Molecule Information

General Information of the Molecule (ID: Mol00603)

• Name: E3 ubiquitin-protein ligase RING2 (RING2) ,Homo sapiens
• Synonyms: Huntingtin-interacting protein 2-interacting protein 3; HIP2-interacting protein 3; Protein DinG; RING finger protein 1B; RING1b; RING finger protein 2; RING finger protein BAP-1; RING-type E3 ubiquitin transferase RING2; BAP1; DING; HIPI3; RING1B
• Molecule Type: Protein
• Gene Name: RNF2
• Gene ID: 6045
• Location: chr1:185045526-185102603[+]
• Sequence:
  MSQAVQTNGTQPLSKTWELSLYELQRTPQEAITDGLEIVVSPRSLHSELMCPICLDMLKN
  TMTTKECLHRFCADCIITALRSGNKECPTCRKKLVSKRSLRPDPNFDALISKIYPSRDEY
  EAHQERVLARINKHNNQQALSHSIEEGLKIQAMNRLQRGKKQQIENGSGAEDNGDSSHCS
  NASTHSNQEAGPSNKRTKTSDDSGLELDNNNAAMAIDPVMDGASEIELVFRPHPTLMEKD
  DSAQTRYIKTSGNATVDHLSKYLAVRLALEELRSKGESNQMNLDTASEKQYTIYIATASG
  QFTVLNGSFSLELVSEKYWKVNKPMELYYAPTKEHK
• Function: E3 ubiquitin-protein ligase that mediates monoubiquitination of 'Lys-119' of histone H2A (H2AK119Ub), thereby playing a central role in histone code and gene regulation. H2AK119Ub gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals. May be involved in the initiation of both imprinted and random X inactivation. Essential component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones, rendering chromatin heritably changed in its expressibility. E3 ubiquitin-protein ligase activity is enhanced by BMI1/PCGF4. Acts as the main E3 ubiquitin ligase on histone H2A of the PRC1 complex, while RING1 may rather act as a modulator of RNF2/RING2 activity (Probable). Association with the chromosomal DNA is cell-cycle dependent. In resting B- and T-lymphocytes, interaction with AURKB leads to block its activity, thereby maintaining transcription in resting lymphocytes. Also acts as a negative regulator of autophagy by mediating ubiquitination of AMBRA1, leading to its subsequent degradation.
• Uniprot ID: RING2_HUMAN
• Ensembl ID: ENSG00000121481
• HGNC ID: HGNC:10061

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Cisplatin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Ovarian cancer [1]

• Sensitive Disease: Ovarian cancer [ICD-11: 2C73.0]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• Cell Pathway Regulation: MAPK signaling pathway; Inhibition; hsa04010
• In Vitro Model: A2780 cells; Ovary; Homo sapiens (Human); CVCL_0134
• In Vitro Model: A2780/DDP cells; Ovary; Homo sapiens (Human); CVCL_D619
• In Vivo Model: Nude mouse model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometry assay
• Mechanism Description: miR-139-5p overexpression combined with inactivation of the MAPk signaling pathway can reverse the cisplatin resistance of OC by suppressing RNF2.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Ovarian cancer [ICD-11: 2C73]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Ovary
• The Specified Disease: Ovarian cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.51E-01; Fold-change: 8.15E-02; Z-score: 2.52E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 9.92E-01; Fold-change: -4.74E-02; Z-score: -8.27E-02

References

• Ref 1: Reversal of cisplatin resistance by microRNA-139-5p-independent RNF2 downregulation and MAPK inhibition in ovarian cancer. Am J Physiol Cell Physiol. 2018 Aug 1;315(2):C225-C235. doi: 10.1152/ajpcell.00283.2017. Epub 2018 May 2.