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MKNK2 MAPK interacting serine/threonine kinase 2 [ Homo sapiens (human) ]

Gene ID: 2872, updated on 27-Nov-2024

Summary

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Official Symbol
MKNK2provided by HGNC
Official Full Name
MAPK interacting serine/threonine kinase 2provided by HGNC
Primary source
HGNC:HGNC:7111
See related
Ensembl:ENSG00000099875 MIM:605069; AllianceGenome:HGNC:7111
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
MNK2; GPRK7
Summary
This gene encodes a member of the calcium/calmodulin-dependent protein kinases (CAMK) Ser/Thr protein kinase family, which belongs to the protein kinase superfamily. This protein contains conserved DLG (asp-leu-gly) and ENIL (glu-asn-ile-leu) motifs, and an N-terminal polybasic region which binds importin A and the translation factor scaffold protein eukaryotic initiation factor 4G (eIF4G). This protein is one of the downstream kinases activated by mitogen-activated protein (MAP) kinases. It phosphorylates the eukaryotic initiation factor 4E (eIF4E), thus playing important roles in the initiation of mRNA translation, oncogenic transformation and malignant cell proliferation. In addition to eIF4E, this protein also interacts with von Hippel-Lindau tumor suppressor (VHL), ring-box 1 (Rbx1) and Cullin2 (Cul2), which are all components of the CBC(VHL) ubiquitin ligase E3 complex. Multiple alternatively spliced transcript variants have been found, but the full-length nature and biological activity of only two variants are determined. These two variants encode distinct isoforms which differ in activity and regulation, and in subcellular localization. [provided by RefSeq, Aug 2011]
Expression
Ubiquitous expression in esophagus (RPKM 52.7), bone marrow (RPKM 47.1) and 25 other tissues See more
Orthologs
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Genomic context

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See MKNK2 in Genome Data Viewer
Location:
19p13.3
Exon count:
14
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (2037471..2051244, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (2010542..2024317, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (2037470..2051243, complement)

Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124904610 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:1993311-1993811 Neighboring gene BTB domain containing 2 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:2012303-2012494 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9757 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9758 Neighboring gene uncharacterized LOC107985278 Neighboring gene OCT4-NANOG-H3K4me1 hESC enhancer GRCh37_chr19:2028556-2029190 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:2035637-2036137 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:2037698-2038472 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9759 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:2046519-2047019 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:2047523-2048180 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:2048181-2048837 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:2049495-2050151 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13640 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9761 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:2053416-2053640 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13641 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9762 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:2058351-2059250 Neighboring gene CRISPRi-validated cis-regulatory element chr19.488 Neighboring gene CRISPRi-validated cis-regulatory element chr19.489 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:2061953-2062851 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13643 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13644 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13645 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13646 Neighboring gene MOB kinase activator 3A Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13647 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13648 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:2085331-2086056 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13650 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13651 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13652 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:2089069-2090031 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13654 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13655 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:2096431-2096958 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:2096959-2097484 Neighboring gene IZUMO family member 4

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Crystal structures of the Mnk2 kinase domain reveal an inhibitory conformation and a zinc binding site. Jauch R, et al. Structure, 2005 Oct. PMID 16216586
  2. The Mnks: MAP kinase-interacting kinases (MAP kinase signal-integrating kinases). Buxade M, et al. Front Biosci, 2008 May 1. PMID 18508592
  3. MAP kinase-interacting serine/threonine kinase 2 promotes proliferation, metastasis, and predicts poor prognosis in non-small cell lung cancer. Guo Z, et al. Sci Rep, 2017 Sep 6. PMID 28878291, Free PMC Article
  4. Modulation of MKNK2 alternative splicing by splice-switching oligonucleotides as a novel approach for glioblastoma treatment. Mogilevsky M, et al. Nucleic Acids Res, 2018 Nov 30. PMID 30329087, Free PMC Article
  5. Reciprocal signaling between mTORC1 and MNK2 controls cell growth and oncogenesis. Xie J, et al. Cell Mol Life Sci, 2021 Jan. PMID 32170339, Free PMC Article

See all (53) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. RBM25 depletion suppresses the growth of colon cancer cells through regulating alternative splicing of MNK2.
    Title: RBM25 depletion suppresses the growth of colon cancer cells through regulating alternative splicing of MNK2.
  2. MNK1 and MNK2 Expression in the Human Dorsal Root and Trigeminal Ganglion.
    Title: MNK1 and MNK2 Expression in the Human Dorsal Root and Trigeminal Ganglion.
  3. SRPK1/2 and PP1alpha exert opposite functions by modulating SRSF1-guided MKNK2 alternative splicing in colon adenocarcinoma.
    Title: SRPK1/2 and PP1α exert opposite functions by modulating SRSF1-guided MKNK2 alternative splicing in colon adenocarcinoma.
  4. MNK1 and MNK2 enforce expression of E2F1, FOXM1, and WEE1 to drive soft tissue sarcoma.
    Title: MNK1 and MNK2 enforce expression of E2F1, FOXM1, and WEE1 to drive soft tissue sarcoma.
  5. MKNK2 enhances chemoresistance of ovarian cancer by suppressing autophagy via miR-125b.
    Title: MKNK2 enhances chemoresistance of ovarian cancer by suppressing autophagy via miR-125b.
  6. Reciprocal signaling between mTORC1 and MNK2 controls cell growth and oncogenesis.
    Title: Reciprocal signaling between mTORC1 and MNK2 controls cell growth and oncogenesis.
  7. Induction of Mnk2a by splice switching oligonucleotides in glioblastoma cells activated the p38-MAPK pathway, inhibited the oncogenic properties of the cells, re-sensitized the cells to chemotherapy and inhibited glioblastoma development in vivo
    Title: Modulation of MKNK2 alternative splicing by splice-switching oligonucleotides as a novel approach for glioblastoma treatment.
  8. We conclude that MNK2 overexpression in NSCLC is associated with proliferation, migration, invasion, and lower survival rates in patients via the phosphorylated eIF4E-mediated signaling pathway.
    Title: MAP kinase-interacting serine/threonine kinase 2 promotes proliferation, metastasis, and predicts poor prognosis in non-small cell lung cancer.
  9. Data show that galeterone (gal) and VNPT55 inhibit migration and invasion of prostate cancer cells, possibly by down-regulating protein expression via antagonizing the Mnk1/2-eIF4E axis.
    Title: Galeterone and VNPT55 disrupt Mnk-eIF4E to inhibit prostate cancer cell migration and invasion.
  10. Data suggest MNK1/MNK2 stimulate mRNA translation but only of mRNA containing both 5-prime-terminal cap and hairpin duplex; this stimulation involves up-regulation of phosphorylation/mRNA un-winding activity of eIF4E (via decreased binding to eIF4G).
    Title: Inhibition of Mitogen-activated Protein Kinase (MAPK)-interacting Kinase (MNK) Preferentially Affects Translation of mRNAs Containing Both a 5'-Terminal Cap and Hairpin.
Submit: New GeneRIF Correction See all GeneRIFs (20)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Vpr vpr HIV-1 Vpr downregulates expression of genes involved in the MEK2-ERK pathway, including MAP2K2 (MEK2) and MKNK2, and overexpression of Vpr decreases phosphorylation of MEK2 PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables 3-phosphoinositide-dependent protein kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables AMP-activated protein kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables ATP binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables DNA-dependent protein kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables Rho-dependent protein serine/threonine kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables calcium-dependent protein serine/threonine kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables calcium/calmodulin-dependent protein kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables calmodulin binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables eukaryotic translation initiation factor 2alpha kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables histone H2AS1 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables histone H2AS121 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables histone H2AT120 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables histone H2AXS139 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables histone H2BS14 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables histone H2BS36 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables histone H3S10 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables histone H3S28 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables histone H3S57 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables histone H3T11 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables histone H3T3 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables histone H3T45 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables histone H3T6 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables histone H4S1 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein serine kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables protein serine/threonine kinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables ribosomal protein S6 kinase activity IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in cell surface receptor signaling pathway TAS
Traceable Author Statement
more info
 PubMed 
involved_in cellular response to arsenic-containing substance IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in chromatin remodeling IEA
Inferred from Electronic Annotation
more info
  
involved_in extrinsic apoptotic signaling pathway in absence of ligand IEA
Inferred from Electronic Annotation
more info
  
involved_in hemopoiesis IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in intracellular signal transduction IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in intracellular signal transduction IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein phosphorylation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of translation IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in PML body IEA
Inferred from Electronic Annotation
more info
  
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in nuclear body IDA
Inferred from Direct Assay
more info
  
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  
is_active_in nucleus IBA
Inferred from Biological aspect of Ancestor
more info
  

General protein information

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Preferred Names
MAP kinase-interacting serine/threonine-protein kinase 2
Names
G protein-coupled receptor kinase 7
MAP kinase interacting serine/threonine kinase 2
MAP kinase signal-integrating kinase 2
MAPK signal-integrating kinase 2
NP_060042.2
NP_951009.1

NCBI Reference Sequences (RefSeq)

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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_029798.1 RefSeqGene

    Range
    5001..18774
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_017572.4 → NP_060042.2  MAP kinase-interacting serine/threonine-protein kinase 2 isoform 1

    See identical proteins and their annotated locations for NP_060042.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) differs in the 3' exon including 3' coding region and 3' UTR, compared to variant 2. The resulting protein (isoform 1, also known as isoform b) has a shorter and distinct C-terminus, compared to isoform 2. This isoform is found in the nucleus and lacks the MAP kinase-binding region.
    Source sequence(s)
    AL137615, BC073140, DA950743
    Consensus CDS
    CCDS12079.1
    UniProtKB/TrEMBL
    A4CYL7
    Related
    ENSP00000309485.6, ENST00000309340.11
    Conserved Domains (2) summary
    smart00220
    Location:83 → 368
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cd14173
    Location:81 → 368
    STKc_Mnk2; Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase signal-integrating kinase 2

  2. NM_199054.3 → NP_951009.1  MAP kinase-interacting serine/threonine-protein kinase 2 isoform 2

    See identical proteins and their annotated locations for NP_951009.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) is the longer transcript and it encodes the longer protein (isoform 2, also known as isoform a), which is located in the cytoplasm and has an MAP kinase-binding region at the C-terminus.
    Source sequence(s)
    AK092536, AL137615, BC073140, DA950743
    Consensus CDS
    CCDS12080.1
    UniProtKB/Swiss-Prot
    Q6GPI3, Q9HBH8, Q9HBH9, Q9UHR0, Q9Y2N6
    UniProtKB/TrEMBL
    A4CYL7
    Related
    ENSP00000250896.3, ENST00000250896.9
    Conserved Domains (2) summary
    smart00220
    Location:83 → 368
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cd14173
    Location:81 → 368
    STKc_Mnk2; Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase signal-integrating kinase 2

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000019.10 Reference GRCh38.p14 Primary Assembly

    Range
    2037471..2051244 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060943.1 Alternate T2T-CHM13v2.0

    Range
    2010542..2024317 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9HBH9.3 GenPept UniProtKB/Swiss-Prot:Q9HBH9

Gene LinkOut

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Chemical Information
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