P27005 (S10A8_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein S100-A8

Alternative name(s):
Calgranulin-A
Chemotactic cytokine CP-10
Leukocyte L1 complex light chain
Migration inhibitory factor-related protein 8
Short name=MRP-8
Short name=p8
Pro-inflammatory S100 cytokine
S100 calcium-binding protein A8

Gene names

Name:	S100a8
Synonyms:	Caga, Mrp8

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	89 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

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. 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
Subunit structure	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
Subcellular location	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
Disruption phenotype	Death at an early embryonic stage due to embryo resorption, starting about 8 days after fertilization. Ref.6
Miscellaneous	Binds two calcium ions per molecule with an affinity similar to that of the S-100 proteins By similarity.
Sequence similarities	Belongs to the S-100 family. Contains 2 EF-hand domains.

Ontologies

Keywords
Biological process	Apoptosis Autophagy Chemotaxis Immunity Inflammatory response Innate immunity
Cellular component	Cell membrane Cytoplasm Cytoskeleton Membrane Secreted
Domain	Repeat
Ligand	Calcium Metal-binding Zinc
Molecular function	Antimicrobial Antioxidant
PTM	S-nitrosylation
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	activation of cysteine-type endopeptidase activity involved in apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB acute inflammatory response Inferred from electronic annotation. Source: Compara autophagy Inferred from sequence or structural similarity. Source: UniProtKB chronic inflammatory response Inferred from electronic annotation. Source: Compara induction of apoptosis Inferred from sequence or structural similarity. Source: UniProtKB innate immune response Inferred from electronic annotation. Source: UniProtKB-KW leukocyte migration involved in inflammatory response Inferred from sequence or structural similarity. Source: UniProtKB neutrophil aggregation Inferred from sequence or structural similarity. Source: UniProtKB neutrophil chemotaxis Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of inflammatory response Inferred from sequence or structural similarity. Source: UniProtKB response to ethanol Inferred from electronic annotation. Source: Compara response to lipopolysaccharide Inferred from electronic annotation. Source: Compara response to zinc ion Inferred from electronic annotation. Source: Compara wound healing Inferred from electronic annotation. Source: Compara
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell cytoskeleton Inferred from electronic annotation. Source: UniProtKB-SubCell extracellular space Inferred from electronic annotation. Source: Compara plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	antioxidant activity Inferred from electronic annotation. Source: UniProtKB-KW calcium ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Ref.5
	Chain	2 – 89	88	Protein S100-A8		PRO_0000143994
Regions
	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
Sites
	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
Experimental info
	Sequence conflict	57	1	E → D in CAA61204. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P27005 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: D2AFF46ACE867A28	FASTA	89	10,295
	10 20 30 40 50 60 MPSELEKALS NLIDVYHNYS NIQGNHHALY KNDFKKMVTT ECPQFVQNIN IENLFRELDI 70 80 NSDNAINFEE FLAMVIKVGV ASHKDSHKE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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]. Strain: BALB/c.
[2]	"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].
[3]	"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]. Strain: 129/SvJ. Tissue: Liver.
[4]	"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]. Strain: C57BL/6J. Tissue: Mammary gland.
[5]	"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. Tissue: Spleen.
[6]	"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.
[7]	"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.
[8]	"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.
[9]	"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.
[10]	"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.
[11]	"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.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M83218 mRNA. Translation: AAB07229.1. S57123 mRNA. Translation: AAB25840.1. X87966 Genomic DNA. Translation: CAA61204.1. BC078629 mRNA. Translation: AAH78629.1.
IPI	IPI00230768.
PIR	I56163.
RefSeq	NP_038678.1. NM_013650.2.
UniGene	Mm.21567.
3D structure databases
ProteinModelPortal	P27005.
SMR	P27005. Positions 1-89.
ModBase	Search...
Protein-protein interaction databases
IntAct	P27005. 1 interaction.
PTM databases
PhosphoSite	P27005.
Proteomic databases
PaxDb	P27005.
PRIDE	P27005.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000069927; ENSMUSP00000064385; ENSMUSG00000056054.
GeneID	20201.
KEGG	mmu:20201.
Organism-specific databases
CTD	6279.
MGI	MGI:88244. S100a8.
Phylogenomic databases
eggNOG	NOG39611.
HOGENOM	HOG000246968.
HOVERGEN	HBG001479.
InParanoid	P27005.
OMA	KDADTWF.
OrthoDB	EOG4V9TS7.
Gene expression databases
ArrayExpress	P27005.
Bgee	P27005.
CleanEx	MM_S100A8.
Genevestigator	P27005.
GermOnline	ENSMUSG00000056054. Mus musculus.
Family and domain databases
Gene3D	1.10.238.10. 1 hit.
InterPro	IPR011992. EF-hand-like_dom. IPR018247. EF_Hand_1_Ca_BS. IPR002048. EF_hand_dom. IPR001751. S100/CaBP-9k_CS. IPR013787. S100_Ca-bd_sub. [Graphical view]
Pfam	PF00036. efhand. 1 hit. PF01023. S_100. 1 hit. [Graphical view]
PROSITE	PS00018. EF_HAND_1. 1 hit. PS50222. EF_HAND_2. 1 hit. PS00303. S100_CABP. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	297779.
SOURCE	Search...

Entry information

Entry name

S10A8_MOUSE

Accession

Primary (citable) accession number: P27005
Secondary accession number(s): P31724

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1992
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 106 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program