Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

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
Cards
AtlasMARK4ID419
Entrez_Gene (NCBI)MARK4  57787  MAP/microtubule affinity-regulating kinase 4
GeneCards (Weizmann)MARK4
Ensembl (Hinxton)ENSG00000007047 [Gene_View]  chr19:45754516-45808541 [Contig_View]  MARK4 [Vega]
ICGC DataPortalENSG00000007047
cBioPortalMARK4
AceView (NCBI)MARK4
Genatlas (Paris)MARK4
WikiGenes57787
SOURCE (Princeton)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 (Entrez)NM_001199867 NM_031417
RefSeq genomic (Entrez)AC_000151 NC_000019 NC_018930 NT_011109 NW_001838496 NW_004929415
Consensus coding sequences : CCDS (NCBI)MARK4
Cluster EST : UnigeneHs.34314 [ NCBI ]
CGAP (NCI)Hs.34314
Alternative Splicing : Fast-db (Paris)GSHG0015013
Alternative Splicing GalleryENSG00000007047
Gene ExpressionMARK4 [ NCBI-GEO ]     MARK4 [ SEEK ]   MARK4 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ96L34 (Uniprot)
NextProtQ96L34  [Medical]
With graphics : InterProQ96L34
Splice isoforms : SwissVarQ96L34 (Swissvar)
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 ]   
Domaine pattern : Prosite (Expaxy)KA1 (PS50032)    PROTEIN_KINASE_ATP (PS00107)    PROTEIN_KINASE_DOM (PS50011)    PROTEIN_KINASE_ST (PS00108)    UBA (PS50030)   
Domains : Interpro (EBI)KA1/Ssp2_C [organisation]   KA1_dom [organisation]   Kinase-like_dom [organisation]   Prot_kinase_dom [organisation]   Protein_kinase_ATP_BS [organisation]   Ser/Thr_dual-sp_kinase_dom [organisation]   Ser/Thr_kinase_AS [organisation]   UBA/transl_elong_EF1B_N_euk [organisation]   UBA/Ts_N [organisation]  
Related proteins : CluSTrQ96L34
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)  
DMDM Disease mutations57787
Blocks (Seattle)Q96L34
Human Protein AtlasENSG00000007047 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasQ96L34
HPRD09402
IPIIPI00064797   IPI00297959   IPI00020326   IPI00450789   IPI00384052   IPI01013157   
Protein Interaction databases
DIP (DOE-UCLA)Q96L34
IntAct (EBI)Q96L34
FunCoupENSG00000007047
BioGRIDMARK4
InParanoidQ96L34
Interologous Interaction database Q96L34
IntegromeDBMARK4
STRING (EMBL)MARK4
Ontologies - Pathways
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  
Protein Interaction DatabaseMARK4
Wikipedia pathwaysMARK4
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)MARK4
snp3D : Map Gene to Disease57787
SNP (GeneSNP Utah)MARK4
SNP : HGBaseMARK4
Genetic variants : HAPMAPMARK4
Exome VariantMARK4
1000_GenomesMARK4 
ICGC programENSG00000007047 
Somatic Mutations in Cancer : COSMICMARK4 
CONAN: Copy Number AnalysisMARK4 
Mutations and Diseases : HGMDMARK4
Mutations and Diseases : intOGenMARK4
Genomic VariantsMARK4  MARK4 [DGVbeta]
dbVarMARK4
ClinVarMARK4
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM606495   
MedgenMARK4
GENETestsMARK4
Disease Genetic AssociationMARK4
Huge Navigator MARK4 [HugePedia]  MARK4 [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneMARK4
Homology/Alignments : Family Browser (UCSC)MARK4
Phylogenetic Trees/Animal Genes : TreeFamMARK4
Chemical/Protein Interactions : CTD57787
Chemical/Pharm GKB GenePA30641
Clinical trialMARK4
Cancer Resource (Charite)ENSG00000007047
Other databases
Probes
Litterature
PubMed31 Pubmed reference(s) in Entrez
CoreMineMARK4
iHOPMARK4
OncoSearchMARK4

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

Search in all EBI   NCBI

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. 2003;7(3):162-164.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/MARK4ID419.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Tue Aug 26 15:27:58 CEST 2014

Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.