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Q61532

- MK06_MOUSE

UniProt

Q61532 - MK06_MOUSE

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
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    • History
      Entry version 126 (01 Oct 2014)
      Sequence version 3 (13 Sep 2004)
      Previous versions | rss
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    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 binding Source: MGI
    4. protein heterodimerization activity Source: UniProtKB
    5. protein kinase binding Source: UniProtKB

    GO - Biological processi

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

    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

    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

    ArrayExpressiQ61532.
    BgeeiQ61532.
    CleanExiMM_MAPK6.
    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_dom.
    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.

    Q61532-1 [UniParc]FASTAAdd to Basket

    « Hide

    MAEKFESLMN IHGFDLGSRY MDLKPLGCGG NGLVFSAVDN DCDKRVAIKK    50
    IVLTDPQSVK HALREIKIIR RLDHDNIVKV FEILGPSGSQ LTDDVGSLTE 100
    LNSVYIVQEY METDLANVLE QGPLLEEHAR LFMYQLLRGL KYIHSANVLH 150
    RDLKPANLFI NTEDLVLKIG DFGLARIMDP HYSHKGHLSE GLVTKWYRSP 200
    RLLLSPNNYT KAIDMWAAGC IFAEMLTGKT LFAGAHELEQ MQLILDSIPV 250
    VHEEDRQELL SVIPVYIRND MTEPHRPLTQ LLPGISREAL DFLEQILTFS 300
    PMDRLTAEEA LSHPYMSIYS FPTDEPISSH PFHIEDEVDD ILLMDETHSH 350
    IYNWERYHDC QFSEHDWPIH NNFDIDEVQL DPRALSDVTD EEEVQVDPRK 400
    YLDGDREKYL EDPAFDTSYS AEPCWQYPDH HENKYCDLEC SHTCNYKTRS 450
    SPYLDNLVWR ESEVNHYYEP KLIIDLSNWK EQSKEKSDKR GKSKCERNGL 500
    VKAQIALEEA SQQLAERERG QGFDFDSFIA GTIQLSAQHQ SADVVDKLND 550
    LNSSVSQLEL KSLISKSVSR EKQEKGRANL AQLGALYQSS WDSQFVSGGE 600
    ECFLISQFCC EVRKDEHAEK ENTYTSYLDK FFSRKEDSEM LETEPVEEGK 650
    RGERGREAGL LSGGGEFLLS KQLESIGTPQ FHSPVGSPLK SIQATLTPSA 700
    MKSSPQIPHK TYSSILKHLN 720
    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

    ArrayExpressi Q61532.
    Bgeei Q61532.
    CleanExi MM_MAPK6.
    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_dom.
    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

    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 1, 2014
    This is version 126 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