P31725 (S10A9_MOUSE) Reviewed, UniProtKB/Swiss-Prot
Last modified May 1, 2013. Version 118. History...
Names and origin
|Protein names||Recommended name:|
Leukocyte L1 complex heavy chain
Migration inhibitory factor-related protein 14
S100 calcium-binding protein A9
|Organism||Mus musculus (Mouse) [Reference proteome]|
|Taxonomic identifier||10090 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus|
|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, transfering 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.6 Ref.7 Ref.8 Ref.10 Ref.12 Ref.13
Homodimer. Preferentially exists as a heterodimer or heterotetramer with S100A8 known as calprotectin (S100A8/A9). S100A9 interacts with beta-APP40 (beta-amyloid protein 40) peptide of APP By similarity. S100A9 interacts with AGER and 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 ATP2A2. Calprotectin (S100A8/9) interacts with NCF2/P67PHOX, RAC1, RAC2, CYBA and CYBB By similarity. Heterotetrameric calprotectin (S100A8/A9) interacts with ANXA6 and associates with tubulin filaments in activated monocytes By similarity. Calprotectin (S100A8/9) interacts with CEACAM3 and tubulin filaments in a calcium-dependent manner. Ref.6 Ref.7 Ref.8 Ref.10
Secreted By similarity. Cytoplasm. Cytoplasm › cytoskeleton. Cell membrane; 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. Ref.7 Ref.10
Phosphorylated. Phosphorylation inhibits activation of tubulin polymerization By similarity. Ref.6
Has been shown to bind calcium.
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.4|
|Chain||2 – 113||112||Protein S100-A9||PRO_0000143998|
|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.4|
|Modified residue||107||1||Pros-methylhistidine Ref.4|
|||"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].
|||"Molecular analysis of the mouse S100A9 gene and evidence that the myeloid specific transcription factor C/EBPepsilon is not required for the regulation of the S100A9/A8 gene expression in neutrophils."|
Nacken W.K.F., Lekstrom-Himes J.A., Sorg C., Manitz M.
J. Cell. Biochem. 80:606-616(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
|||"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].
Tissue: Mammary gland.
|||"Isolation of the murine S100 protein MRP14 (14 kDa migration-inhibitory-factor-related protein) from activated spleen cells: characterization of post-translational modifications and zinc binding."|
Raftery M.J., Harrison C.A., Alewood P.F., Jones A., Geczy C.L.
Biochem. J. 316:285-293(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-10; 76-93 AND 95-109, MASS SPECTROMETRY.
|||"Loss of S100A9 (MRP14) results in reduced interleukin-8-induced CD11b surface expression, a polarized microfilament system, and diminished responsiveness to chemoattractants in vitro."|
Manitz M.-P., Horst B., Seeliger S., Strey A., Skryabin B.V., Gunzer M., Frings W., Schoenlau F., Roth J., Sorg C., Nacken W.
Mol. Cell. Biol. 23:1034-1043(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
|||"MRP8 and MRP14 control microtubule reorganization during transendothelial migration of phagocytes."|
Vogl T., Ludwig S., Goebeler M., Strey A., Thorey I.S., Reichelt R., Foell D., Gerke V., Manitz M.P., Nacken W., Werner S., Sorg C., Roth J.
Blood 104:4260-4268(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH TUBULIN, PHOSPHORYLATION.
|||"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: DISRUPTION PHENOTYPE, FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, INTERACTION WITH TLR4 AND LY96.
|||"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 ATP2A2 AND AGER.
|||"Anti-infective protective properties of S100 calgranulins."|
Hsu K., Champaiboon C., Guenther B.D., Sorenson B.S., Khammanivong A., Ross K.F., Geczy C.L., Herzberg M.C.
Antiinflamm. Antiallergy Agents Med. Chem. 8:290-305(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
|||"Identification of human S100A9 as a novel target for treatment of autoimmune disease via binding to quinoline-3-carboxamides."|
Bjoerk P., Bjoerk A., Vogl T., Stenstroem M., Liberg D., Olsson A., Roth J., Ivars F., Leanderson T.
PLoS Biol. 7:E97-E97(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, INTERACTION WITH TLR4; LY96 AND AGER, QUINOLINE-3-CARBOXAMIDE BINDING.
|||"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.
|||"S100A9 differentially modifies phenotypic states of neutrophils, macrophages, and dendritic cells: implications for atherosclerosis and adipose tissue inflammation."|
Averill M.M., Barnhart S., Becker L., Li X., Heinecke J.W., Leboeuf R.C., Hamerman J.A., Sorg C., Kerkhoff C., Bornfeldt K.E.
Circulation 123:1216-1226(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
|||"Induction of nuclear factor-kappaB responses by the S100A9 protein is Toll-like receptor-4-dependent."|
Riva M., Kaellberg E., Bjoerk P., Hancz D., Vogl T., Roth J., Ivars F., Leanderson T.
Immunology 137:172-182(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
|+||Additional computationally mapped references.|
|M83219 mRNA. Translation: AAB07228.1.|
AJ250496 Genomic DNA. Translation: CAC14292.1.
BC027635 mRNA. Translation: AAH27635.1.
|RefSeq||NP_033140.1. NM_009114.2. |
3D structure databases
|SMR||P31725. Positions 7-87. |
Protein-protein interaction databases
|IntAct||P31725. 1 interaction.|
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSMUST00000069960; ENSMUSP00000070842; ENSMUSG00000056071. |
ENSMUST00000117167; ENSMUSP00000112843; ENSMUSG00000056071.
|MGI||MGI:1338947. S100a9. |
Gene expression databases
|GermOnline||ENSMUSG00000056071. Mus musculus. |
Family and domain databases
|Gene3D||184.108.40.206. 1 hit. |
|InterPro||IPR011992. EF-hand-like_dom. |
|Pfam||PF01023. S_100. 1 hit. |
|PROSITE||PS00018. EF_HAND_1. False negative. |
PS50222. EF_HAND_2. 2 hits.
PS00303. S100_CABP. 1 hit.
|ChiTaRS||S100A9. mouse. |
|Accession||Primary (citable) accession number: P31725|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|