ID S10A9_HUMAN Reviewed; 114 AA.
AC P06702; D3DV36; Q6FGA1; Q9NYM0; Q9UCJ1;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1988, sequence version 1.
DT 27-MAR-2024, entry version 243.
DE RecName: Full=Protein S100-A9;
DE AltName: Full=Calgranulin-B;
DE AltName: Full=Calprotectin L1H subunit;
DE AltName: Full=Leukocyte L1 complex heavy chain;
DE AltName: Full=Migration inhibitory factor-related protein 14 {ECO:0000303|Ref.4};
DE Short=MRP-14 {ECO:0000303|Ref.4};
DE Short=p14 {ECO:0000303|PubMed:2478889};
DE AltName: Full=S100 calcium-binding protein A9 {ECO:0000303|PubMed:12626582};
GN Name=S100A9 {ECO:0000303|PubMed:12626582, ECO:0000312|HGNC:HGNC:10499};
GN Synonyms=CAGB, CFAG, MRP14 {ECO:0000303|Ref.4};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=3313057; DOI=10.1038/330080a0;
RA Odink K., Cerletti N., Bruggen J., Clerc R.G., Tarcsay L., Zwaldo G.,
RA Gerhards G., Schlegel R., Sorg C.;
RT "Two calcium-binding proteins in infiltrate macrophages of rheumatoid
RT arthritis.";
RL Nature 330:80-82(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY.
RX PubMed=3405210; DOI=10.1128/mcb.8.6.2402-2410.1988;
RA Lagasse E., Clerc R.G.;
RT "Cloning and expression of two human genes encoding calcium-binding
RT proteins that are regulated during myeloid differentiation.";
RL Mol. Cell. Biol. 8:2402-2410(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND BLOCKAGE OF N-TERMINUS.
RX PubMed=2656677; DOI=10.1016/s0021-9258(18)83189-1;
RA Murao S., Collart F.R., Huberman E.;
RT "A protein containing the cystic fibrosis antigen is an inhibitor of
RT protein kinases.";
RL J. Biol. Chem. 264:8356-8360(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ARG-20.
RA Wang M., Xu X., Cai Y., Xu H., Han Y., Xu Z., Wu M.;
RT "Human gene for migration inhibitory factor-related protein 14 (MRP14),
RT variant allele.";
RL Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P.,
RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y.,
RA LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP PROTEIN SEQUENCE OF 84-114, AND PHOSPHORYLATION AT THR-113.
RX PubMed=2478889; DOI=10.1038/342189a0;
RA Edgeworth J., Freemont P., Hogg N.;
RT "Ionomycin-regulated phosphorylation of the myeloid calcium-binding protein
RT p14.";
RL Nature 342:189-192(1989).
RN [10]
RP PROTEIN SEQUENCE, AND BLOCKAGE OF N-TERMINUS.
RX PubMed=2776242; DOI=10.1248/cpb.37.1576;
RA Tobe T., Murakami K., Tomita M., Nozawa R.;
RT "Amino acid sequences of 60B8 antigens induced in HL-60 cells by 1,25-
RT dihydroxyvitamin D3. The antigens are identical with macrophage-related
RT protein-14 and -8.";
RL Chem. Pharm. Bull. 37:1576-1580(1989).
RN [11]
RP PROTEIN SEQUENCE OF 11-19; 26-37 AND 94-107.
RC TISSUE=Keratinocyte;
RX PubMed=1286667; DOI=10.1002/elps.11501301199;
RA Rasmussen H.H., van Damme J., Puype M., Gesser B., Celis J.E.,
RA Vandekerckhove J.;
RT "Microsequences of 145 proteins recorded in the two-dimensional gel protein
RT database of normal human epidermal keratinocytes.";
RL Electrophoresis 13:960-969(1992).
RN [12]
RP PROTEIN SEQUENCE OF 5-34, SUBCELLULAR LOCATION, IDENTIFICATION IN THE
RP CALPROTECTIN COMPLEX, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=8423249; DOI=10.1177/00220345930720020801;
RA Miyasaki K.T., Bodeau A.L., Murthy A.R., Lehrer R.I.;
RT "In vitro antimicrobial activity of the human neutrophil cytosolic S-100
RT protein complex, calprotectin, against Capnocytophaga sputigena.";
RL J. Dent. Res. 72:517-523(1993).
RN [13]
RP SUBCELLULAR LOCATION, SUBUNIT, AND TISSUE SPECIFICITY.
RX PubMed=9083090; DOI=10.1074/jbc.272.14.9496;
RA Rammes A., Roth J., Goebeler M., Klempt M., Hartmann M., Sorg C.;
RT "Myeloid-related protein (MRP) 8 and MRP14, calcium-binding proteins of the
RT S100 family, are secreted by activated monocytes via a novel, tubulin-
RT dependent pathway.";
RL J. Biol. Chem. 272:9496-9502(1997).
RN [14]
RP INTERACTION WITH CEACAM3.
RX PubMed=11708798; DOI=10.1006/bbrc.2001.5955;
RA Streichert T., Ebrahimnejad A., Ganzer S., Flayeh R., Wagener C.,
RA Bruemmer J.;
RT "The microbial receptor CEACAM3 is linked to the calprotectin complex in
RT granulocytes.";
RL Biochem. Biophys. Res. Commun. 289:191-197(2001).
RN [15]
RP FUNCTION.
RX PubMed=12626582; DOI=10.4049/jimmunol.170.6.3233;
RA Ryckman C., Vandal K., Rouleau P., Talbot M., Tessier P.A.;
RT "Proinflammatory activities of S100: proteins S100A8, S100A9, and S100A8/A9
RT induce neutrophil chemotaxis and adhesion.";
RL J. Immunol. 170:3233-3242(2003).
RN [16]
RP FUNCTION, AND PHOSPHORYLATION AT THR-113.
RX PubMed=15331440; DOI=10.1182/blood-2004-02-0446;
RA Vogl T., Ludwig S., Goebeler M., Strey A., Thorey I.S., Reichelt R.,
RA Foell D., Gerke V., Manitz M.P., Nacken W., Werner S., Sorg C., Roth J.;
RT "MRP8 and MRP14 control microtubule reorganization during transendothelial
RT migration of phagocytes.";
RL Blood 104:4260-4268(2004).
RN [17]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RX PubMed=15598812; DOI=10.1182/blood-2004-07-2520;
RA Viemann D., Strey A., Janning A., Jurk K., Klimmek K., Vogl T., Hirono K.,
RA Ichida F., Foell D., Kehrel B., Gerke V., Sorg C., Roth J.;
RT "Myeloid-related proteins 8 and 14 induce a specific inflammatory response
RT in human microvascular endothelial cells.";
RL Blood 105:2955-2962(2005).
RN [18]
RP FUNCTION, AND INTERACTION WITH NCF2/P67PHOX; RAC1 AND RAC2.
RX PubMed=15642721; DOI=10.1096/fj.04-2377fje;
RA Kerkhoff C., Nacken W., Benedyk M., Dagher M.C., Sopalla C., Doussiere J.;
RT "The arachidonic acid-binding protein S100A8/A9 promotes NADPH oxidase
RT activation by interaction with p67phox and Rac-2.";
RL FASEB J. 19:467-469(2005).
RN [19]
RP PHOSPHORYLATION AT THR-113.
RX PubMed=15905572; DOI=10.4049/jimmunol.174.11.7257;
RA Lominadze G., Rane M.J., Merchant M., Cai J., Ward R.A., McLeish K.R.;
RT "Myeloid-related protein-14 is a p38 MAPK substrate in human neutrophils.";
RL J. Immunol. 174:7257-7267(2005).
RN [20]
RP FUNCTION, INHIBITION BY ZINC IONS, AND SUBUNIT.
RX PubMed=16258195; DOI=10.1155/mi.2005.280;
RA Nakatani Y., Yamazaki M., Chazin W.J., Yui S.;
RT "Regulation of S100A8/A9 (calprotectin) binding to tumor cells by zinc ion
RT and its implication for apoptosis-inducing activity.";
RL Mediators Inflamm. 2005:280-292(2005).
RN [21]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH ANXA6.
RX PubMed=18786929; DOI=10.1074/jbc.m803908200;
RA Bode G., Lueken A., Kerkhoff C., Roth J., Ludwig S., Nacken W.;
RT "Interaction between S100A8/A9 and annexin A6 is involved in the calcium-
RT induced cell surface exposition of S100A8/A9.";
RL J. Biol. Chem. 283:31776-31784(2008).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-113, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=T-cell;
RX PubMed=19367720; DOI=10.1021/pr800500r;
RA Carrascal M., Ovelleiro D., Casas V., Gay M., Abian J.;
RT "Phosphorylation analysis of primary human T lymphocytes using sequential
RT IMAC and titanium oxide enrichment.";
RL J. Proteome Res. 7:5167-5176(2008).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-113, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=18318008; DOI=10.1002/pmic.200700884;
RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D.,
RA Zou H., Gu J.;
RT "Large-scale phosphoproteome analysis of human liver tissue by enrichment
RT and fractionation of phosphopeptides with strong anion exchange
RT chromatography.";
RL Proteomics 8:1346-1361(2008).
RN [24]
RP REVIEW.
RX PubMed=20523765; DOI=10.2174/187152309789838975;
RA Hsu K., Champaiboon C., Guenther B.D., Sorenson B.S., Khammanivong A.,
RA Ross K.F., Geczy C.L., Herzberg M.C.;
RT "Anti-infective protective properties of S100 calgranulins.";
RL Antiinflamm. Antiallergy Agents Med. Chem. 8:290-305(2009).
RN [25]
RP FUNCTION.
RX PubMed=19534726; DOI=10.1042/bj20090465;
RA Li C., Chen H., Ding F., Zhang Y., Luo A., Wang M., Liu Z.;
RT "A novel p53 target gene, S100A9, induces p53-dependent cellular apoptosis
RT and mediates the p53 apoptosis pathway.";
RL Biochem. J. 422:363-372(2009).
RN [26]
RP REVIEW.
RX PubMed=19835859; DOI=10.1016/j.ejphar.2009.08.044;
RA Ghavami S., Chitayat S., Hashemi M., Eshraghi M., Chazin W.J.,
RA Halayko A.J., Kerkhoff C.;
RT "S100A8/A9: a Janus-faced molecule in cancer therapy and tumorgenesis.";
RL Eur. J. Pharmacol. 625:73-83(2009).
RN [27]
RP FUNCTION, SUBUNIT, MUTAGENESIS OF MET-63; MET-81 AND MET-83, AND INHIBITION
RP BY ZINC IONS.
RX PubMed=19087201; DOI=10.1111/j.1574-695x.2008.00498.x;
RA Sroussi H.Y., Koehler G.A., Agabian N., Villines D., Palefsky J.M.;
RT "Substitution of methionine 63 or 83 in S100A9 and cysteine 42 in S100A8
RT abrogate the antifungal activities of S100A8/A9: potential role for
RT oxidative regulation.";
RL FEMS Immunol. Med. Microbiol. 55:55-61(2009).
RN [28]
RP FUNCTION, SUBUNIT, AND MUTAGENESIS OF GLU-36 AND GLU-78.
RX PubMed=19122197; DOI=10.1074/jbc.m806605200;
RA Champaiboon C., Sappington K.J., Guenther B.D., Ross K.F., Herzberg M.C.;
RT "Calprotectin S100A9 calcium-binding loops I and II are essential for
RT keratinocyte resistance to bacterial invasion.";
RL J. Biol. Chem. 284:7078-7090(2009).
RN [29]
RP REVIEW.
RX PubMed=19451397; DOI=10.1189/jlb.1008647;
RA Ehrchen J.M., Sunderkoetter C., Foell D., Vogl T., Roth J.;
RT "The endogenous Toll-like receptor 4 agonist S100A8/S100A9 (calprotectin)
RT as innate amplifier of infection, autoimmunity, and cancer.";
RL J. Leukoc. Biol. 86:557-566(2009).
RN [30]
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, INTERACTION WITH TLR4; LY96 AND
RP AGER, AND QUINOLINE-3-CARBOXAMIDE BINDING.
RX PubMed=19402754; DOI=10.1371/journal.pbio.1000097;
RA Bjoerk P., Bjoerk A., Vogl T., Stenstroem M., Liberg D., Olsson A.,
RA Roth J., Ivars F., Leanderson T.;
RT "Identification of human S100A9 as a novel target for treatment of
RT autoimmune disease via binding to quinoline-3-carboxamides.";
RL PLoS Biol. 7:E97-E97(2009).
RN [31]
RP FUNCTION.
RX PubMed=19935772; DOI=10.1038/cr.2009.129;
RA Ghavami S., Eshragi M., Ande S.R., Chazin W.J., Klonisch T., Halayko A.J.,
RA McNeill K.D., Hashemi M., Kerkhoff C., Los M.;
RT "S100A8/A9 induces autophagy and apoptosis via ROS-mediated cross-talk
RT between mitochondria and lysosomes that involves BNIP3.";
RL Cell Res. 20:314-331(2010).
RN [32]
RP REVIEW.
RX PubMed=19935766; DOI=10.1038/icb.2009.88;
RA Perera C., McNeil H.P., Geczy C.L.;
RT "S100 Calgranulins in inflammatory arthritis.";
RL Immunol. Cell Biol. 88:41-49(2010).
RN [33]
RP FUNCTION.
RX PubMed=20103766; DOI=10.1189/jlb.1009676;
RA Simard J.C., Girard D., Tessier P.A.;
RT "Induction of neutrophil degranulation by S100A9 via a MAPK-dependent
RT mechanism.";
RL J. Leukoc. Biol. 87:905-914(2010).
RN [34]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-113, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [35]
RP REVIEW.
RX PubMed=20213444; DOI=10.1007/s00726-010-0528-0;
RA Goyette J., Geczy C.L.;
RT "Inflammation-associated S100 proteins: new mechanisms that regulate
RT function.";
RL Amino Acids 41:821-842(2011).
RN [36]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [37]
RP FUNCTION.
RX PubMed=21325622; DOI=10.4049/jimmunol.1002956;
RA Simard J.C., Simon M.M., Tessier P.A., Girard D.;
RT "Damage-associated molecular pattern S100A9 increases bactericidal activity
RT of human neutrophils by enhancing phagocytosis.";
RL J. Immunol. 186:3622-3631(2011).
RN [38]
RP REVIEW.
RX PubMed=22095980; DOI=10.1161/atvbaha.111.236927;
RA Averill M.M., Kerkhoff C., Bornfeldt K.E.;
RT "S100A8 and S100A9 in cardiovascular biology and disease.";
RL Arterioscler. Thromb. Vasc. Biol. 32:223-229(2012).
RN [39]
RP FUNCTION.
RX PubMed=22804476; DOI=10.1111/j.1365-2567.2012.03619.x;
RA Riva M., Kaellberg E., Bjoerk P., Hancz D., Vogl T., Roth J., Ivars F.,
RA Leanderson T.;
RT "Induction of nuclear factor-kappaB responses by the S100A9 protein is
RT Toll-like receptor-4-dependent.";
RL Immunology 137:172-182(2012).
RN [40]
RP FUNCTION.
RX PubMed=21487906; DOI=10.1007/s10753-011-9330-8;
RA Koike A., Arai S., Yamada S., Nagae A., Saita N., Itoh H., Uemoto S.,
RA Totani M., Ikemoto M.;
RT "Dynamic mobility of immunological cells expressing S100A8 and S100A9 in
RT vivo: a variety of functional roles of the two proteins as regulators in
RT acute inflammatory reaction.";
RL Inflammation 35:409-419(2012).
RN [41]
RP REVIEW.
RX PubMed=22489132; DOI=10.3390/ijms13032893;
RA Vogl T., Gharibyan A.L., Morozova-Roche L.A.;
RT "Pro-inflammatory S100A8 and S100A9 proteins: self-assembly into
RT multifunctional native and amyloid complexes.";
RL Int. J. Mol. Sci. 13:2893-2917(2012).
RN [42]
RP REVIEW.
RX PubMed=21912088; DOI=10.1159/000330095;
RA Srikrishna G.;
RT "S100A8 and S100A9: new insights into their roles in malignancy.";
RL J. Innate Immun. 4:31-40(2012).
RN [43]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CYBA AND CYBB.
RX PubMed=22808130; DOI=10.1371/journal.pone.0040277;
RA Berthier S., Nguyen M.V., Baillet A., Hograindleur M.A., Paclet M.H.,
RA Polack B., Morel F.;
RT "Molecular interface of S100A8 with cytochrome b and NADPH oxidase
RT activation.";
RL PLoS ONE 7:E40277-E40277(2012).
RN [44]
RP INTERACTION WITH APP.
RX PubMed=22457725; DOI=10.1371/journal.pone.0032953;
RA Zhang C., Liu Y., Gilthorpe J., van der Maarel J.R.;
RT "MRP14 (S100A9) protein interacts with Alzheimer beta-amyloid peptide and
RT induces its fibrillization.";
RL PLoS ONE 7:E32953-E32953(2012).
RN [45]
RP FUNCTION, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=22363402; DOI=10.1371/journal.pone.0029333;
RA Atallah M., Krispin A., Trahtemberg U., Ben-Hamron S., Grau A.,
RA Verbovetski I., Mevorach D.;
RT "Constitutive neutrophil apoptosis: regulation by cell concentration via
RT S100 A8/9 and the MEK-ERK pathway.";
RL PLoS ONE 7:E29333-E29333(2012).
RN [46]
RP FUNCTION, ASSEMBLY IN THE INOS-S100A8/A9 COMPLEX, MUTAGENESIS OF CYS-3, AND
RP S-NITROSYLATION AT CYS-3.
RX PubMed=25417112; DOI=10.1016/j.cell.2014.09.032;
RA Jia J., Arif A., Terenzi F., Willard B., Plow E.F., Hazen S.L., Fox P.L.;
RT "Target-selective protein S-nitrosylation by sequence motif recognition.";
RL Cell 159:623-634(2014).
RN [47]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-113, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [48]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH CALCIUM IONS, MASS
RP SPECTROMETRY, AND SUBUNIT.
RX PubMed=11851337; DOI=10.1006/jmbi.2001.5340;
RA Itou H., Yao M., Fujita I., Watanabe N., Suzuki M., Nishihira J.,
RA Tanaka I.;
RT "The crystal structure of human MRP14 (S100A9), a Ca(2+)-dependent
RT regulator protein in inflammatory process.";
RL J. Mol. Biol. 316:265-276(2002).
RN [49]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 4-114 IN COMPLEX WITH S100A8 AND
RP CALCIUM, SUBUNIT, AND ZINC-BINDING.
RX PubMed=17553524; DOI=10.1016/j.jmb.2007.04.065;
RA Korndoerfer I.P., Brueckner F., Skerra A.;
RT "The crystal structure of the human (S100A8/S100A9)2 heterotetramer,
RT calprotectin, illustrates how conformational changes of interacting alpha-
RT helices can determine specific association of two EF-hand proteins.";
RL J. Mol. Biol. 370:887-898(2007).
CC -!- FUNCTION: S100A9 is a calcium- and zinc-binding protein which plays a
CC prominent role in the regulation of inflammatory processes and immune
CC response (PubMed:12626582, PubMed:15331440, PubMed:20103766,
CC PubMed:8423249, PubMed:16258195, PubMed:19122197, PubMed:21325622). It
CC can induce neutrophil chemotaxis, adhesion, can increase the
CC bactericidal activity of neutrophils by promoting phagocytosis via
CC activation of SYK, PI3K/AKT, and ERK1/2 and can induce degranulation of
CC neutrophils by a MAPK-dependent mechanism (PubMed:12626582,
CC PubMed:15331440, PubMed:20103766). Predominantly found as calprotectin
CC (S100A8/A9) which has a wide plethora of intra- and extracellular
CC functions (PubMed:8423249, PubMed:16258195, PubMed:19122197). The
CC intracellular functions include: facilitating leukocyte arachidonic
CC acid trafficking and metabolism, modulation of the tubulin-dependent
CC cytoskeleton during migration of phagocytes and activation of the
CC neutrophilic NADPH-oxidase (PubMed:15331440, PubMed:21325622).
CC Activates NADPH-oxidase by facilitating the enzyme complex assembly at
CC the cell membrane, transferring arachidonic acid, an essential
CC cofactor, to the enzyme complex and S100A8 contributes to the enzyme
CC assembly by directly binding to NCF2/P67PHOX (PubMed:15642721,
CC PubMed:22808130). The extracellular functions involve pro-inflammatory,
CC antimicrobial, oxidant-scavenging and apoptosis-inducing activities
CC (PubMed:8423249, PubMed:19534726). Its pro-inflammatory activity
CC includes recruitment of leukocytes, promotion of cytokine and chemokine
CC production, and regulation of leukocyte adhesion and migration
CC (PubMed:15598812, PubMed:21487906). Acts as an alarmin or a danger
CC associated molecular pattern (DAMP) molecule and stimulates innate
CC immune cells via binding to pattern recognition receptors such as Toll-
CC like receptor 4 (TLR4) and receptor for advanced glycation endproducts
CC (AGER) (PubMed:19402754). Binding to TLR4 and AGER activates the MAP-
CC kinase and NF-kappa-B signaling pathways resulting in the amplification
CC of the pro-inflammatory cascade (PubMed:19402754, PubMed:22804476). Has
CC antimicrobial activity towards bacteria and fungi and exerts its
CC antimicrobial activity probably via chelation of Zn(2+) which is
CC essential for microbial growth (PubMed:19087201). Can induce cell death
CC via autophagy and apoptosis and this occurs through the cross-talk of
CC mitochondria and lysosomes via reactive oxygen species (ROS) and the
CC process involves BNIP3 (PubMed:19935772). Can regulate neutrophil
CC number and apoptosis by an anti-apoptotic effect; regulates cell
CC survival via ITGAM/ITGB and TLR4 and a signaling mechanism involving
CC MEK-ERK (PubMed:22363402). Its role as an oxidant scavenger has a
CC protective role in preventing exaggerated tissue damage by scavenging
CC oxidants (PubMed:22489132, PubMed:21912088). Can act as a potent
CC amplifier of inflammation in autoimmunity as well as in cancer
CC development and tumor spread (PubMed:16258195). Has transnitrosylase
CC activity; in oxidatively-modified low-densitity lipoprotein (LDL(ox))-
CC induced S-nitrosylation of GAPDH on 'Cys-247' proposed to transfer the
CC NO moiety from NOS2/iNOS to GAPDH via its own S-nitrosylated Cys-3
CC (PubMed:25417112). The iNOS-S100A8/A9 transnitrosylase complex is
CC proposed to also direct selective inflammatory stimulus-dependent S-
CC nitrosylation of multiple targets such as ANXA5, EZR, MSN and VIM by
CC recognizing a [IL]-x-C-x-x-[DE] motif (PubMed:25417112).
CC {ECO:0000269|PubMed:12626582, ECO:0000269|PubMed:15331440,
CC ECO:0000269|PubMed:15598812, ECO:0000269|PubMed:15642721,
CC ECO:0000269|PubMed:16258195, ECO:0000269|PubMed:19087201,
CC ECO:0000269|PubMed:19122197, ECO:0000269|PubMed:19402754,
CC ECO:0000269|PubMed:19534726, ECO:0000269|PubMed:19935772,
CC ECO:0000269|PubMed:20103766, ECO:0000269|PubMed:21325622,
CC ECO:0000269|PubMed:21487906, ECO:0000269|PubMed:22363402,
CC ECO:0000269|PubMed:22804476, ECO:0000269|PubMed:22808130,
CC ECO:0000269|PubMed:25417112, ECO:0000269|PubMed:8423249,
CC ECO:0000303|PubMed:21912088, ECO:0000303|PubMed:22489132}.
CC -!- SUBUNIT: Homodimer (PubMed:11851337, PubMed:16258195). Preferentially
CC exists as a heterodimer or heterotetramer with S100A8 known as
CC calprotectin (S100A8/A9) (PubMed:16258195, PubMed:17553524,
CC PubMed:19087201, PubMed:19122197, PubMed:8423249, PubMed:9083090,
CC PubMed:25417112). S100A9 interacts with ATP2A2 (By similarity). S100A9
CC interacts with AGER, and with the heterodimeric complex formed by TLR4
CC and LY96 in the presence of calcium and/or zinc ions (PubMed:19402754).
CC S100A9 binds quinoline-3-carboxamides in the presence of calcium and/or
CC zinc ions (PubMed:19402754). S100A9 interacts with amyloid-beta protein
CC 40 (PubMed:22457725). Calprotectin (S100A8/9) interacts with CEACAM3
CC and tubulin filaments in a calcium-dependent manner (PubMed:11708798).
CC Heterotetrameric calprotectin (S100A8/A9) interacts with ANXA6 and
CC associates with tubulin filaments in activated monocytes
CC (PubMed:18786929). Calprotectin (S100A8/9) interacts with NCF2/P67PHOX,
CC RAC1, RAC2, CYBA and CYBB (PubMed:15642721, PubMed:22808130).
CC Calprotectin (S100A8/9) interacts with NOS2 to form the iNOS-S100A8/A9
CC transnitrosylase complex; induced by LDL(ox) (PubMed:25417112).
CC {ECO:0000250|UniProtKB:P31725, ECO:0000269|PubMed:11708798,
CC ECO:0000269|PubMed:11851337, ECO:0000269|PubMed:15642721,
CC ECO:0000269|PubMed:16258195, ECO:0000269|PubMed:17553524,
CC ECO:0000269|PubMed:18786929, ECO:0000269|PubMed:19087201,
CC ECO:0000269|PubMed:19122197, ECO:0000269|PubMed:19402754,
CC ECO:0000269|PubMed:22457725, ECO:0000269|PubMed:22808130,
CC ECO:0000269|PubMed:25417112, ECO:0000269|PubMed:8423249,
CC ECO:0000269|PubMed:9083090}.
CC -!- INTERACTION:
CC P06702; P49407: ARRB1; NbExp=2; IntAct=EBI-1055001, EBI-743313;
CC P06702; P32121: ARRB2; NbExp=2; IntAct=EBI-1055001, EBI-714559;
CC P06702; P20138: CD33; NbExp=5; IntAct=EBI-1055001, EBI-3906571;
CC P06702; P43355: MAGEA1; NbExp=3; IntAct=EBI-1055001, EBI-740978;
CC P06702; P43357: MAGEA3; NbExp=3; IntAct=EBI-1055001, EBI-5651459;
CC P06702; P43360: MAGEA6; NbExp=3; IntAct=EBI-1055001, EBI-1045155;
CC P06702; P05109: S100A8; NbExp=7; IntAct=EBI-1055001, EBI-355281;
CC P06702; P04271: S100B; NbExp=3; IntAct=EBI-1055001, EBI-458391;
CC -!- SUBCELLULAR LOCATION: Secreted. Cytoplasm {ECO:0000269|PubMed:15598812,
CC ECO:0000269|PubMed:8423249}. Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:22489132, ECO:0000269|PubMed:9083090}. Cell
CC membrane {ECO:0000269|PubMed:18786929}; Peripheral membrane protein
CC {ECO:0000305|PubMed:18786929}. Note=Predominantly localized in the
CC cytoplasm. Upon elevation of the intracellular calcium level,
CC translocated from the cytoplasm to the cytoskeleton and the cell
CC membrane (PubMed:18786929). Upon neutrophil activation or endothelial
CC adhesion of monocytes, is secreted via a microtubule-mediated,
CC alternative pathway (PubMed:15598812). {ECO:0000269|PubMed:15598812,
CC ECO:0000269|PubMed:18786929}.
CC -!- TISSUE SPECIFICITY: Calprotectin (S100A8/9) is predominantly expressed
CC in myeloid cells. Except for inflammatory conditions, the expression is
CC restricted to a specific stage of myeloid differentiation since both
CC proteins are expressed in circulating neutrophils and monocytes but are
CC absent in normal tissue macrophages and lymphocytes. Under chronic
CC inflammatory conditions, such as psoriasis and malignant disorders,
CC also expressed in the epidermis. Found in high concentrations at local
CC sites of inflammation or in the serum of patients with inflammatory
CC diseases such as rheumatoid, cystic fibrosis, inflammatory bowel
CC disease, Crohn's disease, giant cell arteritis, cystic fibrosis,
CC Sjogren's syndrome, systemic lupus erythematosus, and progressive
CC systemic sclerosis. Involved in the formation and deposition of
CC amyloids in the aging prostate known as corpora amylacea inclusions.
CC Strongly up-regulated in many tumors, including gastric, esophageal,
CC colon, pancreatic, bladder, ovarian, thyroid, breast and skin cancers.
CC {ECO:0000269|PubMed:15598812, ECO:0000269|PubMed:3313057,
CC ECO:0000269|PubMed:3405210, ECO:0000269|PubMed:8423249,
CC ECO:0000269|PubMed:9083090}.
CC -!- PTM: Phosphorylated. Phosphorylation inhibits activation of tubulin
CC polymerization. {ECO:0000269|PubMed:15331440,
CC ECO:0000269|PubMed:15905572, ECO:0000269|PubMed:2478889}.
CC -!- PTM: S-nitrosylation of Cys-3 is implicated in LDL(ox)-induced S-
CC nitrosylation of GAPDH at 'Cys-247' through a transnitrosylase
CC mechanism involving a iNOS-S100A8/9 complex (PubMed:25417112).
CC {ECO:0000305|PubMed:25417112}.
CC -!- PTM: Methylation at His-105 by METTL9 reduces zinc-binding without
CC affecting heterodimerization with S100A8.
CC {ECO:0000250|UniProtKB:P31725}.
CC -!- MASS SPECTROMETRY: Mass=13115; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:11851337};
CC -!- SIMILARITY: Belongs to the S-100 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="https://atlasgeneticsoncology.org/gene/45569/S100A9";
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DR EMBL; X06233; CAA29579.1; -; mRNA.
DR EMBL; M21064; AAA36326.1; -; Genomic_DNA.
DR EMBL; M26311; AAA68480.1; -; mRNA.
DR EMBL; AF237581; AAF62536.1; -; Genomic_DNA.
DR EMBL; AF237582; AAF62537.1; -; Genomic_DNA.
DR EMBL; CR542207; CAG47003.1; -; mRNA.
DR EMBL; CR542224; CAG47020.1; -; mRNA.
DR EMBL; AL591704; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471121; EAW53333.1; -; Genomic_DNA.
DR EMBL; CH471121; EAW53334.1; -; Genomic_DNA.
DR EMBL; BC047681; AAH47681.1; -; mRNA.
DR CCDS; CCDS1036.1; -.
DR PIR; B31848; B31848.
DR RefSeq; NP_002956.1; NM_002965.3.
DR PDB; 1IRJ; X-ray; 2.10 A; A/B/C/D/E/F/G/H=2-114.
DR PDB; 1XK4; X-ray; 1.80 A; C/D/G/H/K/L=2-114.
DR PDB; 4GGF; X-ray; 1.60 A; C/L/T/V=1-114.
DR PDB; 4XJK; X-ray; 1.76 A; B/D/F/H/J=1-114.
DR PDB; 5I8N; NMR; -; A/B=1-114.
DR PDB; 5W1F; X-ray; 2.60 A; B/D/F/H=1-114.
DR PDB; 6DS2; X-ray; 2.10 A; B/D/F/H=1-114.
DR PDB; 7QUV; X-ray; 1.85 A; B=1-114.
DR PDB; 7UI5; NMR; -; A/B=1-114.
DR PDBsum; 1IRJ; -.
DR PDBsum; 1XK4; -.
DR PDBsum; 4GGF; -.
DR PDBsum; 4XJK; -.
DR PDBsum; 5I8N; -.
DR PDBsum; 5W1F; -.
DR PDBsum; 6DS2; -.
DR PDBsum; 7QUV; -.
DR PDBsum; 7UI5; -.
DR AlphaFoldDB; P06702; -.
DR SMR; P06702; -.
DR BioGRID; 112188; 288.
DR ComplexPortal; CPX-37; Calprotectin heterotetramer.
DR ComplexPortal; CPX-39; Calprotectin heterodimer.
DR ComplexPortal; CPX-48; S100A9 complex.
DR ComplexPortal; CPX-52; iNOS-S100A8/A9 complex.
DR CORUM; P06702; -.
DR DIP; DIP-1166N; -.
DR IntAct; P06702; 104.
DR MINT; P06702; -.
DR STRING; 9606.ENSP00000357727; -.
DR BindingDB; P06702; -.
DR ChEMBL; CHEMBL4296265; -.
DR DrugBank; DB01373; Calcium.
DR DrugBank; DB01593; Zinc.
DR DrugBank; DB14487; Zinc acetate.
DR DrugBank; DB14533; Zinc chloride.
DR DrugBank; DB14548; Zinc sulfate, unspecified form.
DR MoonProt; P06702; -.
DR GlyGen; P06702; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P06702; -.
DR MetOSite; P06702; -.
DR PhosphoSitePlus; P06702; -.
DR SwissPalm; P06702; -.
DR BioMuta; S100A9; -.
DR DMDM; 115444; -.
DR OGP; P06702; -.
DR SWISS-2DPAGE; P06702; -.
DR UCD-2DPAGE; P06702; -.
DR CPTAC; CPTAC-1294; -.
DR CPTAC; CPTAC-1295; -.
DR CPTAC; non-CPTAC-1155; -.
DR EPD; P06702; -.
DR jPOST; P06702; -.
DR MassIVE; P06702; -.
DR MaxQB; P06702; -.
DR PaxDb; 9606-ENSP00000357727; -.
DR PeptideAtlas; P06702; -.
DR PRIDE; P06702; -.
DR ProteomicsDB; 51910; -.
DR Pumba; P06702; -.
DR TopDownProteomics; P06702; -.
DR Antibodypedia; 1084; 1479 antibodies from 46 providers.
DR CPTC; P06702; 2 antibodies.
DR DNASU; 6280; -.
DR Ensembl; ENST00000368738.4; ENSP00000357727.3; ENSG00000163220.11.
DR GeneID; 6280; -.
DR KEGG; hsa:6280; -.
DR MANE-Select; ENST00000368738.4; ENSP00000357727.3; NM_002965.4; NP_002956.1.
DR UCSC; uc001fbq.3; human.
DR AGR; HGNC:10499; -.
DR CTD; 6280; -.
DR DisGeNET; 6280; -.
DR GeneCards; S100A9; -.
DR HGNC; HGNC:10499; S100A9.
DR HPA; ENSG00000163220; Tissue enhanced (bone marrow, esophagus, vagina).
DR MIM; 123886; gene.
DR neXtProt; NX_P06702; -.
DR OpenTargets; ENSG00000163220; -.
DR PharmGKB; PA34911; -.
DR VEuPathDB; HostDB:ENSG00000163220; -.
DR eggNOG; ENOG502SA01; Eukaryota.
DR GeneTree; ENSGT00940000161606; -.
DR HOGENOM; CLU_138624_6_0_1; -.
DR InParanoid; P06702; -.
DR OMA; HEEMHKT; -.
DR OrthoDB; 4607525at2759; -.
DR PhylomeDB; P06702; -.
DR TreeFam; TF332727; -.
DR PathwayCommons; P06702; -.
DR Reactome; R-HSA-1236974; ER-Phagosome pathway.
DR Reactome; R-HSA-166058; MyD88:MAL(TIRAP) cascade initiated on plasma membrane.
DR Reactome; R-HSA-5602498; MyD88 deficiency (TLR2/4).
DR Reactome; R-HSA-5603041; IRAK4 deficiency (TLR2/4).
DR Reactome; R-HSA-5668599; RHO GTPases Activate NADPH Oxidases.
DR Reactome; R-HSA-5686938; Regulation of TLR by endogenous ligand.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-6799990; Metal sequestration by antimicrobial proteins.
DR SignaLink; P06702; -.
DR SIGNOR; P06702; -.
DR BioGRID-ORCS; 6280; 11 hits in 1152 CRISPR screens.
DR ChiTaRS; S100A9; human.
DR EvolutionaryTrace; P06702; -.
DR GeneWiki; S100A9; -.
DR GenomeRNAi; 6280; -.
DR Pharos; P06702; Tchem.
DR PRO; PR:P06702; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P06702; Protein.
DR Bgee; ENSG00000163220; Expressed in monocyte and 165 other cell types or tissues.
DR Genevisible; P06702; HS.
DR GO; GO:1990660; C:calprotectin complex; IPI:ComplexPortal.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; TAS:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; HDA:BHF-UCL.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:UniProtKB.
DR GO; GO:1990662; C:S100A9 complex; IPI:ComplexPortal.
DR GO; GO:0034774; C:secretory granule lumen; TAS:Reactome.
DR GO; GO:0016209; F:antioxidant activity; IEA:UniProtKB-KW.
DR GO; GO:0050544; F:arachidonic acid binding; TAS:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IBA:GO_Central.
DR GO; GO:0048306; F:calcium-dependent protein binding; IBA:GO_Central.
DR GO; GO:0008017; F:microtubule binding; TAS:UniProtKB.
DR GO; GO:0050786; F:RAGE receptor binding; TAS:UniProtKB.
DR GO; GO:0035662; F:Toll-like receptor 4 binding; TAS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; TAS:UniProtKB.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB.
DR GO; GO:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; IDA:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0014002; P:astrocyte development; IBA:GO_Central.
DR GO; GO:0035425; P:autocrine signaling; IBA:GO_Central.
DR GO; GO:0006914; P:autophagy; IDA:UniProtKB.
DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR GO; GO:0002544; P:chronic inflammatory response; IBA:GO_Central.
DR GO; GO:0042742; P:defense response to bacterium; TAS:UniProtKB.
DR GO; GO:0050832; P:defense response to fungus; TAS:UniProtKB.
DR GO; GO:0043542; P:endothelial cell migration; IBA:GO_Central.
DR GO; GO:0006954; P:inflammatory response; TAS:ProtInc.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0002523; P:leukocyte migration involved in inflammatory response; IDA:UniProtKB.
DR GO; GO:0035821; P:modulation of process of another organism; IDA:UniProtKB.
DR GO; GO:0070488; P:neutrophil aggregation; IDA:UniProtKB.
DR GO; GO:0030593; P:neutrophil chemotaxis; IDA:UniProtKB.
DR GO; GO:0035606; P:peptidyl-cysteine S-trans-nitrosylation; IDA:UniProtKB.
DR GO; GO:0030307; P:positive regulation of cell growth; TAS:UniProtKB.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IDA:UniProtKB.
DR GO; GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; IDA:UniProtKB.
DR GO; GO:0010976; P:positive regulation of neuron projection development; ISS:ARUK-UCL.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; TAS:UniProtKB.
DR GO; GO:0051493; P:regulation of cytoskeleton organization; TAS:UniProtKB.
DR GO; GO:0045113; P:regulation of integrin biosynthetic process; IBA:GO_Central.
DR GO; GO:0060264; P:regulation of respiratory burst involved in inflammatory response; NAS:ComplexPortal.
DR GO; GO:0034121; P:regulation of toll-like receptor signaling pathway; NAS:ComplexPortal.
DR GO; GO:0032496; P:response to lipopolysaccharide; IBA:GO_Central.
DR GO; GO:0032119; P:sequestering of zinc ion; TAS:UniProtKB.
DR CDD; cd05030; calgranulins; 1.
DR Gene3D; 1.10.238.10; EF-hand; 1.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR001751; S100/CaBP7/8-like_CS.
DR InterPro; IPR013787; S100_Ca-bd_sub.
DR PANTHER; PTHR11639:SF79; PROTEIN S100-A9; 1.
DR PANTHER; PTHR11639; S100 CALCIUM-BINDING PROTEIN; 1.
DR Pfam; PF01023; S_100; 1.
DR SMART; SM00054; EFh; 1.
DR SMART; SM01394; S_100; 1.
DR SUPFAM; SSF47473; EF-hand; 1.
DR PROSITE; PS00018; EF_HAND_1; 1.
DR PROSITE; PS50222; EF_HAND_2; 1.
DR PROSITE; PS00303; S100_CABP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antimicrobial; Antioxidant; Apoptosis; Autophagy; Calcium;
KW Cell membrane; Chemotaxis; Cytoplasm; Cytoskeleton;
KW Direct protein sequencing; Immunity; Inflammatory response;
KW Innate immunity; Membrane; Metal-binding; Methylation; Phosphoprotein;
KW Reference proteome; Repeat; S-nitrosylation; Secreted; Zinc.
FT CHAIN 1..114
FT /note="Protein S100-A9"
FT /id="PRO_0000143997"
FT DOMAIN 12..47
FT /note="EF-hand 1"
FT /evidence="ECO:0000305"
FT DOMAIN 54..89
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 93..114
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 20
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000305|PubMed:17553524"
FT BINDING 23
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /ligand_note="low affinity"
FT /evidence="ECO:0000269|PubMed:11851337,
FT ECO:0000269|PubMed:17553524, ECO:0007744|PDB:1IRJ,
FT ECO:0007744|PDB:1XK4"
FT BINDING 26
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /ligand_note="low affinity"
FT /evidence="ECO:0000269|PubMed:11851337,
FT ECO:0000269|PubMed:17553524, ECO:0007744|PDB:1IRJ,
FT ECO:0007744|PDB:1XK4"
FT BINDING 28
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /ligand_note="low affinity"
FT /evidence="ECO:0000269|PubMed:11851337,
FT ECO:0000269|PubMed:17553524, ECO:0007744|PDB:1IRJ,
FT ECO:0007744|PDB:1XK4"
FT BINDING 30
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000305|PubMed:17553524"
FT BINDING 31
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /ligand_note="low affinity"
FT /evidence="ECO:0000269|PubMed:11851337,
FT ECO:0000269|PubMed:17553524, ECO:0007744|PDB:1IRJ,
FT ECO:0007744|PDB:1XK4"
FT BINDING 36
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /ligand_note="low affinity"
FT /evidence="ECO:0000269|PubMed:11851337,
FT ECO:0000269|PubMed:17553524, ECO:0007744|PDB:1IRJ,
FT ECO:0007744|PDB:1XK4"
FT BINDING 67
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /ligand_note="high affinity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:11851337, ECO:0000269|PubMed:17553524,
FT ECO:0007744|PDB:1IRJ, ECO:0007744|PDB:1XK4"
FT BINDING 69
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /ligand_note="high affinity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:11851337, ECO:0000269|PubMed:17553524,
FT ECO:0007744|PDB:1IRJ, ECO:0007744|PDB:1XK4"
FT BINDING 71
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /ligand_note="high affinity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:11851337, ECO:0000269|PubMed:17553524,
FT ECO:0007744|PDB:1IRJ, ECO:0007744|PDB:1XK4"
FT BINDING 73
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /ligand_note="high affinity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:11851337, ECO:0000269|PubMed:17553524,
FT ECO:0007744|PDB:1IRJ, ECO:0007744|PDB:1XK4"
FT BINDING 78
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /ligand_note="high affinity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:11851337, ECO:0000269|PubMed:17553524,
FT ECO:0007744|PDB:1IRJ, ECO:0007744|PDB:1XK4"
FT BINDING 91
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000305|PubMed:17553524"
FT BINDING 95
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000305|PubMed:17553524"
FT MOD_RES 2
FT /note="Blocked amino end (Thr)"
FT MOD_RES 3
FT /note="S-nitrosocysteine; transient"
FT /evidence="ECO:0000305|PubMed:25417112"
FT MOD_RES 105
FT /note="Pros-methylhistidine"
FT /evidence="ECO:0000250|UniProtKB:P50116"
FT MOD_RES 113
FT /note="Phosphothreonine; by MAPK14"
FT /evidence="ECO:0000269|PubMed:15331440,
FT ECO:0000269|PubMed:15905572, ECO:0000269|PubMed:2478889,
FT ECO:0007744|PubMed:18318008, ECO:0007744|PubMed:19367720,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:24275569"
FT VARIANT 20
FT /note="H -> R"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_013008"
FT MUTAGEN 3
FT /note="C->A: Disrupts interaction with NOS2 and inhibits
FT LDL(ox)-induced GAPDH S-nitrosylation; no effect on
FT interaction with S100A8."
FT /evidence="ECO:0000269|PubMed:25417112"
FT MUTAGEN 36
FT /note="E->Q: Loss of resistance to bacterial invasion; when
FT associated with Q-78."
FT /evidence="ECO:0000269|PubMed:19122197"
FT MUTAGEN 63
FT /note="M->A: Loss of antifungal activity."
FT /evidence="ECO:0000269|PubMed:19087201"
FT MUTAGEN 78
FT /note="E->Q: Loss of resistance to bacterial invasion; when
FT associated with Q-36."
FT /evidence="ECO:0000269|PubMed:19122197"
FT MUTAGEN 81
FT /note="M->A: No effect on antifungal activity."
FT /evidence="ECO:0000269|PubMed:19087201"
FT MUTAGEN 83
FT /note="M->A: Loss of antifungal activity."
FT /evidence="ECO:0000269|PubMed:19087201"
FT CONFLICT 6
FT /note="S -> H (in Ref. 12; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 25
FT /note="K -> F (in Ref. 12; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 28
FT /note="H -> L (in Ref. 12; AA sequence)"
FT /evidence="ECO:0000305"
FT HELIX 7..23
FT /evidence="ECO:0007829|PDB:4GGF"
FT STRAND 25..28
FT /evidence="ECO:0007829|PDB:4GGF"
FT HELIX 34..44
FT /evidence="ECO:0007829|PDB:4GGF"
FT TURN 45..49
FT /evidence="ECO:0007829|PDB:4GGF"
FT HELIX 50..53
FT /evidence="ECO:0007829|PDB:4GGF"
FT HELIX 56..66
FT /evidence="ECO:0007829|PDB:4GGF"
FT STRAND 71..74
FT /evidence="ECO:0007829|PDB:4GGF"
FT HELIX 76..94
FT /evidence="ECO:0007829|PDB:4GGF"
FT TURN 95..97
FT /evidence="ECO:0007829|PDB:4GGF"
FT TURN 108..110
FT /evidence="ECO:0007829|PDB:5I8N"
SQ SEQUENCE 114 AA; 13242 MW; C3BE19729E14C078 CRC64;
MTCKMSQLER NIETIINTFH QYSVKLGHPD TLNQGEFKEL VRKDLQNFLK KENKNEKVIE
HIMEDLDTNA DKQLSFEEFI MLMARLTWAS HEKMHEGDEG PGHHHKPGLG EGTP
//
