Biology:S100A12

Short description: Protein-coding gene in the species Homo sapiens

Generic protein structure example

S100 calcium-binding protein A12 (S100A12) is a protein that in humans is encoded by the S100A12 gene. Human S100A12, also known as calgranulin C, was first described in 1995.

The protein encoded by this gene is a member of the S100 family of proteins containing 2 EF-hand calcium-binding motifs.

Function

Generally, S100A12 has a significant anti-infectious and antibacterial role that is related to its ability to uptake ions. For example, it inhibits the spread and virulence of H. pylori.

Tissue distribution

Neutrophils and monocytes / macrophages are important source of S100A12 in the cell although some epithelial cells and dendritic cells are capable of its secretion. Some tissues are rich in these cells, and so in this protein. These include the spleen or lungs. It occurs intracellularly but is also produced into the extracellular environment where it occurs as a homodimer or hexamer.

Clinical significance

Its presence is associated with cardiovascular and kidney diseases. Like other S100 proteins, S100A12 signals through the RAGE receptor and TLR. In general, this signalling leads to cytokine production, chemotaxis and increased oxidative stress. In endothelial cells, this signaling leads to activation of NFκB, under which the production of adhesion molecules such as ICAMs, VCAM or selectins is increased. This protein is proposed to be involved in specific calcium-dependent signal transduction pathways and its regulatory effect on cytoskeletal components may modulate various neutrophil activities.

Cascades that are triggered by interaction of S100A12 with RAGE may play an important role in renal failure in hemodialysis patients. The relationship between S100A12 and renal dialysis mortality rates has been repeatedly reported. S100A12 may play a role in monitoring SLE patients as a marker of kidney damage in glomerulonephritis. It is also associated with gastrointestinal diseases. In inflammatory bowel diseases, it significantly correlates with disease activity and, together with other 100S family proteins, can predict disease relapse.

Further reading

• "Phagocyte-specific S100 proteins: a novel group of proinflammatory molecules". Trends in Immunology 24 (4): 155–8. April 2003. doi:10.1016/S1471-4906(03)00062-0. PMID 12697438. 
• "Identification and characterization of a novel human neutrophil protein related to the S100 family". The Biochemical Journal 309 ( Pt 2) (2): 395–401. July 1995. doi:10.1042/bj3090395. PMID 7626002. 
• "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 (3): 638–43. February 1995. doi:10.1016/0888-7543(95)80005-7. PMID 7759097. 
• "Human CAAF1 gene--molecular cloning, gene structure, and chromosome mapping". Biochemical and Biophysical Research Communications 221 (2): 356–60. April 1996. doi:10.1006/bbrc.1996.0600. PMID 8619860. 
• "Host-parasite interaction in human onchocerciasis: identification and sequence analysis of a novel human calgranulin". Biochemical and Biophysical Research Communications 221 (2): 454–8. April 1996. doi:10.1006/bbrc.1996.0616. PMID 8619876. 
• "Amino acid sequence determination of human S100A12 (P6, calgranulin C, CGRP, CAAF1) by tandem mass spectrometry". Biochemical and Biophysical Research Communications 225 (1): 146–50. August 1996. doi:10.1006/bbrc.1996.1144. PMID 8769108. 
• "RAGE mediates a novel proinflammatory axis: a central cell surface receptor for S100/calgranulin polypeptides". Cell 97 (7): 889–901. June 1999. doi:10.1016/S0092-8674(00)80801-6. PMID 10399917. 
• "Crystallization and preliminary X-ray diffraction analysis of human calcium-binding protein S100A12". Acta Crystallographica. Section D, Biological Crystallography 56 (Pt 2): 189–91. February 2000. doi:10.1107/S0907444999014936. PMID 10666601. Bibcode: 2000AcCrD..56..189M. 
• "The three-dimensional structure of human S100A12". Acta Crystallographica. Section D, Biological Crystallography 57 (Pt 1): 20–9. January 2001. doi:10.1107/S090744490001458X. PMID 11134923. Bibcode: 2001AcCrD..57...20M. 
• "Calcitermin, a novel antimicrobial peptide isolated from human airway secretions". FEBS Letters 504 (1–2): 5–10. August 2001. doi:10.1016/S0014-5793(01)02731-4. PMID 11522286. 
• "The structure of S100A12 in a hexameric form and its proposed role in receptor signalling". Acta Crystallographica. Section D, Biological Crystallography 58 (Pt 3): 407–13. March 2002. doi:10.1107/S0907444901021278. PMID 11856825. Bibcode: 2002AcCrD..58..407M. 
• "Circulating levels of neuropeptides (CGRP, VIP, NPY) in patients with fulminant hepatic failure". Neuropeptides 35 (3–4): 174–80. 2002. doi:10.1054/npep.2001.0861. PMID 11884208. 
• "Calcitonin gene related peptide in familial dysautonomia". Neuropeptides 35 (3–4): 189–95. 2002. doi:10.1054/npep.2001.0863. PMID 11884210. 
• "CacyBP/SIP, a calcyclin and Siah-1-interacting protein, binds EF-hand proteins of the S100 family". The Journal of Biological Chemistry 277 (32): 28848–52. August 2002. doi:10.1074/jbc.M203602200. PMID 12042313. 
• "HIV-1 transcription and virus production are both accentuated by the proinflammatory myeloid-related proteins in human CD4+ T lymphocytes". Journal of Immunology 169 (6): 3307–13. September 2002. doi:10.4049/jimmunol.169.6.3307. PMID 12218151. 
• "S100A12 (EN-RAGE) in monitoring Kawasaki disease". Lancet 361 (9365): 1270–2. April 2003. doi:10.1016/S0140-6736(03)12986-8. PMID 12699958. 
• "Neutrophil derived human S100A12 (EN-RAGE) is strongly expressed during chronic active inflammatory bowel disease". Gut 52 (6): 847–53. June 2003. doi:10.1136/gut.52.6.847. PMID 12740341.