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P27005

- S10A8_MOUSE

UniProt

P27005 - S10A8_MOUSE

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Protein

Protein S100-A8

Gene

S100a8

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.2 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi17 – 171ZincBy similarity
Metal bindingi27 – 271ZincBy similarity
Metal bindingi83 – 831ZincBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Calcium bindingi20 – 33141; low affinityPROSITE-ProRule annotationAdd
BLAST
Calcium bindingi59 – 70122; high affinityPROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. antioxidant activity Source: UniProtKB-KW
  2. arachidonic acid binding Source: InterPro
  3. calcium ion binding Source: InterPro
  4. zinc ion binding Source: InterPro

GO - Biological processi

  1. activation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
  2. acute inflammatory response Source: Ensembl
  3. autophagy Source: UniProtKB
  4. chronic inflammatory response Source: Ensembl
  5. innate immune response Source: UniProtKB-KW
  6. leukocyte migration involved in inflammatory response Source: UniProtKB
  7. neutrophil aggregation Source: UniProtKB
  8. neutrophil chemotaxis Source: UniProtKB
  9. positive regulation of inflammatory response Source: UniProtKB
  10. positive regulation of intrinsic apoptotic signaling pathway Source: UniProtKB
  11. response to ethanol Source: Ensembl
  12. response to lipopolysaccharide Source: Ensembl
  13. response to zinc ion Source: Ensembl
  14. wound healing Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Antimicrobial, Antioxidant

Keywords - Biological processi

Apoptosis, Autophagy, Chemotaxis, Immunity, Inflammatory response, Innate immunity

Keywords - Ligandi

Calcium, Metal-binding, Zinc

Names & Taxonomyi

Protein namesi
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 namesi
Name:S100a8
Synonyms:Caga, Mrp8
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 3

Organism-specific databases

MGIiMGI:88244. S100a8.

Subcellular locationi

Secreted 1 Publication. Cytoplasm By similarity. Cytoplasmcytoskeleton By similarity. Cell membrane By similarity; 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.

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB-KW
  2. cytoskeleton Source: UniProtKB-KW
  3. extracellular space Source: Ensembl
  4. extracellular vesicular exosome Source: Ensembl
  5. nucleus Source: Ensembl
  6. plasma membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoskeleton, Membrane, Secreted

Pathology & Biotechi

Disruption phenotypei

Death at an early embryonic stage due to embryo resorption, starting about 8 days after fertilization.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed1 Publication
Chaini2 – 8988Protein S100-A8PRO_0000143994Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei42 – 421S-nitrosocysteine1 Publication

Keywords - PTMi

S-nitrosylation

Proteomic databases

MaxQBiP27005.
PaxDbiP27005.
PRIDEiP27005.

PTM databases

PhosphoSiteiP27005.

Expressioni

Gene expression databases

BgeeiP27005.
CleanExiMM_S100A8.
ExpressionAtlasiP27005. baseline and differential.
GenevestigatoriP27005.

Interactioni

Subunit structurei

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.By similarity2 Publications

Protein-protein interaction databases

IntActiP27005. 3 interactions.
MINTiMINT-4133571.

Structurei

3D structure databases

ProteinModelPortaliP27005.
SMRiP27005. Positions 1-89.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini13 – 4836EF-hand 1PROSITE-ProRule annotationAdd
BLAST
Domaini46 – 8136EF-hand 2PROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Belongs to the S-100 family.Curated
Contains 2 EF-hand domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiNOG39611.
HOGENOMiHOG000246968.
HOVERGENiHBG001479.
InParanoidiP27005.
OMAiDTWFKEL.
OrthoDBiEOG76HQ48.
PhylomeDBiP27005.
TreeFamiTF332727.

Family and domain databases

Gene3Di1.10.238.10. 1 hit.
InterProiIPR011992. 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]
PANTHERiPTHR11639:SF5. PTHR11639:SF5. 1 hit.
PfamiPF00036. EF-hand_1. 1 hit.
PF01023. S_100. 1 hit.
[Graphical view]
PROSITEiPS00018. EF_HAND_1. 1 hit.
PS50222. EF_HAND_2. 1 hit.
PS00303. S100_CABP. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P27005-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MPSELEKALS NLIDVYHNYS NIQGNHHALY KNDFKKMVTT ECPQFVQNIN
60 70 80
IENLFRELDI NSDNAINFEE FLAMVIKVGV ASHKDSHKE
Length:89
Mass (Da):10,295
Last modified:January 23, 2007 - v3
Checksum:iD2AFF46ACE867A28
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti57 – 571E → D in CAA61204. (PubMed:8611640)Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M83218 mRNA. Translation: AAB07229.1.
S57123 mRNA. Translation: AAB25840.1.
X87966 Genomic DNA. Translation: CAA61204.1.
BC078629 mRNA. Translation: AAH78629.1.
CCDSiCCDS38507.1.
PIRiI56163.
RefSeqiNP_038678.1. NM_013650.2.
UniGeneiMm.21567.

Genome annotation databases

EnsembliENSMUST00000069927; ENSMUSP00000064385; ENSMUSG00000056054.
GeneIDi20201.
KEGGimmu:20201.
UCSCiuc008qdd.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M83218 mRNA. Translation: AAB07229.1 .
S57123 mRNA. Translation: AAB25840.1 .
X87966 Genomic DNA. Translation: CAA61204.1 .
BC078629 mRNA. Translation: AAH78629.1 .
CCDSi CCDS38507.1.
PIRi I56163.
RefSeqi NP_038678.1. NM_013650.2.
UniGenei Mm.21567.

3D structure databases

ProteinModelPortali P27005.
SMRi P27005. Positions 1-89.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi P27005. 3 interactions.
MINTi MINT-4133571.

PTM databases

PhosphoSitei P27005.

Proteomic databases

MaxQBi P27005.
PaxDbi P27005.
PRIDEi P27005.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000069927 ; ENSMUSP00000064385 ; ENSMUSG00000056054 .
GeneIDi 20201.
KEGGi mmu:20201.
UCSCi uc008qdd.1. mouse.

Organism-specific databases

CTDi 6279.
MGIi MGI:88244. S100a8.

Phylogenomic databases

eggNOGi NOG39611.
HOGENOMi HOG000246968.
HOVERGENi HBG001479.
InParanoidi P27005.
OMAi DTWFKEL.
OrthoDBi EOG76HQ48.
PhylomeDBi P27005.
TreeFami TF332727.

Miscellaneous databases

NextBioi 297779.
PROi P27005.
SOURCEi Search...

Gene expression databases

Bgeei P27005.
CleanExi MM_S100A8.
ExpressionAtlasi P27005. baseline and differential.
Genevestigatori P27005.

Family and domain databases

Gene3Di 1.10.238.10. 1 hit.
InterProi IPR011992. 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 ]
PANTHERi PTHR11639:SF5. PTHR11639:SF5. 1 hit.
Pfami PF00036. EF-hand_1. 1 hit.
PF01023. S_100. 1 hit.
[Graphical view ]
PROSITEi PS00018. EF_HAND_1. 1 hit.
PS50222. EF_HAND_2. 1 hit.
PS00303. S100_CABP. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. Cited for: S-NITROSYLATION AT CYS-42.
  10. 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.

Entry informationi

Entry nameiS10A8_MOUSE
AccessioniPrimary (citable) accession number: P27005
Secondary accession number(s): P31724
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: January 23, 2007
Last modified: October 29, 2014
This is version 119 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

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

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3