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

Summary

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, Nov 2024]
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

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_000070.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
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.
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.
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.
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)

Endonuclease-mediated (4)
Gene trapped (1)
Targeted (4) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

AI327312 (e-PCR)
- UniSTS:163341

Melk (e-PCR), detects polymorphism
- UniSTS:507065

X95351 (e-PCR)
- UniSTS:125896

Melk (e-PCR), detects polymorphism
- UniSTS:143856

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables 3-phosphoinositide-dependent protein kinase activity	IEA Inferred from Electronic Annotation more info
enables AMP-activated protein kinase activity	IEA Inferred from Electronic Annotation more info
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables DNA-dependent protein kinase activity	IEA Inferred from Electronic Annotation more info
enables Rho-dependent protein serine/threonine kinase activity	IEA Inferred from Electronic Annotation more info
enables calcium ion binding	ISO Inferred from Sequence Orthology more info
enables calcium ion binding	ISS Inferred from Sequence or Structural Similarity more info
enables eukaryotic translation initiation factor 2alpha kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AS1 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AS121 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AT120 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AXS139 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2AXY142 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2BS14 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2BS36 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3S10 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3S28 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3S57 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3T11 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3T3 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3T45 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3T6 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3Y41 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H4S1 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 non-membrane spanning protein tyrosine kinase activity	ISS Inferred from Sequence or Structural Similarity 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 kinase activity	IEA Inferred from Electronic Annotation more info
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 ribosomal protein S6 kinase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in apoptotic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in cell population proliferation	ISO Inferred from Sequence Orthology more info
involved_in cell population proliferation	ISS Inferred from Sequence or Structural Similarity more info
involved_in chromatin remodeling	IEA Inferred from Electronic Annotation more info
involved_in hemopoiesis	ISS Inferred from Sequence or Structural Similarity 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
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 autophosphorylation	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
located_in cell cortex	ISO Inferred from Sequence Orthology more info
located_in cell cortex	ISS Inferred from Sequence or Structural Similarity more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	ISO Inferred from Sequence Orthology more info
located_in plasma membrane	ISS Inferred from Sequence or Structural Similarity 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

EC 2.7.10.2

EC 2.7.11.1

NP_001405929.1

EC 2.7.10.2

EC 2.7.11.1

NP_034920.2

EC 2.7.10.2

EC 2.7.11.1

XP_036019676.1

EC 2.7.10.2

EC 2.7.11.1

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)

NM_001418999.1 → NP_001405928.1 maternal embryonic leucine zipper kinase isoform 2

Status: VALIDATED

Source sequence(s)

AL805952, AL807399
NM_001419000.1 → NP_001405929.1 maternal embryonic leucine zipper kinase isoform 3

Status: VALIDATED

Source sequence(s)

AL805952, AL807399
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

NC_000070.7 Reference GRCm39 C57BL/6J

Range

44300876..44364301

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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