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Q61532

- MK06_MOUSE

UniProt

Q61532 - MK06_MOUSE

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Protein

Mitogen-activated protein kinase 6

Gene

Mapk6

Organism
Mus musculus (Mouse)
Status
Reviewed - 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.2 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Magnesium.By similarity

Enzyme regulationi

Activated by phosphorylation at Ser-189.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei49 – 491ATPPROSITE-ProRule annotation
Active sitei152 – 1521Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi26 – 349ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. MAP kinase activity Source: UniProtKB
  3. protein heterodimerization activity Source: UniProtKB
  4. protein kinase binding Source: UniProtKB

GO - Biological processi

  1. cell cycle Source: UniProtKB-KW
  2. MAPK cascade Source: GOC
  3. protein phosphorylation Source: UniProtKB
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. 3474.

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 9

Organism-specific databases

MGIiMGI:1354946. Mapk6.

Subcellular locationi

Cytoplasm. Nucleus
Note: Translocates to the cytoplasm following interaction with MAPKAPK5.

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi171 – 1711D → A: Kinase defective mutant, abolishes activity. 1 Publication
Mutagenesisi189 – 1891S → A: Unable to activate MAPKAPK5 promote MAPKAPK5 localization to the cytoplasm. 2 Publications
Mutagenesisi189 – 1891S → E: Mimicks phosphorylation state and induces constitutive protein kinase activity. 2 Publications
Mutagenesisi334 – 3341I → K: Abolishes binding to MAPKAPK5. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 720720Mitogen-activated protein kinase 6PRO_0000186258Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Cross-linki1 – 1Peptide (Met-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei189 – 1891Phosphoserine; by PAK1, PAK2 and PAK31 Publication

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

PaxDbiQ61532.
PRIDEiQ61532.

PTM databases

PhosphoSiteiQ61532.

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

BgeeiQ61532.
CleanExiMM_MAPK6.
ExpressionAtlasiQ61532. baseline and differential.
GenevestigatoriQ61532.

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

Protein-protein interaction databases

BioGridi206104. 4 interactions.

Structurei

3D structure databases

ProteinModelPortaliQ61532.
SMRiQ61532. Positions 13-341.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini20 – 316297Protein kinasePROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi189 – 1913SEG motif
Motifi332 – 3376FRIEDE motif

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

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00550000074298.
HOVERGENiHBG104376.
InParanoidiQ61532.
KOiK06855.
OMAiEHDWPIH.
OrthoDBiEOG780RKS.
PhylomeDBiQ61532.
TreeFamiTF105098.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR008350. MAPK_ERK3/4.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
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.

Q61532 [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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti19 – 191R → T in AAN64588. (PubMed:12504858)Curated
Sequence conflicti40 – 412ND → KY in AAN64588. (PubMed:12504858)Curated
Sequence conflicti63 – 631L → P in AAI00386. (PubMed:15489334)Curated
Sequence conflicti123 – 1231P → S in AAF61348. (PubMed:10657254)Curated
Sequence conflicti574 – 5741E → K in AAN64588. (PubMed:12504858)Curated

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.
UniGeneiMm.480076.

Genome annotation databases

EnsembliENSMUST00000049355; ENSMUSP00000040315; ENSMUSG00000042688.
ENSMUST00000168937; ENSMUSP00000129024; ENSMUSG00000042688.
GeneIDi50772.
KEGGimmu:50772.
UCSCiuc009qsd.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS23342.1.
PIRi PN0481.
RefSeqi NP_056621.4. NM_015806.5.
NP_081694.1. NM_027418.2.
UniGenei Mm.480076.

3D structure databases

ProteinModelPortali Q61532.
SMRi Q61532. Positions 13-341.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 206104. 4 interactions.

PTM databases

PhosphoSitei Q61532.

Proteomic databases

PaxDbi Q61532.
PRIDEi Q61532.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000049355 ; ENSMUSP00000040315 ; ENSMUSG00000042688 .
ENSMUST00000168937 ; ENSMUSP00000129024 ; ENSMUSG00000042688 .
GeneIDi 50772.
KEGGi mmu:50772.
UCSCi uc009qsd.1. mouse.

Organism-specific databases

CTDi 5597.
MGIi MGI:1354946. Mapk6.

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00550000074298.
HOVERGENi HBG104376.
InParanoidi Q61532.
KOi K06855.
OMAi EHDWPIH.
OrthoDBi EOG780RKS.
PhylomeDBi Q61532.
TreeFami TF105098.

Enzyme and pathway databases

BRENDAi 2.7.11.24. 3474.

Miscellaneous databases

ChiTaRSi MAPK6. mouse.
NextBioi 307695.
PROi Q61532.
SOURCEi Search...

Gene expression databases

Bgeei Q61532.
CleanExi MM_MAPK6.
ExpressionAtlasi Q61532. baseline and differential.
Genevestigatori Q61532.

Family and domain databases

InterProi IPR011009. Kinase-like_dom.
IPR008350. MAPK_ERK3/4.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view ]
Pfami PF00069. Pkinase. 1 hit.
[Graphical view ]
PRINTSi PR01771. ERK3ERK4MAPK.
SMARTi SM00220. S_TKc. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 1 hit.
PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning and characterization of mouse extracellular-signal-regulated protein kinase 3 as a unique gene product of 100 kDa."
    Turgeon B., Saba-El-Leil M.K., Meloche S.
    Biochem. J. 346:169-175(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], DEVELOPMENTAL STAGE.
    Tissue: Pituitary.
  2. "The protein kinase ERK3 is encoded by a single functional gene: genomic analysis of the ERK3 gene family."
    Turgeon B., Lang B.F., Meloche S.
    Genomics 80:673-680(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: 129/Sv.
  3. "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].
    Strain: C57BL/6 and Czech II.
    Tissue: Embryonic brain, Embryonic germ cell, Mammary tumor and Olfactory epithelium.
  4. "Novel CDC2-related protein kinases produced in murine hematopoietic stem cells."
    Ershler M.A., Nagorskaya T.V., Visser J.W.M., Belyavsky A.V.
    Gene 124:305-306(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 156-195.
    Strain: CBA.
    Tissue: Hematopoietic.
  5. Cited for: FUNCTION IN PHOSPHORYLATION OF MAPKAPK5, SUBCELLULAR LOCATION, INTERACTION WITH MAPKAPK5.
  6. "Activation of MK5/PRAK by the atypical MAP kinase ERK3 defines a novel signal transduction pathway."
    Seternes O.M., Mikalsen T., Johansen B., Michaelsen E., Armstrong C.G., Morrice N.A., Turgeon B., Meloche S., Moens U., Keyse S.M.
    EMBO J. 23:4780-4791(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF MAPKAPK5, SUBCELLULAR LOCATION, INTERACTION WITH MAPKAPK5, MUTAGENESIS OF ASP-171 AND SER-189.
  7. "Characterization of the atypical MAPK ERK4 and its activation of the MAPK-activated protein kinase MK5."
    Kant S., Schumacher S., Singh M.K., Kispert A., Kotlyarov A., Gaestel M.
    J. Biol. Chem. 281:35511-35519(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH MAPK4.
  8. "Activation loop phosphorylation of the atypical MAP kinases ERK3 and ERK4 is required for binding, activation and cytoplasmic relocalization of MK5."
    Deleris P., Rousseau J., Coulombe P., Rodier G., Tanguay P.L., Meloche S.
    J. Cell. Physiol. 217:778-788(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH MAPKAPK5, PHOSPHORYLATION AT SER-189, MUTAGENESIS OF SER-189.
  9. "Docking of PRAK/MK5 to the atypical MAPKs ERK3 and ERK4 defines a novel MAPK interaction motif."
    Aberg E., Torgersen K.M., Johansen B., Keyse S.M., Perander M., Seternes O.M.
    J. Biol. Chem. 284:19392-19401(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH MAPKAPK5, DOMAIN FRIEDE MOTIF, MUTAGENESIS OF ILE-334.

Entry informationi

Entry nameiMK06_MOUSE
AccessioniPrimary (citable) accession number: Q61532
Secondary accession number(s): Q497T9
, Q6YKB0, Q7TT30, Q80XH5, Q922U4, Q9JLU6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: September 13, 2004
Last modified: October 29, 2014
This is version 127 of the entry and version 3 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3