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P50116

- S10A9_RAT

UniProt

P50116 - S10A9_RAT

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Protein

Protein S100-A9

Gene

S100a9

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

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
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-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-KW
  2. cytoskeleton Source: UniProtKB-KW
  3. extracellular space Source: RGD
  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

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.
GeneTreeiENSGT00760000119034.
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

        10         20         30         40         50
MAAKTGSQLE RSISTIINVF HQYSRKYGHP DTLNKAEFKE MVNKDLPNFL
60 70 80 90 100
KREKRNENLL RDIMEDLDTN QDNQLSFEEC MMLMGKLIFA CHEKLHENNP
110
RGHDHSHGKG CGK
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 ENSGT00760000119034.
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 29, 2014
This is version 115 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