Protein S100-A9

Details

Name
Protein S100-A9
Synonyms
  • CAGB
  • Calgranulin-B
  • Calprotectin L1H subunit
  • CFAG
  • Leukocyte L1 complex heavy chain
  • Migration inhibitory factor-related protein 14
  • MRP-14
  • MRP14
  • p14
  • S100 calcium-binding protein A9
Gene Name
S100A9
Organism
Humans
Amino acid sequence
>lcl|BSEQ0049700|Protein S100-A9
MTCKMSQLERNIETIINTFHQYSVKLGHPDTLNQGEFKELVRKDLQNFLKKENKNEKVIE
HIMEDLDTNADKQLSFEEFIMLMARLTWASHEKMHEGDEGPGHHHKPGLGEGTP
Number of residues
114
Molecular Weight
13241.955
Theoretical pI
Not Available
GO Classification
Functions
antioxidant activity / arachidonic acid binding / calcium ion binding / microtubule binding / RAGE receptor binding / signal transducer activity / Toll-like receptor 4 binding / zinc ion binding
Processes
actin cytoskeleton reorganization / activation of cysteine-type endopeptidase activity involved in apoptotic process / antimicrobial humoral response / apoptotic process / astrocyte development / autophagy / cell-cell signaling / chemokine production / cytokine production / defense response to bacterium / defense response to fungus / inflammatory response / innate immune response / leukocyte migration involved in inflammatory response / neutrophil aggregation / neutrophil chemotaxis / neutrophil degranulation / peptidyl-cysteine S-trans-nitrosylation / positive regulation of blood coagulation / positive regulation of cell growth / positive regulation of inflammatory response / positive regulation of intrinsic apoptotic signaling pathway / positive regulation of NF-kappaB transcription factor activity / positive regulation of peptide secretion / regulation of cytoskeleton organization / regulation of integrin biosynthetic process / regulation of translation / sequestering of zinc ion / toll-like receptor signaling pathway
Components
cell junction / cytoskeleton / cytosol / extracellular exosome / extracellular matrix / extracellular region / extracellular space / nucleoplasm / nucleus / plasma membrane / secretory granule lumen
General Function
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 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. Can act as a potent amplifier of inflammation in autoimmunity as well as in cancer development and tumor spread. Has transnitrosylase activity; in oxidatively-modified low-densitity lipoprotein (LDL(ox))-induced S-nitrosylation of GAPDH on 'Cys-247' proposed to transfer the NO moiety from NOS2/iNOS to GAPDH via its own S-nitrosylated Cys-3. The iNOS-S100A8/A9 transnitrosylase complex is proposed to also direct selective inflammatory stimulus-dependent S-nitrosylation of multiple targets such as ANXA5, EZR, MSN and VIM by recognizing a [IL]-x-C-x-x-[DE] motif.
Specific Function
Antioxidant activity
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Secreted
Gene sequence
>lcl|BSEQ0049701|Protein S100-A9 (S100A9)
ATGACTTGCAAAATGTCGCAGCTGGAACGCAACATAGAGACCATCATCAACACCTTCCAC
CAATACTCTGTGAAGCTGGGGCACCCAGACACCCTGAACCAGGGGGAATTCAAAGAGCTG
GTGCGAAAAGATCTGCAAAATTTTCTCAAGAAGGAGAATAAGAATGAAAAGGTCATAGAA
CACATCATGGAGGACCTGGACACAAATGCAGACAAGCAGCTGAGCTTCGAGGAGTTCATC
ATGCTGATGGCGAGGCTAACCTGGGCCTCCCACGAGAAGATGCACGAGGGTGACGAGGGC
CCTGGCCACCACCATAAGCCAGGCCTCGGGGAGGGCACCCCCTAA
Chromosome Location
1
Locus
1q21.3
External Identifiers
ResourceLink
UniProtKB IDP06702
UniProtKB Entry NameS10A9_HUMAN
HGNC IDHGNC:10499
General References
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB01373Calciumapproved, nutraceuticalunknownDetails
DB01593Zincapproved, investigationalunknownDetails
DB14487Zinc acetateapproved, investigationalunknownDetails
DB14533Zinc chlorideapproved, investigationalunknownDetails