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

    Gene ID: 4293, updated on 2-Nov-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 molecular function activator activity and protein serine/threonine kinase activity. Involved in protein autophosphorylation. Predicted to be located in membrane. [provided by Alliance of Genome Resources, Nov 2024]
    Expression
    Broad expression in brain (RPKM 3.6), testis (RPKM 3.0) and 22 other tissues See more
    Orthologs
    mouse all
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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_2024_08 current GRCh38.p14 (GCF_000001405.40) 14 NC_000014.9 (70722526..70809513, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 14 NC_060938.1 (64928525..65015550, complement)
    RS_2024_09 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 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. Mixed-lineage kinase 1 and mixed-lineage kinase 3 subtype-selective dihydronaphthyl[3,4-a]pyrrolo[3,4-c]carbazole-5-ones: optimization, mixed-lineage kinase 1 crystallography, and oral in vivo activity in 1-methyl-4-phenyltetrahydropyridine models. Hudkins RL, et al. J Med Chem, 2008 Sep 25. PMID 18714982
    3. 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
    4. Identification of a new family of human epithelial protein kinases containing two leucine/isoleucine-zipper domains. Dorow DS, et al. Eur J Biochem, 1993 Apr 15. PMID 8477742
    5. Complete nucleotide sequence, expression, and chromosomal localisation of human mixed-lineage kinase 2. Dorow DS, et al. Eur J Biochem, 1995 Dec 1. PMID 8536694

    See all (37) 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 
    involved_in signal transduction IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    is_active_in cellular_component ND
    No biological Data available
    more info
    		  
    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 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_2024_08

    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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