MAP2K4 mitogen-activated protein kinase kinase 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: MAP2K4provided by HGNC
Official Full Name: mitogen-activated protein kinase kinase 4provided by HGNC
Primary source: HGNC:HGNC:6844
See related: Ensembl:ENSG00000065559 MIM:601335; AllianceGenome:HGNC:6844
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: JNKK; MEK4; MKK4; SEK1; SKK1; JNKK1; SERK1; MAPKK4; PRKMK4; SAPKK1; SAPKK-1
Summary: This gene encodes a member of the mitogen-activated protein kinase (MAPK) family. Members of this family act as an integration point for multiple biochemical signals and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation, and development. They form a three-tiered signaling module composed of MAPKKKs, MAPKKs, and MAPKs. This protein is phosphorylated at serine and threonine residues by MAPKKKs and subsequently phosphorylates downstream MAPK targets at threonine and tyrosine residues. A similar protein in mouse has been reported to play a role in liver organogenesis. A pseudogene of this gene is located on the long arm of chromosome X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]
Expression: Ubiquitous expression in brain (RPKM 23.5), thyroid (RPKM 10.1) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 17p12

Exon count:: 15

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	17	NC_000017.11 (12020877..12143828)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	17	NC_060941.1 (11928859..12051837)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	17	NC_000017.10 (11924194..12047145)

Chromosome 17 - NC_000017.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

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?

Hsa_circ_0081069 facilitates tongue squamous cell carcinoma progression by modulating MAP2K4 expression via miR-634.
Title: Hsa_circ_0081069 facilitates tongue squamous cell carcinoma progression by modulating MAP2K4 expression via miR-634.
PCAT19 Regulates the Proliferation and Apoptosis of Lung Cancer Cells by Inhibiting miR-25-3p via Targeting the MAP2K4 Signal Axis.
Title: PCAT19 Regulates the Proliferation and Apoptosis of Lung Cancer Cells by Inhibiting miR-25-3p via Targeting the MAP2K4 Signal Axis.
Is there any correlation among MKK4 (mitogen-activated protein kinase kinase 4) expression, clinicopathological features, and KRAS/NRAS mutation in colorectal cancer.
Title: Is there any correlation among MKK4 (mitogen-activated protein kinase kinase 4) expression, clinicopathological features, and KRAS/NRAS mutation in colorectal cancer.
A new prognosis prediction model combining TNM stage with MAP2K4 and JNK in postoperative pancreatic cancer patients.
Title: A new prognosis prediction model combining TNM stage with MAP2K4 and JNK in postoperative pancreatic cancer patients.
Long noncoding RNA HNF1A-AS1 regulates proliferation and apoptosis of glioma through activation of the JNK signaling pathway via miR-363-3p/MAP2K4.
Title: Long noncoding RNA HNF1A-AS1 regulates proliferation and apoptosis of glioma through activation of the JNK signaling pathway via miR-363-3p/MAP2K4.
microRNA-124-3p inhibits tumourigenesis by targeting mitogen-activated protein kinase 4 in papillary thyroid carcinoma.
Title: microRNA-124-3p inhibits tumourigenesis by targeting mitogen-activated protein kinase 4 in papillary thyroid carcinoma.
MAP2K4 interacts with Vimentin to activate the PI3K/AKT pathway and promotes breast cancer pathogenesis.
Title: MAP2K4 interacts with Vimentin to activate the PI3K/AKT pathway and promotes breast cancer pathogenesis.
The ensemble structures provided more detailed mechanisms for regulating MAP2K4 in addition to those delineated only by the crystal structures in three states.
Title: Ensemble structural analyses depict the regulatory mechanism of non-phosphorylated human MAP2K4.
The initial characterization of tumor-suppressing kinases- in particular members of the protein kinase C (PKC) family, MKK4 of the mitogen-activated protein kinase kinase family, and DAPK3 of the death-associated protein kinase family- laid the foundation for bioinformatic approaches that enable the identification of other tumor-suppressing kinases.
Title: Orange is the new black: Kinases are the new master regulators of tumor suppression.
high MKK4 expression and its combination with high MKK7 expression both predicted favorable prognosis in resectable pancreatic ductal adenocarcinoma.
Title: Clinicopathological and prognostic significance of MKK4 and MKK7 in resectable pancreatic ductal adenocarcinoma.

Submit: New GeneRIF Correction See all GeneRIFs (104)

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

EBI GWAS Catalog

Description
Genome-wide association study of d-amphetamine response in healthy volunteers identifies putative associations, including cadherin 13 (CDH13). EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D11S2921 (e-PCR)
- UniSTS:152074

RH46488 (e-PCR)
- UniSTS:87850

D8S2278 (e-PCR)
- UniSTS:473906

D8S2279 (e-PCR)
- UniSTS:473907

RH48101 (e-PCR)
- UniSTS:55091

RH70575 (e-PCR)
- UniSTS:74809

SHGC-171541 (e-PCR)
- UniSTS:183105

L18426 (e-PCR)
- UniSTS:34648

SHGC-35988 (e-PCR)
- UniSTS:62560

D1S1423 (e-PCR)
- UniSTS:149619

RH12704 (e-PCR)
- UniSTS:43438

A003B48 (e-PCR)
- UniSTS:36273

MAP2K4_908 (e-PCR)
- UniSTS:277468

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables JUN kinase kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables JUN kinase kinase activity	TAS Traceable Author Statement more info
enables molecular adaptor activity	EXP Inferred from Experiment more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase activity	TAS Traceable Author Statement more info	PubMed
enables protein serine kinase activity	IEA Inferred from Electronic Annotation more info
enables protein serine/threonine kinase activity	IEA Inferred from Electronic Annotation more info
enables protein tyrosine kinase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in Fc-epsilon receptor signaling pathway	TAS Traceable Author Statement more info
involved_in JNK cascade	TAS Traceable Author Statement more info
involved_in MAPK cascade	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell growth involved in cardiac muscle cell development	IEA Inferred from Electronic Annotation more info
involved_in cellular response to mechanical stimulus	IEP Inferred from Expression Pattern more info	PubMed
involved_in cellular response to sorbitol	IEA Inferred from Electronic Annotation more info
involved_in cellular senescence	TAS Traceable Author Statement more info
involved_in intrinsic apoptotic signaling pathway in response to hydrogen peroxide	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of motor neuron apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in phosphorylation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of DNA replication	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of JNK cascade	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of neuron apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of nitric-oxide synthase biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of protein phosphorylation	IEA Inferred from Electronic Annotation more info
involved_in response to wounding	IEA Inferred from Electronic Annotation more info
involved_in signal transduction	TAS Traceable Author Statement more info	PubMed
involved_in smooth muscle cell apoptotic process	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in axon	IEA Inferred from Electronic Annotation more info
located_in cytosol	TAS Traceable Author Statement more info
located_in dendrite cytoplasm	IEA Inferred from Electronic Annotation more info
located_in nucleus	IEA Inferred from Electronic Annotation more info
located_in perikaryon	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: dual specificity mitogen-activated protein kinase kinase 4

Names: JNK-activated kinase 1; JNK-activating kinase 1; MAP kinase kinase 4; MAPK/ERK kinase 4; MAPKK 4; MEK 4; SAPK/ERK kinase 1; c-Jun N-terminal kinase kinase 1; c-Jun NH2-terminal kinase kinase 1; stress-activated protein kinase kinase 1

NP_001268364.1

EC 2.7.12.2

NP_003001.1

EC 2.7.12.2

XP_005256810.1

EC 2.7.12.2

XP_011522278.1

EC 2.7.12.2

XP_054172877.1

EC 2.7.12.2

XP_054172878.1

EC 2.7.12.2

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_033952.1 RefSeqGene

Range

5060..128011

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001281435.2 → NP_001268364.1 dual specificity mitogen-activated protein kinase kinase 4 isoform 2

See identical proteins and their annotated locations for NP_001268364.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) contains an alternate in-frame exon in the 5' coding region compared to variant 1. It encodes isoform 2 which is longer compared to isoform 1.

Source sequence(s)

AC005244, AC005410, AK131544

Consensus CDS

CCDS62095.1

UniProtKB/TrEMBL

B4DH44

Related

ENSP00000410402.3, ENST00000415385.7

Conserved Domains (1) summary

cd06616
Location:106 → 396

PKc_MKK4; Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 4
NM_003010.4 → NP_003001.1 dual specificity mitogen-activated protein kinase kinase 4 isoform 1

See identical proteins and their annotated locations for NP_003001.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes isoform 1.

Source sequence(s)

AU150695, BC036032, BQ028457, L36870

Consensus CDS

CCDS11162.1

UniProtKB/Swiss-Prot

B2R7N7, B3KYB2, D3DTS5, P45985, Q5U0B8, Q6FHX4, Q6P9H2, Q6PIE6

UniProtKB/TrEMBL

B4DH44

Related

ENSP00000262445.5, ENST00000353533.10

Conserved Domains (1) summary

cd06616
Location:95 → 385

PKc_MKK4; Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 4

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000017.11 Reference GRCh38.p14 Primary Assembly

Range

12020877..12143828

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011523976.3 → XP_011522278.1 dual specificity mitogen-activated protein kinase kinase 4 isoform X1

Conserved Domains (2) summary

smart00220
Location:114 → 310

S_TKc; Serine/Threonine protein kinases, catalytic domain

cl21453
Location:106 → 309

PKc_like; Protein Kinases, catalytic domain
XM_005256753.4 → XP_005256810.1 dual specificity mitogen-activated protein kinase kinase 4 isoform X2

See identical proteins and their annotated locations for XP_005256810.1

UniProtKB/TrEMBL

B7Z9Y5

Conserved Domains (1) summary

cd06616
Location:1 → 267

PKc_MKK4; Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 4

RNA

XR_007065381.1 RNA Sequence
XR_007065382.1 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

NC_060941.1 Alternate T2T-CHM13v2.0

Range

11928859..12051837

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054316902.1 → XP_054172877.1 dual specificity mitogen-activated protein kinase kinase 4 isoform X1
XM_054316903.1 → XP_054172878.1 dual specificity mitogen-activated protein kinase kinase 4 isoform X2