Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P50116 (S10A9_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 112. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:S100a9
Synonyms:Mrp14
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length113 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.3 Ref.4

Subunit structure

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. Ref.3

Subcellular location

Secreted By similarity. Cytoplasm By similarity. Cytoplasmcytoskeleton By similarity. Cell membrane; Peripheral membrane protein. 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 By similarity. Ref.4

Tissue specificity

Highly expressed at sites of inflammation. Ref.1 Ref.3

Post-translational modification

Phosphorylated. Phosphorylation inhibits activation of tubulin polymerization By similarity.

Sequence similarities

Belongs to the S-100 family.

Contains 2 EF-hand domains.

Mass spectrometry

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

Ontologies

Keywords
   Biological processApoptosis
Autophagy
Chemotaxis
Immunity
Inflammatory response
Innate immunity
   Cellular componentCell membrane
Cytoplasm
Cytoskeleton
Membrane
Secreted
   DomainRepeat
   LigandCalcium
Metal-binding
Zinc
   Molecular functionAntimicrobial
Antioxidant
   PTMAcetylation
Methylation
Phosphoprotein
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processactin cytoskeleton reorganization

Inferred from electronic annotation. Source: Ensembl

activation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

autophagy

Inferred from sequence or structural similarity. Source: UniProtKB

chronic inflammatory response

Inferred from expression pattern Ref.1. Source: RGD

innate immune response

Inferred from electronic annotation. Source: UniProtKB-KW

leukocyte migration involved in inflammatory response

Inferred from sequence or structural similarity. Source: UniProtKB

neutrophil aggregation

Inferred from sequence or structural similarity. Source: UniProtKB

neutrophil chemotaxis

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of inflammatory response

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of intrinsic apoptotic signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of integrin biosynthetic process

Inferred from electronic annotation. Source: Ensembl

response to ethanol

Inferred from expression pattern PubMed 17207109. Source: RGD

response to lipopolysaccharide

Inferred from expression pattern PubMed 17207109. Source: RGD

response to zinc ion

Inferred from expression pattern PubMed 19111725. Source: RGD

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytoskeleton

Inferred from electronic annotation. Source: UniProtKB-SubCell

extracellular space

Inferred from direct assay PubMed 15221771. Source: RGD

nucleus

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionantioxidant activity

Inferred from electronic annotation. Source: UniProtKB-KW

calcium ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.2
Chain2 – 113112Protein S100-A9
PRO_0000143999

Regions

Domain13 – 4836EF-hand 1
Domain55 – 9036EF-hand 2
Calcium binding24 – 37141; low affinity Potential
Calcium binding68 – 79122; high affinity Potential

Sites

Metal binding211Zinc By similarity
Metal binding311Zinc By similarity
Metal binding921Zinc By similarity
Metal binding961Zinc By similarity

Amino acid modifications

Modified residue21N-acetylalanine Ref.2
Modified residue1071Pros-methylhistidine Ref.2

Experimental info

Sequence conflict171I → Q AA sequence Ref.3
Sequence conflict241S → C AA sequence Ref.3
Sequence conflict1061S → R in AAA18214. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P50116 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: 6C3A0044A7AEC4FA

FASTA11313,145
        10         20         30         40         50         60 
MAAKTGSQLE RSISTIINVF HQYSRKYGHP DTLNKAEFKE MVNKDLPNFL KREKRNENLL 

        70         80         90        100        110 
RDIMEDLDTN QDNQLSFEEC MMLMGKLIFA CHEKLHENNP RGHDHSHGKG CGK 

« Hide

References

[1]"Expression and cloning of migration inhibitory factor-related protein (MRP)8 and MRP14 in arthritis-susceptible rats."
Imamichi T., Uchida I., Wahl S.M., McCartney-Francis N.
Biochem. Biophys. Res. Commun. 194:819-825(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
Strain: Lewis/N.
Tissue: Peritoneal cavity.
[2]"Identification of posttranslational modifications and cDNA sequencing errors in the rat S100 proteins MRP8 and 14 using electrospray ionization mass spectrometry."
Raftery M.J., Geczy C.L.
Anal. Biochem. 258:285-292(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-57; 62-65 AND 72-113, MASS SPECTROMETRY, ACETYLATION AT ALA-2, METHYLATION AT HIS-107.
Tissue: Spleen.
[3]"Fibroblast growth-stimulating activity of S100A9 (MRP-14)."
Shibata F., Miyama K., Shinoda F., Mizumoto J., Takano K., Nakagawa H.
Eur. J. Biochem. 271:2137-2143(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 3-113, PROTEIN SEQUENCE OF 11-25; 38-67; 81-90 AND 94-112, FUNCTION, SUBUNIT, TISSUE SPECIFICITY.
Strain: Wistar.
Tissue: Macrophage and Peritoneal cavity.
[4]"Dynamic mobility of immunological cells expressing S100A8 and S100A9 in vivo: a variety of functional roles of the two proteins as regulators in acute inflammatory reaction."
Koike A., Arai S., Yamada S., Nagae A., Saita N., Itoh H., Uemoto S., Totani M., Ikemoto M.
Inflammation 35:409-419(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L18948 mRNA. Translation: AAA18214.1.
AB118215 mRNA. Translation: BAC82423.1.
PIRJN0686.
RefSeqNP_446039.1. NM_053587.1.
UniGeneRn.6703.

3D structure databases

ProteinModelPortalP50116.
SMRP50116. Positions 7-96.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING10116.ENSRNOP00000015351.

Proteomic databases

PRIDEP50116.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000015351; ENSRNOP00000015351; ENSRNOG00000011483.
GeneID94195.
KEGGrno:94195.
UCSCRGD:620267. rat.

Organism-specific databases

CTD6280.
RGD620267. S100a9.

Phylogenomic databases

eggNOGNOG47012.
GeneTreeENSGT00740000114986.
HOGENOMHOG000246968.
HOVERGENHBG001479.
InParanoidP50116.
OMASFTENAC.
OrthoDBEOG73807B.
PhylomeDBP50116.
TreeFamTF332727.

Gene expression databases

GenevestigatorP50116.

Family and domain databases

Gene3D1.10.238.10. 1 hit.
InterProIPR011992. EF-hand-dom_pair.
IPR002048. EF_hand_dom.
IPR028475. S100-A9.
IPR001751. S100/CaBP-9k_CS.
IPR013787. S100_Ca-bd_sub.
[Graphical view]
PANTHERPTHR11639:SF53. PTHR11639:SF53. 1 hit.
PfamPF01023. S_100. 1 hit.
[Graphical view]
PROSITEPS50222. EF_HAND_2. 1 hit.
PS00303. S100_CABP. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio617850.
PROP50116.

Entry information

Entry nameS10A9_RAT
AccessionPrimary (citable) accession number: P50116
Secondary accession number(s): Q761U7
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: January 23, 2007
Last modified: June 11, 2014
This is version 112 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families