UniProt functional annotation for Q9NP99

UniProt code: Q9NP99.

Organism: Homo sapiens (Human).
Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
 
Function: [Isoform 1]: Cell surface receptor that plays important roles in innate and adaptive immunity by amplifying inflammatory responses (PubMed:10799849, PubMed:21393102). Upon activation by various ligands such as PGLYRP1, HMGB1 or HSP70, multimerizes and forms a complex with transmembrane adapter TYROBP/DAP12 (PubMed:25595774, PubMed:17568691, PubMed:29568119). In turn, initiates a SYK-mediated cascade of tyrosine phosphorylation, activating multiple downstream mediators such as BTK, MAPK1, MAPK3 or phospholipase C-gamma (PubMed:21659545, PubMed:14656437). This cascade promotes the neutrophil- and macrophage- mediated release of proinflammatory cytokines and/or chemokines, as well as their migration and thereby amplifies inflammatory responses that are triggered by bacterial and fungal infections (PubMed:17568691, PubMed:17098818). By also promoting the amplification of inflammatory signals that are initially triggered by Toll-like receptor (TLR) and NOD-like receptor engagement, plays a major role in the pathophysiology of acute and chronic inflammatory diseases of different etiologies including septic shock and atherosclerosis (PubMed:21393102, PubMed:11323674). {ECO:0000269|PubMed:10799849, ECO:0000269|PubMed:11323674, ECO:0000269|PubMed:14656437, ECO:0000269|PubMed:17098818, ECO:0000269|PubMed:17568691, ECO:0000269|PubMed:21393102, ECO:0000269|PubMed:21659545, ECO:0000269|PubMed:25595774, ECO:0000269|PubMed:29568119}.
 
Function: [Isoform 2]: Acts as a decoy receptor, counterbalancing TREM1 proinflammatory activity through the neutralization of its lignad. {ECO:0000269|PubMed:26561551}.
 
Subunit: Monomer (PubMed:29568119). Homomultimer; when activated (PubMed:29568119). Interacts with TYROBP/DAP12 (PubMed:10799849, PubMed:15351648). Interacts with TLR4 (PubMed:17098818, PubMed:21393102). {ECO:0000269|PubMed:10799849, ECO:0000269|PubMed:15351648, ECO:0000269|PubMed:17098818, ECO:0000269|PubMed:21393102, ECO:0000269|PubMed:29568119}.
Subcellular location: [Isoform 1]: Cell membrane {ECO:0000269|PubMed:17098818, ECO:0000269|PubMed:21393102}; Single-pass type I membrane protein {ECO:0000305}. Note=Recruited to lipid rafts when activated. {ECO:0000269|PubMed:17098818}.
Subcellular location: [Isoform 2]: Secreted {ECO:0000269|PubMed:26561551}.
Tissue specificity: Mostly expressed by immune cells of the myeloid lineage, such as monocytes, macrophages, neutrophils and dendritic cells (PubMed:10799849). Expression is associated with a mature stage of myeloid development (PubMed:11922939). Highly expressed in adult liver, lung and spleen than in corresponding fetal tissue. Also expressed in the lymph node, placenta, spinal cord and heart tissues. Isoform 2 was detected in the lung, liver and mature monocytes. {ECO:0000269|PubMed:10799849, ECO:0000269|PubMed:11922939, ECO:0000269|PubMed:21393102}.
Induction: Up-regulated by bacteria, fungi and bacterial lipopolysaccharides (LPS). {ECO:0000269|PubMed:10799849}.
Ptm: Glycosylated. {ECO:0000269|PubMed:10799849}.

Annotations taken from UniProtKB at the EBI.