Gene Report

Basic Information

Approved Symbol	MARCKS
Approved Name	myristoylated alanine-rich protein kinase C substrate
Previous Symbol	MACS
Previous Name	"myristoylated alanine-rich protein kinase C substrate (MARCKS, 80K-L)"
Symbol Alias	PKCSL, 80K-L
Location	6q21
Position	chr6:114181756-114184652 (+)
External Links	Entrez Gene: 4082 Ensembl: ENSG00000155130 UCSC: uc003pvy.4 HGNC ID: 6759
No. of Studies (Positive/Negative)	1(1/0)
Type	Literature-origin

Positive relationships between MARCKS and MDD (count: 1)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
MARCKS	Redei, 2015	Patients and nomal controls	P-value=0.005	Blood transcript levels of nine markers¡ªADCY3(adenylate cyc...... Blood transcript levels of nine markers¡ªADCY3(adenylate cyclase 3, which shows suggestive associationin GWASs with MDD,52 but highly significant association with body mass index in children53), DGKA, FAM46A, IGSF4A/CADM1,KIAA1539, MARCKS (myristoylated alanine-rich protein kinase C substrate, regulated by Ca2+/calmodulin), PSME1, RAPH1, and TLR7 differed significantly between MDD patients and ND controls at baseline. More...

Positive relationships between MARCKS and other components at different levels (count: 0)

Positive relationship network of MARCKS in MK4MDD

Network loading ...

Note:
1. The different color of the nodes denotes the level of the nodes.

Genetic/Epigenetic Locus	Protein and Other Molecule	Cell and Molecular Pathway	Neural System	Cognition and Behavior	Symptoms and Signs	Environment	MDD

2. Besides the component related relationships from literature, gene mapped protein and protein mapped gene are also shown in the network. If the mapped gene or protein is not from literature, square node would be used instead of Circle node. Accordingly, the relationship is marked with dot line.
2. User can drag the nodes to rearrange the layout of the network. Click the node will enter the report page of the node. Right-click will show also the menus to link to the report page of the node and remove the node and related edges. Hover the node will show the level of the node and hover the edge will show the evidence/description of the edge.
3. The network is generated using Cytoscape Web

Negative relationships between MARCKS and MDD (count: 0)

Negative relationships between MARCKS and other components at different levels (count: 0)

MARCKS related SNPs in MK4MDD (count: 0)

MARCKS related proteins in MK4MDD (count: 0)

MARCKS related GO terms (count: 33)

ID	Name	Type	Evidence
Literature-origin GO terms
GO:0043197	dendritic spine	cellular component	IEA

ID	Name	Type	Evidence
Gene mapped GO terms
GO:0001786	phosphatidylserine binding	molecular function	IEA
GO:0005938	cell cortex	cellular component	IEA
GO:0005080	protein kinase C binding	molecular function	IEA
GO:0043679	axon terminus	cellular component	IEA
GO:0032059	bleb	cellular component	IEA
GO:0031589	cell-substrate adhesion	biological process	IEA
GO:0006112	energy reserve metabolic process	biological process	TAS
GO:0042585	germinal vesicle	cellular component	IEA
GO:0031584	activation of phospholipase D activity	biological process	IEA
GO:0006886	intracellular protein transport	biological process	IEA
GO:0015629	actin cytoskeleton	cellular component	TAS[1560845]
GO:0001520	outer dense fiber	cellular component	IEA
GO:0070062	extracellular exosome	cellular component	IDA[19056867\|20458337\|23376485]
GO:1900020	positive regulation of protein kinase C activity	biological process	IEA
GO:0007015	actin filament organization	biological process	IEA
GO:0005813	centrosome	cellular component	IEA
GO:0061003	positive regulation of dendritic spine morphogenesis	biological process	IEA
GO:0033391	chromatoid body	cellular component	IEA
GO:0051015	actin filament binding	molecular function	TAS[1560845]
GO:0003229	ventricular cardiac muscle tissue development	biological process	IEA
GO:0005516	calmodulin binding	molecular function	IEA
GO:0005925	focal adhesion	cellular component	IDA[21423176]
GO:0007420	brain development	biological process	IEA
GO:0005874	microtubule	cellular component	IEA
GO:0050796	regulation of insulin secretion	biological process	TAS
GO:0030426	growth cone	cellular component	IEA
GO:2001275	positive regulation of glucose import in response to insulin stimulus	biological process	IEA
GO:0044281	small molecule metabolic process	biological process	TAS
GO:0005829	cytosol	cellular component	IEA
GO:0044307	dendritic branch	cellular component	IEA
GO:0005764	lysosome	cellular component	IEA
GO:0005886	plasma membrane	cellular component	TAS

MARCKS related KEGG pathways (count: 1)

ID	Name	Brief Description	Full Description
Gene mapped KEGG pathways
hsa04666	fc gamma_r_mediated_phagocytosis	Fc gamma R-mediated phagocytosis	Phagocytosis plays an essential role in host-defense mechani...... Phagocytosis plays an essential role in host-defense mechanisms through the uptake and destruction of infectious pathogens. Specialized cell types including macrophages, neutrophils, and monocytes take part in this process in higher organisms. After opsonization with antibodies (IgG), foreign extracellular materials are recognized by Fc gamma receptors. Cross-linking of Fc gamma receptors initiates a variety of signals mediated by tyrosine phosphorylation of multiple proteins, which lead through the actin cytoskeleton rearrangements and membrane remodeling to the formation of phagosomes. Nascent phagosomes undergo a process of maturation that involves fusion with lysosomes. The acquisition of lysosomal proteases and release of reactive oxygen species are crucial for digestion of engulfed materials in phagosomes. More...

MARCKS related BioCarta pathways (count: 1)

ID	Name	Brief Description	Full Description
Gene mapped BioCarta pathways
CALCINEURIN_PATHWAY	calcineurin pathway	Effects of calcineurin in Keratinocyte Differentiation	The differentiation of keratinocytes constantly replenishes ...... The differentiation of keratinocytes constantly replenishes the upper layers of human skin we lose each day. One factor that contributes to terminal keratinocyte differentiation is increased levels of intracellular calcium. Adding calcium to the medium of cultured keratinocytes elevates intracellular calcium and triggers differentiation. Intracellular calcium levels are also increased in response to phospholipase C activation, producing IP3 and releasing calcium from stores in the ER. Intracellular calcium alters multiple signaling pathways, one of which is binding to calmodulin to activate the serine-threonine protein phosphatase calcineurin. Calcineurin dephosphorylates and activates the transcription factor NFAT and both calcineurin and NFAT are expressed in differentiating keratinocytes. Activated NFAT can regulate transcription through binding its own cognate DNA binding site. One marker of keratinocyte differentiation, the p21 gene, is activated by NFAT by a different mechanism, with NFAT activating the p21 promoter by acting as a coactivator for the transcription factors Sp1 and Sp3. Another protein activated by calcium that may be involved in keratinocyte differentiation is protein kinase C (PKC). One substrate of activated PKC is MARCKS (myristoylated alanine-rich kinase C substrate). Phosphorylation of MARCKS by PKC in intact keratinocytes is not induced during calcium-induced differentiation, but does increase when tested in vitro. PKC activity is increased by calcium during keratinocyte differentiation but PKC MARCKS phosphorylation is blocked by the formation of a complex between calmodulin and MARCKS. The immunosuppressants cyclosporin-A (CsA) and FK506 inhibit T cell activation through indirect inhibition of NFAT activation and have several side effects including changes in the skin, suggesting that calcineurin activity may play a role in normal skin physiology. CsA is used to treat psoriasis, a disease involving abnormal proliferation of skin cells. The activity of CsA in treating psoriasis may involve inhibition of immune cells, but may also directly involve inhibition of calcineurin activity in keratinocytes. More...

MARCKS related Reactome pathways (count: 3)

ID	Name	Description
Gene mapped Reactome pathways
REACT_18405	regulation of_insulin_secretion_by_acetylcholine	Acetylcholine released by parasympathetic nerve endings in t...... Acetylcholine released by parasympathetic nerve endings in the pancreas causes a potentiation of insulin release when glucose is present at concentrations greater than about 7 mM. Acetylcholine binds the Muscarinic Acetylcholine Receptor M3 on pancreatic beta cells. The binding has two effects: an increase in permeability of the cell to Na+ ions through an unknown mechanism, and the activation of Phospholipase C beta-1 through a heterotrimeric G protein, G(q). After acetylcholine binds the Muscarinic Acetycholine Receptor M3, the receptor activates the G protein Gq by causing the alpha subunit of Gq to exchange GDP for GTP. Activation of Gq in turn activates Phospholipase C beta-1. Phospholipase C beta-1 hydrolyzes the phosphodiester bond at the third position of phosphoinositol 4,5-bisphosphate, producing diacylglycerols (DAG) and inositol 1,4,5-trisphosphate. DAG remains in the cell membrane and causes Protein Kinase C alpha (PKC alpha) to translocate from the cytosol to the membrane. This results in the activation of PKC alpha which then phosphorylates target proteins on serine and threonine residues. One known target of PKC alpha is Myristoylated Alanine-rich C Kinase Substrate (MARCKS), which is believed to affect vesicle transport and may be responsible for the increased traffic of insulin granules seen in response to acetylcholine. Inositol trisphophate binds a receptor, the IP3 receptor, on calcium stores in the cell (probably the endoplasmic reticulum). The release of calcium into the cytosol stimulates the exocytosis of insulin granules. More...
REACT_15380	diabetes pathways
REACT_18325	regulation of_insulin_secretion	Pancreatic beta cells integrate signals from several metabol...... Pancreatic beta cells integrate signals from several metabolites and hormones to control the secretion of insulin. In general, glucose triggers insulin secretion while other factors can amplify or inhibit the amount of insulin secreted in response to glucose. Factors which increase insulin secretion include the incretin hormones Glucose-dependent insulinotropic polypeptide (GIP and glucagon-like peptide-1 (GLP-1), acetylcholine, and fatty acids. Factors which inhibit insulin secretion include adrenaline and noradrenaline. More...

MARCKS related interactors from protein-protein interaction data in HPRD (count: 7)

Gene	Interactor	Interactor in MK4MDD?	Experiment Type	PMID
MARCKS	PKN1	No	in vitro	11930178 , 8557118
MARCKS	CALM2	Yes	in vitro	12577052
MARCKS	CTSB	Yes	in vitro	9295331
MARCKS	PRKCA	No	in vitro;in vivo	11930178 , 8557118 , 8034575 , 2473066
MARCKS	NMT1	No	in vitro	10734119
MARCKS	TOB1	Yes	in vitro;yeast 2-hybrid	11327693
MARCKS	PRKCB	Yes	in vitro	11930178 , 8557118 , 7588787

Gene Report

Literature-origin GO terms

Gene mapped GO terms

Gene mapped KEGG pathways

Gene mapped BioCarta pathways

Gene mapped Reactome pathways