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. The iNOS-S100A8/A9 transnitrosylase complex is proposed to direct selective inflammatory stimulus-dependent S-nitrosylation of multiple targets such as GAPDH, ANXA5, EZR, MSN and VIM by recognizing a [IL]-x-C-x-x-[DE] motif; S100A8 seems to contribute to S-nitrosylation site selectivity (By similarity).By similarity2 Publications

Miscellaneous

Binds two calcium ions per molecule with an affinity similar to that of the S-100 proteins.By similarity

Sites

Feature key	Position(s)	DescriptionActions	Length
Metal bindingⁱ	17	ZincBy similarity	1
Metal bindingⁱ	27	ZincBy similarity	1
Metal bindingⁱ	83	ZincBy similarity	1

Regions

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Calcium bindingⁱ	20 – 33	1; low affinityPROSITE-ProRule annotationAdd BLAST		14
Calcium bindingⁱ	59 – 70	2; high affinityPROSITE-ProRule annotationAdd BLAST		12

GO - Molecular functionⁱ

antioxidant activity Source: UniProtKB-KW
arachidonic acid binding Source: InterPro
calcium ion binding Source: InterPro
microtubule binding Source: InterPro
RAGE receptor binding Source: InterPro
Toll-like receptor 4 binding Source: InterPro
zinc ion binding Source: InterPro

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

activation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
apoptotic process Source: UniProtKB-KW
astrocyte development
Source: MGI
Inferred from genetic interactionⁱ
- 22577135
autophagy Source: UniProtKB
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: MGI
positive regulation of inflammatory response Source: UniProtKB
positive regulation of intrinsic apoptotic signaling pathway Source: UniProtKB
positive regulation of peptide secretion
Source: MGI
Inferred from direct assayⁱ
- 18820689

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Antimicrobial, Antioxidant
Biological process	Apoptosis, Autophagy, Chemotaxis, Immunity, Inflammatory response, Innate immunity
Ligand	Calcium, Metal-binding, Zinc

Enzyme and pathway databases

Reactomeⁱ	R-MMU-5686938 Regulation of TLR by endogenous ligand R-MMU-6798695 Neutrophil degranulation R-MMU-6799990 Metal sequestration by antimicrobial proteins

Reactomeⁱ

R-MMU-5686938 Regulation of TLR by endogenous ligand
R-MMU-6798695 Neutrophil degranulation
R-MMU-6799990 Metal sequestration by antimicrobial proteins

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: Protein S100-A8 Alternative name(s): Calgranulin-A Chemotactic cytokine CP-10 Leukocyte L1 complex light chain Migration inhibitory factor-related protein 8 Short name: MRP-8 Short name: p8 Pro-inflammatory S100 cytokine S100 calcium-binding protein A8
Gene namesⁱ	Name:S100a8 Synonyms:Caga, Mrp8
Organismⁱ	Mus musculus (Mouse)
Taxonomic identifierⁱ	10090 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus
Proteomesⁱ	UP000000589 Componentⁱ: Chromosome 3

Organism-specific databases

MGIⁱ	MGI:88244 S100a8

Keywords - Cellular componentⁱ

Cell membrane, Cytoplasm, Cytoskeleton, Membrane, Secreted

Pathology & Biotechⁱ

Disruption phenotypeⁱ

Death at an early embryonic stage due to embryo resorption, starting about 8 days after fertilization.1 Publication

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Initiator methionineⁱ		Removed1 Publication
ChainⁱPRO_0000143994	2 – 89	Protein S100-A8Add BLAST		88

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Modified residueⁱ	42	S-nitrosocysteine1 Publication		1

Keywords - PTMⁱ

S-nitrosylation

Proteomic databases

PaxDbⁱ	P27005
PeptideAtlas More...PeptideAtlasⁱ	P27005
PRIDEⁱ	P27005

PTM databases

iPTMnetⁱ	P27005
PhosphoSitePlusⁱ	P27005

Expressionⁱ

Gene expression databases

Bgeeⁱ	ENSMUSG00000056054 Expressed in 166 organ(s), highest expression level in bone marrow
CleanExⁱ	MM_S100A8
ExpressionAtlasⁱ	P27005 baseline and differential
Genevisibleⁱ	P27005 MM

Interactionⁱ

Subunit structureⁱ

Homodimer. Preferentially exists as a heterodimer or heterotetramer with S100A9 known as calprotectin (S100A8/A9). 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 (By similarity). S100A8 interacts with AGER, ATP2A2 and with the heterodimeric complex formed by TLR4 and LY96. Calprotectin (S100A8/9) interacts with NOS2 to form the iNOS-S100A8/A9 transnitrosylase complex (By similarity).By similarity2 Publications

GO - Molecular functionⁱ

microtubule binding Source: InterPro
RAGE receptor binding Source: InterPro
Toll-like receptor 4 binding Source: InterPro

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

ComplexPortalⁱ	CPX-40 Calprotectin heterotetramer CPX-41 Calprotectin heterodimer CPX-47 S100A8 complex CPX-53 iNOS-S100A8/A9 complex
IntActⁱ	P27005, 3 interactors
Molecular INTeraction database More...MINTⁱ	P27005
STRINGⁱ	10090.ENSMUSP00000064385

Structureⁱ

3D structure databases

ProteinModelPortalⁱ	P27005
SMRⁱ	P27005
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Domainⁱ	13 – 48	EF-hand 1PROSITE-ProRule annotationAdd BLAST		36
Domainⁱ	46 – 81	EF-hand 2PROSITE-ProRule annotationAdd BLAST		36

Sequence similaritiesⁱ

Belongs to the S-100 family.Curated

Keywords - Domainⁱ

Repeat

Phylogenomic databases

eggNOGⁱ	ENOG410J2UM Eukaryota ENOG4111CN5 LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00910000144329
HOGENOMⁱ	HOG000246968
HOVERGENⁱ	HBG001479
InParanoidⁱ	P27005
KEGG Orthology (KO) More...KOⁱ	K21127
OMAⁱ	YHKYSLE
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G13NB
PhylomeDBⁱ	P27005
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
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF01023 S_100, 1 hit
SMARTⁱ	View protein in SMART SM00054 EFh, 1 hit 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

Sequenceⁱ

Sequence statusⁱ: Complete.

Sequence processingⁱ: The displayed sequence is further processed into a mature form.

P27005-1 [UniParc]FASTA Add to basket

« Hide

        10         20         30         40         50
MPSELEKALS NLIDVYHNYS NIQGNHHALY KNDFKKMVTT ECPQFVQNIN 
        60         70         80 
IENLFRELDI NSDNAINFEE FLAMVIKVGV ASHKDSHKE

Length:89

Mass (Da):10,295

Last modified:January 23, 2007 - v3

Checksum:ⁱD2AFF46ACE867A28

GO

Experimental Info

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Sequence conflictⁱ	57	E → D in CAA61204 (PubMed:8611640).Curated		1

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	M83218 mRNA Translation: AAB07229.1 S57123 mRNA Translation: AAB25840.1 X87966 Genomic DNA Translation: CAA61204.1 BC078629 mRNA Translation: AAH78629.1
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS38507.1
PIRⁱ	I56163
NCBI Reference Sequences More...RefSeqⁱ	NP_038678.1, NM_013650.2
UniGeneⁱ	Mm.21567

Genome annotation databases

Ensemblⁱ	ENSMUST00000069927; ENSMUSP00000064385; ENSMUSG00000056054
GeneIDⁱ	20201
KEGGⁱ	mmu:20201
UCSC genome browser More...UCSCⁱ	uc008qdd.1 mouse

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
P27005	Protein S100		MOUSE		89	UniRef100_P27005

Protein	Similar proteins		Species	Score	Length	Source
P27005	Protein S100		MOUSE		89	UniRef90_P27005
UPI000A31A804		MUSCR		89

Protein	Similar proteins		Species	Score	Length	Source
P27005	Protein S100-A8		RAT		89	UniRef50_P27005
Protein S100-A8		BOVIN		89
Protein S100		MOUSE		89
Protein S100		ERIEU		89
Protein S100-A8		PTEAL		93
+100

Cross-referencesⁱ

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	M83218 mRNA Translation: AAB07229.1 S57123 mRNA Translation: AAB25840.1 X87966 Genomic DNA Translation: CAA61204.1 BC078629 mRNA Translation: AAH78629.1
CCDSⁱ	CCDS38507.1
PIRⁱ	I56163
RefSeqⁱ	NP_038678.1, NM_013650.2
UniGeneⁱ	Mm.21567

3D structure databases

ProteinModelPortalⁱ	P27005
SMRⁱ	P27005
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

ComplexPortalⁱ	CPX-40 Calprotectin heterotetramer CPX-41 Calprotectin heterodimer CPX-47 S100A8 complex CPX-53 iNOS-S100A8/A9 complex
IntActⁱ	P27005, 3 interactors
MINTⁱ	P27005
STRINGⁱ	10090.ENSMUSP00000064385

PTM databases

iPTMnetⁱ	P27005
PhosphoSitePlusⁱ	P27005

Proteomic databases

PaxDbⁱ	P27005
PeptideAtlasⁱ	P27005
PRIDEⁱ	P27005

Protocols and materials databases

Structural Biology Knowledgebase	Search...

Structural Biology Knowledgebase

Search...

Genome annotation databases

Ensemblⁱ	ENSMUST00000069927; ENSMUSP00000064385; ENSMUSG00000056054
GeneIDⁱ	20201
KEGGⁱ	mmu:20201
UCSCⁱ	uc008qdd.1 mouse

Organism-specific databases

CTDⁱ	6279
MGIⁱ	MGI:88244 S100a8

Phylogenomic databases

eggNOGⁱ	ENOG410J2UM Eukaryota ENOG4111CN5 LUCA
GeneTreeⁱ	ENSGT00910000144329
HOGENOMⁱ	HOG000246968
HOVERGENⁱ	HBG001479
InParanoidⁱ	P27005
KOⁱ	K21127
OMAⁱ	YHKYSLE
OrthoDBⁱ	EOG091G13NB
PhylomeDBⁱ	P27005
TreeFamⁱ	TF332727

Enzyme and pathway databases

Reactomeⁱ	R-MMU-5686938 Regulation of TLR by endogenous ligand R-MMU-6798695 Neutrophil degranulation R-MMU-6799990 Metal sequestration by antimicrobial proteins

Reactomeⁱ

R-MMU-5686938 Regulation of TLR by endogenous ligand
R-MMU-6798695 Neutrophil degranulation
R-MMU-6799990 Metal sequestration by antimicrobial proteins

Miscellaneous databases

Protein Ontology More...PROⁱ	PR:P27005
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSMUSG00000056054 Expressed in 166 organ(s), highest expression level in bone marrow
CleanExⁱ	MM_S100A8
ExpressionAtlasⁱ	P27005 baseline and differential
Genevisibleⁱ	P27005 MM

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 SM00054 EFh, 1 hit 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
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	S10A8_MOUSE
Accessionⁱ	P27005Primary (citable) accession number: P27005 Secondary accession number(s): P31724
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	August 1, 1992
	Last sequence update:	January 23, 2007
	Last modified:	November 7, 2018
	This is version 148 of the entry and version 3 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program

Miscellaneousⁱ

Keywords - Technical termⁱ

Complete proteome, Direct protein sequencing, Reference proteome

Documents

SIMILARITY comments
Index of protein domains and families
MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

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UniParc

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Supporting data

UniProtKB - P27005 (S10A8_MOUSE)

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Protein S100-A8

Select a section on the left to see content.

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Miscellaneous

Sites

Regions

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted

Cytoskeleton

Plasma membrane

Other locations

Cytoskeleton

Cytosol

Extracellular region or secreted

Plasma Membrane

Keywords - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Keywords - PTMi

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

GO - Molecular functioni

Protein-protein interaction databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Keywords - Domaini

Phylogenomic databases

Family and domain databases

Experimental Info

Sequence databases

Genome annotation databases

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

Documents

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Keywords - Domainⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ