WDR77 (WD repeat domain 77)

2008-10-01   Garrett Daniels , Zhenxing Wang , Peng Lee 

Department of Pathology, New York University School of Medicine, 423 East 23rd St., New York, USA (GD, PL) ; The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA (ZW)

Identity

HGNC
LOCATION
1p13.2
LOCUSID
ALIAS
HKMT1069,MEP-50,MEP50,Nbla10071,p44,p44/Mep50
FUSION GENES

DNA/RNA

Description

Spans 9.3kb/ 7.9kb; 10 exons.

Transcription

2428/ 1029 nucleotides mRNA.

Proteins

Description

342 amino acids. 44 kDa protein. 5 WD repeats (Hosohata et al., 2003).

Expression

p44 is expressed in heart, skeletal muscle, spleen, thymus, prostate, testis, pancreas, and uterus (Hosohata et al., 2003).
In adult prostate, p44 is expressed as nuclear protein in glandular epithelial cells and not in stromal cells (Zhou et al., 2006).
In testis, p44 expression is seen in germ cells and Leydig cells, but not expressed in peritubular myocytes and Sertolis cells (Liang et al., 2006).

Localisation

p44 has both nuclear and cytolasmic localization patterns (Zhou et al., 2006; Liang et al., 2006; Peng et al., 2008). In benign prostate and testicular cells, p44 is found predominantly in the nucleus. In prostate cancer and malignant testicular cells (seminomas and leydig cell tumor), p44 is found in the cytoplasm. The p44 cytoplasmic translocation may be an indicative marker of cancer in these tissues.

Function

p44 interacts with androgen receptor and acts as a positive coactivator for androgen-dependent AR transactivation (Hosohata, 2003). Nuclear p44 causes an androgen-dependent G1 arrest growth inhibition in prostate cells expressing androgen receptor (Zhou et al., 2006; Peng et al., 2008). Cytoplasmic and nuclear p44 may have opposite functions, as introduction of p44 to the cytoplasm accelerates growth (Peng et al., 2008).
p44 is part of the PRMT5 (protein arginine methyl transferase 5) complex important for methylosome activity (Hosohata et al., 2003; Friesen et al., 2002). p44 interacts with FCP1 phosphatase (Licciardo et al., 2002) and histone H2A (Furuno et al., 2006).

Homology

WD repeats commonly seen for multiple protein interactions.

Mutations

Note

Unknown

Implicated in

Entity name
Androgen-dependent prostate cancer
Disease
In androgen-dependent prostate cancer p44 is found predominantly in the cytoplasm, as opposed to nuclear localization in benign tissue (Zhou et al., 2006). Translocation from the nucleus in benign cells to the cytoplasm is strongly associated with prostate tumorigenesis (Zhou et al., 2006; Peng et al., 2008). Cytoplasmic expressed p44 also leads to increased growth in androgen dependent prostate cell line LNCaP (Peng et al., 2008).
Entity name
Androgen-independent prostate cancer
Disease
In androgen-independent cancers p44 is found both in the nucleus and the cytoplasm (Peng et al., 2008). P44 may be able to serve as a diagnostic marker of androgen-independent prostate cancer.
Entity name
Testicular cancer
Disease
Testicular tumor cells have an increased cytoplasmic localization of p44 similar to the pattern observed in prostate cancer (Jiang et al., 2006). This is also similar to the pattern seen in the germ cells of fetal testis that express cytoplasmic p44. P44 is predominantly found in the nucleus of benign testicular cells and adult testis germ cells. Translocation of p44 to the cytoplasm in testis cells shows an association with tumorigenesis.

Bibliography

Pubmed IDLast YearTitleAuthors
117564522002A novel WD repeat protein component of the methylosome binds Sm proteins.Friesen WJ et al
167127892006Association of Polycomb group SUZ12 with WD-repeat protein MEP50 that binds to histone H2A selectively in vitro.Furuno K et al
129726182003Purification and identification of a novel complex which is involved in androgen receptor-dependent transcription.Hosohata K et al
174378482007The expression and function of androgen receptor coactivator p44 and protein arginine methyltransferase 5 in the developing testis and testicular tumors.Liang JJ et al
125604962003The FCP1 phosphatase interacts with RNA polymerase II and with MEP50 a component of the methylosome complex involved in the assembly of snRNP.Licciardo P et al
183562972008Distinct nuclear and cytoplasmic functions of androgen receptor cofactor p44 and association with androgen-independent prostate cancer.Peng Y et al
170327452006Roles of the androgen receptor cofactor p44 in the growth of prostate epithelial cells.Zhou L et al

Other Information

Locus ID:

NCBI: 79084
MIM: 611734
HGNC: 29652
Ensembl: ENSG00000116455

Variants:

dbSNP: 79084
ClinVar: 79084
TCGA: ENSG00000116455
COSMIC: WDR77

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000116455ENST00000235090Q9BQA1
ENSG00000116455ENST00000235090A0A024R0H7
ENSG00000116455ENST00000449340H0Y711

Expression (GTEx)

0
10
20
30
40
50
60

Pathways

PathwaySourceExternal ID
Gene ExpressionREACTOMER-HSA-74160
Metabolism of non-coding RNAREACTOMER-HSA-194441
snRNP AssemblyREACTOMER-HSA-191859
Chromatin organizationREACTOMER-HSA-4839726
Chromatin modifying enzymesREACTOMER-HSA-3247509
RMTs methylate histone argininesREACTOMER-HSA-3214858

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
117564522002A novel WD repeat protein component of the methylosome binds Sm proteins.90
230713342012Crystal structure of the human PRMT5:MEP50 complex.81
183562972008Distinct nuclear and cytoplasmic functions of androgen receptor cofactor p44 and association with androgen-independent prostate cancer.35
257130802015Histone H2A and H4 N-terminal tails are positioned by the MEP50 WD repeat protein for efficient methylation by the PRMT5 arginine methyltransferase.21
290421952017Circular RNA WDR77 target FGF-2 to regulate vascular smooth muscle cells proliferation and migration by sponging miR-124.21
170327452006Roles of the androgen receptor cofactor p44 in the growth of prostate epithelial cells.20
273379562016Yeast two-hybrid screening identified WDR77 as a novel interacting partner of TSC22D2.19
167127892006Association of Polycomb group SUZ12 with WD-repeat protein MEP50 that binds to histone H2A selectively in vitro.17
220225812011Expression and function of androgen receptor coactivator p44/Mep50/WDR77 in ovarian cancer.14
217892562011Nuclear transport signals control cellular localization and function of androgen receptor cofactor p44/WDR77.12

Citation

Garrett Daniels ; Zhenxing Wang ; Peng Lee

WDR77 (WD repeat domain 77)

Atlas Genet Cytogenet Oncol Haematol. 2008-10-01

Online version: http://atlasgeneticsoncology.org/gene/44142/wdr77