P29966 · MARCS_HUMAN
- ProteinMyristoylated alanine-rich C-kinase substrate
- GeneMARCKS
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids332 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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).
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 annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | actin cytoskeleton | |
Cellular Component | actin filament bundle | |
Cellular Component | cell cortex | |
Cellular Component | centrosome | |
Cellular Component | cytoplasm | |
Cellular Component | extracellular exosome | |
Cellular Component | focal adhesion | |
Cellular Component | germinal vesicle | |
Cellular Component | plasma membrane | |
Molecular Function | actin filament binding | |
Molecular Function | calmodulin binding | |
Molecular Function | identical protein binding | |
Molecular Function | protein kinase C binding | |
Biological Process | actin crosslink formation | |
Biological Process | actin filament bundle assembly | |
Biological Process | actin filament organization | |
Biological Process | apoptotic process | |
Biological Process | central nervous system development | |
Biological Process | mitochondrion organization | |
Biological Process | neural tube development | |
Biological Process | neurogenesis | |
Biological Process | response to endoplasmic reticulum stress |
Keywords
- Molecular function
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameMyristoylated alanine-rich C-kinase substrate
- Short namesMARCKS
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP29966
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Lipid-anchor
Note: PKC-dependent phosphorylation displaces MARCKS from the cell membrane and subsequent dephosphorylation is accompanied by its reassociation with the membrane.
Keywords
- Cellular component
Disease & Variants
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_025825 | 250 | in dbSNP:rs45593337 | |||
Sequence: P → L | ||||||
Natural variant | VAR_025826 | 274 | in dbSNP:rs3734458 | |||
Sequence: A → V |
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.
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).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Initiator methionine | 1 | UniProt | Removed | ||||
Sequence: M | |||||||
Lipidation | 2 | UniProt | N-myristoyl glycine | ||||
Sequence: G | |||||||
Chain | PRO_0000157148 | 2-332 | UniProt | Myristoylated alanine-rich C-kinase substrate | |||
Sequence: GAQFSKTAAKGEAAAERPGEAAVASSPSKANGQENGHVKVNGDASPAAAESGAKEELQANGSAPAADKEEPAAAGSGAASPSAAEKGEPAAAAAPEAGASPVEKEAPAEGEAAEPGSPTAAEGEAASAASSTSSPKAEDGATPSPSNETPKKKKKRFSFKKSFKLSGFSFKKNKKEAGEGGEAEAPAAEGGKDEAAGGAAAAAAEAGAASGEQAAAPGEEAAAGEEGAAGGDPQEAKPQEAAVAPEKPPASDETKAAEEPSKVEEKKAEEAGASAAACEAPSAAGPGAPPEQEAAPAEEPAAAAASSACAAPSQEAQPECSPEAPPAEAAE | |||||||
Modified residue | 26 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 26 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 27 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 27 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 29 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 29 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 46 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 46 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 52 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 63 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 63 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 77 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 77 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 81 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 81 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 83 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 101 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 101 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 118 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 118 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 120 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 128 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 128 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 131 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 134 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 135 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 135 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 143 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 143 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 145 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 145 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 147 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 147 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 150 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 150 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 159 | UniProt | Phosphoserine; by PKC | ||||
Sequence: S | |||||||
Modified residue | 163 | UniProt | Phosphoserine; by PKC | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 163 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 167 | UniProt | Phosphoserine; by PKC | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 167 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 170 | UniProt | Phosphoserine; by PKC | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 170 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 172 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 252 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 262 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 314 | UniProt | Phosphoserine | ||||
Sequence: S |
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
- PTM
Proteomic databases
PTM databases
Structure
Family & Domains
Features
Showing features for region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-332 | Disordered | ||||
Sequence: MGAQFSKTAAKGEAAAERPGEAAVASSPSKANGQENGHVKVNGDASPAAAESGAKEELQANGSAPAADKEEPAAAGSGAASPSAAEKGEPAAAAAPEAGASPVEKEAPAEGEAAEPGSPTAAEGEAASAASSTSSPKAEDGATPSPSNETPKKKKKRFSFKKSFKLSGFSFKKNKKEAGEGGEAEAPAAEGGKDEAAGGAAAAAAEAGAASGEQAAAPGEEAAAGEEGAAGGDPQEAKPQEAAVAPEKPPASDETKAAEEPSKVEEKKAEEAGASAAACEAPSAAGPGAPPEQEAAPAEEPAAAAASSACAAPSQEAQPECSPEAPPAEAAE | ||||||
Compositional bias | 125-148 | Polar residues | ||||
Sequence: EAASAASSTSSPKAEDGATPSPSN | ||||||
Region | 152-176 | Calmodulin-binding (PSD) | ||||
Sequence: KKKKKRFSFKKSFKLSGFSFKKNKK | ||||||
Compositional bias | 170-190 | Basic and acidic residues | ||||
Sequence: SFKKNKKEAGEGGEAEAPAAE | ||||||
Compositional bias | 252-273 | Basic and acidic residues | ||||
Sequence: SDETKAAEEPSKVEEKKAEEAG |
Sequence similarities
Belongs to the MARCKS family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length332
- Mass (Da)31,555
- Last updated2007-01-23 v4
- Checksum0AB247801EF8FCBF
Features
Showing features for sequence conflict, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 84 | in Ref. 2; BAA01392 | ||||
Sequence: A → S | ||||||
Sequence conflict | 119 | in Ref. 2; BAA01392 | ||||
Sequence: P → A | ||||||
Compositional bias | 125-148 | Polar residues | ||||
Sequence: EAASAASSTSSPKAEDGATPSPSN | ||||||
Compositional bias | 170-190 | Basic and acidic residues | ||||
Sequence: SFKKNKKEAGEGGEAEAPAAE | ||||||
Sequence conflict | 225 | in Ref. 7 | ||||
Sequence: G → R | ||||||
Sequence conflict | 234 | in Ref. 1; AAA59555 | ||||
Sequence: P → S | ||||||
Sequence conflict | 235 | in Ref. 7 | ||||
Sequence: Q → E | ||||||
Compositional bias | 252-273 | Basic and acidic residues | ||||
Sequence: SDETKAAEEPSKVEEKKAEEAG | ||||||
Sequence conflict | 287-308 | in Ref. 1; AAA59555 | ||||
Sequence: PGAPPEQEAAPAEEPAAAAASS → LVCPRRGGSPRGGARGRRSLNQ |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
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 |