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Protein

Protein S100-A9

Gene

S100a9

Organism
Rattus norvegicus (Rat)
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 similarity2 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

Keywordsi

Molecular functionAntimicrobial, Antioxidant
Biological processApoptosis, Autophagy, Chemotaxis, Immunity, Inflammatory response, Innate immunity
LigandCalcium, Metal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Protein S100-A9
Alternative name(s):
Calgranulin-B
Migration inhibitory factor-related protein 14
Short name:
MRP-14
Short name:
p14
Myeloid-related protein 14
S100 calcium-binding protein A9
Gene namesi
Name:S100a9
Synonyms:Mrp14
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi620267. S100a9.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB-SubCell
  • cytoskeleton Source: UniProtKB-SubCell
  • extracellular space Source: RGD
  • plasma membrane Source: UniProtKB-SubCell

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoskeleton, Membrane, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00001439992 – 113Protein S100-A9Add BLAST112

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanine1 Publication1
Modified residuei107Pros-methylhistidine1 Publication1

Post-translational modificationi

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

Keywords - PTMi

Acetylation, Methylation, Phosphoprotein

Proteomic databases

PaxDbiP50116.
PRIDEiP50116.

PTM databases

iPTMnetiP50116.
PhosphoSitePlusiP50116.

Expressioni

Tissue specificityi

Highly expressed at sites of inflammation.2 Publications

Gene expression databases

GenevisibleiP50116. RN.

Interactioni

Subunit structurei

Homodimer. Preferentially exists as a heterodimer or heterotetramer with S100A8 known as calprotectin (S100A8/A9). S100A9 interacts with ATP2A2. S100A9 interacts with AGER, and with 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 beta-APP40 (beta-amyloid protein 40) peptide of APP. 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. Calprotectin (S100A8/9) interacts with NCF2/P67PHOX, RAC1, RAC2, CYBA and CYBB (By similarity). Calprotectin (S100A8/9) interacts with NOS2 to form the iNOS-S100A8/A9 transnitrosylase complex (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000015351.

Structurei

3D structure databases

ProteinModelPortaliP50116.
SMRiP50116.
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.
HOGENOMiHOG000246968.
HOVERGENiHBG001479.
InParanoidiP50116.
KOiK21128.
OrthoDBiEOG091G12NB.
PhylomeDBiP50116.
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:SF110. PTHR11639:SF110. 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. 1 hit.
PS00303. S100_CABP. 1 hit.

Sequencei

Sequence statusi: Complete.

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

P50116-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAAKTGSQLE RSISTIINVF HQYSRKYGHP DTLNKAEFKE MVNKDLPNFL
60 70 80 90 100
KREKRNENLL RDIMEDLDTN QDNQLSFEEC MMLMGKLIFA CHEKLHENNP
110
RGHDHSHGKG CGK
Length:113
Mass (Da):13,145
Last modified:January 23, 2007 - v3
Checksum:i6C3A0044A7AEC4FA
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti17I → Q AA sequence (PubMed:15153104).Curated1
Sequence conflicti24S → C AA sequence (PubMed:15153104).Curated1
Sequence conflicti106S → R in AAA18214 (PubMed:8343166).Curated1

Mass spectrometryi

Molecular mass is 13069±2 Da from positions 2 - 113. Determined by ESI. 1 Publication

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L18948 mRNA. Translation: AAA18214.1.
AB118215 mRNA. Translation: BAC82423.1.
PIRiJN0686.
RefSeqiNP_446039.1. NM_053587.1.
UniGeneiRn.6703.

Genome annotation databases

GeneIDi94195.
KEGGirno:94195.
UCSCiRGD:620267. rat.

Similar proteinsi

Entry informationi

Entry nameiS10A9_RAT
AccessioniPrimary (citable) accession number: P50116
Secondary accession number(s): Q761U7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: January 23, 2007
Last modified: August 30, 2017
This is version 137 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