MARK4 (MAP/microtubule affinity-regulating kinase 4)

2003-05-01   Alessandro Beghini 

University of Milan, Medical Faculty, Department of Biology, Genetics for Medical Sciences, via Viotti 5, 20133-Milan, Italy

Identity

HGNC
LOCATION
19q13.32
IMAGE
Atlas Image
LOCUSID
ALIAS
MARK4L,MARK4S,MARKL1,MARKL1L,PAR-1D
FUSION GENES

DNA/RNA

Atlas Image

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 ).

Proteins

Atlas Image

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 name
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 name
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

Pubmed IDLast YearTitleAuthors
127353022003The 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 et al
97578321998MAPs, MARKs and microtubule dynamics.Drewes G et al
113263102001Isolation of a novel human gene, MARKL1, homologous to MARK3 and its involvement in hepatocellular carcinogenesis.Kato T et al
113479062001Prediction 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 et al

Other Information

Locus ID:

NCBI: 57787
MIM: 606495
HGNC: 13538
Ensembl: ENSG00000007047

Variants:

dbSNP: 57787
ClinVar: 57787
TCGA: ENSG00000007047
COSMIC: MARK4

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000007047ENST00000262891Q96L34
ENSG00000007047ENST00000300843Q96L34
ENSG00000007047ENST00000587566K7EK17
ENSG00000007047ENST00000590909K7EKG8
ENSG00000007047ENST00000592207K7EN95
ENSG00000007047ENST00000592762Q6IPE9
ENSG00000007047ENST00000620044Q6IPE9
ENSG00000007047ENST00000622871Q96GZ3

Expression (GTEx)

0
10
20
30
40
50
60
70

Pathways

PathwaySourceExternal ID
Organelle biogenesis and maintenanceREACTOMER-HSA-1852241
Cilium AssemblyREACTOMER-HSA-5617833
Anchoring of the basal body to the plasma membraneREACTOMER-HSA-5620912

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
204606222010Genome-wide analysis of genetic loci associated with Alzheimer disease.461
182547242008Control of AMPK-related kinases by USP9X and atypical Lys(29)/Lys(33)-linked polyubiquitin chains.89
145949452004MARK4 is a novel microtubule-associated proteins/microtubule affinity-regulating kinase that binds to the cellular microtubule network and to centrosomes.44
268825472016miR-515-5p controls cancer cell migration through MARK4 regulation.32
234009992013The microtubule affinity regulating kinase MARK4 promotes axoneme extension during early ciliogenesis.30
281838532017MARK4 inhibits Hippo signaling to promote proliferation and migration of breast cancer cells.21
231849422013Microtubule-associated protein/microtubule affinity-regulating kinase 4 (MARK4) is a negative regulator of the mammalian target of rapamycin complex 1 (mTORC1).19
206348912010Maternal genes and facial clefts in offspring: a comprehensive search for genetic associations in two population-based cleft studies from Scandinavia.18
127353022003The 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.15
236667622013Role of individual MARK isoforms in phosphorylation of tau at Ser²⁶² in Alzheimer's disease.15

Citation

Alessandro Beghini

MARK4 (MAP/microtubule affinity-regulating kinase 4)

Atlas Genet Cytogenet Oncol Haematol. 2003-05-01

Online version: http://atlasgeneticsoncology.org/gene/419/mark4