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Protein

Protein S100-A9

Gene

S100a9

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

Functioni

S100A9 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, adhesion, can increase the bactericidal activity of neutrophils by promoting phagocytosis via activation of SYK, PI3K/AKT, and ERK1/2 and can induce degranulation of neutrophils by a MAPK-dependent mechanism. 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, NXA5, EZR, MSN and VIM by recognizing a [IL]-x-C-x-x-[DE] motif (By similarity).By similarity6 Publications

Miscellaneous

Has been shown to bind calcium.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi21ZincBy similarity1
Metal bindingi31ZincBy similarity1
Metal bindingi92ZincBy similarity1
Metal bindingi96ZincBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Calcium bindingi24 – 371; low affinityPROSITE-ProRule annotationAdd BLAST14
Calcium bindingi68 – 792; 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-A9
Alternative name(s):
Calgranulin-B
Leukocyte L1 complex heavy chain
Migration inhibitory factor-related protein 14
Short name:
MRP-14
Short name:
p14
S100 calcium-binding protein A9
Gene namesi
Name:S100a9
Synonyms:Cagb, Mrp14
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:1338947 S100a9

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

No visible phenotype. Alters response of phagocytes to stimulation with bacterial lipopolysaccharide (LPS).2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00001439982 – 113Protein S100-A9Add BLAST112

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanine1 Publication1
Modified residuei107Pros-methylhistidineBy similarity1

Post-translational modificationi

Phosphorylated. Phosphorylation inhibits activation of tubulin polymerization (By similarity).By similarity

Keywords - PTMi

Acetylation, Methylation, Phosphoprotein

Proteomic databases

PaxDbiP31725
PeptideAtlasiP31725
PRIDEiP31725

PTM databases

iPTMnetiP31725
PhosphoSitePlusiP31725

Expressioni

Gene expression databases

BgeeiENSMUSG00000056071 Expressed in 163 organ(s), highest expression level in bone marrow
CleanExiMM_S100A9
ExpressionAtlasiP31725 baseline and differential
GenevisibleiP31725 MM

Interactioni

Subunit structurei

Homodimer. Preferentially exists as a heterodimer or heterotetramer with S100A8 known as calprotectin (S100A8/A9). S100A9 interacts with beta-APP40 (amyloid-beta protein 40) peptide of APP (By similarity). S100A9 interacts with AGER and the heterodimeric complex formed by TLR4 and LY96 in the presence of calcium and/or zinc ions. S100A9 binds quinoline-3-carboxamides in the presence of calcium and/or zinc ions. S100A9 interacts with ATP2A2. Calprotectin (S100A8/9) interacts with NCF2/P67PHOX, RAC1, RAC2, CYBA and CYBB (By similarity). Heterotetrameric calprotectin (S100A8/A9) interacts with ANXA6 and associates with tubulin filaments in activated monocytes (By similarity). Calprotectin (S100A8/9) interacts with CEACAM3 and tubulin filaments in a calcium-dependent manner. Calprotectin (S100A8/9) interacts with NOS2 to form the iNOS-S100A8/A9 transnitrosylase complex (By similarity).By similarity4 Publications

GO - Molecular functioni

Protein-protein interaction databases

ComplexPortaliCPX-40 Calprotectin heterotetramer
CPX-41 Calprotectin heterodimer
CPX-49 S100A9 complex
CPX-53 iNOS-S100A8/A9 complex
IntActiP31725, 2 interactors
MINTiP31725
STRINGi10090.ENSMUSP00000070842

Structurei

3D structure databases

ProteinModelPortaliP31725
SMRiP31725
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini13 – 48EF-hand 1PROSITE-ProRule annotationAdd BLAST36
Domaini55 – 90EF-hand 2PROSITE-ProRule annotationAdd BLAST36

Sequence similaritiesi

Belongs to the S-100 family.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG410J1XC Eukaryota
ENOG4111C30 LUCA
GeneTreeiENSGT00910000144230
HOGENOMiHOG000246968
HOVERGENiHBG001479
InParanoidiP31725
KOiK21128
OMAiDHIMEDL
OrthoDBiEOG091G12NB
PhylomeDBiP31725
TreeFamiTF332727

Family and domain databases

InterProiView protein in InterPro
IPR011992 EF-hand-dom_pair
IPR002048 EF_hand_dom
IPR028475 S100-A9
IPR001751 S100/CaBP-9k_CS
IPR013787 S100_Ca-bd_sub
PANTHERiPTHR11639:SF79 PTHR11639:SF79, 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
PS50222 EF_HAND_2, 2 hits
PS00303 S100_CABP, 1 hit

Sequencei

Sequence statusi: Complete.

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

P31725-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MANKAPSQME RSITTIIDTF HQYSRKEGHP DTLSKKEFRQ MVEAQLATFM
60 70 80 90 100
KKEKRNEALI NDIMEDLDTN QDNQLSFEEC MMLMAKLIFA CHEKLHENNP
110
RGHGHSHGKG CGK
Length:113
Mass (Da):13,049
Last modified:January 23, 2007 - v3
Checksum:iF4DCFBD1A181F812
GO

Mass spectrometryi

Molecular mass is 12972±2 Da from positions 2 - 113. Determined by ESI. 1 Publication

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M83219 mRNA Translation: AAB07228.1
AJ250496 Genomic DNA Translation: CAC14292.1
BC027635 mRNA Translation: AAH27635.1
CCDSiCCDS17543.1
PIRiS68242
RefSeqiNP_001268781.1, NM_001281852.1
NP_033140.1, NM_009114.3
UniGeneiMm.2128

Genome annotation databases

EnsembliENSMUST00000069960; ENSMUSP00000070842; ENSMUSG00000056071
ENSMUST00000117167; ENSMUSP00000112843; ENSMUSG00000056071
GeneIDi20202
KEGGimmu:20202
UCSCiuc008qde.2 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M83219 mRNA Translation: AAB07228.1
AJ250496 Genomic DNA Translation: CAC14292.1
BC027635 mRNA Translation: AAH27635.1
CCDSiCCDS17543.1
PIRiS68242
RefSeqiNP_001268781.1, NM_001281852.1
NP_033140.1, NM_009114.3
UniGeneiMm.2128

3D structure databases

ProteinModelPortaliP31725
SMRiP31725
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

ComplexPortaliCPX-40 Calprotectin heterotetramer
CPX-41 Calprotectin heterodimer
CPX-49 S100A9 complex
CPX-53 iNOS-S100A8/A9 complex
IntActiP31725, 2 interactors
MINTiP31725
STRINGi10090.ENSMUSP00000070842

PTM databases

iPTMnetiP31725
PhosphoSitePlusiP31725

Proteomic databases

PaxDbiP31725
PeptideAtlasiP31725
PRIDEiP31725

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000069960; ENSMUSP00000070842; ENSMUSG00000056071
ENSMUST00000117167; ENSMUSP00000112843; ENSMUSG00000056071
GeneIDi20202
KEGGimmu:20202
UCSCiuc008qde.2 mouse

Organism-specific databases

CTDi6280
MGIiMGI:1338947 S100a9

Phylogenomic databases

eggNOGiENOG410J1XC Eukaryota
ENOG4111C30 LUCA
GeneTreeiENSGT00910000144230
HOGENOMiHOG000246968
HOVERGENiHBG001479
InParanoidiP31725
KOiK21128
OMAiDHIMEDL
OrthoDBiEOG091G12NB
PhylomeDBiP31725
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

ChiTaRSiS100a9 mouse
PROiPR:P31725
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000056071 Expressed in 163 organ(s), highest expression level in bone marrow
CleanExiMM_S100A9
ExpressionAtlasiP31725 baseline and differential
GenevisibleiP31725 MM

Family and domain databases

InterProiView protein in InterPro
IPR011992 EF-hand-dom_pair
IPR002048 EF_hand_dom
IPR028475 S100-A9
IPR001751 S100/CaBP-9k_CS
IPR013787 S100_Ca-bd_sub
PANTHERiPTHR11639:SF79 PTHR11639:SF79, 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
PS50222 EF_HAND_2, 2 hits
PS00303 S100_CABP, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiS10A9_MOUSE
AccessioniPrimary (citable) accession number: P31725
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: January 23, 2007
Last modified: September 12, 2018
This is version 167 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

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