S100A12

Last updated
S100A12
Protein S100A12 PDB 1e8a.png
Available structures
PDB Human UniProt search: PDBe RCSB
Identifiers
Aliases S100A12 , CAAF1, CAGC, CGRP, ENRAGE, MRP-6, MRP6, p6, S100 calcium binding protein A12, EN-RAGE
External IDs OMIM: 603112; HomoloGene: 48361; GeneCards: S100A12; OMA:S100A12 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_005621

n/a

RefSeq (protein)

NP_005612

n/a

Location (UCSC) Chr 1: 153.37 – 153.38 Mb n/a
PubMed search [2] n/a
Wikidata
View/Edit Human

S100 calcium-binding protein A12 (S100A12) is a protein that in humans is encoded by the S100A12 gene. [3] [4] Human S100A12, also known as calgranulin C, was first described in 1995. [5]

Contents

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 . [6] [7]

Tissue distribution

Neutrophils and monocytes / macrophages are important source of S100A12 in the cell [8] although some epithelial cells and dendritic cells are capable of its secretion. [9] 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. [10]

Clinical significance

Its presence is associated with cardiovascular and kidney diseases. [10] 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. [10] 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. [4]

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. [11] [12] 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. [13] [14]

Related Research Articles

<span class="mw-page-title-main">Interleukin 8</span> Mammalian protein found in humans

Interleukin 8 is a chemokine produced by macrophages and other cell types such as epithelial cells, airway smooth muscle cells and endothelial cells. Endothelial cells store IL-8 in their storage vesicles, the Weibel–Palade bodies. In humans, the interleukin-8 protein is encoded by the CXCL8 gene. IL-8 is initially produced as a precursor peptide of 99 amino acids which then undergoes cleavage to create several active IL-8 isoforms. In culture, a 72 amino acid peptide is the major form secreted by macrophages.

<span class="mw-page-title-main">S100 protein</span> Family of vertebrate proteins involved in cell division and inflammation

The S100 proteins are a family of low molecular-weight proteins found in vertebrates characterized by two calcium-binding sites that have helix-loop-helix ("EF-hand-type") conformation. At least 21 different S100 proteins are known. They are encoded by a family of genes whose symbols use the S100 prefix, for example, S100A1, S100A2, S100A3. They are also considered as damage-associated molecular pattern molecules (DAMPs), and knockdown of aryl hydrocarbon receptor downregulates the expression of S100 proteins in THP-1 cells.

<span class="mw-page-title-main">Calgranulin</span> Protein

Calgranulin is an S100 calcium-binding protein that is expressed in multiple cell types, including renal epithelial cells and neutrophils.

<span class="mw-page-title-main">S100A4</span> Protein-coding gene in the species Homo sapiens

Protein S100-A4 (S100A4) is a protein that in humans is encoded by the S100A4 gene.

<span class="mw-page-title-main">S100A2</span> Protein-coding gene in the species Homo sapiens

S100 calcium-binding protein A2 (S100A2) is a protein that in humans is encoded by the S100A2 gene and it is located on chromosome 1q21 with other S100 proteins.

<span class="mw-page-title-main">S100B</span> Human protein and coding gene

S100 calcium-binding protein B (S100B) is a protein of the S100 protein family.

<span class="mw-page-title-main">S100A8</span> Protein-coding gene in Homo sapiens

S100 calcium-binding protein A8 (S100A8) is a protein that in humans is encoded by the S100A8 gene. It is also known as calgranulin A.

<span class="mw-page-title-main">S100A9</span> Protein-coding gene in the species Homo sapiens

S100 calcium-binding protein A9 (S100A9) also known as migration inhibitory factor-related protein 14 (MRP14) or calgranulin B is a protein that in humans is encoded by the S100A9 gene.

<span class="mw-page-title-main">S100A6</span> Human protein and coding gene

S100 calcium-binding protein A6 (S100A6) is a protein that in humans is encoded by the S100A6 gene.

<span class="mw-page-title-main">S100A11</span> Protein-coding gene in the species Homo sapiens

S100 calcium-binding protein A11 (S100A11) is a protein that in humans is encoded by the S100A11 gene.

<span class="mw-page-title-main">S100P</span> Protein-coding gene in the species Homo sapiens

S100 calcium-binding protein P (S100P) is a protein that in humans is encoded by the S100P gene.

<span class="mw-page-title-main">S100A13</span> Protein-coding gene in the species Homo sapiens

S100 calcium-binding protein A13 (S100A13) is a protein that in humans is encoded by the S100A13 gene.

<span class="mw-page-title-main">S100A3</span> Protein-coding gene in the species Homo sapiens

S100 calcium-binding protein A3 (S100A3) is a protein that in humans is encoded by the S100A3 gene.

<span class="mw-page-title-main">S100A5</span> Protein-coding gene in the species Homo sapiens

S100 calcium-binding protein A5 (S100A5) is a protein that is encoded by the S100A5 gene in humans.

<span class="mw-page-title-main">S100A16</span> Protein-coding gene in the species Homo sapiens

S100 calcium-binding protein A16 (S100A16) is a protein that in humans is encoded by the S100A16 gene.

Calprotectin is a complex of the mammalian proteins S100A8 and S100A9. Other names for calprotectin include MRP8-MRP14, calgranulin A and B, cystic fibrosis antigen, L1, 60BB antigen, and 27E10 antigen. The proteins exist as homodimers but preferentially exist as S100A8/A9 heterodimers or heterotetramers (calprotectin) with antimicrobial, proinflammatory and prothrombotic properties. In the presence of calcium, calprotectin is capable of sequestering the transition metals iron, manganese and zinc via chelation. This metal sequestration affords the complex antimicrobial properties. Calprotectin is the only known antimicrobial manganese sequestration protein complex. Calprotectin comprises as much as 60% of the soluble protein content of the cytosol of a neutrophil, and it is secreted by an unknown mechanism during inflammation. Faecal calprotectin has been used to detect intestinal inflammation and can serve as a biomarker for inflammatory bowel diseases. Blood-based calprotectin is used in diagnostics of multiple inflammatory diseases, including autoimmune diseases, like arthritis, and severe infections including sepsis.

<span class="mw-page-title-main">S100A7A</span> Protein-coding gene in the species Homo sapiens

Protein S100-A7A (S100A7A), also known as koebnerisin, is a protein that in humans is encoded by the S100A7A gene.

<span class="mw-page-title-main">S100A14</span> Protein-coding gene in the species Homo sapiens

S100 calcium binding protein A14 (S100A14) is a protein that in humans is encoded by the S100A14 gene.

The S100 calcium-binding protein mS100a7a15 is the murine ortholog of human S100A7 (Psoriasin) and human S100A15 (Koebnerisin). mS100a7a15 is also known as S100a15, mS100a7 and mS100a7a and is encoded by the mS100a7a gene

The epidermal differentiation complex (EDC) is a gene complex comprising over fifty genes encoding proteins involved in the terminal differentiation and cornification of keratinocytes, the primary cell type of the epidermis. In humans, the complex is located on a 1.9 Mbp stretch within chromosome 1q21. The proteins encoded by EDC genes are closely related in terms of function, and evolutionarily they belong to three distinct gene families: the cornified envelope precursor family, the S100 protein family and the S100 fused type protein (SFTP) family.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000163221 Ensembl, May 2017
  2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. Wicki R, Marenholz I, Mischke D, Schäfer BW, Heizmann CW (December 1996). "Characterization of the human S100A12 (calgranulin C, p6, CAAF1, CGRP) gene, a new member of the S100 gene cluster on chromosome 1q21". Cell Calcium. 20 (6): 459–64. doi:10.1016/S0143-4160(96)90087-1. PMID   8985590.
  4. 1 2 "Entrez Gene: S100A12 S100 calcium binding protein A12".
  5. Wicki R, Marenholz I, Mischke D, Schäfer BW, Heizmann CW (December 1996). "Characterization of the human S100A12 (calgranulin C, p6, CAAF1, CGRP) gene, a new member of the S100 gene cluster on chromosome 1q21". Cell Calcium. 20 (6): 459–64. doi:10.1016/S0143-4160(96)90087-1. PMID   8985590.
  6. Yang Z, Yan WX, Cai H, Tedla N, Armishaw C, Di Girolamo N, et al. (January 2007). "S100A12 provokes mast cell activation: a potential amplification pathway in asthma and innate immunity". The Journal of Allergy and Clinical Immunology. 119 (1): 106–14. doi: 10.1016/j.jaci.2006.08.021 . PMID   17208591.
  7. Li D, Zeng Z, Yu T, Qin J, Wu J, Song JC, et al. (May 2016). "Expression and clinical implication of S100A12 in gastric carcinoma". Tumour Biology. 37 (5): 6551–9. doi:10.1007/s13277-015-4460-5. PMID   26638166. S2CID   25627754.
  8. Khorramdelazad H, Bagheri V, Hassanshahi G, Karami H, Moogooei M, Zeinali M, Abedinzadeh M (2015-04-14). "S100A12 and RAGE expression in human bladder transitional cell carcinoma: a role for the ligand/RAGE axis in tumor progression?". Asian Pacific Journal of Cancer Prevention. 16 (7): 2725–9. doi: 10.7314/APJCP.2015.16.7.2725 . PMID   25854354.
  9. Bagheri V, Hassanshahi G, Zeinali M, Abedinzadeh M, Khorramdelazad H (March 2016). "Elevated levels of S100A12 in the seminal plasma of infertile men with varicocele". International Urology and Nephrology. 48 (3): 343–7. doi:10.1007/s11255-015-1188-5. PMID   26725070. S2CID   21403491.[ permanent dead link ]
  10. 1 2 3 Nazari A, Khorramdelazad H, Hassanshahi G, Day AS, Sardoo AM, Fard ET, et al. (December 2017). "S100A12 in renal and cardiovascular diseases". Life Sciences. 191: 253–258. doi:10.1016/j.lfs.2017.10.036. PMID   29080693. S2CID   25458683.
  11. Shiotsu Y, Mori Y, Nishimura M, Hatta T, Imada N, Maki N, et al. (January 2013). "Prognostic utility of plasma S100A12 levels to establish a novel scoring system for predicting mortality in maintenance hemodialysis patients: a two-year prospective observational study in Japan". BMC Nephrology. 14 (1): 16. doi: 10.1186/1471-2369-14-16 . PMC   3552940 . PMID   23324110.
  12. Tydén H, Lood C, Gullstrand B, Jönsen A, Ivars F, Leanderson T, Bengtsson AA (February 2017). "Pro-inflammatory S100 proteins are associated with glomerulonephritis and anti-dsDNA antibodies in systemic lupus erythematosus". Lupus. 26 (2): 139–149. doi:10.1177/0961203316655208. PMID   27407135. S2CID   4256425.
  13. Foell D, Kucharzik T, Kraft M, Vogl T, Sorg C, Domschke W, Roth J (June 2003). "Neutrophil derived human S100A12 (EN-RAGE) is strongly expressed during chronic active inflammatory bowel disease". Gut. 52 (6): 847–53. doi:10.1136/gut.52.6.847. PMC   1773692 . PMID   12740341.
  14. Wright EK, De Cruz P, Gearry R, Day AS, Kamm MA (September 2014). "Fecal biomarkers in the diagnosis and monitoring of Crohn's disease". Inflammatory Bowel Diseases. 20 (9): 1668–77. doi: 10.1097/MIB.0000000000000087 . PMID   24918319. S2CID   10059250.

Further reading