dbPTM

HCST_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	HCST_HUMAN
UniProt AC	Q9UBK5
Protein Name	Hematopoietic cell signal transducer
Gene Name	HCST
Organism	Homo sapiens (Human).
Sequence Length	93
Subcellular Localization	Membrane Single-pass type I membrane protein .
Protein Description	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..
Protein Sequence	MIHLGHILFLLLLPVAAAQTTPGERSSLPAFYPGTSGSCSGCGSLSLPLLAGLVAADAVASLLIVGAVFLCARPRRSPAQEDGKVYINMPGRG

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference	Orthologous Protein Cluster
84	Ubiquitination	SPAQEDGKVYINMPG CCCCCCCCEEECCCC	44.16	22505724
86	Phosphorylation	AQEDGKVYINMPGRG CCCCCCEEECCCCCC	7.06	28796482

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
Oops, there are no upstream regulatory protein records of HCST_HUMAN !!

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
Oops, there are no descriptions of PTM sites of HCST_HUMAN !!

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of HCST_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference	Domain-Domain Interactions
NKG2D_HUMAN	KLRK1	physical	10426994

Drug and Disease Associations

Kegg Disease
There are no disease associations of PTM sites.
OMIM Disease
There are no disease associations of PTM sites.
Kegg Drug
There are no disease associations of PTM sites.
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of HCST_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"NKG2D-mediated signaling requires a DAP10-bound Grb2-Vav1intermediate and phosphatidylinositol-3-kinase in human natural killercells."; Upshaw J.L., Arneson L.N., Schoon R.A., Dick C.J., Billadeau D.D.,Leibson P.J.; Nat. Immunol. 7:524-532(2006). Cited for: FUNCTION, INTERACTION WITH GRB2-VAV1 AND PIK3R1, PHOSPHORYLATION ATTYR-86, AND MUTAGENESIS OF ASN-88 AND MET-89.	16582911 [Abstract]