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

    Gene ID: 4296, updated on 2-Nov-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
    mouse all
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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_2024_08 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (65597757..65614221, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (65591917..65608380, complement)
    RS_2024_09 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 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. Hepatitis C virus NS5A inhibits mixed lineage kinase 3 to block apoptosis. Amako Y, et al. J Biol Chem, 2013 Aug 23. PMID 23857585, Free PMC Article
    2. 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
    3. MLK3 is critical for breast cancer cell migration and promotes a malignant phenotype in mammary epithelial cells. Chen J, et al. Oncogene, 2010 Aug 5. PMID 20514022
    4. Induced, selective proteolysis of MLK3 negatively regulates MLK3/JNK signalling. Liou GY, et al. Biochem J, 2010 Apr 14. PMID 20158498
    5. MLK-3: identification of a widely-expressed protein kinase bearing an SH3 domain and a leucine zipper-basic region domain. Ing YL, et al. Oncogene, 1994 Jun. PMID 8183572

    See all (122) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. MLK3 promotes prooncogenic signaling in hepatocellular carcinoma via TGFbeta pathway.
      Title: MLK3 promotes prooncogenic signaling in hepatocellular carcinoma via TGFβ pathway.
    2. 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.
    3. 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.
    4. The role of mixed lineage kinase 3 (MLK3) in cancers.
      Title: The role of mixed lineage kinase 3 (MLK3) in cancers.
    5. 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.
    6. 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.
    7. Mechanisms underlying melanoma invasion as a consequence of MLK3 loss.
      Title: Mechanisms underlying melanoma invasion as a consequence of MLK3 loss.
    8. 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.
    9. 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.
    10. 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.
    Submit: New GeneRIF Correction See all GeneRIFs (68)

    Phenotypes

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    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)

    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 IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    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 
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    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_2024_08

    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

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