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P27005 (S10A8_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 117. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length89 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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, 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 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. Cytoplasmcytoskeleton 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 processApoptosis
Autophagy
Chemotaxis
Immunity
Inflammatory response
Innate immunity
   Cellular componentCell membrane
Cytoplasm
Cytoskeleton
Membrane
Secreted
   DomainRepeat
   LigandCalcium
Metal-binding
Zinc
   Molecular functionAntimicrobial
Antioxidant
   PTMS-nitrosylation
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processactivation 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: Ensembl

autophagy

Inferred from sequence or structural similarity. Source: UniProtKB

chronic inflammatory response

Inferred from electronic annotation. Source: Ensembl

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

positive regulation of intrinsic apoptotic signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

response to ethanol

Inferred from electronic annotation. Source: Ensembl

response to lipopolysaccharide

Inferred from electronic annotation. Source: Ensembl

response to zinc ion

Inferred from electronic annotation. Source: Ensembl

wound healing

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytoskeleton

Inferred from electronic annotation. Source: UniProtKB-SubCell

extracellular space

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionantioxidant activity

Inferred from electronic annotation. Source: UniProtKB-KW

arachidonic acid binding

Inferred from electronic annotation. Source: InterPro

calcium ion binding

Inferred from electronic annotation. Source: InterPro

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.5
Chain2 – 8988Protein S100-A8
PRO_0000143994

Regions

Domain13 – 4836EF-hand 1
Domain46 – 8136EF-hand 2
Calcium binding20 – 33141; low affinity Potential
Calcium binding59 – 70122; high affinity Potential

Sites

Metal binding171Zinc By similarity
Metal binding271Zinc By similarity
Metal binding831Zinc By similarity

Amino acid modifications

Modified residue421S-nitrosocysteine Ref.9

Experimental info

Sequence conflict571E → D in CAA61204. Ref.3

Sequences

Sequence LengthMass (Da)Tools
P27005 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: D2AFF46ACE867A28

FASTA8910,295
        10         20         30         40         50         60 
MPSELEKALS NLIDVYHNYS NIQGNHHALY KNDFKKMVTT ECPQFVQNIN IENLFRELDI 

        70         80 
NSDNAINFEE FLAMVIKVGV ASHKDSHKE 

« Hide

References

« Hide '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.
CCDSCCDS38507.1.
PIRI56163.
RefSeqNP_038678.1. NM_013650.2.
UniGeneMm.21567.

3D structure databases

ProteinModelPortalP27005.
SMRP27005. Positions 1-89.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP27005. 3 interactions.
MINTMINT-4133571.

PTM databases

PhosphoSiteP27005.

Proteomic databases

MaxQBP27005.
PaxDbP27005.
PRIDEP27005.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000069927; ENSMUSP00000064385; ENSMUSG00000056054.
GeneID20201.
KEGGmmu:20201.
UCSCuc008qdd.1. mouse.

Organism-specific databases

CTD6279.
MGIMGI:88244. S100a8.

Phylogenomic databases

eggNOGNOG39611.
HOGENOMHOG000246968.
HOVERGENHBG001479.
InParanoidP27005.
OMADTWFKEL.
OrthoDBEOG76HQ48.
PhylomeDBP27005.
TreeFamTF332727.

Gene expression databases

ArrayExpressP27005.
BgeeP27005.
CleanExMM_S100A8.
GenevestigatorP27005.

Family and domain databases

Gene3D1.10.238.10. 1 hit.
InterProIPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
IPR001751. S100/CaBP-9k_CS.
IPR013787. S100_Ca-bd_sub.
IPR028474. S100A8.
[Graphical view]
PANTHERPTHR11639:SF5. PTHR11639:SF5. 1 hit.
PfamPF00036. EF-hand_1. 1 hit.
PF01023. S_100. 1 hit.
[Graphical view]
PROSITEPS00018. EF_HAND_1. 1 hit.
PS50222. EF_HAND_2. 1 hit.
PS00303. S100_CABP. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio297779.
PROP27005.
SOURCESearch...

Entry information

Entry nameS10A8_MOUSE
AccessionPrimary (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: July 9, 2014
This is version 117 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot