P29966 · MARCS_HUMAN

  • Protein
    Myristoylated alanine-rich C-kinase substrate
  • Gene
    MARCKS
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Membrane-associated protein that plays a role in the structural modulation of the actin cytoskeleton, chemotaxis, motility, cell adhesion, phagocytosis, and exocytosis through lipid sequestering and/or protein docking to membranes (PubMed:23704996, PubMed:36009319).
Thus, exerts an influence on a plethora of physiological processes, such as embryonic development, tissue regeneration, neuronal plasticity, and inflammation. Sequesters phosphatidylinositol 4,5-bisphosphate (PIP2) at lipid rafts in the plasma membrane of quiescent cells, an action reversed by protein kinase C, ultimately inhibiting exocytosis (PubMed:23704996).
During inflammation, promotes the migration and adhesion of inflammatory cells and the secretion of cytokines such as tumor necrosis factor (TNF), particularly in macrophages (PubMed:37949888).
Plays an essential role in bacteria-induced intracellular reactive oxygen species (ROS) formation in the monocytic cell type. Participates in the regulation of neurite initiation and outgrowth by interacting with components of cellular machinery including CDC42 that regulates cell shape and process extension through modulation of the cytoskeleton (By similarity).
Plays also a role in axon development by mediating docking and fusion of RAB10-positive vesicles with the plasma membrane (By similarity).

GO annotations

all annotationsall molecular functionvirus receptor activitydna bindingrna bindingcytoskeletal motor activitycatalytic activitygtpase activitystructural molecule activitytransporter activitycytoskeletal protein bindinglipid bindingcyclase activityantioxidant activityoxidoreductase activitytransferase activityhydrolase activitylyase activityisomerase activityligase activityprotein tag activitycargo receptor activityhistone bindingprotein folding chaperonetranslation regulator activitynutrient reservoir activityreceptor ligand activitymolecular transducer activitymolecular adaptor activitytoxin activitycell adhesion mediator activitymolecular function regulator activityvirus coreceptor activitycatalytic activity, acting on a proteincatalytic activity, acting on dnacatalytic activity, acting on rnamolecular carrier activitytranscription regulator activitygeneral transcription initiation factor activitymolecular sensor activitymolecular sequestering activityatp-dependent activityother molecular functionall biological processmitotic cell cyclecytokinesiscytoplasmic translationimmune system processmuscle system processcirculatory system processrenal system processrespiratory system processcarbohydrate metabolic processgeneration of precursor metabolites and energydna replicationdna repairdna recombinationchromatin organizationdna-templated transcriptionregulation of dna-templated transcriptiontrna metabolic processprotein foldingprotein glycosylationamino acid metabolic processmodified amino acid metabolic processlipid metabolic processvitamin metabolic processsulfur compound metabolic processintracellular protein transportnucleocytoplasmic transportautophagyinflammatory responsemitochondrion organizationcytoskeleton organizationmicrotubule-based movementperoxisome organizationlysosome organizationchromosome segregationcell adhesionestablishment or maintenance of cell polarityprogrammed cell deathphotosynthesismrna metabolic processsnrna metabolic processvesicle-mediated transportreproductive processdigestive system processsignalingcell differentiationprotein catabolic processextracellular matrix organizationregulatory ncrna-mediated gene silencingtelomere organizationcell junction organizationwound healingribosome biogenesiscilium organizationanatomical structure developmentcell motilitynervous system processendocrine processprotein maturationtransmembrane transportnucleobase-containing small molecule metabolic processhepaticobiliary system processmembrane organizationprotein-containing complex assemblycell wall organization or biogenesisnitrogen cycle metabolic processprotein localization to plasma membranedefense response to other organismdetoxificationmeiotic nuclear divisionmitotic nuclear divisionmitochondrial gene expressioncarbohydrate derivative metabolic processother biological processall cellular componentnuclear chromosomeextracellular regionextracellular spacecell wallnucleusnuclear envelopenucleoplasmchromosomenucleolusmitochondrionlysosomeendosomevacuoleperoxisomeendoplasmic reticulumgolgi apparatuslipid dropletmicrotubule organizing centercytosolribosomecytoskeletonplasma membraneciliumplastidthylakoidexternal encapsulating structureextracellular matrixcytoplasmic vesicleorganelleother cellular component
Cell color indicative of number of GO terms
AspectTerm
Cellular Componentactin cytoskeleton
Cellular Componentactin filament bundle
Cellular Componentcell cortex
Cellular Componentcentrosome
Cellular Componentcytoplasm
Cellular Componentextracellular exosome
Cellular Componentfocal adhesion
Cellular Componentgerminal vesicle
Cellular Componentplasma membrane
Molecular Functionactin filament binding
Molecular Functioncalmodulin binding
Molecular Functionidentical protein binding
Molecular Functionprotein kinase C binding
Biological Processactin crosslink formation
Biological Processactin filament bundle assembly
Biological Processactin filament organization
Biological Processapoptotic process
Biological Processcentral nervous system development
Biological Processmitochondrion organization
Biological Processneural tube development
Biological Processneurogenesis
Biological Processresponse to endoplasmic reticulum stress

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Myristoylated alanine-rich C-kinase substrate
  • Short names
    MARCKS
  • Alternative names
    • Protein kinase C substrate, 80 kDa protein, light chain (80K-L protein; PKCSL)

Gene names

    • Name
      MARCKS
    • Synonyms
      MACS, PRKCSL

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo

Accessions

  • Primary accession
    P29966
  • Secondary accessions
    • E1P560
    • Q2LA83
    • Q5TDB7

Proteomes

Organism-specific databases

Subcellular Location

Cell membrane
; Lipid-anchor
Cytoplasm
Note: PKC-dependent phosphorylation displaces MARCKS from the cell membrane and subsequent dephosphorylation is accompanied by its reassociation with the membrane.

Keywords

Disease & Variants

Features

Showing features for natural variant.

TypeIDPosition(s)Description
Natural variantVAR_025825250in dbSNP:rs45593337
Natural variantVAR_025826274in dbSNP:rs3734458

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 478 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

Organism-specific databases

Miscellaneous

Chemistry

Genetic variation databases

PTM/Processing

Features

Showing features for initiator methionine, lipidation, chain, modified residue, modified residue (large scale data).

TypeIDPosition(s)SourceDescription
Initiator methionine1UniProtRemoved
Lipidation2UniProtN-myristoyl glycine
ChainPRO_00001571482-332UniProtMyristoylated alanine-rich C-kinase substrate
Modified residue26UniProtPhosphoserine
Modified residue (large scale data)26PRIDEPhosphoserine
Modified residue27UniProtPhosphoserine
Modified residue (large scale data)27PRIDEPhosphoserine
Modified residue29UniProtPhosphoserine
Modified residue (large scale data)29PRIDEPhosphoserine
Modified residue46UniProtPhosphoserine
Modified residue (large scale data)46PRIDEPhosphoserine
Modified residue (large scale data)52PRIDEPhosphoserine
Modified residue63UniProtPhosphoserine
Modified residue (large scale data)63PRIDEPhosphoserine
Modified residue77UniProtPhosphoserine
Modified residue (large scale data)77PRIDEPhosphoserine
Modified residue81UniProtPhosphoserine
Modified residue (large scale data)81PRIDEPhosphoserine
Modified residue (large scale data)83PRIDEPhosphoserine
Modified residue101UniProtPhosphoserine
Modified residue (large scale data)101PRIDEPhosphoserine
Modified residue118UniProtPhosphoserine
Modified residue (large scale data)118PRIDEPhosphoserine
Modified residue (large scale data)120PRIDEPhosphothreonine
Modified residue128UniProtPhosphoserine
Modified residue (large scale data)128PRIDEPhosphoserine
Modified residue (large scale data)131PRIDEPhosphoserine
Modified residue (large scale data)134PRIDEPhosphoserine
Modified residue135UniProtPhosphoserine
Modified residue (large scale data)135PRIDEPhosphoserine
Modified residue143UniProtPhosphothreonine
Modified residue (large scale data)143PRIDEPhosphothreonine
Modified residue145UniProtPhosphoserine
Modified residue (large scale data)145PRIDEPhosphoserine
Modified residue147UniProtPhosphoserine
Modified residue (large scale data)147PRIDEPhosphoserine
Modified residue150UniProtPhosphothreonine
Modified residue (large scale data)150PRIDEPhosphothreonine
Modified residue159UniProtPhosphoserine; by PKC
Modified residue163UniProtPhosphoserine; by PKC
Modified residue (large scale data)163PRIDEPhosphoserine
Modified residue167UniProtPhosphoserine; by PKC
Modified residue (large scale data)167PRIDEPhosphoserine
Modified residue170UniProtPhosphoserine; by PKC
Modified residue (large scale data)170PRIDEPhosphoserine
Modified residue172UniProtN6-acetyllysine
Modified residue (large scale data)252PRIDEPhosphoserine
Modified residue262UniProtPhosphoserine
Modified residue314UniProtPhosphoserine

Post-translational modification

Phosphorylation by PKC displaces MARCKS from the membrane. It also inhibits the F-actin cross-linking activity. PKC-mediated phosphorylation increases 4 to 5-fold upon TNF-alpha or LPS induction.
Myristoylated. A proper myristoylation is essential for the proper distribution to the plasma membrane.
Acetylated at Lys-172 by KAT5; acetylation is required for its subsequent phosphorylation. Deacetylated by SIRT2.

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Detected in spermatozoa.

Induction

By TNF-alpha and LPS in monocytes.

Gene expression databases

Organism-specific databases

Interaction

Subunit

Interacts with CDC42 (By similarity).
Interacts with GTP-bound form of RAB10 (By similarity).
Interacts with calmodulin/CALM1 (By similarity).

Protein-protein interaction databases

Miscellaneous

Structure

Family & Domains

Features

Showing features for region, compositional bias.

TypeIDPosition(s)Description
Region1-332Disordered
Compositional bias125-148Polar residues
Region152-176Calmodulin-binding (PSD)
Compositional bias170-190Basic and acidic residues
Compositional bias252-273Basic and acidic residues

Sequence similarities

Belongs to the MARCKS family.

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    332
  • Mass (Da)
    31,555
  • Last updated
    2007-01-23 v4
  • Checksum
    0AB247801EF8FCBF
MGAQFSKTAAKGEAAAERPGEAAVASSPSKANGQENGHVKVNGDASPAAAESGAKEELQANGSAPAADKEEPAAAGSGAASPSAAEKGEPAAAAAPEAGASPVEKEAPAEGEAAEPGSPTAAEGEAASAASSTSSPKAEDGATPSPSNETPKKKKKRFSFKKSFKLSGFSFKKNKKEAGEGGEAEAPAAEGGKDEAAGGAAAAAAEAGAASGEQAAAPGEEAAAGEEGAAGGDPQEAKPQEAAVAPEKPPASDETKAAEEPSKVEEKKAEEAGASAAACEAPSAAGPGAPPEQEAAPAEEPAAAAASSACAAPSQEAQPECSPEAPPAEAAE

Features

Showing features for sequence conflict, compositional bias.

TypeIDPosition(s)Description
Sequence conflict84in Ref. 2; BAA01392
Sequence conflict119in Ref. 2; BAA01392
Compositional bias125-148Polar residues
Compositional bias170-190Basic and acidic residues
Sequence conflict225in Ref. 7
Sequence conflict234in Ref. 1; AAA59555
Sequence conflict235in Ref. 7
Compositional bias252-273Basic and acidic residues
Sequence conflict287-308in Ref. 1; AAA59555

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
M68956
EMBL· GenBank· DDBJ
AAA59555.1
EMBL· GenBank· DDBJ
mRNA
M68955
EMBL· GenBank· DDBJ
AAA59554.1
EMBL· GenBank· DDBJ
Genomic DNA
D10522
EMBL· GenBank· DDBJ
BAA01392.1
EMBL· GenBank· DDBJ
mRNA
DQ341274
EMBL· GenBank· DDBJ
ABC67467.1
EMBL· GenBank· DDBJ
Genomic DNA
AL132660
EMBL· GenBank· DDBJ
CAI19942.1
EMBL· GenBank· DDBJ
Genomic DNA
CH471051
EMBL· GenBank· DDBJ
EAW48258.1
EMBL· GenBank· DDBJ
Genomic DNA
CH471051
EMBL· GenBank· DDBJ
EAW48259.1
EMBL· GenBank· DDBJ
Genomic DNA
BC089040
EMBL· GenBank· DDBJ
AAH89040.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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