RCHY1 (ring finger and CHY zinc finger domain containing 1)

2006-03-01   Wenrui Duan , Miguel A. Villalona-Calero 

Comprehensive Cancer Center, 1230 JCHRI, 300 West 10th Ave, Columbus, Ohio 43210, USA

Identity

HGNC
LOCATION
4q21.1
LOCUSID
ALIAS
ARNIP,CHIMP,PIRH2,PRO1996,RNF199,ZCHY,ZNF363
FUSION GENES

DNA/RNA

Description

The gene encompasses 32 kb of DNA; 9 exons.

Transcription

4.3 kb nucleotides mRNA. 783 bp open reading frame.

Proteins

Atlas Image
Immunohistochemical detection of human RCHY1 protein in non-small cell lung cancers. (A) squamous cell carcinoma, and (B) large cell carcinoma.

Description

261 amino acids; 32 kDa protein.

Expression

RCHY1 expresses at higher level in liver, testis and heart. Lower expression is detected in lung, brain, muscle and spleen. RCHY1 is overexpressed in non-small cell lung cancers.

Localisation

The localization of RCHY1 protein in human lung tumors was evaluated immunohistochemically. RCHY1 protein was found primarily in the cytoplasm and membrane and a small portion in the nucleus of malignant cells.

Function

RCHY1 is an ubiquitin-protein E3 ligase that promotes p53 degradation. The RCHY1 gene encodes a RING-H2 domain-containing protein with intrinsic ubiquitin-protein ligase activity. It has been reported that RCHY1( Pirh2) physically interacts with p53 and promotes ubiquitination of p53 independently of Mdm2. RCHY1 was also reported to be transactivated by the p53 product in MEFs, murine proB cell BaF3 and human BJT fibroblasts cells. Therefore, like MDM2, RCHY1 participates in an autoregulatory feedback loop that controls p53 function. Expression of RCHY1 decreased the level of p53 protein, while abrogation of endogenous RCHY1 expression increased the level of p53. Furthermore, RCHY1 represses p53 functions, including p53-dependent transactivation and growth inhibition. RCHY1 is overexpressed in both human and murine lung cancers by comparing Pirh2 mRNA and protein level between lung neoplastic tissues and uninvolved adjacent lung tissue. The increased RCHY1 protein could cause degradation of wild type p53 and reduce the tumor suppression function in tumor cells.
It has been reported that coexpression of RCHY1(ARNIP) and androgen receptor (AR) in COS-1 cells reduces the interaction between AR N- and C-terminus. The RING-H2 domain of the RCHY1 functions as an ubiquitin-protein ligase in vitro in the presence of a specific ubiquitin-conjugating enzyme, Ubc4-1. Mutation of a single cysteine residue in the RCHY RING-H2 domain (Cys145Ala) abolished this E3 ubiquitin ligase activity. Fluorescent protein tagging studies revealed that AR-RCHY1 interaction was hormone-independent in COS-1 cells, and suggest that co-localization of both AR and RCHY1to the nucleus upon androgen addition may allow RCHY1 to play a role in nuclear processes.
It has been reported that wild-type RCHY1is an unstable protein with a short half-life and coexpression of TIP60 enhances RCHY1 protein stability and alters RCHY1 subcellular localization. In addition, MVP (measles virus phosphoprotein ) is able to specifically interact with and stabilize the RCHY1 by preventing its ubiquitination. It has been reported that the RCHY1 also interacts with NTKL-BP1 (N-terminal kinase-like protein-binding protein 1) protein

Homology

It belongs to the ring finger ubiquitin protein E3 ligase family. Containing Conserved RING-finger Domain (residues 145 - 186 ) and CHY zinc finger (residues 20-94).

Mutations

Note

Unknown

Implicated in

Entity name
Non-Small Cell Lung Cancer
Disease
Lung cancers are pathologically classified as small cell lung cancer and non-small cell lung cancer (non-small cell lung cancer includes large cell carcinomas, squamous cell carcinomas and adenocarcinomas).
Oncogenesis
RCHY1 protein is overexpressed in about 84% human lung cancers compared to uninvolved lung tissue. The RCHY1 protein was also elevated in about 93% of murine lung tumors. Because RCHY1 is an ubiquitin-protein ligase that promotes p53 protein degradation, the increased RCHY1 expression could play an important role in lung tumorigenesis.

Bibliography

Pubmed IDLast YearTitleAuthors
122002282002Cloning and characterization of an androgen receptor N-terminal-interacting protein with ubiquitin-protein ligase activity.Beitel LK et al
161407592005Inhibition of ubiquitination and stabilization of human ubiquitin E3 ligase PIRH2 by measles virus phosphoprotein.Chen M et al
155471852004Expression of Pirh2, a newly identified ubiquitin protein ligase, in lung cancer.Duan W et al
126542452003Pirh2, a p53-induced ubiquitin-protein ligase, promotes p53 degradation.Leng RP et al
147018042004Control of human PIRH2 protein stability: involvement of TIP60 and the proteosome.Logan IR et al
157812632005A new human gene hNTKL-BP1 interacts with hPirh2.Zhang L et al

Other Information

Locus ID:

NCBI: 25898
MIM: 607680
HGNC: 17479
Ensembl: ENSG00000163743

Variants:

dbSNP: 25898
ClinVar: 25898
TCGA: ENSG00000163743
COSMIC: RCHY1

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000163743ENST00000324439Q96PM5
ENSG00000163743ENST00000380840Q96PM5
ENSG00000163743ENST00000504085D6RAF6
ENSG00000163743ENST00000505105Q96PM5
ENSG00000163743ENST00000507014Q96PM5
ENSG00000163743ENST00000512706Q96PM5
ENSG00000163743ENST00000513257Q96PM5
ENSG00000163743ENST00000513909H0YAI4

Expression (GTEx)

0
5
10
15
20
25

Pathways

PathwaySourceExternal ID
p53 signaling pathwayKEGGko04115
Ubiquitin mediated proteolysisKEGGko04120
p53 signaling pathwayKEGGhsa04115
Ubiquitin mediated proteolysisKEGGhsa04120
MeaslesKEGGko05162
MeaslesKEGGhsa05162
Immune SystemREACTOMER-HSA-168256
Adaptive Immune SystemREACTOMER-HSA-1280218
Class I MHC mediated antigen processing & presentationREACTOMER-HSA-983169
Antigen processing: Ubiquitination & Proteasome degradationREACTOMER-HSA-983168
DNA RepairREACTOMER-HSA-73894
DNA Damage BypassREACTOMER-HSA-73893
Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA templateREACTOMER-HSA-110313
Translesion Synthesis by POLHREACTOMER-HSA-110320

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
126542452003Pirh2, a p53-induced ubiquitin-protein ligase, promotes p53 degradation.233
126542452003Pirh2, a p53-induced ubiquitin-protein ligase, promotes p53 degradation.233
190434142008Molecular basis of Pirh2-mediated p53 ubiquitylation.42
180068232007Pirh2 promotes ubiquitin-dependent degradation of the cyclin-dependent kinase inhibitor p27Kip1.36
200085552010Pirh2 E3 ubiquitin ligase targets DNA polymerase eta for 20S proteasomal degradation.34
155471852004Expression of Pirh2, a newly identified ubiquitin protein ligase, in lung cancer.33
169147342006Human PIRH2 enhances androgen receptor signaling through inhibition of histone deacetylase 1 and is overexpressed in prostate cancer.28
221254902011Role of Pirh2 in mediating the regulation of p53 and c-Myc.27
217916032011Pirh2 E3 ubiquitin ligase monoubiquitinates DNA polymerase eta to suppress translesion DNA synthesis.26
122002282002Cloning and characterization of an androgen receptor N-terminal-interacting protein with ubiquitin-protein ligase activity.24

Citation

Wenrui Duan ; Miguel A. Villalona-Calero

RCHY1 (ring finger and CHY zinc finger domain containing 1)

Atlas Genet Cytogenet Oncol Haematol. 2006-03-01

Online version: http://atlasgeneticsoncology.org/gene/43012/rchy1