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MAP3K9 mitogen-activated protein kinase kinase kinase 9 [ Homo sapiens (human) ]

Gene ID: 4293, updated on 13-Apr-2024

Summary

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Official Symbol
MAP3K9provided by HGNC
Official Full Name
mitogen-activated protein kinase kinase kinase 9provided by HGNC
Primary source
HGNC:HGNC:6861
See related
Ensembl:ENSG00000006432 MIM:600136; AllianceGenome:HGNC:6861
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
MLK1; MEKK9; PRKE1
Summary
Enables protein serine/threonine kinase activity. Involved in protein autophosphorylation. [provided by Alliance of Genome Resources, Apr 2022]
Expression
Broad expression in brain (RPKM 3.6), testis (RPKM 3.0) and 22 other tissues See more
Orthologs
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Genomic context

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See MAP3K9 in Genome Data Viewer
Location:
14q24.2
Exon count:
16
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 14 NC_000014.9 (70722526..70809513, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 14 NC_060938.1 (64928525..65015550, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 14 NC_000014.8 (71189243..71276230, complement)

Chromosome 14 - NC_000014.9Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5887 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5888 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5889 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr14:71120238-71120824 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5890 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8658 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8659 Neighboring gene tetratricopeptide repeat domain 9 Neighboring gene H3K27ac hESC enhancer GRCh37_chr14:71133100-71133600 Neighboring gene H3K27ac hESC enhancer GRCh37_chr14:71133601-71134101 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr14:71164525-71165724 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8660 Neighboring gene long intergenic non-protein coding RNA 1269 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8661 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:71208701-71209202 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8662 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8663 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8664 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8665 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8666 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5891 Neighboring gene MAP3K9 divergent transcript Neighboring gene Sharpr-MPRA regulatory region 11364/13366 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5892 Neighboring gene uncharacterized LOC124903341 Neighboring gene TMEM183A pseudogene 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. Elevation of miR-125b-5p is related to improved prognosis in laryngeal squamous cell carcinoma and inhibits the malignancy and glycometabolic disorder by targeting MAP3K9. Chen F, et al. Neoplasma, 2022 May. PMID 35188403
  2. Promoter methylation-regulated miR-148a-3p inhibits lung adenocarcinoma (LUAD) progression by targeting MAP3K9. Liang L, et al. Acta Pharmacol Sin, 2022 Nov. PMID 35388129, Free PMC Article
  3. MicroRNA-148a regulates the MAPK/ERK signaling pathway and suppresses the development of esophagus squamous cell carcinoma via targeting MAP3K9. Zhang BX, et al. Eur Rev Med Pharmacol Sci, 2019 Aug. PMID 31378889
  4. miR‑490‑5p regulates the proliferation, migration, invasion and epithelial‑mesenchymal transition of pharyngolaryngeal cancer cells by targeting mitogen‑activated protein kinase kinasekinase 9. Abdeyrim A, et al. Int J Mol Med, 2019 Jul. PMID 31115491, Free PMC Article
  5. MKL1 defines the H3K4Me3 landscape for NF-κB dependent inflammatory response. Yu L, et al. Sci Rep, 2017 Mar 15. PMID 28298643, Free PMC Article

See all (36) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Promoter methylation-regulated miR-148a-3p inhibits lung adenocarcinoma (LUAD) progression by targeting MAP3K9.
    Title: Promoter methylation-regulated miR-148a-3p inhibits lung adenocarcinoma (LUAD) progression by targeting MAP3K9.
  2. CircSPI1_005 ameliorates osteoarthritis by sponging miR-370-3p to regulate the expression of MAP3K9.
    Title: CircSPI1_005 ameliorates osteoarthritis by sponging miR-370-3p to regulate the expression of MAP3K9.
  3. Elevation of miR-125b-5p is related to improved prognosis in laryngeal squamous cell carcinoma and inhibits the malignancy and glycometabolic disorder by targeting MAP3K9.
    Title: Elevation of miR-125b-5p is related to improved prognosis in laryngeal squamous cell carcinoma and inhibits the malignancy and glycometabolic disorder by targeting MAP3K9.
  4. MicroRNA-148a regulates the MAPK/ERK signaling pathway and suppresses the development of esophagus squamous cell carcinoma via targeting MAP3K9.
    Title: MicroRNA-148a regulates the MAPK/ERK signaling pathway and suppresses the development of esophagus squamous cell carcinoma via targeting MAP3K9.
  5. The overexpression of MAP3K9 could promote cell viability, migration and invasion rates, EMT process and ability of cloning, miR4905p could target MAP3K9 and further modulate the proliferation, migration, invasion and EMT of pharyngolaryngeal cancer cells.
    Title: miR‑490‑5p regulates the proliferation, migration, invasion and epithelial‑mesenchymal transition of pharyngolaryngeal cancer cells by targeting mitogen‑activated protein kinase kinasekinase 9.
  6. Data report that MKL1 was both sufficient and necessary for p65-dependent pro-inflammatory transcriptional program. MKL1 deficiency erased key histone modifications synonymous with transactivation on p65 target promoters. Specifically, MKL1 defined histone H3K4 trimethylation landscape for NF-kappaB dependent transcription.
    Title: MKL1 defines the H3K4Me3 landscape for NF-κB dependent inflammatory response.
  7. There was a negatively relationship between miR-15a and MAP3K9 expression in NP cells.
    Title: Role of miR-15a in intervertebral disc degeneration through targeting MAP3K9.
  8. miR148b directly targeted mitogenactivated protein kinase (MAPK) kinase kinase 9 (MAP3K9), an upstream activator of MAPK kinase/cJun Nterminal kinase (JNK) signaling, suppressing the protein but not the mRNA levels.
    Title: MicroRNA-148b enhances proliferation and apoptosis in human renal cancer cells via directly targeting MAP3K9.
  9. identified three kinases with gain-of-function mutations in lung cancer, namely FGFR4, MAP3K9, and PAK5. Mutations in these kinases are activating toward the ERK pathway, and targeted depletion of the mutated kinases inhibits proliferation
    Title: Targeted genetic dependency screen facilitates identification of actionable mutations in FGFR4, MAP3K9, and PAK5 in lung cancer.
  10. It was found that 24% of melanoma cell lines have mutations in the protein-coding regions of either MAP3K5 or MAP3K9.
    Title: Frequent somatic mutations in MAP3K5 and MAP3K9 in metastatic melanoma identified by exome sequencing.
Submit: New GeneRIF Correction See all GeneRIFs (12)

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 pharmacogenomic study of neurocognition as an indicator of antipsychotic treatment response in schizophrenia.
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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Replication interactions

Interaction Pubs
Knockdown of mitogen-activated protein kinase kinase kinase 9 (MAP3K9) by siRNA inhibits HIV-1 replication in HeLa P4/R5 cells 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 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 ISS
Inferred from Sequence or Structural Similarity
more info
 PubMed 
enables MAP kinase kinase activity NAS
Non-traceable Author Statement
more info
 PubMed 
enables molecular function activator activity EXP
Inferred from Experiment
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein homodimerization activity ISS
Inferred from Sequence or Structural Similarity
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 MAPK cascade IEA
Inferred from Electronic Annotation
more info
  
involved_in apoptotic process IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of 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 cellular_component ND
No biological Data available
more info
  

General protein information

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Preferred Names
mitogen-activated protein kinase kinase kinase 9
Names
mixed lineage kinase 1 (tyr and ser/thr specificity)
NP_001271159.1
NP_001271160.1
NP_001271161.1
NP_149132.2
XP_005267740.1
XP_011535090.1
XP_011535094.1
XP_011535096.1
XP_054232090.1
XP_054232091.1
XP_054232092.1
XP_054232093.1

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_001284230.2 → NP_001271159.1  mitogen-activated protein kinase kinase kinase 9 isoform 2

    See identical proteins and their annotated locations for NP_001271159.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (2) lacks an alternate in-frame exon in the 3' coding region, compared to variant 1. The encoded isoform (2) is shorter than isoform 1.
    Source sequence(s)
    AC004816
    Consensus CDS
    CCDS61488.1
    UniProtKB/Swiss-Prot
    A3KN85, P80192, Q0D2G7, Q6EH31, Q9H2N5
    UniProtKB/TrEMBL
    B4DGF4
    Related
    ENSP00000451612.2, ENST00000554752.7
    Conserved Domains (2) summary
    cd12059
    Location:56 → 113
    SH3_MLK1-3; Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3
    cd14145
    Location:137 → 406
    STKc_MLK1; Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 1

  2. NM_001284231.1 → NP_001271160.1  mitogen-activated protein kinase kinase kinase 9 isoform 3

    Status: VALIDATED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR and contains multiple differences in the coding region, compared to variant 1. It initiates translation at an alternate start codon. The encoded isoform (3) is shorter and has a distinct N-terminus, compared to isoform 1.
    Source sequence(s)
    AC004816, AK302849, BC033197, BX648924, DB099391
    UniProtKB/TrEMBL
    G3V4P9
    Related
    ENSP00000451921.1, ENST00000554146.1
    Conserved Domains (2) summary
    pfam13863
    Location:164 → 249
    DUF4200; Domain of unknown function (DUF4200)
    cl21453
    Location:6 → 143
    PKc_like; Protein Kinases, catalytic domain

  3. NM_001284232.1 → NP_001271161.1  mitogen-activated protein kinase kinase kinase 9 isoform 4

    Status: VALIDATED

    Description
    Transcript Variant: This variant (4) differs in the 5' UTR and lacks an alternate in-frame exon in the 3' coding region, compared to variant 1. It initiates translation at a downstream in-frame start codon. The encoded isoform (4) is shorter and has a shorter N-terminus, compared to isoform 1.
    Source sequence(s)
    AC004816, BC033197, BX648924, DB099391
    Consensus CDS
    CCDS61485.1
    UniProtKB/TrEMBL
    G3V347, G3V4P9
    Related
    ENSP00000451038.1, ENST00000553414.5
    Conserved Domains (2) summary
    pfam13863
    Location:121 → 206
    DUF4200; Domain of unknown function (DUF4200)
    cl21453
    Location:1 → 100
    PKc_like; Protein Kinases, catalytic domain

  4. NM_033141.4 → NP_149132.2  mitogen-activated protein kinase kinase kinase 9 isoform 1

    See identical proteins and their annotated locations for NP_149132.2

    Status: VALIDATED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
    Source sequence(s)
    AC004816, AY327900, BC033197, BX648924
    Consensus CDS
    CCDS32112.1
    UniProtKB/TrEMBL
    B4DGF4
    Related
    ENSP00000451263.2, ENST00000555993.6
    Conserved Domains (3) summary
    smart00219
    Location:144 → 403
    TyrKc; Tyrosine kinase, catalytic domain
    cd12059
    Location:56 → 113
    SH3_MLK1-3; Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3
    cd14145
    Location:137 → 406
    STKc_MLK1; Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 1

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_000014.9 Reference GRCh38.p14 Primary Assembly

    Range
    70722526..70809513 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_005267683.6 → XP_005267740.1  mitogen-activated protein kinase kinase kinase 9 isoform X2

    UniProtKB/TrEMBL
    J3KPI6
    Related
    ENSP00000370649.4, ENST00000381250.8
    Conserved Domains (3) summary
    smart00219
    Location:144 → 403
    TyrKc; Tyrosine kinase, catalytic domain
    cd12059
    Location:56 → 113
    SH3_MLK1-3; Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3
    cd14145
    Location:137 → 406
    STKc_MLK1; Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 1

  2. XM_011536788.4 → XP_011535090.1  mitogen-activated protein kinase kinase kinase 9 isoform X1

    Conserved Domains (3) summary
    smart00219
    Location:144 → 403
    TyrKc; Tyrosine kinase, catalytic domain
    cd12059
    Location:56 → 113
    SH3_MLK1-3; Src Homology 3 domain of Mixed Lineage Kinases 1, 2, and 3
    cd14145
    Location:137 → 406
    STKc_MLK1; Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 1

  3. XM_011536792.1 → XP_011535094.1  mitogen-activated protein kinase kinase kinase 9 isoform X3

    See identical proteins and their annotated locations for XP_011535094.1

    UniProtKB/TrEMBL
    G3V4P9
    Conserved Domains (2) summary
    pfam13863
    Location:121 → 206
    DUF4200; Domain of unknown function (DUF4200)
    cl21453
    Location:1 → 100
    PKc_like; Protein Kinases, catalytic domain

  4. XM_011536794.3 → XP_011535096.1  mitogen-activated protein kinase kinase kinase 9 isoform X4

    UniProtKB/TrEMBL
    G3V4P9
    Conserved Domains (2) summary
    pfam13863
    Location:65 → 150
    DUF4200; Domain of unknown function (DUF4200)
    cl21453
    Location:1 → 44
    PKc_like; Protein Kinases, catalytic domain

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060938.1 Alternate T2T-CHM13v2.0

    Range
    64928525..65015550 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054376116.1 → XP_054232091.1  mitogen-activated protein kinase kinase kinase 9 isoform X2

    UniProtKB/TrEMBL
    J3KPI6

  2. XM_054376115.1 → XP_054232090.1  mitogen-activated protein kinase kinase kinase 9 isoform X1

  3. XM_054376117.1 → XP_054232092.1  mitogen-activated protein kinase kinase kinase 9 isoform X3

  4. XM_054376118.1 → XP_054232093.1  mitogen-activated protein kinase kinase kinase 9 isoform X4

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P80192.3 GenPept UniProtKB/Swiss-Prot:P80192

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