Tbio RNF111 E3 ubiquitin-protein ligase Arkadia

Protein Summary

Description

E3 ubiquitin-protein ligase (PubMed:26656854). Required for mesoderm patterning during embryonic development (By similarity). Acts as an enhancer of the transcriptional responses of the SMAD2/SMAD3 effectors, which are activated downstream of BMP (PubMed:14657019, PubMed:16601693). Acts by mediating ubiquitination and degradation of SMAD inhibitors such as SMAD7, inducing their proteasomal degradation and thereby enhancing the transcriptional activity of TGF-beta and BMP (PubMed:14657019, PubMed:16601693). In addition to enhance transcription of SMAD2/SMAD3 effectors, also regulates their turnover by mediating their ubiquitination and subsequent degradation, coupling their activation with degradation, thereby ensuring that only effectors 'in use' are degraded (By similarity). Activates SMAD3/SMAD4-dependent transcription by triggering signal-induced degradation of SNON isoform of SKIL (PubMed:17591695). Associates with UBE2D2 as an E2 enzyme (PubMed:22411132). Specifically binds polysumoylated chains via SUMO interaction motifs (SIMs) and mediates ubiquitination of sumoylated substrates (PubMed:23751493). Catalyzes 'Lys-63'-linked ubiquitination of sumoylated XPC in response to UV irradiation, promoting nucleotide excision repair (PubMed:23751493). Mediates ubiquitination and degradation of sumoylated PML (By similarity). The regulation of the BMP-SMAD signaling is however independent of sumoylation and is not dependent of SUMO interaction motifs (SIMs) (By similarity). The protein encoded by this gene is a nuclear RING-domain containing E3 ubiquitin ligase. This protein interacts with the transforming growth factor (TGF) -beta/NODAL signaling pathway by promoting the ubiquitination and proteosomal degradation of negative regulators, like SMAD proteins, and thereby enhances TGF-beta target-gene transcription. As a modulator of the nodal signaling cascade, this gene plays a critical role in the induction of mesoderm during embryonic development. Alternative splicing of this gene results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2012]

Uniprot Accession IDs

• Q6ZNA4
• C9JUS4
• H0YN55
• Q6P9A4
• Q6ZMU2
• Q7L428
• Q7Z346
• Q8N1P9
• Q8WUA3
• Q9NSR1

Gene Name

• RNF111

Ensembl ID

• ENST00000348370
• ENSP00000288199
• ENSG00000157450
• ENST00000557998
• ENSP00000452732
• ENST00000559209
• ENSP00000453872
• ENST00000561186
• ENSP00000453015

Symbol

• ARK
• hRNF111

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
virus perturbation	0.85
biological process	0.83
microRNA	0.81
molecular function	0.67
kinase perturbation	0.66

Protein Classes

No PANTHER Classes or DTO Classes found

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 54.24   (req: < 5)

Gene RIFs: 28   (req: <= 3)

Antibodies: 116   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 54.24   (req: >= 5)

Gene RIFs: 28   (req: > 3)

Antibodies: 116   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 14

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0