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UL16-binding protein 1 (ULBP1), UL16-binding protein 2 (ULBP2), UL16-binding protein 3 (ULBP3), UL16-binding protein 4 (ULBP4), UL16-binding protein 5 (ULBP5), UL16-binding protein 6 (ULBP6) (ULBP1, ULBP2, ULBP3, ULBP4, ULBP5, ULBP6)

Target
ULBP1, ULBP2, ULBP3, ULBP4, ULBP5, ULBP6
Molecular classification
Stress-induced ligand, Receptor ligand, Cell surface glycoprotein (GPI-anchored for ULBP1), MHC class I-related protein
01

Overview

UL16-binding proteins 1 through 6 are a family of human cell surface glycoproteins structurally related to MHC class I molecules but distinct in lacking the α3 domain and transmembrane segments (ULBP1 is GPI-anchored). They function as stress-induced ligands for the NKG2D receptor on cytotoxic lymphocytes, triggering immune responses against infected, malignant, or otherwise stressed cells. Their expression is often upregulated during viral infection or cellular transformation; viruses such as HCMV may target these ligands to evade immune surveillance, for example via interaction with the viral UL16 glycoprotein to prevent their surface localization. The clinical relevance of these molecules spans cancer prognosis, immune system modulation, and potentially therapeutic targeting or biomarker identification for immune-related diseases.

Other names
NKG2D ligand familyRAET1 familyretinoic acid early transcript 1 family (RAET1E/ULBP4, RAET1L/ULBP6, etc.)
02

Mechanism of action

Stimulate cytotoxicity by binding to and activating the NKG2D receptor on natural killer cells, CD8+ T cells, and γδ T cells. Promote immune recognition and clearance of stressed, infected, or transformed cells

03

Biological functions

Immune response (activation of natural killer cell and T cell cytotoxicity via NKG2D receptor)Cell signalingModulation of immune cell infiltration in tumorsInterference with immune evasion during viral infection (e.g., HCMV)
04

Disease associations

Cancer (prognostic marker; role in immune surveillance and tumor escape mechanisms)Infection (upregulated in cells infected by certain viruses such as HCMV)Other (osteoblast differentiation regulation)
05

Safety considerations

Possible immune-related toxicity in therapies modulating NKG2D signaling (e.g., cytokine release; off-target immune activation)Tumor immune escape via downregulation or sequestration of ULBPs
06

Biomarkers

ULBP1 expression level (prognostic marker in cancers including gastric and breast cancer)NKG2D receptor expression in immune cell populations

Beyond the preview

Go deeper on UL16-binding protein 1 (ULBP1), UL16-binding protein 2 (ULBP2), UL16-binding protein 3 (ULBP3), UL16-binding protein 4 (ULBP4), UL16-binding protein 5 (ULBP5), UL16-binding protein 6 (ULBP6) (ULBP1, ULBP2, ULBP3, ULBP4, ULBP5, ULBP6).

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