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

Summary

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: mouse all
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Genomic context

Location:: 19p13.3

Exon count:: 14

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (2037471..2051244, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (2010542..2024317, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (2037470..2051243, complement)

Chromosome 19 - NC_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
Reciprocal signaling between mTORC1 and MNK2 controls cell growth and oncogenesis.
Title: Reciprocal signaling between mTORC1 and MNK2 controls cell growth and oncogenesis.
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.
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.
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.
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.
MNK1 and MNK2 inhibition ablates eIF4E1 phosphorylation and concurrently enhances eIF4E3 expression in diffuse large B-cell lymphoma.
Title: MNKs act as a regulatory switch for eIF4E1 and eIF4E3 driven mRNA translation in DLBCL.

Submit: New GeneRIF Correction See all GeneRIFs (19)

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

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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

D19S642E (e-PCR)
- UniSTS:150565

RH78432 (e-PCR)
- UniSTS:68270

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IDA Inferred from Direct Assay more info	PubMed
enables calcium-dependent protein serine/threonine kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables calmodulin binding	IBA Inferred from Biological aspect of Ancestor more info
enables calmodulin-dependent protein kinase activity	IBA Inferred from Biological aspect of Ancestor 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

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 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 peptidyl-serine phosphorylation	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein autophosphorylation	IBA Inferred from Biological aspect of Ancestor more info
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

EC 2.7.11.1

NP_951009.1

EC 2.7.11.1

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

NG_029798.1 RefSeqGene

Range

5001..18774

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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