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    Melk maternal embryonic leucine zipper kinase [ Mus musculus (house mouse) ]

    Gene ID: 17279, updated on 11-Apr-2024

    Summary

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    Official Symbol
    Melkprovided by MGI
    Official Full Name
    maternal embryonic leucine zipper kinaseprovided by MGI
    Primary source
    MGI:MGI:106924
    See related
    Ensembl:ENSMUSG00000035683 AllianceGenome:MGI:106924
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Mus musculus
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
    Also known as
    MPK38; mKIAA0175
    Summary
    Enables protein serine/threonine kinase activity. Involved in neural precursor cell proliferation and positive regulation of apoptotic process. Acts upstream of or within intrinsic apoptotic signaling pathway in response to oxidative stress. Located in cytoplasm. Is expressed in several structures, including alimentary system; central nervous system; early conceptus; genitourinary system; and sensory organ. Orthologous to human MELK (maternal embryonic leucine zipper kinase). [provided by Alliance of Genome Resources, Apr 2022]
    Expression
    Biased expression in CNS E11.5 (RPKM 14.4), placenta adult (RPKM 9.4) and 14 other tissues See more
    Orthologs
    human all
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    Genomic context

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    Location:
    4 B1; 4 23.46 cM
    Exon count:
    18
    Annotation release Status Assembly Chr Location
    RS_2024_02 current GRCm39 (GCF_000001635.27) 4 NC_000070.7 (44300876..44364301)
    108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 4 NC_000070.6 (44300909..44364675)

    Chromosome 4 - NC_000070.7Genomic Context describing neighboring genes Neighboring gene ring finger protein 38 Neighboring gene microRNA 5106 Neighboring gene STARR-seq mESC enhancer starr_10071 Neighboring gene STARR-seq mESC enhancer starr_10072 Neighboring gene predicted gene, 54218 Neighboring gene STARR-positive B cell enhancer ABC_E6169 Neighboring gene STARR-seq mESC enhancer starr_10073 Neighboring gene predicted gene, 24376 Neighboring gene STARR-seq mESC enhancer starr_10075 Neighboring gene STARR-seq mESC enhancer starr_10079 Neighboring gene paired box 5 Neighboring gene microRNA 5120

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Mouse ENCODE transcriptome data
    • Description: RNA profiling data sets generated by the Mouse ENCODE project.
    • BioProject: PRJNA66167
    • Publication: PMID 25409824
    • Analysis date: n/a

    Bibliography

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    Related articles in PubMed

    1. MELK predicts poor prognosis and promotes metastasis in esophageal squamous cell carcinoma via activating the NF‑κB pathway. Ye J, et al. Int J Oncol, 2022 Aug. PMID 35730614, Free PMC Article
    2. Ablation of AMPK-Related Kinase MPK38/MELK Leads to Male-Specific Obesity in Aged Mature Adult Mice. Seong HA, et al. Diabetes, 2021 Feb. PMID 33268463
    3. Thr55 phosphorylation of p21 by MPK38/MELK ameliorates defects in glucose, lipid, and energy metabolism in diet-induced obese mice. Seong HA, et al. Cell Death Dis, 2019 May 16. PMID 31097688, Free PMC Article
    4. Smad proteins differentially regulate obesity-induced glucose and lipid abnormalities and inflammation via class-specific control of AMPK-related kinase MPK38/MELK activity. Seong HA, et al. Cell Death Dis, 2018 May 1. PMID 29700281, Free PMC Article
    5. Maternal embryonic leucine zipper kinase regulates pancreatic ductal, but not β-cell, regeneration. Chung CH, et al. Physiol Rep, 2014 Sep 1. PMID 25194022, Free PMC Article

    See all (45) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. MELK predicts poor prognosis and promotes metastasis in esophageal squamous cell carcinoma via activating the NFkappaB pathway.
      Title: MELK predicts poor prognosis and promotes metastasis in esophageal squamous cell carcinoma via activating the NF‑κB pathway.
    2. DAXX ameliorates metabolic dysfunction in mice with diet-induced obesity by activating the AMP-activated protein kinase-related kinase MPK38/MELK.
      Title: DAXX ameliorates metabolic dysfunction in mice with diet-induced obesity by activating the AMP-activated protein kinase-related kinase MPK38/MELK.
    3. Ablation of AMPK-Related Kinase MPK38/MELK Leads to Male-Specific Obesity in Aged Mature Adult Mice.
      Title: Ablation of AMPK-Related Kinase MPK38/MELK Leads to Male-Specific Obesity in Aged Mature Adult Mice.
    4. MPK38 phosphorylates p21 at Thr55 stimulating its nuclear translocation, which results in greater association of p21 with peroxisome proliferator-activated receptor gamma (PPARgamma), preventing the PPARgamma transactivation required for adipogenesis.
      Title: Thr55 phosphorylation of p21 by MPK38/MELK ameliorates defects in glucose, lipid, and energy metabolism in diet-induced obese mice.
    5. These findings suggest that Smad proteins have class-specific impacts on obesity-associated metabolism by differentially regulating MPK38 activity in diet-induced obese mice.
      Title: Smad proteins differentially regulate obesity-induced glucose and lipid abnormalities and inflammation via class-specific control of AMPK-related kinase MPK38/MELK activity.
    6. MELK promotes cell migration and invasion via the FAK/Paxillin pathway, and plays an important role in the occurrence and development of gastric cancer.
      Title: Maternal embryonic leucine zipper kinase enhances gastric cancer progression via the FAK/Paxillin pathway.
    7. Phosphorylation of the activation loop of MPK38 induces its movement resulting in kinase activation.
      Title: The structures of the kinase domain and UBA domain of MPK38 suggest the activation mechanism for kinase activity.
    8. These results indicate that Trx functions as a physiological inhibitor of MPK38, which plays an important role in inducing ASK1-, TGF-beta, and p53-mediated activity
      Title: Thioredoxin inhibits MPK38-induced ASK1, TGF-β, and p53 function in a phosphorylation-dependent manner.
    9. an important role for MPK38-mediated phosphorylation of PDK1 in the negative regulation of PDK1 activity.
      Title: PDK1 protein phosphorylation at Thr354 by murine protein serine-threonine kinase 38 contributes to negative regulation of PDK1 protein activity.
    10. MPK38 may act as a novel regulator for promoting p53 activity through direct phosphorylation of p53 at Ser(15).
      Title: Murine protein serine-threonine kinase 38 activates p53 function through Ser15 phosphorylation.
    Submit: New GeneRIF Correction See all GeneRIFs (14)

    Variation

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    Alleles

    Alleles of this type are documented at Mouse Genome Informatics  (MGI)
    • Gene trapped (1) 
    • Targeted (4)  1 citation
    • Endonuclease-mediated (4) 

    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 MGI

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables calcium ion binding ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables lipid binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables non-membrane spanning protein tyrosine kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables non-membrane spanning protein tyrosine kinase activity ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables nucleotide binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein serine/threonine kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein serine/threonine kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein serine/threonine kinase activity ISA
    Inferred from Sequence Alignment
    more info
    		 PubMed 
    enables protein serine/threonine kinase activity ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables protein serine/threonine kinase activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    enables protein tyrosine kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables transferase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in apoptotic process ISO
    Inferred from Sequence Orthology
    more info
    		  
    acts_upstream_of_or_within cell cycle IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cell population proliferation ISO
    Inferred from Sequence Orthology
    more info
    		  
    acts_upstream_of_or_within intrinsic apoptotic signaling pathway in response to oxidative stress IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in neural precursor cell proliferation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    acts_upstream_of_or_within phosphorylation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of apoptotic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein autophosphorylation ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in protein phosphorylation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    located_in cell cortex ISO
    Inferred from Sequence Orthology
    more info
    		  
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in plasma membrane ISO
    Inferred from Sequence Orthology
    more info
    		  

    General protein information

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    Preferred Names
    maternal embryonic leucine zipper kinase
    Names
    protein kinase PK38
    tyrosine-protein kinase MELK
    NP_001405928.1
    NP_001405929.1
    NP_034920.2
    XP_036019676.1

    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_001418999.1 → NP_001405928.1  maternal embryonic leucine zipper kinase isoform 2

      Status: VALIDATED

      Source sequence(s)
      AL805952, AL807399

    2. NM_001419000.1 → NP_001405929.1  maternal embryonic leucine zipper kinase isoform 3

      Status: VALIDATED

      Source sequence(s)
      AL805952, AL807399

    3. NM_010790.3 → NP_034920.2  maternal embryonic leucine zipper kinase isoform 1

      See identical proteins and their annotated locations for NP_034920.2

      Status: VALIDATED

      Source sequence(s)
      AL805952, AL807399
      Consensus CDS
      CCDS18124.1
      UniProtKB/Swiss-Prot
      Q3TPU1, Q61804, Q61846, Q6ZQH6
      UniProtKB/TrEMBL
      Q3TJF3, Q3TU15
      Related
      ENSMUSP00000043806.6, ENSMUST00000045607.12
      Conserved Domains (4) summary
      cd12198
      Location:547 → 641
      MELK_C; C-terminal kinase associated domain 1 (KA1) of Maternal embryonic leucine zipper kinase
      smart00220
      Location:11 → 263
      S_TKc; Serine/Threonine protein kinases, catalytic domain
      cd14341
      Location:281 → 332
      UBA_MELK; UBA domain found in maternal embryonic leucine zipper kinase (MELK) and similar proteins
      cd14078
      Location:7 → 263
      STKc_MELK; Catalytic domain of the Serine/Threonine Kinase, Maternal Embryonic Leucine zipper Kinase

    RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCm39 C57BL/6J

    Genomic

    1. NC_000070.7 Reference GRCm39 C57BL/6J

      Range
      44300876..44364301
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_036163783.1 → XP_036019676.1  maternal embryonic leucine zipper kinase isoform X2

      UniProtKB/TrEMBL
      Q3TU15
      Conserved Domains (2) summary
      cd14341
      Location:281 → 332
      UBA_MELK; UBA domain found in maternal embryonic leucine zipper kinase (MELK) and similar proteins
      cd14078
      Location:7 → 263
      STKc_MELK; Catalytic domain of the Serine/Threonine Kinase, Maternal Embryonic Leucine zipper Kinase
    Nucleotide Protein Strain
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q61846.2 GenPept UniProtKB/Swiss-Prot:Q61846

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