P27005 · S10A8_MOUSE

  • Protein
    Protein S100-A8
  • Gene
    S100a8
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

S100A8 is a calcium- and zinc-binding protein which plays a prominent role in the regulation of inflammatory processes and immune response. It can induce neutrophil chemotaxis and adhesion. Predominantly found as calprotectin (S100A8/A9) which has a wide plethora of intra- and extracellular functions. The intracellular functions include: facilitating leukocyte arachidonic acid trafficking and metabolism, modulation of the tubulin-dependent cytoskeleton during migration of phagocytes and activation of the neutrophilic NADPH-oxidase. Participates also in regulatory T-cell differentiation together with CD69. Activates NADPH-oxidase by facilitating the enzyme complex assembly at the cell membrane, transferring arachidonic acid, an essential cofactor, to the enzyme complex and S100A8 contributes to the enzyme assembly by directly binding to NCF2/P67PHOX. The extracellular functions involve pro-inflammatory, antimicrobial, oxidant-scavenging and apoptosis-inducing activities. Its pro-inflammatory activity includes recruitment of leukocytes, promotion of cytokine and chemokine production, and regulation of leukocyte adhesion and migration. Acts as an alarmin or a danger associated molecular pattern (DAMP) molecule and stimulates innate immune cells via binding to pattern recognition receptors such as Toll-like receptor 4 (TLR4) and receptor for advanced glycation endproducts (AGER). Binding to TLR4 and AGER activates the MAP-kinase and NF-kappa-B signaling pathways resulting in the amplification of the pro-inflammatory cascade. Has antimicrobial activity towards bacteria and fungi and exerts its antimicrobial activity probably via chelation of Zn2+ which is essential for microbial growth. Can induce cell death via autophagy and apoptosis and this occurs through the cross-talk of mitochondria and lysosomes via reactive oxygen species (ROS) and the process involves BNIP3. Can regulate neutrophil number and apoptosis by an anti-apoptotic effect; regulates cell survival via ITGAM/ITGB and TLR4 and a signaling mechanism involving MEK-ERK. Its role as an oxidant scavenger has a protective role in preventing exaggerated tissue damage by scavenging oxidants. The iNOS-S100A8/A9 transnitrosylase complex is proposed to direct selective inflammatory stimulus-dependent S-nitrosylation of multiple targets such as GAPDH, ANXA5, EZR, MSN and VIM by recognizing a [IL]-x-C-x-x-[DE] motif; S100A8 seems to contribute to S-nitrosylation site selectivity (By similarity).
(Microbial infection) Upon infection by murine coronavirus (MHV-A59), induces expansion of aberrant immature neutrophils in a TLR4-dependent manner.

Miscellaneous

Binds two calcium ions per molecule with an affinity similar to that of the S-100 proteins.

Activity regulation

Calprotectin (S100A8/A9) activity on TLR4 signaling is inhibited by paquinimod.

Features

Showing features for binding site.

TypeIDPosition(s)Description
Binding site17Zn2+ (UniProtKB | ChEBI)
Binding site27Zn2+ (UniProtKB | ChEBI)
Binding site33Ca2+ 1 (UniProtKB | ChEBI); low affinity
Binding site59Ca2+ 2 (UniProtKB | ChEBI); high affinity
Binding site61Ca2+ 2 (UniProtKB | ChEBI); high affinity
Binding site63Ca2+ 2 (UniProtKB | ChEBI); high affinity
Binding site70Ca2+ 2 (UniProtKB | ChEBI); high affinity
Binding site83Zn2+ (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentcalprotectin complex
Cellular Componentcytosol
Cellular Componentextracellular space
Cellular Componentintermediate filament cytoskeleton
Cellular Componentplasma membrane
Molecular Functionantioxidant activity
Molecular Functioncalcium ion binding
Molecular Functioncalcium-dependent protein binding
Biological Processactivation of cysteine-type endopeptidase activity involved in apoptotic process
Biological Processapoptotic process
Biological Processastrocyte development
Biological Processautocrine signaling
Biological Processautophagy
Biological Processinnate immune response
Biological Processleukocyte migration involved in inflammatory response
Biological Processneutrophil aggregation
Biological Processneutrophil chemotaxis
Biological Processpeptide secretion
Biological Processpositive regulation of inflammatory response
Biological Processpositive regulation of intrinsic apoptotic signaling pathway
Biological Processpositive regulation of peptide secretion
Biological Processregulation of toll-like receptor signaling pathway
Biological Processresponse to lipopolysaccharide

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Protein S100-A8
  • Alternative names
    • Calgranulin-A
    • Chemotactic cytokine CP-10
    • Leukocyte L1 complex light chain
    • Migration inhibitory factor-related protein 8 (MRP-8; p8)
    • Pro-inflammatory S100 cytokine
    • S100 calcium-binding protein A8

Gene names

    • Name
      S100a8
    • Synonyms
      Caga, Mrp8

Organism names

  • Taxonomic identifier
  • Strains
    • BALB/cJ
    • 129/SvJ
    • C57BL/6J
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    P27005
  • Secondary accessions
    • P31724

Proteomes

Organism-specific databases

Subcellular Location

Secreted
Cytoplasm
Cell membrane
; Peripheral membrane protein
Note: Predominantly localized in the cytoplasm. Upon elevation of the intracellular calcium level, translocated from the cytoplasm to the cytoskeleton and the cell membrane. Upon neutrophil activation or endothelial adhesion of monocytes, is secreted via a microtubule-mediated, alternative pathway.

Keywords

Phenotypes & Variants

Disruption phenotype

Death at an early embryonic stage due to embryo resorption, starting about 8 days after fertilization.

Variants

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

The viewer provides 20 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

PTM/Processing

Features

Showing features for initiator methionine, chain, modified residue.

TypeIDPosition(s)Description
Initiator methionine1Removed
ChainPRO_00001439942-89Protein S100-A8
Modified residue42S-nitrosocysteine

Keywords

Proteomic databases

PTM databases

Expression

Gene expression databases

Interaction

Subunit

Homodimer. Preferentially exists as a heterodimer or heterotetramer with S100A9 known as calprotectin (S100A8/A9). Calprotectin (S100A8/9) interacts with CEACAM3 and tubulin filaments in a calcium-dependent manner. Heterotetrameric calprotectin (S100A8/A9) interacts with ANXA6 and associates with tubulin filaments in activated monocytes. S100A8 and calprotectin (S100A8/9) interact with NCF2/P67PHOX, RAC1 and RAC2. Calprotectin (S100A8/9) interacts with CYBA and CYBB (By similarity).
S100A8 interacts with AGER, ATP2A2 and with the heterodimeric complex formed by TLR4 and LY96. Calprotectin (S100A8/9) interacts with NOS2 to form the iNOS-S100A8/A9 transnitrosylase complex (By similarity).
Calprotectin (S100A8/9) interacts with CD69 (By similarity).

Protein-protein interaction databases

Miscellaneous

Structure

Family & Domains

Features

Showing features for domain.

TypeIDPosition(s)Description
Domain13-48EF-hand 1
Domain46-81EF-hand 2

Sequence similarities

Belongs to the S-100 family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    89
  • Mass (Da)
    10,295
  • Last updated
    2007-01-23 v3
  • Checksum
    D2AFF46ACE867A28
MPSELEKALSNLIDVYHNYSNIQGNHHALYKNDFKKMVTTECPQFVQNINIENLFRELDINSDNAINFEEFLAMVIKVGVASHKDSHKE

Features

Showing features for sequence conflict.

TypeIDPosition(s)Description
Sequence conflict57in Ref. 3; CAA61204

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
M83218
EMBL· GenBank· DDBJ
AAB07229.1
EMBL· GenBank· DDBJ
mRNA
S57123
EMBL· GenBank· DDBJ
AAB25840.1
EMBL· GenBank· DDBJ
mRNA
X87966
EMBL· GenBank· DDBJ
CAA61204.1
EMBL· GenBank· DDBJ
Genomic DNA
BC078629
EMBL· GenBank· DDBJ
AAH78629.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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