WDR77 WD repeat domain 77 [Homo sapiens (human)] - Gene

Summary

Official Symbol: WDR77provided by HGNC
Official Full Name: WD repeat domain 77provided by HGNC
Primary source: HGNC:HGNC:29652
See related: Ensembl:ENSG00000116455 MIM:611734; AllianceGenome:HGNC:29652
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: p44; MEP50; MEP-50; HKMT1069; Nbla10071; p44/Mep50
Summary: The protein encoded by this gene is an androgen receptor coactivator that forms a complex with protein arginine methyltransferase 5, which modifies specific arginines to dimethylarginines in several spliceosomal Sm proteins. The encoded protein may be involved in the early stages of prostate cancer, with most of the protein being nuclear-localized in benign cells but cytoplasmic in cancer cells. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2015]
Expression: Ubiquitous expression in lymph node (RPKM 14.0), urinary bladder (RPKM 11.8) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1p13.2

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (111439890..111449256, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (111454574..111463940, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (111982512..111991878, complement)

Chromosome 1 - NC_000001.11 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?

Inhibition of PRMT5/MEP50 Arginine Methyltransferase Activity Causes Cancer Vulnerability in NDRG2[low] Adult T-Cell Leukemia/Lymphoma.
Title: Inhibition of PRMT5/MEP50 Arginine Methyltransferase Activity Causes Cancer Vulnerability in NDRG2(low) Adult T-Cell Leukemia/Lymphoma.
HBx represses WDR77 to enhance HBV replication by DDB1-mediated WDR77 degradation in the liver.
Title: HBx represses WDR77 to enhance HBV replication by DDB1-mediated WDR77 degradation in the liver.
Biochemical Investigation of the Interaction of pICln, RioK1 and COPR5 with the PRMT5-MEP50 Complex.
Title: Biochemical Investigation of the Interaction of pICln, RioK1 and COPR5 with the PRMT5-MEP50 Complex.
Germ-line mutations in WDR77 predispose to familial papillary thyroid cancer.
Title: Germ-line mutations in WDR77 predispose to familial papillary thyroid cancer.
WD Repeat Domain 77 Protein Regulates Translation of E2F1 and E2F3 mRNA.
Title: WD Repeat Domain 77 Protein Regulates Translation of E2F1 and E2F3 mRNA.
These results suggest that MEP50/PRMT5 is important for HH signal-induced GLI1 activation, especially in cancers.
Title: MEP50/PRMT5-mediated methylation activates GLI1 in Hedgehog signalling through inhibition of ubiquitination by the ITCH/NUMB complex.
curcumin affects the PRMT5-MEP50 methyltransferase expression might be explored for its therapeutic application.
Title: Curcumin ameliorates PRMT5-MEP50 arginine methyltransferase expression by decreasing the Sp1 and NF-YA transcription factors in the A549 and MCF-7 cells.
Deacetylation of WDR77 at Lys-3 and Lys-243 suppresses cancer cell growth by reducing WDR77/PRMT5 transmethylase complex activity.
Title: Sirtuin 7-mediated deacetylation of WD repeat domain 77 (WDR77) suppresses cancer cell growth by reducing WDR77/PRMT5 transmethylase complex activity.
A 3.7 A structure of PRMT5, solved in complex with regulatory binding subunit MEP50 (methylosome associated protein 50, WDR77, p44), by single particle (SP) cryo-Electron Microscopy (cryo-EM) using micrographs of particles that are visibly crowded and aggregated. The catalytic PRMT5 subunits form a core tetramer and the MEP50 subunits are arranged peripherally in complex with the PRMT5 N-terminal domain.
Title: Cryo-electron microscopy structure of a human PRMT5:MEP50 complex.
Data indicate that ZNF326 is an interaction partner and substrate of the PRMT5/WDR77 complex.
Title: The PRMT5/WDR77 complex regulates alternative splicing through ZNF326 in breast cancer.

Submit: New GeneRIF Correction See all GeneRIFs (29)

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)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH11857 (e-PCR)
- UniSTS:90883

AL033683 (e-PCR)
- UniSTS:93541

SHGC-75307 (e-PCR)
- UniSTS:36478

NIB1144 (e-PCR)
- UniSTS:82840

D1S2199 (e-PCR)
- UniSTS:14789

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables methyl-CpG binding	IDA Inferred from Direct Assay more info	PubMed
enables nuclear receptor coactivator activity	IGI Inferred from Genetic Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables ubiquitin-like ligase-substrate adaptor activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in epithelial cell proliferation involved in prostate gland development	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of epithelial cell proliferation involved in prostate gland development	IEA Inferred from Electronic Annotation more info
involved_in oocyte axis specification	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of DNA-templated transcription	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of cell population proliferation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of mRNA splicing, via spliceosome	NAS Non-traceable Author Statement more info	PubMed
involved_in protein polyubiquitination	IEA Inferred from Electronic Annotation more info
involved_in regulation of transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info
involved_in secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development	IEA Inferred from Electronic Annotation more info
involved_in spliceosomal snRNP assembly	NAS Non-traceable Author Statement more info	PubMed
involved_in ubiquitin-dependent protein catabolic process	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
part_of Cul4B-RING E3 ubiquitin ligase complex	IEA Inferred from Electronic Annotation more info
located_in Golgi apparatus	IDA Inferred from Direct Assay more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IGI Inferred from Genetic Interaction more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
part_of methylosome	IBA Inferred from Biological aspect of Ancestor more info
part_of methylosome	IDA Inferred from Direct Assay more info	PubMed
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	IGI Inferred from Genetic Interaction more info	PubMed

General protein information

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Preferred Names: methylosome protein WDR77

Names: WD repeat-containing protein 77; androgen receptor cofactor p44; methylosome protein 50; testis tissue sperm-binding protein Li 44a

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_001317062.2 → NP_001303991.1 methylosome protein WDR77 isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

AL390195, BC016946, BI195029, DB105102

UniProtKB/TrEMBL

H0Y711

Related

ENSP00000409300.1, ENST00000449340.1

Conserved Domains (3) summary

COG2319
Location:98 → 341

WD40; WD40 repeat [General function prediction only]

sd00039
Location:128 → 164

7WD40; WD40 repeat [structural motif]

cl02567
Location:80 → 331

WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...
NM_001317063.2 → NP_001303992.1 methylosome protein WDR77 isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses two alternate in-frame splice junctions in the 3' end compared to variant 1. The resulting isoform (3) has the same N- and C-termini but is shorter compared to isoform 1.

Source sequence(s)

AL390195, AL557974, BC016946, DB105102

UniProtKB/TrEMBL

H0Y711

Conserved Domains (3) summary

COG2319
Location:98 → 327

WD40; WD40 repeat [General function prediction only]

sd00039
Location:128 → 164

7WD40; WD40 repeat [structural motif]

cl02567
Location:80 → 317

WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...
NM_001317064.2 → NP_001303993.1 methylosome protein WDR77 isoform 4

Status: REVIEWED

Description

Transcript Variant: This variant (4) lacks an alternate in-frame segment in the 5' end and uses an alternate in-frame splice junction in the 3' end compared to variant 1. The resulting isoform (4) has the same N- and C-termini but is shorter compared to isoform 1.

Source sequence(s)

AK298179, BC016946, DB105102

UniProtKB/Swiss-Prot

Q9BQA1

Conserved Domains (3) summary

COG2319
Location:87 → 258

WD40; WD40 repeat [General function prediction only]

sd00039
Location:106 → 143

7WD40; WD40 repeat [structural motif]

cl02567
Location:88 → 258

WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...
NM_024102.4 → NP_077007.1 methylosome protein WDR77 isoform 2

See identical proteins and their annotated locations for NP_077007.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate in-frame splice junction in the 3' end compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1.

Source sequence(s)

BC016946, DB105102

Consensus CDS

CCDS835.1

UniProtKB/Swiss-Prot

B3KMW6, B4DP38, Q3LID2, Q53FU2, Q6JZZ5, Q96GK4, Q9BQA1, Q9BWY3

UniProtKB/TrEMBL

A0A024R0H7, A0A140VKC7, H0Y711

Related

ENSP00000235090.5, ENST00000235090.10

Conserved Domains (3) summary

COG2319
Location:98 → 329

WD40; WD40 repeat [General function prediction only]

sd00039
Location:128 → 164

7WD40; WD40 repeat [structural motif]

cl02567
Location:80 → 319

WD40; WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from ...

RNA

NR_133654.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (5) lacks an alternate exon in the 5' end and uses an alternate splice junction in the 3' end compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AK296163, BC016946, DB105102