P06702 (S10A9_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	114 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. 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. Cytoplasm › cytoskeleton. 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 process	Apoptosis Autophagy Chemotaxis Immunity Inflammatory response Innate immunity
Cellular component	Cell membrane Cytoplasm Cytoskeleton Membrane Secreted
Coding sequence diversity	Polymorphism
Domain	Repeat
Ligand	Calcium Metal-binding Zinc
Molecular function	Antimicrobial Antioxidant
PTM	Methylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	actin cytoskeleton reorganization Inferred from electronic annotation. Source: Compara activation 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: Compara defense response to bacterium Traceable author statement Ref.41. Source: UniProtKB defense response to fungus Traceable author statement Ref.41. Source: UniProtKB induction of apoptosis Inferred from direct assay Ref.31. 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 regulation of cytoskeleton organization Traceable author statement Ref.41. Source: UniProtKB regulation of integrin biosynthetic process Inferred from electronic annotation. Source: Compara 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 sequestering of zinc ion Traceable author statement Ref.41. Source: UniProtKB
Cellular_component	cytoskeleton Traceable author statement Ref.41. Source: UniProtKB cytosol Traceable author statement Ref.41. Source: UniProtKB extracellular region Traceable author statement Ref.41. Source: UniProtKB extracellular space Inferred from electronic annotation. Source: Compara nucleus Inferred from direct assay. Source: HPA plasma membrane Traceable author statement Ref.41. Source: UniProtKB
Molecular_function	RAGE 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

With	Entry	#Exp.	IntAct	Notes
ARRB1	P49407	2	EBI-1055001,EBI-743313
ARRB2	P32121	2	EBI-1055001,EBI-714559
S100A8	P05109	3	EBI-1055001,EBI-355281

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 114

113

Protein S100-A9

PRO_0000143997

Regions

Domain

12 – 47

36

EF-hand 1

Domain

54 – 89

36

EF-hand 2

Calcium binding

23 – 36

14

1; low affinity

Calcium binding

67 – 78

12

2; high affinity Probable

Sites

Metal binding

20

1

Zinc Probable

Metal binding

30

1

Zinc Probable

Metal binding

91

1

Zinc Probable

Metal binding

95

1

Zinc Probable

Amino acid modifications

Modified residue

2

1

Blocked amino end (Thr)

Modified residue

105

1

Pros-methylhistidine By similarity

Modified residue

113

1

Phosphothreonine; by MAPK14 Ref.9 Ref.16 Ref.19 Ref.22 Ref.23 Ref.34

Natural variations

Natural variant

20

1

H → R. Ref.4

VAR_013008

Experimental info

Mutagenesis

36

1

E → Q: Loss of resistance to bacterial invasion; when associated with Q-78. Ref.28

Mutagenesis

63

1

M → A: Loss of antifungal activity. Ref.27

Mutagenesis

78

1

E → Q: Loss of resistance to bacterial invasion; when associated with Q-36. Ref.28

Mutagenesis

81

1

M → A: No effect on antifungal activity. Ref.27

Mutagenesis

83

1

M → A: Loss of antifungal activity. Ref.27

Sequence conflict

6

1

S → H AA sequence Ref.12

Sequence conflict

25

1

K → F AA sequence Ref.12

Sequence conflict

28

1

H → L AA sequence Ref.12

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

114

Helix Strand Turn

Details...

Helix

7 – 23

17

Beta strand

26 – 28

3

Helix

34 – 44

11

Turn

45 – 51

7

Helix

52 – 54

3

Helix

56 – 66

11

Beta strand

71 – 74

4

Helix

76 – 91

16

Sequences

	Sequence		Length	Mass (Da)
	P06702 [UniParc]. Last modified January 1, 1988. Version 1. Checksum: C3BE19729E14C078	FASTA	114	13,242
	10 20 30 40 50 60 MTCKMSQLER NIETIINTFH QYSVKLGHPD TLNQGEFKEL VRKDLQNFLK KENKNEKVIE 70 80 90 100 110 HIMEDLDTNA DKQLSFEEFI MLMARLTWAS HEKMHEGDEG PGHHHKPGLG EGTP

References

	« Hide 'large scale' referencesShow '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. , 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. , 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. 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.

IPI

IPI00027462.

PIR

B31848.

RefSeq

NP_002956.1. NM_002965.3.

UniGene

Hs.112405.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1IRJ	X-ray	2.10	A/B/C/D/E/F/G/H	2-114	[»]
1XK4	X-ray	1.80	C/D/G/H/K/L	4-114	[»]
4GGF	X-ray	1.60	C/L/T/V	1-114	[»]

ProteinModelPortal

P06702.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-1166N.

IntAct

P06702. 16 interactions.

STRING

9606.ENSP00000357727.

PTM databases

PhosphoSite

P06702.

Polymorphism databases

DMDM

115444.

2D gel databases

OGP

P06702.

SWISS-2DPAGE

P06702.

UCD-2DPAGE

P06702.

Proteomic databases

PaxDb

P06702.

PeptideAtlas

P06702.

PRIDE

P06702.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000368738; ENSP00000357727; ENSG00000163220.

GeneID

6280.

KEGG

hsa:6280.

UCSC

uc001fbq.3. human.

Organism-specific databases

CTD

6280.

GeneCards

GC01P153330.

HGNC

HGNC:10499. S100A9.

HPA

CAB009441.
HPA004193.

MIM

123886. gene.

neXtProt

NX_P06702.

PharmGKB

PA34911.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG47012.

HOGENOM

HOG000246968.

HOVERGEN

HBG001479.

InParanoid

P06702.

OMA

HEKMHEN.

OrthoDB

EOG4FFD3C.

PhylomeDB

P06702.

Gene expression databases

Bgee

P06702.

CleanEx

HS_S100A9.

Genevestigator

P06702.

GermOnline

ENSG00000163220. Homo sapiens.

Family and domain databases

Gene3D

1.10.238.10. 1 hit.

InterPro

IPR011992. EF-hand-like_dom.
IPR018247. EF_Hand_1_Ca_BS.
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. 1 hit.
PS50222. EF_HAND_2. 1 hit.
PS00303. S100_CABP. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

S100A9. human.

EvolutionaryTrace

P06702.

GenomeRNAi

6280.

NextBio

24377.

SOURCE

Search...

Entry information

Entry name

S10A9_HUMAN

Accession

Primary (citable) accession number: P06702
Secondary accession number(s): D3DV36 , Q6FGA1, Q9NYM0, Q9UCJ1

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1988
Last sequence update:	January 1, 1988
Last modified:	May 1, 2013
This is version 154 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.