P27005 (S10A8_MOUSE) Reviewed, UniProtKB/Swiss-Prot
Last modified November 13, 2013. Version 111. History...
Names and origin
|Protein names||Recommended name:|
Chemotactic cytokine CP-10
Leukocyte L1 complex light chain
Migration inhibitory factor-related protein 8
Pro-inflammatory S100 cytokine
S100 calcium-binding protein A8
|Organism||Mus musculus (Mouse) [Reference proteome]|
|Taxonomic identifier||10090 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus|
|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.7 Ref.8
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. Ref.7 Ref.8
Secreted. Cytoplasm By similarity. 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. Ref.7
Death at an early embryonic stage due to embryo resorption, starting about 8 days after fertilization. Ref.6
Binds two calcium ions per molecule with an affinity similar to that of the S-100 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.5|
|Chain||2 – 89||88||Protein S100-A8||PRO_0000143994|
|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||42||1||S-nitrosocysteine Ref.9|
|Sequence conflict||57||1||E → D in CAA61204. Ref.3|
|||"Mouse MRP8 and MRP14, two intracellular calcium-binding proteins associated with the development of the myeloid lineage."|
Lagasse E., Weissman I.L.
Blood 79:1907-1915(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
|||"Identification of a chemotactic domain of the pro-inflammatory S100 protein CP-10."|
Lackmann M., Rajasekariah P., Iismaa S.E., Jones G., Cornish C.J., Hu S., Simpson R.J., Moritz R.L., Geczy C.L.
J. Immunol. 150:2981-2991(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
|||"Molecular characterisation of the genomic locus of the mouse MRP8 gene."|
Nacken W.K.F., Manitz M.P., Sorg C.
Biochim. Biophys. Acta 1315:1-5(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
|||"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."|
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Mammary gland.
|||"Purification and structural analysis of a murine chemotactic cytokine (CP-10) with sequence homology to S100 proteins."|
Lackmann M., Cornish C.J., Simpson R.J., Moritz R.L., Geczy C.L.
J. Biol. Chem. 267:7499-7504(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-77.
|||"A null mutation in the inflammation-associated S100 protein S100A8 causes early resorption of the mouse embryo."|
Passey R.J., Williams E., Lichanska A.M., Wells C., Hu S., Geczy C.L., Little M.H., Hume D.A.
J. Immunol. 163:2209-2216(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
|||"Mrp8 and Mrp14 are endogenous activators of Toll-like receptor 4, promoting lethal, endotoxin-induced shock."|
Vogl T., Tenbrock K., Ludwig S., Leukert N., Ehrhardt C., van Zoelen M.A.D., Nacken W., Foell D., van der Poll T., Sorg C., Roth J.
Nat. Med. 13:1042-1049(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, INTERACTION WITH TLR4 AND LY96.
|||"S100A8 and S100A9 mediate endotoxin-induced cardiomyocyte dysfunction via the receptor for advanced glycation end products."|
Boyd J.H., Kan B., Roberts H., Wang Y., Walley K.R.
Circ. Res. 102:1239-1246(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH AGER AND ATP2A2.
|||"S-nitrosylated S100A8: novel anti-inflammatory properties."|
Lim S.Y., Raftery M., Cai H., Hsu K., Yan W.X., Hseih H.L., Watts R.N., Richardson D., Thomas S., Perry M., Geczy C.L.
J. Immunol. 181:5627-5636(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: S-NITROSYLATION AT CYS-42.
|||"Anti-infective protective properties of S100 calgranulins."|
Hsu K., Champaiboon C., Guenther B.D., Sorenson B.S., Khammanivong A., Ross K.F., Geczy C.L., Herzberg M.C.
Antiinflamm. Antiallergy Agents Med. Chem. 8:290-305(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
|||"Inflammation-associated S100 proteins: new mechanisms that regulate function."|
Goyette J., Geczy C.L.
Amino Acids 41:821-842(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
|+||Additional computationally mapped references.|
|M83218 mRNA. Translation: AAB07229.1.|
S57123 mRNA. Translation: AAB25840.1.
X87966 Genomic DNA. Translation: CAA61204.1.
BC078629 mRNA. Translation: AAH78629.1.
|RefSeq||NP_038678.1. NM_013650.2. |
3D structure databases
|SMR||P27005. Positions 1-89. |
Protein-protein interaction databases
|IntAct||P27005. 3 interactions.|
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSMUST00000069927; ENSMUSP00000064385; ENSMUSG00000056054. |
|UCSC||uc008qdd.1. mouse. |
|MGI||MGI:88244. S100a8. |
Gene expression databases
Family and domain databases
|Gene3D||126.96.36.199. 1 hit. |
|InterPro||IPR011992. EF-hand-dom_pair. |
|Pfam||PF00036. EF-hand_1. 1 hit. |
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: P27005|
Secondary accession number(s): P31724
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|