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Protein

Protein S100-A9

Gene

S100a9

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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 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, NXA5, EZR, MSN and VIM by recognizing a [IL]-x-C-x-x-[DE] motif (By similarity).By similarity6 Publications

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

  • actin cytoskeleton reorganization Source: MGI
  • activation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
  • apoptotic process Source: UniProtKB-KW
  • astrocyte development Source: MGI
  • autophagy Source: UniProtKB
  • innate immune response Source: UniProtKB-KW
  • leukocyte chemotaxis Source: MGI
  • leukocyte migration involved in inflammatory response Source: UniProtKB
  • neutrophil aggregation Source: UniProtKB
  • neutrophil chemotaxis Source: UniProtKB
  • peptidyl-cysteine S-nitrosylation Source: UniProtKB
  • peptidyl-cysteine S-trans-nitrosylation Source: MGI
  • positive regulation of blood coagulation Source: CACAO
  • positive regulation of inflammatory response Source: UniProtKB
  • positive regulation of intrinsic apoptotic signaling pathway Source: UniProtKB
  • positive regulation of peptide secretion Source: MGI
  • regulation of integrin biosynthetic process Source: MGI
  • regulation of translation Source: UniProtKB
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-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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:1338947. S100a9.

Subcellular locationi

  • Secreted By similarity
  • Cytoplasm
  • Cytoplasmcytoskeleton
  • Cell membrane By similarity; Peripheral membrane protein By similarity

  • 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.

GO - Cellular componenti

Complete GO annotation...

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.
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 (beta-amyloid 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

Protein-protein interaction databases

IntActiP31725. 2 interactors.
MINTiMINT-4133588.
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
Contains 2 EF-hand domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG410J1XC. Eukaryota.
ENOG4111C30. LUCA.
GeneTreeiENSGT00760000119034.
HOGENOMiHOG000246968.
HOVERGENiHBG001479.
InParanoidiP31725.
OMAiDHIMEDL.
OrthoDBiEOG091G12NB.
PhylomeDBiP31725.
TreeFamiTF332727.

Family and domain databases

Gene3Di1.10.238.10. 1 hit.
InterProiIPR011992. EF-hand-dom_pair.
IPR002048. EF_hand_dom.
IPR028475. S100-A9.
IPR001751. S100/CaBP-9k_CS.
IPR013787. S100_Ca-bd_sub.
[Graphical view]
PANTHERiPTHR11639:SF79. PTHR11639:SF79. 1 hit.
PfamiPF01023. S_100. 1 hit.
[Graphical view]
SMARTiSM00054. EFh. 1 hit.
SM01394. S_100. 1 hit.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 1 hit.
PROSITEiPS50222. EF_HAND_2. 2 hits.
PS00303. S100_CABP. 1 hit.
[Graphical view]

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.

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

IntActiP31725. 2 interactors.
MINTiMINT-4133588.
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.
GeneTreeiENSGT00760000119034.
HOGENOMiHOG000246968.
HOVERGENiHBG001479.
InParanoidiP31725.
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.
PROiP31725.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000056071.
CleanExiMM_S100A9.
ExpressionAtlasiP31725. baseline and differential.
GenevisibleiP31725. MM.

Family and domain databases

Gene3Di1.10.238.10. 1 hit.
InterProiIPR011992. EF-hand-dom_pair.
IPR002048. EF_hand_dom.
IPR028475. S100-A9.
IPR001751. S100/CaBP-9k_CS.
IPR013787. S100_Ca-bd_sub.
[Graphical view]
PANTHERiPTHR11639:SF79. PTHR11639:SF79. 1 hit.
PfamiPF01023. S_100. 1 hit.
[Graphical view]
SMARTiSM00054. EFh. 1 hit.
SM01394. S_100. 1 hit.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 1 hit.
PROSITEiPS50222. EF_HAND_2. 2 hits.
PS00303. S100_CABP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiS10A9_MOUSE
AccessioniPrimary (citable) accession number: P31725
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 155 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Has been shown to bind calcium.

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.