD:62087. rat.

Organism-specific databases

CTDi5597.
RGDi62087. Mapk6.

Phylogenomic databases

eggNOGiKOG0660. Eukaryota.
ENOG410XNY0. LUCA.
GeneTreeiENSGT00550000074298.
HOGENOMiHOG000233020.
HOVERGENiHBG104376.
InParanoidiP27704.
KOiK06855.
OMAiSEHDWPI.
OrthoDBiEOG091G03RQ.
PhylomeDBiP27704.
TreeFamiTF105098.

Enzyme and pathway databases

BRENDAi2.7.11.24. 5301.
ReactomeiR-RNO-5687128. MAPK6/MAPK4 signaling.

Miscellaneous databases

PROiP27704.

Gene expression databases

BgeeiENSRNOG00000009381.
ExpressionAtlasiP27704. baseline and differential.
GenevisibleiP27704. RN.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR008350. MAPK_ERK3/4.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
PRINTSiPR01771. ERK3ERK4MAPK.
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 nameiMK06_RAT
AccessioniPrimary (citable) accession number: P27704
Secondary accession number(s): Q32LY4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: November 1, 1997
Last modified: November 2, 2016
This is version 134 of the entry and version 2 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.