Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Protein S100-A8

Gene

S100a8

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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 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 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

Keywordsi

Molecular functionAntimicrobial, Antioxidant
Biological processApoptosis, Autophagy, Chemotaxis, Immunity, Inflammatory response, Innate immunity
LigandCalcium, 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:88244 S100a8

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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 Expressed in 166 organ(s), highest expression level in bone marrow
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

GO - Molecular functioni

Protein-protein interaction databases

ComplexPortaliCPX-40 Calprotectin heterotetramer
CPX-41 Calprotectin heterodimer
CPX-47 S100A8 complex
CPX-53 iNOS-S100A8/A9 complex
IntActiP27005, 3 interactors
MINTiP27005
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

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG410J2UM Eukaryota
ENOG4111CN5 LUCA
GeneTreeiENSGT00910000144329
HOGENOMiHOG000246968
HOVERGENiHBG001479
InParanoidiP27005
KOiK21127
OMAiYHKYSLE
OrthoDBiEOG091G13NB
PhylomeDBiP27005
TreeFamiTF332727

Family and domain databases

InterProiView 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
PANTHERiPTHR11639:SF5 PTHR11639:SF5, 1 hit
PfamiView protein in Pfam
PF01023 S_100, 1 hit
SMARTiView protein in SMART
SM00054 EFh, 1 hit
SM01394 S_100, 1 hit
SUPFAMiSSF47473 SSF47473, 1 hit
PROSITEiView 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]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

Similar proteinsi

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

ComplexPortaliCPX-40 Calprotectin heterotetramer
CPX-41 Calprotectin heterodimer
CPX-47 S100A8 complex
CPX-53 iNOS-S100A8/A9 complex
IntActiP27005, 3 interactors
MINTiP27005
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
GeneTreeiENSGT00910000144329
HOGENOMiHOG000246968
HOVERGENiHBG001479
InParanoidiP27005
KOiK21127
OMAiYHKYSLE
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

PROiPR:P27005
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000056054 Expressed in 166 organ(s), highest expression level in bone marrow
CleanExiMM_S100A8
ExpressionAtlasiP27005 baseline and differential
GenevisibleiP27005 MM

Family and domain databases

InterProiView 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
PANTHERiPTHR11639:SF5 PTHR11639:SF5, 1 hit
PfamiView protein in Pfam
PF01023 S_100, 1 hit
SMARTiView protein in SMART
SM00054 EFh, 1 hit
SM01394 S_100, 1 hit
SUPFAMiSSF47473 SSF47473, 1 hit
PROSITEiView protein in PROSITE
PS00018 EF_HAND_1, 1 hit
PS50222 EF_HAND_2, 1 hit
PS00303 S100_CABP, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiS10A8_MOUSE
AccessioniPrimary (citable) accession number: P27005
Secondary accession number(s): P31724
Entry historyiIntegrated 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 statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again