UniProt Accession

 S10A9_RAT; P50116; Q761U7 

Genbank Protein ID

 L18948; AB118215 

Genbank Nucleotide ID

 AAA18214.1; BAC82423.1 

Protein Name

 Protein S100-A9 

Protein Synonyms/Alias

 Calgranulin-B; Migration inhibitory factor-related protein 14; MRP-14; p14; Myeloid-related protein 14; S100 calcium-binding protein A9 

Gene Name

 S100a9 

Gene Synonyms/Alias

 Mrp14 

Created Date

 July 27, 2013 

Organism

 Rattus norvegicus (Rat) 

NCBI Taxa ID

 10116 

Lysine Modification

Position	Peptide	Type	References
26	VFHQYSRKYGHPDTL	acetylation	[1]

Reference

 [1] Proteomic analysis of lysine acetylation sites in rat tissues reveals organ specificity and subcellular patterns.
 Lundby A, Lage K, Weinert BT, Bekker-Jensen DB, Secher A, Skovgaard T, Kelstrup CD, Dmytriyev A, Choudhary C, Lundby C, Olsen JV.
 Cell Rep. 2012 Aug 30;2(2):419-31. [PMID: 22902405] 

Functional Description

 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 Zn(2+) 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. 

Sequence Annotation

 DOMAIN 13 48 EF-hand 1.
 DOMAIN 55 90 EF-hand 2.
 METAL 21 21 Zinc (By similarity).
 METAL 31 31 Zinc (By similarity).
 METAL 92 92 Zinc (By similarity).
 METAL 96 96 Zinc (By similarity).
 MOD_RES 2 2 N-acetylalanine.
 MOD_RES 107 107 Pros-methylhistidine.  

Keyword

 Acetylation; Antimicrobial; Antioxidant; Apoptosis; Autophagy; Calcium; Cell membrane; Chemotaxis; Complete proteome; Cytoplasm; Cytoskeleton; Direct protein sequencing; Immunity; Inflammatory response; Innate immunity; Membrane; Metal-binding; Methylation; Phosphoprotein; Reference proteome; Repeat; Secreted; Zinc. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 113 AA 

Protein Sequence

Gene Ontology

 GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
 GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
 GO:0005615; C:extracellular space; IDA:RGD.
 GO:0005634; C:nucleus; IEA:Compara.
 GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
 GO:0016209; F:antioxidant activity; IEA:UniProtKB-KW.
 GO:0005509; F:calcium ion binding; IEA:InterPro.
 GO:0031532; P:actin cytoskeleton reorganization; IEA:Compara.
 GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:UniProtKB.
 GO:0006914; P:autophagy; ISS:UniProtKB.
 GO:0002544; P:chronic inflammatory response; IEP:RGD.
 GO:0006917; P:induction of apoptosis; ISS:UniProtKB.
 GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
 GO:0002523; P:leukocyte migration involved in inflammatory response; ISS:UniProtKB.
 GO:0070488; P:neutrophil aggregation; ISS:UniProtKB.
 GO:0030593; P:neutrophil chemotaxis; ISS:UniProtKB.
 GO:0050729; P:positive regulation of inflammatory response; ISS:UniProtKB.
 GO:0045113; P:regulation of integrin biosynthetic process; IEA:Compara.
 GO:0045471; P:response to ethanol; IEP:RGD.
 GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
 GO:0010043; P:response to zinc ion; IEP:RGD. 

Interpro

 IPR011992; EF-hand-like_dom.
 IPR002048; EF_hand_dom.
 IPR001751; S100/CaBP-9k_CS.
 IPR013787; S100_Ca-bd_sub. 

Pfam

 PF01023; S_100 

SMART

  

PROSITE

 PS00018; EF_HAND_1
 PS50222; EF_HAND_2
 PS00303; S100_CABP 

PRINTS