WRAP53 (WD repeat containing, antisense to TP53)

2010-11-01 Marianne Farnebo Affiliation

Karolinska Institutet, Cancer Center Karolinska (CCK) R8 :04, 17176 Stockholm, Sweden

Identity

HGNC

WRAP53

LOCATION

17p13.1

LOCUSID

55135

ALIAS

DKCB3,TCAB1,WDR79

FUSION GENES

Show Gene Fusions

DNA/RNA

Description

The WRAP53 gene encompasses 16 kb of DNA; 13 exons (three non-coding alternative start exons: exon 1alpha, 1beta and 1gamma. Exon 1alpha directly overlaps the first exon of TP53 in an antisense fashion by up to 227 base pairs (bp), depending on transcription start site (TSS) usage. Exon 1gamma of WRAP53 is located in the first intron of TP53 overlapping the previously identified transcript Hp53int1 in an antisense fashion.

Transcription

At least 17 splice variants. 1.9 kb mRNA; 1647 bp open reading frame.

Regulatory antisense RNA
Expression: widely expressed at low levels.
Localisation: cytoplasm and nucleus.
Function: regulates p53 mRNA levels by interacting with the 5UTR of p53 mRNA.
Homology: conserved in mouse.
Diseases implication currently not analysed.

Pseudogene

Not known.

Proteins

Description

548 amino acids; 75 kDa protein; contains from N-term to C-term, a proline-rich region (aa 8-57), a WD40 domain, 5 repeats (160-441), and a glycin-rich region (533-545).

Expression

Widely expressed, overexpressed in cancer.

Localisation

Cytoplasm and nucleus (enriched in Cajal bodies).

Function

Essential for Cajal body formation and maintenance. Targets the SMN complex, scaRNAs and telomerase enzyme (via TERC) to Cajal bodies. Inhibition of WRAP53 triggers mitochondrial-dependent apoptosis specifically in cancer cells.

Homology

Highly-conserved in mammals, the WD40 domain is conserved from human to fly.

Mutations

Note

Single nucleotide polymorphisms (SNPs) in women with breast cancer (see below).

Germinal

Not reported.

Somatic

Not reported.

Implicated in

Entity name

Breast and ovarian cancer

Note

Single nucleotide polymorphisms (SNPs) in WRAP53 were found to be overrepresented in women with breast cancer, in particular estrogen receptor negative breast cancer. The same SNPs were also associated with aggressive ovarian cancer. The SNPs are located in the coding region of WRAP53 and results in the amino acid change R68G.

Entity name

Spinal muscular atrophy (SMA)

Note

WRAP53 targets the SMN complex to Cajal Bodies. WRAP53 and SMN association is disrupted in SMA patients suggesting a role of WRAP53 in SMA pathogenesis.

Disease

Spinal muscular atrophy (SMA) is a common neurodegenerative disorder caused by reduced levels of SMN due to mutations or deletions of the SMN1 gene. SMA is the leading genetic cause of infant mortality worldwide, affecting approximately 1 in 6000 infants.

Bibliography

Pubmed ID	Last Year	Title	Authors
17683073	2007	Common genetic variation in TP53 and its flanking genes, WDR79 and ATP1B2, and susceptibility to breast cancer.	Garcia-Closas M et al
19276375	2009	Single nucleotide polymorphisms in the TP53 region and susceptibility to invasive epithelial ovarian cancer.	Schildkraut JM et al
19285445	2009	A conserved WD40 protein binds the Cajal body localization signal of scaRNP particles.	Tycowski KT et al
19179534	2009	A human telomerase holoenzyme protein required for Cajal body localization and telomere synthesis.	Venteicher AS et al

Other Information

Locus ID:

NCBI: 55135
MIM: 612661
HGNC: 25522
Ensembl: ENSG00000141499

Variants:

dbSNP: 55135
ClinVar: 55135
TCGA: ENSG00000141499
COSMIC: WRAP53

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000141499	ENST00000316024	Q9BUR4
ENSG00000141499	ENST00000396463	Q9BUR4
ENSG00000141499	ENST00000431639	Q9BUR4
ENSG00000141499	ENST00000457584	Q9BUR4
ENSG00000141499	ENST00000463804	K7EJ50
ENSG00000141499	ENST00000498311	E9PMR3
ENSG00000141499	ENST00000534050	E9PMG4

Expression (GTEx)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
Metabolism of proteins	REACTOME	R-HSA-392499
Protein folding	REACTOME	R-HSA-391251
Chaperonin-mediated protein folding	REACTOME	R-HSA-390466
Association of TriC/CCT with target proteins during biosynthesis	REACTOME	R-HSA-390471
Cell Cycle	REACTOME	R-HSA-1640170
Chromosome Maintenance	REACTOME	R-HSA-73886
Telomere Maintenance	REACTOME	R-HSA-157579
Extension of Telomeres	REACTOME	R-HSA-180786
Telomere Extension By Telomerase	REACTOME	R-HSA-171319

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
19179534	2009	A human telomerase holoenzyme protein required for Cajal body localization and telomere synthesis.	220
21205863	2011	Disruption of telomerase trafficking by TCAB1 mutation causes dyskeratosis congenita.	103
19250907	2009	Wrap53, a natural p53 antisense transcript required for p53 induction upon DNA damage.	102
21072240	2010	WRAP53 is essential for Cajal body formation and for targeting the survival of motor neuron complex to Cajal bodies.	61
22547674	2012	Telomerase recruitment requires both TCAB1 and Cajal bodies independently.	55
26551349	2016	Investigation of long noncoding RNAs expression profile as potential serum biomarkers in patients with hepatocellular carcinoma.	36
25467444	2014	Proteostatic control of telomerase function through TRiC-mediated folding of TCAB1.	35
18676680	2008	Pathway-based evaluation of 380 candidate genes and lung cancer susceptibility suggests the importance of the cell cycle pathway.	32
25512560	2014	The scaffold protein WRAP53β orchestrates the ubiquitin response critical for DNA double-strand break repair.	27
19692168	2010	Genetic susceptibility to distinct bladder cancer subphenotypes.	25

Citation

Marianne Farnebo

WRAP53 (WD repeat containing, antisense to TP53)

Atlas Genet Cytogenet Oncol Haematol. 2010-11-01

Online version: http://atlasgeneticsoncology.org/gene/50705/wrap53