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MAP3K11 mitogen-activated protein kinase kinase kinase 11 [ Homo sapiens (human) ]

Gene ID: 4296, updated on 5-Mar-2024

Summary

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Official Symbol
MAP3K11provided by HGNC
Official Full Name
mitogen-activated protein kinase kinase kinase 11provided by HGNC
Primary source
HGNC:HGNC:6850
See related
Ensembl:ENSG00000173327 MIM:600050; AllianceGenome:HGNC:6850
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
MLK3; PTK1; SPRK; MLK-3; MEKK11
Summary
The protein encoded by this gene is a member of the serine/threonine kinase family. This kinase contains a SH3 domain and a leucine zipper-basic motif. This kinase preferentially activates MAPK8/JNK kinase, and functions as a positive regulator of JNK signaling pathway. This kinase can directly phosphorylate, and activates IkappaB kinase alpha and beta, and is found to be involved in the transcription activity of NF-kappaB mediated by Rho family GTPases and CDC42. [provided by RefSeq, Jul 2008]
Expression
Ubiquitous expression in spleen (RPKM 25.3), fat (RPKM 22.6) and 25 other tissues See more
Orthologs
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Genomic context

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See MAP3K11 in Genome Data Viewer
Location:
11q13.1
Exon count:
11
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (65597757..65614221, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (65591917..65608380, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (65365228..65381692, complement)

Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124902692 Neighboring gene EH domain binding protein 1 like 1 Neighboring gene H3K4me1 hESC enhancers GRCh37_chr11:65355424-65355944 and GRCh37_chr11:65355945-65356464 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:65356597-65357098 Neighboring gene potassium two pore domain channel subfamily K member 7 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3544 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:65380127-65381014 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3545 Neighboring gene H3K27ac hESC enhancer GRCh37_chr11:65381903-65382789 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4994 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4995 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4996 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3546 Neighboring gene pecanex 3 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:65404393-65405183 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3547 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4997 Neighboring gene microRNA 4690 Neighboring gene signal-induced proliferation-associated 1 Neighboring gene microRNA 4489

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. MAP3K11 facilitates autophagy activity and is correlated with malignancy of oral squamous cell carcinoma. Liu PF, et al. J Cell Physiol, 2022 Nov. PMID 36103355
  2. The role of mixed lineage kinase 3 (MLK3) in cancers. Ramachandraiah K, et al. Pharmacol Ther, 2022 Oct. PMID 36038020
  3. Phosphorylation of mixed lineage kinase MLK3 by cyclin-dependent kinases CDK1 and CDK2 controls ovarian cancer cell division. Cedeno-Rosario L, et al. J Biol Chem, 2022 Aug. PMID 35843311, Free PMC Article
  4. Mechanisms underlying melanoma invasion as a consequence of MLK3 loss. Balinda HU, et al. Exp Cell Res, 2022 Jun 1. PMID 35307409, Free PMC Article
  5. Identification of two distinct peptide-binding pockets in the SH3 domain of human mixed-lineage kinase 3. Kokoszka ME, et al. J Biol Chem, 2018 Aug 31. PMID 29980598, Free PMC Article

See all (117) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. MLK3 localizes mainly to the cytoplasm and promotes oxidative stress injury via a positive feedback loop.
    Title: MLK3 localizes mainly to the cytoplasm and promotes oxidative stress injury via a positive feedback loop.
  2. MAP3K11 facilitates autophagy activity and is correlated with malignancy of oral squamous cell carcinoma.
    Title: MAP3K11 facilitates autophagy activity and is correlated with malignancy of oral squamous cell carcinoma.
  3. The role of mixed lineage kinase 3 (MLK3) in cancers.
    Title: The role of mixed lineage kinase 3 (MLK3) in cancers.
  4. MLK3 Regulates Inflammatory Response via Activation of AP-1 Pathway in HEK293 and RAW264.7 Cells.
    Title: MLK3 Regulates Inflammatory Response via Activation of AP-1 Pathway in HEK293 and RAW264.7 Cells.
  5. Phosphorylation of mixed lineage kinase MLK3 by cyclin-dependent kinases CDK1 and CDK2 controls ovarian cancer cell division.
    Title: Phosphorylation of mixed lineage kinase MLK3 by cyclin-dependent kinases CDK1 and CDK2 controls ovarian cancer cell division.
  6. Mechanisms underlying melanoma invasion as a consequence of MLK3 loss.
    Title: Mechanisms underlying melanoma invasion as a consequence of MLK3 loss.
  7. MAP4K4 promotes pancreatic tumorigenesis via phosphorylation and activation of mixed lineage kinase 3.
    Title: MAP4K4 promotes pancreatic tumorigenesis via phosphorylation and activation of mixed lineage kinase 3.
  8. Mixed Lineage Kinase 3 phosphorylates prolyl-isomerase PIN1 and potentiates GLI1 signaling in pancreatic cancer development.
    Title: Mixed Lineage Kinase 3 phosphorylates prolyl-isomerase PIN1 and potentiates GLI1 signaling in pancreatic cancer development.
  9. LATS1 Regulates Mixed-Lineage Kinase 3 (MLK3) Subcellular Localization and MLK3-Mediated Invasion in Ovarian Epithelial Cells.
    Title: LATS1 Regulates Mixed-Lineage Kinase 3 (MLK3) Subcellular Localization and MLK3-Mediated Invasion in Ovarian Epithelial Cells.
  10. MLK3 silence induces cervical cancer cell apoptosis via the Notch-1/autophagy network.
    Title: MLK3 silence induces cervical cancer cell apoptosis via the Notch-1/autophagy network.
Submit: New GeneRIF Correction See all GeneRIFs (67)

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 identifies three novel susceptibility loci for severe Acne vulgaris.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env Treatment of neurons with HIV-1 gp120 in culture produces apoptotic neuronal death through the mixed lineage kinase 3 (MLK3) signaling pathway 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

Clone Names

  • MGC17114

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 IBA
Inferred from Biological aspect of Ancestor
more info
  
enables JUN kinase kinase kinase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables JUN kinase kinase kinase activity ISS
Inferred from Sequence or Structural Similarity
more info
  
enables MAP kinase kinase kinase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables identical protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables mitogen-activated protein kinase kinase binding IEA
Inferred from Electronic Annotation
more info
  
enables mitogen-activated protein kinase kinase kinase binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein homodimerization activity 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 IDA
Inferred from Direct Assay
more info
 PubMed 
enables small GTPase binding IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in JNK cascade IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in MAPK cascade IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in cell cycle G1/S phase transition IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in microtubule-based process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in microtubule-based process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of JNK cascade IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of JUN kinase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of apoptotic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in positive regulation of neuron apoptotic process IEA
Inferred from Electronic Annotation
more info
  
involved_in protein autophosphorylation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein phosphorylation IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
is_active_in centrosome IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in centrosome IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in membrane HDA PubMed 
located_in microtubule IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
mitogen-activated protein kinase kinase kinase 11
Names
SH3 domain-containing proline-rich kinase
mixed lineage kinase 3
protein-tyrosine kinase PTK1
src-homology 3 domain-containing proline-rich kinase
NP_002410.1
XP_047282918.1
XP_054224804.1

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.

mRNA and Protein(s)

  1. NM_002419.4 → NP_002410.1  mitogen-activated protein kinase kinase kinase 11

    See identical proteins and their annotated locations for NP_002410.1

    Status: REVIEWED

    Source sequence(s)
    L32976, U07747
    Consensus CDS
    CCDS8107.1
    UniProtKB/Swiss-Prot
    B4DS76, Q16584, Q53H00, Q59F06, Q6P2G4
    UniProtKB/TrEMBL
    B2RDI6
    Related
    ENSP00000309597.3, ENST00000309100.8
    Conserved Domains (3) summary
    cd12059
    Location:45 → 102
    SH3_MLK1-3; Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3
    smart00221
    Location:117 → 376
    STYKc; Protein kinase; unclassified specificity
    cd14147
    Location:113 → 379
    STKc_MLK3; Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 3

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

  1. NC_000011.10 Reference GRCh38.p14 Primary Assembly

    Range
    65597757..65614221 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047426962.1 → XP_047282918.1  mitogen-activated protein kinase kinase kinase 11 isoform X1

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060935.1 Alternate T2T-CHM13v2.0

    Range
    65591917..65608380 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054368829.1 → XP_054224804.1  mitogen-activated protein kinase kinase kinase 11 isoform X1

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q16584.1 GenPept UniProtKB/Swiss-Prot:Q16584

Gene LinkOut

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

Chemical Information
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