S10AC_HUMAN
ID S10AC_HUMAN Reviewed; 92 AA.
AC P80511; P83219; Q5SY66; Q7M4R1;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 194.
DE RecName: Full=Protein S100-A12;
DE AltName: Full=CGRP;
DE AltName: Full=Calcium-binding protein in amniotic fluid 1;
DE Short=CAAF1;
DE AltName: Full=Calgranulin-C;
DE Short=CAGC;
DE AltName: Full=Extracellular newly identified RAGE-binding protein;
DE Short=EN-RAGE;
DE AltName: Full=Migration inhibitory factor-related protein 6;
DE Short=MRP-6;
DE Short=p6;
DE AltName: Full=Neutrophil S100 protein;
DE AltName: Full=S100 calcium-binding protein A12;
DE Contains:
DE RecName: Full=Calcitermin;
GN Name=S100A12;
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 [GENOMIC DNA / MRNA].
RX PubMed=8619860; DOI=10.1006/bbrc.1996.0600;
RA Yamamura T., Hitomi J., Nagasaki K., Suzuki M., Takahashi E., Saito S.,
RA Tsukada T., Yamaguchi K.;
RT "Human CAAF1 gene -- molecular cloning, gene structure, and chromosome
RT mapping.";
RL Biochem. Biophys. Res. Commun. 221:356-360(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX PubMed=8985590; DOI=10.1016/s0143-4160(96)90087-1;
RA Wicki R., Marenholz I., Mischke D., Schaefer B.W., Heizmann C.W.;
RT "Characterization of the human S100A12 (calgranulin C, p6, CAAF1, CGRP)
RT gene, a new member of the S100 gene cluster on chromosome 1q21.";
RL Cell Calcium 20:459-464(1996).
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Blood;
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 [5]
RP PROTEIN SEQUENCE OF 2-92.
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 [6]
RP PROTEIN SEQUENCE OF 2-92.
RC TISSUE=Neutrophil;
RX PubMed=8769108; DOI=10.1006/bbrc.1996.1144;
RA Ilg E.C., Troxler H., Buergisser D.M., Kuster T., Markert M., Guignard F.,
RA Hunziker P., Birchler N., Heizmann C.W.;
RT "Amino acid sequence determination of human S100A12 (P6, calgranulin C,
RT CGRP, CAAF1) by tandem mass spectrometry.";
RL Biochem. Biophys. Res. Commun. 225:146-150(1996).
RN [7]
RP PROTEIN SEQUENCE OF 2-21.
RX PubMed=7626002; DOI=10.1042/bj3090395;
RA Guignard F., Mauel J., Markert M.;
RT "Identification and characterization of a novel human neutrophil protein
RT related to the S100 family.";
RL Biochem. J. 309:395-401(1995).
RN [8]
RP PROTEIN SEQUENCE OF 2-16.
RX PubMed=1860454; DOI=10.3109/01902149109062865;
RA Singh G., Katyal S.L., Brown W.E., Kennedy A.L., Wong-Chong M.-L.,
RA Gottron S.A.;
RT "Identification, isolation, and partial characterization of a 7.5-kDa
RT surfactant-associated protein.";
RL Exp. Lung Res. 17:559-567(1991).
RN [9]
RP PROTEIN SEQUENCE OF 78-92, FUNCTION AS AN ANTIMICROBIAL PROTEIN, AND MASS
RP SPECTROMETRY.
RC TISSUE=Nasal mucus;
RX PubMed=11522286; DOI=10.1016/s0014-5793(01)02731-4;
RA Cole A.M., Kim Y.-H., Tahk S., Hong T., Weis P., Waring A.J., Ganz T.;
RT "Calcitermin, a novel antimicrobial peptide isolated from human airway
RT secretions.";
RL FEBS Lett. 504:5-10(2001).
RN [10]
RP INTERACTION WITH CACYBP.
RX PubMed=12042313; DOI=10.1074/jbc.m203602200;
RA Filipek A., Jastrzebska B., Nowotny M., Kuznicki J.;
RT "CacyBP/SIP, a calcyclin and Siah-1-interacting protein, binds EF-hand
RT proteins of the S100 family.";
RL J. Biol. Chem. 277:28848-28852(2002).
RN [11]
RP REVIEW.
RX PubMed=12645006; DOI=10.1002/jemt.10300;
RA Moroz O.V., Dodson G.G., Wilson K.S., Lukanidin E., Bronstein I.B.;
RT "Multiple structural states of S100A12: A key to its functional
RT diversity.";
RL Microsc. Res. Tech. 60:581-592(2003).
RN [12]
RP FUNCTION.
RX PubMed=17208591; DOI=10.1016/j.jaci.2006.08.021;
RA Yang Z., Yan W.X., Cai H., Tedla N., Armishaw C., Di Girolamo N.,
RA Wang H.W., Hampartzoumian T., Simpson J.L., Gibson P.G., Hunt J., Hart P.,
RA Hughes J.M., Perry M.A., Alewood P.F., Geczy C.L.;
RT "S100A12 provokes mast cell activation: a potential amplification pathway
RT in asthma and innate immunity.";
RL J. Allergy Clin. Immunol. 119:106-114(2007).
RN [13]
RP FUNCTION, AND DOMAIN HINGE.
RX PubMed=18292089; DOI=10.1074/jbc.m710388200;
RA Yan W.X., Armishaw C., Goyette J., Yang Z., Cai H., Alewood P., Geczy C.L.;
RT "Mast cell and monocyte recruitment by S100A12 and its hinge domain.";
RL J. Biol. Chem. 283:13035-13043(2008).
RN [14]
RP REVIEW.
RX PubMed=18443896; DOI=10.1007/s00726-008-0097-7;
RA Pietzsch J., Hoppmann S.;
RT "Human S100A12: a novel key player in inflammation?";
RL Amino Acids 36:381-389(2009).
RN [15]
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 [16]
RP FUNCTION, SUBUNIT, AND INTERACTION WITH AGER.
RX PubMed=19386136; DOI=10.1186/1471-2091-10-11;
RA Moroz O.V., Burkitt W., Wittkowski H., He W., Ianoul A., Novitskaya V.,
RA Xie J., Polyakova O., Lednev I.K., Shekhtman A., Derrick P.J., Bjoerk P.,
RA Foell D., Bronstein I.B.;
RT "Both Ca2+ and Zn2+ are essential for S100A12 protein oligomerization and
RT function.";
RL BMC Biochem. 10:11-11(2009).
RN [17]
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 [18]
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 [19]
RP REVIEW, AND SUBCELLULAR LOCATION.
RX PubMed=22811950; DOI=10.1155/2012/907078;
RA Meijer B., Gearry R.B., Day A.S.;
RT "The role of S100A12 as a systemic marker of inflammation.";
RL Int. J. Inflamm. 2012:907078-907078(2012).
RN [20]
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 [21] {ECO:0007744|PDB:1E8A}
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) IN COMPLEX WITH CALCIUM.
RX PubMed=11134923; DOI=10.1107/s090744490001458x;
RA Moroz O.V., Antson A.A., Murshudov G.N., Maitland N.J., Dodson G.G.,
RA Wilson K.S., Skibshoj I., Lukanidin E.M., Bronstein I.B.;
RT "The three-dimensional structure of human S100A12.";
RL Acta Crystallogr. D 57:20-29(2001).
RN [22] {ECO:0007744|PDB:1ODB}
RP X-RAY CRYSTALLOGRAPHY (2.19 ANGSTROMS) IN COMPLEX WITH CALCIUM AND COPPER.
RX PubMed=12777802; DOI=10.1107/s0907444903004700;
RA Moroz O.V., Antson A.A., Grist S.J., Maitland N.J., Dodson G.G.,
RA Wilson K.S., Lukanidin E., Bronstein I.B.;
RT "Structure of the human S100A12-copper complex: implications for host-
RT parasite defence.";
RL Acta Crystallogr. D 59:859-867(2003).
RN [23] {ECO:0007744|PDB:2WC8, ECO:0007744|PDB:2WCB, ECO:0007744|PDB:2WCE, ECO:0007744|PDB:2WCF}
RP X-RAY CRYSTALLOGRAPHY (1.88 ANGSTROMS) OF 2-92 IN COMPLEX WITH ZINC.
RX PubMed=19501594; DOI=10.1016/j.jmb.2009.06.004;
RA Moroz O.V., Blagova E.V., Wilkinson A.J., Wilson K.S., Bronstein I.B.;
RT "The crystal structures of human S100A12 in apo form and in complex with
RT zinc: new insights into S100A12 oligomerisation.";
RL J. Mol. Biol. 391:536-551(2009).
CC -!- FUNCTION: S100A12 is a calcium-, zinc- and copper-binding protein which
CC plays a prominent role in the regulation of inflammatory processes and
CC immune response. Its pro-inflammatory activity involves recruitment of
CC leukocytes, promotion of cytokine and chemokine production, and
CC regulation of leukocyte adhesion and migration. Acts as an alarmin or a
CC danger associated molecular pattern (DAMP) molecule and stimulates
CC innate immune cells via binding to receptor for advanced glycation
CC endproducts (AGER). Binding to AGER activates the MAP-kinase and NF-
CC kappa-B signaling pathways leading to production of pro-inflammatory
CC cytokines and up-regulation of cell adhesion molecules ICAM1 and VCAM1.
CC Acts as a monocyte and mast cell chemoattractant. Can stimulate mast
CC cell degranulation and activation which generates chemokines, histamine
CC and cytokines inducing further leukocyte recruitment to the sites of
CC inflammation. Can inhibit the activity of matrix metalloproteinases;
CC MMP2, MMP3 and MMP9 by chelating Zn(2+) from their active sites.
CC Possesses filariacidal and filariastatic activity. Calcitermin
CC possesses antifungal activity against C.albicans and is also active
CC against E.coli and P.aeruginosa but not L.monocytogenes and S.aureus.
CC {ECO:0000269|PubMed:11522286, ECO:0000269|PubMed:17208591,
CC ECO:0000269|PubMed:18292089, ECO:0000269|PubMed:19386136}.
CC -!- SUBUNIT: Homodimer. Homooligomer (tetramer or hexamer) in the presence
CC of calcium, zinc and copper ions. Interacts with AGER and both calcium
CC and zinc are essential for the interaction. Interacts with CACYBP in a
CC calcium-dependent manner. {ECO:0000269|PubMed:12042313,
CC ECO:0000269|PubMed:19386136}.
CC -!- INTERACTION:
CC P80511; Q15109: AGER; NbExp=2; IntAct=EBI-2823305, EBI-1646426;
CC P80511; P80511: S100A12; NbExp=6; IntAct=EBI-2823305, EBI-2823305;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:22811950}. Cytoplasm
CC {ECO:0000269|PubMed:22811950}. Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:22811950}. Cell membrane
CC {ECO:0000269|PubMed:22811950}; Peripheral membrane protein
CC {ECO:0000269|PubMed:22811950}. Note=Predominantly localized in the
CC cytoplasm. Upon elevation of the intracellular calcium level,
CC translocated from the cytoplasm to the cytoskeleton and the cell
CC membrane. Upon neutrophil activation is secreted via a microtubule-
CC mediated, alternative pathway.
CC -!- TISSUE SPECIFICITY: Predominantly expressed by neutrophils, monocytes
CC and activated macrophages. Expressed by eosinophils and macrophages in
CC asthmatic airways in regions where mast cells accumulate. Found in high
CC concentrations in the serum of patients suffering from various
CC inflammatory disorders, such as rheumatoid arthritis, psoriatic
CC arthritis, Crohn's disease, ulcerative colitis, and Kawasaki disease.
CC -!- DOMAIN: The hinge domain contributes significantly to its chemotactic
CC properties. {ECO:0000269|PubMed:18292089}.
CC -!- MASS SPECTROMETRY: [Protein S100-A12]: Mass=10444; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:11522286};
CC -!- MASS SPECTROMETRY: [Calcitermin]: Mass=1688.9; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:11522286};
CC -!- SIMILARITY: Belongs to the S-100 family. {ECO:0000305}.
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DR EMBL; D49549; BAA08497.1; -; mRNA.
DR EMBL; D83657; BAA12030.1; -; Genomic_DNA.
DR EMBL; D83664; BAA12036.1; -; mRNA.
DR EMBL; X97859; CAA66453.1; -; mRNA.
DR EMBL; X98289; CAB94792.1; -; Genomic_DNA.
DR EMBL; X98290; CAB94792.1; JOINED; Genomic_DNA.
DR EMBL; AL591704; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC070294; AAH70294.1; -; mRNA.
DR CCDS; CCDS1037.1; -.
DR PIR; A61522; A61522.
DR PIR; JC4712; JC4712.
DR RefSeq; NP_005612.1; NM_005621.1.
DR PDB; 1E8A; X-ray; 1.95 A; A/B=2-92.
DR PDB; 1GQM; X-ray; 2.70 A; A/B/C/D/E/F/G/H/I/J/K/L=2-92.
DR PDB; 1ODB; X-ray; 2.19 A; A/B/C/D/E/F=2-92.
DR PDB; 2M9G; NMR; -; A/B=1-92.
DR PDB; 2WC8; X-ray; 1.88 A; A/B/C/D=2-92.
DR PDB; 2WCB; X-ray; 1.73 A; A/B=2-92.
DR PDB; 2WCE; X-ray; 1.77 A; A/B=2-92.
DR PDB; 2WCF; X-ray; 2.78 A; A/B/C/D/E/F=2-92.
DR PDBsum; 1E8A; -.
DR PDBsum; 1GQM; -.
DR PDBsum; 1ODB; -.
DR PDBsum; 2M9G; -.
DR PDBsum; 2WC8; -.
DR PDBsum; 2WCB; -.
DR PDBsum; 2WCE; -.
DR PDBsum; 2WCF; -.
DR AlphaFoldDB; P80511; -.
DR BMRB; P80511; -.
DR SMR; P80511; -.
DR BioGRID; 112191; 3.
DR IntAct; P80511; 4.
DR STRING; 9606.ENSP00000357726; -.
DR DrugBank; DB01025; Amlexanox.
DR DrugBank; DB00768; Olopatadine.
DR iPTMnet; P80511; -.
DR PhosphoSitePlus; P80511; -.
DR BioMuta; S100A12; -.
DR DMDM; 2507565; -.
DR CPTAC; non-CPTAC-1154; -.
DR jPOST; P80511; -.
DR MassIVE; P80511; -.
DR PaxDb; P80511; -.
DR PeptideAtlas; P80511; -.
DR PRIDE; P80511; -.
DR ProteomicsDB; 57687; -.
DR TopDownProteomics; P80511; -.
DR Antibodypedia; 1076; 347 antibodies from 30 providers.
DR CPTC; P80511; 1 antibody.
DR DNASU; 6283; -.
DR Ensembl; ENST00000368737.5; ENSP00000357726.3; ENSG00000163221.9.
DR GeneID; 6283; -.
DR KEGG; hsa:6283; -.
DR MANE-Select; ENST00000368737.5; ENSP00000357726.3; NM_005621.2; NP_005612.1.
DR UCSC; uc001fbr.2; human.
DR CTD; 6283; -.
DR DisGeNET; 6283; -.
DR GeneCards; S100A12; -.
DR HGNC; HGNC:10489; S100A12.
DR HPA; ENSG00000163221; Tissue enriched (bone).
DR MIM; 603112; gene.
DR neXtProt; NX_P80511; -.
DR OpenTargets; ENSG00000163221; -.
DR PharmGKB; PA34901; -.
DR VEuPathDB; HostDB:ENSG00000163221; -.
DR eggNOG; ENOG502SA01; Eukaryota.
DR GeneTree; ENSGT00940000162189; -.
DR HOGENOM; CLU_138624_6_2_1; -.
DR InParanoid; P80511; -.
DR OMA; TKLEDHM; -.
DR OrthoDB; 1521098at2759; -.
DR PhylomeDB; P80511; -.
DR TreeFam; TF332727; -.
DR PathwayCommons; P80511; -.
DR Reactome; R-HSA-445989; TAK1-dependent IKK and NF-kappa-B activation.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-879415; Advanced glycosylation endproduct receptor signaling.
DR Reactome; R-HSA-933542; TRAF6 mediated NF-kB activation.
DR SignaLink; P80511; -.
DR BioGRID-ORCS; 6283; 13 hits in 1076 CRISPR screens.
DR EvolutionaryTrace; P80511; -.
DR GeneWiki; S100A12; -.
DR GenomeRNAi; 6283; -.
DR Pharos; P80511; Tbio.
DR PRO; PR:P80511; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P80511; protein.
DR Bgee; ENSG00000163221; Expressed in trabecular bone tissue and 136 other tissues.
DR Genevisible; P80511; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; TAS:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:UniProtKB.
DR GO; GO:0034774; C:secretory granule lumen; TAS:Reactome.
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:0005507; F:copper ion binding; TAS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0050786; F:RAGE receptor binding; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; TAS:UniProtKB.
DR GO; GO:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; IDA:UniProtKB.
DR GO; GO:0042742; P:defense response to bacterium; TAS:UniProtKB.
DR GO; GO:0050832; P:defense response to fungus; IDA:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; TAS:ProtInc.
DR GO; GO:0045087; P:innate immune response; TAS:UniProtKB.
DR GO; GO:0031640; P:killing of cells of another organism; IDA:UniProtKB.
DR GO; GO:0045576; P:mast cell activation; TAS:UniProtKB.
DR GO; GO:0002548; P:monocyte chemotaxis; TAS:UniProtKB.
DR GO; GO:0030593; P:neutrophil chemotaxis; TAS:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IDA:UniProtKB.
DR GO; GO:0050729; P:positive regulation of inflammatory response; TAS:UniProtKB.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; TAS:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; TAS:UniProtKB.
DR GO; GO:0006805; P:xenobiotic metabolic process; IDA:UniProtKB.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR001751; S100/CaBP7/8-like_CS.
DR InterPro; IPR013787; S100_Ca-bd_sub.
DR Pfam; PF01023; S_100; 1.
DR SMART; SM01394; S_100; 1.
DR SUPFAM; SSF47473; SSF47473; 1.
DR PROSITE; PS50222; EF_HAND_2; 1.
DR PROSITE; PS00303; S100_CABP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic; Antimicrobial; Calcium; Cell membrane; Copper;
KW Cytoplasm; Cytoskeleton; Direct protein sequencing; Fungicide; Immunity;
KW Inflammatory response; Innate immunity; Membrane; Metal-binding;
KW Reference proteome; Repeat; Secreted; Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:1860454,
FT ECO:0000269|PubMed:7626002, ECO:0000269|PubMed:8619876,
FT ECO:0000269|PubMed:8769108"
FT CHAIN 2..92
FT /note="Protein S100-A12"
FT /id="PRO_0000045383"
FT PEPTIDE 78..92
FT /note="Calcitermin"
FT /id="PRO_0000004774"
FT DOMAIN 13..48
FT /note="EF-hand 1"
FT /evidence="ECO:0000305"
FT DOMAIN 49..84
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 38..53
FT /note="Hinge domain"
FT BINDING 16
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /evidence="ECO:0000269|PubMed:12777802,
FT ECO:0007744|PDB:1ODB"
FT BINDING 16
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:19501594,
FT ECO:0007744|PDB:2WC8, ECO:0007744|PDB:2WCB"
FT BINDING 19
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /ligand_note="low affinity"
FT /evidence="ECO:0000269|PubMed:11134923,
FT ECO:0000269|PubMed:12777802, ECO:0007744|PDB:1E8A,
FT ECO:0007744|PDB:1ODB"
FT BINDING 22
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /ligand_note="low affinity"
FT /evidence="ECO:0000269|PubMed:11134923,
FT ECO:0000269|PubMed:12777802, ECO:0007744|PDB:1E8A,
FT ECO:0007744|PDB:1ODB"
FT BINDING 24
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /ligand_note="low affinity"
FT /evidence="ECO:0000269|PubMed:11134923,
FT ECO:0000269|PubMed:12777802, ECO:0007744|PDB:1E8A,
FT ECO:0007744|PDB:1ODB"
FT BINDING 26
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /evidence="ECO:0000269|PubMed:12777802,
FT ECO:0007744|PDB:1ODB"
FT BINDING 26
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:19501594,
FT ECO:0007744|PDB:2WC8, ECO:0007744|PDB:2WCB"
FT BINDING 27
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /ligand_note="low affinity"
FT /evidence="ECO:0000269|PubMed:11134923,
FT ECO:0000269|PubMed:12777802, ECO:0007744|PDB:1E8A,
FT ECO:0007744|PDB:1ODB"
FT BINDING 32
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /ligand_note="low affinity"
FT /evidence="ECO:0000269|PubMed:11134923,
FT ECO:0000269|PubMed:12777802, ECO:0007744|PDB:1E8A,
FT ECO:0007744|PDB:1ODB"
FT BINDING 62
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /ligand_note="high affinity"
FT /evidence="ECO:0000269|PubMed:11134923,
FT ECO:0000269|PubMed:12777802, ECO:0007744|PDB:1E8A,
FT ECO:0007744|PDB:1ODB"
FT BINDING 64
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /ligand_note="high affinity"
FT /evidence="ECO:0000269|PubMed:11134923,
FT ECO:0000269|PubMed:12777802, ECO:0007744|PDB:1E8A,
FT ECO:0007744|PDB:1ODB"
FT BINDING 66
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /ligand_note="high affinity"
FT /evidence="ECO:0000269|PubMed:11134923,
FT ECO:0000269|PubMed:12777802, ECO:0007744|PDB:1E8A,
FT ECO:0007744|PDB:1ODB"
FT BINDING 68
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /ligand_note="high affinity"
FT /evidence="ECO:0000269|PubMed:11134923,
FT ECO:0000269|PubMed:12777802, ECO:0007744|PDB:1E8A,
FT ECO:0007744|PDB:1ODB"
FT BINDING 73
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /ligand_note="high affinity"
FT /evidence="ECO:0000269|PubMed:11134923,
FT ECO:0000269|PubMed:12777802, ECO:0007744|PDB:1E8A,
FT ECO:0007744|PDB:1ODB"
FT BINDING 86
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /evidence="ECO:0000269|PubMed:12777802,
FT ECO:0007744|PDB:1ODB"
FT BINDING 86
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:19501594,
FT ECO:0007744|PDB:2WC8, ECO:0007744|PDB:2WCB"
FT BINDING 90
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /evidence="ECO:0000269|PubMed:12777802,
FT ECO:0007744|PDB:1ODB"
FT BINDING 90
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:19501594,
FT ECO:0007744|PDB:2WC8, ECO:0007744|PDB:2WCB"
FT CONFLICT 7
FT /note="H -> V (in Ref. 8; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 12..13
FT /note="VN -> YS (in Ref. 8; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 16
FT /note="H -> F (in Ref. 8; AA sequence)"
FT /evidence="ECO:0000305"
FT HELIX 3..19
FT /evidence="ECO:0007829|PDB:2WCB"
FT STRAND 21..24
FT /evidence="ECO:0007829|PDB:2WCB"
FT STRAND 27..29
FT /evidence="ECO:0007829|PDB:2WCB"
FT HELIX 30..40
FT /evidence="ECO:0007829|PDB:2WCB"
FT HELIX 42..47
FT /evidence="ECO:0007829|PDB:2WCB"
FT HELIX 51..58
FT /evidence="ECO:0007829|PDB:2WCB"
FT STRAND 61..64
FT /evidence="ECO:0007829|PDB:2WCB"
FT STRAND 67..70
FT /evidence="ECO:0007829|PDB:2WCB"
FT HELIX 71..89
FT /evidence="ECO:0007829|PDB:2WCB"
SQ SEQUENCE 92 AA; 10575 MW; 52AF75A31BDC222A CRC64;
MTKLEEHLEG IVNIFHQYSV RKGHFDTLSK GELKQLLTKE LANTIKNIKD KAVIDEIFQG
LDANQDEQVD FQEFISLVAI ALKAAHYHTH KE
