S100A12 Human

S100 Calcium Binding Protein A12 Human Recombinant
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Description

Introduction to S100A12 Human

S100 calcium-binding protein A12 (S100A12), also known as calgranulin C, is a 12 kDa EF-hand calcium-binding protein encoded by the S100A12 gene in humans . First identified in 1995, it is primarily expressed in neutrophils and monocytes/macrophages, with extracellular roles in innate immunity and intracellular regulatory functions . S100A12 acts as a damage-associated molecular pattern (DAMP) molecule, linking cellular stress to inflammatory responses via receptors such as TLR4 and RAGE .

Functional Roles

  1. Calcium-dependent signaling: Modulates cytoskeletal dynamics and neutrophil migration .

  2. Immune activation:

    • Promotes monocyte migration and cytokine production (e.g., TNF-α, IL-6) via TLR4 .

    • Enhances endothelial cell adhesion molecule expression (ICAM-1, VCAM-1) through NF-κB activation .

  3. Antimicrobial activity: Sequesters zinc and copper, limiting pathogen virulence .

Table 1: Disease Associations of S100A12

Disease/ConditionRole of S100A12Key FindingsReferences
SepsisProinflammatory amplifierSerum levels correlate with organ failure (MODS) and mortality .
Inflammatory Bowel Disease (IBD)Biomarker of activityPredicts relapse; correlates with fecal calprotectin .
Papillary Thyroid Cancer (PTC)Oncogenic driverSilencing S100A12 reduces proliferation, migration, and ERK signaling .
Asthma/COPDAirway smooth muscle modulatorOverexpression reduces smooth muscle mass and hyperreactivity in murine models .

Inflammatory Pathways

  • TLR4 activation: S100A12 binds TLR4 on monocytes, inducing chemotaxis and proinflammatory gene expression (e.g., CXCL10, CCL3) .

  • RAGE interaction: Drives oxidative stress and vascular dysfunction in chronic kidney disease .

Oncogenic Role in Cancer

  • PTC: S100A12 upregulation promotes tumor growth by enhancing CyclinD1 and CDK4 expression .

Therapeutic Implications

  • Biomarker potential: Elevated serum S100A12 predicts sepsis severity (AUC = 0.89) and IBD relapse .

  • Targeted inhibition: Blocking TLR4 or RAGE reduces S100A12-driven inflammation in preclinical models .

Product Specs

Introduction
S100A12 is a member of the S100 protein family, which is characterized by the presence of two EF-hand calcium-binding domains. These proteins are typically found within the cytoplasm and/or nucleus of various cells, where they play a role in regulating cellular processes such as cell cycle progression and differentiation. S100A12 is thought to participate in specific calcium-dependent signaling pathways, and its regulatory effects on cytoskeletal components may influence different neutrophil activities.
Description
Recombinant Human S100A12, expressed in E. coli, is a 11.63 kDa protein comprising 101 amino acid residues of the human S100A12 protein with an N-terminal 10-amino acid His tag.
Formulation
S100A12 is provided lyophilized at a concentration of 0.5 mg/ml in a buffer consisting of 20mM Tris and 50mM NaCl, pH 7.5, and has been filtered through a 0.4 μm filter.
Solubility
To prepare a working stock solution, reconstitute the lyophilized S100A12 with deionized water to a concentration of approximately 0.5 mg/ml. Allow the lyophilized pellet to dissolve completely. Please note that this product is not sterile. Before using in cell culture, it is essential to filter the reconstituted protein through an appropriate sterile filter.
Stability
The lyophilized protein should be stored at -20°C. To prevent repeated freeze-thaw cycles, aliquot the reconstituted product. While the reconstituted protein can be stored at 4°C for a short period, it is stable for up to two weeks at this temperature without any noticeable changes.
Synonyms
Extracellular newly identified RAGE-binding protein, Protein S100-A12, CGRP, Calcium-binding protein in amniotic fluid 1, CAAF1, Calgranulin-C, CAGC, EN-RAGE, Neutrophil S100 protein, S100 calcium-binding protein A12, p6, S100A12, MRP6, ENRAGE.
Source
Escherichia Coli.
Amino Acid Sequence
MKHHHHHHAS TKLEEHLEGI VNIFHQYSVR KGHFDTLSKG ELKQLLTKEL ANTIKNIKDK AVIDEIFQGL DANQDEQVDFQEFISLVAIA LKAAHYHTHK E.

Product Science Overview

Introduction

S100 Calcium Binding Protein A12 (S100A12), also known as calgranulin C, is a member of the S100 family of EF-hand calcium-binding proteins. This family comprises at least 21 low molecular weight proteins characterized by the presence of two calcium-binding EF-hand motifs . S100A12 is predominantly expressed in neutrophils and plays a significant role in the inflammatory response .

Structure and Function

S100A12 is organized as a symmetric, anti-parallel homodimer, with each monomer containing a C-terminal EF-hand motif and an N-terminal pseudo EF-hand motif . The C-terminal EF-hand motif has a high affinity for calcium, while the N-terminal pseudo EF-hand motif binds calcium with lower affinity . In addition to calcium, S100A12 also binds zinc and copper, which are essential for its oligomerization and function .

Biological Role

S100A12 is involved in various physiological and pathophysiological processes, including host defense, inflammation, and cell signaling . It is secreted and upregulated during acute and chronic infections, functioning as a proinflammatory alarmin . Upon calcium-dependent activation, S100A12 interacts with target proteins to regulate cellular functions . Extracellularly, it exists as homodimers and hexamers, exhibiting cytokine-like characteristics .

Clinical Significance

Elevated serum levels of S100A12 are found in patients with various inflammatory, neurodegenerative, metabolic, and neoplastic disorders . It interacts with the Receptor for Advanced Glycation End products (RAGE) and its soluble form (sRAGE), playing a central role in the pathogenesis of these conditions . S100A12 has potential as a sensitive and specific diagnostic marker for localized inflammatory processes .

Research and Applications

Research has shown that both calcium and zinc are essential for the oligomerization and target recognition of S100A12 . This protein has been implicated in the regulation of zinc metabolism and the cross-talk between zinc and calcium in cell signaling . Human recombinant S100A12 is used in various research applications to study its role in inflammation and other diseases.

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