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

Identity

Other namesPIRH2
ARNIP
CHIMP
RNF199
ZNF363
PRO1996
DKFZp586C1620
HGNC (Hugo) RCHY1
LocusID (NCBI) 25898
Location 4q21.1
Location_base_pair Starts at 76404247 and ends at 76439640 bp from pter ( according to hg19-Feb_2009)  [Mapping]

DNA/RNA

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

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).

Mutations

Note Unknown

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.
  

External links

Nomenclature
HGNC (Hugo)RCHY1   17479
Cards
AtlasRCHY1ID43012ch04q21
Entrez_Gene (NCBI)RCHY1  25898  ring finger and CHY zinc finger domain containing 1, E3 ubiquitin protein ligase
GeneCards (Weizmann)RCHY1
Ensembl (Hinxton)ENSG00000163743 [Gene_View]  chr4:76404247-76439640 [Contig_View]  RCHY1 [Vega]
ICGC DataPortalENSG00000163743
cBioPortalRCHY1
AceView (NCBI)RCHY1
Genatlas (Paris)RCHY1
WikiGenes25898
SOURCE (Princeton)NM_001008925 NM_001009922 NM_001278536 NM_001278537 NM_001278538 NM_001278539 NM_015436
Genomic and cartography
GoldenPath (UCSC)RCHY1  -  4q21.1   chr4:76404247-76439640 -  4q21.1-q21.3   [Description]    (hg19-Feb_2009)
EnsemblRCHY1 - 4q21.1-q21.3 [CytoView]
Mapping of homologs : NCBIRCHY1 [Mapview]
OMIM607680   
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)AC_000136 NC_000004 NC_018915 NG_029152 NT_016354 NW_001838915 NW_004929320
Consensus coding sequences : CCDS (NCBI)RCHY1
Cluster EST : UnigeneHs.48297 [ NCBI ]
CGAP (NCI)Hs.48297
Alternative Splicing : Fast-db (Paris)GSHG0023327
Alternative Splicing GalleryENSG00000163743
Gene ExpressionRCHY1 [ NCBI-GEO ]     RCHY1 [ SEEK ]   RCHY1 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ96PM5 (Uniprot)
NextProtQ96PM5  [Medical]
With graphics : InterProQ96PM5
Splice isoforms : SwissVarQ96PM5 (Swissvar)
Catalytic activity : Enzyme6.3.2.- [ Enzyme-Expasy ]   6.3.2.-6.3.2.- [ IntEnz-EBI ]   6.3.2.- [ BRENDA ]   6.3.2.- [ KEGG ]   
Domaine pattern : Prosite (Expaxy)ZF_CHY (PS51266)    ZF_CTCHY (PS51270)    ZF_RING_2 (PS50089)   
Domains : Interpro (EBI)Rubredoxin-type_fold [organisation]   Znf_CHY [organisation]   Znf_CTCHY [organisation]   Znf_RING [organisation]   Znf_RING/FYVE/PHD [organisation]  
Related proteins : CluSTrQ96PM5
Domain families : Pfam (Sanger)zf-CHY (PF05495)    zf-RING_2 (PF13639)   
Domain families : Pfam (NCBI)pfam05495    pfam13639   
Domain families : Smart (EMBL)RING (SM00184)  
DMDM Disease mutations25898
Blocks (Seattle)Q96PM5
PDB (SRS)2JRJ    2K2C    2K2D   
PDB (PDBSum)2JRJ    2K2C    2K2D   
PDB (IMB)2JRJ    2K2C    2K2D   
PDB (RSDB)2JRJ    2K2C    2K2D   
Human Protein AtlasENSG00000163743 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasQ96PM5
HPRD07607
IPIIPI00289787   IPI00552384   IPI00021192   IPI00552504   IPI00967694   IPI00964860   IPI00966948   IPI00965022   IPI00965612   
Protein Interaction databases
DIP (DOE-UCLA)Q96PM5
IntAct (EBI)Q96PM5
FunCoupENSG00000163743
BioGRIDRCHY1
InParanoidQ96PM5
Interologous Interaction database Q96PM5
IntegromeDBRCHY1
STRING (EMBL)RCHY1
Ontologies - Pathways
Ontology : AmiGOubiquitin ligase complex  p53 binding  ubiquitin-protein transferase activity  receptor binding  protein binding  nucleus  nucleolus  cytoplasm  zinc ion binding  protein ubiquitination  nuclear speck  ligase activity  positive regulation of protein ubiquitination  positive regulation of proteasomal ubiquitin-dependent protein catabolic process  protein ubiquitination involved in ubiquitin-dependent protein catabolic process  protein homodimerization activity  protein autoubiquitination  
Ontology : EGO-EBIubiquitin ligase complex  p53 binding  ubiquitin-protein transferase activity  receptor binding  protein binding  nucleus  nucleolus  cytoplasm  zinc ion binding  protein ubiquitination  nuclear speck  ligase activity  positive regulation of protein ubiquitination  positive regulation of proteasomal ubiquitin-dependent protein catabolic process  protein ubiquitination involved in ubiquitin-dependent protein catabolic process  protein homodimerization activity  protein autoubiquitination  
Pathways : KEGGp53 signaling pathway    Ubiquitin mediated proteolysis    Measles   
Protein Interaction DatabaseRCHY1
Wikipedia pathwaysRCHY1
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)RCHY1
snp3D : Map Gene to Disease25898
SNP (GeneSNP Utah)RCHY1
SNP : HGBaseRCHY1
Genetic variants : HAPMAPRCHY1
Exome VariantRCHY1
1000_GenomesRCHY1 
ICGC programENSG00000163743 
Somatic Mutations in Cancer : COSMICRCHY1 
CONAN: Copy Number AnalysisRCHY1 
Mutations and Diseases : HGMDRCHY1
Mutations and Diseases : intOGenRCHY1
Genomic VariantsRCHY1  RCHY1 [DGVbeta]
dbVarRCHY1
ClinVarRCHY1
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM607680   
MedgenRCHY1
GENETestsRCHY1
Disease Genetic AssociationRCHY1
Huge Navigator RCHY1 [HugePedia]  RCHY1 [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneRCHY1
Homology/Alignments : Family Browser (UCSC)RCHY1
Phylogenetic Trees/Animal Genes : TreeFamRCHY1
Chemical/Protein Interactions : CTD25898
Chemical/Pharm GKB GenePA38240
Clinical trialRCHY1
Cancer Resource (Charite)ENSG00000163743
Other databases
Probes
Litterature
PubMed55 Pubmed reference(s) in Entrez
CoreMineRCHY1
iHOPRCHY1
OncoSearchRCHY1

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
 
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
 
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
 
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
 
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
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written03-2006Wenrui Duan, Miguel A. Villalona-Calero

Citation

This paper should be referenced as such :
Duan, W ; Villalona-Calero, MA
RCHY1 (ring finger and CHY zinc finger domain containing 1)
Atlas Genet Cytogenet Oncol Haematol. 2006;10(3):173-174.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/RCHY1ID43012ch04q21.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Tue Sep 23 18:53:00 CEST 2014

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