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Protein

Protein S100-A8

Gene

S100a8

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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 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 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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi17ZincBy similarity1
Metal bindingi27ZincBy similarity1
Metal bindingi83ZincBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Calcium bindingi20 – 331; low affinityPROSITE-ProRule annotationAdd BLAST14
Calcium bindingi59 – 702; high affinityPROSITE-ProRule annotationAdd BLAST12

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Antimicrobial, Antioxidant

Keywords - Biological processi

Apoptosis, Autophagy, Chemotaxis, Immunity, Inflammatory response, Innate immunity

Keywords - Ligandi

Calcium, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:88244. S100a8.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

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 keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00001439942 – 89Protein S100-A8Add BLAST88

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei42S-nitrosocysteine1 Publication1

Keywords - PTMi

S-nitrosylation

Proteomic databases

PaxDbiP27005.
PeptideAtlasiP27005.
PRIDEiP27005.

PTM databases

iPTMnetiP27005.
PhosphoSitePlusiP27005.

Expressioni

Gene expression databases

BgeeiENSMUSG00000056054.
CleanExiMM_S100A8.
ExpressionAtlasiP27005. baseline and differential.
GenevisibleiP27005. 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

Protein-protein interaction databases

IntActiP27005. 3 interactors.
MINTiMINT-4133571.
STRINGi10090.ENSMUSP00000064385.

Structurei

3D structure databases

ProteinModelPortaliP27005.
SMRiP27005.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini13 – 48EF-hand 1PROSITE-ProRule annotationAdd BLAST36
Domaini46 – 81EF-hand 2PROSITE-ProRule annotationAdd BLAST36

Sequence similaritiesi

Belongs to the S-100 family.Curated
Contains 2 EF-hand domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG410J2UM. Eukaryota.
ENOG4111CN5. LUCA.
GeneTreeiENSGT00730000111352.
HOGENOMiHOG000246968.
HOVERGENiHBG001479.
InParanoidiP27005.
OMAiIKGNYHA.
OrthoDBiEOG091G13NB.
PhylomeDBiP27005.
TreeFamiTF332727.

Family and domain databases

Gene3Di1.10.238.10. 1 hit.
InterProiIPR011992. 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.
[Graphical view]
PANTHERiPTHR11639:SF5. PTHR11639:SF5. 1 hit.
PfamiPF01023. S_100. 1 hit.
[Graphical view]
SMARTiSM00054. EFh. 1 hit.
SM01394. S_100. 1 hit.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 1 hit.
PROSITEiPS00018. EF_HAND_1. 1 hit.
PS50222. EF_HAND_2. 1 hit.
PS00303. S100_CABP. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

P27005-1 [UniParc]FASTAAdd 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 keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti57E → D in CAA61204 (PubMed:8611640).Curated1

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.
CCDSiCCDS38507.1.
PIRiI56163.
RefSeqiNP_038678.1. NM_013650.2.
UniGeneiMm.21567.

Genome annotation databases

EnsembliENSMUST00000069927; ENSMUSP00000064385; ENSMUSG00000056054.
GeneIDi20201.
KEGGimmu:20201.
UCSCiuc008qdd.1. mouse.

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.
CCDSiCCDS38507.1.
PIRiI56163.
RefSeqiNP_038678.1. NM_013650.2.
UniGeneiMm.21567.

3D structure databases

ProteinModelPortaliP27005.
SMRiP27005.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP27005. 3 interactors.
MINTiMINT-4133571.
STRINGi10090.ENSMUSP00000064385.

PTM databases

iPTMnetiP27005.
PhosphoSitePlusiP27005.

Proteomic databases

PaxDbiP27005.
PeptideAtlasiP27005.
PRIDEiP27005.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000069927; ENSMUSP00000064385; ENSMUSG00000056054.
GeneIDi20201.
KEGGimmu:20201.
UCSCiuc008qdd.1. mouse.

Organism-specific databases

CTDi6279.
MGIiMGI:88244. S100a8.

Phylogenomic databases

eggNOGiENOG410J2UM. Eukaryota.
ENOG4111CN5. LUCA.
GeneTreeiENSGT00730000111352.
HOGENOMiHOG000246968.
HOVERGENiHBG001479.
InParanoidiP27005.
OMAiIKGNYHA.
OrthoDBiEOG091G13NB.
PhylomeDBiP27005.
TreeFamiTF332727.

Enzyme and pathway databases

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

Miscellaneous databases

PROiP27005.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000056054.
CleanExiMM_S100A8.
ExpressionAtlasiP27005. baseline and differential.
GenevisibleiP27005. MM.

Family and domain databases

Gene3Di1.10.238.10. 1 hit.
InterProiIPR011992. 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.
[Graphical view]
PANTHERiPTHR11639:SF5. PTHR11639:SF5. 1 hit.
PfamiPF01023. S_100. 1 hit.
[Graphical view]
SMARTiSM00054. EFh. 1 hit.
SM01394. S_100. 1 hit.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 1 hit.
PROSITEiPS00018. EF_HAND_1. 1 hit.
PS50222. EF_HAND_2. 1 hit.
PS00303. S100_CABP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiS10A8_MOUSE
AccessioniPrimary (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 30, 2016
This is version 137 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

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

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.