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P27005

- S10A8_MOUSE

UniProt

P27005 - S10A8_MOUSE

Protein

Protein S100-A8

Gene

S100a8

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
  1. 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

    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-SubCell
    2. cytoskeleton Source: UniProtKB-SubCell
    3. extracellular space Source: Ensembl
    4. plasma membrane Source: UniProtKB-SubCell

    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

    ArrayExpressiP27005.
    BgeeiP27005.
    CleanExiMM_S100A8.
    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

    MPSELEKALS NLIDVYHNYS NIQGNHHALY KNDFKKMVTT ECPQFVQNIN   50
    IENLFRELDI NSDNAINFEE FLAMVIKVGV ASHKDSHKE 89
    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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

    ArrayExpressi P27005.
    Bgeei P27005.
    CleanExi MM_S100A8.
    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

    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 1, 2014
    This is version 118 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