P50116 (S10A9_RAT) Reviewed, UniProtKB/Swiss-Prot
Last modified June 11, 2014. Version 112. History...
Names and origin
|Protein names||Recommended name:|
Migration inhibitory factor-related protein 14
Myeloid-related protein 14
S100 calcium-binding protein A9
|Organism||Rattus norvegicus (Rat) [Reference proteome]|
|Taxonomic identifier||10116 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus|
|Sequence length||113 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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. Ref.3 Ref.4
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. Ref.3
Secreted By similarity. Cytoplasm By similarity. Cytoplasm › cytoskeleton By similarity. Cell membrane; Peripheral membrane protein. 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. Ref.4
Phosphorylated. Phosphorylation inhibits activation of tubulin polymerization By similarity.
Belongs to the S-100 family.
Contains 2 EF-hand domains.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Initiator methionine||1||1||Removed Ref.2|
|Chain||2 – 113||112||Protein S100-A9||PRO_0000143999|
|Domain||13 – 48||36||EF-hand 1|
|Domain||55 – 90||36||EF-hand 2|
|Calcium binding||24 – 37||14||1; low affinity Potential|
|Calcium binding||68 – 79||12||2; high affinity Potential|
|Metal binding||21||1||Zinc By similarity|
|Metal binding||31||1||Zinc By similarity|
|Metal binding||92||1||Zinc By similarity|
|Metal binding||96||1||Zinc By similarity|
Amino acid modifications
|Modified residue||2||1||N-acetylalanine Ref.2|
|Modified residue||107||1||Pros-methylhistidine Ref.2|
|Sequence conflict||17||1||I → Q AA sequence Ref.3|
|Sequence conflict||24||1||S → C AA sequence Ref.3|
|Sequence conflict||106||1||S → R in AAA18214. Ref.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.
Tissue: Peritoneal cavity.
|||"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.
|||"Fibroblast growth-stimulating activity of S100A9 (MRP-14)."|
Shibata F., Miyama K., Shinoda F., Mizumoto J., Takano K., Nakagawa H.
Eur. J. Biochem. 271:2137-2143(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 3-113, PROTEIN SEQUENCE OF 11-25; 38-67; 81-90 AND 94-112, FUNCTION, SUBUNIT, TISSUE SPECIFICITY.
Tissue: Macrophage and Peritoneal cavity.
|||"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.
|+||Additional computationally mapped references.|
|L18948 mRNA. Translation: AAA18214.1.|
AB118215 mRNA. Translation: BAC82423.1.
|RefSeq||NP_446039.1. NM_053587.1. |
3D structure databases
|SMR||P50116. Positions 7-96. |
Protein-protein interaction databases
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSRNOT00000015351; ENSRNOP00000015351; ENSRNOG00000011483. |
|UCSC||RGD:620267. rat. |
|RGD||620267. S100a9. |
Gene expression databases
Family and domain databases
|Gene3D||184.108.40.206. 1 hit. |
|InterPro||IPR011992. EF-hand-dom_pair. |
|PANTHER||PTHR11639:SF53. PTHR11639:SF53. 1 hit. |
|Pfam||PF01023. S_100. 1 hit. |
|PROSITE||PS50222. EF_HAND_2. 1 hit. |
PS00303. S100_CABP. 1 hit.
|Accession||Primary (citable) accession number: P50116|
Secondary accession number(s): Q761U7
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families