P50115 (S10A8_RAT) Reviewed, UniProtKB/Swiss-Prot
Last modified May 1, 2013. Version 102. History...
Names and origin
|Protein names||Recommended name:|
Migration inhibitory factor-related protein 8
S100 calcium-binding protein A8
|Organism||Rattus norvegicus (Rat) [Reference proteome]|
|Taxonomic identifier||10116 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus|
|Sequence length||89 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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. Activates NADPH-oxidase by facilitating the enzyme complex assembly at the cell membrane, transfering 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 proinfammatory, antimicrobial, oxidant-scavenging and apoptosis-inducing activities. Its proinflammatory 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 proinflammatory 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. Ref.3
Homodimer. Preferentially exists as a heterodimer or heterotetramer with S100A9 known as calprotectin (S100A8/A9). S100A8 interacts with AGER, ATP2A2 and with the heterodimeric complex formed by TLR4 and LY96. 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.
Secreted By similarity. Cytoplasm. Cytoplasm › cytoskeleton By similarity. Cell membrane; Peripheral membrane protein By similarity. 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 By similarity. Ref.3
Binds two calcium ions per molecule with an affinity similar to that of the S100 proteins By similarity.
Belongs to the S-100 family.
Contains 2 EF-hand domains.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Initiator methionine||1||1||Removed Ref.2|
|Chain||2 – 89||88||Protein S100-A8||PRO_0000143995|
|Domain||13 – 48||36||EF-hand 1|
|Domain||46 – 81||36||EF-hand 2|
|Calcium binding||20 – 33||14||1; low affinity Potential|
|Calcium binding||59 – 70||12||2; high affinity Potential|
|Metal binding||17||1||Zinc By similarity|
|Metal binding||27||1||Zinc By similarity|
|Metal binding||83||1||Zinc By similarity|
Amino acid modifications
|Modified residue||2||1||N-acetylalanine Ref.2|
|Modified residue||42||1||S-nitrosocysteine By similarity|
|Sequence conflict||73||1||V → A in AAA41637. Ref.1|
|||"Expression and cloning of migration inhibitory factor-related protein (MRP)8 and MRP14 in arthritis-susceptible rats."|
Imamichi T., Uchida I., Wahl S.M., McCartney-Francis N.
Biochem. Biophys. Res. Commun. 194:819-825(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Peritoneal cavity.
|||"Identification of posttranslational modifications and cDNA sequencing errors in the rat S100 proteins MRP8 and 14 using electrospray ionization mass spectrometry."|
Raftery M.J., Geczy C.L.
Anal. Biochem. 258:285-292(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-89, MASS SPECTROMETRY, ACETYLATION AT ALA-2.
|||"Dynamic mobility of immunological cells expressing S100A8 and S100A9 in vivo: a variety of functional roles of the two proteins as regulators in acute inflammatory reaction."|
Koike A., Arai S., Yamada S., Nagae A., Saita N., Itoh H., Uemoto S., Totani M., Ikemoto M.
Inflammation 35:409-419(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
|+||Additional computationally mapped references.|
|L18891 mRNA. Translation: AAA41637.1.|
|RefSeq||NP_446274.2. NM_053822.2. |
3D structure databases
|SMR||P50115. Positions 1-89. |
Protein-protein interaction databases
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSRNOT00000015473; ENSRNOP00000015473; ENSRNOG00000011557. |
|RGD||620265. S100a8. |
Gene expression databases
|GermOnline||ENSRNOG00000011557. Rattus norvegicus. |
Family and domain databases
|Gene3D||126.96.36.199. 1 hit. |
|InterPro||IPR011992. EF-hand-like_dom. |
|Pfam||PF01023. S_100. 1 hit. |
|PROSITE||PS00018. EF_HAND_1. 1 hit. |
PS50222. EF_HAND_2. 1 hit.
PS00303. S100_CABP. 1 hit.
|Accession||Primary (citable) accession number: P50115|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families