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MARCKS (myristoylated alanine-rich protein kinase C substrate)

Written2012-11Atsuhiro Tanabe, Maho Saito
Division of Biochemistry, Department of Bioscience, Engineering, Shibaura Institute of Technology, Saitama, Japan

(Note : for Links provided by Atlas : click)


Alias (NCBI)80K-L
HGNC Alias symbPKCSL
HGNC Previous nameMACS
HGNC Previous namemyristoylated alanine-rich protein kinase C substrate (MARCKS, 80K-L)
LocusID (NCBI) 4082
Atlas_Id 50926
Location 6q21  [Link to chromosome band 6q21]
Location_base_pair Starts at 113857345 and ends at 113863475 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping MARCKS.png]
  Figure 1. A) MARCKS location on chromosome 6 is indicated. MARCKS gene starts at 114178527 and ends at 114184652. B) MARCKS gene is indicated. It has two exons and one intron.
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
MARCKS (6q21)::MARCKS (6q21)


Note The MARCKS gene is located 6q21 (114178527..114184652).
Transcription The transcription product is 6,1 kb with 2 exons. The mRNA has 996 bp open reading frame. The promoter region has no TATA box and contained multiple transcription initiation sites in a region spanning 57 base pairs (bp) (Harlan et al., 1991).


Note MARCKS was cloned as a protein kinase C (PKC) substrate. The protein binds plasma membrane via N-terminus myristoylation and the phosphorylation site domain (PSD), which is also called effector domain (ED), with electrostatic interaction. MARCKS interacts with actin, calmodulin, PIP2 on the PSD.
  Figure 2. A) MARCKS phosphorylation site domain (PSD (also called effector domain (ED)) is shown. It is mainly consisted of basic amino asids (K and R) and has serin residues phosphorylatable by PKC (159, 163 and 170) and by ROCK (at least 159). B) Dephospho MARCKS binds to plasma membrane and cross-links actin. Phospho MARCKS detached from plasma membrane and disrupts actin filaments.
Description Phosphorylation of MARCKS is instrumental in its redistribution. MARCKS possesses a basic phosphorylation site domain (PSD). Phosphorylation of this PSD domain prevents the electrostatic interaction of the effector region of the MARCKS to the plasma membrane (George and Blackshear, 1992; Taniguchi and Manenti, 1993; Kim et al., 1994).
Expression The MARCKS protein is highly expressed in the brain, spleen, and lung, and is virtually absent in skeletal muscle and liver in adult animal (Stumpo et al., 1989; Blackshear et al., 1986; Albert et al., 1986).
Localisation Dephosphorylated and phosphorylated MARCKS are located at plasma membrane and in cytosol, respectively.
Function MARCKS closs-links actin filament (Yarmola et al., 2001) and changes cell morphology responsing to cell stimulations in its phosphorylation/dephosphorylation-dependent manner (Tanabe et al., 2012). MARCKS participates in thrombin-induced noradrenaline release from platelets (Elzagallaai et al., 2001) and PMA- or bonbesin-induced neurotensin release from BON cells (Li et al., 2005). MARCKS regulates the proliferation and/or movement of some type of cells (Brooks et al.,1996; Zhao et al., 2000; Weimer et al., 2009). MARCKS plays a vital role in the normal developmental processes of neurulation, hemisphere fusion, forebrain commissure formation, and formation of cortical and retinal laminations (Stumpo et al., 1995). Long-term potentiation (LTP) is significantly impaired in the mossy fiber-CA3 pathway in MARCKS heterozygous mutant mice (Hussain et al., 2006).
Homology Human MARCKS protein (332 amino acids) was approximately 89, 74, and 59% identical to the bovine, mouse, and chicken proteins. N-terminal domain and phosphorylation site domain (PSD) are highly-conserved between species (from human to Xenopus).

Implicated in

Entity Melanoma
Note In MARCKS over expressed human tumor-derived choroidal melanoma cells (OCM-1) the growth was reduced by 35-40% when compared with control cells (Manenti et al., 1998). In a highly motile melanoma cell line WM-1617 melanoma cells nonphosphorylated MARCKS works as an adhesion stabilizer (Estrada-Bernal et al., 2009).
Entity Alzheimer disease (AD)
Note PKC-induced phosphorylation of MARCKS in cortical neurons in AD brains was weaker than that in control brains. However, phosphorylation of MARCKS was detected in microglia and dystrophic neurites within neuritic plaques (Kimura et al., 2000). In microglia amyloid β induces phosphorylation of MARCKS through mitogen-activatd protein kinase (MAPK) (Hasegawa et al., 2001) and PKCδ (Nakai et al., 2001).


Widespread occurrence of "87 kDa," a major specific substrate for protein kinase C.
Albert KA, Walaas SI, Wang JK, Greengard P.
Proc Natl Acad Sci U S A. 1986 May;83(9):2822-6.
PMID 3458242
Protein kinase C-stimulated phosphorylation in vitro of a Mr 80,000 protein phosphorylated in response to phorbol esters and growth factors in intact fibroblasts. Distinction from protein kinase C and prominence in brain.
Blackshear PJ, Wen L, Glynn BP, Witters LA.
J Biol Chem. 1986 Jan 25;261(3):1459-69.
PMID 3080427
MARCKS functions as a novel growth suppressor in cells of melanocyte origin.
Brooks G, Brooks SF, Goss MW.
Carcinogenesis. 1996 Apr;17(4):683-9.
PMID 8625478
Myristoylated alanine-rich C kinase substrate phosphorylation is involved in thrombin-induced serotonin release from platelets.
Elzagallaai A, Rose SD, Brandan NC, Trifaro JM.
Br J Haematol. 2001 Mar;112(3):593-602.
PMID 11260059
Dynamic adhesions and MARCKS in melanoma cells.
Estrada-Bernal A, Gatlin JC, Sunpaweravong S, Pfenninger KH.
J Cell Sci. 2009 Jul 1;122(Pt 13):2300-10. doi: 10.1242/jcs.047860. Epub 2009 Jun 9.
PMID 19509053
Membrane association of the myristoylated alanine-rich C kinase substrate (MARCKS) protein appears to involve myristate-dependent binding in the absence of a myristoyl protein receptor.
George DJ, Blackshear PJ.
J Biol Chem. 1992 Dec 5;267(34):24879-85.
PMID 1332970
The human myristoylated alanine-rich C kinase substrate (MARCKS) gene (MACS). Analysis of its gene product, promoter, and chromosomal localization.
Harlan DM, Graff JM, Stumpo DJ, Eddy RL Jr, Shows TB, Boyle JM, Blackshear PJ.
J Biol Chem. 1991 Aug 5;266(22):14399-405.
PMID 1860846
Microglial signaling by amyloid beta protein through mitogen-activated protein kinase mediating phosphorylation of MARCKS.
Hasegawa H, Nakai M, Tanimukai S, Taniguchi T, Terashima A, Kawamata T, Fukunaga K, Miyamoto E, Misaki K, Mukai H, Tanaka C.
Neuroreport. 2001 Aug 8;12(11):2567-71.
PMID 11496150
Myristoylated alanine rich C kinase substrate (MARCKS) heterozygous mutant mice exhibit deficits in hippocampal mossy fiber-CA3 long-term potentiation.
Hussain RJ, Stumpo DJ, Blackshear PJ, Lenox RH, Abel T, McNamara RK.
Hippocampus. 2006;16(5):495-503.
PMID 16572394
Phosphorylation, high ionic strength, and calmodulin reverse the binding of MARCKS to phospholipid vesicles.
Kim J, Shishido T, Jiang X, Aderem A, McLaughlin S.
J Biol Chem. 1994 Nov 11;269(45):28214-9.
PMID 7961759
Phosphorylation of MARCKS in Alzheimer disease brains.
Kimura T, Yamamoto H, Takamatsu J, Yuzuriha T, Miyamoto E, Miyakawa T.
Neuroreport. 2000 Mar 20;11(4):869-73.
PMID 10757536
Myristoylated alanine-rich C kinase substrate-mediated neurotensin release via protein kinase C-delta downstream of the Rho/ROK pathway.
Li J, O'Connor KL, Greeley GH Jr, Blackshear PJ, Townsend CM Jr, Evers BM.
J Biol Chem. 2005 Mar 4;280(9):8351-7. Epub 2004 Dec 28.
PMID 15623535
Overexpression of the myristoylated alanine-rich C kinase substrate in human choroidal melanoma cells affects cell proliferation.
Manenti S, Malecaze F, Chap H, Darbon JM.
Cancer Res. 1998 Apr 1;58(7):1429-34.
PMID 9537244
Amyloid beta protein activates PKC-delta and induces translocation of myristoylated alanine-rich C kinase substrate (MARCKS) in microglia.
Nakai M, Tanimukai S, Yagi K, Saito N, Taniguchi T, Terashima A, Kawamata T, Yamamoto H, Fukunaga K, Miyamoto E, Tanaka C.
Neurochem Int. 2001 Jun;38(7):593-600.
PMID 11290384
MARCKS deficiency in mice leads to abnormal brain development and perinatal death.
Stumpo DJ, Bock CB, Tuttle JS, Blackshear PJ.
Proc Natl Acad Sci U S A. 1995 Feb 14;92(4):944-8.
PMID 7862670
Molecular cloning, characterization, and expression of a cDNA encoding the "80- to 87-kDa" myristoylated alanine-rich C kinase substrate: a major cellular substrate for protein kinase C.
Stumpo DJ, Graff JM, Albert KA, Greengard P, Blackshear PJ.
Proc Natl Acad Sci U S A. 1989 Jun;86(11):4012-6.
PMID 2726763
MARCKS dephosphorylation is involved in bradykinin-induced neurite outgrowth in neuroblastoma SH-SY5Y cells.
Tanabe A, Shiraishi M, Negishi M, Saito N, Tanabe M, Sasaki Y.
J Cell Physiol. 2012 Feb;227(2):618-29. doi: 10.1002/jcp.22763.
PMID 21448919
Interaction of myristoylated alanine-rich protein kinase C substrate (MARCKS) with membrane phospholipids.
Taniguchi H, Manenti S.
J Biol Chem. 1993 May 15;268(14):9960-3.
PMID 8486722
MARCKS modulates radial progenitor placement, proliferation and organization in the developing cerebral cortex.
Weimer JM, Yokota Y, Stanco A, Stumpo DJ, Blackshear PJ, Anton ES.
Development. 2009 Sep;136(17):2965-75. doi: 10.1242/dev.036616.
PMID 19666823
Actin filament cross-linking by MARCKS: characterization of two actin-binding sites within the phosphorylation site domain.
Yarmola EG, Edison AS, Lenox RH, Bubb MR.
J Biol Chem. 2001 Jun 22;276(25):22351-8. Epub 2001 Apr 6.
PMID 11294839
Role of MARCKS in regulating endothelial cell proliferation.
Zhao Y, Neltner BS, Davis HW.
Am J Physiol Cell Physiol. 2000 Nov;279(5):C1611-20.
PMID 11029309


This paper should be referenced as such :
Tanabe, A ; Saito, M
MARCKS (myristoylated alanine-rich protein kinase C substrate)
Atlas Genet Cytogenet Oncol Haematol. 2013;17(4):266-268.
Free journal version : [ pdf ]   [ DOI ]

External links


HGNC (Hugo)MARCKS   6759
Atlas Explorer : (Salamanque)MARCKS
Entrez_Gene (NCBI)MARCKS    myristoylated alanine rich protein kinase C substrate
GeneCards (Weizmann)MARCKS
Ensembl hg19 (Hinxton)ENSG00000277443 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000277443 [Gene_View]  ENSG00000277443 [Sequence]  chr6:113857345-113863475 [Contig_View]  MARCKS [Vega]
ICGC DataPortalENSG00000277443
Genatlas (Paris)MARCKS
Genetics Home Reference (NIH)MARCKS
Genomic and cartography
GoldenPath hg38 (UCSC)MARCKS  -     chr6:113857345-113863475 +  6q21   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)MARCKS  -     6q21   [Description]    (hg19-Feb_2009)
GoldenPathMARCKS - 6q21 [CytoView hg19]  MARCKS - 6q21 [CytoView hg38]
Genome Data Viewer NCBIMARCKS [Mapview hg19]  
Gene and transcription
Genbank (Entrez)AI142997 AK027274 AK074526 AW163148 BC013004
RefSeq transcript (Entrez)NM_002356
Consensus coding sequences : CCDS (NCBI)MARCKS
Gene Expression Viewer (FireBrowse)MARCKS [ Firebrowse - Broad ]
GenevisibleExpression of MARCKS in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)4082
GTEX Portal (Tissue expression)MARCKS
Human Protein AtlasENSG00000277443-MARCKS [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP29966   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP29966  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP29966
Domaine pattern : Prosite (Expaxy)MARCKS_1 (PS00826)    MARCKS_2 (PS00827)   
Domains : Interpro (EBI)MARCKS   
Domain families : Pfam (Sanger)MARCKS (PF02063)   
Domain families : Pfam (NCBI)pfam02063   
Conserved Domain (NCBI)MARCKS
AlphaFold pdb e-kbP29966   
Human Protein Atlas [tissue]ENSG00000277443-MARCKS [tissue]
Protein Interaction databases
IntAct (EBI)P29966
Ontologies - Pathways
Ontology : AmiGOprotein kinase C binding  calmodulin binding  cytoplasm  centrosome  plasma membrane  plasma membrane  focal adhesion  cell cortex  actin filament organization  central nervous system development  actin cytoskeleton  actin filament bundle  germinal vesicle  identical protein binding  actin filament binding  actin filament bundle assembly  actin crosslink formation  extracellular exosome  
Ontology : EGO-EBIprotein kinase C binding  calmodulin binding  cytoplasm  centrosome  plasma membrane  plasma membrane  focal adhesion  cell cortex  actin filament organization  central nervous system development  actin cytoskeleton  actin filament bundle  germinal vesicle  identical protein binding  actin filament binding  actin filament bundle assembly  actin crosslink formation  extracellular exosome  
REACTOMEP29966 [protein]
REACTOME PathwaysR-HSA-399997 [pathway]   
Atlas of Cancer Signalling NetworkMARCKS
Wikipedia pathwaysMARCKS
Orthology - Evolution
GeneTree (enSembl)ENSG00000277443
Phylogenetic Trees/Animal Genes : TreeFamMARCKS
Homologs : HomoloGeneMARCKS
Homology/Alignments : Family Browser (UCSC)MARCKS
Gene fusions - Rearrangements
Fusion : QuiverMARCKS
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerMARCKS [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)MARCKS
Exome Variant ServerMARCKS
GNOMAD BrowserENSG00000277443
Varsome BrowserMARCKS
Genomic Variants (DGV)MARCKS [DGVbeta]
DECIPHERMARCKS [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisMARCKS 
Broad Tumor PortalMARCKS
OASIS PortalMARCKS [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICMARCKS  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DMARCKS
Mutations and Diseases : HGMDMARCKS
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
DgiDB (Drug Gene Interaction Database)MARCKS
DoCM (Curated mutations)MARCKS
CIViC (Clinical Interpretations of Variants in Cancer)MARCKS
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry MARCKS
NextProtP29966 [Medical]
Target ValidationMARCKS
Huge Navigator MARCKS [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTDMARCKS
Pharm GKB GenePA30637
Clinical trialMARCKS
DataMed IndexMARCKS
PubMed152 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Wed Jan 19 18:50:50 CET 2022

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