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MELK (maternal embryonic leucine zipper kinase)

Written2011-11Jean-Pierre Tassan
CNRS UMR 6061 Universite de Rennes 1, IFR140 GFAS, Faculte de medecine, 2 avenue du Professeur Leon Bernard, CS 34317, 35043 Rennes Cedex, France

(Note : for Links provided by Atlas : click)

Identity

Alias_symbol (synonym)KIAA0175
Other aliasHPK38
pEg3 kinase
HGNC (Hugo) MELK
LocusID (NCBI) 9833
Atlas_Id 43360
Location 9p13.2  [Link to chromosome band 9p13]
Location_base_pair Starts at 36572862 and ends at 36677683 bp from pter ( according to hg19-Feb_2009)  [Mapping MELK.png]
Fusion genes
(updated 2016)
GPR35 (2q37.3) / MELK (9p13.2)MELK (9p13.2) / STARD7 (2q11.2)MELK (9p13.2) / ZCCHC7 (9p13.2)
TRIM32 (9q33.1) / MELK (9p13.2)

DNA/RNA

Description The gene encompasses 105 kb; it has 18 exons.
Transcription The MELK gene generates multiple variants (potentially 28 different mRNAs). The longest mRNA is composed of 3218 nucleotides.

Protein

Note MELK (Maternal Embryonic Leucine zipper Kinase) belongs to the CAMK serine/threonine protein kinase superfamily. Melk is a protein serine/threonine kinase that is maximally active during mitosis. It is involved in diverse functions such as cell cycle, cytokinesis, mRNA splicing and apoptosis.
Description The full-length protein is 651 amino acids with an estimated molecular weight of approximately 74,5 kDa.
Expression MELK is expressed in cells of various tissue origins. MELK is highly expressed in oocytes, spermatogonia and embryos, which is indicative of a role in the germ-cell development. MELK is highly expressed in a large panel of cancers MELK expression is dependant on cell transformation (Gray et al., 2005). Its expression is strongly dependant on cell-cycle: MELK is undetectable in cells which have exited cell cycle (Badouel et al., 2010).
Localisation Cytoplasm, nucleus and cell cortex.
Function The exact function of MELK is currently unknown, however MELK was shown to be involved in cell cycle progression via the protein phosphatase CDC25B phosphorylation (Blot et al., 2002), in cytokinesis (Le Page et al., 2011), in apoptosis via its interaction with the Bcl-2 family of proapoptotic genes (Lin et al., 2007) and apoptosis signal-regulating kinase (ASK1) (Jung et al., 2008) and in inhibition of mRNA splicing during mitosis via its association with NIPP1 (Vulsteke et al., 2004). MELK function is required for mammary tumorigenesis in vivo (Hebbard et al., 2010).
Homology MELK belongs to the Kin1/PAR-1/MARK family of protein kinases found from yeast to human. These kinases are involved in cell polarity, dynamics of microtubules and intracellular signalisation.

Implicated in

Note
  
Entity Various cancers
Note Expression of MELK is more elevated in multiple cancers including colon, lung and ovary relative to corresponding normal tissues. Elevated MELK expression is correlated with cell transformation (Gray et al., 2005).
  
  
Entity Brain tumors
Note Expression of MELK was significantly higher in highly invasive glioblastomas multiform compared to benign pilocytic astrocytomas (Marie et al., 2008).
Prognosis Elevated MELK expression is associated with more aggressive behaviour and associated with poor prognosis of glioblastomas patients (Marie et al., 2008; Nakano et al., 2008).
  
  
Entity Breast cancer
Note MELK expression was found significantly upregulated in the breast cancers (Pickard et al., 2009).
Prognosis MELK expression is associated with poor patient survival.
  

Bibliography

Maternal embryonic leucine zipper kinase is stabilized in mitosis by phosphorylation and is partially degraded upon mitotic exit.
Badouel C, Chartrain I, Blot J, Tassan JP.
Exp Cell Res. 2010 Aug 1;316(13):2166-73. Epub 2010 Apr 24.
PMID 20420823
 
Cell cycle regulation of pEg3, a new Xenopus protein kinase of the KIN1/PAR-1/MARK family.
Blot J, Chartrain I, Roghi C, Philippe M, Tassan JP.
Dev Biol. 2002 Jan 15;241(2):327-38.
PMID 11784115
 
Maternal embryonic leucine zipper kinase/murine protein serine-threonine kinase 38 is a promising therapeutic target for multiple cancers.
Gray D, Jubb AM, Hogue D, Dowd P, Kljavin N, Yi S, Bai W, Frantz G, Zhang Z, Koeppen H, de Sauvage FJ, Davis DP.
Cancer Res. 2005 Nov 1;65(21):9751-61.
PMID 16266996
 
Maternal embryonic leucine zipper kinase is upregulated and required in mammary tumor-initiating cells in vivo.
Hebbard LW, Maurer J, Miller A, Lesperance J, Hassell J, Oshima RG, Terskikh AV.
Cancer Res. 2010 Nov 1;70(21):8863-73. Epub 2010 Sep 22.
PMID 20861186
 
Murine protein serine/threonine kinase 38 activates apoptosis signal-regulating kinase 1 via Thr 838 phosphorylation.
Jung H, Seong HA, Ha H.
J Biol Chem. 2008 Dec 12;283(50):34541-53. Epub 2008 Oct 23.
PMID 18948261
 
A functional analysis of MELK in cell division reveals a transition in the mode of cytokinesis during Xenopus development.
Le Page Y, Chartrain I, Badouel C, Tassan JP.
J Cell Sci. 2011 Mar 15;124(Pt 6):958-68.
PMID 21378312
 
Involvement of maternal embryonic leucine zipper kinase (MELK) in mammary carcinogenesis through interaction with Bcl-G, a pro-apoptotic member of the Bcl-2 family.
Lin ML, Park JH, Nishidate T, Nakamura Y, Katagiri T.
Breast Cancer Res. 2007;9(1):R17.
PMID 17280616
 
Maternal embryonic leucine zipper kinase transcript abundance correlates with malignancy grade in human astrocytomas.
Marie SK, Okamoto OK, Uno M, Hasegawa AP, Oba-Shinjo SM, Cohen T, Camargo AA, Kosoy A, Carlotti CG Jr, Toledo S, Moreira-Filho CA, Zago MA, Simpson AJ, Caballero OL.
Int J Cancer. 2008 Feb 15;122(4):807-15.
PMID 17960622
 
Maternal embryonic leucine zipper kinase is a key regulator of the proliferation of malignant brain tumors, including brain tumor stem cells.
Nakano I, Masterman-Smith M, Saigusa K, Paucar AA, Horvath S, Shoemaker L, Watanabe M, Negro A, Bajpai R, Howes A, Lelievre V, Waschek JA, Lazareff JA, Freije WA, Liau LM, Gilbertson RJ, Cloughesy TF, Geschwind DH, Nelson SF, Mischel PS, Terskikh AV, Kornblum HI.
J Neurosci Res. 2008 Jan;86(1):48-60.
PMID 17722061
 
Dysregulated expression of Fau and MELK is associated with poor prognosis in breast cancer.
Pickard MR, Green AR, Ellis IO, Caldas C, Hedge VL, Mourtada-Maarabouni M, Williams GT.
Breast Cancer Res. 2009;11(4):R60. Epub 2009 Aug 11.
PMID 19671159
 
Inhibition of spliceosome assembly by the cell cycle-regulated protein kinase MELK and involvement of splicing factor NIPP1.
Vulsteke V, Beullens M, Boudrez A, Keppens S, Van Eynde A, Rider MH, Stalmans W, Bollen M.
J Biol Chem. 2004 Mar 5;279(10):8642-7. Epub 2003 Dec 29.
PMID 14699119
 

Citation

This paper should be referenced as such :
Tassan, JP
MELK (maternal embryonic leucine zipper kinase)
Atlas Genet Cytogenet Oncol Haematol. 2012;16(4):273-274.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/MELKID43360ch9p13.html


External links

Nomenclature
HGNC (Hugo)MELK   16870
Cards
AtlasMELKID43360ch9p13
Entrez_Gene (NCBI)MELK  9833  maternal embryonic leucine zipper kinase
AliasesHPK38
GeneCards (Weizmann)MELK
Ensembl hg19 (Hinxton)ENSG00000165304 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000165304 [Gene_View]  chr9:36572862-36677683 [Contig_View]  MELK [Vega]
ICGC DataPortalENSG00000165304
TCGA cBioPortalMELK
AceView (NCBI)MELK
Genatlas (Paris)MELK
WikiGenes9833
SOURCE (Princeton)MELK
Genetics Home Reference (NIH)MELK
Genomic and cartography
GoldenPath hg38 (UCSC)MELK  -     chr9:36572862-36677683 +  9p13.2   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)MELK  -     9p13.2   [Description]    (hg19-Feb_2009)
EnsemblMELK - 9p13.2 [CytoView hg19]  MELK - 9p13.2 [CytoView hg38]
Mapping of homologs : NCBIMELK [Mapview hg19]  MELK [Mapview hg38]
OMIM607025   
Gene and transcription
Genbank (Entrez)AB183427 AB183428 AB267395 AI590871 AK222811
RefSeq transcript (Entrez)NM_001256685 NM_001256687 NM_001256688 NM_001256689 NM_001256690 NM_001256691 NM_001256692 NM_001256693 NM_014791
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)MELK
Cluster EST : UnigeneHs.184339 [ NCBI ]
CGAP (NCI)Hs.184339
Alternative Splicing GalleryENSG00000165304
Gene ExpressionMELK [ NCBI-GEO ]   MELK [ EBI - ARRAY_EXPRESS ]   MELK [ SEEK ]   MELK [ MEM ]
Gene Expression Viewer (FireBrowse)MELK [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)9833
GTEX Portal (Tissue expression)MELK
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ14680   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ14680  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ14680
Splice isoforms : SwissVarQ14680
Catalytic activity : Enzyme2.7.11.1 [ Enzyme-Expasy ]   2.7.11.12.7.11.1 [ IntEnz-EBI ]   2.7.11.1 [ BRENDA ]   2.7.11.1 [ KEGG ]   
PhosPhoSitePlusQ14680
Domaine pattern : Prosite (Expaxy)KA1 (PS50032)    PROTEIN_KINASE_ATP (PS00107)    PROTEIN_KINASE_DOM (PS50011)    PROTEIN_KINASE_ST (PS00108)   
Domains : Interpro (EBI)KA1/Ssp2_C    KA1_dom    Kinase-like_dom    MARK/par1    Prot_kinase_dom    Protein_kinase_ATP_BS    Ser/Thr_kinase_AS   
Domain families : Pfam (Sanger)KA1 (PF02149)    Pkinase (PF00069)   
Domain families : Pfam (NCBI)pfam02149    pfam00069   
Domain families : Smart (EMBL)S_TKc (SM00220)  
Conserved Domain (NCBI)MELK
DMDM Disease mutations9833
Blocks (Seattle)MELK
PDB (SRS)4BKY    4BKZ    4BL1    4D2P    4D2T    4D2V    4D2W    4IXP    4UMP    4UMQ    4UMR    4UMT    4UMU    5IH8    5IH9    5IHA    5IHC   
PDB (PDBSum)4BKY    4BKZ    4BL1    4D2P    4D2T    4D2V    4D2W    4IXP    4UMP    4UMQ    4UMR    4UMT    4UMU    5IH8    5IH9    5IHA    5IHC   
PDB (IMB)4BKY    4BKZ    4BL1    4D2P    4D2T    4D2V    4D2W    4IXP    4UMP    4UMQ    4UMR    4UMT    4UMU    5IH8    5IH9    5IHA    5IHC   
PDB (RSDB)4BKY    4BKZ    4BL1    4D2P    4D2T    4D2V    4D2W    4IXP    4UMP    4UMQ    4UMR    4UMT    4UMU    5IH8    5IH9    5IHA    5IHC   
Structural Biology KnowledgeBase4BKY    4BKZ    4BL1    4D2P    4D2T    4D2V    4D2W    4IXP    4UMP    4UMQ    4UMR    4UMT    4UMU    5IH8    5IH9    5IHA    5IHC   
SCOP (Structural Classification of Proteins)4BKY    4BKZ    4BL1    4D2P    4D2T    4D2V    4D2W    4IXP    4UMP    4UMQ    4UMR    4UMT    4UMU    5IH8    5IH9    5IHA    5IHC   
CATH (Classification of proteins structures)4BKY    4BKZ    4BL1    4D2P    4D2T    4D2V    4D2W    4IXP    4UMP    4UMQ    4UMR    4UMT    4UMU    5IH8    5IH9    5IHA    5IHC   
SuperfamilyQ14680
Human Protein AtlasENSG00000165304
Peptide AtlasQ14680
HPRD06119
IPIIPI00006471   IPI01012261   IPI01013813   IPI01011824   IPI01011744   IPI01013337   IPI01018865   IPI00922782   
Protein Interaction databases
DIP (DOE-UCLA)Q14680
IntAct (EBI)Q14680
FunCoupENSG00000165304
BioGRIDMELK
STRING (EMBL)MELK
ZODIACMELK
Ontologies - Pathways
QuickGOQ14680
Ontology : AmiGOG2/M transition of mitotic cell cycle  microtubule cytoskeleton organization  protein serine/threonine kinase activity  non-membrane spanning protein tyrosine kinase activity  calcium ion binding  protein binding  ATP binding  nucleus  plasma membrane  cell cortex  apoptotic process  cell proliferation  lipid binding  intrinsic apoptotic signaling pathway in response to oxidative stress  membrane  peptidyl-tyrosine phosphorylation  establishment of cell polarity  hemopoiesis  intracellular signal transduction  positive regulation of apoptotic process  protein autophosphorylation  neural precursor cell proliferation  
Ontology : EGO-EBIG2/M transition of mitotic cell cycle  microtubule cytoskeleton organization  protein serine/threonine kinase activity  non-membrane spanning protein tyrosine kinase activity  calcium ion binding  protein binding  ATP binding  nucleus  plasma membrane  cell cortex  apoptotic process  cell proliferation  lipid binding  intrinsic apoptotic signaling pathway in response to oxidative stress  membrane  peptidyl-tyrosine phosphorylation  establishment of cell polarity  hemopoiesis  intracellular signal transduction  positive regulation of apoptotic process  protein autophosphorylation  neural precursor cell proliferation  
NDEx NetworkMELK
Atlas of Cancer Signalling NetworkMELK
Wikipedia pathwaysMELK
Orthology - Evolution
OrthoDB9833
GeneTree (enSembl)ENSG00000165304
Phylogenetic Trees/Animal Genes : TreeFamMELK
HOVERGENQ14680
HOGENOMQ14680
Homologs : HomoloGeneMELK
Homology/Alignments : Family Browser (UCSC)MELK
Gene fusions - Rearrangements
Fusion : MitelmanGPR35/MELK [2q37.3/9p13.2]  [t(2;9)(q37;p13)]  
Fusion : MitelmanTRIM32/MELK [9q33.1/9p13.2]  [t(9;9)(p13;q33)]  
Fusion: TCGAGPR35 2q37.3 MELK 9p13.2 BRCA
Fusion: TCGATRIM32 9q33.1 MELK 9p13.2 BRCA
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerMELK [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)MELK
dbVarMELK
ClinVarMELK
1000_GenomesMELK 
Exome Variant ServerMELK
ExAC (Exome Aggregation Consortium)MELK (select the gene name)
Genetic variants : HAPMAP9833
Genomic Variants (DGV)MELK [DGVbeta]
DECIPHERMELK [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisMELK 
Mutations
ICGC Data PortalMELK 
TCGA Data PortalMELK 
Broad Tumor PortalMELK
OASIS PortalMELK [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICMELK  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDMELK
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch MELK
DgiDB (Drug Gene Interaction Database)MELK
DoCM (Curated mutations)MELK (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)MELK (select a term)
intoGenMELK
NCG5 (London)MELK
Cancer3DMELK(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM607025   
Orphanet
MedgenMELK
Genetic Testing Registry MELK
NextProtQ14680 [Medical]
TSGene9833
GENETestsMELK
Target ValidationMELK
Huge Navigator MELK [HugePedia]
snp3D : Map Gene to Disease9833
BioCentury BCIQMELK
ClinGenMELK
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD9833
Chemical/Pharm GKB GenePA134902874
Clinical trialMELK
Miscellaneous
canSAR (ICR)MELK (select the gene name)
Probes
Litterature
PubMed41 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineMELK
EVEXMELK
GoPubMedMELK
iHOPMELK
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Mon Sep 25 18:32:06 CEST 2017

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