Full text data of S100A9
S100A9
(CAGB, CFAG, MRP14)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Protein S100-A9 (Calgranulin-B; Calprotectin L1H subunit; Leukocyte L1 complex heavy chain; Migration inhibitory factor-related protein 14; MRP-14; p14; S100 calcium-binding protein A9)
Protein S100-A9 (Calgranulin-B; Calprotectin L1H subunit; Leukocyte L1 complex heavy chain; Migration inhibitory factor-related protein 14; MRP-14; p14; S100 calcium-binding protein A9)
UniProt
P06702
ID S10A9_HUMAN Reviewed; 114 AA.
AC P06702; D3DV36; Q6FGA1; Q9NYM0; Q9UCJ1;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JAN-1988, sequence version 1.
DT 22-JAN-2014, entry version 161.
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;
DE Short=MRP-14;
DE Short=p14;
DE AltName: Full=S100 calcium-binding protein A9;
GN Name=S100A9; Synonyms=CAGB, CFAG, MRP14;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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;
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;
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
RT (MRP14), 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.,
RA Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W.,
RA Korn B., Zuo D., Hu Y., 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.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA 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.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA 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.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: 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
RT protein p14.";
RL Nature 342:189-192(1989).
RN [10]
RP PROTEIN SEQUENCE, AND BLOCKAGE OF N-TERMINUS.
RX PubMed=2776242;
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-
RT related 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
RT protein 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;
RA Miyasaki K.T., Bodeau A.L., Murthy A.R., Lehrer R.I.;
RT "In vitro antimicrobial activity of the human neutrophil cytosolic S-
RT 100 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
RT of the S100 family, are secreted by activated monocytes via a novel,
RT tubulin-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
RT in granulocytes.";
RL Biochem. Biophys. Res. Commun. 289:191-197(2001).
RN [15]
RP FUNCTION.
RX PubMed=12626582;
RA Ryckman C., Vandal K., Rouleau P., Talbot M., Tessier P.A.;
RT "Proinflammatory activities of S100: proteins S100A8, S100A9, and
RT S100A8/A9 induce neutrophil chemotaxis and adhesion.";
RL J. Immunol. 170:3233-3242(2003).
RN [16]
RP FUNCTION, INTERACTION WITH TUBULIN, 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.,
RA Roth J.;
RT "MRP8 and MRP14 control microtubule reorganization during
RT transendothelial migration of phagocytes.";
RL Blood 104:4260-4268(2004).
RN [17]
RP FUNCTION, MASS SPECTROMETRY, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=15598812; DOI=10.1182/blood-2004-07-2520;
RA Viemann D., Strey A., Janning A., Jurk K., Klimmek K., Vogl T.,
RA Hirono K., Ichida F., Foell D., Kehrel B., Gerke V., Sorg C., Roth J.;
RT "Myeloid-related proteins 8 and 14 induce a specific inflammatory
RT response 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.,
RA 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;
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
RT 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
RT ion 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
RT calcium-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 MASS
RP SPECTROMETRY.
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
RT sequential IMAC and titanium oxide enrichment.";
RL J. Proteome Res. 7:5167-5176(2008).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-113, AND MASS
RP SPECTROMETRY.
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
RT enrichment and fractionation of phosphopeptides with strong anion
RT exchange chromatography.";
RL Proteomics 8:1346-1361(2008).
RN [24]
RP REVIEW.
RX PubMed=20523765;
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
RT apoptosis 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
RT tumorgenesis.";
RL Eur. J. Pharmacol. 625:73-83(2009).
RN [27]
RP FUNCTION, SUBUNIT, MUTAGENESIS OF MET-63; MET-81 AND MET-83, AND
RP INHIBITION 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
RT S100A8 abrogate the antifungal activities of S100A8/A9: potential role
RT for 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.,
RA 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
RT (calprotectin) as innate amplifier of infection, autoimmunity, and
RT cancer.";
RL J. Leukoc. Biol. 86:557-566(2009).
RN [30]
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, INTERACTION WITH TLR4; LY96
RP AND 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.,
RA Halayko A.J., 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 MASS
RP SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation 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.,
RA Buerckstuemmer T., 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
RT activity 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.,
RA Ivars F., 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
RT in vivo: a variety of functional roles of the two proteins as
RT regulators in 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
RT and 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
RT via S100 A8/9 and the MEK-ERK pathway.";
RL PLoS ONE 7:E29333-E29333(2012).
RN [46]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH CALCIUM IONS,
RP MASS 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 [47]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 4-114 IN COMPLEX WITH S100A8,
RP 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
RT alpha-helices can determine specific association of two EF-hand
RT proteins.";
RL J. Mol. Biol. 370:887-898(2007).
CC -!- FUNCTION: S100A9 is a calcium- and zinc-binding protein which
CC plays a prominent role in the regulation of inflammatory processes
CC and immune response. It can induce neutrophil chemotaxis,
CC adhesion, can increase the bactericidal activity of neutrophils by
CC promoting phagocytosis via activation of SYK, PI3K/AKT, and ERK1/2
CC and can induce degranulation of neutrophils by a MAPK-dependent
CC mechanism. Predominantly found as calprotectin (S100A8/A9) which
CC has a wide plethora of intra- and extracellular functions. The
CC intracellular functions include: facilitating leukocyte
CC arachidonic acid trafficking and metabolism, modulation of the
CC tubulin-dependent cytoskeleton during migration of phagocytes and
CC activation of the neutrophilic NADPH-oxidase. Activates NADPH-
CC oxidase by facilitating the enzyme complex assembly at the cell
CC membrane, transfering arachidonic acid, an essential cofactor, to
CC the enzyme complex and S100A8 contributes to the enzyme assembly
CC by directly binding to NCF2/P67PHOX. The extracellular functions
CC involve proinfammatory, antimicrobial, oxidant-scavenging and
CC apoptosis-inducing activities. Its proinflammatory activity
CC includes recruitment of leukocytes, promotion of cytokine and
CC chemokine production, and regulation of leukocyte adhesion and
CC migration. Acts as an alarmin or a danger associated molecular
CC pattern (DAMP) molecule and stimulates innate immune cells via
CC binding to pattern recognition receptors such as Toll-like
CC receptor 4 (TLR4) and receptor for advanced glycation endproducts
CC (AGER). Binding to TLR4 and AGER activates the MAP-kinase and NF-
CC kappa-B signaling pathways resulting in the amplification of the
CC proinflammatory cascade. Has antimicrobial activity towards
CC bacteria and fungi and exerts its antimicrobial activity probably
CC via chelation of Zn(2+) which is essential for microbial growth.
CC Can induce cell death via autophagy and apoptosis and this occurs
CC through the cross-talk of mitochondria and lysosomes via reactive
CC oxygen species (ROS) and the process involves BNIP3. Can regulate
CC neutrophil number and apoptosis by an anti-apoptotic effect;
CC regulates cell survival via ITGAM/ITGB and TLR4 and a signaling
CC mechanism involving MEK-ERK. Its role as an oxidant scavenger has
CC a protective role in preventing exaggerated tissue damage by
CC scavenging oxidants. Can act as a potent amplifier of inflammation
CC in autoimmunity as well as in cancer development and tumor spread.
CC -!- SUBUNIT: Homodimer. Preferentially exists as a heterodimer or
CC heterotetramer with S100A8 known as calprotectin (S100A8/A9).
CC S100A9 interacts with ATP2A2 (By similarity). S100A9 interacts
CC with AGER, and with the heterodimeric complex formed by TLR4 and
CC LY96 in the presence of calcium and/or zinc ions. S100A9 binds
CC quinoline-3-carboxamides in the presence of calcium and/or zinc
CC ions. S100A9 interacts with beta-APP40 (beta-amyloid protein 40)
CC peptide of APP. Calprotectin (S100A8/9) interacts with CEACAM3 and
CC tubulin filaments in a calcium-dependent manner. Heterotetrameric
CC calprotectin (S100A8/A9) interacts with ANXA6 and associates with
CC tubulin filaments in activated monocytes. Calprotectin (S100A8/9)
CC interacts with NCF2/P67PHOX, RAC1, RAC2, CYBA and CYBB.
CC -!- INTERACTION:
CC P49407:ARRB1; NbExp=2; IntAct=EBI-1055001, EBI-743313;
CC P32121:ARRB2; NbExp=2; IntAct=EBI-1055001, EBI-714559;
CC P05109:S100A8; NbExp=3; IntAct=EBI-1055001, EBI-355281;
CC -!- SUBCELLULAR LOCATION: Secreted. Cytoplasm. Cytoplasm,
CC cytoskeleton. Cell membrane; Peripheral membrane protein.
CC Note=Predominantly localized in the cytoplasm. Upon elevation of
CC the intracellular calcium level, translocated from the cytoplasm
CC to the cytoskeleton and the cell membrane. Upon neutrophil
CC activation or endothelial adhesion of monocytes, is secreted via a
CC microtubule-mediated, alternative pathway.
CC -!- TISSUE SPECIFICITY: Calprotectin (S100A8/9) is predominantly
CC expressed in myeloid cells. Except for inflammatory conditions,
CC the expression is restricted to a specific stage of myeloid
CC differentiation since both proteins are expressed in circulating
CC neutrophils and monocytes but are absent in normal tissue
CC macrophages and lymphocytes. Under chronic inflammatory
CC conditions, such as psoriasis and malignant disorders, also
CC expressed in the epidermis. Found in high concentrations at local
CC sites of inflammation or in the serum of patients with
CC inflammatory diseases such as rheumatoid, cystic fibrosis,
CC inflammatory bowel disease, Crohn's disease, giant cell arteritis,
CC cystic fibrosis, Sjogren's syndrome, systemic lupus erythematosus,
CC and progressive systemic sclerosis. Involved in the formation and
CC deposition of amyloids in the aging prostate known as corpora
CC amylacea inclusions. Strongly up-regulated in many tumors,
CC including gastric, esophageal, colon, pancreatic, bladder,
CC ovarian, thyroid, breast and skin cancers.
CC -!- PTM: Phosphorylated. Phosphorylation inhibits activation of
CC tubulin polymerization.
CC -!- MASS SPECTROMETRY: Mass=13115; Method=MALDI; Range=2-114;
CC Source=PubMed:11851337;
CC -!- SIMILARITY: Belongs to the S-100 family.
CC -!- SIMILARITY: Contains 2 EF-hand domains.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/S100A9ID45569ch1q21.html";
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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; CAI19494.1; -; Genomic_DNA.
DR EMBL; CH471121; EAW53333.1; -; Genomic_DNA.
DR EMBL; CH471121; EAW53334.1; -; Genomic_DNA.
DR EMBL; BC047681; AAH47681.1; -; mRNA.
DR PIR; B31848; B31848.
DR RefSeq; NP_002956.1; NM_002965.3.
DR UniGene; Hs.112405; -.
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=4-114.
DR PDB; 4GGF; X-ray; 1.60 A; C/L/T/V=1-114.
DR PDBsum; 1IRJ; -.
DR PDBsum; 1XK4; -.
DR PDBsum; 4GGF; -.
DR ProteinModelPortal; P06702; -.
DR SMR; P06702; 4-112.
DR DIP; DIP-1166N; -.
DR IntAct; P06702; 19.
DR MINT; MINT-5002390; -.
DR STRING; 9606.ENSP00000357727; -.
DR PhosphoSite; P06702; -.
DR DMDM; 115444; -.
DR OGP; P06702; -.
DR SWISS-2DPAGE; P06702; -.
DR UCD-2DPAGE; P06702; -.
DR PaxDb; P06702; -.
DR PeptideAtlas; P06702; -.
DR PRIDE; P06702; -.
DR Ensembl; ENST00000368738; ENSP00000357727; ENSG00000163220.
DR GeneID; 6280; -.
DR KEGG; hsa:6280; -.
DR UCSC; uc001fbq.3; human.
DR CTD; 6280; -.
DR GeneCards; GC01P153330; -.
DR HGNC; HGNC:10499; S100A9.
DR HPA; CAB009441; -.
DR HPA; HPA004193; -.
DR MIM; 123886; gene.
DR neXtProt; NX_P06702; -.
DR PharmGKB; PA34911; -.
DR eggNOG; NOG47012; -.
DR HOGENOM; HOG000246968; -.
DR HOVERGEN; HBG001479; -.
DR InParanoid; P06702; -.
DR OMA; HEKMHEN; -.
DR OrthoDB; EOG73807B; -.
DR PhylomeDB; P06702; -.
DR ChiTaRS; S100A9; human.
DR EvolutionaryTrace; P06702; -.
DR GeneWiki; S100A9; -.
DR GenomeRNAi; 6280; -.
DR NextBio; 24377; -.
DR PRO; PR:P06702; -.
DR Bgee; P06702; -.
DR CleanEx; HS_S100A9; -.
DR Genevestigator; P06702; -.
DR GO; GO:0005856; C:cytoskeleton; TAS:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; TAS:UniProtKB.
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; TAS:UniProtKB.
DR GO; GO:0008017; F:microtubule binding; TAS:UniProtKB.
DR GO; GO:0050786; F:RAGE receptor binding; TAS:UniProtKB.
DR GO; GO:0004871; F:signal transducer activity; TAS:ProtInc.
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:0006914; P:autophagy; IDA:UniProtKB.
DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR GO; GO:0032602; P:chemokine production; TAS:UniProtKB.
DR GO; GO:0002544; P:chronic inflammatory response; IEA:Ensembl.
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:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0002523; P:leukocyte migration involved in inflammatory response; IDA:UniProtKB.
DR GO; GO:0070488; P:neutrophil aggregation; IDA:UniProtKB.
DR GO; GO:0030593; P:neutrophil chemotaxis; 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: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:0045471; P:response to ethanol; IEA:Ensembl.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0010043; P:response to zinc ion; IEA:Ensembl.
DR GO; GO:0032119; P:sequestering of zinc ion; TAS:UniProtKB.
DR Gene3D; 1.10.238.10; -; 1.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR028475; S100-A9.
DR InterPro; IPR001751; S100/CaBP-9k_CS.
DR InterPro; IPR013787; S100_Ca-bd_sub.
DR PANTHER; PTHR11639:SF10; PTHR11639:SF10; 1.
DR Pfam; PF01023; S_100; 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;
KW Calcium; Cell membrane; Chemotaxis; Complete proteome; Cytoplasm;
KW Cytoskeleton; Direct protein sequencing; Immunity;
KW Inflammatory response; Innate immunity; Membrane; Metal-binding;
KW Methylation; Phosphoprotein; Polymorphism; Reference proteome; Repeat;
KW Secreted; Zinc.
FT INIT_MET 1 1 Removed (By similarity).
FT CHAIN 2 114 Protein S100-A9.
FT /FTId=PRO_0000143997.
FT DOMAIN 12 47 EF-hand 1.
FT DOMAIN 54 89 EF-hand 2.
FT CA_BIND 23 36 1; low affinity.
FT CA_BIND 67 78 2; high affinity (Probable).
FT METAL 20 20 Zinc (Probable).
FT METAL 30 30 Zinc (Probable).
FT METAL 91 91 Zinc (Probable).
FT METAL 95 95 Zinc (Probable).
FT MOD_RES 2 2 Blocked amino end (Thr).
FT MOD_RES 105 105 Pros-methylhistidine (By similarity).
FT MOD_RES 113 113 Phosphothreonine; by MAPK14.
FT VARIANT 20 20 H -> R.
FT /FTId=VAR_013008.
FT MUTAGEN 36 36 E->Q: Loss of resistance to bacterial
FT invasion; when associated with Q-78.
FT MUTAGEN 63 63 M->A: Loss of antifungal activity.
FT MUTAGEN 78 78 E->Q: Loss of resistance to bacterial
FT invasion; when associated with Q-36.
FT MUTAGEN 81 81 M->A: No effect on antifungal activity.
FT MUTAGEN 83 83 M->A: Loss of antifungal activity.
FT CONFLICT 6 6 S -> H (in Ref. 12; AA sequence).
FT CONFLICT 25 25 K -> F (in Ref. 12; AA sequence).
FT CONFLICT 28 28 H -> L (in Ref. 12; AA sequence).
FT HELIX 7 23
FT STRAND 25 28
FT HELIX 34 44
FT TURN 45 49
FT HELIX 50 53
FT HELIX 56 66
FT STRAND 71 74
FT HELIX 76 94
FT TURN 95 97
SQ SEQUENCE 114 AA; 13242 MW; C3BE19729E14C078 CRC64;
MTCKMSQLER NIETIINTFH QYSVKLGHPD TLNQGEFKEL VRKDLQNFLK KENKNEKVIE
HIMEDLDTNA DKQLSFEEFI MLMARLTWAS HEKMHEGDEG PGHHHKPGLG EGTP
//
ID S10A9_HUMAN Reviewed; 114 AA.
AC P06702; D3DV36; Q6FGA1; Q9NYM0; Q9UCJ1;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JAN-1988, sequence version 1.
DT 22-JAN-2014, entry version 161.
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;
DE Short=MRP-14;
DE Short=p14;
DE AltName: Full=S100 calcium-binding protein A9;
GN Name=S100A9; Synonyms=CAGB, CFAG, MRP14;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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;
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;
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
RT (MRP14), 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.,
RA Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W.,
RA Korn B., Zuo D., Hu Y., 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.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA 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.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA 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.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: 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
RT protein p14.";
RL Nature 342:189-192(1989).
RN [10]
RP PROTEIN SEQUENCE, AND BLOCKAGE OF N-TERMINUS.
RX PubMed=2776242;
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-
RT related 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
RT protein 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;
RA Miyasaki K.T., Bodeau A.L., Murthy A.R., Lehrer R.I.;
RT "In vitro antimicrobial activity of the human neutrophil cytosolic S-
RT 100 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
RT of the S100 family, are secreted by activated monocytes via a novel,
RT tubulin-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
RT in granulocytes.";
RL Biochem. Biophys. Res. Commun. 289:191-197(2001).
RN [15]
RP FUNCTION.
RX PubMed=12626582;
RA Ryckman C., Vandal K., Rouleau P., Talbot M., Tessier P.A.;
RT "Proinflammatory activities of S100: proteins S100A8, S100A9, and
RT S100A8/A9 induce neutrophil chemotaxis and adhesion.";
RL J. Immunol. 170:3233-3242(2003).
RN [16]
RP FUNCTION, INTERACTION WITH TUBULIN, 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.,
RA Roth J.;
RT "MRP8 and MRP14 control microtubule reorganization during
RT transendothelial migration of phagocytes.";
RL Blood 104:4260-4268(2004).
RN [17]
RP FUNCTION, MASS SPECTROMETRY, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=15598812; DOI=10.1182/blood-2004-07-2520;
RA Viemann D., Strey A., Janning A., Jurk K., Klimmek K., Vogl T.,
RA Hirono K., Ichida F., Foell D., Kehrel B., Gerke V., Sorg C., Roth J.;
RT "Myeloid-related proteins 8 and 14 induce a specific inflammatory
RT response 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.,
RA 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;
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
RT 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
RT ion 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
RT calcium-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 MASS
RP SPECTROMETRY.
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
RT sequential IMAC and titanium oxide enrichment.";
RL J. Proteome Res. 7:5167-5176(2008).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-113, AND MASS
RP SPECTROMETRY.
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
RT enrichment and fractionation of phosphopeptides with strong anion
RT exchange chromatography.";
RL Proteomics 8:1346-1361(2008).
RN [24]
RP REVIEW.
RX PubMed=20523765;
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
RT apoptosis 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
RT tumorgenesis.";
RL Eur. J. Pharmacol. 625:73-83(2009).
RN [27]
RP FUNCTION, SUBUNIT, MUTAGENESIS OF MET-63; MET-81 AND MET-83, AND
RP INHIBITION 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
RT S100A8 abrogate the antifungal activities of S100A8/A9: potential role
RT for 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.,
RA 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
RT (calprotectin) as innate amplifier of infection, autoimmunity, and
RT cancer.";
RL J. Leukoc. Biol. 86:557-566(2009).
RN [30]
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, INTERACTION WITH TLR4; LY96
RP AND 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.,
RA Halayko A.J., 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 MASS
RP SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation 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.,
RA Buerckstuemmer T., 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
RT activity 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.,
RA Ivars F., 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
RT in vivo: a variety of functional roles of the two proteins as
RT regulators in 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
RT and 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
RT via S100 A8/9 and the MEK-ERK pathway.";
RL PLoS ONE 7:E29333-E29333(2012).
RN [46]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH CALCIUM IONS,
RP MASS 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 [47]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 4-114 IN COMPLEX WITH S100A8,
RP 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
RT alpha-helices can determine specific association of two EF-hand
RT proteins.";
RL J. Mol. Biol. 370:887-898(2007).
CC -!- FUNCTION: S100A9 is a calcium- and zinc-binding protein which
CC plays a prominent role in the regulation of inflammatory processes
CC and immune response. It can induce neutrophil chemotaxis,
CC adhesion, can increase the bactericidal activity of neutrophils by
CC promoting phagocytosis via activation of SYK, PI3K/AKT, and ERK1/2
CC and can induce degranulation of neutrophils by a MAPK-dependent
CC mechanism. Predominantly found as calprotectin (S100A8/A9) which
CC has a wide plethora of intra- and extracellular functions. The
CC intracellular functions include: facilitating leukocyte
CC arachidonic acid trafficking and metabolism, modulation of the
CC tubulin-dependent cytoskeleton during migration of phagocytes and
CC activation of the neutrophilic NADPH-oxidase. Activates NADPH-
CC oxidase by facilitating the enzyme complex assembly at the cell
CC membrane, transfering arachidonic acid, an essential cofactor, to
CC the enzyme complex and S100A8 contributes to the enzyme assembly
CC by directly binding to NCF2/P67PHOX. The extracellular functions
CC involve proinfammatory, antimicrobial, oxidant-scavenging and
CC apoptosis-inducing activities. Its proinflammatory activity
CC includes recruitment of leukocytes, promotion of cytokine and
CC chemokine production, and regulation of leukocyte adhesion and
CC migration. Acts as an alarmin or a danger associated molecular
CC pattern (DAMP) molecule and stimulates innate immune cells via
CC binding to pattern recognition receptors such as Toll-like
CC receptor 4 (TLR4) and receptor for advanced glycation endproducts
CC (AGER). Binding to TLR4 and AGER activates the MAP-kinase and NF-
CC kappa-B signaling pathways resulting in the amplification of the
CC proinflammatory cascade. Has antimicrobial activity towards
CC bacteria and fungi and exerts its antimicrobial activity probably
CC via chelation of Zn(2+) which is essential for microbial growth.
CC Can induce cell death via autophagy and apoptosis and this occurs
CC through the cross-talk of mitochondria and lysosomes via reactive
CC oxygen species (ROS) and the process involves BNIP3. Can regulate
CC neutrophil number and apoptosis by an anti-apoptotic effect;
CC regulates cell survival via ITGAM/ITGB and TLR4 and a signaling
CC mechanism involving MEK-ERK. Its role as an oxidant scavenger has
CC a protective role in preventing exaggerated tissue damage by
CC scavenging oxidants. Can act as a potent amplifier of inflammation
CC in autoimmunity as well as in cancer development and tumor spread.
CC -!- SUBUNIT: Homodimer. Preferentially exists as a heterodimer or
CC heterotetramer with S100A8 known as calprotectin (S100A8/A9).
CC S100A9 interacts with ATP2A2 (By similarity). S100A9 interacts
CC with AGER, and with the heterodimeric complex formed by TLR4 and
CC LY96 in the presence of calcium and/or zinc ions. S100A9 binds
CC quinoline-3-carboxamides in the presence of calcium and/or zinc
CC ions. S100A9 interacts with beta-APP40 (beta-amyloid protein 40)
CC peptide of APP. Calprotectin (S100A8/9) interacts with CEACAM3 and
CC tubulin filaments in a calcium-dependent manner. Heterotetrameric
CC calprotectin (S100A8/A9) interacts with ANXA6 and associates with
CC tubulin filaments in activated monocytes. Calprotectin (S100A8/9)
CC interacts with NCF2/P67PHOX, RAC1, RAC2, CYBA and CYBB.
CC -!- INTERACTION:
CC P49407:ARRB1; NbExp=2; IntAct=EBI-1055001, EBI-743313;
CC P32121:ARRB2; NbExp=2; IntAct=EBI-1055001, EBI-714559;
CC P05109:S100A8; NbExp=3; IntAct=EBI-1055001, EBI-355281;
CC -!- SUBCELLULAR LOCATION: Secreted. Cytoplasm. Cytoplasm,
CC cytoskeleton. Cell membrane; Peripheral membrane protein.
CC Note=Predominantly localized in the cytoplasm. Upon elevation of
CC the intracellular calcium level, translocated from the cytoplasm
CC to the cytoskeleton and the cell membrane. Upon neutrophil
CC activation or endothelial adhesion of monocytes, is secreted via a
CC microtubule-mediated, alternative pathway.
CC -!- TISSUE SPECIFICITY: Calprotectin (S100A8/9) is predominantly
CC expressed in myeloid cells. Except for inflammatory conditions,
CC the expression is restricted to a specific stage of myeloid
CC differentiation since both proteins are expressed in circulating
CC neutrophils and monocytes but are absent in normal tissue
CC macrophages and lymphocytes. Under chronic inflammatory
CC conditions, such as psoriasis and malignant disorders, also
CC expressed in the epidermis. Found in high concentrations at local
CC sites of inflammation or in the serum of patients with
CC inflammatory diseases such as rheumatoid, cystic fibrosis,
CC inflammatory bowel disease, Crohn's disease, giant cell arteritis,
CC cystic fibrosis, Sjogren's syndrome, systemic lupus erythematosus,
CC and progressive systemic sclerosis. Involved in the formation and
CC deposition of amyloids in the aging prostate known as corpora
CC amylacea inclusions. Strongly up-regulated in many tumors,
CC including gastric, esophageal, colon, pancreatic, bladder,
CC ovarian, thyroid, breast and skin cancers.
CC -!- PTM: Phosphorylated. Phosphorylation inhibits activation of
CC tubulin polymerization.
CC -!- MASS SPECTROMETRY: Mass=13115; Method=MALDI; Range=2-114;
CC Source=PubMed:11851337;
CC -!- SIMILARITY: Belongs to the S-100 family.
CC -!- SIMILARITY: Contains 2 EF-hand domains.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/S100A9ID45569ch1q21.html";
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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; CAI19494.1; -; Genomic_DNA.
DR EMBL; CH471121; EAW53333.1; -; Genomic_DNA.
DR EMBL; CH471121; EAW53334.1; -; Genomic_DNA.
DR EMBL; BC047681; AAH47681.1; -; mRNA.
DR PIR; B31848; B31848.
DR RefSeq; NP_002956.1; NM_002965.3.
DR UniGene; Hs.112405; -.
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=4-114.
DR PDB; 4GGF; X-ray; 1.60 A; C/L/T/V=1-114.
DR PDBsum; 1IRJ; -.
DR PDBsum; 1XK4; -.
DR PDBsum; 4GGF; -.
DR ProteinModelPortal; P06702; -.
DR SMR; P06702; 4-112.
DR DIP; DIP-1166N; -.
DR IntAct; P06702; 19.
DR MINT; MINT-5002390; -.
DR STRING; 9606.ENSP00000357727; -.
DR PhosphoSite; P06702; -.
DR DMDM; 115444; -.
DR OGP; P06702; -.
DR SWISS-2DPAGE; P06702; -.
DR UCD-2DPAGE; P06702; -.
DR PaxDb; P06702; -.
DR PeptideAtlas; P06702; -.
DR PRIDE; P06702; -.
DR Ensembl; ENST00000368738; ENSP00000357727; ENSG00000163220.
DR GeneID; 6280; -.
DR KEGG; hsa:6280; -.
DR UCSC; uc001fbq.3; human.
DR CTD; 6280; -.
DR GeneCards; GC01P153330; -.
DR HGNC; HGNC:10499; S100A9.
DR HPA; CAB009441; -.
DR HPA; HPA004193; -.
DR MIM; 123886; gene.
DR neXtProt; NX_P06702; -.
DR PharmGKB; PA34911; -.
DR eggNOG; NOG47012; -.
DR HOGENOM; HOG000246968; -.
DR HOVERGEN; HBG001479; -.
DR InParanoid; P06702; -.
DR OMA; HEKMHEN; -.
DR OrthoDB; EOG73807B; -.
DR PhylomeDB; P06702; -.
DR ChiTaRS; S100A9; human.
DR EvolutionaryTrace; P06702; -.
DR GeneWiki; S100A9; -.
DR GenomeRNAi; 6280; -.
DR NextBio; 24377; -.
DR PRO; PR:P06702; -.
DR Bgee; P06702; -.
DR CleanEx; HS_S100A9; -.
DR Genevestigator; P06702; -.
DR GO; GO:0005856; C:cytoskeleton; TAS:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; TAS:UniProtKB.
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; TAS:UniProtKB.
DR GO; GO:0008017; F:microtubule binding; TAS:UniProtKB.
DR GO; GO:0050786; F:RAGE receptor binding; TAS:UniProtKB.
DR GO; GO:0004871; F:signal transducer activity; TAS:ProtInc.
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:0006914; P:autophagy; IDA:UniProtKB.
DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR GO; GO:0032602; P:chemokine production; TAS:UniProtKB.
DR GO; GO:0002544; P:chronic inflammatory response; IEA:Ensembl.
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:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0002523; P:leukocyte migration involved in inflammatory response; IDA:UniProtKB.
DR GO; GO:0070488; P:neutrophil aggregation; IDA:UniProtKB.
DR GO; GO:0030593; P:neutrophil chemotaxis; 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: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:0045471; P:response to ethanol; IEA:Ensembl.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0010043; P:response to zinc ion; IEA:Ensembl.
DR GO; GO:0032119; P:sequestering of zinc ion; TAS:UniProtKB.
DR Gene3D; 1.10.238.10; -; 1.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR028475; S100-A9.
DR InterPro; IPR001751; S100/CaBP-9k_CS.
DR InterPro; IPR013787; S100_Ca-bd_sub.
DR PANTHER; PTHR11639:SF10; PTHR11639:SF10; 1.
DR Pfam; PF01023; S_100; 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;
KW Calcium; Cell membrane; Chemotaxis; Complete proteome; Cytoplasm;
KW Cytoskeleton; Direct protein sequencing; Immunity;
KW Inflammatory response; Innate immunity; Membrane; Metal-binding;
KW Methylation; Phosphoprotein; Polymorphism; Reference proteome; Repeat;
KW Secreted; Zinc.
FT INIT_MET 1 1 Removed (By similarity).
FT CHAIN 2 114 Protein S100-A9.
FT /FTId=PRO_0000143997.
FT DOMAIN 12 47 EF-hand 1.
FT DOMAIN 54 89 EF-hand 2.
FT CA_BIND 23 36 1; low affinity.
FT CA_BIND 67 78 2; high affinity (Probable).
FT METAL 20 20 Zinc (Probable).
FT METAL 30 30 Zinc (Probable).
FT METAL 91 91 Zinc (Probable).
FT METAL 95 95 Zinc (Probable).
FT MOD_RES 2 2 Blocked amino end (Thr).
FT MOD_RES 105 105 Pros-methylhistidine (By similarity).
FT MOD_RES 113 113 Phosphothreonine; by MAPK14.
FT VARIANT 20 20 H -> R.
FT /FTId=VAR_013008.
FT MUTAGEN 36 36 E->Q: Loss of resistance to bacterial
FT invasion; when associated with Q-78.
FT MUTAGEN 63 63 M->A: Loss of antifungal activity.
FT MUTAGEN 78 78 E->Q: Loss of resistance to bacterial
FT invasion; when associated with Q-36.
FT MUTAGEN 81 81 M->A: No effect on antifungal activity.
FT MUTAGEN 83 83 M->A: Loss of antifungal activity.
FT CONFLICT 6 6 S -> H (in Ref. 12; AA sequence).
FT CONFLICT 25 25 K -> F (in Ref. 12; AA sequence).
FT CONFLICT 28 28 H -> L (in Ref. 12; AA sequence).
FT HELIX 7 23
FT STRAND 25 28
FT HELIX 34 44
FT TURN 45 49
FT HELIX 50 53
FT HELIX 56 66
FT STRAND 71 74
FT HELIX 76 94
FT TURN 95 97
SQ SEQUENCE 114 AA; 13242 MW; C3BE19729E14C078 CRC64;
MTCKMSQLER NIETIINTFH QYSVKLGHPD TLNQGEFKEL VRKDLQNFLK KENKNEKVIE
HIMEDLDTNA DKQLSFEEFI MLMARLTWAS HEKMHEGDEG PGHHHKPGLG EGTP
//
MIM
123886
*RECORD*
*FIELD* NO
123886
*FIELD* TI
*123886 S100 CALCIUM-BINDING PROTEIN A9; S100A9
;;CYSTIC FIBROSIS ANTIGEN B;;
CALGRANULIN B; CAGB; CGLB;;
read moreMYELOID-RELATED PROTEIN 14; MRP14
S100A9/S100A8 COMPLEX, INCLUDED;;
CALPROTECTIN, INCLUDED
*FIELD* TX
DESCRIPTION
Calprotectin, the heterodimeric protein complex composed of S100A8
(123885) and S100A9, is a major calcium- and zinc-binding protein in the
cytosol of neutrophils, monocytes, and keratinocytes (Sampson et al.,
2002). Vogl et al. (2007) noted that complexes of S100A8 and S100A9 are
the physiologically relevant forms of these proteins.
CLONING
See 123885 for a description of calgranulin A (CAGA) and calgranulin B
(CAGB), which have molecular weights 11,000 and 14,000, respectively,
and together represent the cystic fibrosis antigen (CFAG). They are
coded by separate genes. Odink et al. (1987) identified and cloned the
calgranulin B gene, CAGB, also known as MRP14.
GENE FUNCTION
By study of DNA from a panel of somatic cell hybrids, van Heyningen et
al. (1989) and Dorin et al. (1990) showed that the CAGB gene
cosegregates with CAGA (S100A8; 123885) in somatic cell hybrids and that
both are closely situated to calcyclin (S100A6; 114110) and calcium
placental protein (S100A4; 114210).
Vogl et al. (2007) demonstrated that mice lacking Mrp8-Mrp14 complexes
are protected from endotoxin-induced lethal shock and Escherichia
coli-induced abdominal sepsis. Both proteins are released during
activation of phagocytes, and Mrp8-Mrp14 complexes amplify the
endotoxin-triggered inflammatory responses of phagocytes. Mrp8 is the
active component that induces intracellular translocation of myeloid
differentiation primary response protein-88 (MYD88; 602170) and
activation of interleukin-1 receptor-associated kinase-1 (IRAK1; 300283)
and nuclear factor-kappa-B (NFKB; see 164011), resulting in elevated
expression of tumor necrosis factor-alpha (TNF-alpha; 191160). Using
phagocytes expressing a nonfunctional Toll-like receptor-4 (TLR4;
603030), HEK293 cells transfected with TLR4, CD14 (158120), and MD2
(LY96; 605243), and by surface plasmon resonance studies in vitro, Vogl
et al. (2007) demonstrated that MRP8 specifically interacts with the
TLR4-MD2 complex, thus representing an endogenous ligand of TLR4. The
data demonstrated that MRP8 is the active component of the complex,
while MRP14 seems to regulate MRP8 function. Vogl et al. (2007)
concluded that MRP8-MRP14 complexes are novel inflammatory components
that amplify phagocyte activation during sepsis upstream of
TNF-alpha-dependent effects.
Corbin et al. (2008) found that neutrophil-derived calprotectin
inhibited growth of Staphylococcus aureus in abscesses through chelation
of Mn(2+) and Zn(2+), an activity that resulted in reprogramming of the
bacterial transcriptome. Abscesses of mice lacking calprotectin had
enhanced levels of metals and increased staphylococcal proliferation.
Corbin et al. (2008) concluded that calprotectin is a critical factor in
the innate immune response to infection and that metal chelation is a
mechanism for inhibiting microbial growth inside abscessed tissue.
Using a mouse model of autoimmunity, Loser et al. (2010) showed that
production of the damage-associated molecular pattern (DAMP) molecules
Mrp8 and Mrp14 was essential for induction of autoreactive Cd8 (see
186910)-positive T cells and development of systemic autoimmunity. FACS
analysis demonstrated that this effect of Mrp8 and Mrp14 was associated
with Tlr4 signaling and increased Il17 (603149) expression.
Immunohistochemical analysis revealed upregulated MRP8 and MRP14
expression in human cutaneous lupus erythematosus (see 152700) lesions,
and MRP8 and MRP14 were detectable in sera from individuals with active
disease. IL17 was upregulated in CD8-positive T cells from individuals
with lupus when stimulated with MRP8 and MRP14, suggesting that MRP8 and
MRP14 have a key role in the development of autoreactive lymphocytes
during autoimmune disease. Loser et al. (2010) concluded that there is a
link between the local expression of DAMP molecules and systemic
autoimmunity.
BIOCHEMICAL FEATURES
Psoriasis (see 177900) is an inflammatory skin disorder characterized by
keratinocyte hyperproliferation and altered differentiation. Linkage
analyses have identified at least 7 distinct disease susceptibility
regions. PSORS4 (603935) maps to chromosome 1q21, within the epidermal
differentiation complex (EDC; see 152445), a cluster that contains 13
genes encoding S100 calcium-binding proteins. Semprini et al. (2002)
analyzed S100 gene expression in psoriatic individuals from 2 large
pedigrees characterized by linkage studies, 1 linked and 1 unlinked to
the 1q21 locus. The analyses demonstrated that only the 1q21-linked
family had upregulation of S100A8, S100A9, and, to a lesser extent,
S100A7 (600353) and S100A12 (603112). Later studies confirmed
S100A8/S100A9-specific overexpression in 1q-linked pedigrees.
Calprotectin, the complex of S100A8 and S100A9, is the major calcium-
and zinc-binding protein of phagocytes. Sampson et al. (2002) reported 5
cases of hypercalprotectinemia (194470), a syndrome characterized by
hyperzincemia associated with excessively high plasma concentrations of
calprotectin. All patients presented with recurrent infections,
hepatosplenomegaly, anemia, and evidence of systemic inflammation; 2
patients were mother and son. Sampson et al. (2002) concluded that there
was probably no primary defect in S100A8 or S100A9, but that the
metabolism of calprotectin was defective.
Zenz et al. (2005) showed that inducible epidermal deletion of JunB
(165161) and its functional companion c-Jun (165160) in adult mice leads
within 2 weeks to a phenotype resembling the histologic and molecular
hallmarks of psoriasis, including arthritic lesions. In contrast to the
skin phenotype, the development of arthritic lesions required T and B
cells and signaling through tumor necrosis factor receptor-1 (TNFR1;
191190). Prior to the disease onset, the chemotactic proteins S100A8 and
S100A9, which map to the psoriasis susceptibility region PSORS4, were
strongly induced in mutant keratinocytes in vivo and in vitro. Zenz et
al. (2005) proposed that the abrogation of JunB/activator protein-1
(AP1) in keratinocytes triggers chemokine/cytokine expression, which
recruits neutrophils and macrophages to the epidermis, thereby
contributing to the phenotypic changes observed in psoriasis. Thus,
their data support the hypothesis that epidermal alterations are
sufficient to initiate both skin lesions and arthritis in psoriasis.
NOMENCLATURE
Schafer et al. (1995) isolated a YAC from 1q21 on which 9 different
genes coding for S100 calcium-binding proteins could be localized. The
clustered organization of S100 genes allowed introduction of a new
logical nomenclature based on their physical arrangement on the
chromosome with S100A1 (176940) being closest to the telomere and S100A9
being closest to the centromere. In the new nomenclature, CAGB became
S100A9.
*FIELD* RF
1. Corbin, B. D.; Seeley, E. H.; Raab, A.; Feldmann, J.; Miller, M.
R.; Torres, V. J.; Anderson, K. L.; Dattilo, B. M.; Dunman, P. M.;
Gerads, R.; Caprioli, R. M.; Nacken, W.; Chazin, W. J.; Skaar, E.
P.: Metal chelation and inhibition of bacterial growth in tissue
abscesses. Science 319: 962-965, 2008.
2. Dorin, J. R.; Emslie, E.; van Heyningen, V.: Related calcium-binding
proteins map to the same subregion of chromosome 1q and to an extended
region of synteny on mouse chromosome 3. Genomics 8: 420-426, 1990.
3. Loser, K.; Vogl, T.; Voskort, M.; Lueken, A.; Kupas, V.; Nacken,
W.; Klenner, L.; Kuhn, A.; Foell, D.; Sorokin, L.; Luger, T. A.; Roth,
J.; Beissert, S.: The Toll-like receptor 4 ligands Mrp8 and Mrp14
are crucial in the development of autoreactive CD8+ T cells. Nature
Med. 16: 713-717, 2010.
4. Odink, K.; Cerletti, N.; Bruggen, J.; Clerc, R. G.; Tarcsay, L.;
Zwadlo, G.; Gerhards, G.; Schlegel, R.; Sorg, C.: Two calcium-binding
proteins in infiltrate macrophages of rheumatoid arthritis. Nature 330:
80-82, 1987.
5. Sampson, B.; Fagerhol, M. K.; Sunderkotter, C.; Golden, B. E.;
Richmond, P.; Klein, N.; Kovar, I. Z.; Beattie, J. H.; Wolska-Kusnierz,
B.; Saito, Y.; Roth, J.: Hyperzincaemia and hypercalprotectinaemia:
a new disorder of zinc metabolism. Lancet 360: 1742-1745, 2002.
6. Schafer, B. W.; Wicki, R.; Engelkamp, D.; Mattei, M.-G.; Heizmann,
C. W.: Isolation of a YAC clone covering a cluster of nine S100 genes
on human chromosome 1q21: rationale for a new nomenclature of the
S100 calcium-binding protein family. Genomics 25: 638-643, 1995.
7. Semprini, S.; Capon, F.; Tacconelli, A.; Giardina, E.; Orecchia,
A.; Mingarelli, R.; Gobello, T.; Zambruno, G.; Botta, A.; Fabrizi,
G.; Novelli, G.: Evidence for differential S100 gene over-expression
in psoriatic patients from genetically heterogeneous pedigrees. Hum.
Genet. 111: 310-313, 2002.
8. van Heyningen, V.; Emslie, E.; Dorin, J. R.: Related calcium binding
proteins map to the same sub-region of chromosome 1q and to an extended
region of synteny on mouse chromosome 3. (Abstract) Cytogenet. Cell
Genet. 51: 1095 only, 1989.
9. Vogl, T.; Tenbrock, K.; Ludwig, S.; Leukert, N.; Ehrhardt, C.;
van Zoelen, M. A. D.; Nacken, W.; Foell, D.; van der Poll, T.; Sorg,
C.; Roth, J.: Mrp8 and Mrp14 are endogenous activators of Toll-like
receptor 4, promoting lethal, endotoxin-induced shock. Nature Med. 13:
1042-1049, 2007.
10. Zenz, R.; Eferl, R.; Kenner, L.; Florin, L.; Hummerich, L.; Mehic,
D.; Scheuch, H.; Angel, P.; Tschachler, E.; Wagner, E. F.: Psoriasis-like
skin disease and arthritis caused by inducible epidermal deletion
of Jun proteins. Nature 437: 369-375, 2005. Note: Erratum: Nature
440: 708 only, 2006.
*FIELD* CN
Paul J. Converse - updated: 7/6/2010
Ada Hamosh - updated: 3/26/2008
Paul J. Converse - updated: 2/29/2008
Ada Hamosh - updated: 11/3/2005
Victor A. McKusick - updated: 1/29/2003
Victor A. McKusick - updated: 11/22/2002
*FIELD* CD
Victor A. McKusick: 11/28/1990
*FIELD* ED
mgross: 07/08/2010
terry: 7/6/2010
mgross: 2/13/2009
alopez: 3/27/2008
terry: 3/26/2008
mgross: 2/29/2008
alopez: 6/5/2006
alopez: 11/4/2005
terry: 11/3/2005
carol: 2/4/2003
tkritzer: 1/29/2003
terry: 1/29/2003
tkritzer: 11/22/2002
mark: 12/21/1996
mark: 6/15/1995
mimadm: 6/25/1994
jason: 6/16/1994
supermim: 3/16/1992
carol: 12/4/1990
carol: 11/28/1990
*RECORD*
*FIELD* NO
123886
*FIELD* TI
*123886 S100 CALCIUM-BINDING PROTEIN A9; S100A9
;;CYSTIC FIBROSIS ANTIGEN B;;
CALGRANULIN B; CAGB; CGLB;;
read moreMYELOID-RELATED PROTEIN 14; MRP14
S100A9/S100A8 COMPLEX, INCLUDED;;
CALPROTECTIN, INCLUDED
*FIELD* TX
DESCRIPTION
Calprotectin, the heterodimeric protein complex composed of S100A8
(123885) and S100A9, is a major calcium- and zinc-binding protein in the
cytosol of neutrophils, monocytes, and keratinocytes (Sampson et al.,
2002). Vogl et al. (2007) noted that complexes of S100A8 and S100A9 are
the physiologically relevant forms of these proteins.
CLONING
See 123885 for a description of calgranulin A (CAGA) and calgranulin B
(CAGB), which have molecular weights 11,000 and 14,000, respectively,
and together represent the cystic fibrosis antigen (CFAG). They are
coded by separate genes. Odink et al. (1987) identified and cloned the
calgranulin B gene, CAGB, also known as MRP14.
GENE FUNCTION
By study of DNA from a panel of somatic cell hybrids, van Heyningen et
al. (1989) and Dorin et al. (1990) showed that the CAGB gene
cosegregates with CAGA (S100A8; 123885) in somatic cell hybrids and that
both are closely situated to calcyclin (S100A6; 114110) and calcium
placental protein (S100A4; 114210).
Vogl et al. (2007) demonstrated that mice lacking Mrp8-Mrp14 complexes
are protected from endotoxin-induced lethal shock and Escherichia
coli-induced abdominal sepsis. Both proteins are released during
activation of phagocytes, and Mrp8-Mrp14 complexes amplify the
endotoxin-triggered inflammatory responses of phagocytes. Mrp8 is the
active component that induces intracellular translocation of myeloid
differentiation primary response protein-88 (MYD88; 602170) and
activation of interleukin-1 receptor-associated kinase-1 (IRAK1; 300283)
and nuclear factor-kappa-B (NFKB; see 164011), resulting in elevated
expression of tumor necrosis factor-alpha (TNF-alpha; 191160). Using
phagocytes expressing a nonfunctional Toll-like receptor-4 (TLR4;
603030), HEK293 cells transfected with TLR4, CD14 (158120), and MD2
(LY96; 605243), and by surface plasmon resonance studies in vitro, Vogl
et al. (2007) demonstrated that MRP8 specifically interacts with the
TLR4-MD2 complex, thus representing an endogenous ligand of TLR4. The
data demonstrated that MRP8 is the active component of the complex,
while MRP14 seems to regulate MRP8 function. Vogl et al. (2007)
concluded that MRP8-MRP14 complexes are novel inflammatory components
that amplify phagocyte activation during sepsis upstream of
TNF-alpha-dependent effects.
Corbin et al. (2008) found that neutrophil-derived calprotectin
inhibited growth of Staphylococcus aureus in abscesses through chelation
of Mn(2+) and Zn(2+), an activity that resulted in reprogramming of the
bacterial transcriptome. Abscesses of mice lacking calprotectin had
enhanced levels of metals and increased staphylococcal proliferation.
Corbin et al. (2008) concluded that calprotectin is a critical factor in
the innate immune response to infection and that metal chelation is a
mechanism for inhibiting microbial growth inside abscessed tissue.
Using a mouse model of autoimmunity, Loser et al. (2010) showed that
production of the damage-associated molecular pattern (DAMP) molecules
Mrp8 and Mrp14 was essential for induction of autoreactive Cd8 (see
186910)-positive T cells and development of systemic autoimmunity. FACS
analysis demonstrated that this effect of Mrp8 and Mrp14 was associated
with Tlr4 signaling and increased Il17 (603149) expression.
Immunohistochemical analysis revealed upregulated MRP8 and MRP14
expression in human cutaneous lupus erythematosus (see 152700) lesions,
and MRP8 and MRP14 were detectable in sera from individuals with active
disease. IL17 was upregulated in CD8-positive T cells from individuals
with lupus when stimulated with MRP8 and MRP14, suggesting that MRP8 and
MRP14 have a key role in the development of autoreactive lymphocytes
during autoimmune disease. Loser et al. (2010) concluded that there is a
link between the local expression of DAMP molecules and systemic
autoimmunity.
BIOCHEMICAL FEATURES
Psoriasis (see 177900) is an inflammatory skin disorder characterized by
keratinocyte hyperproliferation and altered differentiation. Linkage
analyses have identified at least 7 distinct disease susceptibility
regions. PSORS4 (603935) maps to chromosome 1q21, within the epidermal
differentiation complex (EDC; see 152445), a cluster that contains 13
genes encoding S100 calcium-binding proteins. Semprini et al. (2002)
analyzed S100 gene expression in psoriatic individuals from 2 large
pedigrees characterized by linkage studies, 1 linked and 1 unlinked to
the 1q21 locus. The analyses demonstrated that only the 1q21-linked
family had upregulation of S100A8, S100A9, and, to a lesser extent,
S100A7 (600353) and S100A12 (603112). Later studies confirmed
S100A8/S100A9-specific overexpression in 1q-linked pedigrees.
Calprotectin, the complex of S100A8 and S100A9, is the major calcium-
and zinc-binding protein of phagocytes. Sampson et al. (2002) reported 5
cases of hypercalprotectinemia (194470), a syndrome characterized by
hyperzincemia associated with excessively high plasma concentrations of
calprotectin. All patients presented with recurrent infections,
hepatosplenomegaly, anemia, and evidence of systemic inflammation; 2
patients were mother and son. Sampson et al. (2002) concluded that there
was probably no primary defect in S100A8 or S100A9, but that the
metabolism of calprotectin was defective.
Zenz et al. (2005) showed that inducible epidermal deletion of JunB
(165161) and its functional companion c-Jun (165160) in adult mice leads
within 2 weeks to a phenotype resembling the histologic and molecular
hallmarks of psoriasis, including arthritic lesions. In contrast to the
skin phenotype, the development of arthritic lesions required T and B
cells and signaling through tumor necrosis factor receptor-1 (TNFR1;
191190). Prior to the disease onset, the chemotactic proteins S100A8 and
S100A9, which map to the psoriasis susceptibility region PSORS4, were
strongly induced in mutant keratinocytes in vivo and in vitro. Zenz et
al. (2005) proposed that the abrogation of JunB/activator protein-1
(AP1) in keratinocytes triggers chemokine/cytokine expression, which
recruits neutrophils and macrophages to the epidermis, thereby
contributing to the phenotypic changes observed in psoriasis. Thus,
their data support the hypothesis that epidermal alterations are
sufficient to initiate both skin lesions and arthritis in psoriasis.
NOMENCLATURE
Schafer et al. (1995) isolated a YAC from 1q21 on which 9 different
genes coding for S100 calcium-binding proteins could be localized. The
clustered organization of S100 genes allowed introduction of a new
logical nomenclature based on their physical arrangement on the
chromosome with S100A1 (176940) being closest to the telomere and S100A9
being closest to the centromere. In the new nomenclature, CAGB became
S100A9.
*FIELD* RF
1. Corbin, B. D.; Seeley, E. H.; Raab, A.; Feldmann, J.; Miller, M.
R.; Torres, V. J.; Anderson, K. L.; Dattilo, B. M.; Dunman, P. M.;
Gerads, R.; Caprioli, R. M.; Nacken, W.; Chazin, W. J.; Skaar, E.
P.: Metal chelation and inhibition of bacterial growth in tissue
abscesses. Science 319: 962-965, 2008.
2. Dorin, J. R.; Emslie, E.; van Heyningen, V.: Related calcium-binding
proteins map to the same subregion of chromosome 1q and to an extended
region of synteny on mouse chromosome 3. Genomics 8: 420-426, 1990.
3. Loser, K.; Vogl, T.; Voskort, M.; Lueken, A.; Kupas, V.; Nacken,
W.; Klenner, L.; Kuhn, A.; Foell, D.; Sorokin, L.; Luger, T. A.; Roth,
J.; Beissert, S.: The Toll-like receptor 4 ligands Mrp8 and Mrp14
are crucial in the development of autoreactive CD8+ T cells. Nature
Med. 16: 713-717, 2010.
4. Odink, K.; Cerletti, N.; Bruggen, J.; Clerc, R. G.; Tarcsay, L.;
Zwadlo, G.; Gerhards, G.; Schlegel, R.; Sorg, C.: Two calcium-binding
proteins in infiltrate macrophages of rheumatoid arthritis. Nature 330:
80-82, 1987.
5. Sampson, B.; Fagerhol, M. K.; Sunderkotter, C.; Golden, B. E.;
Richmond, P.; Klein, N.; Kovar, I. Z.; Beattie, J. H.; Wolska-Kusnierz,
B.; Saito, Y.; Roth, J.: Hyperzincaemia and hypercalprotectinaemia:
a new disorder of zinc metabolism. Lancet 360: 1742-1745, 2002.
6. Schafer, B. W.; Wicki, R.; Engelkamp, D.; Mattei, M.-G.; Heizmann,
C. W.: Isolation of a YAC clone covering a cluster of nine S100 genes
on human chromosome 1q21: rationale for a new nomenclature of the
S100 calcium-binding protein family. Genomics 25: 638-643, 1995.
7. Semprini, S.; Capon, F.; Tacconelli, A.; Giardina, E.; Orecchia,
A.; Mingarelli, R.; Gobello, T.; Zambruno, G.; Botta, A.; Fabrizi,
G.; Novelli, G.: Evidence for differential S100 gene over-expression
in psoriatic patients from genetically heterogeneous pedigrees. Hum.
Genet. 111: 310-313, 2002.
8. van Heyningen, V.; Emslie, E.; Dorin, J. R.: Related calcium binding
proteins map to the same sub-region of chromosome 1q and to an extended
region of synteny on mouse chromosome 3. (Abstract) Cytogenet. Cell
Genet. 51: 1095 only, 1989.
9. Vogl, T.; Tenbrock, K.; Ludwig, S.; Leukert, N.; Ehrhardt, C.;
van Zoelen, M. A. D.; Nacken, W.; Foell, D.; van der Poll, T.; Sorg,
C.; Roth, J.: Mrp8 and Mrp14 are endogenous activators of Toll-like
receptor 4, promoting lethal, endotoxin-induced shock. Nature Med. 13:
1042-1049, 2007.
10. Zenz, R.; Eferl, R.; Kenner, L.; Florin, L.; Hummerich, L.; Mehic,
D.; Scheuch, H.; Angel, P.; Tschachler, E.; Wagner, E. F.: Psoriasis-like
skin disease and arthritis caused by inducible epidermal deletion
of Jun proteins. Nature 437: 369-375, 2005. Note: Erratum: Nature
440: 708 only, 2006.
*FIELD* CN
Paul J. Converse - updated: 7/6/2010
Ada Hamosh - updated: 3/26/2008
Paul J. Converse - updated: 2/29/2008
Ada Hamosh - updated: 11/3/2005
Victor A. McKusick - updated: 1/29/2003
Victor A. McKusick - updated: 11/22/2002
*FIELD* CD
Victor A. McKusick: 11/28/1990
*FIELD* ED
mgross: 07/08/2010
terry: 7/6/2010
mgross: 2/13/2009
alopez: 3/27/2008
terry: 3/26/2008
mgross: 2/29/2008
alopez: 6/5/2006
alopez: 11/4/2005
terry: 11/3/2005
carol: 2/4/2003
tkritzer: 1/29/2003
terry: 1/29/2003
tkritzer: 11/22/2002
mark: 12/21/1996
mark: 6/15/1995
mimadm: 6/25/1994
jason: 6/16/1994
supermim: 3/16/1992
carol: 12/4/1990
carol: 11/28/1990