| Written | 2003-05 | Alessandro Beghini |
| University of Milan, Medical Faculty, Department of Biology, Genetics for Medical Sciences, via Viotti 5, 20133-Milan, Italy |
| Identity |
| Alias (NCBI) | MARKL1 | KIAA1860 |
| HGNC (Hugo) | MARK4 |
| HGNC Alias symb | Nbla00650 | FLJ90097 | KIAA1860 | PAR-1D |
| HGNC Previous name | MARKL1 |
| HGNC Previous name | MAP/microtubule affinity-regulating kinase like 1 | MAP/microtubule affinity-regulating kinase 4 |
| LocusID (NCBI) | 57787 |
| Atlas_Id | 419 |
| Location | 19q13.32 [Link to chromosome band 19q13] |
| Location_base_pair | Starts at 45251271 and ends at 45305284 bp from pter ( according to hg19-Feb_2009) [Mapping MARK4.png] |
 | |
| Fusion genes (updated 2017) | Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands) |
| MARK4 (19q13.32) / LYPD5 (19q13.31) | PLAUR (19q13.31) / MARK4 (19q13.32) | THAP12 (11q13.5) / MARK4 (19q13.32) | |
| 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 |
| Note | |
| 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. |
| Bibliography |
| 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 |
| 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 |
| 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 journal version : [ pdf ] [ DOI ] |
| On line version : http://AtlasGeneticsOncology.org/Genes/MARK4ID419.html |
| Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ] |
|
t(19;19)(q13;q13) PLAUR/MARK4
|
| Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 1 ] |
|
MARK4/LYPD5 (19q13)
|
| External links |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Thu Jul 16 16:47:31 CEST 2020 |
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