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    MKNK1 MAP kinase interacting serine/threonine kinase 1 [ Homo sapiens ]

    Gene ID: 8569, updated on 11-May-2012
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    Summary

    Official Symbol
    MKNK1provided by HGNC
    Official Full Name
    MAP kinase interacting serine/threonine kinase 1provided by HGNC
    Primary source
    HGNC:7110
    Locus tag
    RP11-49P4.3
    See related
    Ensembl:ENSG00000079277; HPRD:09468; MIM:606724; Vega:OTTHUMG00000007983
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    MNK1
    Summary
    This gene encodes a Ser/Thr protein kinase that interacts with, and is activated by ERK1 and p38 mitogen-activated protein kinases, and thus may play a role in the response to environmental stress and cytokines. This kinase may also regulate transcription by phosphorylating eIF4E via interaction with the C-terminal region of eIF4G. Alternatively spliced transcript variants have been noted for this gene. [provided by RefSeq, Jan 2012]
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    Genomic context

    Location :
    1p33
    Sequence :
    Chromosome: 1; NC_000001.10 (47023090..47069966, complement)
    See MKNK1 in Epigenomics, MapViewer

    Chromosome 1 - NC_000001.10Genomic Context describing neighboring genes Neighboring gene diencephalon/mesencephalon homeobox 1 Neighboring gene uncharacterized LOC100507423 Neighboring gene kinocilin Neighboring gene MOB kinase activator 3C Neighboring gene ATP synthase mitochondrial F1 complex assembly factor 1

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    Genomic regions, transcripts, and products

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details
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    Bibliography

    Related articles in PubMed

    1. MNK1 expression increases during cellular senescence and modulates the subcellular localization of hnRNP A1. Ziaei S, et al. Exp Cell Res, 2012 Mar 10. PMID 22227431.
    2. Simultaneous inhibition of mTOR-containing complex 1 (mTORC1) and MNK induces apoptosis of cutaneous T-cell lymphoma (CTCL) cells. Marzec M, et al. PLoS One, 2011. PMID 21949767.
    3. A directed protein interaction network for investigating intracellular signal transduction. Vinayagam A, et al. Sci Signal, 2011 Sep 6. PMID 21900206.
    4. Phosphorylation of eukaryotic translation initiation factor 4G1 (eIF4G1) by protein kinase C{alpha} regulates eIF4G1 binding to Mnk1. Dobrikov M, et al. Mol Cell Biol, 2011 Jul. PMID 21576361.
    5. MAP kinase-interacting kinase 1 regulates SMAD2-dependent TGF-β signaling pathway in human glioblastoma. Grzmil M, et al. Cancer Res, 2011 Mar 15. PMID 21406405.

    See all (41) citations in PubMed

    See citations in PubMed for homologs of this gene provided by HomoloGene

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. These data suggest that MNK1 regulates the phosphorylation and the subcellular distribution of hnRNP A1 and that MNK1 may play a role in the induction of senescence
      Title: MNK1 expression increases during cellular senescence and modulates the subcellular localization of hnRNP A1.
    2. These findings indicate that the combined inhibition of mTORC1 and MNK may prove beneficial in the treatment of cutaneous T-cell lymphoma and other malignancies.
      Title: Simultaneous inhibition of mTOR-containing complex 1 (mTORC1) and MNK induces apoptosis of cutaneous T-cell lymphoma (CTCL) cells.
    3. Data show that PKCalpha activation elicits a cascade of orchestrated phosphorylation events that may modulate eIF4G1 structure and control interaction with the eIF4E kinase, Mnk1.
      Title: Phosphorylation of eukaryotic translation initiation factor 4G1 (eIF4G1) by protein kinase C{alpha} regulates eIF4G1 binding to Mnk1.
    4. Findings offer insights into how MNK1 pathways control translation of cancer-related mRNAs including SMAD2, a key component of the TGF-beta signaling pathway.
      Title: MAP kinase-interacting kinase 1 regulates SMAD2-dependent TGF-β signaling pathway in human glioblastoma.
    5. siRNA-mediated Mnk1/2 knockdown results in partial reversal of the suppressive effects of IFNgamma on human CD34+-derived myeloid (CFU-GM) and erythroid (BFU-E) progenitors.
      Title: Essential role for Mnk kinases in type II interferon (IFNgamma) signaling and its suppressive effects on normal hematopoiesis.
    6. Data suggest that a proportion of breast cancers could be sensitive to inhibiting MNK kinase activity, and that the presence of phosphorylated eIF4E could provide a biomarker for the identification of responsive tumours.
      Title: The role of MNK proteins and eIF4E phosphorylation in breast cancer cell proliferation and survival.
    7. Observational study of gene-disease association, gene-gene interaction, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
      Title: Genetic variants within the MAP kinase signalling network and anti-TNF treatment response in rheumatoid arthritis patients.
    8. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
      Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
    9. A conserved phenylalanine residue in an Mnk-specific insert is playing a key role in governing the ease with which Mnk1a can be phosphorylated.
      Title: The C-terminal domain of Mnk1a plays a dual role in tightly regulating its activity.
    10. mTOR inhibition increases eIF4E phosphorylation through a PI3K-dependent and Mnk-mediated mechanism.
      Title: Inhibition of mammalian target of rapamycin induces phosphatidylinositol 3-kinase-dependent and Mnk-mediated eukaryotic translation initiation factor 4E phosphorylation.
    Submit: New GeneRIF Correction See all (18)
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    Phenotypes

    Review eQTL and phenotype association data in this region using PheGenI

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    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    BAA19885.1 NP_001959.1 EIF4E    BIND  PubMed EIF4E interacts with Mnk1. This interaction was modeled on a demonstrated interaction between mouse eIF4E and human Mnk1. 
    BAA19885.1 NP_004944.2 EIF4G1    BIND  PubMed Mnk1 interacts with eIF4G1. 
    BAA19885.1 MAPK14    BIND  PubMed An unspecified isoform of p38 interacts with and phosphorylates MNK1. 
    BAA19885.1 NP_002737.1 MAPK3    BIND  PubMed ERK1 interacts with and phosphorylates MNK1. 
    Q9BUB5 P06730 EIF4E    HPRD  PubMed  
    Q9BUB5 Q04637 EIF4G1    HPRD  PubMed  
    Q9BUB5 P78344 EIF4G2    HPRD  PubMed  
    Q9BUB5 O43432 EIF4G3    HPRD  PubMed  
    Q9BUB5 P28482 MAPK1    HPRD  PubMed  
    Q9BUB5 Q16539 MAPK14    HPRD  PubMed  
    Q9BUB5 P27361 MAPK3    HPRD  PubMed  
    Q9BUB5 P02686 MBP    HPRD  PubMed  
    Q9BUB5 Q9BUB5 MKNK1    HPRD  PubMed  
    Q9BUB5 Q13177 PAK2    HPRD  PubMed  
    Q9BUB5 P47712 PLA2G4A    HPRD  PubMed  
    BioGRID:114138 BioGRID:110433 ATXN3    BioGRID  PubMed Two-hybrid 
    BioGRID:114138 BioGRID:107777 CREBBP    BioGRID  PubMed Two-hybrid 
    BioGRID:114138 BioGRID:117107 DDAH2    BioGRID  PubMed Two-hybrid 
    BioGRID:114138 BioGRID:113117 DNAJC7    BioGRID  PubMed Two-hybrid 
    BioGRID:114138 BioGRID:108292 EIF4E    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:114138 BioGRID:108296 EIF4G1    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:114138 BioGRID:108297 EIF4G2    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:114138 BioGRID:114220 EIF4G3    BioGRID  PubMed Two-hybrid 
    BioGRID:114138 BioGRID:108472 FANCA    BioGRID  PubMed Two-hybrid 
    BioGRID:114138 BioGRID:109558 HSP90AB1    BioGRID  PubMed Two-hybrid 
    BioGRID:114138 BioGRID:111580 MAPK1    BioGRID  PubMed Reconstituted Complex; Two-hybrid 
    BioGRID:114138 BioGRID:107819 MAPK14    BioGRID  PubMed Affinity Capture-Western; Two-hybrid 
    BioGRID:114138 BioGRID:111581 MAPK3    BioGRID  PubMed Biochemical Activity 
    BioGRID:114138 BioGRID:119734 PHAX    BioGRID  PubMed Two-hybrid 
    NP_077734.1 PLA2G4A    BIND  PubMed An unspecified isoform of MNK1 phosphorylates cPLA2. 
    BioGRID:114138 BioGRID:111577 PRKDC    BioGRID  PubMed Two-hybrid 
    BioGRID:114138 BioGRID:113169 UBE2D1    BioGRID  PubMed Two-hybrid 
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    General gene information

    Markers

    Genotypes

    Homology

    Pathways from BioSystems

    • IL-2 Signaling Pathway, organism-specific biosystem (from WikiPathways)
      IL-2 Signaling Pathway, organism-specific biosystemInterleukin-2 belongs to a family of cytokines, which includes IL-4, IL-7, IL-9, IL-15 and IL-21. IL-2 signals through a receptor complex consisting of IL-2 specific IL-2 receptor alpha (CD25), IL-2 ...
    • Insulin signaling pathway, organism-specific biosystem (from KEGG)
      Insulin signaling pathway, organism-specific biosystemInsulin binding to its receptor results in the tyrosine phosphorylation of insulin receptor substrates (IRS) by the insulin receptor tyrosine kinase (INSR). This allows association of IRSs with the r...
    • Insulin signaling pathway, conserved biosystem (from KEGG)
      Insulin signaling pathway, conserved biosystemInsulin binding to its receptor results in the tyrosine phosphorylation of insulin receptor substrates (IRS) by the insulin receptor tyrosine kinase (INSR). This allows association of IRSs with the r...
    • MAPK signaling pathway, organism-specific biosystem (from KEGG)
      MAPK signaling pathway, organism-specific biosystemThe mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals e...
    • MAPK signaling pathway, conserved biosystem (from KEGG)
      MAPK signaling pathway, conserved biosystemThe mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals e...
    • Negative regulation of FGFR signaling, organism-specific biosystem (from REACTOME)
      Negative regulation of FGFR signaling, organism-specific biosystemOnce activated, the FGFR signaling pathway is regulated by numerous negative feedback mechanisms. These include downregulation of receptors through CBL-mediated ubiquitination and endocytosis, ERK-m...
    • Signal Transduction, organism-specific biosystem (from REACTOME)
      Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
    • Signaling by FGFR, organism-specific biosystem (from REACTOME)
      Signaling by FGFR, organism-specific biosystemThe 22 members of the fibroblast growth factor (FGF) family of growth factors mediate their cellular responses by binding to and activating the different isoforms encoded by the four receptor tyrosin...
    • Signaling mediated by p38-alpha and p38-beta, organism-specific biosystem (from Pathway Interaction Database)
      Signaling mediated by p38-alpha and p38-beta, organism-specific biosystem
      Signaling mediated by p38-alpha and p38-beta
    • Spry regulation of FGF signaling, organism-specific biosystem (from REACTOME)
      Spry regulation of FGF signaling, organism-specific biosystemSprouty was initially characterized as a negative regulator of FGFR signaling in Drosophila. Human cells contain four genes encoding Sprouty proteins, of which Spry2 is the best studied and most wid...
    • p38 MAPK Signaling Pathway, organism-specific biosystem (from WikiPathways)
      p38 MAPK Signaling Pathway, organism-specific biosystemp38 MAPKs are members of the MAPK family that are activated by a variety of environmental stresses and inflammatory cytokines. Stress signals are delivered to this cascade by members of small GTPases...

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    ATP binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    nucleotide binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    protein serine/threonine kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    protein serine/threonine kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    fibroblast growth factor receptor signaling pathway TAS
    Traceable Author Statement
    more info
    		  
    intracellular protein kinase cascade IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    peptidyl-serine phosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    protein phosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    regulation of translation IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    cytoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  
    cytosol TAS
    Traceable Author Statement
    more info
    		  
    nucleus IEA
    Inferred from Electronic Annotation
    more info
    		  
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    General protein information

    Preferred Names
    MAP kinase-interacting serine/threonine-protein kinase 1
    Names
    MAP kinase-interacting serine/threonine-protein kinase 1
    MAPK signal-integrating kinase 1
    MAP kinase signal-integrating kinase 1
    NP_001129025.1
    NP_003675.2
    NP_945324.1
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    NCBI Reference Sequences (RefSeq)

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_032029.1 RefSeqGene

      Range
      5001..51888
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001135553.2 → NP_001129025.1  MAP kinase-interacting serine/threonine-protein kinase 1 isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks an in-frame coding exon compared to variant 1. This results in a shorter isoform (3) missing an internal protein segment compared to isoform 1.
      Source sequence(s)
      AB000409, BC002755, BG722049, BM665342, DA502363
      Consensus CDS
      CCDS44134.1
      UniProtKB/Swiss-Prot
      Q9BUB5
      Related
      ENSP00000361013, OTTHUMP00000009677, ENST00000371945, OTTHUMT00000021900
      Conserved Domains (2) summary
      smart00220
      Location:53 – 333
      Blast Score: 706
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cl09925
      Location:55 – 332
      Blast Score: 532
      PKc_like; Protein Kinases, catalytic domain

    2. NM_003684.5 → NP_003675.2  MAP kinase-interacting serine/threonine-protein kinase 1 isoform 1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1).
      Source sequence(s)
      BC002755, BG722049, BM665342, DA435648, DC366212
      Consensus CDS
      CCDS538.1
      UniProtKB/Swiss-Prot
      Q9BUB5
      Related
      ENSP00000361014, OTTHUMP00000009674, ENST00000371946, OTTHUMT00000021897
      Conserved Domains (2) summary
      smart00220
      Location:53 – 374
      Blast Score: 664
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cl09925
      Location:55 – 373
      Blast Score: 486
      PKc_like; Protein Kinases, catalytic domain

    3. NM_198973.3 → NP_945324.1  MAP kinase-interacting serine/threonine-protein kinase 1 isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks two coding exons, and uses an alternate donor splice site at the 5' non-coding exon compared to variant 1. The second missing exon results in a frame-shift, and a shorter isoform (2) with a distinct C-terminus compared to isoform 1.
      Source sequence(s)
      AK290456, BC002755, BG722049, BM665342, DC376088
      Consensus CDS
      CCDS30705.1
      UniProtKB/TrEMBL
      A8K341
      UniProtKB/Swiss-Prot
      Q9BUB5
      Related
      ENSP00000411135, OTTHUMP00000231552, ENST00000428112, OTTHUMT00000387146
      Conserved Domains (2) summary
      smart00220
      Location:53 – 333
      Blast Score: 700
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cl09925
      Location:55 – 332
      Blast Score: 527
      PKc_like; Protein Kinases, catalytic domain

    RNA

    1. NR_024174.2 RNA Sequence

      Description
      Transcript Variant: This variant (4) lacks three non-consecutive exons compared to variant 1. It is represented as non-coding due to the presence of an upstream ORF that is predicted to interfere with the translation of the longest ORF; translation of the upstream ORF renders this transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AK298839, BC002755, BG722049, BM665342

    2. NR_024176.2 RNA Sequence

      Description
      Transcript Variant: This variant (6) contains an additional exon, and lacks two non-consecutive exons compared to variant 1. It is represented as non-coding due to the presence of an upstream ORF that is predicted to interfere with the translation of the longest ORF; translation of the upstream ORF renders this transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AB000409, AK096423, BG722049, BM665342, BX538193

    RefSeqs of Annotated Genomes: Build 37.3

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh37.p5 Primary Assembly

    Genomic

    1. NC_000001.10 Reference GRCh37.p5 Primary Assembly

      Range
      47023090..47069966, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000133.1 Alternate HuRef

      Range
      45138610..45185470, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NR_024175.1: Suppressed sequence

      Description
      NR_024175.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript.
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    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AL136373.21 CAI14762.1
      CAI14763.1
      CAI14764.1
      CAI14765.1
    genomic CH471059.2 EAX06900.1
      EAX06901.1
      EAX06902.1
      EAX06903.1
      EAX06904.1
      EAX06905.1
    mRNA AB000409.1 BAA19885.1
    mRNA AB451300.1 BAG70114.1
    mRNA AB451432.1 BAG70246.1
    mRNA AK096423.1 BAG53286.1
    mRNA AK290456.1 BAF83145.1
    mRNA AK298839.1 BAG60967.1
    mRNA AK304005.1 BAG64921.1
    mRNA AK310566.1 None
    mRNA AY355461.1 AAQ84219.1
    mRNA BC002755.2 AAH02755.1
    mRNA BG722049.1 None
    mRNA BM665342.1 None
    mRNA BX538193.1 CAD98062.1
    mRNA BX648559.1 None
    mRNA DA435648.1 None
    mRNA DA502363.1 None
    mRNA DC366212.1 None
    mRNA DC376088.1 None
    other-genetic DQ892992.2 ABM83918.1
    other-genetic DQ896240.2 ABM87239.1
    other-genetic EU831624.1 ACE87224.1
    other-genetic EU831709.1 ACE86543.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q5TC08 GenPept UniProtKB/TrEMBL:Q5TC08
    Q7Z319 GenPept UniProtKB/TrEMBL:Q7Z319
    Q9BUB5.1 GenPept UniProtKB/Swiss-Prot:Q9BUB5
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    Additional Links

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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