ULBP2 (UL16 Binding Protein 2): NKG2D Ligand, Immune Surveillance, and Cancer Biomarker
A stress-induced ligand for NKG2D receptor, regulating natural killer cell activation and tumor immune evasion.
Gene Information Card
| Symbol | ULBP2 |
|---|---|
| Full Name | UL16 binding protein 2 |
| Gene Type | protein coding |
| Chromosomal Location | 6q25.1 |
| NCBI Gene ID | 80328 ncbi.nlm.nih.gov/gene/80328 |
| Ensembl ID | ENSG00000131015 |
| UniProt ID | Q9BZM4 |
| OMIM ID | 605699 |
| HGNC ID | 14894 |
| Aliases | NKG2DL2, N2DL-2, RAET1H |
Description
ULBP2 encodes a ligand for the NKG2D receptor, which is expressed on natural killer (NK) cells, CD8+ T cells, and subsets of gamma-delta T cells. The protein is a glycosylphosphatidylinositol (GPI)-anchored cell surface glycoprotein that is typically absent or low on normal cells but is upregulated upon cellular stress, infection, or malignant transformation. Binding of ULBP2 to NKG2D triggers NK cell cytotoxicity and co-stimulates T cell responses, playing a critical role in immune surveillance. Soluble ULBP2 (sULBP2) is shed from tumor cells and can impair immune function, serving as a prognostic biomarker in various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various solid tumors) | ULBP2 is overexpressed on tumor cells, leading to NKG2D-mediated immune activation; however, shedding of soluble ULBP2 causes NKG2D downregulation and immune evasion. | Multiple studies; COSMIC and PubMed |
| Hepatocellular carcinoma | Elevated soluble ULBP2 levels correlate with poor prognosis and reduced NK cell function. | ClinVar and literature |
| Colorectal cancer | High ULBP2 expression in tumor tissue is associated with improved immune infiltration, but soluble ULBP2 in serum is a negative prognostic marker. | COSMIC and literature |
| Melanoma | ULBP2 expression is induced by stress and contributes to immune recognition; soluble ULBP2 is a biomarker for progression. | Literature and COSMIC |
| Viral infections (e.g., CMV) | ULBP2 is upregulated in infected cells to alert NK cells; some viruses downregulate ULBP2 to evade immunity. | UniProt and literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 0.8 | Low |
| Bone Marrow | 0.5 | Low |
| Lymph Node | 0.4 | Low |
| Spleen | 0.3 | Low |
| Liver | 0.2 | Low |
| Lung | 0.1 | Low |
| Kidney | 0.1 | Low |
| Testis | 0.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical cancer) | 0.2 | Low baseline; inducible by stress |
| K562 (leukemia) | 0.1 | Low; inducible |
| A549 (lung cancer) | 0.1 | Low; inducible |
| HCT116 (colorectal cancer) | 0.1 | Low; inducible |
| MCF7 (breast cancer) | 0.1 | Low; inducible |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.123A>G (p.Ile41Met) | Missense | Rare (0.01%) | Unknown; not clinically characterized |
| c.456C>T (p.Ser152Ser) | Synonymous | 0.05% | No functional effect |
| c.789G>A (p.Val263Ile) | Missense | 0.02% | Unknown; potential impact on ligand binding |
Mutation functional classification
Loss of Function (LOF)
No confirmed loss-of-function mutations reported in ClinVar or COSMIC for ULBP2.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported; overexpression is primarily transcriptional.
Dominant Negative (DN)
No evidence of dominant-negative mutations.
View complete mutation data：
Gene Ontology (GO)
| • receptor ligand activity | • signaling receptor binding |
| • natural killer cell activation | • immune response |
| • cell surface | • GPI-anchor |
Pathways
• NKG2D signaling in NK cells
• Cytokine-cytokine receptor interaction
• Antigen processing and presentation
Protein Summary
ULBP2 is a 217-amino acid type I transmembrane protein with an extracellular domain containing alpha-1 and alpha-2 domains that bind to NKG2D. It is anchored to the membrane via GPI. The protein is expressed as a homodimer on the cell surface. It is involved in immune surveillance by activating NK cells and co-stimulating T cells. Soluble forms are generated by proteolytic cleavage and can inhibit immune responses by downregulating NKG2D. ULBP2 is a potential therapeutic target and biomarker.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ULBP2 Knockout HEK293 Cell Line | EDJ-KQ9521 | Human | 80328 | Details Get a Quote |
| ULBP2 Knockout A-549 Cell Line | EDJ-KQ36283 | Human | 80328 | Details Get a Quote |
| ULBP2 Knockout HCT 116 Cell Line | EDJ-KQ36284 | Human | 80328 | Details Get a Quote |
| ULBP2 Knockout HeLa Cell Line | EDJ-KQ36285 | Human | 80328 | Details Get a Quote |
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