Protein S100-A12

Details

Name
Protein S100-A12
Kind
protein
Synonyms
  • CAAF1
  • CAGC
  • Calcium-binding protein in amniotic fluid 1
  • Calgranulin-C
  • CGRP
  • EN-RAGE
  • Extracellular newly identified RAGE-binding protein
  • Migration inhibitory factor-related protein 6
  • MRP-6
  • Neutrophil S100 protein
  • p6
  • S100 calcium-binding protein A12
Gene Name
S100A12
UniProtKB Entry
P80511Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0010840|Protein S100-A12
MTKLEEHLEGIVNIFHQYSVRKGHFDTLSKGELKQLLTKELANTIKNIKDKAVIDEIFQG
LDANQDEQVDFQEFISLVAIALKAAHYHTHKE
Number of residues
92
Molecular Weight
10574.975
Theoretical pI
6.23
GO Classification
Functions
calcium ion binding / copper ion binding / RAGE receptor binding / zinc ion binding
Processes
defense response to bacterium / defense response to fungus / inflammatory response / innate immune response / mast cell activation / monocyte chemotaxis / neutrophil chemotaxis / positive regulation of inflammatory response / positive regulation of MAP kinase activity / positive regulation of NF-kappaB transcription factor activity / xenobiotic metabolic process
Components
cytoplasm / cytoskeleton / cytosol / extracellular region / nucleus / plasma membrane
General Function
S100A12 is a calcium-, zinc- and copper-binding protein which plays a prominent role in the regulation of inflammatory processes and immune response. Its pro-inflammatory activity involves recruitment of leukocytes, promotion of cytokine and chemokine production, and regulation of leukocyte adhesion and migration. Acts as an alarmin or a danger associated molecular pattern (DAMP) molecule and stimulates innate immune cells via binding to receptor for advanced glycation endproducts (AGER). Binding to AGER activates the MAP-kinase and NF-kappa-B signaling pathways leading to production of pro-inflammatory cytokines and up-regulation of cell adhesion molecules ICAM1 and VCAM1. Acts as a monocyte and mast cell chemoattractant. Can stimulate mast cell degranulation and activation which generates chemokines, histamine and cytokines inducing further leukocyte recruitment to the sites of inflammation. Can inhibit the activity of matrix metalloproteinases; MMP2, MMP3 and MMP9 by chelating Zn(2+) from their active sites. Possesses filariacidal and filariastatic activity. Calcitermin possesses antifungal activity against C.albicans and is also active against E.coli and P.aeruginosa but not L.monocytogenes and S.aureus
Specific Function
calcium ion binding
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
Not Available
Cellular Location
Secreted
Gene sequence
>lcl|BSEQ0010841|Protein S100-A12 (S100A12)
ATGACAAAACTTGAAGAGCATCTGGAGGGAATTGTCAATATCTTCCACCAATACTCAGTT
CGGAAGGGGCATTTTGACACCCTCTCTAAGGGTGAGCTGAAGCAGCTGCTTACAAAGGAG
CTTGCAAACACCATCAAGAATATCAAAGATAAAGCTGTCATTGATGAAATATTCCAAGGC
CTGGATGCTAATCAAGATGAACAGGTCGACTTTCAAGAATTCATATCCCTGGTAGCCATT
GCGCTGAAGGCTGCCCATTACCACACCCACAAAGAGTAG
Chromosome Location
1
Locus
1q21.3
External Identifiers
ResourceLink
UniProtKB IDP80511
UniProtKB Entry NameS10AC_HUMAN
GenBank Protein ID1545946
GenBank Gene IDX97859
GeneCard IDS100A12
GenAtlas IDS100A12
HGNC IDHGNC:10489
PDB ID(s)1E8A, 1GQM, 1ODB, 2M9G, 2WC8, 2WCB, 2WCE, 2WCF
KEGG IDhsa:6283
NCBI Gene ID6283
General References
  1. Yamamura T, Hitomi J, Nagasaki K, Suzuki M, Takahashi E, Saito S, Tsukada T, Yamaguchi K: Human CAAF1 gene--molecular cloning, gene structure, and chromosome mapping. Biochem Biophys Res Commun. 1996 Apr 16;221(2):356-60. [Article]
  2. Wicki R, Marenholz I, Mischke D, Schafer BW, Heizmann CW: Characterization of the human S100A12 (calgranulin C, p6, CAAF1, CGRP) gene, a new member of the S100 gene cluster on chromosome 1q21. Cell Calcium. 1996 Dec;20(6):459-64. [Article]
  3. Gregory SG, Barlow KF, McLay KE, Kaul R, Swarbreck D, Dunham A, Scott CE, Howe KL, Woodfine K, Spencer CC, Jones MC, Gillson C, Searle S, Zhou Y, Kokocinski F, McDonald L, Evans R, Phillips K, Atkinson A, Cooper R, Jones C, Hall RE, Andrews TD, Lloyd C, Ainscough R, Almeida JP, Ambrose KD, Anderson F, Andrew RW, Ashwell RI, Aubin K, Babbage AK, Bagguley CL, Bailey J, Beasley H, Bethel G, Bird CP, Bray-Allen S, Brown JY, Brown AJ, Buckley D, Burton J, Bye J, Carder C, Chapman JC, Clark SY, Clarke G, Clee C, Cobley V, Collier RE, Corby N, Coville GJ, Davies J, Deadman R, Dunn M, Earthrowl M, Ellington AG, Errington H, Frankish A, Frankland J, French L, Garner P, Garnett J, Gay L, Ghori MR, Gibson R, Gilby LM, Gillett W, Glithero RJ, Grafham DV, Griffiths C, Griffiths-Jones S, Grocock R, Hammond S, Harrison ES, Hart E, Haugen E, Heath PD, Holmes S, Holt K, Howden PJ, Hunt AR, Hunt SE, Hunter G, Isherwood J, James R, Johnson C, Johnson D, Joy A, Kay M, Kershaw JK, Kibukawa M, Kimberley AM, King A, Knights AJ, Lad H, Laird G, Lawlor S, Leongamornlert DA, Lloyd DM, Loveland J, Lovell J, Lush MJ, Lyne R, Martin S, Mashreghi-Mohammadi M, Matthews L, Matthews NS, McLaren S, Milne S, Mistry S, Moore MJ, Nickerson T, O'Dell CN, Oliver K, Palmeiri A, Palmer SA, Parker A, Patel D, Pearce AV, Peck AI, Pelan S, Phelps K, Phillimore BJ, Plumb R, Rajan J, Raymond C, Rouse G, Saenphimmachak C, Sehra HK, Sheridan E, Shownkeen R, Sims S, Skuce CD, Smith M, Steward C, Subramanian S, Sycamore N, Tracey A, Tromans A, Van Helmond Z, Wall M, Wallis JM, White S, Whitehead SL, Wilkinson JE, Willey DL, Williams H, Wilming L, Wray PW, Wu Z, Coulson A, Vaudin M, Sulston JE, Durbin R, Hubbard T, Wooster R, Dunham I, Carter NP, McVean G, Ross MT, Harrow J, Olson MV, Beck S, Rogers J, Bentley DR, Banerjee R, Bryant SP, Burford DC, Burrill WD, Clegg SM, Dhami P, Dovey O, Faulkner LM, Gribble SM, Langford CF, Pandian RD, Porter KM, Prigmore E: The DNA sequence and biological annotation of human chromosome 1. Nature. 2006 May 18;441(7091):315-21. [Article]
  4. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  5. Marti T, Erttmann KD, Gallin MY: Host-parasite interaction in human onchocerciasis: identification and sequence analysis of a novel human calgranulin. Biochem Biophys Res Commun. 1996 Apr 16;221(2):454-8. [Article]
  6. Ilg EC, Troxler H, Burgisser DM, Kuster T, Markert M, Guignard F, Hunziker P, Birchler N, Heizmann CW: Amino acid sequence determination of human S100A12 (P6, calgranulin C, CGRP, CAAF1) by tandem mass spectrometry. Biochem Biophys Res Commun. 1996 Aug 5;225(1):146-50. [Article]
  7. Guignard F, Mauel J, Markert M: Identification and characterization of a novel human neutrophil protein related to the S100 family. Biochem J. 1995 Jul 15;309 ( Pt 2):395-401. [Article]
  8. Singh G, Katyal SL, Brown WE, Kennedy AL, Wong-Chong ML, Gottron SA: Identification, isolation, and partial characterization of a 7.5-kDa surfactant-associated protein. Exp Lung Res. 1991 May-Jun;17(3):559-67. [Article]
  9. Cole AM, Kim YH, Tahk S, Hong T, Weis P, Waring AJ, Ganz T: Calcitermin, a novel antimicrobial peptide isolated from human airway secretions. FEBS Lett. 2001 Aug 24;504(1-2):5-10. [Article]
  10. Filipek A, Jastrzebska B, Nowotny M, Kuznicki J: CacyBP/SIP, a calcyclin and Siah-1-interacting protein, binds EF-hand proteins of the S100 family. J Biol Chem. 2002 Aug 9;277(32):28848-52. Epub 2002 May 31. [Article]
  11. Moroz OV, Dodson GG, Wilson KS, Lukanidin E, Bronstein IB: Multiple structural states of S100A12: A key to its functional diversity. Microsc Res Tech. 2003 Apr 15;60(6):581-92. [Article]
  12. Yang Z, Yan WX, Cai H, Tedla N, Armishaw C, Di Girolamo N, Wang HW, Hampartzoumian T, Simpson JL, Gibson PG, Hunt J, Hart P, Hughes JM, Perry MA, Alewood PF, Geczy CL: S100A12 provokes mast cell activation: a potential amplification pathway in asthma and innate immunity. J Allergy Clin Immunol. 2007 Jan;119(1):106-14. Epub 2006 Oct 6. [Article]
  13. Yan WX, Armishaw C, Goyette J, Yang Z, Cai H, Alewood P, Geczy CL: Mast cell and monocyte recruitment by S100A12 and its hinge domain. J Biol Chem. 2008 May 9;283(19):13035-43. doi: 10.1074/jbc.M710388200. Epub 2008 Feb 21. [Article]
  14. Pietzsch J, Hoppmann S: Human S100A12: a novel key player in inflammation? Amino Acids. 2009 Mar;36(3):381-9. doi: 10.1007/s00726-008-0097-7. Epub 2008 Apr 29. [Article]
  15. Hsu K, Champaiboon C, Guenther BD, Sorenson BS, Khammanivong A, Ross KF, Geczy CL, Herzberg MC: ANTI-INFECTIVE PROTECTIVE PROPERTIES OF S100 CALGRANULINS. Antiinflamm Antiallergy Agents Med Chem. 2009 Dec 4;8(4):290-305. [Article]
  16. Moroz OV, Burkitt W, Wittkowski H, He W, Ianoul A, Novitskaya V, Xie J, Polyakova O, Lednev IK, Shekhtman A, Derrick PJ, Bjoerk P, Foell D, Bronstein IB: Both Ca2+ and Zn2+ are essential for S100A12 protein oligomerization and function. BMC Biochem. 2009 Apr 23;10:11. doi: 10.1186/1471-2091-10-11. [Article]
  17. Perera C, McNeil HP, Geczy CL: S100 Calgranulins in inflammatory arthritis. Immunol Cell Biol. 2010 Jan;88(1):41-9. doi: 10.1038/icb.2009.88. Epub 2009 Nov 24. [Article]
  18. Goyette J, Geczy CL: Inflammation-associated S100 proteins: new mechanisms that regulate function. Amino Acids. 2011 Oct;41(4):821-42. doi: 10.1007/s00726-010-0528-0. Epub 2010 Mar 6. [Article]
  19. Meijer B, Gearry RB, Day AS: The role of S100A12 as a systemic marker of inflammation. Int J Inflam. 2012;2012:907078. doi: 10.1155/2012/907078. Epub 2012 Jul 3. [Article]
  20. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
  21. Moroz OV, Antson AA, Murshudov GN, Maitland NJ, Dodson GG, Wilson KS, Skibshoj I, Lukanidin EM, Bronstein IB: The three-dimensional structure of human S100A12. Acta Crystallogr D Biol Crystallogr. 2001 Jan;57(Pt 1):20-9. [Article]
  22. Moroz OV, Antson AA, Grist SJ, Maitland NJ, Dodson GG, Wilson KS, Lukanidin E, Bronstein IB: Structure of the human S100A12-copper complex: implications for host-parasite defence. Acta Crystallogr D Biol Crystallogr. 2003 May;59(Pt 5):859-67. Epub 2003 Apr 25. [Article]
  23. Moroz OV, Blagova EV, Wilkinson AJ, Wilson KS, Bronstein IB: The crystal structures of human S100A12 in apo form and in complex with zinc: new insights into S100A12 oligomerisation. J Mol Biol. 2009 Aug 21;391(3):536-51. doi: 10.1016/j.jmb.2009.06.004. Epub 2009 Jun 6. [Article]

Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Amlexanoxapproved, investigational, withdrawnunknowntargetantagonistDetails
OlopatadineapprovedunknowntargetantagonistDetails