P31725 (S10A9_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	S100a9
Synonyms:	Cagb, Mrp14

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	113 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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, transfering 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.6 Ref.7 Ref.8 Ref.10 Ref.12 Ref.13
Subunit structure	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. Ref.6 Ref.7 Ref.8 Ref.10
Subcellular location	Secreted By similarity. Cytoplasm. Cytoplasm › cytoskeleton. Cell membrane; 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. Ref.7 Ref.10
Post-translational modification	Phosphorylated. Phosphorylation inhibits activation of tubulin polymerization By similarity. Ref.6
Disruption phenotype	No visible phenotype. Alters response of phagocytes to stimulation with bacterial lipopolysaccharide (LPS). Ref.5 Ref.7
Miscellaneous	Has been shown to bind calcium.
Sequence similarities	Belongs to the S-100 family. Contains 2 EF-hand domains.
Mass spectrometry	Molecular mass is 12972±2 Da from positions 2 - 113. Determined by ESI. Ref.4

Ontologies

Keywords
Biological process	Apoptosis Autophagy Chemotaxis Immunity Inflammatory response Innate immunity
Cellular component	Cell membrane Cytoplasm Cytoskeleton Membrane Secreted
Domain	Repeat
Ligand	Calcium Metal-binding Zinc
Molecular function	Antimicrobial Antioxidant
PTM	Acetylation Methylation Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	actin cytoskeleton reorganization Inferred from mutant phenotype Ref.5. Source: MGI 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 electronic annotation. Source: Compara induction of apoptosis Inferred from sequence or structural similarity. Source: UniProtKB 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 regulation of integrin biosynthetic process Inferred from mutant phenotype Ref.5. Source: MGI response to ethanol Inferred from electronic annotation. Source: Compara response to lipopolysaccharide Inferred from electronic annotation. Source: Compara response to zinc ion Inferred from electronic annotation. Source: Compara
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell cytoskeleton Inferred from electronic annotation. Source: UniProtKB-SubCell extracellular space Inferred from electronic annotation. Source: Compara nucleus Inferred from electronic annotation. Source: Compara plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	antioxidant activity Inferred from electronic annotation. Source: UniProtKB-KW calcium ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Ref.4
	Chain	2 – 113	112	Protein S100-A9		PRO_0000143998
Regions
	Domain	13 – 48	36	EF-hand 1
	Domain	55 – 90	36	EF-hand 2
	Calcium binding	24 – 37	14	1; low affinity Potential
	Calcium binding	68 – 79	12	2; high affinity Potential
Sites
	Metal binding	21	1	Zinc By similarity
	Metal binding	31	1	Zinc By similarity
	Metal binding	92	1	Zinc By similarity
	Metal binding	96	1	Zinc By similarity
Amino acid modifications
	Modified residue	2	1	N-acetylalanine Ref.4
	Modified residue	107	1	Pros-methylhistidine Ref.4

Sequences

	Sequence		Length	Mass (Da)
	P31725 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: F4DCFBD1A181F812	FASTA	113	13,049
	10 20 30 40 50 60 MANKAPSQME RSITTIIDTF HQYSRKEGHP DTLSKKEFRQ MVEAQLATFM KKEKRNEALI 70 80 90 100 110 NDIMEDLDTN QDNQLSFEEC MMLMAKLIFA CHEKLHENNP RGHGHSHGKG CGK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mouse MRP8 and MRP14, two intracellular calcium-binding proteins associated with the development of the myeloid lineage." Lagasse E., Weissman I.L. Blood 79:1907-1915(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: BALB/c.
[2]	"Molecular analysis of the mouse S100A9 gene and evidence that the myeloid specific transcription factor C/EBPepsilon is not required for the regulation of the S100A9/A8 gene expression in neutrophils." Nacken W.K.F., Lekstrom-Himes J.A., Sorg C., Manitz M. J. Cell. Biochem. 80:606-616(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: 129/SvJ.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Mammary gland.
[4]	"Isolation of the murine S100 protein MRP14 (14 kDa migration-inhibitory-factor-related protein) from activated spleen cells: characterization of post-translational modifications and zinc binding." Raftery M.J., Harrison C.A., Alewood P.F., Jones A., Geczy C.L. Biochem. J. 316:285-293(1996) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-10; 76-93 AND 95-109, MASS SPECTROMETRY.
[5]	"Loss of S100A9 (MRP14) results in reduced interleukin-8-induced CD11b surface expression, a polarized microfilament system, and diminished responsiveness to chemoattractants in vitro." Manitz M.-P., Horst B., Seeliger S., Strey A., Skryabin B.V., Gunzer M., Frings W., Schoenlau F., Roth J., Sorg C., Nacken W. Mol. Cell. Biol. 23:1034-1043(2003) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE.
[6]	"MRP8 and MRP14 control microtubule reorganization during transendothelial migration of phagocytes." Vogl T., Ludwig S., Goebeler M., Strey A., Thorey I.S., Reichelt R., Foell D., Gerke V., Manitz M.P., Nacken W., Werner S., Sorg C., Roth J. Blood 104:4260-4268(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH TUBULIN, PHOSPHORYLATION.
[7]	"Mrp8 and Mrp14 are endogenous activators of Toll-like receptor 4, promoting lethal, endotoxin-induced shock." Vogl T., Tenbrock K., Ludwig S., Leukert N., Ehrhardt C., van Zoelen M.A.D., Nacken W., Foell D., van der Poll T., Sorg C., Roth J. Nat. Med. 13:1042-1049(2007) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE, FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, INTERACTION WITH TLR4 AND LY96.
[8]	"S100A8 and S100A9 mediate endotoxin-induced cardiomyocyte dysfunction via the receptor for advanced glycation end products." Boyd J.H., Kan B., Roberts H., Wang Y., Walley K.R. Circ. Res. 102:1239-1246(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH ATP2A2 AND AGER.
[9]	"Anti-infective protective properties of S100 calgranulins." Hsu K., Champaiboon C., Guenther B.D., Sorenson B.S., Khammanivong A., Ross K.F., Geczy C.L., Herzberg M.C. Antiinflamm. Antiallergy Agents Med. Chem. 8:290-305(2009) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[10]	"Identification of human S100A9 as a novel target for treatment of autoimmune disease via binding to quinoline-3-carboxamides." Bjoerk P., Bjoerk A., Vogl T., Stenstroem M., Liberg D., Olsson A., Roth J., Ivars F., Leanderson T. PLoS Biol. 7:E97-E97(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, INTERACTION WITH TLR4; LY96 AND AGER, QUINOLINE-3-CARBOXAMIDE BINDING.
[11]	"Inflammation-associated S100 proteins: new mechanisms that regulate function." Goyette J., Geczy C.L. Amino Acids 41:821-842(2011) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[12]	"S100A9 differentially modifies phenotypic states of neutrophils, macrophages, and dendritic cells: implications for atherosclerosis and adipose tissue inflammation." Averill M.M., Barnhart S., Becker L., Li X., Heinecke J.W., Leboeuf R.C., Hamerman J.A., Sorg C., Kerkhoff C., Bornfeldt K.E. Circulation 123:1216-1226(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[13]	"Induction of nuclear factor-kappaB responses by the S100A9 protein is Toll-like receptor-4-dependent." Riva M., Kaellberg E., Bjoerk P., Hancz D., Vogl T., Roth J., Ivars F., Leanderson T. Immunology 137:172-182(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M83219 mRNA. Translation: AAB07228.1. AJ250496 Genomic DNA. Translation: CAC14292.1. BC027635 mRNA. Translation: AAH27635.1.
IPI	IPI00222556.
PIR	S68242.
RefSeq	NP_033140.1. NM_009114.2.
UniGene	Mm.2128.
3D structure databases
ProteinModelPortal	P31725.
SMR	P31725. Positions 7-87.
ModBase	Search...
Protein-protein interaction databases
IntAct	P31725. 1 interaction.
STRING	10090.ENSMUSP00000112843.
PTM databases
PhosphoSite	P31725.
Proteomic databases
PaxDb	P31725.
PRIDE	P31725.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000069960; ENSMUSP00000070842; ENSMUSG00000056071. ENSMUST00000117167; ENSMUSP00000112843; ENSMUSG00000056071.
GeneID	20202.
KEGG	mmu:20202.
Organism-specific databases
CTD	6280.
MGI	MGI:1338947. S100a9.
Phylogenomic databases
eggNOG	NOG47012.
HOGENOM	HOG000246968.
HOVERGEN	HBG001479.
InParanoid	P31725.
OMA	HEKMHEN.
OrthoDB	EOG4FFD3C.
Gene expression databases
ArrayExpress	P31725.
Bgee	P31725.
CleanEx	MM_S100A9.
Genevestigator	P31725.
GermOnline	ENSMUSG00000056071. Mus musculus.
Family and domain databases
Gene3D	1.10.238.10. 1 hit.
InterPro	IPR011992. EF-hand-like_dom. IPR002048. EF_hand_dom. IPR001751. S100/CaBP-9k_CS. IPR013787. S100_Ca-bd_sub. [Graphical view]
Pfam	PF01023. S_100. 1 hit. [Graphical view]
PROSITE	PS00018. EF_HAND_1. False negative. PS50222. EF_HAND_2. 2 hits. PS00303. S100_CABP. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	S100A9. mouse.
NextBio	297783.
SOURCE	Search...

Entry information

Entry name

S10A9_MOUSE

Accession

Primary (citable) accession number: P31725

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1993
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 118 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program