UniProt Accession

 HCST_HUMAN; Q9UBK5; Q9UBS1; Q9Y3Y0 

Genbank Protein ID

 AF172929; AF072844; AF072845; AF122904; AF285447; AY359058; AL050163; BC035931; BC046348; BC065224 

Genbank Nucleotide ID

 AAD50293.1; AAD46986.1; AAD46987.1; AAD47911.1; AAG29425.1; AAQ89417.1; CAB43303.2; AAH35931.1; AAH46348.1; AAH65224.1 

Protein Name

 Hematopoietic cell signal transducer 

Protein Synonyms/Alias

 DNAX-activation protein 10; Membrane protein DAP10; Transmembrane adapter protein KAP10 

Gene Name

 HCST 

Gene Synonyms/Alias

 DAP10; KAP10; PIK3AP; UNQ587/PRO1157 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
84	SPAQEDGKVYINMPG	ubiquitination	[1]

Reference

 [1] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724] 

Functional Description

 Transmembrane adapter protein which associates with NKG2D to form an activation receptor NKG2D-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 NKG2D-DAP10 triggers calcium mobilization and activation of the PIK3R1, MAP2K/ERK, and JAK2/STAT5 signaling pathways. Both PIK3R1 and GRB2 are required for full NKG2D-HCST-mediated activation and ultimate killing of target cells. In NK cells, NKG2D-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. NKG2D-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 NKG2D ligands escape from immune surveillance mediated by NK cells. 

Sequence Annotation

 REGION 86 89 PIK3R1 binding site.
 REGION 86 88 GRB2 binding site.
 MOD_RES 86 86 Phosphotyrosine.  

Keyword

 Alternative splicing; Complete proteome; Disulfide bond; Glycoprotein; Membrane; Phosphoprotein; Reference proteome; Signal; Transmembrane; Transmembrane helix. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 93 AA 

Protein Sequence

Gene Ontology

 GO:0009986; C:cell surface; IDA:UniProtKB.
 GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
 GO:0005886; C:plasma membrane; TAS:Reactome.
 GO:0043548; F:phosphatidylinositol 3-kinase binding; IDA:UniProtKB.
 GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase cascade; IDA:UniProtKB.
 GO:0050776; P:regulation of immune response; TAS:Reactome. 

Interpro

 IPR009861; DAP10. 

Pfam

 PF07213; DAP10 

SMART

  

PROSITE

  

PRINTS