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P06702 (S10A9_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 163. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protein S100-A9
Alternative name(s):
Calgranulin-B
Calprotectin L1H subunit
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, CFAG, MRP14
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length114 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, 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. Can act as a potent amplifier of inflammation in autoimmunity as well as in cancer development and tumor spread. Ref.12 Ref.15 Ref.16 Ref.17 Ref.18 Ref.20 Ref.25 Ref.27 Ref.28 Ref.30 Ref.31 Ref.33 Ref.37 Ref.39 Ref.40 Ref.43 Ref.45

Subunit structure

Homodimer. Preferentially exists as a heterodimer or heterotetramer with S100A8 known as calprotectin (S100A8/A9). S100A9 interacts with ATP2A2 By similarity. 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. Ref.12 Ref.13 Ref.14 Ref.16 Ref.18 Ref.20 Ref.21 Ref.27 Ref.28 Ref.30 Ref.43 Ref.44 Ref.46 Ref.47

Subcellular location

Secreted. Cytoplasm. Cytoplasmcytoskeleton. 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. Ref.12 Ref.13 Ref.17 Ref.21 Ref.30 Ref.43

Tissue specificity

Calprotectin (S100A8/9) is predominantly expressed in myeloid cells. Except for inflammatory conditions, the expression is restricted to a specific stage of myeloid differentiation since both proteins are expressed in circulating neutrophils and monocytes but are absent in normal tissue macrophages and lymphocytes. Under chronic inflammatory conditions, such as psoriasis and malignant disorders, also expressed in the epidermis. Found in high concentrations at local sites of inflammation or in the serum of patients with inflammatory diseases such as rheumatoid, cystic fibrosis, inflammatory bowel disease, Crohn's disease, giant cell arteritis, cystic fibrosis, Sjogren's syndrome, systemic lupus erythematosus, and progressive systemic sclerosis. Involved in the formation and deposition of amyloids in the aging prostate known as corpora amylacea inclusions. Strongly up-regulated in many tumors, including gastric, esophageal, colon, pancreatic, bladder, ovarian, thyroid, breast and skin cancers. Ref.1 Ref.2 Ref.12 Ref.13 Ref.17

Post-translational modification

Phosphorylated. Phosphorylation inhibits activation of tubulin polymerization. Ref.9 Ref.16 Ref.19

Sequence similarities

Belongs to the S-100 family.

Contains 2 EF-hand domains.

Mass spectrometry

Molecular mass is 13115 Da from positions 2 - 114. Determined by MALDI. Ref.46

Ontologies

Keywords
   Biological processApoptosis
Autophagy
Chemotaxis
Immunity
Inflammatory response
Innate immunity
   Cellular componentCell membrane
Cytoplasm
Cytoskeleton
Membrane
Secreted
   Coding sequence diversityPolymorphism
   DomainRepeat
   LigandCalcium
Metal-binding
Zinc
   Molecular functionAntimicrobial
Antioxidant
   PTMMethylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from direct assay Ref.31. Source: UniProtKB

autophagy

Inferred from direct assay Ref.31. Source: UniProtKB

cell-cell signaling

Traceable author statement Ref.1. Source: ProtInc

chemokine production

Traceable author statement Ref.41. Source: UniProtKB

chronic inflammatory response

Inferred from electronic annotation. Source: Ensembl

defense response to bacterium

Traceable author statement Ref.41. Source: UniProtKB

defense response to fungus

Traceable author statement Ref.41. Source: UniProtKB

innate immune response

Inferred from electronic annotation. Source: UniProtKB-KW

leukocyte migration involved in inflammatory response

Inferred from direct assay Ref.15. Source: UniProtKB

neutrophil aggregation

Inferred from direct assay Ref.15. Source: UniProtKB

neutrophil chemotaxis

Inferred from direct assay Ref.15. Source: UniProtKB

positive regulation of NF-kappaB transcription factor activity

Traceable author statement Ref.41. Source: UniProtKB

positive regulation of cell growth

Traceable author statement Ref.41. Source: UniProtKB

positive regulation of inflammatory response

Inferred from direct assay Ref.15. Source: UniProtKB

positive regulation of intrinsic apoptotic signaling pathway

Inferred from direct assay Ref.31. Source: UniProtKB

regulation of cytoskeleton organization

Traceable author statement Ref.41. Source: UniProtKB

response to ethanol

Inferred from electronic annotation. Source: Ensembl

response to lipopolysaccharide

Inferred from electronic annotation. Source: Ensembl

response to zinc ion

Inferred from electronic annotation. Source: Ensembl

sequestering of zinc ion

Traceable author statement Ref.41. Source: UniProtKB

   Cellular_componentcytoskeleton

Traceable author statement Ref.41. Source: UniProtKB

cytosol

Traceable author statement Ref.41. Source: UniProtKB

extracellular space

Inferred from direct assay PubMed 22664934PubMed 23580065. Source: UniProt

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867PubMed 19199708. Source: UniProt

nucleus

Inferred from direct assay. Source: HPA

plasma membrane

Traceable author statement Ref.41. Source: UniProtKB

   Molecular_functionRAGE receptor binding

Traceable author statement Ref.41. Source: UniProtKB

Toll-like receptor 4 binding

Traceable author statement Ref.41. Source: UniProtKB

antioxidant activity

Inferred from electronic annotation. Source: UniProtKB-KW

arachidonic acid binding

Traceable author statement Ref.41. Source: UniProtKB

calcium ion binding

Traceable author statement Ref.41. Source: UniProtKB

microtubule binding

Traceable author statement Ref.41. Source: UniProtKB

signal transducer activity

Traceable author statement Ref.1. Source: ProtInc

zinc ion binding

Traceable author statement Ref.41. Source: UniProtKB

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 114113Protein S100-A9
PRO_0000143997

Regions

Domain12 – 4736EF-hand 1
Domain54 – 8936EF-hand 2
Calcium binding23 – 36141; low affinity
Calcium binding67 – 78122; high affinity Probable

Sites

Metal binding201Zinc Probable
Metal binding301Zinc Probable
Metal binding911Zinc Probable
Metal binding951Zinc Probable

Amino acid modifications

Modified residue21Blocked amino end (Thr)
Modified residue1051Pros-methylhistidine By similarity
Modified residue1131Phosphothreonine; by MAPK14 Ref.9 Ref.16 Ref.19 Ref.22 Ref.23 Ref.34

Natural variations

Natural variant201H → R. Ref.4
VAR_013008

Experimental info

Mutagenesis361E → Q: Loss of resistance to bacterial invasion; when associated with Q-78. Ref.28
Mutagenesis631M → A: Loss of antifungal activity. Ref.27
Mutagenesis781E → Q: Loss of resistance to bacterial invasion; when associated with Q-36. Ref.28
Mutagenesis811M → A: No effect on antifungal activity. Ref.27
Mutagenesis831M → A: Loss of antifungal activity. Ref.27
Sequence conflict61S → H AA sequence Ref.12
Sequence conflict251K → F AA sequence Ref.12
Sequence conflict281H → L AA sequence Ref.12

Secondary structure

................ 114
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P06702 [UniParc].

Last modified January 1, 1988. Version 1.
Checksum: C3BE19729E14C078

FASTA11413,242
        10         20         30         40         50         60 
MTCKMSQLER NIETIINTFH QYSVKLGHPD TLNQGEFKEL VRKDLQNFLK KENKNEKVIE 

        70         80         90        100        110 
HIMEDLDTNA DKQLSFEEFI MLMARLTWAS HEKMHEGDEG PGHHHKPGLG EGTP 

« Hide

References

« Hide 'large scale' references
[1]"Two calcium-binding proteins in infiltrate macrophages of rheumatoid arthritis."
Odink K., Cerletti N., Bruggen J., Clerc R.G., Tarcsay L., Zwaldo G., Gerhards G., Schlegel R., Sorg C.
Nature 330:80-82(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
[2]"Cloning and expression of two human genes encoding calcium-binding proteins that are regulated during myeloid differentiation."
Lagasse E., Clerc R.G.
Mol. Cell. Biol. 8:2402-2410(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY.
[3]"A protein containing the cystic fibrosis antigen is an inhibitor of protein kinases."
Murao S., Collart F.R., Huberman E.
J. Biol. Chem. 264:8356-8360(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], BLOCKAGE OF N-TERMINUS.
[4]"Human gene for migration inhibitory factor-related protein 14 (MRP14), variant allele."
Wang M., Xu X., Cai Y., Xu H., Han Y., Xu Z., Wu M.
Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ARG-20.
[5]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"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].
Tissue: Lung.
[9]"Ionomycin-regulated phosphorylation of the myeloid calcium-binding protein p14."
Edgeworth J., Freemont P., Hogg N.
Nature 342:189-192(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 84-114, PHOSPHORYLATION AT THR-113.
[10]"Amino acid sequences of 60B8 antigens induced in HL-60 cells by 1,25-dihydroxyvitamin D3. The antigens are identical with macrophage-related protein-14 and -8."
Tobe T., Murakami K., Tomita M., Nozawa R.
Chem. Pharm. Bull. 37:1576-1580(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE, BLOCKAGE OF N-TERMINUS.
[11]"Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes."
Rasmussen H.H., van Damme J., Puype M., Gesser B., Celis J.E., Vandekerckhove J.
Electrophoresis 13:960-969(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 11-19; 26-37 AND 94-107.
Tissue: Keratinocyte.
[12]"In vitro antimicrobial activity of the human neutrophil cytosolic S-100 protein complex, calprotectin, against Capnocytophaga sputigena."
Miyasaki K.T., Bodeau A.L., Murthy A.R., Lehrer R.I.
J. Dent. Res. 72:517-523(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 5-34, SUBCELLULAR LOCATION, IDENTIFICATION IN THE CALPROTECTIN COMPLEX, FUNCTION, TISSUE SPECIFICITY.
[13]"Myeloid-related protein (MRP) 8 and MRP14, calcium-binding proteins of the S100 family, are secreted by activated monocytes via a novel, tubulin-dependent pathway."
Rammes A., Roth J., Goebeler M., Klempt M., Hartmann M., Sorg C.
J. Biol. Chem. 272:9496-9502(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, SUBUNIT, TISSUE SPECIFICITY.
[14]"The microbial receptor CEACAM3 is linked to the calprotectin complex in granulocytes."
Streichert T., Ebrahimnejad A., Ganzer S., Flayeh R., Wagener C., Bruemmer J.
Biochem. Biophys. Res. Commun. 289:191-197(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CEACAM3.
[15]"Proinflammatory activities of S100: proteins S100A8, S100A9, and S100A8/A9 induce neutrophil chemotaxis and adhesion."
Ryckman C., Vandal K., Rouleau P., Talbot M., Tessier P.A.
J. Immunol. 170:3233-3242(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[16]"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 AT THR-113.
[17]"Myeloid-related proteins 8 and 14 induce a specific inflammatory response in human microvascular endothelial cells."
Viemann D., Strey A., Janning A., Jurk K., Klimmek K., Vogl T., Hirono K., Ichida F., Foell D., Kehrel B., Gerke V., Sorg C., Roth J.
Blood 105:2955-2962(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MASS SPECTROMETRY, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[18]"The arachidonic acid-binding protein S100A8/A9 promotes NADPH oxidase activation by interaction with p67phox and Rac-2."
Kerkhoff C., Nacken W., Benedyk M., Dagher M.C., Sopalla C., Doussiere J.
FASEB J. 19:467-469(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH NCF2/P67PHOX; RAC1 AND RAC2.
[19]"Myeloid-related protein-14 is a p38 MAPK substrate in human neutrophils."
Lominadze G., Rane M.J., Merchant M., Cai J., Ward R.A., McLeish K.R.
J. Immunol. 174:7257-7267(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-113.
[20]"Regulation of S100A8/A9 (calprotectin) binding to tumor cells by zinc ion and its implication for apoptosis-inducing activity."
Nakatani Y., Yamazaki M., Chazin W.J., Yui S.
Mediators Inflamm. 2005:280-292(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INHIBITION BY ZINC IONS, SUBUNIT.
[21]"Interaction between S100A8/A9 and annexin A6 is involved in the calcium-induced cell surface exposition of S100A8/A9."
Bode G., Lueken A., Kerkhoff C., Roth J., Ludwig S., Nacken W.
J. Biol. Chem. 283:31776-31784(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, INTERACTION WITH ANXA6.
[22]"Phosphorylation analysis of primary human T lymphocytes using sequential IMAC and titanium oxide enrichment."
Carrascal M., Ovelleiro D., Casas V., Gay M., Abian J.
J. Proteome Res. 7:5167-5176(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-113, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: T-cell.
[23]"Large-scale phosphoproteome analysis of human liver tissue by enrichment and fractionation of phosphopeptides with strong anion exchange chromatography."
Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D., Zou H., Gu J.
Proteomics 8:1346-1361(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-113, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[24]"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.
[25]"A novel p53 target gene, S100A9, induces p53-dependent cellular apoptosis and mediates the p53 apoptosis pathway."
Li C., Chen H., Ding F., Zhang Y., Luo A., Wang M., Liu Z.
Biochem. J. 422:363-372(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[26]"S100A8/A9: a Janus-faced molecule in cancer therapy and tumorgenesis."
Ghavami S., Chitayat S., Hashemi M., Eshraghi M., Chazin W.J., Halayko A.J., Kerkhoff C.
Eur. J. Pharmacol. 625:73-83(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[27]"Substitution of methionine 63 or 83 in S100A9 and cysteine 42 in S100A8 abrogate the antifungal activities of S100A8/A9: potential role for oxidative regulation."
Sroussi H.Y., Koehler G.A., Agabian N., Villines D., Palefsky J.M.
FEMS Immunol. Med. Microbiol. 55:55-61(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBUNIT, MUTAGENESIS OF MET-63; MET-81 AND MET-83, INHIBITION BY ZINC IONS.
[28]"Calprotectin S100A9 calcium-binding loops I and II are essential for keratinocyte resistance to bacterial invasion."
Champaiboon C., Sappington K.J., Guenther B.D., Ross K.F., Herzberg M.C.
J. Biol. Chem. 284:7078-7090(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBUNIT, MUTAGENESIS OF GLU-36 AND GLU-78.
[29]"The endogenous Toll-like receptor 4 agonist S100A8/S100A9 (calprotectin) as innate amplifier of infection, autoimmunity, and cancer."
Ehrchen J.M., Sunderkoetter C., Foell D., Vogl T., Roth J.
J. Leukoc. Biol. 86:557-566(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[30]"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.
[31]"S100A8/A9 induces autophagy and apoptosis via ROS-mediated cross-talk between mitochondria and lysosomes that involves BNIP3."
Ghavami S., Eshragi M., Ande S.R., Chazin W.J., Klonisch T., Halayko A.J., McNeill K.D., Hashemi M., Kerkhoff C., Los M.
Cell Res. 20:314-331(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[32]"S100 Calgranulins in inflammatory arthritis."
Perera C., McNeil H.P., Geczy C.L.
Immunol. Cell Biol. 88:41-49(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[33]"Induction of neutrophil degranulation by S100A9 via a MAPK-dependent mechanism."
Simard J.C., Girard D., Tessier P.A.
J. Leukoc. Biol. 87:905-914(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[34]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-113, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[35]"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.
[36]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[37]"Damage-associated molecular pattern S100A9 increases bactericidal activity of human neutrophils by enhancing phagocytosis."
Simard J.C., Simon M.M., Tessier P.A., Girard D.
J. Immunol. 186:3622-3631(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[38]"S100A8 and S100A9 in cardiovascular biology and disease."
Averill M.M., Kerkhoff C., Bornfeldt K.E.
Arterioscler. Thromb. Vasc. Biol. 32:223-229(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[39]"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.
[40]"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.
[41]"Pro-inflammatory S100A8 and S100A9 proteins: self-assembly into multifunctional native and amyloid complexes."
Vogl T., Gharibyan A.L., Morozova-Roche L.A.
Int. J. Mol. Sci. 13:2893-2917(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[42]"S100A8 and S100A9: new insights into their roles in malignancy."
Srikrishna G.
J. Innate Immun. 4:31-40(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[43]"Molecular interface of S100A8 with cytochrome b and NADPH oxidase activation."
Berthier S., Nguyen M.V., Baillet A., Hograindleur M.A., Paclet M.H., Polack B., Morel F.
PLoS ONE 7:E40277-E40277(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CYBA AND CYBB.
[44]"MRP14 (S100A9) protein interacts with Alzheimer beta-amyloid peptide and induces its fibrillization."
Zhang C., Liu Y., Gilthorpe J., van der Maarel J.R.
PLoS ONE 7:E32953-E32953(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH APP.
[45]"Constitutive neutrophil apoptosis: regulation by cell concentration via S100 A8/9 and the MEK-ERK pathway."
Atallah M., Krispin A., Trahtemberg U., Ben-Hamron S., Grau A., Verbovetski I., Mevorach D.
PLoS ONE 7:E29333-E29333(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY.
[46]"The crystal structure of human MRP14 (S100A9), a Ca(2+)-dependent regulator protein in inflammatory process."
Itou H., Yao M., Fujita I., Watanabe N., Suzuki M., Nishihira J., Tanaka I.
J. Mol. Biol. 316:265-276(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH CALCIUM IONS, MASS SPECTROMETRY, SUBUNIT.
[47]"The crystal structure of the human (S100A8/S100A9)2 heterotetramer, calprotectin, illustrates how conformational changes of interacting alpha-helices can determine specific association of two EF-hand proteins."
Korndoerfer I.P., Brueckner F., Skerra A.
J. Mol. Biol. 370:887-898(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 4-114 IN COMPLEX WITH S100A8, SUBUNIT, ZINC-BINDING.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X06233 mRNA. Translation: CAA29579.1.
M21064 Genomic DNA. Translation: AAA36326.1.
M26311 mRNA. Translation: AAA68480.1.
AF237581 Genomic DNA. Translation: AAF62536.1.
AF237582 Genomic DNA. Translation: AAF62537.1.
CR542207 mRNA. Translation: CAG47003.1.
CR542224 mRNA. Translation: CAG47020.1.
AL591704 Genomic DNA. Translation: CAI19494.1.
CH471121 Genomic DNA. Translation: EAW53333.1.
CH471121 Genomic DNA. Translation: EAW53334.1.
BC047681 mRNA. Translation: AAH47681.1.
PIRB31848.
RefSeqNP_002956.1. NM_002965.3.
UniGeneHs.112405.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1IRJX-ray2.10A/B/C/D/E/F/G/H2-114[»]
1XK4X-ray1.80C/D/G/H/K/L4-114[»]
4GGFX-ray1.60C/L/T/V1-114[»]
ProteinModelPortalP06702.
SMRP06702. Positions 4-112.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112188. 88 interactions.
DIPDIP-1166N.
IntActP06702. 19 interactions.
MINTMINT-5002390.
STRING9606.ENSP00000357727.

PTM databases

PhosphoSiteP06702.

Polymorphism databases

DMDM115444.

2D gel databases

OGPP06702.
SWISS-2DPAGEP06702.
UCD-2DPAGEP06702.

Proteomic databases

PaxDbP06702.
PeptideAtlasP06702.
PRIDEP06702.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000368738; ENSP00000357727; ENSG00000163220.
GeneID6280.
KEGGhsa:6280.
UCSCuc001fbq.3. human.

Organism-specific databases

CTD6280.
GeneCardsGC01P153330.
HGNCHGNC:10499. S100A9.
HPACAB009441.
HPA004193.
MIM123886. gene.
neXtProtNX_P06702.
PharmGKBPA34911.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG47012.
HOGENOMHOG000246968.
HOVERGENHBG001479.
InParanoidP06702.
OMAHEKMHEN.
OrthoDBEOG73807B.
PhylomeDBP06702.
TreeFamTF332727.

Gene expression databases

BgeeP06702.
CleanExHS_S100A9.
GenevestigatorP06702.

Family and domain databases

Gene3D1.10.238.10. 1 hit.
InterProIPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
IPR028475. S100-A9.
IPR001751. S100/CaBP-9k_CS.
IPR013787. S100_Ca-bd_sub.
[Graphical view]
PANTHERPTHR11639:SF10. PTHR11639:SF10. 1 hit.
PfamPF01023. S_100. 1 hit.
[Graphical view]
PROSITEPS00018. EF_HAND_1. 1 hit.
PS50222. EF_HAND_2. 1 hit.
PS00303. S100_CABP. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSS100A9. human.
EvolutionaryTraceP06702.
GeneWikiS100A9.
GenomeRNAi6280.
NextBio24377.
PROP06702.
SOURCESearch...

Entry information

Entry nameS10A9_HUMAN
AccessionPrimary (citable) accession number: P06702
Secondary accession number(s): D3DV36 expand/collapse secondary AC list , Q6FGA1, Q9NYM0, Q9UCJ1
Entry history
Integrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: January 1, 1988
Last modified: March 19, 2014
This is version 163 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM