ID   S10A8_HUMAN             Reviewed;          93 AA.
AC   P05109; A8K5L3; D3DV37; Q5SY70; Q9UC84; Q9UC92; Q9UCJ0; Q9UCM6;
DT   13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1988, sequence version 1.
DT   29-MAY-2024, entry version 235.
DE   RecName: Full=Protein S100-A8 {ECO:0000305};
DE   AltName: Full=Calgranulin-A;
DE   AltName: Full=Calprotectin L1L subunit;
DE   AltName: Full=Cystic fibrosis antigen;
DE            Short=CFAG;
DE   AltName: Full=Leukocyte L1 complex light chain;
DE   AltName: Full=Migration inhibitory factor-related protein 8;
DE            Short=MRP-8;
DE            Short=p8;
DE   AltName: Full=S100 calcium-binding protein A8;
DE   AltName: Full=Urinary stone protein band A;
GN   Name=S100A8 {ECO:0000312|HGNC:HGNC:10498}; Synonyms=CAGA, CFAG, MRP8;
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].
RX   PubMed=3561500; DOI=10.1038/326614a0;
RA   Dorin J.R., Novak M., Hill R.E., Brock D.J.H., Secher D.S.,
RA   van Heyningen V.;
RT   "A clue to the basic defect in cystic fibrosis from cloning the CF antigen
RT   gene.";
RL   Nature 326:614-617(1987).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
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   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
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   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 1-30.
RX   PubMed=2039599; DOI=10.1515/bchm3.1991.372.1.1;
RA   Schaefer T., Sachse G.E., Gassen H.G.;
RT   "The calcium-binding protein MRP-8 is produced by human pulmonary tumor
RT   cells.";
RL   Biol. Chem. Hoppe-Seyler 372:1-4(1991).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Tongue;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA   Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT   "Cloning of human full open reading frames in Gateway(TM) system entry
RT   vector (pDONR201).";
RL   Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA   Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA   Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA   Phelan M., Farmer A.;
RT   "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL   Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN   [8]
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   [9]
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   [10]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Skeletal muscle;
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   [11]
RP   PROTEIN SEQUENCE OF 1-19; 24-35 AND 63-89.
RX   PubMed=8619876; DOI=10.1006/bbrc.1996.0616;
RA   Marti T., Erttmann K.D., Gallin M.Y.;
RT   "Host-parasite interaction in human onchocerciasis: identification and
RT   sequence analysis of a novel human calgranulin.";
RL   Biochem. Biophys. Res. Commun. 221:454-458(1996).
RN   [12]
RP   PROTEIN SEQUENCE OF 1-27.
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   PROTEIN SEQUENCE OF 1-25.
RC   TISSUE=Neutrophil;
RX   PubMed=1326551; DOI=10.1016/s0021-9258(18)41786-3;
RA   Lemarchand P., Vaglio M., Mauel J., Markert M.;
RT   "Translocation of a small cytosolic calcium-binding protein (MRP-8) to
RT   plasma membrane correlates with human neutrophil activation.";
RL   J. Biol. Chem. 267:19379-19382(1992).
RN   [14]
RP   PROTEIN SEQUENCE OF 1-20.
RX   PubMed=7849642;
RA   Umekawa T., Kurita T.;
RT   "Calprotectin-like protein is related to soluble organic matrix in calcium
RT   oxalate urinary stone.";
RL   Biochem. Mol. Biol. Int. 34:309-313(1994).
RN   [15]
RP   PROTEIN SEQUENCE OF 1-20.
RC   TISSUE=Ascites;
RX   PubMed=7695842;
RA   Nakai M., Ishikawa M., Hamada Y., Sugano S.;
RT   "Isolation of an ascitic oncodevelopmental protein exhibiting high sequence
RT   homology with calcium-binding protein MRP8.";
RL   Biol. Chem. Hoppe-Seyler 375:789-792(1994).
RN   [16]
RP   PROTEIN SEQUENCE OF 38-47 AND 50-56.
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   [17]
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   [18]
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   [19]
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   [20]
RP   FUNCTION, AND INTERACTION WITH TUBULIN.
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   [21]
RP   FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION, AND
RP   TISSUE SPECIFICITY.
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   [22]
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   [23]
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   [24]
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   [25]
RP   S-NITROSYLATION AT CYS-42.
RX   PubMed=18832721; DOI=10.4049/jimmunol.181.8.5627;
RA   Lim S.Y., Raftery M., Cai H., Hsu K., Yan W.X., Hseih H.L., Watts R.N.,
RA   Richardson D., Thomas S., Perry M., Geczy C.L.;
RT   "S-nitrosylated S100A8: novel anti-inflammatory properties.";
RL   J. Immunol. 181:5627-5636(2008).
RN   [26]
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   [27]
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   [28]
RP   FUNCTION, AND MUTAGENESIS OF CYS-42.
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   [29]
RP   FUNCTION, AND SUBUNIT.
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   [30]
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   [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   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   [34]
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   [35]
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   [36]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
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   [37]
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   [38]
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   [39]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA   Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA   Giglione C.;
RT   "Comparative large-scale characterisation of plant vs. mammal proteins
RT   reveals similar and idiosyncratic N-alpha acetylation features.";
RL   Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN   [40]
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   [41]
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   [42]
RP   FUNCTION, INTERACTION WITH GAPDH, AND ASSEMBLY IN THE INOS-S100A8/A9
RP   COMPLEX.
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   [43]
RP   IDENTIFICATION BY 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   [44]
RP   FUNCTION (MICROBIAL INFECTION), INDUCTION BY SARS-COV-2 INFECTION
RP   (MICROBIAL INFECTION), AND TISSUE SPECIFICITY.
RX   PubMed=33388094; DOI=10.1016/j.chom.2020.12.016;
RA   Guo Q., Zhao Y., Li J., Liu J., Yang X., Guo X., Kuang M., Xia H.,
RA   Zhang Z., Cao L., Luo Y., Bao L., Wang X., Wei X., Deng W., Wang N.,
RA   Chen L., Chen J., Zhu H., Gao R., Qin C., Wang X., You F.;
RT   "Induction of alarmin S100A8/A9 mediates activation of aberrant neutrophils
RT   in the pathogenesis of COVID-19.";
RL   Cell Host Microbe 0:0-0(2020).
RN   [45]
RP   X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
RX   PubMed=10771424; DOI=10.1107/s0907444900002833;
RA   Ishikawa K., Nakagawa A., Tanaka I., Suzuki M., Nishihira J.;
RT   "The structure of human MRP8, a member of the S100 calcium-binding protein
RT   family, by MAD phasing at 1.9 A resolution.";
RL   Acta Crystallogr. D 56:559-566(2000).
RN   [46]
RP   X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) IN COMPLEX WITH S100A9, SUBUNIT, AND
RP   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: S100A8 is a calcium- and zinc-binding protein which plays a
CC       prominent role in the regulation of inflammatory processes and immune
CC       response. It can induce neutrophil chemotaxis and adhesion.
CC       Predominantly found as calprotectin (S100A8/A9) which has a wide
CC       plethora of intra- and extracellular functions. The intracellular
CC       functions include: facilitating leukocyte arachidonic acid trafficking
CC       and metabolism, modulation of the tubulin-dependent cytoskeleton during
CC       migration of phagocytes and activation of the neutrophilic NADPH-
CC       oxidase. Activates NADPH-oxidase by facilitating the enzyme complex
CC       assembly at the cell membrane, transferring arachidonic acid, an
CC       essential cofactor, to the enzyme complex and S100A8 contributes to the
CC       enzyme assembly by directly binding to NCF2/P67PHOX. The extracellular
CC       functions involve pro-inflammatory, antimicrobial, oxidant-scavenging
CC       and apoptosis-inducing activities. Its pro-inflammatory activity
CC       includes recruitment of leukocytes, promotion of cytokine and chemokine
CC       production, and regulation of leukocyte adhesion and migration. Acts as
CC       an alarmin or a danger associated molecular pattern (DAMP) molecule and
CC       stimulates innate immune cells via binding to pattern recognition
CC       receptors such as Toll-like receptor 4 (TLR4) and receptor for advanced
CC       glycation endproducts (AGER). Binding to TLR4 and AGER activates the
CC       MAP-kinase and NF-kappa-B signaling pathways resulting in the
CC       amplification of the pro-inflammatory cascade. Has antimicrobial
CC       activity towards bacteria and fungi and exerts its antimicrobial
CC       activity probably via chelation of Zn(2+) which is essential for
CC       microbial growth. Can induce cell death via autophagy and apoptosis and
CC       this occurs through the cross-talk of mitochondria and lysosomes via
CC       reactive oxygen species (ROS) and the process involves BNIP3. Can
CC       regulate 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 a
CC       protective role in preventing exaggerated tissue damage by scavenging
CC       oxidants. Can act as a potent amplifier of inflammation in autoimmunity
CC       as well as in cancer development and tumor spread. The iNOS-S100A8/A9
CC       transnitrosylase complex directs selective inflammatory stimulus-
CC       dependent S-nitrosylation of GAPDH and probably multiple targets such
CC       as ANXA5, EZR, MSN and VIM by recognizing a [IL]-x-C-x-x-[DE] motif;
CC       S100A8 seems to contribute to S-nitrosylation site selectivity.
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:19935772,
CC       ECO:0000269|PubMed:21487906, ECO:0000269|PubMed:22363402,
CC       ECO:0000269|PubMed:22808130, ECO:0000269|PubMed:25417112}.
CC   -!- FUNCTION: (Microbial infection) Upon infection by human coronavirus
CC       SARS-CoV-2, may induce expansion of aberrant immature neutrophils in a
CC       TLR4-dependent manner. {ECO:0000305|PubMed:33388094}.
CC   -!- ACTIVITY REGULATION: Calprotectin (S100A8/A9) activity on TLR4
CC       signaling is inhibited by paquinimod. {ECO:0000250|UniProtKB:P27005}.
CC   -!- SUBUNIT: Homodimer. Preferentially exists as a heterodimer or
CC       heterotetramer with S100A9 known as calprotectin (S100A8/A9). S100A8
CC       interacts with AGER, ATP2A2 and with the heterodimeric complex formed
CC       by TLR4 and LY96 (By similarity). Interacts with GAPDH. Calprotectin
CC       (S100A8/9) interacts with CEACAM3 and tubulin filaments in a calcium-
CC       dependent manner. Heterotetrameric calprotectin (S100A8/A9) interacts
CC       with ANXA6 and associates with tubulin filaments in activated
CC       monocytes. S100A8 and calprotectin (S100A8/9) interact with
CC       NCF2/P67PHOX, RAC1 and RAC2. Calprotectin (S100A8/9) interacts with
CC       CYBA and CYBB. Calprotectin (S100A8/9) interacts with NOS2 to form the
CC       iNOS-S100A8/A9 transnitrosylase complex; induced by LDL(ox)
CC       (PubMed:25417112). {ECO:0000250, ECO:0000269|PubMed:11708798,
CC       ECO:0000269|PubMed:15331440, ECO:0000269|PubMed:15642721,
CC       ECO:0000269|PubMed:16258195, ECO:0000269|PubMed:17553524,
CC       ECO:0000269|PubMed:18786929, ECO:0000269|PubMed:19122197,
CC       ECO:0000269|PubMed:22808130, ECO:0000269|PubMed:25417112,
CC       ECO:0000269|PubMed:9083090}.
CC   -!- INTERACTION:
CC       P05109; P04406: GAPDH; NbExp=6; IntAct=EBI-355281, EBI-354056;
CC       P05109; P06702: S100A9; NbExp=7; IntAct=EBI-355281, EBI-1055001;
CC       P05109; Q8TD43: TRPM4; NbExp=2; IntAct=EBI-355281, EBI-11723041;
CC   -!- SUBCELLULAR LOCATION: Secreted. Cytoplasm. Cytoplasm, cytoskeleton.
CC       Cell membrane; Peripheral membrane protein. Note=Predominantly
CC       localized in the cytoplasm. Upon elevation of the intracellular calcium
CC       level, translocated from the cytoplasm to the cytoskeleton and the cell
CC       membrane. Upon neutrophil activation or endothelial adhesion of
CC       monocytes, is secreted via a microtubule-mediated, alternative pathway.
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:33388094,
CC       ECO:0000269|PubMed:9083090}.
CC   -!- INDUCTION: (Microbial infection) Expression is highly induced in
CC       CD14(+) monocytes, neutrophils, and developing neutrophils of patients
CC       infected by SARS-COV-2. {ECO:0000269|PubMed:33388094}.
CC   -!- MISCELLANEOUS: Binds two calcium ions per molecule with an affinity
CC       similar to that of the S100 proteins.
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/46446/S100A8";
CC   ---------------------------------------------------------------------------
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DR   EMBL; Y00278; CAA68390.1; -; mRNA.
DR   EMBL; X06234; CAA29580.1; -; mRNA.
DR   EMBL; M21005; AAA36327.1; -; Genomic_DNA.
DR   EMBL; AK291328; BAF84017.1; -; mRNA.
DR   EMBL; CR407674; CAG28602.1; -; mRNA.
DR   EMBL; BT007378; AAP36042.1; -; mRNA.
DR   EMBL; AL591704; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471121; EAW53330.1; -; Genomic_DNA.
DR   EMBL; CH471121; EAW53331.1; -; Genomic_DNA.
DR   EMBL; BC005928; AAH05928.1; -; mRNA.
DR   CCDS; CCDS1038.1; -.
DR   PIR; A31848; BCHUCF.
DR   RefSeq; NP_001306126.1; NM_001319197.1.
DR   RefSeq; NP_001306127.1; NM_001319198.1.
DR   RefSeq; NP_001306130.1; NM_001319201.1.
DR   RefSeq; NP_002955.2; NM_002964.4.
DR   PDB; 1MR8; X-ray; 1.90 A; A/B=1-93.
DR   PDB; 1XK4; X-ray; 1.80 A; A/B/E/F/I/J=1-93.
DR   PDB; 4GGF; X-ray; 1.60 A; A/K/S/U=1-93.
DR   PDB; 4XJK; X-ray; 1.76 A; A/C/E/G/I=1-93.
DR   PDB; 5HLO; X-ray; 2.10 A; A/B/C/D=2-93.
DR   PDB; 5HLV; X-ray; 2.20 A; A/B/C/D/E/F/G/H=2-93.
DR   PDB; 5W1F; X-ray; 2.60 A; A/C/E/G=1-93.
DR   PDB; 6DS2; X-ray; 2.10 A; A/C/E/G=1-93.
DR   PDB; 7QUV; X-ray; 1.85 A; A=1-93.
DR   PDBsum; 1MR8; -.
DR   PDBsum; 1XK4; -.
DR   PDBsum; 4GGF; -.
DR   PDBsum; 4XJK; -.
DR   PDBsum; 5HLO; -.
DR   PDBsum; 5HLV; -.
DR   PDBsum; 5W1F; -.
DR   PDBsum; 6DS2; -.
DR   PDBsum; 7QUV; -.
DR   AlphaFoldDB; P05109; -.
DR   SMR; P05109; -.
DR   BioGRID; 112187; 192.
DR   ComplexPortal; CPX-37; Calprotectin heterotetramer.
DR   ComplexPortal; CPX-39; Calprotectin heterodimer.
DR   ComplexPortal; CPX-42; S100A8 complex.
DR   ComplexPortal; CPX-52; iNOS-S100A8/A9 complex.
DR   CORUM; P05109; -.
DR   DIP; DIP-1165N; -.
DR   IntAct; P05109; 74.
DR   MINT; P05109; -.
DR   STRING; 9606.ENSP00000357721; -.
DR   DrugBank; DB01373; Calcium.
DR   DrugBank; DB09130; Copper.
DR   DrugBank; DB01593; Zinc.
DR   DrugBank; DB14487; Zinc acetate.
DR   DrugBank; DB14533; Zinc chloride.
DR   DrugBank; DB14548; Zinc sulfate, unspecified form.
DR   GlyGen; P05109; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; P05109; -.
DR   PhosphoSitePlus; P05109; -.
DR   SwissPalm; P05109; -.
DR   BioMuta; S100A8; -.
DR   DMDM; 115442; -.
DR   EPD; P05109; -.
DR   jPOST; P05109; -.
DR   MassIVE; P05109; -.
DR   MaxQB; P05109; -.
DR   PaxDb; 9606-ENSP00000357722; -.
DR   PeptideAtlas; P05109; -.
DR   PRIDE; P05109; -.
DR   ProteomicsDB; 51795; -.
DR   TopDownProteomics; P05109; -.
DR   ABCD; P05109; 1 sequenced antibody.
DR   Antibodypedia; 3463; 1433 antibodies from 44 providers.
DR   DNASU; 6279; -.
DR   Ensembl; ENST00000368732.5; ENSP00000357721.1; ENSG00000143546.10.
DR   Ensembl; ENST00000368733.4; ENSP00000357722.3; ENSG00000143546.10.
DR   GeneID; 6279; -.
DR   KEGG; hsa:6279; -.
DR   MANE-Select; ENST00000368733.4; ENSP00000357722.3; NM_002964.5; NP_002955.2.
DR   UCSC; uc001fbs.3; human.
DR   AGR; HGNC:10498; -.
DR   CTD; 6279; -.
DR   DisGeNET; 6279; -.
DR   GeneCards; S100A8; -.
DR   HGNC; HGNC:10498; S100A8.
DR   HPA; ENSG00000143546; Tissue enhanced (bone marrow, esophagus, vagina).
DR   MIM; 123885; gene.
DR   neXtProt; NX_P05109; -.
DR   OpenTargets; ENSG00000143546; -.
DR   PharmGKB; PA34910; -.
DR   VEuPathDB; HostDB:ENSG00000143546; -.
DR   eggNOG; ENOG502SA01; Eukaryota.
DR   GeneTree; ENSGT00910000144329; -.
DR   HOGENOM; CLU_138624_6_0_1; -.
DR   InParanoid; P05109; -.
DR   OMA; YHKYSLE; -.
DR   OrthoDB; 5165923at2759; -.
DR   PhylomeDB; P05109; -.
DR   TreeFam; TF332727; -.
DR   PathwayCommons; P05109; -.
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; P05109; -.
DR   SIGNOR; P05109; -.
DR   BioGRID-ORCS; 6279; 7 hits in 1148 CRISPR screens.
DR   ChiTaRS; S100A8; human.
DR   EvolutionaryTrace; P05109; -.
DR   GeneWiki; S100_calcium_binding_protein_A8; -.
DR   GenomeRNAi; 6279; -.
DR   Pharos; P05109; Tbio.
DR   PRO; PR:P05109; -.
DR   Proteomes; UP000005640; Chromosome 1.
DR   RNAct; P05109; Protein.
DR   Bgee; ENSG00000143546; Expressed in pharyngeal mucosa and 185 other cell types or tissues.
DR   GO; GO:1990660; C:calprotectin complex; IPI:ComplexPortal.
DR   GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR   GO; GO:0005856; C:cytoskeleton; TAS:UniProtKB.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
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:0045111; C:intermediate filament cytoskeleton; IDA:HPA.
DR   GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; TAS:UniProtKB.
DR   GO; GO:0034774; C:secretory granule lumen; TAS:Reactome.
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:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR   GO; GO:0014002; P:astrocyte development; IEA:Ensembl.
DR   GO; GO:0035425; P:autocrine signaling; IEA:Ensembl.
DR   GO; GO:0006914; P:autophagy; IDA: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: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:0070488; P:neutrophil aggregation; IDA:UniProtKB.
DR   GO; GO:0030593; P:neutrophil chemotaxis; IDA:UniProtKB.
DR   GO; GO:0002790; P:peptide secretion; IEA:Ensembl.
DR   GO; GO:0018119; P:peptidyl-cysteine S-nitrosylation; IMP: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:0002793; P:positive regulation of peptide secretion; IEA:Ensembl.
DR   GO; GO:0051493; P:regulation of cytoskeleton organization; TAS:UniProtKB.
DR   GO; GO:0034121; P:regulation of toll-like receptor signaling pathway; NAS:ComplexPortal.
DR   GO; GO:0045471; P:response to ethanol; IEA:Ensembl.
DR   GO; GO:0032496; P:response to lipopolysaccharide; IBA:GO_Central.
DR   GO; GO:0010043; P:response to zinc ion; IEA:Ensembl.
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:SF5; PROTEIN S100-A8; 1.
DR   PANTHER; PTHR11639; S100 CALCIUM-BINDING PROTEIN; 1.
DR   Pfam; PF01023; S_100; 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; Apoptosis; Autophagy; Calcium; Cell membrane;
KW   Chemotaxis; Cytoplasm; Cytoskeleton; Direct protein sequencing; Immunity;
KW   Inflammatory response; Innate immunity; Membrane; Metal-binding;
KW   Reference proteome; Repeat; S-nitrosylation; Secreted; Zinc.
FT   CHAIN           1..93
FT                   /note="Protein S100-A8"
FT                   /id="PRO_0000143993"
FT   DOMAIN          12..47
FT                   /note="EF-hand 1"
FT                   /evidence="ECO:0000305"
FT   DOMAIN          46..81
FT                   /note="EF-hand 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   BINDING         17
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000305"
FT   BINDING         27
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000305"
FT   BINDING         33
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /ligand_note="low affinity"
FT                   /evidence="ECO:0000305"
FT   BINDING         59
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   BINDING         61
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   BINDING         63
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   BINDING         70
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   BINDING         83
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000305"
FT   BINDING         87
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000305"
FT   MOD_RES         42
FT                   /note="S-nitrosocysteine"
FT                   /evidence="ECO:0000269|PubMed:18832721"
FT   MUTAGEN         42
FT                   /note="C->A: Loss of antifungal activity."
FT                   /evidence="ECO:0000269|PubMed:19087201"
FT   CONFLICT        80..93
FT                   /note="VAAHKKSHEESHKE -> WQPTKKAMKKATKSS (in Ref. 1;
FT                   CAA68390)"
FT                   /evidence="ECO:0000305"
FT   HELIX           4..20
FT                   /evidence="ECO:0007829|PDB:4GGF"
FT   STRAND          22..25
FT                   /evidence="ECO:0007829|PDB:4GGF"
FT   HELIX           31..41
FT                   /evidence="ECO:0007829|PDB:4GGF"
FT   HELIX           44..47
FT                   /evidence="ECO:0007829|PDB:4GGF"
FT   HELIX           51..58
FT                   /evidence="ECO:0007829|PDB:4GGF"
FT   STRAND          63..66
FT                   /evidence="ECO:0007829|PDB:4GGF"
FT   HELIX           68..86
FT                   /evidence="ECO:0007829|PDB:4GGF"
SQ   SEQUENCE   93 AA;  10835 MW;  78F589140B9CE166 CRC64;
     MLTELEKALN SIIDVYHKYS LIKGNFHAVY RDDLKKLLET ECPQYIRKKG ADVWFKELDI
     NTDGAVNFQE FLILVIKMGV AAHKKSHEES HKE
//