InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: S100A12

Summary

InnateDB Protein

IDBP-102651.4

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

S100A12

Protein Name

S100 calcium binding protein A12

Synonyms

CAAF1; CAGC; CGRP; ENRAGE; MRP-6; MRP6; p6;

Species

Homo sapiens

Ensembl Protein

ENSP00000357726

InnateDB Gene

IDBG-102649 (S100A12)

Protein Structure

UniProt Annotation

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 proinflammatory 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 proinflammatory 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. {ECO:0000269PubMed:11522286, ECO:0000269PubMed:17208591, ECO:0000269PubMed:18292089, ECO:0000269PubMed:19386136}.

Subcellular Localization

Secreted {ECO:0000269PubMed:22811950}. Cytoplasm {ECO:0000269PubMed:22811950}. Cytoplasm, cytoskeleton {ECO:0000269PubMed:22811950}. Cell membrane {ECO:0000269PubMed:22811950}; Peripheral membrane protein {ECO:0000269PubMed:22811950}. Note=Predominantly localized in the cytoplasm. Upon elevation of the intracellular calcium level, translocated from the cytoplasm to the cytoskeleton and the cell membrane. Upon neutrophil activation is secreted via a microtubule-mediated, alternative pathway.

Disease Associations

Tissue Specificity

Predominantly expressed by neutrophils, monocytes and activated macrophages. Expressed by eosinophils and macrophages in asthmatic airways in regions where mast cells accumulate. Found in high concentrations in the serum of patients suffering from various inflammatory disorders, such as rheumatoid arthritis, psoriatic arthritis, Crohn's disease, ulcerative colitis, and Kawasaki disease.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 4 experimentally validated interaction(s) in this database.

Experimentally validated
Total	4 [view]
Protein-Protein	4 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005507	copper ion binding
GO:0005509	calcium ion binding
GO:0005515	protein binding
GO:0008270	zinc ion binding
GO:0050786	RAGE receptor binding

Biological Process

GO:0002548	monocyte chemotaxis
GO:0006805	xenobiotic metabolic process
GO:0006954	inflammatory response
GO:0030593	neutrophil chemotaxis
GO:0031640	killing of cells of other organism
GO:0042742	defense response to bacterium
GO:0043123	positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043406	positive regulation of MAP kinase activity
GO:0045087	innate immune response (InnateDB)
GO:0045576	mast cell activation
GO:0050663	cytokine secretion
GO:0050729	positive regulation of inflammatory response
GO:0050832	defense response to fungus
GO:0051092	positive regulation of NF-kappaB transcription factor activity