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MARK4 (MAP/microtubule affinity-regulating kinase 4)

Identity

Other namesMARKL1
KIAA1860
HGNC (Hugo) MARK4
LocusID (NCBI) 57787
Location 19q13.32
Location_base_pair Starts at 45754516 and ends at 45808541 bp from pter ( according to hg19-Feb_2009)  [Mapping]
 

DNA/RNA

 
Description Spans 55,6 kb; 18 exons
Transcription 3,6kb mRNA of MARK4S isoform, 3,22kb of MARK4L isoform (alternative splicing-skipping of exon 16, which leads to a change in the reading frame ).

Protein

 
Description 688 amino acids (aa) for MARK4S isoform and 752 aa for MARK4L isoform; belongs to the MARK family of protein kinases and contains from aa 59 to 314 a Serine-Threonine kinase catalytic domain with two activating phosphorylation sites. A short sequence (T region) contains a putative membrane-targeting motif. This region is followed by a ubiquitin-associated (UBA) domain. The spacer is the least-conserved region among MARKs proteins. This region is followed by a strikingly conserved C-terminal domain. In MARK4 the C-terminal domain differs between MARK4S and MARK4L isoforms.
Expression The MARK4S isoform is predominantly expressed in the brain and at low levels in the heart. The MARK4L isoform is expressed ubiquitously in all tissues, with a highly abundant expression in testis, neural progenitors and glial tumors. MARK4L is downregulated during glial differentiation.
Localisation Protein was detected homogeneously in cytoplasm.
Function MARK4 is considered to play a role as a messenger of the Wnt-signaling pathway. MARK4L represents a mitogenic-associated isoform.
Homology MARK1, MARK2 (Emk1), MARK3 (p78/C-TAK1), par1, kin1

Mutations

Note Mutations have not been detected.

Implicated in

Entity Hepatocellular carcinogenesis
Oncogenesis RT-PCR anaysis detected upregulated expression in nearly all clinical hepatocellular carcinoma cells in which nuclear accumulation of b-catenin was observed.
  
Entity Up-regulation and overexpression of MARK4 has been described in glial tumors and glioblastoma cell lines.
Oncogenesis MARK4 gene activation (enhanced expression and/or amplification) may result from intrachromosomal duplication upon 19q rearrangements.
  

External links

Nomenclature
HGNC (Hugo)MARK4   13538
Entrez_Gene (NCBI)MARK4  57787  MAP/microtubule affinity-regulating kinase 4
Cards
AtlasMARK4ID419
GeneCards (Weizmann)MARK4
Ensembl (Hinxton)ENSG00000007047 [Gene_View]  chr19:45754516-45808541 [Contig_View]  MARK4 [Vega]
AceView (NCBI)MARK4
Genatlas (Paris)MARK4
SOURCE (Stanford)NM_001199867 NM_031417
Genomic and cartography
GoldenPath (UCSC)MARK4  -  19q13.32   chr19:45754516-45808541 +  19q13.2   [Description]    (hg19-Feb_2009)
EnsemblMARK4 - 19q13.2 [CytoView]
Mapping of homologs : NCBIMARK4 [Mapview]
OMIM606495   
Gene and transcription
Genbank (Entrez)AB049127 AB058763 AB073663 AB088047 AK027619
RefSeq transcript (SRS)NM_001199867 NM_031417
RefSeq transcript (Entrez)NM_001199867 NM_031417
RefSeq genomic (SRS)AC_000151 NC_000019 NC_018930 NT_011109 NW_001838496 NW_004078099
RefSeq genomic (Entrez)AC_000151 NC_000019 NC_018930 NT_011109 NW_001838496 NW_004078099
Consensus coding sequences : CCDS (NCBI)MARK4
Cluster EST : UnigeneHs.34314 [ SRS ] Hs.34314 [ NCBI ]
CGAP (NCI)Hs.34314
Alternative Splicing : Fast-db (Paris)GSHG0015013
Alternative Splicing GalleryENSG00000007047
Gene ExpressionMARK4 [ NCBI-GEO ]   MARK4 [ EBI - ARRAY_EXPRESS ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ96L34 (SRS) Q96L34 (Uniprot)
NextProtQ96L34
With graphics : InterProQ96L34
Splice isoforms : SwissVarQ96L34(Swissvar)
Domaine pattern : Prosite (SRS)KA1 (PS50032)    PROTEIN_KINASE_ATP (PS00107)    PROTEIN_KINASE_DOM (PS50011)    PROTEIN_KINASE_ST (PS00108)    UBA (PS50030)   
Domaine pattern : Prosite (Expaxy)KA1 (PS50032)    PROTEIN_KINASE_ATP (PS00107)    PROTEIN_KINASE_DOM (PS50011)    PROTEIN_KINASE_ST (PS00108)    UBA (PS50030)   
Domains : Interpro (SRS)Kinase-assoc_KA1    Kinase-like_dom    Prot_kinase_cat_dom    Protein_kinase_ATP_BS    Ser/Thr_dual-sp_kinase_dom    Ser/Thr_kinase_AS    UBA/transl_elong_EF1B_N    UBA/transl_elong_EF1B_N_euk   
Domains : Interpro (EBI)Kinase-assoc_KA1    Kinase-like_dom    Prot_kinase_cat_dom    Protein_kinase_ATP_BS    Ser/Thr_dual-sp_kinase_dom    Ser/Thr_kinase_AS    UBA/transl_elong_EF1B_N    UBA/transl_elong_EF1B_N_euk   
Related proteins : CluSTrQ96L34
Domain families : Pfam (SRS)KA1 (PF02149)    Pkinase (PF00069)    UBA (PF00627)   
Domain families : Pfam (Sanger)KA1 (PF02149)    Pkinase (PF00069)    UBA (PF00627)   
Domain families : Pfam (NCBI)pfam02149    pfam00069    pfam00627   
Domain families : Smart (EMBL)S_TKc (SM00220)  UBA (SM00165)  
DMDM57787
Blocks (Seattle)Q96L34
Human Protein AtlasENSG00000007047
HPRD09402
IPIIPI00064797   IPI00297959   IPI00020326   IPI00450789   IPI00384052   IPI01013157   
Protein Interaction databases
DIP (DOE-UCLA)Q96L34
IntAct (EBI)Q96L34
FunCoupENSG00000007047
REACTOMEMARK4
Protein Interaction Database57787
BioGRIDMARK4
InParanoidQ96L34
Interologous Interaction database Q96L34
IntegromeDBMARK4
Polymorphism : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)MARK4
SNP (GeneSNP Utah)MARK4
SNP : HGBaseMARK4
Genetic variants : HAPMAPMARK4
Somatic Mutations in Cancer : COSMICMARK4 
CONAN: Copy Number AnalysisMARK4 
Mutations and Diseases : HGMDMARK4
OMIM606495   
GENETests606495   
Disease Genetic AssociationMARK4
Huge Navigator MARK4 [HugePedia]  MARK4 [HugeCancerGEM]
Genomic VariantsMARK4  MARK4 [DGVbeta]
snp3D : Map Gene to Disease57787
General knowledge
Homologs : HomoloGeneMARK4
Homology/Alignments : Family Browser (UCSC)MARK4
Phylogenetic Trees/Animal Genes : TreeFamMARK4
Catalytic activity : Enzyme2.7.11.1 [ Enzyme-Expasy ]   2.7.11.1 [ Enzyme-SRS ]   2.7.11.1 [ IntEnz-EBI ]   2.7.11.1 [ BRENDA ]   2.7.11.1 [ KEGG ]   
Chemical/Protein Interactions : CTD57787
Chemical/Pharm GKB GenePA30641
Clinical trialMARK4
Cancer Resource (Charite)ENSG00000007047
Ontology : AmiGOmicrotubule cytoskeleton organization  microtubule bundle formation  protein serine/threonine kinase activity  protein binding  ATP binding  centrosome  microtubule organizing center  protein phosphorylation  nervous system development  microtubule binding  microtubule cytoskeleton  neuron projection  gamma-tubulin binding  positive regulation of programmed cell death  ubiquitin binding  tau-protein kinase activity  
Ontology : EGO-EBImicrotubule cytoskeleton organization  microtubule bundle formation  protein serine/threonine kinase activity  protein binding  ATP binding  centrosome  microtubule organizing center  protein phosphorylation  nervous system development  microtubule binding  microtubule cytoskeleton  neuron projection  gamma-tubulin binding  positive regulation of programmed cell death  ubiquitin binding  tau-protein kinase activity  
Other databases
Probes
Litterature
PubMed27 Pubmed reference(s) in Entrez
PubGeneMARK4
iHOPMARK4

Bibliography

MAPs, MARKs and microtubule dynamics.
Drewes G, Ebneth A, Mandelkow EM
Trends in biochemical sciences. 1998 ; 23 (8) : 307-311.
PMID 9757832
 
Isolation of a novel human gene, MARKL1, homologous to MARK3 and its involvement in hepatocellular carcinogenesis.
Kato T, Satoh S, Okabe H, Kitahara O, Ono K, Kihara C, Tanaka T, Tsunoda T, Yamaoka Y, Nakamura Y, Furukawa Y
Neoplasia (New York, N.Y.). 2001 ; 3 (1) : 4-9.
PMID 11326310
 
Prediction of the coding sequences of unidentified human genes. XX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.
Nagase T, Nakayama M, Nakajima D, Kikuno R, Ohara O
DNA research : an international journal for rapid publication of reports on genes and genomes. 2001 ; 8 (2) : 85-95.
PMID 11347906
 
The neural progenitor-restricted isoform of the MARK4 gene in 19q13.2 is upregulated in human gliomas and overexpressed in a subset of glioblastoma cell lines.
Beghini A, Magnani I, Roversi G, Piepoli T, Di Terlizzi S, Moroni RF, Pollo B, Fuhrman Conti AM, Cowell JK, Finocchiaro G, Larizza L
Oncogene. 2003 ; 22 (17) : 2581-2591.
PMID 12735302
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written05-2003Alessandro Beghini

Citation

This paper should be referenced as such :
Beghini A . MARK4 (MAP/microtubule affinity-regulating kinase 4). Atlas Genet Cytogenet Oncol Haematol. May 2003 .
URL : http://AtlasGeneticsOncology.org/Genes/MARK4ID419.html

This paper is referenced by INIST as such :
http://documents.irevues.inist.fr/bitstream/2042/37977/1/05-2003-MARK4ID419.pdf   [ Bibliographic record ]

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indexed on : Wed May 1 13:05:58 CEST 2013

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