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P50116

- S10A9_RAT

UniProt

P50116 - S10A9_RAT

Protein

Protein S100-A9

Gene

S100a9

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
  1. Functioni

    S100A9 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, adhesion, can increase the bactericidal activity of neutrophils by promoting phagocytosis via activation of SYK, PI3K/AKT, and ERK1/2 and can induce degranulation of neutrophils by a MAPK-dependent mechanism. 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 bindingi21 – 211ZincBy similarity
    Metal bindingi31 – 311ZincBy similarity
    Metal bindingi92 – 921ZincBy similarity
    Metal bindingi96 – 961ZincBy similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Calcium bindingi24 – 37141; low affinityPROSITE-ProRule annotationAdd
    BLAST
    Calcium bindingi68 – 79122; 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. actin cytoskeleton reorganization Source: Ensembl
    2. activation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
    3. autophagy Source: UniProtKB
    4. chronic inflammatory response Source: RGD
    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. regulation of integrin biosynthetic process Source: Ensembl
    12. response to ethanol Source: RGD
    13. response to lipopolysaccharide Source: RGD
    14. response to zinc ion 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-A9
    Alternative name(s):
    Calgranulin-B
    Migration inhibitory factor-related protein 14
    Short name:
    MRP-14
    Short name:
    p14
    Myeloid-related protein 14
    S100 calcium-binding protein A9
    Gene namesi
    Name:S100a9
    Synonyms:Mrp14
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Chromosome 2

    Organism-specific databases

    RGDi620267. S100a9.

    Subcellular locationi

    Secreted By similarity. Cytoplasm By similarity. Cytoplasmcytoskeleton By similarity. Cell membrane 1 Publication; Peripheral membrane protein 1 Publication
    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. nucleus Source: Ensembl
    5. 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 – 113112Protein S100-A9PRO_0000143999Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylalanine1 Publication
    Modified residuei107 – 1071Pros-methylhistidine1 Publication

    Post-translational modificationi

    Phosphorylated. Phosphorylation inhibits activation of tubulin polymerization By similarity.By similarity

    Keywords - PTMi

    Acetylation, Methylation, Phosphoprotein

    Proteomic databases

    PRIDEiP50116.

    Expressioni

    Tissue specificityi

    Highly expressed at sites of inflammation.2 Publications

    Gene expression databases

    GenevestigatoriP50116.

    Interactioni

    Subunit structurei

    Homodimer. Preferentially exists as a heterodimer or heterotetramer with S100A8 known as calprotectin (S100A8/A9). S100A9 interacts with ATP2A2. S100A9 interacts with AGER, and with the heterodimeric complex formed by TLR4 and LY96 in the presence of calcium and/or zinc ions. S100A9 binds quinoline-3-carboxamides in the presence of calcium and/or zinc ions. S100A9 interacts with beta-APP40 (beta-amyloid protein 40) peptide of APP. 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. Calprotectin (S100A8/9) interacts with NCF2/P67PHOX, RAC1, RAC2, CYBA and CYBB By similarity.By similarity

    Protein-protein interaction databases

    STRINGi10116.ENSRNOP00000015351.

    Structurei

    3D structure databases

    ProteinModelPortaliP50116.
    SMRiP50116. Positions 7-96.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini13 – 4836EF-hand 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini55 – 9036EF-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

    eggNOGiNOG47012.
    GeneTreeiENSGT00740000114986.
    HOGENOMiHOG000246968.
    HOVERGENiHBG001479.
    InParanoidiP50116.
    OMAiSFTENAC.
    OrthoDBiEOG73807B.
    PhylomeDBiP50116.
    TreeFamiTF332727.

    Family and domain databases

    Gene3Di1.10.238.10. 1 hit.
    InterProiIPR011992. EF-hand-dom_pair.
    IPR002048. EF_hand_dom.
    IPR028475. S100-A9.
    IPR001751. S100/CaBP-9k_CS.
    IPR013787. S100_Ca-bd_sub.
    [Graphical view]
    PANTHERiPTHR11639:SF53. PTHR11639:SF53. 1 hit.
    PfamiPF01023. S_100. 1 hit.
    [Graphical view]
    PROSITEiPS50222. 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.

    P50116-1 [UniParc]FASTAAdd to Basket

    « Hide

    MAAKTGSQLE RSISTIINVF HQYSRKYGHP DTLNKAEFKE MVNKDLPNFL    50
    KREKRNENLL RDIMEDLDTN QDNQLSFEEC MMLMGKLIFA CHEKLHENNP 100
    RGHDHSHGKG CGK 113
    Length:113
    Mass (Da):13,145
    Last modified:January 23, 2007 - v3
    Checksum:i6C3A0044A7AEC4FA
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti17 – 171I → Q AA sequence (PubMed:15153104)Curated
    Sequence conflicti24 – 241S → C AA sequence (PubMed:15153104)Curated
    Sequence conflicti106 – 1061S → R in AAA18214. (PubMed:8343166)Curated

    Mass spectrometryi

    Molecular mass is 13069±2 Da from positions 2 - 113. Determined by ESI. 1 Publication

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L18948 mRNA. Translation: AAA18214.1.
    AB118215 mRNA. Translation: BAC82423.1.
    PIRiJN0686.
    RefSeqiNP_446039.1. NM_053587.1.
    UniGeneiRn.6703.

    Genome annotation databases

    EnsembliENSRNOT00000015351; ENSRNOP00000015351; ENSRNOG00000011483.
    GeneIDi94195.
    KEGGirno:94195.
    UCSCiRGD:620267. rat.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L18948 mRNA. Translation: AAA18214.1 .
    AB118215 mRNA. Translation: BAC82423.1 .
    PIRi JN0686.
    RefSeqi NP_446039.1. NM_053587.1.
    UniGenei Rn.6703.

    3D structure databases

    ProteinModelPortali P50116.
    SMRi P50116. Positions 7-96.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 10116.ENSRNOP00000015351.

    Proteomic databases

    PRIDEi P50116.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSRNOT00000015351 ; ENSRNOP00000015351 ; ENSRNOG00000011483 .
    GeneIDi 94195.
    KEGGi rno:94195.
    UCSCi RGD:620267. rat.

    Organism-specific databases

    CTDi 6280.
    RGDi 620267. S100a9.

    Phylogenomic databases

    eggNOGi NOG47012.
    GeneTreei ENSGT00740000114986.
    HOGENOMi HOG000246968.
    HOVERGENi HBG001479.
    InParanoidi P50116.
    OMAi SFTENAC.
    OrthoDBi EOG73807B.
    PhylomeDBi P50116.
    TreeFami TF332727.

    Miscellaneous databases

    NextBioi 617850.
    PROi P50116.

    Gene expression databases

    Genevestigatori P50116.

    Family and domain databases

    Gene3Di 1.10.238.10. 1 hit.
    InterProi IPR011992. EF-hand-dom_pair.
    IPR002048. EF_hand_dom.
    IPR028475. S100-A9.
    IPR001751. S100/CaBP-9k_CS.
    IPR013787. S100_Ca-bd_sub.
    [Graphical view ]
    PANTHERi PTHR11639:SF53. PTHR11639:SF53. 1 hit.
    Pfami PF01023. S_100. 1 hit.
    [Graphical view ]
    PROSITEi 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], TISSUE SPECIFICITY.
      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 2-57; 62-65 AND 72-113, MASS SPECTROMETRY, ACETYLATION AT ALA-2, METHYLATION AT HIS-107.
      Tissue: Spleen.
    3. Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 3-113, PROTEIN SEQUENCE OF 11-25; 38-67; 81-90 AND 94-112, FUNCTION, SUBUNIT, TISSUE SPECIFICITY.
      Strain: Wistar.
      Tissue: Macrophage and Peritoneal cavity.
    4. "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 nameiS10A9_RAT
    AccessioniPrimary (citable) accession number: P50116
    Secondary accession number(s): Q761U7
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1996
    Last sequence update: January 23, 2007
    Last modified: October 1, 2014
    This is version 114 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3