UniProtKB - P05109 (S10A8_HUMAN)
Protein S100-A8
S100A8
Functioni
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. 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 proinflammatory, 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. 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.
12 Publications(Microbial infection) Upon infection by human coronavirus SARS-CoV-2, may induce expansion of aberrant immature neutrophils in a TLR4-dependent manner.
1 PublicationMiscellaneous
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 17 | ZincCurated | 1 | |
Metal bindingi | 27 | ZincCurated | 1 | |
Metal bindingi | 83 | ZincCurated | 1 | |
Metal bindingi | 87 | ZincCurated | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Calcium bindingi | 20 – 33 | 1; low affinityAdd BLAST | 14 | |
Calcium bindingi | 59 – 70 | 2; high affinityAdd BLAST | 12 |
GO - Molecular functioni
- arachidonic acid binding Source: UniProtKB
- calcium-dependent protein binding Source: GO_Central
- calcium ion binding Source: GO_Central
- microtubule binding Source: UniProtKB
- RAGE receptor binding Source: UniProtKB
- Toll-like receptor 4 binding Source: UniProtKB
- zinc ion binding Source: UniProtKB
GO - Biological processi
- activation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
- acute inflammatory response Source: Ensembl
- apoptotic process Source: UniProtKB-KW
- astrocyte development Source: Ensembl
- autocrine signaling Source: Ensembl
- autophagy Source: UniProtKB
- chronic inflammatory response Source: Ensembl
- defense response to bacterium Source: UniProtKB
- defense response to fungus Source: UniProtKB
- inflammatory response Source: ProtInc
- innate immune response Source: UniProtKB-KW
- leukocyte migration involved in inflammatory response Source: UniProtKB
- neutrophil aggregation Source: UniProtKB
- neutrophil chemotaxis Source: UniProtKB
- peptidyl-cysteine S-nitrosylation Source: UniProtKB
- positive regulation of cell growth Source: UniProtKB
- positive regulation of inflammatory response Source: UniProtKB
- positive regulation of intrinsic apoptotic signaling pathway Source: UniProtKB
- positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
- positive regulation of peptide secretion Source: Ensembl
- regulation of cytoskeleton organization Source: UniProtKB
- response to ethanol Source: Ensembl
- response to lipopolysaccharide Source: GO_Central
- response to zinc ion Source: Ensembl
- sequestering of zinc ion Source: UniProtKB
- wound healing Source: Ensembl
Keywordsi
Molecular function | Antimicrobial |
Biological process | Apoptosis, Autophagy, Chemotaxis, Immunity, Inflammatory response, Innate immunity |
Ligand | Calcium, Metal-binding, Zinc |
Enzyme and pathway databases
PathwayCommonsi | P05109 |
Reactomei | R-HSA-1236974, ER-Phagosome pathway R-HSA-166058, MyD88:MAL(TIRAP) cascade initiated on plasma membrane R-HSA-5602498, MyD88 deficiency (TLR2/4) R-HSA-5603041, IRAK4 deficiency (TLR2/4) R-HSA-5668599, RHO GTPases Activate NADPH Oxidases R-HSA-5686938, Regulation of TLR by endogenous ligand R-HSA-6798695, Neutrophil degranulation R-HSA-6799990, Metal sequestration by antimicrobial proteins |
SignaLinki | P05109 |
SIGNORi | P05109 |
Names & Taxonomyi
Protein namesi | Recommended name: Protein S100-A8CuratedAlternative name(s): Calgranulin-A Calprotectin L1L subunit Cystic fibrosis antigen Short name: CFAG Leukocyte L1 complex light chain Migration inhibitory factor-related protein 8 Short name: MRP-8 Short name: p8 S100 calcium-binding protein A8 Urinary stone protein band A |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:10498, S100A8 |
MIMi | 123885, gene |
neXtProti | NX_P05109 |
VEuPathDBi | HostDB:ENSG00000143546 |
Subcellular locationi
Extracellular region or secreted
Plasma membrane
Cytoplasm and Cytosol
Cytoskeleton
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.
Cytoskeleton
- cytoskeleton Source: UniProtKB
- intermediate filament cytoskeleton Source: HPA
Cytosol
- cytosol Source: HPA
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
- extracellular region Source: BHF-UCL
- extracellular space Source: UniProtKB
Nucleus
- nucleus Source: UniProtKB
Plasma Membrane
- plasma membrane Source: UniProtKB
Other locations
- collagen-containing extracellular matrix Source: BHF-UCL
- secretory granule lumen Source: Reactome
Keywords - Cellular componenti
Cell membrane, Cytoplasm, Cytoskeleton, Membrane, SecretedPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 42 | C → A: Loss of antifungal activity. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 6279 |
OpenTargetsi | ENSG00000143546 |
PharmGKBi | PA34910 |
Miscellaneous databases
Pharosi | P05109, Tbio |
Chemistry databases
DrugBanki | DB01373, Calcium DB09130, Copper DB01593, Zinc DB14487, Zinc acetate DB14533, Zinc chloride DB14548, Zinc sulfate, unspecified form |
Genetic variation databases
BioMutai | S100A8 |
DMDMi | 115442 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000143993 | 1 – 93 | Protein S100-A8Add BLAST | 93 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 42 | S-nitrosocysteine1 Publication | 1 |
Keywords - PTMi
S-nitrosylationProteomic databases
EPDi | P05109 |
jPOSTi | P05109 |
MassIVEi | P05109 |
MaxQBi | P05109 |
PaxDbi | P05109 |
PeptideAtlasi | P05109 |
PRIDEi | P05109 |
ProteomicsDBi | 51795 |
TopDownProteomicsi | P05109 |
2D gel databases
SWISS-2DPAGEi | P05109 |
PTM databases
GlyGeni | P05109, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | P05109 |
PhosphoSitePlusi | P05109 |
Expressioni
Tissue specificityi
Inductioni
Gene expression databases
Bgeei | ENSG00000143546, Expressed in pharyngeal mucosa and 226 other tissues |
Genevisiblei | P05109, HS |
Organism-specific databases
HPAi | ENSG00000143546, Group enriched (bone marrow, esophagus, lymphoid tissue, vagina) |
Interactioni
Subunit structurei
Homodimer. Preferentially exists as a heterodimer or heterotetramer with S100A9 known as calprotectin (S100A8/A9). S100A8 interacts with AGER, ATP2A2 and with the heterodimeric complex formed by TLR4 and LY96 (By similarity).
Interacts with GAPDH. Calprotectin (S100A8/9) interacts with CEACAM3 and tubulin filaments in a calcium-dependent manner. Heterotetrameric calprotectin (S100A8/A9) interacts with ANXA6 and associates with tubulin filaments in activated monocytes. S100A8 and calprotectin (S100A8/9) interact with NCF2/P67PHOX, RAC1 and RAC2. Calprotectin (S100A8/9) interacts with CYBA and CYBB. Calprotectin (S100A8/9) interacts with NOS2 to form the iNOS-S100A8/A9 transnitrosylase complex; induced by LDL(ox) (PubMed:25417112).
By similarity10 PublicationsBinary interactionsi
P05109
With | #Exp. | IntAct |
---|---|---|
GAPDH [P04406] | 6 | EBI-355281,EBI-354056 |
S100A9 [P06702] | 7 | EBI-355281,EBI-1055001 |
TRPM4 [Q8TD43] | 2 | EBI-355281,EBI-11723041 |
GO - Molecular functioni
- calcium-dependent protein binding Source: GO_Central
- microtubule binding Source: UniProtKB
- RAGE receptor binding Source: UniProtKB
- Toll-like receptor 4 binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 112187, 147 interactors |
ComplexPortali | CPX-37, Calprotectin heterotetramer CPX-39, Calprotectin heterodimer CPX-42, S100A8 complex CPX-52, iNOS-S100A8/A9 complex |
CORUMi | P05109 |
DIPi | DIP-1165N |
IntActi | P05109, 63 interactors |
MINTi | P05109 |
STRINGi | 9606.ENSP00000357722 |
Miscellaneous databases
RNActi | P05109, protein |
Structurei
Secondary structure
3D structure databases
SMRi | P05109 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P05109 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 12 – 47 | EF-hand 1PROSITE-ProRule annotationAdd BLAST | 36 | |
Domaini | 46 – 81 | EF-hand 2PROSITE-ProRule annotationAdd BLAST | 36 |
Sequence similaritiesi
Keywords - Domaini
RepeatPhylogenomic databases
eggNOGi | ENOG502SA01, Eukaryota |
GeneTreei | ENSGT00910000144329 |
HOGENOMi | CLU_138624_6_0_1 |
InParanoidi | P05109 |
OMAi | NYHAIYR |
OrthoDBi | 334070at2759 |
PhylomeDBi | P05109 |
TreeFami | TF332727 |
Family and domain databases
InterProi | View protein in InterPro IPR011992, EF-hand-dom_pair IPR018247, EF_Hand_1_Ca_BS IPR002048, EF_hand_dom IPR001751, S100/CaBP-9k_CS IPR013787, S100_Ca-bd_sub IPR028474, S100A8 |
PANTHERi | PTHR11639:SF5, PTHR11639:SF5, 1 hit |
Pfami | View protein in Pfam PF01023, S_100, 1 hit |
SMARTi | View protein in SMART SM01394, S_100, 1 hit |
SUPFAMi | SSF47473, SSF47473, 1 hit |
PROSITEi | View protein in PROSITE PS00018, EF_HAND_1, 1 hit PS50222, EF_HAND_2, 1 hit PS00303, S100_CABP, 1 hit |
i Sequence
Sequence statusi: Complete.
10 20 30 40 50
MLTELEKALN SIIDVYHKYS LIKGNFHAVY RDDLKKLLET ECPQYIRKKG
60 70 80 90
ADVWFKELDI NTDGAVNFQE FLILVIKMGV AAHKKSHEES HKE
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 80 – 93 | VAAHK…ESHKE → WQPTKKAMKKATKSS in CAA68390 (PubMed:3561500).CuratedAdd BLAST | 14 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | Y00278 mRNA Translation: CAA68390.1 X06234 mRNA Translation: CAA29580.1 M21005 Genomic DNA Translation: AAA36327.1 AK291328 mRNA Translation: BAF84017.1 CR407674 mRNA Translation: CAG28602.1 BT007378 mRNA Translation: AAP36042.1 AL591704 Genomic DNA No translation available. CH471121 Genomic DNA Translation: EAW53330.1 CH471121 Genomic DNA Translation: EAW53331.1 BC005928 mRNA Translation: AAH05928.1 |
CCDSi | CCDS1038.1 |
PIRi | A31848, BCHUCF |
RefSeqi | NP_001306126.1, NM_001319197.1 NP_001306127.1, NM_001319198.1 NP_001306130.1, NM_001319201.1 NP_002955.2, NM_002964.4 |
Genome annotation databases
Ensembli | ENST00000368732; ENSP00000357721; ENSG00000143546 ENST00000368733; ENSP00000357722; ENSG00000143546 |
GeneIDi | 6279 |
KEGGi | hsa:6279 |
MANE-Selecti | ENST00000368733.4; ENSP00000357722.3; NM_002964.5; NP_002955.2 |
UCSCi | uc001fbs.3, human |
Similar proteinsi
Cross-referencesi
Web resourcesi
Atlas of Genetics and Cytogenetics in Oncology and Haematology |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | Y00278 mRNA Translation: CAA68390.1 X06234 mRNA Translation: CAA29580.1 M21005 Genomic DNA Translation: AAA36327.1 AK291328 mRNA Translation: BAF84017.1 CR407674 mRNA Translation: CAG28602.1 BT007378 mRNA Translation: AAP36042.1 AL591704 Genomic DNA No translation available. CH471121 Genomic DNA Translation: EAW53330.1 CH471121 Genomic DNA Translation: EAW53331.1 BC005928 mRNA Translation: AAH05928.1 |
CCDSi | CCDS1038.1 |
PIRi | A31848, BCHUCF |
RefSeqi | NP_001306126.1, NM_001319197.1 NP_001306127.1, NM_001319198.1 NP_001306130.1, NM_001319201.1 NP_002955.2, NM_002964.4 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1MR8 | X-ray | 1.90 | A/B | 1-93 | [»] | |
1XK4 | X-ray | 1.80 | A/B/E/F/I/J | 1-93 | [»] | |
4GGF | X-ray | 1.60 | A/K/S/U | 1-93 | [»] | |
4XJK | X-ray | 1.76 | A/C/E/G/I | 1-93 | [»] | |
5HLO | X-ray | 2.10 | A/B/C/D | 2-93 | [»] | |
5HLV | X-ray | 2.20 | A/B/C/D/E/F/G/H | 2-93 | [»] | |
5W1F | X-ray | 2.60 | A/C/E/G | 1-93 | [»] | |
6DS2 | X-ray | 2.10 | A/C/E/G | 1-93 | [»] | |
SMRi | P05109 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 112187, 147 interactors |
ComplexPortali | CPX-37, Calprotectin heterotetramer CPX-39, Calprotectin heterodimer CPX-42, S100A8 complex CPX-52, iNOS-S100A8/A9 complex |
CORUMi | P05109 |
DIPi | DIP-1165N |
IntActi | P05109, 63 interactors |
MINTi | P05109 |
STRINGi | 9606.ENSP00000357722 |
Chemistry databases
DrugBanki | DB01373, Calcium DB09130, Copper DB01593, Zinc DB14487, Zinc acetate DB14533, Zinc chloride DB14548, Zinc sulfate, unspecified form |
PTM databases
GlyGeni | P05109, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | P05109 |
PhosphoSitePlusi | P05109 |
Genetic variation databases
BioMutai | S100A8 |
DMDMi | 115442 |
2D gel databases
SWISS-2DPAGEi | P05109 |
Proteomic databases
EPDi | P05109 |
jPOSTi | P05109 |
MassIVEi | P05109 |
MaxQBi | P05109 |
PaxDbi | P05109 |
PeptideAtlasi | P05109 |
PRIDEi | P05109 |
ProteomicsDBi | 51795 |
TopDownProteomicsi | P05109 |
Protocols and materials databases
Antibodypediai | 3463, 1332 antibodies from 44 providers |
DNASUi | 6279 |
Genome annotation databases
Ensembli | ENST00000368732; ENSP00000357721; ENSG00000143546 ENST00000368733; ENSP00000357722; ENSG00000143546 |
GeneIDi | 6279 |
KEGGi | hsa:6279 |
MANE-Selecti | ENST00000368733.4; ENSP00000357722.3; NM_002964.5; NP_002955.2 |
UCSCi | uc001fbs.3, human |
Organism-specific databases
CTDi | 6279 |
DisGeNETi | 6279 |
GeneCardsi | S100A8 |
HGNCi | HGNC:10498, S100A8 |
HPAi | ENSG00000143546, Group enriched (bone marrow, esophagus, lymphoid tissue, vagina) |
MIMi | 123885, gene |
neXtProti | NX_P05109 |
OpenTargetsi | ENSG00000143546 |
PharmGKBi | PA34910 |
VEuPathDBi | HostDB:ENSG00000143546 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502SA01, Eukaryota |
GeneTreei | ENSGT00910000144329 |
HOGENOMi | CLU_138624_6_0_1 |
InParanoidi | P05109 |
OMAi | NYHAIYR |
OrthoDBi | 334070at2759 |
PhylomeDBi | P05109 |
TreeFami | TF332727 |
Enzyme and pathway databases
PathwayCommonsi | P05109 |
Reactomei | R-HSA-1236974, ER-Phagosome pathway R-HSA-166058, MyD88:MAL(TIRAP) cascade initiated on plasma membrane R-HSA-5602498, MyD88 deficiency (TLR2/4) R-HSA-5603041, IRAK4 deficiency (TLR2/4) R-HSA-5668599, RHO GTPases Activate NADPH Oxidases R-HSA-5686938, Regulation of TLR by endogenous ligand R-HSA-6798695, Neutrophil degranulation R-HSA-6799990, Metal sequestration by antimicrobial proteins |
SignaLinki | P05109 |
SIGNORi | P05109 |
Miscellaneous databases
BioGRID-ORCSi | 6279, 4 hits in 1030 CRISPR screens |
ChiTaRSi | S100A8, human |
EvolutionaryTracei | P05109 |
GeneWikii | S100_calcium_binding_protein_A8 |
GenomeRNAii | 6279 |
Pharosi | P05109, Tbio |
PROi | PR:P05109 |
RNActi | P05109, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000143546, Expressed in pharyngeal mucosa and 226 other tissues |
Genevisiblei | P05109, HS |
Family and domain databases
InterProi | View protein in InterPro IPR011992, EF-hand-dom_pair IPR018247, EF_Hand_1_Ca_BS IPR002048, EF_hand_dom IPR001751, S100/CaBP-9k_CS IPR013787, S100_Ca-bd_sub IPR028474, S100A8 |
PANTHERi | PTHR11639:SF5, PTHR11639:SF5, 1 hit |
Pfami | View protein in Pfam PF01023, S_100, 1 hit |
SMARTi | View protein in SMART SM01394, S_100, 1 hit |
SUPFAMi | SSF47473, SSF47473, 1 hit |
PROSITEi | View protein in PROSITE PS00018, EF_HAND_1, 1 hit PS50222, EF_HAND_2, 1 hit PS00303, S100_CABP, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | S10A8_HUMAN | |
Accessioni | P05109Primary (citable) accession number: P05109 Secondary accession number(s): A8K5L3 Q9UCM6 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 13, 1987 |
Last sequence update: | January 1, 1988 | |
Last modified: | February 23, 2022 | |
This is version 223 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 1
Human chromosome 1: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families