InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: HCST

Summary

InnateDB Protein

IDBP-45996.6

Last Modified

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

Gene Symbol

HCST

Protein Name

hematopoietic cell signal transducer

Synonyms

DAP10; KAP10; PIK3AP;

Species

Homo sapiens

Ensembl Protein

ENSP00000246551

InnateDB Gene

IDBG-45994 (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:10426994, ECO:0000269PubMed:10528161, ECO:0000269PubMed:11015446, ECO:0000269PubMed:11777960, ECO:0000269PubMed:12740575, ECO:0000269PubMed:12740576, ECO:0000269PubMed:16002667, ECO:0000269PubMed:16339517, ECO:0000269PubMed:16582911, ECO:0000269PubMed:18097042}.

Subcellular Localization

Membrane {ECO:0000269PubMed:10426994}; Single-pass type I membrane protein {ECO:0000269PubMed:10426994}.

Disease Associations

Tissue Specificity

Predominantly expressed in hemopoietic cells such as NK cells, subset of T-cells and monocytes. Detected in leukocytes, spleen, and thymus. {ECO:0000269PubMed:10528161}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 4 experimentally validated interaction(s) in this database.
They are also associated with 8 interaction(s) predicted by orthology.