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

Related Tools

Target Illumination GWAS Analytics (TIGA)

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GENEVA

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ARCHS4

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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: 39.92   (req: < 5)

Gene RIFs: 26   (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: 39.92   (req: >= 5)

Gene RIFs: 26   (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

GWAS Traits (2)

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1 – 2 of 2

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
phosphatidylethanolamine measurement	EFO_0010228	1	2	2		52.7
apolipoprotein A 1 measurement	EFO_0004614	1	1	1		16

• Explore on Target Illumination GWAS Analytics (TIGA)

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
phosphatidylethanolamine measurement	EFO_0010228	2		52.7
apolipoprotein A 1 measurement	EFO_0004614	1		16

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Orthologs (13)

1 – 5 of 13

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	ring finger protein 111	VGNC:1887	453477
Macaque	ring finger protein 111		701953
Mouse	ring finger 111	MGI:1934919	93836
Rat	ring finger protein 111	RGD:1310097	300813
Dog	ring finger protein 111	VGNC:45621	478323

Species	Name	OMA	EggNOG	Inparanoid
Chimp	ring finger protein 111
Macaque	ring finger protein 111
Mouse	ring finger 111
Rat	ring finger protein 111
Dog	ring finger protein 111

Protein Structure (3 Structures, 1 AlphaFold Model)

Representation

  axes   backbone   ball+stick   cartoon   rocket   rope   spacefill

Color Scheme

  target   atomindex   bfactor   chainname   electrostatic   element   hydrophobicity   resname   sstruc

Click on a row in the table to change the structure displayed.
More information can be found at RCSB PDB

AF-Q6ZNA4-F1-model_v1

AlphaFold Structures Developed by DeepMind and EMBL-EBI

1 – 3 of 3

PDB Structure Id	Ligand	Method	Resolution (Å)	Residues	Fraction of Total Protein	Pub Year	Title

PDB Structure Id	Fraction of Total Protein	Resolution	Pub Year

Pathways (21)

Reactome (17)

PathwayCommons (2)

UniProt (1)

WikiPathways (1)

Adaptive Immune System (R-HSA-1280218)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Adaptive Immune System	894 targets	R-HSA-1280218
Reactome	Antigen processing: Ubiquitination & Proteasome degradation	307 targets	R-HSA-983168
Reactome	Class I MHC mediated antigen processing & presentation	437 targets	R-HSA-983169
Reactome	DNA Repair	306 targets	R-HSA-73894
Reactome	Downregulation of SMAD2/3:SMAD4 transcriptional activity	23 targets	R-HSA-2173795

Name	Explore in Pharos	Explore in Source
Adaptive Immune System	894 targets	R-HSA-1280218
Antigen processing: Ubiquitination & Proteasome degradation	307 targets	R-HSA-983168
Class I MHC mediated antigen processing & presentation	437 targets	R-HSA-983169
DNA Repair	306 targets	R-HSA-73894
Downregulation of SMAD2/3:SMAD4 transcriptional activity	23 targets	R-HSA-2173795

Gene Ontology Terms (20)

Functions (4)

Components (6)

Processes (10)

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1 – 4 of 4

GO Term	Evidence	Assigned by
SUMO polymer binding	Inferred from Direct Assay (IDA)	UniProtKB
ubiquitin protein ligase activity	Inferred from Mutant Phenotype (IMP)	BHF-UCL
SMAD binding	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
metal ion binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW

Protein-Protein Interactions (330)

Explore Interacting Targets

1 – 10 of 330

• See Interactions on String-DB

CSNK2B

Tbio

Family: Kinase

Novelty: 0.00152367

p_int: 0.999998191

p_ni: 0.000001795

p_wrong: 1.4e-8

Data Source: BioPlex

CSNK2A2

Tchem

Family: Kinase

Novelty: 0.00231447

p_int: 0.999994149

p_ni: 0.000005834

p_wrong: 1.7e-8

Score: 0.205

Data Source: BioPlex,STRINGDB

FAM189B

Tbio

Novelty: 0.21064304

p_int: 0.999957805

p_ni: 0.000021491

p_wrong: 0.000020704

Data Source: BioPlex

UBXN7

Tbio

Novelty: 0.07437638

p_int: 0.999946139

p_ni: 0.000053861

Score: 0.882

Data Source: BioPlex,STRINGDB

UBE2W

Tbio

Novelty: 0.07255713

p_int: 0.999830467

p_ni: 1.52e-7

p_wrong: 0.000169381

Score: 0.927

Data Source: BioPlex,STRINGDB

TPX2

Tbio

Novelty: 0.00435921

p_int: 0.999364525

p_ni: 0.000635464

p_wrong: 1.2e-8

Score: 0.27

Data Source: BioPlex,STRINGDB

DCUN1D5

Tdark

Novelty: 0.56719852

p_int: 0.948596494

p_ni: 0.051375499

p_wrong: 0.000028007

Score: 0.191

Data Source: BioPlex,STRINGDB

TTC9C

Tdark

Novelty: 0.85949913

p_int: 0.948407379

p_ni: 0.049733315

p_wrong: 0.001859306

Score: 0.153

Data Source: BioPlex,STRINGDB

SUGP1

Tbio

Novelty: 0.00434166

p_int: 0.933616351

p_ni: 0.009109862

p_wrong: 0.057273787

Score: 0.175

Data Source: BioPlex,STRINGDB

CGGBP1

Tbio

Novelty: 0.10880271

p_int: 0.904999131

p_ni: 0.094994785

p_wrong: 0.000006084

Score: 0.218

Data Source: BioPlex,STRINGDB

Publication Statistics

PubMed Score  39.92

PubMed score by year

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PubTator Score  33.79

PubTator score by year

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Amino Acid Sequence

Residue Counts

Protein Sequence

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UniProt Keyword Find Similar Targets

3D-structure
Alternative splicing
Complete proteome
Cytoplasm
Developmental protein
DNA damage
DNA repair
Isopeptide bond
Metal-binding
Nucleus

GWAS Trait Find Similar Targets

apolipoprotein A 1 measurement
phosphatidylethanolamine measurement

MGI Phenotype Find Similar Targets

embryo phenotype
mortality/aging
nervous system phenotype