ULBP2

Summary

ULBP2 (UL16 binding protein 2, HGNC:14894) is a protein-coding gene on chromosome 6q25.1, encoding UL16-binding protein 2 (Q9BZM5). Binds and activates the KLRK1/NKG2D receptor, mediating natural killer cell cytotoxicity.

This gene encodes a major histocompatibility complex (MHC) class I-related molecule that binds to the NKG2D receptor on natural killer (NK) cells to trigger release of multiple cytokines and chemokines that in turn contribute to the recruitment and activation of NK cells. The encoded protein undergoes further processing to generate the mature protein that is either anchored to membrane via a glycosylphosphatidylinositol moiety, or secreted. Many malignant cells secrete the encoded protein to evade immunosurveillance by NK cells. This gene is located in a cluster of multiple MHC class I-related genes on chromosome 6.

Source: NCBI Gene 80328 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 59 total
• MANE Select transcript: NM_025217

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14894
Approved symbol	ULBP2
Name	UL16 binding protein 2
Location	6q25.1
Locus type	gene with protein product
Status	Approved
Aliases	RAET1H
Ensembl gene	ENSG00000131015
Ensembl biotype	protein_coding
OMIM	605698
Entrez	80328

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000367351, ENST00000948867

RefSeq mRNA: 1 — MANE Select: NM_025217 NM_025217

CCDS: CCDS5222

Canonical transcript exons

ENST00000367351 — 5 exons

Exon	Start	End
ENSE00001444298	149948723	149949235
ENSE00001444315	149942014	149942157
ENSE00002500196	149947320	149947451
ENSE00002503659	149946372	149946653
ENSE00002513723	149945309	149945572

Expression profiles

Bgee: expression breadth ubiquitous, 183 present calls, max score 89.12.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.5301 / max 188.4355, expressed in 1277 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
70503	5.9931	1232
70502	0.2701	118
70501	0.2669	115

Top tissues by expression

272 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
esophagus squamous epithelium	UBERON:0006920	89.12	gold quality
epithelium of esophagus	UBERON:0001976	89.07	gold quality
gingival epithelium	UBERON:0001949	89.01	gold quality
gingiva	UBERON:0001828	88.87	gold quality
pharyngeal mucosa	UBERON:0000355	87.76	gold quality
oral cavity	UBERON:0000167	86.29	gold quality
buccal mucosa cell	CL:0002336	85.86	silver quality
cartilage tissue	UBERON:0002418	85.39	gold quality
squamous epithelium	UBERON:0006914	83.84	gold quality
stromal cell of endometrium	CL:0002255	78.97	gold quality
cortical plate	UBERON:0005343	74.90	gold quality
sperm	CL:0000019	74.85	silver quality
amniotic fluid	UBERON:0000173	74.50	gold quality
esophagus mucosa	UBERON:0002469	73.95	gold quality
cervix epithelium	UBERON:0004801	73.73	silver quality
right lung	UBERON:0002167	73.03	gold quality
male germ cell	CL:0000015	72.85	silver quality
middle temporal gyrus	UBERON:0002771	71.36	gold quality
body of tongue	UBERON:0011876	71.01	silver quality
Brodmann (1909) area 23	UBERON:0013554	70.50	gold quality
upper lobe of left lung	UBERON:0008952	70.41	gold quality
upper lobe of lung	UBERON:0008948	69.47	gold quality
islet of Langerhans	UBERON:0000006	68.86	gold quality
lower esophagus mucosa	UBERON:0035834	68.14	gold quality
cerebellar cortex	UBERON:0002129	67.59	gold quality
cerebellar hemisphere	UBERON:0002245	67.59	gold quality
right hemisphere of cerebellum	UBERON:0014890	66.96	gold quality
cerebellum	UBERON:0002037	66.63	gold quality
tongue	UBERON:0001723	66.55	silver quality
tendon of biceps brachii	UBERON:0008188	66.26	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.09

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

35 targeting ULBP2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-888-3P	99.53	69.77	1057
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-133A-5P	99.28	69.13	941
HSA-MIR-1253	99.12	67.08	1688
HSA-MIR-382-3P	98.83	67.10	1074
HSA-MIR-2355-5P	98.83	65.51	1589
HSA-MIR-4490	98.51	68.47	943
HSA-MIR-6529-5P	97.85	66.47	673
HSA-MIR-556-5P	97.75	66.17	473
HSA-MIR-4680-5P	96.43	67.15	893

Literature-anchored findings (GeneRIF, showing 40)

• ULBP2 binds to the NKG2D receptor and activates multiple signaling pathways in primary natural killer cells. (PMID:11777960)
• Human cytomegalovirus induces the expression of ULBP2, which is predominantly localized in the endoplasmic reticulum of infected fibroblasts together with viral protein UL16. (PMID:12847260)
• ULBPs and MICA are expressed in lipid rafts at the cell surface of NK and T cells. (PMID:15051759)
• These findings identify NKG2D ligands as targets of leukemia differentiation therapy (PMID:17391757)
• IL-18 treatment increased ULBP2 expression in leukemia cells at the mRNA and protein levels (PMID:18706445)
• ULBP2 was seen on 82.9% of ovarian cancer cells but not on normal ovarian epithelium. Strong expression of ULBP2 in these cells correlated with less intraepithelial infiltration of T cells & may relate to T cell dysfunction in the tumor microenvironment. (PMID:18791713)
• IFN-gamma, by down-regulating ligand expression, might facilitate escape of MHC class I-negative melanoma cells from NKG2D-mediated killing by NK cells. (PMID:19089914)
• administration of ATRA or sodium valproate to patients affected with acute myeloid leukaemia M3 or M1 respectively, leads to the induction of transcription and expression of NKG2D-L at the surface of leukaemic cells. (PMID:19151770)
• RAET1G, like ULBP2, appears broadly expressed, but exhibits a lower apparent avidity for NKG2D due to a mutation in the center of the MHC-like fold. (PMID:19424970)
• Data show upon HSV-1 infection of cell lines, surface levels of NKG2D ligands MICA antigen and UL16 binding protein 2 were downmodulated due to late viral ICP0 gene product(s). (PMID:19508374)
• Only sULBP2 is an independent predictor of prognosis, the significance of which is superior to the well-established and widely used melanoma serum marker S100B. (PMID:19671853)
• Vpr specifically induces surface expression of the unique-long 16 binding proteins (ULBP)-1 and ULBP-2, but not ULBP-3 (PMID:19798433)
• it was shown that high expression of several NKG2D ligands is inversely correlated with ovarian cancer survival (PMID:20054857)
• Levels of soluble ULBP2 were significantly increased in B-cell chronic lymphocytic leukemia. (PMID:20428196)
• The human NKG2D ligand ULBP2 can be expressed at the cell surface with or without a GPI anchor and both forms can activate NK cells (PMID:21224393)
• Data show that IL-32alpha stimulates Fas and ULBP2 expression via activation of p38 MAPK, which increases NK susceptibility of chronic myeloid leukemia cells. (PMID:21321117)
• analysis of the area under receiver operating characteristic curves showed that ULBP2 was superior to CA 19-9 in discriminating patients with early-stage PC from healthy controls (PMID:21625447)
• Findings define the involvement of p53 in the regulation of ULBP1 and ULBP2 which enhance NK cell-mediated target recognition. (PMID:21764762)
• Data show that VSV infection caused an active suppression of NKG2D-ligand surface expression, affecting both endogenous and histone deacetylase (HDAC)-inhibitor induced MICA, MICB and ULBP-2 expression. (PMID:21857986)
• Study shows that tumor-suppressive miR-34a and miR-34c act as ULBP2 repressors. Findings also implicate p53 in ULBP2 regulation, emphasizing the role of the specific NKG2DL in tumor immune surveillance. (PMID:22102694)
• Vpr augments ULBP2 expression on both infected and uninfected bystander cells during HIV-1 infection of primary CD4+ T lymphocytes. (PMID:23726848)
• human tumor cells lost their surface expression of ULBP2, but not ULBP1 and ULBP3, during NK cell-mediated cytolysis. (PMID:24614922)
• This study provides for the first time, the c-Myc dependent regulation of NKG2D ligands, ULBP1/2/3 in acute myeloid leukemia. (PMID:24677544)
• Results suggest that ULBP2 is expressed and released from cervical cancer cells by CRF, which regulates NKG2D expression in natural killer cells. (PMID:24841552)
• c-Cbl regulates MICA- but not ULBP2-induced NKG2D down-modulation in human NK cells. (PMID:24846123)
• the NKG2D ligand ULBP2 is transported to the cell surface through an endosomal pathway dependent on protein kinase C and lysosomal integrity. ULBP2 surface transport is dependent on the invariant chain. (PMID:25024379)
• Human anaplastic thyroid carcinoma cells are sensitive to NK cell-mediated lysis via ULBP2/5/6 and chemoattract NK cells. (PMID:25212604)
• NKG2D and NKG2DL are involved in allergen-induced activation of dendritic epidermal T cells and the NKG2D/NKG2DL pathway might be a potential target for treatment of contact hypersensitivity. (PMID:25634359)
• Data inticate that heat shock protein 60 (HSP60) interacted constitutively with NKG2D ligand ULBP2 and phosphatase of regenerating liver 3 (PRL-3) regulated HSP60 tyrosine phosphorylation. (PMID:25687758)
• This study suggests that NKG2D ligands shedding of MICA, MICB and ULBP-2 is a novel pathway in endometriosis complex pathogenesis that impairs Natural Killer Cells cell function. (PMID:25775242)
• A conserved WW domain-like motif regulates CD74 antigen-dependent cell-surface transport of the NKG2D ligand ULBP2. (PMID:25983110)
• Varicella-Zoster Virus differentially modulates expression of the NKG2D ligands by upregulating MICA expression and reducing ULBP2 and ULBP3 expression in the infected cells. (PMID:25995251)
• By suppressing AR and up-regulating ULBP2 in HCC, cisplatin could up-regulate cytotoxicity of NK cells to better target HCC. (PMID:26805759)
• IMP3 directly interacts with ULBP2 mRNA, leading to ULBP2 transcript destabilization and reduced ULBP2 surface expression and indirectly downregulates MICB with a mechanism functionally distinct from that of ULBP2. (PMID:26982091)
• High ULBP2 expression is associated with lymphoma. (PMID:27477692)
• Data show that the response of NK cells activated by ULBP2 was augmented by an interaction between NKG2D ligand 2 protein (ULBP2)-bound natural killer group 2D (NKG2D) and IL- interleukin 15 receptor (IL-15R). (PMID:29636390)
• NK cells are important cytotoxic cells in the immune system, and the activated NKG2D receptor on the NK cell surface can bind to NKG2D ligands expressed in tumor cells, enabling NK cells to activate and kill tumor cells. (Review) (PMID:30813924)
• Soluble ULBP2 but neither soluble ULBP1 nor soluble ULBP3, was etected in the supernatants of pancreatic cancer cells. Soluble ULBP2 derived from pancreatic cancer cells could reduce the cytotoxicity of Natural killer cells. Multivariate analysis demonstrated that serum soluble ULBP2 was a significant independent factor associated with poor overall survival . (PMID:31303272)
• MiR-873, as a suppressor in cervical cancer, inhibits cells proliferation, invasion and migration via negatively regulating ULBP2. (PMID:31902110)
• Fumarate Upregulates Surface Expression of ULBP2/ULBP5 by Scavenging Glutathione Antioxidant Capacity. (PMID:32144161)

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
danio_rerio	mhc1laa	ENSDARG00000016056
danio_rerio	mhc1lba	ENSDARG00000016227
danio_rerio	mhc1lda	ENSDARG00000023203
danio_rerio		ENSDARG00000051710
danio_rerio		ENSDARG00000051711
danio_rerio	mhc1lfa	ENSDARG00000051712
danio_rerio	mhc1lga	ENSDARG00000051713
danio_rerio	mhc1lca	ENSDARG00000055813
danio_rerio	mhc1lja	ENSDARG00000096830
danio_rerio	si:dkey-52p2.5	ENSDARG00000096940
danio_rerio	mhc1lla	ENSDARG00000096977
mus_musculus	Ulbp1	ENSMUSG00000079685

Paralogs (22): HFE (ENSG00000010704), FCGRT (ENSG00000104870), ULBP1 (ENSG00000111981), ULBP3 (ENSG00000131019), MR1 (ENSG00000153029), RAET1L (ENSG00000155918), CD1D (ENSG00000158473), CD1A (ENSG00000158477), CD1C (ENSG00000158481), CD1B (ENSG00000158485), CD1E (ENSG00000158488), AZGP1 (ENSG00000160862), RAET1E (ENSG00000164520), RAET1G (ENSG00000203722), MICB (ENSG00000204516), MICA (ENSG00000204520), HLA-C (ENSG00000204525), HLA-E (ENSG00000204592), HLA-G (ENSG00000204632), HLA-F (ENSG00000204642), HLA-A (ENSG00000206503), HLA-B (ENSG00000234745)

Protein

Protein identifiers

UL16-binding protein 2 — Q9BZM5 (reviewed: Q9BZM5)

Alternative names: ALCAN-alpha, NKG2D ligand 2, Retinoic acid early transcript 1H

All UniProt accessions (1): Q9BZM5

UniProt curated annotations — full annotation on UniProt →

Function. Binds and activates the KLRK1/NKG2D receptor, mediating natural killer cell cytotoxicity.

Subunit / interactions. Interacts with KLRK1/NKG2D. Does not bind to beta2-microglobulin. (Microbial infection) In CMV-infected cells, interacts with the viral glycoprotein UL16; this interaction causes ULBP2 retention in the endoplasmic reticulum and cis-Golgi and prevents binding to and activation of KLRK1/NKG2D, providing CMV with an immune evasion mechanism.

Subcellular location. Cell membrane. Endoplasmic reticulum. Secreted.

Tissue specificity. Expressed in various types of cancer cell lines and in the fetus, but not in normal tissues.

Miscellaneous. UL16-binding proteins (ULBPs) are unusual members of the extended MHC class I superfamily. They do not contain the alpha 3 domain and lack a transmembrane domain.

Similarity. Belongs to the MHC class I family.

RefSeq proteins (1): NP_079493* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011161	MHC_I-like_Ag-recog	Domain
IPR011162	MHC_I/II-like_Ag-recog	Homologous_superfamily
IPR037055	MHC_I-like_Ag-recog_sf	Homologous_superfamily
IPR050208	MHC_class-I_related	Family

Pfam: PF00129

UniProt features (18 total): mutagenesis site 4, disulfide bond 2, helix 2, region of interest 2, glycosylation site 2, signal peptide 1, chain 1, turn 1, propeptide 1, binding site 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
8IMX	ELECTRON MICROSCOPY	2.85
8IMY	ELECTRON MICROSCOPY	3.22

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BZM5-F1	82.99	0.64

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (1): 216

Post-translational modifications (1): 217

Disulfide bonds (2): 127–190, 50–66

Glycosylation sites (2): 68, 82

Mutagenesis-validated functional residues (4):

Position	Phenotype
208–210	secreted.
216–218	not secreted.
216	does not affect gpi-anchor attachment. loss of gpi-anchor attachment; when associated with q-217.
217	does not affect gpi-anchor attachment. loss of gpi-anchor attachment; when associated with q-216.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-163125	Post-translational modification: synthesis of GPI-anchored proteins

MSigDB gene sets: 124 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, HORIUCHI_WTAP_TARGETS_DN, GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, BENPORATH_ES_WITH_H3K27ME3, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, PEREZ_TP63_TARGETS, GOCC_CELL_SURFACE, SATO_SILENCED_BY_DEACETYLATION_IN_PANCREATIC_CANCER, GOBP_LEUKOCYTE_MEDIATED_CYTOTOXICITY, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_VIA_MHC_CLASS_IB, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_OF_PEPTIDE_ANTIGEN, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, BILD_HRAS_ONCOGENIC_SIGNATURE, GOBP_POSITIVE_REGULATION_OF_T_CELL_MEDIATED_CYTOTOXICITY, chr6q25

GO Biological Process (8): positive regulation of T cell mediated cytotoxicity (GO:0001916), antigen processing and presentation of endogenous peptide antigen via MHC class Ib (GO:0002476), antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independent (GO:0002486), immune response (GO:0006955), natural killer cell activation (GO:0030101), natural killer cell mediated cytotoxicity (GO:0042267), immune system process (GO:0002376), signal transduction (GO:0007165)

GO Molecular Function (4): GPI anchor binding (GO:0034235), natural killer cell lectin-like receptor binding (GO:0046703), receptor ligand activity (GO:0048018), protein binding (GO:0005515)

GO Cellular Component (8): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), endoplasmic reticulum (GO:0005783), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), membrane (GO:0016020), side of membrane (GO:0098552)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
signaling receptor binding	2
membrane	2
positive regulation of leukocyte mediated cytotoxicity	1
T cell mediated cytotoxicity	1
regulation of T cell mediated cytotoxicity	1
positive regulation of T cell mediated immunity	1
antigen processing and presentation of peptide antigen via MHC class Ib	1
antigen processing and presentation of endogenous peptide antigen	1
antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway	1
immune system process	1
response to stimulus	1
lymphocyte activation	1
leukocyte mediated cytotoxicity	1
natural killer cell mediated immunity	1
biological_process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
phospholipid binding	1
glycolipid binding	1
signal transduction	1
signaling receptor activator activity	1
binding	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
leaflet of membrane bilayer	1

Protein interactions and networks

STRING

698 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ULBP2	KLRK1	P26718	999
ULBP2	MICB	P79525	958
ULBP2	HCST	Q9UBK5	862
ULBP2	KLRD1	Q13241	823
ULBP2	CD226	Q15762	816
ULBP2	NCR3	O14931	782
ULBP2	LILRB1	Q8NHL6	773
ULBP2	MICA	P79506	768
ULBP2	NCR2	O95944	742
ULBP2	CCR8	P51685	723
ULBP2	NECTIN2	Q92692	718
ULBP2	PVR	P15151	712
ULBP2	NCR1	O76036	659
ULBP2	NCR3LG1	Q68D85	659
ULBP2	B2M	P01884	637

IntAct

39 interactions, top by confidence:

A	B	Type	Score
MED21	MED19	psi-mi:“MI:0914”(association)	0.880
TNFSF8	TOR1B	psi-mi:“MI:0914”(association)	0.640
KLRK1	ULBP2	psi-mi:“MI:0407”(direct interaction)	0.610
KLRK1	ULBP2	psi-mi:“MI:0915”(physical association)	0.610
ULBP2	KLRK1	psi-mi:“MI:0915”(physical association)	0.610
DERL3	ULBP2	psi-mi:“MI:0915”(physical association)	0.560
YIPF6	ULBP2	psi-mi:“MI:0915”(physical association)	0.560
SLC39A5	TMEM223	psi-mi:“MI:0914”(association)	0.530
TMEM30B	KLRG2	psi-mi:“MI:0914”(association)	0.530
HOXB5	VPS37C	psi-mi:“MI:0914”(association)	0.530
GJB7	PALM3	psi-mi:“MI:0914”(association)	0.530
FCGRT	GOLIM4	psi-mi:“MI:0914”(association)	0.530
UL16	ULBP2	psi-mi:“MI:0915”(physical association)	0.400
ULBP2	PDGFRA	psi-mi:“MI:0915”(physical association)	0.370
M2	IPO5	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
MED21	MED19	psi-mi:“MI:0914”(association)	0.350
DUSP22	POTEF	psi-mi:“MI:0914”(association)	0.350
SLC4A8	ABCC4	psi-mi:“MI:0914”(association)	0.350
IDO2	FAM171A2	psi-mi:“MI:0914”(association)	0.350
TNFSF8	NME4	psi-mi:“MI:0914”(association)	0.350
RAET1E	GOLIM4	psi-mi:“MI:0914”(association)	0.350
MTUS2	CCP110	psi-mi:“MI:0914”(association)	0.350
ANKRD12	SLIT2	psi-mi:“MI:0914”(association)	0.350
DUS4L	HRAS	psi-mi:“MI:0914”(association)	0.350
ZBTB18	DNASE1L1	psi-mi:“MI:0914”(association)	0.350

BioGRID (33): ULBP2 (Affinity Capture-MS), ULBP2 (Affinity Capture-MS), ULBP2 (Affinity Capture-MS), ULBP2 (Affinity Capture-MS), ULBP2 (Affinity Capture-MS), ULBP2 (Affinity Capture-MS), ULBP2 (Affinity Capture-MS), ULBP2 (Affinity Capture-MS), ULBP2 (Affinity Capture-MS), ULBP2 (Affinity Capture-MS), ULBP2 (Affinity Capture-MS), ULBP2 (Affinity Capture-MS), ULBP2 (Affinity Capture-MS), ULBP2 (Affinity Capture-MS), ULBP2 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2K7V7, C1ITJ8, O08602, O08603, O08604, O19477, O35799, P01901, P01902, P06339, P13599, P14427, P14432, P16391, P25311, P26151, P30383, P55899, P60018, P70387, Q01965, Q29980, Q29983, Q2KN22, Q30201, Q3B8P2, Q5RD09, Q60I18, Q61559, Q63678, Q64726, Q6H3X3, Q8HWB0, Q8HWE5, Q8HWE7, Q8SPV9, Q8VD31, Q920A9, Q95460, Q9BCU3

Diamond homologs: Q5VY80, Q6H3X3, Q8TD07, Q9BZM4, Q9BZM5, Q9BZM6

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ULBP2	up-regulates	KLRK1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

59 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	50
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

696 predictions. Top by Δscore:

Variant	Effect	Δscore
6:149942154:GCCG:G	donor_gain	1.0000
6:149942155:CCGG:C	donor_loss	0.9900
6:149942157:GGT:G	donor_loss	0.9900
6:149942158:G:GA	donor_loss	0.9900
6:149942158:G:GG	donor_gain	0.9900
6:149942159:T:A	donor_loss	0.9900
6:149942160:GAGT:G	donor_loss	0.9900
6:149945514:G:GA	donor_gain	0.9800
6:149945571:GG:G	donor_gain	0.9800
6:149945572:GG:G	donor_gain	0.9800
6:149945307:A:AG	acceptor_gain	0.9700
6:149945308:G:GG	acceptor_gain	0.9700
6:149945308:GACC:G	acceptor_gain	0.9700
6:149947318:A:AG	acceptor_gain	0.9700
6:149947319:G:GG	acceptor_gain	0.9700
6:149947319:GCACC:G	acceptor_gain	0.9700
6:149947432:A:T	donor_gain	0.9700
6:149945304:CACA:C	acceptor_loss	0.9600
6:149945305:ACAGA:A	acceptor_loss	0.9600
6:149945308:G:A	acceptor_loss	0.9600
6:149945572:GGTAA:G	donor_loss	0.9600
6:149945573:G:C	donor_loss	0.9600
6:149945574:TAAGT:T	donor_loss	0.9600
6:149945308:GAC:G	acceptor_gain	0.9500
6:149945308:GACCC:G	acceptor_gain	0.9500
6:149945348:A:G	acceptor_gain	0.9500
6:149945513:T:TA	donor_gain	0.9500
6:149945573:G:GG	donor_gain	0.9500
6:149945575:AAGTT:A	donor_loss	0.9500
6:149947319:GC:G	acceptor_gain	0.9400

AlphaMissense

1608 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:149945404:T:C	F61L	0.960
6:149945406:T:A	F61L	0.960
6:149945406:T:G	F61L	0.960
6:149946443:T:C	F141L	0.959
6:149946445:C:A	F141L	0.959
6:149946445:C:G	F141L	0.959
6:149946494:T:A	W158R	0.941
6:149946494:T:C	W158R	0.941
6:149946444:T:C	F141S	0.940
6:149946538:G:C	W172C	0.938
6:149946538:G:T	W172C	0.938
6:149946437:T:A	W139R	0.932
6:149946437:T:C	W139R	0.932
6:149946496:G:C	W158C	0.930
6:149946496:G:T	W158C	0.930
6:149946464:T:C	F148L	0.929
6:149946466:C:A	F148L	0.929
6:149946466:C:G	F148L	0.929
6:149945484:G:C	W87C	0.921
6:149945484:G:T	W87C	0.921
6:149946473:T:C	F151L	0.919
6:149946475:T:A	F151L	0.919
6:149946475:T:G	F151L	0.919
6:149946439:G:C	W139C	0.913
6:149946439:G:T	W139C	0.913
6:149945482:T:A	W87R	0.909
6:149945482:T:C	W87R	0.909
6:149946536:T:A	W172R	0.909
6:149946536:T:C	W172R	0.909
6:149945383:G:C	G54R	0.903

dbSNP variants (sampled 300 via entrez): RS1000120528 (6:149947692 C>G), RS1000385896 (6:149942066 G>A), RS1000669629 (6:149943068 G>A), RS1000847299 (6:149948872 T>C), RS1000991586 (6:149942961 C>T), RS1001668092 (6:149943923 T>C), RS1001992026 (6:149943759 T>A), RS1002136432 (6:149949607 G>A,T), RS1002828655 (6:149940697 T>A), RS1003682778 (6:149947264 G>A,T), RS1003782831 (6:149941612 G>A), RS1004353855 (6:149940030 C>A,T), RS1004684835 (6:149940248 C>G,T), RS1004836385 (6:149942695 C>A,G,T), RS1005186461 (6:149942432 TC>T)

Disease associations

OMIM: gene MIM:605698 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008478_63	Neurological blood protein biomarker levels	5.000000e-11

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

50 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression	4
Cisplatin	increases expression, affects expression, affects cotreatment	3
Arsenic Trioxide	increases expression	2
Benzo(a)pyrene	increases expression, increases methylation	2
Nickel	increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	2
Cadmium Chloride	increases expression	2
Particulate Matter	increases abundance, increases expression, affects expression, increases reaction	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
methylmercuric chloride	increases expression	1
propionaldehyde	increases expression	1
beta-lapachone	increases expression	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
pentanal	increases expression	1
2-palmitoylglycerol	increases expression	1
oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine	affects expression, increases reaction	1
nutlin 3	affects cotreatment, increases expression, increases secretion	1
abrine	increases expression	1
jinfukang	affects cotreatment, increases expression	1
NSC 689534	affects binding, increases expression	1
NSC668394	increases expression	1
Irinotecan	increases expression	1
Resveratrol	decreases reaction, increases expression	1
Temozolomide	increases expression	1
Decitabine	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Aldehydes	increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_C0B5	Abcam THP-1 ULBP2 KO	Cancer cell line	Male
CVCL_C7CT	Abcam PC-3 ULBP2 KO	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.