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

Written2006-03Wenrui Duan, Miguel A. Villalona-Calero
Comprehensive Cancer Center, 1230 JCHRI, 300 West 10th Ave, Columbus, Ohio 43210, USA

(Note : for Links provided by Atlas : click)

1. Identity

General Information
zinc finger protein 363
ring finger and CHY zinc finger domain containing 1
ring finger and CHY zinc finger domain containing 1, E3 ubiquitin protein ligase
Alias_symbol (synonym)CHIMP
Other alias
LocusID (NCBI) 25898
Atlas_Id 43012
Location 4q21.1  [Link to chromosome band 4q21]
Location_base_pair Starts at 75479037 and ends at 75514430 bp from pter ( according to hg19-Feb_2009)  [Mapping RCHY1.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
RCHY1 (4q21.1) / YWHAG (7q11.23)SFXN3 (10q24.31) / RCHY1 (4q21.1)


Description The gene encompasses 32 kb of DNA; 9 exons.
Transcription 4.3 kb nucleotides mRNA. 783 bp open reading frame.

3. Protein

  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).

4. Mutations

Note Unknown

5. Implicated in

Entity 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.

6. Bibliography

Cloning and characterization of an androgen receptor N-terminal-interacting protein with ubiquitin-protein ligase activity.
Beitel LK, Elhaji YA, Lumbroso R, Wing SS, Panet-Raymond V, Gottlieb B, Pinsky L, Trifiro MA
Journal of molecular endocrinology. 2002 ; 29 (1) : 41-60.
PMID 12200228
Inhibition of ubiquitination and stabilization of human ubiquitin E3 ligase PIRH2 by measles virus phosphoprotein.
Chen M, Cortay JC, Logan IR, Sapountzi V, Robson CN, Gerlier D
Journal of virology. 2005 ; 79 (18) : 11824-11836.
PMID 16140759
Expression of Pirh2, a newly identified ubiquitin protein ligase, in lung cancer.
Duan W, Gao L, Druhan LJ, Zhu WG, Morrison C, Otterson GA, Villalona-Calero MA
Journal of the National Cancer Institute. 2004 ; 96 (22) : 1718-1721.
PMID 15547185
Pirh2, a p53-induced ubiquitin-protein ligase, promotes p53 degradation.
Leng RP, Lin Y, Ma W, Wu H, Lemmers B, Chung S, Parant JM, Lozano G, Hakem R, Benchimol S
Cell. 2003 ; 112 (6) : 779-791.
PMID 12654245
Control of human PIRH2 protein stability: involvement of TIP60 and the proteosome.
Logan IR, Sapountzi V, Gaughan L, Neal DE, Robson CN
The Journal of biological chemistry. 2004 ; 279 (12) : 11696-11704.
PMID 14701804
A new human gene hNTKL-BP1 interacts with hPirh2.
Zhang L, Li J, Wang C, Ma Y, Huo K
Biochemical and biophysical research communications. 2005 ; 330 (1) : 293-297.
PMID 15781263

7. Citation

This paper should be referenced as such :
Duan, W ; Villalona-Calero, MA
RCHY1 (ring finger, CHY zinc finger domain containing 1)
Atlas Genet Cytogenet Oncol Haematol. 2006;10(3):173-174.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://atlasgeneticsoncology.usal.es/classic/Genes/RCHY1ID43012ch04q21.html

8. External links

HGNC (Hugo)RCHY1   17479
Entrez_Gene (NCBI)RCHY1  25898  ring finger and CHY zinc finger domain containing 1
AliasesARNIP; CHIMP; PIRH2; PRO1996; 
RNF199; ZCHY; ZNF363
GeneCards (Weizmann)RCHY1
Ensembl hg19 (Hinxton)ENSG00000163743 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000163743 [Gene_View] &nbspENSG00000163743 [Sequence]  chr4:75479037-75514430 [Contig_View]  RCHY1 [Vega]
ICGC DataPortalENSG00000163743
TCGA cBioPortalRCHY1
Genatlas (Paris)RCHY1
SOURCE (Princeton)RCHY1
Genetics Home Reference (NIH)RCHY1
Genomic and cartography
GoldenPath hg38 (UCSC)RCHY1  -     chr4:75479037-75514430 -  4q21.1   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)RCHY1  -     4q21.1   [Description]    (hg19-Feb_2009)
EnsemblRCHY1 - 4q21.1 [CytoView hg19]  RCHY1 - 4q21.1 [CytoView hg38]
Mapping of homologs : NCBIRCHY1 [Mapview hg19]  RCHY1 [Mapview hg38]
Gene and transcription
Genbank (Entrez)AB209072 AF247041 AF255666 AF305424 AK091501
RefSeq transcript (Entrez)NM_001008925 NM_001009922 NM_001278536 NM_001278537 NM_001278538 NM_001278539 NM_015436
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)RCHY1
Cluster EST : UnigeneHs.48297 [ NCBI ]
CGAP (NCI)Hs.48297
Alternative Splicing GalleryENSG00000163743
Gene ExpressionRCHY1 [ NCBI-GEO ]   RCHY1 [ EBI - ARRAY_EXPRESS ]   RCHY1 [ SEEK ]   RCHY1 [ MEM ]
Gene Expression Viewer (FireBrowse)RCHY1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets] &nbsp [Normal Tissue Atlas] &nbsp[carcinoma Classsification] &nbsp[NCI60]
GenevestigatorExpression in : [tissues] &nbsp[cell-lines] &nbsp[cancer] &nbsp[perturbations] &nbsp
BioGPS (Tissue expression)25898
GTEX Portal (Tissue expression)RCHY1
Human Protein AtlasENSG00000163743-RCHY1 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ96PM5   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ96PM5  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ96PM5
Splice isoforms : SwissVarQ96PM5
Catalytic activity : Enzyme2.3.2.27 [ Enzyme-Expasy ] [ IntEnz-EBI ] [ BRENDA ] [ KEGG ]   
Domaine pattern : Prosite (Expaxy)ZF_CHY (PS51266)    ZF_CTCHY (PS51270)    ZF_RING_2 (PS50089)   
Domains : Interpro (EBI)Znf_CHY    Znf_CHY_sf    Znf_CTCHY    Znf_CTCHY_sf    Znf_RING    Znf_RING/FYVE/PHD   
Domain families : Pfam (Sanger)zf-CHY (PF05495)    zf-RING_2 (PF13639)   
Domain families : Pfam (NCBI)pfam05495    pfam13639   
Domain families : Smart (EMBL)RING (SM00184)  
Conserved Domain (NCBI)RCHY1
DMDM Disease mutations25898
Blocks (Seattle)RCHY1
PDB (RSDB)2JRJ    2K2C    2K2D   
PDB Europe2JRJ    2K2C    2K2D   
PDB (PDBSum)2JRJ    2K2C    2K2D   
PDB (IMB)2JRJ    2K2C    2K2D   
Structural Biology KnowledgeBase2JRJ    2K2C    2K2D   
SCOP (Structural Classification of Proteins)2JRJ    2K2C    2K2D   
CATH (Classification of proteins structures)2JRJ    2K2C    2K2D   
Human Protein Atlas [tissue]ENSG00000163743-RCHY1 [tissue]
Peptide AtlasQ96PM5
IPIIPI00289787   IPI00552384   IPI00021192   IPI00552504   IPI00967694   IPI00964860   IPI00966948   IPI00965022   IPI00965612   
Protein Interaction databases
IntAct (EBI)Q96PM5
Ontologies - Pathways
Ontology : AmiGOubiquitin ligase complex  p53 binding  ubiquitin-protein transferase activity  ubiquitin-protein transferase activity  protein binding  nucleus  nucleoplasm  nucleoplasm  cytoplasm  cytosol  ubiquitin-dependent protein catabolic process  zinc ion binding  protein ubiquitination  protein ubiquitination  nuclear speck  positive regulation of protein ubiquitination  positive regulation of proteasomal ubiquitin-dependent protein catabolic process  protein homodimerization activity  error-free translesion synthesis  
Ontology : EGO-EBIubiquitin ligase complex  p53 binding  ubiquitin-protein transferase activity  ubiquitin-protein transferase activity  protein binding  nucleus  nucleoplasm  nucleoplasm  cytoplasm  cytosol  ubiquitin-dependent protein catabolic process  zinc ion binding  protein ubiquitination  protein ubiquitination  nuclear speck  positive regulation of protein ubiquitination  positive regulation of proteasomal ubiquitin-dependent protein catabolic process  protein homodimerization activity  error-free translesion synthesis  
Pathways : KEGGp53 signaling pathway    Ubiquitin mediated proteolysis    Measles   
REACTOMEQ96PM5 [protein]
REACTOME PathwaysR-HSA-983168 [pathway]   
NDEx NetworkRCHY1
Atlas of Cancer Signalling NetworkRCHY1
Wikipedia pathwaysRCHY1
Orthology - Evolution
GeneTree (enSembl)ENSG00000163743
Phylogenetic Trees/Animal Genes : TreeFamRCHY1
Homologs : HomoloGeneRCHY1
Homology/Alignments : Family Browser (UCSC)RCHY1
Gene fusions - Rearrangements
Fusion : QuiverRCHY1
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerRCHY1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)RCHY1
Exome Variant ServerRCHY1
ExAC (Exome Aggregation Consortium)ENSG00000163743
GNOMAD BrowserENSG00000163743
Varsome BrowserRCHY1
Genetic variants : HAPMAP25898
Genomic Variants (DGV)RCHY1 [DGVbeta]
DECIPHERRCHY1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisRCHY1 
ICGC Data PortalRCHY1 
TCGA Data PortalRCHY1 
Broad Tumor PortalRCHY1
OASIS PortalRCHY1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICRCHY1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDRCHY1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch RCHY1
DgiDB (Drug Gene Interaction Database)RCHY1
DoCM (Curated mutations)RCHY1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)RCHY1 (select a term)
NCG5 (London)RCHY1
Cancer3DRCHY1(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry RCHY1
NextProtQ96PM5 [Medical]
Target ValidationRCHY1
Huge Navigator RCHY1 [HugePedia]
snp3D : Map Gene to Disease25898
BioCentury BCIQRCHY1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD25898
Chemical/Pharm GKB GenePA38240
Clinical trialRCHY1
canSAR (ICR)RCHY1 (select the gene name)
DataMed IndexRCHY1
PubMed70 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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