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Protein

Mitogen-activated protein kinase 6

Gene

MAPK6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

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

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

BioCyciZFISH:HS00975-MONOMER.
BRENDAi2.7.11.24. 2681.
ReactomeiR-HSA-5687128. MAPK6/MAPK4 signaling.
SignaLinkiQ16659.
SIGNORiQ16659.

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

HGNCiHGNC:6879. 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

Pathology & Biotechi

Organism-specific databases

DisGeNETi5597.
OpenTargetsiENSG00000069956.
PharmGKBiPA30624.

Chemistry databases

ChEMBLiCHEMBL5121.
GuidetoPHARMACOLOGYi2092.

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.

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.
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

WithEntry#Exp.IntActNotes
EGLN3Q9H6Z96EBI-1384105,EBI-1175354
MAPKAPK5Q8IW417EBI-1384105,EBI-1201460
vifP125042EBI-1384105,EBI-779991From a different organism.

Protein-protein interaction databases

BioGridi111583. 193 interactors.
IntActiQ16659. 367 interactors.
MINTiMINT-8247530.
STRINGi9606.ENSP00000261845.

Chemistry databases

BindingDBiQ16659.

Structurei

Secondary structure

1721
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi14 – 16Combined sources3
Turni17 – 19Combined sources3
Beta strandi20 – 25Combined sources6
Beta strandi34 – 39Combined sources6
Turni40 – 42Combined sources3
Beta strandi45 – 52Combined sources8
Helixi56 – 70Combined sources15
Beta strandi80 – 84Combined sources5
Beta strandi102 – 109Combined sources8
Beta strandi112 – 114Combined sources3
Helixi115 – 119Combined sources5
Helixi126 – 145Combined sources20
Helixi155 – 157Combined sources3
Beta strandi158 – 161Combined sources4
Turni162 – 165Combined sources4
Beta strandi166 – 169Combined sources4
Helixi190 – 192Combined sources3
Helixi200 – 204Combined sources5
Helixi211 – 227Combined sources17
Helixi237 – 247Combined sources11
Helixi253 – 260Combined sources8
Helixi265 – 270Combined sources6
Helixi278 – 281Combined sources4
Helixi287 – 294Combined sources8
Helixi301 – 303Combined sources3
Helixi307 – 311Combined sources5
Helixi314 – 317Combined sources4

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...

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

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0660. Eukaryota.
ENOG410XNY0. LUCA.
GeneTreeiENSGT00550000074298.
HOGENOMiHOG000233020.
HOVERGENiHBG104376.
InParanoidiQ16659.
KOiK06855.
OMAiSEHDWPI.
OrthoDBiEOG091G03RQ.
PhylomeDBiQ16659.
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.

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 → V.2 PublicationsCorresponds to variant rs35697691dbSNPEnsembl.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

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. 193 interactors.
IntActiQ16659. 367 interactors.
MINTiMINT-8247530.
STRINGi9606.ENSP00000261845.

Chemistry databases

BindingDBiQ16659.
ChEMBLiCHEMBL5121.
GuidetoPHARMACOLOGYi2092.

PTM databases

iPTMnetiQ16659.
PhosphoSitePlusiQ16659.

Polymorphism and mutation databases

BioMutaiMAPK6.
DMDMi2499596.

Proteomic databases

EPDiQ16659.
MaxQBiQ16659.
PaxDbiQ16659.
PeptideAtlasiQ16659.
PRIDEiQ16659.

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.
GeneCardsiMAPK6.
HGNCiHGNC:6879. MAPK6.
HPAiCAB005184.
HPA030262.
MIMi602904. gene.
neXtProtiNX_Q16659.
OpenTargetsiENSG00000069956.
PharmGKBiPA30624.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0660. Eukaryota.
ENOG410XNY0. LUCA.
GeneTreeiENSGT00550000074298.
HOGENOMiHOG000233020.
HOVERGENiHBG104376.
InParanoidiQ16659.
KOiK06855.
OMAiSEHDWPI.
OrthoDBiEOG091G03RQ.
PhylomeDBiQ16659.
TreeFamiTF105098.

Enzyme and pathway databases

BioCyciZFISH:HS00975-MONOMER.
BRENDAi2.7.11.24. 2681.
ReactomeiR-HSA-5687128. MAPK6/MAPK4 signaling.
SignaLinkiQ16659.
SIGNORiQ16659.

Miscellaneous databases

ChiTaRSiMAPK6. human.
EvolutionaryTraceiQ16659.
GeneWikiiMAPK6.
GenomeRNAii5597.
PROiQ16659.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000069956.
CleanExiHS_MAPK6.
GenevisibleiQ16659. HS.

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_HUMAN
AccessioniPrimary (citable) accession number: Q16659
Secondary accession number(s): B2R945
, B5BU65, Q68DH4, Q8IYN8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: November 30, 2016
This is version 159 of the entry and version 1 of the sequence. [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. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. 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.