Query author contributions in Reactome
Reactome depends on collaboration between our curation team and outside experts to assemble and peer-review its pathway modules. The integration of ORCID within Reactome enables us to meet a key challenge with authoring, curating and reviewing biological information by incentivizing and crediting the external experts that contribute their expertise and time to the Reactome curation process. More information is available at ORCID and Reactome.
If you have an ORCID ID that is not listed on this page, please forward this information to us and we will update your Reactome pathway records.
Details on Person Two members of the S100 protein family, S100A8 (also know as...
| Class:Id | Summation:6799953 |
|---|---|
| _displayName | Two members of the S100 protein family, S100A8 (also know as... |
| _timestamp | 2016-09-21 15:35:29 |
| created | [InstanceEdit:6799952] Shamovsky, Veronica, 2015-09-26 |
| literatureReference | [LiteratureReference:6799914] MRP-8 and MRP-14, two abundant Ca(2+)-binding proteins of neutrophils and monocytes [LiteratureReference:6799862] Interleukin-10 influences the expression of MRP8 and MRP14 in human dendritic cells [LiteratureReference:6799881] Myeloid-related proteins 8 and 14 induce a specific inflammatory response in human microvascular endothelial cells [LiteratureReference:6799887] Platelet expression profiling and clinical validation of myeloid-related protein-14 as a novel determinant of cardiovascular events [LiteratureReference:6799916] S100A8 and S100A9 in human arterial wall. Implications for atherogenesis [LiteratureReference:6799852] Regulation of S100A8 by glucocorticoids [LiteratureReference:6799885] S100 proteins in the epidermis [LiteratureReference:6799929] Alarmins S100A8 and S100A9 elicit a catabolic effect in human osteoarthritic chondrocytes that is dependent on Toll-like receptor 4 [LiteratureReference:6799895] Human calprotectin is an iron-sequestering host-defense protein [LiteratureReference:6798470] High-affinity manganese coordination by human calprotectin is calcium-dependent and requires the histidine-rich site formed at the dimer interface [LiteratureReference:6798486] Manganese binding properties of human calprotectin under conditions of high and low calcium: X-ray crystallographic and advanced electron paramagnetic resonance spectroscopic analysis [LiteratureReference:6798544] Molecular basis for manganese sequestration by calprotectin and roles in the innate immune response to invading bacterial pathogens [LiteratureReference:5432754] The crystal structure of the human (S100A8/S100A9)2 heterotetramer, calprotectin, illustrates how conformational changes of interacting alpha-helices can determine specific association of two EF-hand proteins [LiteratureReference:6799868] Functions of S100 proteins [LiteratureReference:5432752] Mrp8 and Mrp14 are endogenous activators of Toll-like receptor 4, promoting lethal, endotoxin-induced shock [LiteratureReference:6799899] Nutritional Immunity: S100 Proteins at the Host-Pathogen Interface [LiteratureReference:6799878] S100 proteins: structure, functions and pathology [LiteratureReference:6799847] The structure of calcyclin reveals a novel homodimeric fold for S100 Ca(2+)-binding proteins [LiteratureReference:6798498] Zinc-binding site of an S100 protein revealed. Two crystal structures of Ca2+-bound human psoriasin (S100A7) in the Zn2+-loaded and Zn2+-free states [LiteratureReference:6799870] Both Ca2+ and Zn2+ are essential for S100A12 protein oligomerization and function [LiteratureReference:6799939] Nutrient metal sequestration by calprotectin inhibits bacterial superoxide defense, enhancing neutrophil killing of Staphylococcus aureus [LiteratureReference:6799908] Calcium ion gradients modulate the zinc affinity and antibacterial activity of human calprotectin [LiteratureReference:6798433] Calcium-dependent tetramer formation of S100A8 and S100A9 is essential for biological activity [LiteratureReference:6799917] Contributions of the S100A9 C-terminal tail to high-affinity Mn(II) chelation by the host-defense protein human calprotectin |
| modified | [InstanceEdit:8939822] Shamovsky, Veronica, 2016-09-21 |
| text | Two members of the S100 protein family, S100A8 (also know as migration inhibitory factor-related proteins 8 (MRP8)) and S100A9 (MRP14) are calcium-binding regulators of inflammatory processes and immune response. S100A8 & S100A9 are constitutively expressed in neutrophils, myeloid-derived dendritic cells, platelets, osteoclasts and hypertrophic chondrocytes (Hessian PA et al. 1993; Kumar A et al. 2003; Healy AM et al. 2006; Schelbergen RF et al 2012). In contrast, these molecules are induced under inflammatory stimuli in monocytes/macrophages, microvascular endothelial cells, keratinocytes and fibroblasts (Hessian PA et al. 1993; Eckert RL et al. 2004; Viemann D et al. 2005; McCormick MM et al. 2005; Hsu K et al. 2005). S100A8 & S100A9 are known to have diverse functions including antimicrobial activities. During infectious processes S100A8 and S100A9 are delivered to the tissue abscess by recruited neutrophils. S100A8 & S100A9 exist mainly as a S100A8:S100A9 heterodimer which is termed calprotectin based on its role in innate immunity (Korndorfer IP et al. 2007). Calprotectin inhibits bacterial growth through chelation of extracellular manganese Mn(2+), zinc Zn(2+) and possibly iron Fe(2+) and thus restricts metal-ion availability during infection (Damo SM et al. 2013; Brophy MB et al. 2012, 2013; Hayden JA et al. 2013; Gagnon DM et al. 2015; Nakashige TG et al. 2015). Calprotectin exhibited antimicrobial activity for a broad range of Gram-positive and Gram-negative bacterial pathogens including Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus lugdunensis, Enterococcus faecalis, Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli, Shigella flexneri and Acinetobacter baumannii (Damo SM et al. 2013; Kehl-Fie TE et al. 2011; Nakashige TG et al. 2015). Both S100A8 and S100A9 belong to the S100 family of helix-turn-helix (EF-hand) calcium Ca(2+)-binding proteins. S100 proteins are involved in a wide range of cellular functions (Donato R et al. 2013; Zackular JP et al. 2015; Vogl et al. 2007). Within cells, S100 proteins are involved in aspects of regulation of proliferation, differentiation, apoptosis, Ca(2+) homeostasis, inflammation and migration/invasion (Donato R et al. 2013). During infection, certain S100 proteins can be secreted or released by cells to act as damage-associated molecular patterns (DAMPs) and interact with pattern recognition receptors to modulate inflammatory responses (Foell D et al. 2007; Vogl et al. 2007). In addition, these inflammatory S100 proteins have antimicrobial function by sequestering essential transition metals from bacteria, preventing their growth (Zackular JP et al. 2015). The fundamental structural unit of S100 proteins is a highly integrated antiparallel dimer (Potts BC et al. 1995; Heizmann CW et al. 2002; Brodersen DE et al. 1999; Moroz OV et al. 2009; Gagnon DM et al. 2015). All S100 proteins form this structure as homodimers. S100A8 and S100A9 are unique among all members of the S100 family because they preferentially form a heterodimer. Calprotectin (S100A8:S100A9) and other S100 proteins are Ca(2+)-activated regulators (Brophy MB et al. 2012; Donato R et al. 2013). Inside the cell, where the basal level of Ca(2+) is in the nanomolar range, S100 proteins can serve as a sensor of Ca(2+)-mediated signals. In the extracellular milieu, S100 proteins are perpetually (Ca2+)-bound because Ca(2+) concentration is in the millimolar range. Ca(2+) is also known to stimulate formation of higher order oligomers of S100 proteins, including S100A8/S100A9 tetramers (Leukert N et al. 2006; Korndörfer IP et al. 2007). Upon dimerization S100A8 and S100A9 form two metal binding sites at the dimer interface, both of which can bind to Zn(2+) with high affinity (Kd Zn(2+) about 10e-9 M) (Damo SM et al. 2013; Brophy MB et al. 2013). A chelation of Mn(2+) involves a single binding site (Kd Mn(2+) around 10e-7 - 10e-8 M) (Damo SM et al. 2013; Hayden JA et al. 2013; Gagnon DM et al. 2015). Thus, calprotectin S100A8:S100A9 inhibits bacterial growth by targeting transition metals and sequestering these metals in a process referred to as nutritional immunity. |
| (summation) | [Reaction:6798474] S100A8:S100A9 binds Zn2+ [Homo sapiens] |
| [Change default viewing format] | |
