Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Mitogen-activated protein kinase 6

Gene

MAPK6

Organism
Homo sapiens (Human)
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 (By similarity).By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mg2+By similarity

Activity 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

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

BRENDAi2.7.11.24 2681
ReactomeiR-HSA-5687128 MAPK6/MAPK4 signaling
SignaLinkiQ16659
SIGNORiQ16659

Protein family/group databases

MoonDBiQ16659 Predicted

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
MAP kinase isoform p97
Short name:
p97-MAPK
Gene namesi
Name:MAPK6
Synonyms:ERK3, PRKM6
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

EuPathDBiHostDB:ENSG00000069956.11
HGNCiHGNC:6879 MAPK6
MIMi602904 gene
neXtProtiNX_Q16659

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

Organism-specific databases

DisGeNETi5597
OpenTargetsiENSG00000069956
PharmGKBiPA30624

Chemistry databases

ChEMBLiCHEMBL5121

Polymorphism and mutation databases

BioMutaiMAPK6
DMDMi2499596

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001862571 – 721Mitogen-activated protein kinase 6Add BLAST721

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki1Peptide (Met-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei189Phosphoserine; by PAK1, PAK2 and PAK3Combined sources1 Publication1
Modified residuei386PhosphoserineCombined sources1
Modified residuei452PhosphoserineCombined sources1
Modified residuei556PhosphoserineCombined sources1
Modified residuei558PhosphoserineCombined sources1
Modified residuei665PhosphoserineCombined sources1
Modified residuei684PhosphoserineCombined sources1

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.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ16659
MaxQBiQ16659
PaxDbiQ16659
PeptideAtlasiQ16659
PRIDEiQ16659
ProteomicsDBi61018

PTM databases

iPTMnetiQ16659
PhosphoSitePlusiQ16659

Expressioni

Tissue specificityi

Highest expression in the skeletal muscle, followed by the brain. Also found in heart, placenta, lung, liver, pancreas, kidney and skin fibroblasts.

Gene expression databases

BgeeiENSG00000069956 Expressed in 240 organ(s), highest expression level in cerebellar vermis
CleanExiHS_MAPK6
GenevisibleiQ16659 HS

Organism-specific databases

HPAiCAB005184
HPA030262

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 similarity1 Publication

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi111583, 199 interactors
IntActiQ16659, 382 interactors
MINTiQ16659
STRINGi9606.ENSP00000261845

Chemistry databases

BindingDBiQ16659

Structurei

Secondary structure

1721
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ16659
SMRiQ16659
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ16659

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

Phylogenomic databases

eggNOGiKOG0660 Eukaryota
ENOG410XNY0 LUCA
GeneTreeiENSGT00910000144035
HOGENOMiHOG000233020
HOVERGENiHBG104376
InParanoidiQ16659
KOiK06855
OMAiSEHDWPI
OrthoDBiEOG091G03RQ
PhylomeDBiQ16659
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.

Q16659-1 [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 FPMDEPISSH PFHIEDEVDD ILLMDETHSH
360 370 380 390 400
IYNWERYHDC QFSEHDWPVH NNFDIDEVQL DPRALSDVTD EEEVQVDPRK
410 420 430 440 450
YLDGDREKYL EDPAFDTNYS TEPCWQYSDH HENKYCDLEC SHTCNYKTRS
460 470 480 490 500
SSYLDNLVWR ESEVNHYYEP KLIIDLSNWK EQSKEKSDKK GKSKCERNGL
510 520 530 540 550
VKAQIALEEA SQQLAGKERE KNQGFDFDSF IAGTIQLSSQ HEPTDVVDKL
560 570 580 590 600
NDLNSSVSQL ELKSLISKSV SQEKQEKGMA NLAQLEALYQ SSWDSQFVSG
610 620 630 640 650
GEDCFFINQF CEVRKDEQVE KENTYTSYLD KFFSRKEDTE MLETEPVEDG
660 670 680 690 700
KLGERGHEEG FLNNSGEFLF NKQLESIGIP QFHSPVGSPL KSIQATLTPS
710 720
AMKSSPQIPH QTYSSILKHL N
Length:721
Mass (Da):82,681
Last modified:November 1, 1996 - v1
Checksum:iDAA3AAA9B98BB31F
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti229K → R in BAG36392 (PubMed:14702039).Curated1
Sequence conflicti527F → L in BAG70115 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_042256290L → V2 PublicationsCorresponds to variant dbSNP:rs35697691Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X80692 mRNA Translation: CAA56709.1
L77964 mRNA Translation: AAA98769.1
AF420474 mRNA Translation: AAL17605.1
AK313633 mRNA Translation: BAG36392.1
CR749401 mRNA Translation: CAH18246.1
AB451301 mRNA Translation: BAG70115.1
BC035492 mRNA Translation: AAH35492.1
CCDSiCCDS10147.1
PIRiA56352
RefSeqiNP_002739.1, NM_002748.3
XP_005254594.1, XM_005254537.2
XP_005254595.1, XM_005254538.2
XP_005254596.1, XM_005254539.3
XP_011520084.1, XM_011521782.1
UniGeneiHs.411847

Genome annotation databases

EnsembliENST00000261845; ENSP00000261845; ENSG00000069956
GeneIDi5597
KEGGihsa:5597
UCSCiuc002abp.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X80692 mRNA Translation: CAA56709.1
L77964 mRNA Translation: AAA98769.1
AF420474 mRNA Translation: AAL17605.1
AK313633 mRNA Translation: BAG36392.1
CR749401 mRNA Translation: CAH18246.1
AB451301 mRNA Translation: BAG70115.1
BC035492 mRNA Translation: AAH35492.1
CCDSiCCDS10147.1
PIRiA56352
RefSeqiNP_002739.1, NM_002748.3
XP_005254594.1, XM_005254537.2
XP_005254595.1, XM_005254538.2
XP_005254596.1, XM_005254539.3
XP_011520084.1, XM_011521782.1
UniGeneiHs.411847

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2I6LX-ray2.25A/B9-327[»]
ProteinModelPortaliQ16659
SMRiQ16659
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111583, 199 interactors
IntActiQ16659, 382 interactors
MINTiQ16659
STRINGi9606.ENSP00000261845

Chemistry databases

BindingDBiQ16659
ChEMBLiCHEMBL5121

Protein family/group databases

MoonDBiQ16659 Predicted

PTM databases

iPTMnetiQ16659
PhosphoSitePlusiQ16659

Polymorphism and mutation databases

BioMutaiMAPK6
DMDMi2499596

Proteomic databases

EPDiQ16659
MaxQBiQ16659
PaxDbiQ16659
PeptideAtlasiQ16659
PRIDEiQ16659
ProteomicsDBi61018

Protocols and materials databases

DNASUi5597
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000261845; ENSP00000261845; ENSG00000069956
GeneIDi5597
KEGGihsa:5597
UCSCiuc002abp.4 human

Organism-specific databases

CTDi5597
DisGeNETi5597
EuPathDBiHostDB:ENSG00000069956.11
GeneCardsiMAPK6
HGNCiHGNC:6879 MAPK6
HPAiCAB005184
HPA030262
MIMi602904 gene
neXtProtiNX_Q16659
OpenTargetsiENSG00000069956
PharmGKBiPA30624
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0660 Eukaryota
ENOG410XNY0 LUCA
GeneTreeiENSGT00910000144035
HOGENOMiHOG000233020
HOVERGENiHBG104376
InParanoidiQ16659
KOiK06855
OMAiSEHDWPI
OrthoDBiEOG091G03RQ
PhylomeDBiQ16659
TreeFamiTF105098

Enzyme and pathway databases

BRENDAi2.7.11.24 2681
ReactomeiR-HSA-5687128 MAPK6/MAPK4 signaling
SignaLinkiQ16659
SIGNORiQ16659

Miscellaneous databases

ChiTaRSiMAPK6 human
EvolutionaryTraceiQ16659
GeneWikiiMAPK6
GenomeRNAii5597
PROiPR:Q16659
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000069956 Expressed in 240 organ(s), highest expression level in cerebellar vermis
CleanExiHS_MAPK6
GenevisibleiQ16659 HS

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
ProtoNetiSearch...

Entry informationi

Entry nameiMK06_HUMAN
AccessioniPrimary (citable) accession number: Q16659
Secondary accession number(s): B2R945
, B5BU65, Q68DH4, Q8IYN8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: September 12, 2018
This is version 174 of the entry and version 1 of the sequence. See 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 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families
  4. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  7. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again