InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Hcst

Summary

InnateDB Protein

IDBP-168831.6

Last Modified

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

Gene Symbol

Hcst

Protein Name

hematopoietic cell signal transducer

Synonyms

DAP10; KAP10;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000074573

InnateDB Gene

IDBG-168829 (Hcst)

Protein Structure

UniProt Annotation

Function

Transmembrane adapter protein which associates with KLRK1 to form an activation receptor KLRK1-HCST in lymphoid and myeloid cells; this receptor plays a major role in triggering cytotoxicity against target cells expressing cell surface ligands such as MHC class I chain-related MICA and MICB, and UL16-binding proteins (ULBPs); these ligands are up-regulated by stress conditions and pathological state such as viral infection and tumor transformation. Functions as docking site for PI3-kinase PIK3R1 and GRB2. Interaction of ULBPs with KLRK1-HCST triggers calcium mobilization and activation of the PIK3R1, MAP2K/ERK, and JAK2/STAT5 signaling pathways. Both PIK3R1 and GRB2 are required for full KLRK1-HCST-mediated activation and ultimate killing of target cells. In NK cells, KLRK1-HCST signaling directly induces cytotoxicity and enhances cytokine production initiated via DAP12/TYROBP-associated receptors. In T-cells, it provides primarily costimulation for TCR-induced signals. KLRK1-HCST receptor plays a role in immune surveillance against tumors and is required for cytolysis of tumors cells; indeed, melanoma cells that do not express KLRK1 ligands escape from immune surveillance mediated by NK cells. {ECO:0000269PubMed:10528161, ECO:0000269PubMed:12426565, ECO:0000269PubMed:15365099, ECO:0000269PubMed:16086018, ECO:0000269PubMed:16887996, ECO:0000269PubMed:17100879}.

Subcellular Localization

Membrane {ECO:0000269PubMed:17100879}; Single-pass type I membrane protein {ECO:0000269PubMed:17100879}.

Disease Associations

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 9 experimentally validated interaction(s) in this database.
They are also associated with 3 interaction(s) predicted by orthology.