S100A8
entrez
6279
canonical
uniprot
P05109
canonical
ensembl
ENSG00000143546
resolver
ensp
ENSP00000357721
resolver
ensp
ENSP00000357722
resolver
ensp
ENSP00000579809
resolver
ensp
ENSP00000579810
resolver
ensp
ENSP00000625502
resolver
enst
ENST00000368732
resolver
enst
ENST00000368733
resolver
enst
ENST00000909750
resolver
enst
ENST00000909751
resolver
enst
ENST00000955443
resolver
genesymbol
S100A8
resolver
genesymbol_syn
CAGA
resolver
genesymbol_syn
CFAG
resolver
genesymbol_syn
MRP8
resolver
hgnc
HGNC:10498
resolver
uniprot
A8K5L3
resolver
uniprot
D3DV37
resolver
uniprot
Q5SY70
resolver
uniprot
Q9UC84
resolver
uniprot
Q9UC92
resolver
uniprot
Q9UCJ0
resolver
uniprot
Q9UCM6
resolver
uniprot_entry
S10A8_HUMAN
resolver
uniprot_sec
A8K5L3
resolver
uniprot_sec
D3DV37
resolver
uniprot_sec
Q5SY70
resolver
uniprot_sec
Q9UC84
resolver
uniprot_sec
Q9UC92
resolver
uniprot_sec
Q9UCJ0
resolver
uniprot_sec
Q9UCM6
resolver
activity_regulation
ACTIVITY REGULATION: Calprotectin (S100A8/A9) activity on TLR4 signaling is inhibited by paquinimod. {ECO:0000250|UniProtKB:P27005}.
uniprot
proteins
amino_acid_sequence
MLTELEKALNSIIDVYHKYSLIKGNFHAVYRDDLKKLLETECPQYIRKKGADVWFKELDINTDGAVNFQEFLILVIKMGVAAHKKSHEESHKE
uniprot
proteins
function
FUNCTION: S100A8 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 and adhesion. 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. 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. The extracellular functions involve pro-inflammatory, antimicrobial, oxidant-scavenging and apoptosis-inducing activities. Its pro-inflammatory 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 pro-inflammatory 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. The iNOS-S100A8/A9 transnitrosylase complex directs selective inflammatory stimulus-dependent S-nitrosylation of GAPDH and probably multiple targets such as ANXA5, EZR, MSN and VIM by recognizing a [IL]-x-C-x-x-[DE] motif; S100A8 seems to contribute to S-nitrosylation site selectivity. {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:19935772, ECO:0000269|PubMed:21487906, ECO:0000269|PubMed:22363402, ECO:0000269|PubMed:22808130, ECO:0000269|PubMed:25417112, ECO:0000269|PubMed:26296369}.; FUNCTION: (Microbial infection) Upon infection by human coronavirus SARS-CoV-2, may induce expansion of aberrant immature neutrophils in a TLR4-dependent manner. {ECO:0000305|PubMed:33388094}.
uniprot
proteins
mass_dalton
10835
uniprot
proteins
mutagenesis
MUTAGEN 42; /note="C->A: Loss of antifungal activity."; /evidence="ECO:0000269|PubMed:19087201
uniprot
proteins
protein_family
S-100 family
uniprot
proteins
pubmed
10771424
uniprot
proteins
pubmed
11708798
uniprot
proteins
pubmed
12626582
uniprot
proteins
pubmed
1286667
uniprot
proteins
pubmed
1326551
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15331440
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15598812
uniprot
proteins
pubmed
15642721
uniprot
proteins
pubmed
16258195
uniprot
proteins
pubmed
16710414
uniprot
proteins
pubmed
17553524
uniprot
proteins
pubmed
18786929
uniprot
proteins
pubmed
18832721
uniprot
proteins
pubmed
19087201
uniprot
proteins
pubmed
19122197
uniprot
proteins
pubmed
19451397
uniprot
proteins
pubmed
19835859
uniprot
proteins
pubmed
19935766
uniprot
proteins
pubmed
19935772
uniprot
proteins
pubmed
20213444
uniprot
proteins
pubmed
2039599
uniprot
proteins
pubmed
20523765
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21487906
uniprot
proteins
pubmed
21912088
uniprot
proteins
pubmed
22095980
uniprot
proteins
pubmed
22223895
uniprot
proteins
pubmed
22363402
uniprot
proteins
pubmed
22489132
uniprot
proteins
pubmed
22808130
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
25417112
uniprot
proteins
pubmed
26296369
uniprot
proteins
pubmed
3313057
uniprot
proteins
pubmed
33388094
uniprot
proteins
pubmed
3405210
uniprot
proteins
pubmed
3561500
uniprot
proteins
pubmed
7695842
uniprot
proteins
pubmed
7849642
uniprot
proteins
pubmed
8423249
uniprot
proteins
pubmed
8619876
uniprot
proteins
pubmed
9083090
uniprot
proteins
sequence_length
93
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Secreted. Cytoplasm. Cytoplasm, cytoskeleton. 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.
uniprot
proteins