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    MAP3K13 mitogen-activated protein kinase kinase kinase 13 [ Homo sapiens (human) ]

    Gene ID: 9175, updated on 5-Mar-2024

    Summary

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    Official Symbol
    MAP3K13provided by HGNC
    Official Full Name
    mitogen-activated protein kinase kinase kinase 13provided by HGNC
    Primary source
    HGNC:HGNC:6852
    See related
    Ensembl:ENSG00000073803 MIM:604915; AllianceGenome:HGNC:6852
    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
    LZK; MLK; MEKK13
    Summary
    The protein encoded by this gene is a member of serine/threonine protein kinase family. This kinase contains a dual leucine-zipper motif, and has been shown to form dimers/oligomers through its leucine-zipper motif. This kinase can phosphorylate and activate MAPK8/JNK, MAP2K7/MKK7, which suggests a role in the JNK signaling pathway. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in adrenal (RPKM 3.8), kidney (RPKM 3.4) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    3q27.2
    Exon count:
    18
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (185282961..185489094)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (188098494..188304852)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (185000749..185206882)

    Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase Neighboring gene uncharacterized LOC124900548 Neighboring gene microRNA 5588 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14973 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr3:184999880-185001079 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20921 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20922 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14974 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20924 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20923 Neighboring gene small nucleolar RNA U13 Neighboring gene ribosomal protein L4 pseudogene 4 Neighboring gene MPRA-validated peak4968 silencer Neighboring gene uncharacterized LOC124906312 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr3:185190839-185192038 Neighboring gene uncharacterized LOC101929018 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr3:185197816-185199015 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14975 Neighboring gene uncharacterized LOC105374254 Neighboring gene transmembrane protein 41A

    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. Clinical significance of mitogen-activated protein kinase kinase kinases in hepatitis B virus -related hepatocellular carcinoma and underlying mechanism exploration. Liu Z, et al. Bioengineered, 2022 Mar. PMID 35311629, Free PMC Article
    2. Genomic organization and fine-mapping of the human leucine zipper-bearing kinase (LZK) gene. Ikeda A, et al. J Biochem Mol Biol Biophys, 2002 Apr. PMID 12186766
    3. Identification and characterization of functional domains in a mixed lineage kinase LZK. Ikeda A, et al. FEBS Lett, 2001 Jan 19. PMID 11163770
    4. microRNA-206 impairs c-Myc-driven cancer in a synthetic lethal manner by directly inhibiting MAP3K13. Han H, et al. Oncotarget, 2016 Mar 29. PMID 26918941, Free PMC Article
    5. Molecular cloning and functional expression of a cDNA encoding a new member of mixed lineage protein kinase from human brain. Sakuma H, et al. J Biol Chem, 1997 Nov 7. PMID 9353328

    See all (24) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Clinical significance of mitogen-activated protein kinase kinase kinases in hepatitis B virus -related hepatocellular carcinoma and underlying mechanism exploration.
      Title: Clinical significance of mitogen-activated protein kinase kinase kinases in hepatitis B virus -related hepatocellular carcinoma and underlying mechanism exploration.
    2. The MAP3K13-TRIM25-FBXW7alpha axis affects c-Myc protein stability and tumor development.
      Title: The MAP3K13-TRIM25-FBXW7α axis affects c-Myc protein stability and tumor development.
    3. Data indicate that miR-206's effect on Myc was mediated through MAP3K13.
      Title: microRNA-206 impairs c-Myc-driven cancer in a synthetic lethal manner by directly inhibiting MAP3K13.
    4. LZK cooperates with DLK to promote retinal ganglion cell death in response to axon injury.
      Title: Enhanced Functional Genomic Screening Identifies Novel Mediators of Dual Leucine Zipper Kinase-Dependent Injury Signaling in Neurons.
    5. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
      Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
    6. Chromosomal localization studies involving FISH mapping demonstrated that the human LZK gene is located at 3q27.
      Title: Genomic organization and fine-mapping of the human leucine zipper-bearing kinase (LZK) gene.
    Submit: New GeneRIF Correction

    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 studies identify CHRNA5/3 and HTR4 in the development of airflow obstruction.
    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

    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

    • MGC133196

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables IkappaB kinase complex binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables JUN kinase kinase kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables MAP kinase kinase kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables enzyme binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein homodimerization activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein kinase binding 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 activator activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables protein serine/threonine kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein serine/threonine kinase activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Process Evidence Code Pubs
    involved_in JNK cascade IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in JNK cascade IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in JNK cascade ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in peptidyl-serine phosphorylation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of JUN kinase activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of NF-kappaB transcription factor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of axon extension ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of branching morphogenesis of a nerve ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of neuron maturation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of neuron projection arborization ISS
    Inferred from Sequence or Structural Similarity
    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 stress-activated MAPK cascade IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in cytoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    mitogen-activated protein kinase kinase kinase 13
    Names
    leucine zipper-bearing kinase
    mixed lineage kinase
    NP_001229243.1
    NP_001229246.1
    NP_004712.1
    XP_011511612.1
    XP_016862945.1
    XP_016862946.1
    XP_047305149.1
    XP_054204332.1
    XP_054204333.1
    XP_054204334.1
    XP_054204335.1

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    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_001242314.2 → NP_001229243.1  mitogen-activated protein kinase kinase kinase 13 isoform 1

      See identical proteins and their annotated locations for NP_001229243.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Both variants 1 and 2 encode the same protein.
      Source sequence(s)
      AC099661, AK312714, BQ432918
      Consensus CDS
      CCDS3270.1
      UniProtKB/Swiss-Prot
      B2R6U2, B4DLE3, B4DMV2, B4DZJ4, D3DNU1, O43283, Q05BY6, Q15450, Q2NKN3
      Related
      ENSP00000399910.1, ENST00000424227.5
      Conserved Domains (2) summary
      smart00221
      Location:168 → 402
      STYKc; Protein kinase; unclassified specificity
      cd14059
      Location:174 → 410
      STKc_MAP3K12_13; Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinases 12 and 13

    2. NM_001242317.2 → NP_001229246.1  mitogen-activated protein kinase kinase kinase 13 isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (2) has a distinct N-terminus and is shorter than isoform 1.
      Source sequence(s)
      AC099661, AK297646
      Consensus CDS
      CCDS56298.1
      UniProtKB/Swiss-Prot
      O43283
      Related
      ENSP00000411483.1, ENST00000446828.5
      Conserved Domains (1) summary
      cl21453
      Location:13 → 203
      PKc_like; Protein Kinases, catalytic domain

    3. NM_004721.5 → NP_004712.1  mitogen-activated protein kinase kinase kinase 13 isoform 1

      See identical proteins and their annotated locations for NP_004712.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript. Both variants 1 and 2 encode the same protein.
      Source sequence(s)
      AB001872, AC099661, AC132516
      Consensus CDS
      CCDS3270.1
      UniProtKB/Swiss-Prot
      B2R6U2, B4DLE3, B4DMV2, B4DZJ4, D3DNU1, O43283, Q05BY6, Q15450, Q2NKN3
      Related
      ENSP00000265026.3, ENST00000265026.8
      Conserved Domains (2) summary
      smart00221
      Location:168 → 402
      STYKc; Protein kinase; unclassified specificity
      cd14059
      Location:174 → 410
      STKc_MAP3K12_13; Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinases 12 and 13

    RNA

    1. NR_038322.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) lacks eleven exons and contains an alternate 3' exon, compared to variant 3. This variant is represented as non-coding because it lacks a large portion of the coding region found in variant 3.
      Source sequence(s)
      AI690808, BC015996, BC036593, BQ432918
      Related
      ENST00000448876.5

    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_000003.12 Reference GRCh38.p14 Primary Assembly

      Range
      185282961..185489094
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047449193.1 → XP_047305149.1  mitogen-activated protein kinase kinase kinase 13 isoform X1

      UniProtKB/Swiss-Prot
      B2R6U2, B4DLE3, B4DMV2, B4DZJ4, D3DNU1, O43283, Q05BY6, Q15450, Q2NKN3

    2. XM_017007456.2 → XP_016862945.1  mitogen-activated protein kinase kinase kinase 13 isoform X1

      UniProtKB/Swiss-Prot
      B2R6U2, B4DLE3, B4DMV2, B4DZJ4, D3DNU1, O43283, Q05BY6, Q15450, Q2NKN3
      Conserved Domains (2) summary
      smart00221
      Location:168 → 402
      STYKc; Protein kinase; unclassified specificity
      cd14059
      Location:174 → 410
      STKc_MAP3K12_13; Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinases 12 and 13

    3. XM_011513310.3 → XP_011511612.1  mitogen-activated protein kinase kinase kinase 13 isoform X1

      See identical proteins and their annotated locations for XP_011511612.1

      UniProtKB/Swiss-Prot
      B2R6U2, B4DLE3, B4DMV2, B4DZJ4, D3DNU1, O43283, Q05BY6, Q15450, Q2NKN3
      Conserved Domains (2) summary
      smart00221
      Location:168 → 402
      STYKc; Protein kinase; unclassified specificity
      cd14059
      Location:174 → 410
      STKc_MAP3K12_13; Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinases 12 and 13

    4. XM_017007457.2 → XP_016862946.1  mitogen-activated protein kinase kinase kinase 13 isoform X2

      Related
      ENSP00000409325.1, ENST00000443863.5

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060927.1 Alternate T2T-CHM13v2.0

      Range
      188098494..188304852
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054348357.1 → XP_054204332.1  mitogen-activated protein kinase kinase kinase 13 isoform X1

      UniProtKB/Swiss-Prot
      B2R6U2, B4DLE3, B4DMV2, B4DZJ4, D3DNU1, O43283, Q05BY6, Q15450, Q2NKN3

    2. XM_054348358.1 → XP_054204333.1  mitogen-activated protein kinase kinase kinase 13 isoform X1

      UniProtKB/Swiss-Prot
      B2R6U2, B4DLE3, B4DMV2, B4DZJ4, D3DNU1, O43283, Q05BY6, Q15450, Q2NKN3

    3. XM_054348359.1 → XP_054204334.1  mitogen-activated protein kinase kinase kinase 13 isoform X1

      UniProtKB/Swiss-Prot
      B2R6U2, B4DLE3, B4DMV2, B4DZJ4, D3DNU1, O43283, Q05BY6, Q15450, Q2NKN3

    4. XM_054348360.1 → XP_054204335.1  mitogen-activated protein kinase kinase kinase 13 isoform X2

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O43283.1 GenPept UniProtKB/Swiss-Prot:O43283

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