Rh type C glycoprotein (RHCG), encoded by the gene RHCG, is a member of Rhesus (Rh) family. It was originally identified as Rh blood group antigens in human erythroid cells and is widely expressed in ammonia-transporting organs, including kidneys, CNS, testes, lung, liver, stomach and intestinal tract. Especially, RHCG is widely expressed in different tissues where ammonia metabolism is indispensable for exerting normal biological functions. RHCG shares a common folding structure with ammonia transporter that is characterized by the presence of 12 transmembrane-spanning segments.
Basic Information of RHCG | |
Protein Name | Ammonium transporter Rh type C |
Gene Name | RHCG |
Aliases | Rh glycoprotein kidney, Rhesus blood group family type C glycoprotein, Rh family type C glycoprotein, Rh type C glycoprotein, Tumor-related protein DRC2 |
Organism | Homo sapiens (Human) |
UniProt ID | Q9UBD6 |
Transmembrane Times | 12 |
Length (aa) | 479 |
Sequence | MAWNTNLRWRLPLTCLLLQVIMVILFGVFVRYDFEADAHWWSERTHKNLSDMENEFYYRYPSFQDVHVMVFVGFGFLMTFLQRYGFSAVGFNFLLAAFGIQWALLMQGWFHFLQDRYIVVGVENLINADFCVASVCVAFGAVLGKVSPIQLLIMTFFQVTLFAVNEFILLNLLKVKDAGGSMTIHTFGAYFGLTVTRILYRRNLEQSKERQNSVYQSDLFAMIGTLFLWMYWPSFNSAISYHGDSQHRAAINTYCSLAACVLTSVAISSALHKKGKLDMVHIQNATLAGGVAVGTAAEMMLMPYGALIIGFVCGIISTLGFVYLTPFLESRLHIQDTCGINNLHGIPGIIGGIVGAVTAASASLEVYGKEGLVHSFDFQGFNGDWTARTQGKFQIYGLLVTLAMALMGGIIVGLILRLPFWGQPSDENCFEDAVYWEMPEGNSTVYIPEDPTFKPSGPSVPSVPMVSPLPMASSVPLVP |
Functioning as an ammonia-specific transporter, RHCG plays a critical role in ammonium handling and pH homeostasis in many physiological processes. Recently, RHCG is widely studied in oncology. It has been confirmed that RHCG could exert suppression effects on cell proliferation, migration, and invasions in various cancers, such as esophageal squamous cell carcinoma (ESCC), cervical cancer, and prostate cancer. RHCG is shown to suppress cancer progression through inhibiting migration and inducing apoptosis regulated by TGF-β1, suggesting the potential as a prognostic biomarker and therapeutic target for human cancers. In addition, it is reported that TNF-α may promote ammonia transport from the blood to brain tissues and then exacerbate the toxic effects of ammonia by upregulating RHCG.
Fig.1 A model illustrating how the Rh proteins-Rhag (in the erythrocyte membranes). (Wright, 2009)
This article indicates that RHCG can suppress cervical cancer progression through inhibiting migration and inducing apoptosis regulated by TGF-β1, suggesting the potential as a prognostic biomarker and therapeutic target for human cervical cancer.
This article demonstrates that RHCG can inhibit clonogenicity, cell motility, tumor formation and metastasis of esophageal squamous cell carcinoma (ESCC) by inhibiting NF-κB signaling and MMP1 expression.
This article suggests that methylation of the RHCG-TCAF1 panel adds significant independent prognostic value to established prognostic parameters for prostate cancer and thus may help to guide treatment decisions in the future.
This article suggests that RhCG modulates the proton-ATPase function and urinary acidification, whereas proton-ATPase activity does not affect RhCG function, which may help to coordinate ammonia and proton secretion beyond physicochemical driving forces.
This article concludes that both Rhbg and Rhcg are highly expressed in specific cells in the male reproductive tract where they can contribute to multiple components of male fertility.
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