MAP3K21 mitogen-activated protein kinase kinase kinase 21 [Homo sapiens (human)] - Gene

Summary

Official Symbol: MAP3K21provided by HGNC
Official Full Name: mitogen-activated protein kinase kinase kinase 21provided by HGNC
Primary source: HGNC:HGNC:29798
See related: Ensembl:ENSG00000143674 MIM:614793; AllianceGenome:HGNC:29798
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: MLK4; dJ862P8.3
Summary: Predicted to enable JUN kinase kinase kinase activity and protein homodimerization activity. Predicted to be involved in protein autophosphorylation and signal transduction. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Jan 2025]
Expression: Broad expression in testis (RPKM 6.4), kidney (RPKM 5.7) and 21 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1q42.2

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (233327724..233385148)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (232714101..232771515)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (233463470..233520894)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

MLK4 as an immune marker and its correlation with immune infiltration in Cervical squamous cell carcinoma and endocervical adenocarcinoma(CESC).
Title: MLK4 as an immune marker and its correlation with immune infiltration in Cervical squamous cell carcinoma and endocervical adenocarcinoma(CESC).
MLK4 was over-expressed in tumor samples of Hepatocellular carcinoma patients.
Title: Decrease of MLK4 prevents hepatocellular carcinoma (HCC) through reducing metastasis and inducing apoptosis regulated by ROS/MAPKs signaling.
High expression of MLK4 promotes migratory and invasive phenotype.
Title: Upregulation of MLK4 promotes migratory and invasive potential of breast cancer cells.
These results suggest that in the early response to stressful stimuli, MLK4beta-MLK3 binding is important for regulating MLK3 activity and MAPK signalling, and after prolonged periods of stress exposure, MLK4beta and MLK3 proteins decline via CHIP-dependent degradation.
Title: Osmotic and heat stress-dependent regulation of MLK4β and MLK3 by the CHIP E3 ligase in ovarian cancer cells.
results uncover MLK4 as an upstream regulator of NF-kappaB signaling and a potential molecular target for the MES subtype of glioblastomas
Title: Serine/Threonine Kinase MLK4 Determines Mesenchymal Identity in Glioma Stem Cells in an NF-κB-dependent Manner.
In establishing the role of MLK4 in intracellular signaling, we show it directly phosphorylates MEK1 (MAP2K1) and that MEK/ERK (MAPK1) signaling is impaired in MLK4 knockout cells
Title: Mixed lineage kinase MLK4 is activated in colorectal cancers where it synergistically cooperates with activated RAS signaling in driving tumorigenesis.
MLK4 is a negative regulator of TLR4 signaling.
Title: MLK4 has negative effect on TLR4 signaling.

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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 periodontal pathogen colonization. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide meta-analysis for severe diabetic retinopathy. 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

RH93433 (e-PCR)
- UniSTS:86615

SHGC-83555 (e-PCR)
- UniSTS:101759

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables JUN kinase kinase kinase activity	ISS Inferred from Sequence or Structural Similarity more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	ISS Inferred from Sequence or Structural Similarity more info
enables protein kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein serine kinase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in MAPK cascade	IEA Inferred from Electronic Annotation more info
involved_in protein autophosphorylation	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein phosphorylation	ISS Inferred from Sequence or Structural Similarity more info
involved_in signal transduction	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: mitogen-activated protein kinase kinase kinase 21

Names: mitogen-activated protein kinase kinase kinase MLK4; mixed lineage kinase 4

NP_115811.2

EC 2.7.11.25

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.