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 ... See more...

Aliases for ULBP2 Gene

Aliases for ULBP2 Gene

  • UL16 Binding Protein 2 2 3 5
  • RAET1H 2 3 4
  • Retinoic Acid Early Transcript 1H 3 4
  • UL16-Binding Protein 2 3 4
  • NKG2D Ligand 2 3 4
  • ALCAN-Alpha 3 4
  • NKG2DL2 3 4
  • N2DL2 3 4
  • Retinoic Acid Early Transcript 1L 3
  • RAET1L 3
  • N2DL-2 4
  • ULBP2 5

External Ids for ULBP2 Gene

Previous GeneCards Identifiers for ULBP2 Gene

  • GC06P149824
  • GC06P150158
  • GC06P150294
  • GC06P150355
  • GC06P150304
  • GC06P150263
  • GC06P147828
  • GC06P149935

Summaries for ULBP2 Gene

Entrez Gene Summary for ULBP2 Gene

  • 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]

GeneCards Summary for ULBP2 Gene

ULBP2 (UL16 Binding Protein 2) is a Protein Coding gene. Among its related pathways are Post-translational modification- synthesis of GPI-anchored proteins and Immune response Role of DAP12 receptors in NK cells. Gene Ontology (GO) annotations related to this gene include peptide antigen binding and natural killer cell lectin-like receptor binding. An important paralog of this gene is RAET1L.

UniProtKB/Swiss-Prot Summary for ULBP2 Gene

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

Gene Wiki entry for ULBP2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for ULBP2 Gene

Genomics for ULBP2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for ULBP2 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH06J149941 Promoter/Enhancer 1.9 EPDnew Ensembl ENCODE CraniofacialAtlas 262.5 +0.3 253 2 SP1 ZIC2 ZBTB10 NONO ZNF341 ZNF217 KLF9 SP2 ZBTB5 SIN3A ULBP2 HSALNG0054285 LATS1 PPIL4 KATNA1 NUP43 RPS18P9 ENSG00000233330 RAET1K ULBP1
GH06J149962 Promoter/Enhancer 1.9 EPDnew FANTOM5 Ensembl ENCODE 8.8 +22.3 22252 3.1 IKZF1 MYC ZNF600 ZNF580 ZNF592 ATF2 ZNF223 ZNF10 ATF3 ZSCAN16 ULBP1 LATS1 NUP43 PPIL4 KATNA1 RAET1K ENSG00000233330 ULBP2 HSALNG0054287 ENSG00000219298
GH06J150025 Promoter/Enhancer 1.2 EPDnew Ensembl ENCODE 11.3 +83.7 83712 1.3 ZNF217 EP300 CTBP1 TBP JUND KLF1 ATF3 FOS CC2D1A ZBTB5 RAET1L ULBP2 lnc-ULBP1-2 HSALNG0054292-001 ULBP3
GH06J150032 Enhancer 0.5 Ensembl 12.1 +91.4 91353 1 JUND SPI1 ATF2 JUN CREB1 ATF1 ATF3 ATF7 RAET1M lnc-ULBP1-2 ULBP2 ENSG00000231760 ENSG00000235972 RAET1L HSALNG0054292-001 ULBP3
GH06J149074 Enhancer 1.2 Ensembl ENCODE dbSUPER 4.5 -865.8 -865843 3.9 JUND CEBPA NFIC MXD4 KLF11 FEZF1 HOMEZ THAP11 FOXA2 KDM6A UST-AS2 LATS1 PPIL4 RNU7-3P TAB2-AS1 ULBP2 HSALNG0054230 LOC105378046 TAB2 UST
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around ULBP2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for ULBP2

Top Transcription factor binding sites by QIAGEN in the ULBP2 gene promoter:
  • AP-2alpha
  • AP-2alpha isoform 2
  • AP-2alpha isoform 3
  • AP-2alpha isoform 4
  • AP-2alphaA

Genomic Locations for ULBP2 Gene

Latest Assembly
chr6:149,941,947-149,949,235
(GRCh38/hg38)
Size:
7,289 bases
Orientation:
Plus strand

Previous Assembly
chr6:150,263,150-150,270,371
(GRCh37/hg19 by Entrez Gene)
Size:
7,222 bases
Orientation:
Plus strand

chr6:150,263,136-150,270,371
(GRCh37/hg19 by Ensembl)
Size:
7,236 bases
Orientation:
Plus strand

Genomic View for ULBP2 Gene

Genes around ULBP2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ULBP2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ULBP2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ULBP2 Gene

Proteins for ULBP2 Gene

  • Protein details for ULBP2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9BZM5-ULBP2_HUMAN
    Recommended name:
    UL16-binding protein 2
    Protein Accession:
    Q9BZM5
    Secondary Accessions:
    • Q5VUN4

    Protein attributes for ULBP2 Gene

    Size:
    246 amino acids
    Molecular mass:
    27368 Da
    Quaternary structure:
    • Interacts with KLRK1/NKG2D (PubMed:11777960). Does not bind to beta2-microglobulin (PubMed:12782710).
    • (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.
    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.

neXtProt entry for ULBP2 Gene

Post-translational modifications for ULBP2 Gene

  • Glycosylation at Asn68 and Asn82
  • Modification sites at PhosphoSitePlus

Other Protein References for ULBP2 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibodies for research

  • Abcam antibodies for ULBP2
  • Boster Bio Antibodies for ULBP2

No data available for DME Specific Peptides for ULBP2 Gene

Domains & Families for ULBP2 Gene

Gene Families for ULBP2 Gene

Human Protein Atlas (HPA):
  • Predicted membrane proteins
  • Predicted secreted proteins

Protein Domains for ULBP2 Gene

InterPro:
Blocks:
  • MHC class I signature

Suggested Antigen Peptide Sequences for ULBP2 Gene

GenScript: Design optimal peptide antigens:
  • UL16-binding protein 2 (N2DL2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9BZM5

UniProtKB/Swiss-Prot:

ULBP2_HUMAN :
  • Belongs to the MHC class I family.
Family:
  • Belongs to the MHC class I family.
genes like me logo Genes that share domains with ULBP2: view

Function for ULBP2 Gene

Molecular function for ULBP2 Gene

UniProtKB/Swiss-Prot Function:
Binds and activates the KLRK1/NKG2D receptor, mediating natural killer cell cytotoxicity.

Phenotypes From GWAS Catalog for ULBP2 Gene

Gene Ontology (GO) - Molecular Function for ULBP2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 19424970
GO:0046703 natural killer cell lectin-like receptor binding IDA 11239445
genes like me logo Genes that share ontologies with ULBP2: view
genes like me logo Genes that share phenotypes with ULBP2: view

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for ULBP2

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for ULBP2 Gene

Localization for ULBP2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ULBP2 Gene

Cell membrane. Lipid-anchor, GPI-anchor. Endoplasmic reticulum. Secreted. Note=In CMV-infected fibroblasts, detected in the endoplasmic reticulum/cis-Golgi. {ECO:0000269 PubMed:12782710}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for ULBP2 gene
Compartment Confidence
plasma membrane 5
extracellular 5
endoplasmic reticulum 4
nucleus 2
cytosol 2
lysosome 2
cytoskeleton 1
mitochondrion 1
endosome 1
golgi apparatus 1
peroxisome 0

Subcellular locations from the

Human Protein Atlas (HPA)
  • Plasma membrane (3)
  • Vesicles (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for ULBP2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005615 extracellular space IBA,IDA 18676862
GO:0005783 endoplasmic reticulum IEA --
GO:0005886 plasma membrane TAS --
GO:0009897 external side of plasma membrane IBA 21873635
genes like me logo Genes that share ontologies with ULBP2: view

Pathways & Interactions for ULBP2 Gene

genes like me logo Genes that share pathways with ULBP2: view

SIGNOR curated interactions for ULBP2 Gene

Activates:

Gene Ontology (GO) - Biological Process for ULBP2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002376 immune system process IEA --
GO:0006955 immune response IBA 21873635
GO:0016032 viral process IEA --
GO:0030101 natural killer cell activation IDA 11239445
GO:0042267 natural killer cell mediated cytotoxicity IDA 11239445
genes like me logo Genes that share ontologies with ULBP2: view

Drugs & Compounds for ULBP2 Gene

(1) Drugs for ULBP2 Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Calcium Nutra 6959
genes like me logo Genes that share compounds with ULBP2: view

Transcripts for ULBP2 Gene

mRNA/cDNA for ULBP2 Gene

1 REFSEQ mRNAs :
9 NCBI additional mRNA sequence :
1 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for ULBP2

Alternative Splicing Database (ASD) splice patterns (SP) for ULBP2 Gene

No ASD Table

Relevant External Links for ULBP2 Gene

GeneLoc Exon Structure for
ULBP2

Expression for ULBP2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for ULBP2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for ULBP2 Gene

This gene is overexpressed in Esophagus - Mucosa (x5.6).

Protein differential expression in normal tissues from HIPED for ULBP2 Gene

This gene is overexpressed in Amniocyte (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for ULBP2 Gene



Protein tissue co-expression partners for ULBP2 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for ULBP2

SOURCE GeneReport for Unigene cluster for ULBP2 Gene:

Hs.656778

mRNA Expression by UniProt/SwissProt for ULBP2 Gene:

Q9BZM5-ULBP2_HUMAN
Tissue specificity: Expressed in various types of cancer cell lines and in the fetus, but not in normal tissues.

Evidence on tissue expression from TISSUES for ULBP2 Gene

  • Skin(4.3)
  • Stomach(2.8)
  • Heart(2.5)
  • Nervous system(2.5)
  • Liver(2.4)
  • Intestine(2.3)
  • Kidney(2.2)
  • Blood(2.2)
genes like me logo Genes that share expression patterns with ULBP2: view

Primer products for research

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for ULBP2 Gene

Orthologs for ULBP2 Gene

This gene was present in the common ancestor of mammals.

Orthologs for ULBP2 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia ULBP2 29
  • 96.88 (n)
-- 30
  • 93 (a)
ManyToMany
-- 30
  • 91 (a)
ManyToMany
Cow
(Bos Taurus)
Mammalia ULBP3 30
  • 34 (a)
ManyToMany
Dog
(Canis familiaris)
Mammalia -- 30
  • 32 (a)
OneToMany
Species where no ortholog for ULBP2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Lizard (Anolis carolinensis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Mouse (Mus musculus)
  • Oppossum (Monodelphis domestica)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Platypus (Ornithorhynchus anatinus)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rat (Rattus norvegicus)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)
  • Zebrafish (Danio rerio)

Evolution for ULBP2 Gene

ENSEMBL:
Gene Tree for ULBP2 (if available)
TreeFam:
Gene Tree for ULBP2 (if available)
Alliance of Genome Resources:
Additional Orthologs for ULBP2

Paralogs for ULBP2 Gene

(9) SIMAP similar genes for ULBP2 Gene using alignment to 1 proteins:

  • N2DL2_HUMAN
genes like me logo Genes that share paralogs with ULBP2: view

Variants for ULBP2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for ULBP2 Gene

SNP ID Clinical significance and condition Chr 06 pos Variation AA Info Type
rs145177180 Benign: not provided 149,947,338(+) C/T
NM_025217.4(ULBP2):c.650C>T (p.Ser217Leu)
MISSENSE
rs146872141 Benign: not provided 149,947,397(+) A/C
NM_025217.4(ULBP2):c.709A>C (p.Ile237Leu)
MISSENSE
rs780818906 Likely Benign: not provided 149,946,451(+) C/T
NM_025217.4(ULBP2):c.429C>T (p.Phe143=)
SYNONYMOUS

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for ULBP2 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for ULBP2 Gene

Variant ID Type Subtype PubMed ID
esv2732866 CNV deletion 23290073
esv3611217 CNV loss 21293372
esv3890963 CNV loss 25118596
nsv517022 CNV gain+loss 19592680
nsv969456 CNV duplication 23825009

Variation tolerance for ULBP2 Gene

Residual Variation Intolerance Score: 71.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.31; 53.35% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for ULBP2 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
ULBP2
Leiden Open Variation Database (LOVD)
ULBP2

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for ULBP2 Gene

Disorders for ULBP2 Gene

Additional Disease Information for ULBP2

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform

No disorders were found for ULBP2 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for ULBP2 Gene

Publications for ULBP2 Gene

  1. Single nucleotide polymorphism analysis of the NKG2D ligand cluster on the long arm of chromosome 6: Extensive polymorphisms and evidence of diversity between human populations. (PMID: 20219610) Antoun A … Briggs DC (Human immunology 2010) 3 22 40
  2. Polymorphisms of NKG2D ligands: diverse RAET1/ULBP genes in northeastern Thais. (PMID: 19688209) Romphruk AV … Leelayuwat C (Immunogenetics 2009) 3 22 40
  3. ULBPs, novel MHC class I-related molecules, bind to CMV glycoprotein UL16 and stimulate NK cytotoxicity through the NKG2D receptor. (PMID: 11239445) Cosman D … Chalupny NJ (Immunity 2001) 2 3 4
  4. Differential NKG2D binding to highly related human NKG2D ligands ULBP2 and RAET1G is determined by a single amino acid in the alpha2 domain. (PMID: 19424970) Wittenbrink M … Steinle A (European journal of immunology 2009) 3 22
  5. Interferon-gamma down-regulates NKG2D ligand expression and impairs the NKG2D-mediated cytolysis of MHC class I-deficient melanoma by natural killer cells. (PMID: 19089914) Schwinn N … Paschen A (International journal of cancer 2009) 3 22

Products for ULBP2 Gene

  • Boster Bio Antibodies for ULBP2
  • Boster Bio ELISA Kits for ULBP2

Sources for ULBP2 Gene