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Aliases for RNF111 Gene

Aliases for RNF111 Gene

  • Ring Finger Protein 111 2 3 5
  • RING-Type E3 Ubiquitin Transferase Arkadia 3 4
  • HRNF111 3 4
  • E3 Ubiquitin-Protein Ligase Arkadia 3
  • RING Finger Protein 111 4
  • EC 2.3.2.27 4
  • Arkadia 3
  • ARK 3

External Ids for RNF111 Gene

Previous GeneCards Identifiers for RNF111 Gene

  • GC15P056902
  • GC15P056995
  • GC15P057067
  • GC15P059279
  • GC15P036102
  • GC15P059160

Summaries for RNF111 Gene

Entrez Gene Summary for RNF111 Gene

  • 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]

GeneCards Summary for RNF111 Gene

RNF111 (Ring Finger Protein 111) is a Protein Coding gene. Among its related pathways are Gene Expression and Class I MHC mediated antigen processing and presentation. Gene Ontology (GO) annotations related to this gene include ligase activity and ubiquitin protein ligase activity. An important paralog of this gene is RNF165.

UniProtKB/Swiss-Prot for RNF111 Gene

  • 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).

Gene Wiki entry for RNF111 Gene

Additional gene information for RNF111 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for RNF111 Gene

Genomics for RNF111 Gene

GeneHancer (GH) Regulatory Elements for RNF111 Gene

Promoters and enhancers for RNF111 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH15J058986 Promoter/Enhancer 2 EPDnew Ensembl ENCODE 663.3 +122.8 122821 3.1 HDGF ZFP64 SIN3A FEZF1 DMAP1 ZNF2 YY1 POLR2B E2F8 FOS RNF111 MYO1E LOC100420929 RPL21P113
GH15J058864 Promoter/Enhancer 1.9 FANTOM5 Ensembl ENCODE 653.3 +0.6 572 3.3 PKNOX1 ATF1 FOXA2 ARNT ARID4B SIN3A DMAP1 BRCA1 ZNF48 ATF7 ENSG00000259353 RNF111 ZNF444P1 MINDY2 SLTM ENSG00000225798 LOC101928725 SNORD3P1 ADAM10 RPL21P14
GH15J059012 Promoter 0.8 EPDnew 661.6 +146.4 146360 0.1 MEIS2 SMARCA4 ATF7 RUNX3 RNF111 RPL21P113 LOC100420929
GH15J058931 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE dbSUPER 22.5 +68.0 67979 4.1 FOXA2 PKNOX1 CLOCK ARNT ARID4B SIN3A DMAP1 ZNF2 YY1 POLR2B SLTM RNF111 BNIP2 ENSG00000225798 PIGHP1 ENSG00000259353
GH15J058769 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE 23.5 -93.3 -93287 3.8 HDGF PKNOX1 SMAD1 MLX ARNT ARID4B SIN3A FEZF1 DMAP1 YY1 LOC101928725 MINDY2 SLTM RNF111 ADAM10 BNIP2 PIGHP1 ENSG00000259402
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around RNF111 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the RNF111 gene promoter:
  • AML1a
  • AP-1
  • AP-4
  • POU2F1a
  • POU2F1
  • p300
  • GATA-1
  • Evi-1
  • Pbx1a
  • LHX3b

Genomic Locations for RNF111 Gene

Genomic Locations for RNF111 Gene
chr15:58,865,175-59,097,419
(GRCh38/hg38)
Size:
232,245 bases
Orientation:
Plus strand
chr15:59,157,374-59,389,618
(GRCh37/hg19)
Size:
232,245 bases
Orientation:
Plus strand

Genomic View for RNF111 Gene

Genes around RNF111 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
RNF111 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for RNF111 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for RNF111 Gene

Proteins for RNF111 Gene

  • Protein details for RNF111 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q6ZNA4-RN111_HUMAN
    Recommended name:
    E3 ubiquitin-protein ligase Arkadia
    Protein Accession:
    Q6ZNA4
    Secondary Accessions:
    • C9JUS4
    • H0YN55
    • Q6P9A4
    • Q6ZMU2
    • Q7L428
    • Q7Z346
    • Q8N1P9
    • Q8WUA3
    • Q9NSR1

    Protein attributes for RNF111 Gene

    Size:
    994 amino acids
    Molecular mass:
    108862 Da
    Quaternary structure:
    • Monomer (PubMed:26656854). Interacts with SMAD6, SMAD7, AXIN1, AXIN2 and SKIL isoform SNON (PubMed:16601693, PubMed:17591695). Interacts with (phosphorylated) SMAD2 and SMAD3 (By similarity). Part of a complex containing RNF111, AXIN1 and SMAD7 (PubMed:16601693). Interacts (via SIM domains) with SUMO1 and SUMO2 (PubMed:23086935).
    SequenceCaution:
    • Sequence=AAH10369.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=BAC04531.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=BAD18633.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for RNF111 Gene

    Alternative splice isoforms for RNF111 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for RNF111 Gene

Post-translational modifications for RNF111 Gene

  • Ubiquitination at Lys927
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for RNF111 Gene

Domains & Families for RNF111 Gene

Gene Families for RNF111 Gene

HGNC:
Human Protein Atlas (HPA):
  • Enzymes
  • Predicted intracellular proteins

Protein Domains for RNF111 Gene

Suggested Antigen Peptide Sequences for RNF111 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q6ZNA4

UniProtKB/Swiss-Prot:

RN111_HUMAN :
  • The SUMO interaction motifs (SIMs) mediates the binding to polysumoylated substrate.
  • Belongs to the Arkadia family.
Domain:
  • The SUMO interaction motifs (SIMs) mediates the binding to polysumoylated substrate.
  • The RING-type zinc finger mediates the E3 ubiquitin-protein ligase activity and binds directly to free ubiquitin (PubMed:26656854). Non-covalent ubiquitin-binding stabilizes the ubiquitin-conjugating enzyme E2 (donor ubiquitin) in the closed conformation and stimulates ubiquitin transfer (By similarity).
Family:
  • Belongs to the Arkadia family.
genes like me logo Genes that share domains with RNF111: view

Function for RNF111 Gene

Molecular function for RNF111 Gene

UniProtKB/Swiss-Prot Function:
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).
UniProtKB/Swiss-Prot CatalyticActivity:
S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.
UniProtKB/Swiss-Prot EnzymeRegulation:
Binds free ubiquitin non-covalently via its RING-type zinc finger. Ubiquitin-binding leads to enhance the E3 ubiquitin-protein ligase activity by stabilizing the ubiquitin-conjugating enzyme E2 (donor ubiquitin) in the closed conformation and activating ubiquitin transfer.

Enzyme Numbers (IUBMB) for RNF111 Gene

Phenotypes From GWAS Catalog for RNF111 Gene

Gene Ontology (GO) - Molecular Function for RNF111 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 16601693
GO:0016740 transferase activity IEA --
GO:0032184 SUMO polymer binding IDA 23086935
GO:0046332 SMAD binding IEA --
GO:0046872 metal ion binding IEA --
genes like me logo Genes that share ontologies with RNF111: view
genes like me logo Genes that share phenotypes with RNF111: view

Animal Model Products

miRNA for RNF111 Gene

miRTarBase miRNAs that target RNF111

Clone Products

No data available for Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for RNF111 Gene

Localization for RNF111 Gene

Subcellular locations from UniProtKB/Swiss-Prot for RNF111 Gene

Nucleus. Cytoplasm. Nucleus, PML body. Note=Upon TGF-beta treatment, translocates from nucleus to cytosol. {ECO:0000269 PubMed:16601693}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for RNF111 gene
Compartment Confidence
nucleus 5
cytosol 5
extracellular 2

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (3)
  • Nucleus (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for RNF111 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IBA,IDA --
GO:0005654 nucleoplasm TAS --
GO:0005737 cytoplasm IBA --
GO:0005829 cytosol IDA --
GO:0016605 PML body IEA --
genes like me logo Genes that share ontologies with RNF111: view

Pathways & Interactions for RNF111 Gene

genes like me logo Genes that share pathways with RNF111: view

UniProtKB/Swiss-Prot Q6ZNA4-RN111_HUMAN

  • Pathway: Protein modification; protein ubiquitination.

SIGNOR curated interactions for RNF111 Gene

Activates:
Inactivates:
Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for RNF111 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000209 protein polyubiquitination IBA --
GO:0006281 DNA repair IEA --
GO:0006974 cellular response to DNA damage stimulus IEA --
GO:0007275 multicellular organism development IEA --
GO:0007389 pattern specification process IEA --
genes like me logo Genes that share ontologies with RNF111: view

Drugs & Compounds for RNF111 Gene

No Compound Related Data Available

Transcripts for RNF111 Gene

Unigene Clusters for RNF111 Gene

Ring finger protein 111:
Representative Sequences:

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for RNF111 Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4a · 4b ^ 5 ^ 6a · 6b ^ 7 ^ 8 ^ 9 ^ 10 ^ 11a · 11b ^ 12a · 12b ^ 13 ^ 14 ^ 15a · 15b · 15c ^ 16a · 16b
SP1: - - - - -
SP2: - - - -
SP3: - - -
SP4: - - - - -
SP5: -
SP6: - -
SP7:
SP8: -

Relevant External Links for RNF111 Gene

GeneLoc Exon Structure for
RNF111
ECgene alternative splicing isoforms for
RNF111

Expression for RNF111 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for RNF111 Gene

Protein differential expression in normal tissues from HIPED for RNF111 Gene

This gene is overexpressed in Esophagus (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for RNF111 Gene



Protein tissue co-expression partners for RNF111 Gene

NURSA nuclear receptor signaling pathways regulating expression of RNF111 Gene:

RNF111

SOURCE GeneReport for Unigene cluster for RNF111 Gene:

Hs.404423

mRNA Expression by UniProt/SwissProt for RNF111 Gene:

Q6ZNA4-RN111_HUMAN
Tissue specificity: Broadly expressed.

Evidence on tissue expression from TISSUES for RNF111 Gene

  • Nervous system(4.6)
  • Intestine(4.2)
  • Kidney(2)
genes like me logo Genes that share expression patterns with RNF111: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for RNF111 Gene

Orthologs for RNF111 Gene

This gene was present in the common ancestor of animals.

Orthologs for RNF111 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia RNF111 34 33
  • 99.66 (n)
OneToOne
dog
(Canis familiaris)
Mammalia RNF111 34 33
  • 94.53 (n)
OneToOne
cow
(Bos Taurus)
Mammalia RNF111 34 33
  • 94.13 (n)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia RNF111 34
  • 89 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Rnf111 16 34 33
  • 88.74 (n)
rat
(Rattus norvegicus)
Mammalia Rnf111 33
  • 88.15 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia -- 34
  • 70 (a)
OneToMany
-- 34
  • 56 (a)
OneToMany
-- 34
  • 54 (a)
OneToMany
chicken
(Gallus gallus)
Aves RNF111 34 33
  • 82.48 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia RNF111 34
  • 77 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia rnf111 33
  • 73.28 (n)
Str.17326 33
African clawed frog
(Xenopus laevis)
Amphibia arkadia 33
zebrafish
(Danio rerio)
Actinopterygii rnf111 33
  • 61.14 (n)
RNF111 34
  • 59 (a)
OneToOne
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.6895 33
fruit fly
(Drosophila melanogaster)
Insecta CG6923 34
  • 9 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea toe-4 34
  • 18 (a)
OneToMany
Species where no ortholog for RNF111 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for RNF111 Gene

ENSEMBL:
Gene Tree for RNF111 (if available)
TreeFam:
Gene Tree for RNF111 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for RNF111: view image

Paralogs for RNF111 Gene

Paralogs for RNF111 Gene

(2) SIMAP similar genes for RNF111 Gene using alignment to 5 proteins:

  • RN111_HUMAN
  • H0YKK5_HUMAN
  • H0YKS2_HUMAN
  • H0YLK9_HUMAN
  • L0R5C6_HUMAN
genes like me logo Genes that share paralogs with RNF111: view

Variants for RNF111 Gene

Sequence variations from dbSNP and Humsavar for RNF111 Gene

SNP ID Clin Chr 15 pos Variation AA Info Type
rs1000027195 -- 59,050,285(+) G/C intron_variant
rs1000028856 -- 59,086,441(+) A/G intron_variant
rs1000088480 -- 59,056,061(+) C/G intron_variant
rs1000094341 -- 59,049,391(+) A/C intron_variant
rs1000124563 -- 59,019,207(+) G/A genic_upstream_transcript_variant, intron_variant

Structural Variations from Database of Genomic Variants (DGV) for RNF111 Gene

Variant ID Type Subtype PubMed ID
dgv151n21 CNV gain 19592680
esv34110 CNV loss 18971310
nsv1108958 CNV deletion 24896259
nsv510663 CNV deletion 20534489
nsv520769 CNV gain 19592680
nsv527307 CNV gain 19592680
nsv7266 OTHER inversion 18451855
nsv819459 CNV loss 19587683
nsv833025 CNV gain 17160897
nsv984077 CNV duplication 23825009

Variation tolerance for RNF111 Gene

Residual Variation Intolerance Score: 14.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 9.29; 88.22% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for RNF111 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
RNF111

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for RNF111 Gene

Disorders for RNF111 Gene

Additional Disease Information for RNF111

No disorders were found for RNF111 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for RNF111 Gene

Publications for RNF111 Gene

  1. Secondary ubiquitin-RING docking enhances Arkadia and Ark2C E3 ligase activity. (PMID: 26656854) Wright JD … Day CL (Nature structural & molecular biology 2016) 3 4 58
  2. RNF111/Arkadia is a SUMO-targeted ubiquitin ligase that facilitates the DNA damage response. (PMID: 23751493) Poulsen SL … Mailand N (The Journal of cell biology 2013) 3 4 58
  3. NMR-based insights into the conformational and interaction properties of Arkadia RING-H2 E3 Ub ligase. (PMID: 22411132) Chasapis CT … Spyroulias GA (Proteins 2012) 3 4 58
  4. Poly-small ubiquitin-like modifier (PolySUMO)-binding proteins identified through a string search. (PMID: 23086935) Sun H … Hunter T (The Journal of biological chemistry 2012) 3 4 58
  5. Arkadia activates Smad3/Smad4-dependent transcription by triggering signal-induced SnoN degradation. (PMID: 17591695) Levy L … Hill CS (Molecular and cellular biology 2007) 3 4 58

Products for RNF111 Gene

Sources for RNF111 Gene

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