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Q5U2N4

- MKNK2_RAT

UniProt

Q5U2N4 - MKNK2_RAT

Protein

MAP kinase-interacting serine/threonine-protein kinase 2

Gene

Mknk2

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 4 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 91 (01 Oct 2014)
      Sequence version 1 (07 Dec 2004)
      Previous versions | rss
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    Functioni

    Serine/threonine-protein kinase that phosphorylates SFPQ/PSF, HNRNPA1 and EIF4E. May play a role in the response to environmental stress and cytokines. Appears to regulate translation by phosphorylating EIF4E, thus increasing the affinity of this protein for the 7-methylguanosine-containing mRNA cap. Required for mediating PP2A-inhibition-induced EIF4E phosphorylation. Triggers EIF4E shuttling from cytoplasm to nucleus. Enhances the formation of EIF4F complex in pachytene spermatocytes, thus promoting mRNA translation during spermatogenesis. Displays a high basal kinase activity. Acts as a mediator of the suppressive effects of IFNgamma on hematopoiesis. Negative regulator for signals that control generation of arsenic trioxide As2O(3)-dependent apoptosis and anti-leukemic responses. Involved in anti-apoptotic signaling in response to serum withdrawal By similarity.By similarity

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.

    Cofactori

    Magnesium.By similarity
    Binds 1 zinc ion per subunit.By similarity

    Enzyme regulationi

    Inhibited by CGP57380 and staurosporine.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei113 – 1131ATPPROSITE-ProRule annotation
    Active sitei205 – 2051Proton acceptorPROSITE-ProRule annotation
    Binding sitei209 – 2091StaurosporineBy similarity
    Metal bindingi299 – 2991ZincBy similarity
    Metal bindingi311 – 3111ZincBy similarity
    Metal bindingi314 – 3141ZincBy similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi90 – 989ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. metal ion binding Source: UniProtKB-KW
    3. protein serine/threonine kinase activity Source: UniProtKB-KW

    GO - Biological processi

    1. cellular response to arsenic-containing substance Source: Ensembl
    2. extrinsic apoptotic signaling pathway in absence of ligand Source: Ensembl
    3. hemopoiesis Source: Ensembl
    4. intracellular signal transduction Source: Ensembl
    5. regulation of translation Source: UniProtKB-KW

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Biological processi

    Apoptosis, Translation regulation

    Keywords - Ligandi

    ATP-binding, Magnesium, Metal-binding, Nucleotide-binding, Zinc

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    MAP kinase-interacting serine/threonine-protein kinase 2 (EC:2.7.11.1)
    Alternative name(s):
    MAP kinase signal-integrating kinase 2
    Short name:
    MAPK signal-integrating kinase 2
    Short name:
    Mnk2
    Gene namesi
    Name:Mknk2
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Chromosome 7

    Organism-specific databases

    RGDi1305728. Mknk2.

    Subcellular locationi

    Cytoplasm By similarity. NucleusPML body By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-SubCell
    2. PML body Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 459459MAP kinase-interacting serine/threonine-protein kinase 2PRO_0000226965Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei74 – 741PhosphoserineBy similarity
    Modified residuei244 – 2441PhosphothreonineBy similarity
    Modified residuei249 – 2491PhosphothreonineBy similarity
    Modified residuei379 – 3791PhosphothreonineBy similarity
    Modified residuei431 – 4311PhosphoserineBy similarity
    Modified residuei434 – 4341PhosphoserineBy similarity
    Modified residuei446 – 4461PhosphoserineBy similarity
    Modified residuei450 – 4501PhosphothreonineBy similarity

    Post-translational modificationi

    Dual phosphorylation of Thr-244 and Thr-249 activates the kinase. Phosphorylation of Thr-379 activates the kinase. Phosphorylated upon arsenic trioxide As2O3 treatment. Phosphorylated by MAPK1/ERK2, MAPK11 and MAPK14. Dephosphorylated by PP2A By similarity.By similarity

    Keywords - PTMi

    Phosphoprotein

    Expressioni

    Gene expression databases

    GenevestigatoriQ5U2N4.

    Interactioni

    Subunit structurei

    Monomer. Interacts with the C-terminal regions of EIF4G1 and EIF4G2; this interaction is promoted when MAPK pathways are repressed but repressed upon ERK proteins activation. Also binds to dephosphorylated MAPK3/ERK1 and MAPK1/ER2K. Interaction with phosphorylated MAPK3/ERK1 and MAPK1/ER2K protects it from dephosphorylation and inactivation. Interacts with ESR2 and EIF4E in the nucleus By similarity.By similarity

    Protein-protein interaction databases

    STRINGi10116.ENSRNOP00000039672.

    Structurei

    3D structure databases

    ProteinModelPortaliQ5U2N4.
    SMRiQ5U2N4. Positions 71-369.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini84 – 368285Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni160 – 1623Staurosporine bindingBy similarity

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi60 – 667Nuclear localization signalBy similarity
    Motifi438 – 4425MAP kinase bindingBy similarity

    Sequence similaritiesi

    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG0515.
    GeneTreeiENSGT00730000110339.
    HOGENOMiHOG000231140.
    HOVERGENiHBG106949.
    InParanoidiQ5U2N4.
    KOiK04372.
    OMAiVQKKTAE.
    OrthoDBiEOG7SV0VB.
    PhylomeDBiQ5U2N4.
    TreeFamiTF314050.

    Family and domain databases

    InterProiIPR011009. Kinase-like_dom.
    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]
    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.

    Q5U2N4-1 [UniParc]FASTAAdd to Basket

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    MVQKRTAELQ GFHRSFKGQN PFELAFTLDP AQHGDSDFSP QCEARPDMPS    50
    SQPIDIPDAK KRGRKKKRCR ATDSFSGRFE DVYQLQEDVL GEGAHARVQT 100
    CVNLITNQEY AVKIIEKQLG HIRSRVFREV EMLYQCQGHR NVLELIEFFE 150
    EEDRFYLVFE KMRGGSILSH IHRRRHFNEL EASVVVQDVA SALDFLHNKG 200
    IAHRDLKPEN ILCEHPNQVS PVKICDFDLG SGIKLNGDCS PISTPELLTP 250
    CGSAEYMAPE VVEAFSEEAS IYDKRCDLWS LGVILYILLS GYPPFVGHCG 300
    SDCGWDRGEA CPACQNMLFE SIQEGKYEFP DKDWSHISFA AKDLISKLLV 350
    RDAKQRLSAA QVLQHPWVQG CAPENTLPTP LVLQRNSCAK DLTSFAAEAI 400
    AMNRQLAQCE EDAGQDQPVL IRATSRCLQL SPPSQSKLAQ RRQRASLSAT 450
    PVVLVGDRV 459
    Length:459
    Mass (Da):51,574
    Last modified:December 7, 2004 - v1
    Checksum:i7D26909FB98AC34D
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    BC085941 mRNA. Translation: AAH85941.1.
    RefSeqiNP_001011985.1. NM_001011985.1.
    XP_006240945.1. XM_006240883.1.
    UniGeneiRn.231923.

    Genome annotation databases

    EnsembliENSRNOT00000041106; ENSRNOP00000039672; ENSRNOG00000029028.
    GeneIDi299618.
    KEGGirno:299618.
    UCSCiRGD:1305728. rat.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    BC085941 mRNA. Translation: AAH85941.1 .
    RefSeqi NP_001011985.1. NM_001011985.1.
    XP_006240945.1. XM_006240883.1.
    UniGenei Rn.231923.

    3D structure databases

    ProteinModelPortali Q5U2N4.
    SMRi Q5U2N4. Positions 71-369.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 10116.ENSRNOP00000039672.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSRNOT00000041106 ; ENSRNOP00000039672 ; ENSRNOG00000029028 .
    GeneIDi 299618.
    KEGGi rno:299618.
    UCSCi RGD:1305728. rat.

    Organism-specific databases

    CTDi 2872.
    RGDi 1305728. Mknk2.

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00730000110339.
    HOGENOMi HOG000231140.
    HOVERGENi HBG106949.
    InParanoidi Q5U2N4.
    KOi K04372.
    OMAi VQKKTAE.
    OrthoDBi EOG7SV0VB.
    PhylomeDBi Q5U2N4.
    TreeFami TF314050.

    Miscellaneous databases

    NextBioi 645528.
    PROi Q5U2N4.

    Gene expression databases

    Genevestigatori Q5U2N4.

    Family and domain databases

    InterProi IPR011009. Kinase-like_dom.
    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 ]
    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. "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].
      Tissue: Lung.

    Entry informationi

    Entry nameiMKNK2_RAT
    AccessioniPrimary (citable) accession number: Q5U2N4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: March 7, 2006
    Last sequence update: December 7, 2004
    Last modified: October 1, 2014
    This is version 91 of the entry and version 1 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. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3