ULBP2 UL16 binding protein 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: ULBP2provided by HGNC
Official Full Name: UL16 binding protein 2provided by HGNC
Primary source: HGNC:HGNC:14894
See related: Ensembl:ENSG00000131015 MIM:605698; AllianceGenome:HGNC:14894
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: N2DL2; RAET1H; RAET1L; NKG2DL2; ALCAN-alpha
Summary: 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. [provided by RefSeq, Jul 2015]
Expression: Biased expression in esophagus (RPKM 5.0), lung (RPKM 1.3) and 11 other tissues See more
Orthologs: all
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Genomic context

Location:: 6q25.1

Exon count:: 5

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	6	NC_000006.12 (149942014..149949235)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	6	NC_060930.1 (151141356..151148578)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (150263150..150270371)

Chromosome 6 - NC_000006.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

ULBP2 is a biomarker related to prognosis and immunity in colon cancer.
Title: ULBP2 is a biomarker related to prognosis and immunity in colon cancer.
Staphylococcus aureus induces cell-surface expression of immune stimulatory NKG2D ligands on human monocytes.
Title: Staphylococcus aureus induces cell-surface expression of immune stimulatory NKG2D ligands on human monocytes.
MiR-873, as a suppressor in cervical cancer, inhibits cells proliferation, invasion and migration via negatively regulating ULBP2.
Title: MiR-873, as a suppressor in cervical cancer, inhibits cells proliferation, invasion and migration via negatively regulating ULBP2.
Fumarate Upregulates Surface Expression of ULBP2/ULBP5 by Scavenging Glutathione Antioxidant Capacity.
Title: Fumarate Upregulates Surface Expression of ULBP2/ULBP5 by Scavenging Glutathione Antioxidant Capacity.
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 .
Title: Soluble UL16-binding protein 2 is associated with a poor prognosis in pancreatic cancer patients.
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).
Title: A nanoscale reorganization of the IL-15 receptor is triggered by NKG2D in a ligand-dependent manner.
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)
Title: Natural killer group 2D receptor and its ligands in cancer immune escape.
High ULBP2 expression is associated with lymphoma.
Title: CBP/p300 acetyltransferases regulate the expression of NKG2D ligands on tumor cells.
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.
Title: The RNA binding protein IMP3 facilitates tumor immune escape by downregulating the stress-induced ligands ULPB2 and MICB.
By suppressing AR and up-regulating ULBP2 in HCC, cisplatin could up-regulate cytotoxicity of NK cells to better target HCC.
Title: Cisplatin enhances NK cells immunotherapy efficacy to suppress HCC progression via altering the androgen receptor (AR)-ULBP2 signals.

Submit: New GeneRIF Correction See all GeneRIFs (45)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Nef	nef	HIV-1 (SF2) Nef downregulates ULBP2; downregulation is dependent upon residues G2 and F195 and a di-lysine motif in Nef as shown in A3.01 T cells and HeLa TZM-bl cells	PubMed
	nef	HIV-1 Nef downregulates cell surface expression of MICA, ULBP1 and ULBP2 in natural killer (NK) cells	PubMed
Vif	vif	HIV-1 Vif expression in HIV-1 infected cells results in less HIV-1 Vpr-dependent upregulation of NKG2D ligands	PubMed
	vif	A3G upregulates NKG2D ligands through an ATM pathway and in which HIV-1 Vif counteracts this upregulation by decreasing A3G expression	PubMed
	vif	Vpr-dependent induction and Vif-mediated attenuation of NKG2D ligands are required for Chk2 phosphorylation in HIV infection	PubMed
Vpr	vpr	HIV-1 Vpr from most HIV-1 primary isolates can upregulate ULBP2 expression and induce NKG2D-dependent NK cell killing	PubMed
	vpr	Soluble HIV-1 Vpr promotes cell cycle arrest and upregulates cell-surface expression of ULBP2 in T cells	PubMed
	vpr	HIV-1 Vpr upregulates NKG2D ligands via the ATR pathway	PubMed
	vpr	HIV-1-Vpr induced upregulation of NKG2D ligands in HIV-infected T cells by activating UNG2-dependent repair of uridine-containing DNA	PubMed
	vpr	Vpr-dependent induction and Vif-mediated attenuation of NKG2D ligands are required for Chk2 phosphorylation in HIV infection	PubMed
	vpr	HIV-1 Vif expression in HIV-1 infected cells results in less HIV-1 Vpr-dependent upregulation of NKG2D ligands	PubMed
	vpr	Upregulation of NKG2D ligands is dependent on HIV-1 Vpr-mediated activation of the TAR DNA damage/stress pathway, which requires the recruitment of the Cul4/DDB1/DCAF1 E3 ubiquitin ligase complex	PubMed
Vpu	vpu	HIV-1 (NL4-3) Vpu downregulates ULBP2; downregulation is dependent upon amino acids R30/K31, V25/Y29, the acidic di-leucine motif in Vpu helix 2 as shown in A3.01 T cells and HeLa TZM-bl cells	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables natural killer cell lectin-like receptor binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independent	IBA Inferred from Biological aspect of Ancestor more info
involved_in antigen processing and presentation of endogenous peptide antigen via MHC class Ib	IBA Inferred from Biological aspect of Ancestor more info
involved_in immune response	IBA Inferred from Biological aspect of Ancestor more info
involved_in natural killer cell activation	IDA Inferred from Direct Assay more info	PubMed
involved_in natural killer cell mediated cytotoxicity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of T cell mediated cytotoxicity	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
located_in cell surface	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum	IEA Inferred from Electronic Annotation more info
is_active_in external side of plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular region	TAS Traceable Author Statement more info
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
located_in intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: UL16-binding protein 2

Names: NKG2D ligand 2; retinoic acid early transcript 1H; retinoic acid early transcript 1L

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_025217.4 → NP_079493.1 UL16-binding protein 2 preproprotein

See identical proteins and their annotated locations for NP_079493.1

Status: REVIEWED

Source sequence(s)

AL583835, AY358665, BG718474

Consensus CDS

CCDS5222.1

UniProtKB/Swiss-Prot

Q5VUN4, Q9BZM5

UniProtKB/TrEMBL

Q8IZX9

Related

ENSP00000356320.3, ENST00000367351.4

Conserved Domains (1) summary

cl08246
Location:30 → 198

MHC_I; Class I Histocompatibility antigen, domains alpha 1 and 2

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000006.12 Reference GRCh38.p14 Primary Assembly

Range

149942014..149949235

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017011321.2 → XP_016866810.1 UL16-binding protein 2 isoform X2

UniProtKB/TrEMBL

B4DSS7

Conserved Domains (1) summary

cl08246
Location:30 → 198

MHC_I; Class I Histocompatibility antigen, domains alpha 1 and 2
XM_047419377.1 → XP_047275333.1 UL16-binding protein 2 isoform X1

UniProtKB/Swiss-Prot

Q5VUN4, Q9BZM5

Alternate T2T-CHM13v2.0

Genomic

NC_060930.1 Alternate T2T-CHM13v2.0

Range

151141356..151148578

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054356467.1 → XP_054212442.1 UL16-binding protein 2 isoform X2
XM_054356466.1 → XP_054212441.1 UL16-binding protein 2 isoform X1

UniProtKB/Swiss-Prot

Q5VUN4, Q9BZM5