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MARK4 (MAP/microtubule affinity-regulating kinase 4)

Identity

Other namesMARKL1
KIAA1860
Hugo MARK4
Location 19q13.2
 

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
HugoMARK4
GDBMARK4
Entrez_GeneMARK4  57787  MAP/microtubule affinity-regulating kinase 4
Cards
AtlasMARK4ID419
GeneCardsMARK4
EnsemblMARK4 [Search_View]   ENSG00000007047 [Gene_View]
GenatlasMARK4
GeneLynxMARK4
eGenomeMARK4
euGene57787
Genomic and cartography
GoldenPathMARK4  -  19q13.2   chr19:50446682-50500381 +  19q13.3   [Description]    (hg18-Mar_2006)
EnsemblMARK4 - 19q13.3 [CytoView]
NCBIMapview
OMIMDisease map [OMIM]
HomoloGeneMARK4
Gene and transcription
GenbankAB049127 [ ENTREZ ]
GenbankAB058763 [ ENTREZ ]
GenbankAB073663 [ ENTREZ ]
GenbankAB088047 [ ENTREZ ]
GenbankAK027619 [ ENTREZ ]
RefSeqNM_031417 [ SRS ]    NM_031417 [ ENTREZ ]
RefSeqAC_000062 [ SRS ]    AC_000062 [ ENTREZ ]
RefSeqNC_000019 [ SRS ]    NC_000019 [ ENTREZ ]
RefSeqNT_011109 [ SRS ]    NT_011109 [ ENTREZ ]
RefSeqNW_927217 [ SRS ]    NW_927217 [ ENTREZ ]
AceViewMARK4 AceView - NCBI
UnigeneHs.34314 [ SRS ]    Hs.34314 [ NCBI ]     HS34314 [ spliceNest ]
Fast-db13305 (alternative variants)
Protein : pattern, domain, 3D structure
SwissProtQ96L34 [ SRS]    Q96L34 [ EXPASY ]     Q96L34 [ INTERPRO ]
PrositePS50032 KA1 [ SRS ]    PS50032 KA1 [ Expasy ]
PrositePS00107 PROTEIN_KINASE_ATP [ SRS ]    PS00107 PROTEIN_KINASE_ATP [ Expasy ]
PrositePS50011 PROTEIN_KINASE_DOM [ SRS ]    PS50011 PROTEIN_KINASE_DOM [ Expasy ]
PrositePS00108 PROTEIN_KINASE_ST [ SRS ]    PS00108 PROTEIN_KINASE_ST [ Expasy ]
PrositePS50030 UBA [ SRS ]    PS50030 UBA [ Expasy ]
InterproIPR001772 Kinase_KA1 [ SRS ]    IPR001772 Kinase_KA1 [ EBI ]
InterproIPR000719 Prot_kinase_core [ SRS ]    IPR000719 Prot_kinase_core [ EBI ]
InterproIPR008271 Ser_thr_pkin_AS [ SRS ]    IPR008271 Ser_thr_pkin_AS [ EBI ]
InterproIPR002290 Ser_thr_pkinase [ SRS ]    IPR002290 Ser_thr_pkinase [ EBI ]
InterproIPR000449 UBA/transl_elong_EF1B_N [ SRS ]    IPR000449 UBA/transl_elong_EF1B_N [ EBI ]
InterproIPR015940 UBA/transl_elong_EF1B_N_euk [ SRS ]    IPR015940 UBA/transl_elong_EF1B_N_euk [ EBI ]
CluSTrQ96L34
PfamPF02149 KA1 [ SRS ]    PF02149 KA1 [ Sanger ]    pfam02149 [ NCBI-CDD ]
PfamPF00069 Pkinase [ SRS ]    PF00069 Pkinase [ Sanger ]    pfam00069 [ NCBI-CDD ]
PfamPF00627 UBA [ SRS ]    PF00627 UBA [ Sanger ]    pfam00627 [ NCBI-CDD ]
SmartSM00220 S_TKc [EMBL]
SmartSM00165 UBA [EMBL]
ProdomPD000001 Prot_kinase[INRA-Toulouse]
ProdomQ96L34 MARK4_HUMAN [ Domain structure ]   Q96L34 MARK4_HUMAN  [ sequences sharing at least 1 domain ]
BlocksQ96L34
HPRD09402
Protein Interaction databases
DIPQ96L34
IntActQ96L34
Polymorphism : SNP, mutations, diseases
OMIM606495    [ map ]   
GENECLINICS606495
SNPMARK4 [dbSNP-NCBI]  
SNPNM_031417 [SNP-NCI]  
SNPMARK4 [GeneSNPs - Utah]  MARK4] [HGBASE - SRS]
HAPMAPMARK4 [HAPMAP]  
COSMICMARK4 [Somatic mutation (COSMIC-CGP-Sanger)]  
HGMDMARK4
General knowledge
Family BrowserMARK4 [UCSC Family Browser]
SOURCENM_031417
SMDHs.34314
SAGEHs.34314
Enzyme2.7.11.1 [ Enzyme-SRS ]   2.7.11.1 [ Brenda-SRS ]   2.7.11.1 [ KEGG ]   2.7.11.1 [ WIT ]
GOG1/S transition of mitotic cell cycle [Amigo]  G1/S transition of mitotic cell cycle
GOG2/M transition of mitotic cell cycle [Amigo]  G2/M transition of mitotic cell cycle
GOnucleotide binding [Amigo]  nucleotide binding
GOgamma-tubulin complex [Amigo]  gamma-tubulin complex
GOmicrotubule bundle formation [Amigo]  microtubule bundle formation
GOmicrotubule bundle formation [Amigo]  microtubule bundle formation
GOprotein serine/threonine kinase activity [Amigo]  protein serine/threonine kinase activity
GOprotein serine/threonine kinase activity [Amigo]  protein serine/threonine kinase activity
GOprotein serine/threonine kinase activity [Amigo]  protein serine/threonine kinase activity
GOprotein serine/threonine kinase activity [Amigo]  protein serine/threonine kinase activity
GOprotein-tyrosine kinase activity [Amigo]  protein-tyrosine kinase activity
GOprotein binding [Amigo]  protein binding
GOATP binding [Amigo]  ATP binding
GOATP binding [Amigo]  ATP binding
GOcytoplasm [Amigo]  cytoplasm
GOcentrosome [Amigo]  centrosome
GOcentrosome [Amigo]  centrosome
GOmicrotubule organizing center [Amigo]  microtubule organizing center
GOmicrotubule [Amigo]  microtubule
GOprotein amino acid phosphorylation [Amigo]  protein amino acid phosphorylation
GOprotein amino acid phosphorylation [Amigo]  protein amino acid phosphorylation
GOprotein amino acid phosphorylation [Amigo]  protein amino acid phosphorylation
GOnervous system development [Amigo]  nervous system development
GOnervous system development [Amigo]  nervous system development
GOmicrotubule binding [Amigo]  microtubule binding
GOmicrotubule binding [Amigo]  microtubule binding
GOpositive regulation of cell proliferation [Amigo]  positive regulation of cell proliferation
GOWnt receptor signaling pathway [Amigo]  Wnt receptor signaling pathway
GOtransferase activity [Amigo]  transferase activity
GOneuron projection [Amigo]  neuron projection
GOneuron projection [Amigo]  neuron projection
GOgamma-tubulin binding [Amigo]  gamma-tubulin binding
GOgamma-tubulin binding [Amigo]  gamma-tubulin binding
GOpositive regulation of programmed cell death [Amigo]  positive regulation of programmed cell death
GOubiquitin binding [Amigo]  ubiquitin binding
GOtau-protein kinase activity [Amigo]  tau-protein kinase activity
GOtau-protein kinase activity [Amigo]  tau-protein kinase activity
PubGeneMARK4
TreeFamMARK4
CTD57787 [Comparative ToxicoGenomics Database]
Other databases
Probes
ProbeMARK4 Related clones (RZPD - Berlin)
PubMed
PubMed11 Pubmed reference(s) in LocusLink

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. May 2003 .
URL : http://AtlasGeneticsOncology.org/Genes/MARK4ID419.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Wed Jul 2 08:24:51 2008


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