The protein encoded by this gene contains a RING finger domain, a motif present in a variety of functionally distinct proteins and known to be involved in protein-protein and protein-DNA interactions. This gene is located in a chromosomal region known to be frequently deleted in patients with neurofibromatosis. Alternatively spliced transcript variants encoding distinct isoform... See more...

Aliases for RNF135 Gene

Aliases for RNF135 Gene

  • Ring Finger Protein 135 2 3 5
  • Riplet 2 3 4
  • RING Finger Protein Leading To RIG-I Activation 3 4
  • RING-Type E3 Ubiquitin Transferase RNF135 3 4
  • E3 Ubiquitin-Protein Ligase RNF135 3 4
  • RIG-I E3 Ubiquitin Ligase 3 4
  • REUL 3 4
  • RING Finger Protein 135 4
  • EC 2.3.2.27 4
  • MGC13061 2
  • RNF135 5
  • MMFD 3
  • L13 3

External Ids for RNF135 Gene

Previous GeneCards Identifiers for RNF135 Gene

  • GC17P029147
  • GC17P029443
  • GC17P026322
  • GC17P029297
  • GC17P025508
  • GC17P030958

Summaries for RNF135 Gene

Entrez Gene Summary for RNF135 Gene

  • The protein encoded by this gene contains a RING finger domain, a motif present in a variety of functionally distinct proteins and known to be involved in protein-protein and protein-DNA interactions. This gene is located in a chromosomal region known to be frequently deleted in patients with neurofibromatosis. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

GeneCards Summary for RNF135 Gene

RNF135 (Ring Finger Protein 135) is a Protein Coding gene. Diseases associated with RNF135 include Overgrowth-Macrocephaly-Facial Dysmorphism Syndrome and Chromosome 17Q11.2 Deletion Syndrome, 1.4-Mb. Among its related pathways are RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways and Deubiquitination. Gene Ontology (GO) annotations related to this gene include ligase activity and ribonucleoprotein complex binding. An important paralog of this gene is RFPL1.

UniProtKB/Swiss-Prot Summary for RNF135 Gene

  • E2-dependent E3 ubiquitin-protein ligase that functions as a RIG-I/DDX58 coreceptor in the sensing of viral RNAs in cell cytoplasm and the activation of the antiviral innate immune response (PubMed:19017631, PubMed:19484123, PubMed:21147464, PubMed:23950712, PubMed:28469175, PubMed:31006531). Together with the UBE2D3, UBE2N and UB2V1 E2 ligases, catalyzes the 'Lys-63'-linked polyubiquitination of RIG-I/DDX58 oligomerized on viral RNAs, an essential step in the activation of the RIG-I signaling pathway (PubMed:19017631, PubMed:21147464, PubMed:28469175, PubMed:31006531). Through a ubiquitin-independent parallel mechanism, which consists in bridging RIG-I/DDX58 filaments forming on longer viral RNAs, further activates the RIG-I signaling pathway (PubMed:31006531). This second mechanism that synergizes with the ubiquitin-dependent one would thereby allow an RNA length-dependent regulation of the RIG-I signaling pathway (Probable). Associated with the E2 ligase UBE2N, also constitutively synthesizes unanchored 'Lys-63'-linked polyubiquitin chains that may also activate the RIG-I signaling pathway (PubMed:28469175, PubMed:31006531).

Gene Wiki entry for RNF135 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for RNF135 Gene

Genomics for RNF135 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for RNF135 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around RNF135 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for RNF135

Top Transcription factor binding sites by QIAGEN in the RNF135 gene promoter:
  • NF-1
  • NF-1/L

Genomic Locations for RNF135 Gene

Latest Assembly
chr17:30,968,642-30,999,911
(GRCh38/hg38)
Size:
31,270 bases
Orientation:
Plus strand

Previous Assembly
chr17:29,298,057-29,326,929
(GRCh37/hg19 by Entrez Gene)
Size:
28,873 bases
Orientation:
Plus strand

chr17:29,295,803-29,326,929
(GRCh37/hg19 by Ensembl)
Size:
31,127 bases
Orientation:
Plus strand

Genomic View for RNF135 Gene

Genes around RNF135 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
RNF135 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for RNF135 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for RNF135 Gene

Proteins for RNF135 Gene

  • Protein details for RNF135 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8IUD6-RN135_HUMAN
    Recommended name:
    E3 ubiquitin-protein ligase RNF135
    Protein Accession:
    Q8IUD6
    Secondary Accessions:
    • A0AVM5
    • B2R7G9
    • B6ZLM5
    • F5GX60
    • Q9BSE9

    Protein attributes for RNF135 Gene

    Size:
    432 amino acids
    Molecular mass:
    47888 Da
    Quaternary structure:
    • Homodimer (PubMed:31006531). Interacts (homodimer) with DDX58 (double-stranded RNA-bound oligomeric form); involved in both DDX58 ubiquitination, oligomerization into filaments associated with viral RNAs and the bridging of these filaments (PubMed:19017631, PubMed:19484123, PubMed:23950712, PubMed:28469175, PubMed:31006531). Interacts with UBE2D3 and UBE2N; E2 ubiquitin ligases involved in RNF135-mediated ubiquitination of DDX58 and activation of the RIG-I signaling pathway (PubMed:28469175). Interacts with PCBP2 (PubMed:19881509).

    Alternative splice isoforms for RNF135 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for RNF135 Gene

Post-translational modifications for RNF135 Gene

  • (Microbial infection) Cleaved and inactivated by hepatitis C virus NS3/NS4A.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for RNF135 Gene

Domains & Families for RNF135 Gene

Gene Families for RNF135 Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Enzymes
  • Potential drug targets
  • Predicted intracellular proteins

Protein Domains for RNF135 Gene

InterPro:
Blocks:
  • Zn-finger, RING
  • Butyrophylin C-terminal DUF signature
  • SPRY-associated domain

Suggested Antigen Peptide Sequences for RNF135 Gene

GenScript: Design optimal peptide antigens:
  • cDNA, FLJ93440 (B2R7G9_HUMAN)
  • cDNA FLJ16196 fis, clone COLON2006417, highly similar to Homo sapiens ring finger protein 135 (RNF135), transcript variant 1, mRNA (B3KV69_HUMAN)
  • Riplet (B6ZLM5_HUMAN)
  • Riplet (RN135_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q8IUD6

UniProtKB/Swiss-Prot:

RN135_HUMAN :
  • The B30.2/SPRY domain mediates the interaction with the substrate RIG-I/DDX58.
Domain:
  • The B30.2/SPRY domain mediates the interaction with the substrate RIG-I/DDX58.
  • The coiled-coil domains mediate homodimerization and the bridging of viral RNA-associated RIG-I/DDX58 filaments.
genes like me logo Genes that share domains with RNF135: view

Function for RNF135 Gene

Molecular function for RNF135 Gene

UniProtKB/Swiss-Prot Function:
E2-dependent E3 ubiquitin-protein ligase that functions as a RIG-I/DDX58 coreceptor in the sensing of viral RNAs in cell cytoplasm and the activation of the antiviral innate immune response (PubMed:19017631, PubMed:19484123, PubMed:21147464, PubMed:23950712, PubMed:28469175, PubMed:31006531). Together with the UBE2D3, UBE2N and UB2V1 E2 ligases, catalyzes the 'Lys-63'-linked polyubiquitination of RIG-I/DDX58 oligomerized on viral RNAs, an essential step in the activation of the RIG-I signaling pathway (PubMed:19017631, PubMed:21147464, PubMed:28469175, PubMed:31006531). Through a ubiquitin-independent parallel mechanism, which consists in bridging RIG-I/DDX58 filaments forming on longer viral RNAs, further activates the RIG-I signaling pathway (PubMed:31006531). This second mechanism that synergizes with the ubiquitin-dependent one would thereby allow an RNA length-dependent regulation of the RIG-I signaling pathway (Probable). Associated with the E2 ligase UBE2N, also constitutively synthesizes unanchored 'Lys-63'-linked polyubiquitin chains that may also activate the RIG-I signaling pathway (PubMed:28469175, PubMed:31006531).
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=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.; EC=2.3.2.27; Evidence={ECO:0000269|PubMed:31006531};.

Enzyme Numbers (IUBMB) for RNF135 Gene

Phenotypes From GWAS Catalog for RNF135 Gene

Gene Ontology (GO) - Molecular Function for RNF135 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004842 ubiquitin-protein transferase activity IBA,IDA 19484123
GO:0005515 protein binding IPI 19017631
GO:0016740 transferase activity IEA --
GO:0039552 RIG-I binding IPI 23950712
GO:0042802 identical protein binding IPI 25416956
genes like me logo Genes that share ontologies with RNF135: view
genes like me logo Genes that share phenotypes with RNF135: view

Human Phenotype Ontology for RNF135 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for RNF135

No data available for Animal Models , Transcription Factor Targets and HOMER Transcription for RNF135 Gene

Localization for RNF135 Gene

Subcellular locations from UniProtKB/Swiss-Prot for RNF135 Gene

Cytoplasm. Cytoplasm, Stress granule.

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 RNF135 gene
Compartment Confidence
cytosol 5
nucleus 4
mitochondrion 2
endosome 2
plasma membrane 1
extracellular 1
cytoskeleton 1
peroxisome 1
endoplasmic reticulum 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for RNF135 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IBA,IDA 19484123
GO:0005829 cytosol TAS --
GO:0010494 cytoplasmic stress granule IEA,IDA 23950712
GO:1990904 ribonucleoprotein complex IDA 31006531
genes like me logo Genes that share ontologies with RNF135: view

Pathways & Interactions for RNF135 Gene

genes like me logo Genes that share pathways with RNF135: view

Pathways by source for RNF135 Gene

UniProtKB/Swiss-Prot Q8IUD6-RN135_HUMAN

  • Pathway: Protein modification; protein ubiquitination.

Gene Ontology (GO) - Biological Process for RNF135 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000209 protein polyubiquitination IDA 31006531
GO:0002376 immune system process IEA --
GO:0010994 free ubiquitin chain polymerization IDA 31006531
GO:0016567 protein ubiquitination IEA,IDA 19017631
GO:0032480 negative regulation of type I interferon production TAS --
genes like me logo Genes that share ontologies with RNF135: view

No data available for SIGNOR curated interactions for RNF135 Gene

Drugs & Compounds for RNF135 Gene

No Compound Related Data Available

Transcripts for RNF135 Gene

mRNA/cDNA for RNF135 Gene

3 REFSEQ mRNAs :
14 NCBI additional mRNA sequence :
6 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for RNF135

Alternative Splicing Database (ASD) splice patterns (SP) for RNF135 Gene

ExUns: 1a · 1b · 1c · 1d ^ 2 ^ 3a · 3b ^ 4 ^ 5 ^ 6a · 6b · 6c
SP1:
SP2: -
SP3: - -
SP4: - - -
SP5: - - - -
SP6: -

Relevant External Links for RNF135 Gene

GeneLoc Exon Structure for
RNF135

Expression for RNF135 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for RNF135 Gene

mRNA differential expression in normal tissues according to GTEx for RNF135 Gene

This gene is overexpressed in Whole Blood (x5.0).

Protein differential expression in normal tissues from HIPED for RNF135 Gene

This gene is overexpressed in Testis (19.2), Urinary Bladder (17.6), Rectum (16.7), and Monocytes (12.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for RNF135 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for RNF135

SOURCE GeneReport for Unigene cluster for RNF135 Gene:

Hs.29874

mRNA Expression by UniProt/SwissProt for RNF135 Gene:

Q8IUD6-RN135_HUMAN
Tissue specificity: Expressed in skeletal muscle, spleen, kidney, placenta, prostate, stomach, thyroid and tongue. Also weakly expressed in heart, thymus, liver and lung.

Evidence on tissue expression from TISSUES for RNF135 Gene

  • Nervous system(4.3)
  • Spleen(2.1)
  • Kidney(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for RNF135 Gene

Germ Layers:
  • ectoderm
  • mesoderm
Systems:
  • integumentary
  • nervous
  • skeleton
Regions:
Head and neck:
  • brain
  • eye
  • eyelid
  • face
  • forehead
  • head
  • lip
  • nose
  • skull
General:
  • skin
genes like me logo Genes that share expression patterns with RNF135: view

Primer products for research

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and Protein tissue co-expression partners for RNF135 Gene

Orthologs for RNF135 Gene

This gene was present in the common ancestor of chordates.

Orthologs for RNF135 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia RNF135 29 30
  • 98.92 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia RNF135 29 30
  • 81.54 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia RNF135 29 30
  • 77.75 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Rnf135 29
  • 74.15 (n)
Mouse
(Mus musculus)
Mammalia Rnf135 29 16 30
  • 72.98 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia RNF135 30
  • 38 (a)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia RNF135 30
  • 38 (a)
OneToOne
Zebrafish
(Danio rerio)
Actinopterygii AL954746.1 30
  • 26 (a)
OneToOne
Species where no ortholog for RNF135 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • 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)
  • Chicken (Gallus gallus)
  • 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)
  • Fruit Fly (Drosophila melanogaster)
  • 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)
  • Oppossum (Monodelphis domestica)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (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)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for RNF135 Gene

ENSEMBL:
Gene Tree for RNF135 (if available)
TreeFam:
Gene Tree for RNF135 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for RNF135: view image
Alliance of Genome Resources:
Additional Orthologs for RNF135

Paralogs for RNF135 Gene

(4) SIMAP similar genes for RNF135 Gene using alignment to 4 proteins:

  • RN135_HUMAN
  • H7C3H8_HUMAN
  • J3QS68_HUMAN
  • K7EQF1_HUMAN
genes like me logo Genes that share paralogs with RNF135: view

Variants for RNF135 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for RNF135 Gene

SNP ID Clinical significance and condition Chr 17 pos Variation AA Info Type
1032947 Pathogenic: Chromosome 17q11.2 deletion syndrome, 1.4 MB 30,984,701(+) C/T
NM_032322.4(RNF135):c.457C>T (p.Gln153Ter)
NONSENSE
1032948 Uncertain Significance: Chromosome 17q11.2 deletion syndrome, 1.4 MB 30,988,002(+) C/T
NM_032322.4(RNF135):c.575C>T (p.Thr192Ile)
MISSENSE_VARIANT,INTRON
931426 Uncertain Significance: not provided 30,971,093(+) G/C
NM_032322.4(RNF135):c.20G>C (p.Gly7Ala)
MISSENSE
rs111902263 Benign: not specified; not provided 30,971,417(+) G/Ap.Arg115Lys
NM_032322.4(RNF135):c.344G>A (p.Arg115Lys)
MISSENSE
rs121918161 Uncertain Significance: Macrocephaly, macrosomia, facial dysmorphism syndrome 30,997,289(+) C/T
NM_032322.4(RNF135):c.727C>T (p.Gln243Ter)
NONSENSE,SYNONYMOUS

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for RNF135 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for RNF135 Gene

Variant ID Type Subtype PubMed ID
esv24402 CNV loss 19812545
esv2715813 CNV deletion 23290073
nsv457720 CNV loss 19166990
nsv833412 CNV loss 17160897

Variation tolerance for RNF135 Gene

Residual Variation Intolerance Score: 57.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 8.06; 84.37% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for RNF135 Gene

Human Gene Mutation Database (HGMD)
RNF135
SNPedia medical, phenotypic, and genealogical associations of SNPs for
RNF135
Leiden Open Variation Database (LOVD)
RNF135

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for RNF135 Gene

Disorders for RNF135 Gene

MalaCards: The human disease database

(10) MalaCards diseases for RNF135 Gene - From: CVR, ORP, COP, and GCD

- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for RNF135

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with RNF135: view

No data available for UniProtKB/Swiss-Prot and Genatlas for RNF135 Gene

Publications for RNF135 Gene

  1. Riplet/RNF135, a RING finger protein, ubiquitinates RIG-I to promote interferon-beta induction during the early phase of viral infection. (PMID: 19017631) Oshiumi H … Seya T (The Journal of biological chemistry 2009) 2 3 4
  2. RNF135 mutations are not present in patients with Sotos syndrome-like features. (PMID: 19291764) Visser R … Losekoot M (American journal of medical genetics. Part A 2009) 3 4 40
  3. Mutations in RNF135, a gene within the NF1 microdeletion region, cause phenotypic abnormalities including overgrowth. (PMID: 17632510) Douglas J … Rahman N (Nature genetics 2007) 3 4 72
  4. Ubiquitin-Dependent and -Independent Roles of E3 Ligase RIPLET in Innate Immunity. (PMID: 31006531) Cadena C … Hur S (Cell 2019) 3 4
  5. Ube2D3 and Ube2N are essential for RIG-I-mediated MAVS aggregation in antiviral innate immunity. (PMID: 28469175) Shi Y … Hou F (Nature communications 2017) 3 4

Products for RNF135 Gene

Sources for RNF135 Gene