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P50115

- S10A8_RAT

UniProt

P50115 - S10A8_RAT

Protein

Protein S100-A8

Gene

S100a8

Organism
Rattus norvegicus (Rat)
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.1 Publication

    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: RGD
    3. autophagy Source: UniProtKB
    4. chronic inflammatory response Source: RGD
    5. inflammatory response Source: RGD
    6. innate immune response Source: UniProtKB-KW
    7. leukocyte migration involved in inflammatory response Source: UniProtKB
    8. neutrophil aggregation Source: UniProtKB
    9. neutrophil chemotaxis Source: UniProtKB
    10. positive regulation of inflammatory response Source: UniProtKB
    11. positive regulation of intrinsic apoptotic signaling pathway Source: UniProtKB
    12. response to ethanol Source: RGD
    13. response to lipopolysaccharide Source: RGD
    14. response to zinc ion Source: RGD
    15. wound healing Source: RGD

    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
    Migration inhibitory factor-related protein 8
    Short name:
    MRP-8
    Short name:
    p8
    S100 calcium-binding protein A8
    Gene namesi
    Name:S100a8
    Synonyms:Mrp8
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Chromosome 2

    Organism-specific databases

    RGDi620265. S100a8.

    Subcellular locationi

    Secreted By similarity. Cytoplasm 1 Publication. 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 By similarity.By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-SubCell
    2. cytoskeleton Source: UniProtKB-SubCell
    3. extracellular space Source: RGD
    4. plasma membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Cytoskeleton, Membrane, Secreted

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11Removed1 Publication
    Chaini2 – 8988Protein S100-A8PRO_0000143995Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylalanine1 Publication
    Modified residuei42 – 421S-nitrosocysteineBy similarity

    Keywords - PTMi

    Acetylation, S-nitrosylation

    Proteomic databases

    PaxDbiP50115.
    PRIDEiP50115.

    Expressioni

    Gene expression databases

    GenevestigatoriP50115.

    Interactioni

    Subunit structurei

    Homodimer. Preferentially exists as a heterodimer or heterotetramer with S100A9 known as calprotectin (S100A8/A9). S100A8 interacts with AGER, ATP2A2 and with the heterodimeric complex formed by TLR4 and LY96. 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.By similarity

    Protein-protein interaction databases

    STRINGi10116.ENSRNOP00000015473.

    Structurei

    3D structure databases

    ProteinModelPortaliP50115.
    SMRiP50115. 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.
    GeneTreeiENSGT00730000111352.
    HOGENOMiHOG000246968.
    HOVERGENiHBG001479.
    InParanoidiP50115.
    OMAiWNENALE.
    OrthoDBiEOG76HQ48.
    PhylomeDBiP50115.
    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.
    PfamiPF01023. 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.

    P50115-1 [UniParc]FASTAAdd to Basket

    « Hide

    MATELEKALS NVIEVYHNYS GIKGNHHALY RDDFRKMVTT ECPQFVQNKN   50
    TESLFKELDV NSDNAINFEE FLVLVIRVGV AAHKDSHKE 89
    Length:89
    Mass (Da):10,239
    Last modified:January 23, 2007 - v3
    Checksum:i6AC1AFAF3429B01E
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti73 – 731V → A in AAA41637. (PubMed:8343166)Curated

    Mass spectrometryi

    Molecular mass is 10149±2 Da from positions 2 - 89. Determined by ESI. 1 Publication

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L18891 mRNA. Translation: AAA41637.1.
    PIRiJN0685.
    RefSeqiNP_446274.2. NM_053822.2.
    XP_006232627.1. XM_006232565.1.
    UniGeneiRn.31839.

    Genome annotation databases

    EnsembliENSRNOT00000015473; ENSRNOP00000015473; ENSRNOG00000011557.
    GeneIDi116547.
    KEGGirno:116547.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L18891 mRNA. Translation: AAA41637.1 .
    PIRi JN0685.
    RefSeqi NP_446274.2. NM_053822.2.
    XP_006232627.1. XM_006232565.1.
    UniGenei Rn.31839.

    3D structure databases

    ProteinModelPortali P50115.
    SMRi P50115. Positions 1-89.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 10116.ENSRNOP00000015473.

    Proteomic databases

    PaxDbi P50115.
    PRIDEi P50115.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSRNOT00000015473 ; ENSRNOP00000015473 ; ENSRNOG00000011557 .
    GeneIDi 116547.
    KEGGi rno:116547.

    Organism-specific databases

    CTDi 6279.
    RGDi 620265. S100a8.

    Phylogenomic databases

    eggNOGi NOG39611.
    GeneTreei ENSGT00730000111352.
    HOGENOMi HOG000246968.
    HOVERGENi HBG001479.
    InParanoidi P50115.
    OMAi WNENALE.
    OrthoDBi EOG76HQ48.
    PhylomeDBi P50115.
    TreeFami TF332727.

    Miscellaneous databases

    NextBioi 619165.
    PROi P50115.

    Gene expression databases

    Genevestigatori P50115.

    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 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. "Expression and cloning of migration inhibitory factor-related protein (MRP)8 and MRP14 in arthritis-susceptible rats."
      Imamichi T., Uchida I., Wahl S.M., McCartney-Francis N.
      Biochem. Biophys. Res. Commun. 194:819-825(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: Lewis/N.
      Tissue: Peritoneal cavity.
    2. "Identification of posttranslational modifications and cDNA sequencing errors in the rat S100 proteins MRP8 and 14 using electrospray ionization mass spectrometry."
      Raftery M.J., Geczy C.L.
      Anal. Biochem. 258:285-292(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 2-89, MASS SPECTROMETRY, ACETYLATION AT ALA-2.
      Tissue: Spleen.
    3. "Dynamic mobility of immunological cells expressing S100A8 and S100A9 in vivo: a variety of functional roles of the two proteins as regulators in acute inflammatory reaction."
      Koike A., Arai S., Yamada S., Nagae A., Saita N., Itoh H., Uemoto S., Totani M., Ikemoto M.
      Inflammation 35:409-419(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION.

    Entry informationi

    Entry nameiS10A8_RAT
    AccessioniPrimary (citable) accession number: P50115
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1996
    Last sequence update: January 23, 2007
    Last modified: October 1, 2014
    This is version 113 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 S100 proteins.By similarity

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3