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Protein

Mitogen-activated protein kinase 6

Gene

Mapk6

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein 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.2 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mg2+By similarity

Enzyme regulationi

Activated by phosphorylation at Ser-189.

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

  • ATP binding Source: UniProtKB-KW
  • MAP kinase activity Source: UniProtKB
  • protein heterodimerization activity Source: UniProtKB
  • protein kinase activity Source: MGI
  • protein kinase binding Source: UniProtKB

GO - Biological processi

  • cell cycle Source: UniProtKB-KW
  • cellular response to organic substance Source: GO_Central
  • positive regulation of dendritic spine development Source: MGI
  • protein phosphorylation Source: UniProtKB
  • regulation of gene expression Source: GO_Central

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processCell cycle
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.24 3474
ReactomeiR-MMU-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
Gene namesi
Name:Mapk6
Synonyms:Erk3, Prkm4, Prkm6
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:1354946 Mapk6

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi171D → A: Kinase defective mutant, abolishes activity. 1 Publication1
Mutagenesisi189S → A: Unable to activate MAPKAPK5 promote MAPKAPK5 localization to the cytoplasm. 2 Publications1
Mutagenesisi189S → E: Mimicks phosphorylation state and induces constitutive protein kinase activity. 2 Publications1
Mutagenesisi334I → K: Abolishes binding to MAPKAPK5. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001862581 – 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 PAK31 Publication1
Modified residuei386PhosphoserineBy 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.1 Publication
Ubiquitination at Met-1 leads to degradation by the proteasome pathway.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ61532
PaxDbiQ61532
PeptideAtlasiQ61532
PRIDEiQ61532

PTM databases

iPTMnetiQ61532
PhosphoSitePlusiQ61532

Expressioni

Developmental stagei

Expression increases markedly from days 9 to 11 in the developing embryo, followed by a gradual decrease up to birth.1 Publication

Gene expression databases

BgeeiENSMUSG00000042688
CleanExiMM_MAPK6
GenevisibleiQ61532 MM

Interactioni

Subunit structurei

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

GO - Molecular functioni

  • protein heterodimerization activity Source: UniProtKB
  • protein kinase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi206104, 4 interactors
STRINGi10090.ENSMUSP00000040315

Structurei

3D structure databases

ProteinModelPortaliQ61532
SMRiQ61532
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.1 Publication

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0660 Eukaryota
ENOG410XNY0 LUCA
GeneTreeiENSGT00910000144035
HOVERGENiHBG104376
InParanoidiQ61532
KOiK06855
OMAiSEHDWPI
OrthoDBiEOG091G03RQ
PhylomeDBiQ61532
TreeFamiTF105098

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR008350 MAPK_ERK3/4
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
PRINTSiPR01771 ERK3ERK4MAPK
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

Sequencei

Sequence statusi: Complete.

Q61532-1 [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 MQLILDSIPV
260 270 280 290 300
VHEEDRQELL SVIPVYIRND MTEPHRPLTQ 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
SPYLDNLVWR ESEVNHYYEP KLIIDLSNWK EQSKEKSDKR GKSKCERNGL
510 520 530 540 550
VKAQIALEEA SQQLAERERG QGFDFDSFIA GTIQLSAQHQ SADVVDKLND
560 570 580 590 600
LNSSVSQLEL KSLISKSVSR EKQEKGRANL AQLGALYQSS WDSQFVSGGE
610 620 630 640 650
ECFLISQFCC EVRKDEHAEK ENTYTSYLDK FFSRKEDSEM LETEPVEEGK
660 670 680 690 700
RGERGREAGL LSGGGEFLLS KQLESIGTPQ FHSPVGSPLK SIQATLTPSA
710 720
MKSSPQIPHK TYSSILKHLN
Length:720
Mass (Da):82,199
Last modified:September 13, 2004 - v3
Checksum:iD8BC667DEF6F62E2
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti19R → T in AAN64588 (PubMed:12504858).Curated1
Sequence conflicti40 – 41ND → KY in AAN64588 (PubMed:12504858).Curated2
Sequence conflicti63L → P in AAI00386 (PubMed:15489334).Curated1
Sequence conflicti123P → S in AAF61348 (PubMed:10657254).Curated1
Sequence conflicti574E → K in AAN64588 (PubMed:12504858).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF132850 mRNA Translation: AAF61348.1
AY134883
, AY134660, AY134880, AY134881, AY134882 Genomic DNA Translation: AAN64588.1
BC006778 mRNA Translation: AAH06778.1
BC048779 mRNA Translation: AAH48779.1
BC052420 mRNA Translation: AAH52420.2
BC100385 mRNA Translation: AAI00386.1
X64607 mRNA Translation: CAA45891.1
CCDSiCCDS23342.1
PIRiPN0481
RefSeqiNP_056621.4, NM_015806.5
NP_081694.1, NM_027418.2
XP_011241069.1, XM_011242767.2
UniGeneiMm.480076

Genome annotation databases

EnsembliENSMUST00000049355; ENSMUSP00000040315; ENSMUSG00000042688
ENSMUST00000168937; ENSMUSP00000129024; ENSMUSG00000042688
GeneIDi50772
KEGGimmu:50772
UCSCiuc009qsd.2 mouse

Similar proteinsi

Entry informationi

Entry nameiMK06_MOUSE
AccessioniPrimary (citable) accession number: Q61532
Secondary accession number(s): Q497T9
, Q6YKB0, Q7TT30, Q80XH5, Q922U4, Q9JLU6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: September 13, 2004
Last modified: May 23, 2018
This is version 150 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
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Main funding by: National Institutes of Health