S100A9
entrez
6280
canonical
uniprot
P06702
canonical
ensembl
ENSG00000163220
resolver
ensp
ENSP00000357727
resolver
ensp
ENSP00000542691
resolver
ensp
ENSP00000542693
resolver
enst
ENST00000368738
resolver
enst
ENST00000872632
resolver
enst
ENST00000872634
resolver
genesymbol
S100A9
resolver
genesymbol_syn
CAGB
resolver
genesymbol_syn
CFAG
resolver
genesymbol_syn
MRP14
resolver
hgnc
HGNC:10499
resolver
uniprot
D3DV36
resolver
uniprot
Q6FGA1
resolver
uniprot
Q9NYM0
resolver
uniprot
Q9UCJ1
resolver
uniprot_entry
S10A9_HUMAN
resolver
uniprot_sec
D3DV36
resolver
uniprot_sec
Q6FGA1
resolver
uniprot_sec
Q9NYM0
resolver
uniprot_sec
Q9UCJ1
resolver
amino_acid_sequence
MTCKMSQLERNIETIINTFHQYSVKLGHPDTLNQGEFKELVRKDLQNFLKKENKNEKVIEHIMEDLDTNADKQLSFEEFIMLMARLTWASHEKMHEGDEGPGHHHKPGLGEGTP
uniprot
proteins
function
FUNCTION: S100A9 is a calcium- and zinc-binding protein which plays a prominent role in the regulation of inflammatory processes and immune response (PubMed:12626582, PubMed:15331440, PubMed:16258195, PubMed:19122197, PubMed:20103766, PubMed:21325622, PubMed:8423249). 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 (PubMed:12626582, PubMed:15331440, PubMed:20103766). Predominantly found as calprotectin (S100A8/A9) which has a wide plethora of intra- and extracellular functions (PubMed:16258195, PubMed:19122197, PubMed:8423249). 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 (PubMed:15331440, PubMed:21325622). Also participates in regulatory T-cell differentiation together with CD69 (PubMed:26296369). 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 (PubMed:15642721, PubMed:22808130). The extracellular functions involve pro-inflammatory, antimicrobial, oxidant-scavenging and apoptosis-inducing activities (PubMed:19534726, PubMed:8423249). Its pro-inflammatory activity includes recruitment of leukocytes, promotion of cytokine and chemokine production, and regulation of leukocyte adhesion and migration (PubMed:15598812, PubMed:21487906). 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) (PubMed:19402754). Binding to TLR4 and AGER activates the MAP-kinase and NF-kappa-B signaling pathways resulting in the amplification of the pro-inflammatory cascade (PubMed:19402754, PubMed:22804476). Has antimicrobial activity towards bacteria and fungi and exerts its antimicrobial activity probably via chelation of Zn(2+) which is essential for microbial growth (PubMed:19087201). 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 (PubMed:19935772). 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 (PubMed:22363402). Its role as an oxidant scavenger has a protective role in preventing exaggerated tissue damage by scavenging oxidants (PubMed:21912088, PubMed:22489132). Can act as a potent amplifier of inflammation in autoimmunity as well as in cancer development and tumor spread (PubMed:16258195). 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 (PubMed:25417112). 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 (PubMed:25417112). {ECO:0000269|PubMed:12626582, ECO:0000269|PubMed:15331440, ECO:0000269|PubMed:15598812, ECO:0000269|PubMed:15642721, ECO:0000269|PubMed:16258195, ECO:0000269|PubMed:19087201, ECO:0000269|PubMed:19122197, ECO:0000269|PubMed:19402754, ECO:0000269|PubMed:19534726, ECO:0000269|PubMed:19935772, ECO:0000269|PubMed:20103766, ECO:0000269|PubMed:21325622, ECO:0000269|PubMed:21487906, ECO:0000269|PubMed:22363402, ECO:0000269|PubMed:22804476, ECO:0000269|PubMed:22808130, ECO:0000269|PubMed:25417112, ECO:0000269|PubMed:26296369, ECO:0000269|PubMed:8423249, ECO:0000303|PubMed:21912088, ECO:0000303|PubMed:22489132}.
uniprot
proteins
mass_dalton
13242
uniprot
proteins
mutagenesis
MUTAGEN 3; /note="C->A: Disrupts interaction with NOS2 and inhibits LDL(ox)-induced GAPDHS-nitrosylation; no effect on interaction with S100A8."; /evidence="ECO:0000269|PubMed:25417112"; MUTAGEN 36; /note="E->Q: Loss of resistance to bacterial invasion; when associated with Q-78."; /evidence="ECO:0000269|PubMed:19122197"; MUTAGEN 63; /note="M->A: Loss of antifungal activity."; /evidence="ECO:0000269|PubMed:19087201"; MUTAGEN 78; /note="E->Q: Loss of resistance to bacterial invasion; when associated with Q-36."; /evidence="ECO:0000269|PubMed:19122197"; MUTAGEN 81; /note="M->A: No effect on antifungal activity."; /evidence="ECO:0000269|PubMed:19087201"; MUTAGEN 83; /note="M->A: Loss of antifungal activity."; /evidence="ECO:0000269|PubMed:19087201
uniprot
proteins
post_translational_modification
PTM: Phosphorylated. Phosphorylation inhibits activation of tubulin polymerization. {ECO:0000269|PubMed:15331440, ECO:0000269|PubMed:15905572, ECO:0000269|PubMed:2478889}.; PTM: S-nitrosylation of Cys-3 is implicated in LDL(ox)-induced S-nitrosylation of GAPDH at 'Cys-247' through a transnitrosylase mechanism involving a iNOS-S100A8/9 complex (PubMed:25417112). {ECO:0000305|PubMed:25417112}.; PTM: Methylation at His-105 by METTL9 reduces zinc-binding without affecting heterodimerization with S100A8. {ECO:0000250|UniProtKB:P31725}.
uniprot
proteins
protein_family
S-100 family
uniprot
proteins
pubmed
11708798
uniprot
proteins
pubmed
11851337
uniprot
proteins
pubmed
12626582
uniprot
proteins
pubmed
1286667
uniprot
proteins
pubmed
15331440
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15598812
uniprot
proteins
pubmed
15642721
uniprot
proteins
pubmed
15905572
uniprot
proteins
pubmed
16258195
uniprot
proteins
pubmed
16710414
uniprot
proteins
pubmed
17553524
uniprot
proteins
pubmed
18318008
uniprot
proteins
pubmed
18786929
uniprot
proteins
pubmed
19087201
uniprot
proteins
pubmed
19122197
uniprot
proteins
pubmed
19367720
uniprot
proteins
pubmed
19402754
uniprot
proteins
pubmed
19451397
uniprot
proteins
pubmed
19534726
uniprot
proteins
pubmed
19835859
uniprot
proteins
pubmed
19935766
uniprot
proteins
pubmed
19935772
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20103766
uniprot
proteins
pubmed
20213444
uniprot
proteins
pubmed
20523765
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21325622
uniprot
proteins
pubmed
21487906
uniprot
proteins
pubmed
21912088
uniprot
proteins
pubmed
22095980
uniprot
proteins
pubmed
22363402
uniprot
proteins
pubmed
22457725
uniprot
proteins
pubmed
22489132
uniprot
proteins
pubmed
22804476
uniprot
proteins
pubmed
22808130
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
2478889
uniprot
proteins
pubmed
25417112
uniprot
proteins
pubmed
26296369
uniprot
proteins
pubmed
2656677
uniprot
proteins
pubmed
2776242
uniprot
proteins
pubmed
3313057
uniprot
proteins
pubmed
3405210
uniprot
proteins
pubmed
34905516
uniprot
proteins
pubmed
8423249
uniprot
proteins
pubmed
9083090
uniprot
proteins
sequence_length
114
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Secreted. Cytoplasm {ECO:0000269|PubMed:15598812, ECO:0000269|PubMed:8423249}. Cytoplasm, cytoskeleton {ECO:0000269|PubMed:22489132, ECO:0000269|PubMed:9083090}. Cell membrane {ECO:0000269|PubMed:18786929}; Peripheral membrane protein {ECO:0000305|PubMed:18786929}. Note=Predominantly localized in the cytoplasm. Upon elevation of the intracellular calcium level, translocated from the cytoplasm to the cytoskeleton and the cell membrane (PubMed:18786929). Upon neutrophil activation or endothelial adhesion of monocytes, is secreted via a microtubule-mediated, alternative pathway (PubMed:15598812). {ECO:0000269|PubMed:15598812, ECO:0000269|PubMed:18786929}.
uniprot
proteins