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Protein

E3 ubiquitin-protein ligase RNF135

Gene

RNF135

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Acts as an E2-dependent E3 ubiquitin-protein ligase, involved in innate immune defense against viruses. Ubiquitinates DDX58 and is required for full activation of the DDX58 signaling resulting in interferon beta production.2 Publications

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri21 – 63RING-typePROSITE-ProRule annotationAdd BLAST43

GO - Molecular functioni

  • ligase activity Source: UniProtKB-KW
  • ribonucleoprotein complex binding Source: UniProtKB
  • ubiquitin-protein transferase activity Source: UniProtKB
  • zinc ion binding Source: InterPro

GO - Biological processi

  • innate immune response Source: Reactome
  • negative regulation of type I interferon production Source: Reactome
  • positive regulation of interferon-beta production Source: UniProtKB
  • protein ubiquitination Source: UniProtKB
  • regulation of innate immune response Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Immunity, Innate immunity, Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-168928. RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways.
R-HSA-5689896. Ovarian tumor domain proteases.
R-HSA-918233. TRAF3-dependent IRF activation pathway.
R-HSA-933541. TRAF6 mediated IRF7 activation.
R-HSA-933542. TRAF6 mediated NF-kB activation.
R-HSA-933543. NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10.
R-HSA-936440. Negative regulators of RIG-I/MDA5 signaling.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase RNF135 (EC:6.3.2.-)
Alternative name(s):
RIG-I E3 ubiquitin ligase
Short name:
REUL
RING finger protein 135
Riplet
Gene namesi
Name:RNF135
ORF Names:L13
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:21158. RNF135.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Macrocephaly, macrosomia, facial dysmorphism syndrome (MMFD)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant disorder characterized by the association of macrothrombocytopathy and progressive sensorineural hearing loss without renal dysfunction.
See also OMIM:614192
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_037652286R → H in MMFD; an individual with overgrowth, learning disability and dysmorphic features. 1 PublicationCorresponds to variant rs121918162dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi84282.
MalaCardsiRNF135.
MIMi614192. phenotype.
OpenTargetsiENSG00000181481.
Orphaneti137634. Overgrowth - macrocephaly - facial dysmorphism.
PharmGKBiPA134978537.

Polymorphism and mutation databases

BioMutaiRNF135.
DMDMi269849639.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002805571 – 432E3 ubiquitin-protein ligase RNF135Add BLAST432

Proteomic databases

EPDiQ8IUD6.
MaxQBiQ8IUD6.
PaxDbiQ8IUD6.
PeptideAtlasiQ8IUD6.
PRIDEiQ8IUD6.

PTM databases

iPTMnetiQ8IUD6.
PhosphoSitePlusiQ8IUD6.

Expressioni

Tissue specificityi

Expressed in skeletal muscle, spleen, kidney, placenta, prostate, stomach, thyroid and tongue. Also weakly expressed in heart, thymus, liver and lung.1 Publication

Gene expression databases

BgeeiENSG00000181481.
CleanExiHS_RNF135.
ExpressionAtlasiQ8IUD6. baseline and differential.
GenevisibleiQ8IUD6. HS.

Organism-specific databases

HPAiHPA021576.
HPA052404.

Interactioni

Subunit structurei

Interacts with DDX58. Interacts with PCBP2.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself3EBI-9916363,EBI-9916363
CTNNAL1Q9UBT75EBI-9916363,EBI-514206
GOLGA2Q083793EBI-9916363,EBI-618309

Protein-protein interaction databases

BioGridi124009. 14 interactors.
IntActiQ8IUD6. 9 interactors.
STRINGi9606.ENSP00000328340.

Structurei

3D structure databases

ProteinModelPortaliQ8IUD6.
SMRiQ8IUD6.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini241 – 432B30.2/SPRYPROSITE-ProRule annotationAdd BLAST192

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili121 – 156Sequence analysisAdd BLAST36
Coiled coili191 – 216Sequence analysisAdd BLAST26

Sequence similaritiesi

Contains 1 B30.2/SPRY domain.PROSITE-ProRule annotation
Contains 1 RING-type zinc finger.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri21 – 63RING-typePROSITE-ProRule annotationAdd BLAST43

Keywords - Domaini

Coiled coil, Zinc-finger

Phylogenomic databases

eggNOGiKOG2177. Eukaryota.
ENOG4111G04. LUCA.
GeneTreeiENSGT00830000128449.
HOGENOMiHOG000059562.
HOVERGENiHBG056606.
InParanoidiQ8IUD6.
KOiK16272.
OMAiSCCVEWK.
OrthoDBiEOG091G062V.
PhylomeDBiQ8IUD6.
TreeFamiTF351089.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR001870. B30.2/SPRY.
IPR003879. Butyrophylin.
IPR013320. ConA-like_dom.
IPR006574. PRY.
IPR003877. SPRY_dom.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
PfamiPF00622. SPRY. 1 hit.
[Graphical view]
PRINTSiPR01407. BUTYPHLNCDUF.
SMARTiSM00589. PRY. 1 hit.
SM00184. RING. 1 hit.
SM00449. SPRY. 1 hit.
[Graphical view]
SUPFAMiSSF49899. SSF49899. 1 hit.
PROSITEiPS50188. B302_SPRY. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8IUD6-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAGLGLGSAV PVWLAEDDLG CIICQGLLDW PATLPCGHSF CRHCLEALWG
60 70 80 90 100
ARDARRWACP TCRQGAAQQP HLRKNTLLQD LADKYRRAAR EIQAGSDPAH
110 120 130 140 150
CPCPGSSSLS SAAARPRRRP ELQRVAVEKS ITEVAQELTE LVEHLVDIVR
160 170 180 190 200
SLQNQRPLSE SGPDNELSIL GKAFSSGVDL SMASPKLVTS DTAAGKIRDI
210 220 230 240 250
LHDLEEIQEK LQESVTWKEA PEAQMQGELL EAPSSSSCPL PDQSHPALRR
260 270 280 290 300
ASRFAQWAIH PTFNLKSLSC SLEVSKDSRT VTVSHRPQPY RWSCERFSTS
310 320 330 340 350
QVLCSQALSS GKHYWEVDTR NCSHWAVGVA SWEMSRDQVL GRTMDSCCVE
360 370 380 390 400
WKGTSQLSAW HMVKETVLGS DRPGVVGIWL NLEEGKLAFY SVDNQEKLLY
410 420 430
ECTISASSPL YPAFWLYGLH PGNYLIIKQV KV
Length:432
Mass (Da):47,888
Last modified:November 24, 2009 - v2
Checksum:i488F05406996311D
GO
Isoform 2 (identifier: Q8IUD6-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     173-210: AFSSGVDLSM...LHDLEEIQEK → ENSWKPRLPP...LSGPSIQPLT
     211-432: Missing.

Note: No experimental confirmation available.
Show »
Length:210
Mass (Da):22,891
Checksum:i8E57034E5F6DF444
GO
Isoform 3 (identifier: Q8IUD6-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     228-286: ELLEAPSSSS...DSRTVTVSHR → SLLPRLECSG...LSGPSIQPLT
     287-432: Missing.

Note: No experimental confirmation available.
Show »
Length:286
Mass (Da):30,989
Checksum:iC08F98D2BBF6544E
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti274V → G in CAD43140 (PubMed:12696059).Curated1
Sequence conflicti274V → G in AAT06743 (PubMed:15334068).Curated1
Sequence conflicti293S → N in CAD43140 (PubMed:12696059).Curated1
Sequence conflicti293S → N in AAT06743 (PubMed:15334068).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03116571H → Q.1 PublicationCorresponds to variant rs7225888dbSNPEnsembl.1
Natural variantiVAR_031166108S → P.1 PublicationCorresponds to variant rs7211440dbSNPEnsembl.1
Natural variantiVAR_063495115R → K.1 PublicationCorresponds to variant rs111902263dbSNPEnsembl.1
Natural variantiVAR_037652286R → H in MMFD; an individual with overgrowth, learning disability and dysmorphic features. 1 PublicationCorresponds to variant rs121918162dbSNPEnsembl.1
Natural variantiVAR_063496415W → C.1 PublicationCorresponds to variant rs61749868dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_023785173 – 210AFSSG…EIQEK → ENSWKPRLPPHAHCLTRATL HSGELLGLLSGPSIQPLT in isoform 2. 2 PublicationsAdd BLAST38
Alternative sequenceiVSP_023786211 – 432Missing in isoform 2. 2 PublicationsAdd BLAST222
Alternative sequenceiVSP_045359228 – 286ELLEA…TVSHR → SLLPRLECSGTITAASISQA QENSWKPRLPPHAHCLTRAT LHSGELLGLLSGPSIQPLT in isoform 3. 1 PublicationAdd BLAST59
Alternative sequenceiVSP_045360287 – 432Missing in isoform 3. 1 PublicationAdd BLAST146

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ496729 mRNA. Translation: CAD43140.1.
AY598332 mRNA. Translation: AAT06743.1.
AB470605 mRNA. Translation: BAG84604.1.
AK122646 mRNA. Translation: BAG53638.1.
AK312979 mRNA. Translation: BAG35816.1.
AC138207 Genomic DNA. No translation available.
CH471147 Genomic DNA. Translation: EAW80286.1.
BC005084 mRNA. Translation: AAH05084.1.
BC082262 mRNA. No translation available.
BC126420 mRNA. Translation: AAI26421.1.
BC126422 mRNA. Translation: AAI26423.1.
CCDSiCCDS11262.1. [Q8IUD6-1]
CCDS11263.1. [Q8IUD6-2]
CCDS54104.1. [Q8IUD6-3]
RefSeqiNP_001171921.1. NM_001184992.1. [Q8IUD6-3]
NP_115698.3. NM_032322.3. [Q8IUD6-1]
NP_922921.1. NM_197939.1. [Q8IUD6-2]
UniGeneiHs.29874.

Genome annotation databases

EnsembliENST00000324689; ENSP00000323693; ENSG00000181481. [Q8IUD6-2]
ENST00000328381; ENSP00000328340; ENSG00000181481. [Q8IUD6-1]
ENST00000535306; ENSP00000440470; ENSG00000181481. [Q8IUD6-3]
GeneIDi84282.
KEGGihsa:84282.
UCSCiuc002hfz.4. human. [Q8IUD6-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Leiden Open Variation Database

Ring finger protein 135 (RNF135)

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ496729 mRNA. Translation: CAD43140.1.
AY598332 mRNA. Translation: AAT06743.1.
AB470605 mRNA. Translation: BAG84604.1.
AK122646 mRNA. Translation: BAG53638.1.
AK312979 mRNA. Translation: BAG35816.1.
AC138207 Genomic DNA. No translation available.
CH471147 Genomic DNA. Translation: EAW80286.1.
BC005084 mRNA. Translation: AAH05084.1.
BC082262 mRNA. No translation available.
BC126420 mRNA. Translation: AAI26421.1.
BC126422 mRNA. Translation: AAI26423.1.
CCDSiCCDS11262.1. [Q8IUD6-1]
CCDS11263.1. [Q8IUD6-2]
CCDS54104.1. [Q8IUD6-3]
RefSeqiNP_001171921.1. NM_001184992.1. [Q8IUD6-3]
NP_115698.3. NM_032322.3. [Q8IUD6-1]
NP_922921.1. NM_197939.1. [Q8IUD6-2]
UniGeneiHs.29874.

3D structure databases

ProteinModelPortaliQ8IUD6.
SMRiQ8IUD6.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi124009. 14 interactors.
IntActiQ8IUD6. 9 interactors.
STRINGi9606.ENSP00000328340.

PTM databases

iPTMnetiQ8IUD6.
PhosphoSitePlusiQ8IUD6.

Polymorphism and mutation databases

BioMutaiRNF135.
DMDMi269849639.

Proteomic databases

EPDiQ8IUD6.
MaxQBiQ8IUD6.
PaxDbiQ8IUD6.
PeptideAtlasiQ8IUD6.
PRIDEiQ8IUD6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000324689; ENSP00000323693; ENSG00000181481. [Q8IUD6-2]
ENST00000328381; ENSP00000328340; ENSG00000181481. [Q8IUD6-1]
ENST00000535306; ENSP00000440470; ENSG00000181481. [Q8IUD6-3]
GeneIDi84282.
KEGGihsa:84282.
UCSCiuc002hfz.4. human. [Q8IUD6-1]

Organism-specific databases

CTDi84282.
DisGeNETi84282.
GeneCardsiRNF135.
HGNCiHGNC:21158. RNF135.
HPAiHPA021576.
HPA052404.
MalaCardsiRNF135.
MIMi611358. gene.
614192. phenotype.
neXtProtiNX_Q8IUD6.
OpenTargetsiENSG00000181481.
Orphaneti137634. Overgrowth - macrocephaly - facial dysmorphism.
PharmGKBiPA134978537.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2177. Eukaryota.
ENOG4111G04. LUCA.
GeneTreeiENSGT00830000128449.
HOGENOMiHOG000059562.
HOVERGENiHBG056606.
InParanoidiQ8IUD6.
KOiK16272.
OMAiSCCVEWK.
OrthoDBiEOG091G062V.
PhylomeDBiQ8IUD6.
TreeFamiTF351089.

Enzyme and pathway databases

UniPathwayiUPA00143.
ReactomeiR-HSA-168928. RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways.
R-HSA-5689896. Ovarian tumor domain proteases.
R-HSA-918233. TRAF3-dependent IRF activation pathway.
R-HSA-933541. TRAF6 mediated IRF7 activation.
R-HSA-933542. TRAF6 mediated NF-kB activation.
R-HSA-933543. NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10.
R-HSA-936440. Negative regulators of RIG-I/MDA5 signaling.

Miscellaneous databases

ChiTaRSiRNF135. human.
GeneWikiiRNF135.
GenomeRNAii84282.
PROiQ8IUD6.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000181481.
CleanExiHS_RNF135.
ExpressionAtlasiQ8IUD6. baseline and differential.
GenevisibleiQ8IUD6. HS.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR001870. B30.2/SPRY.
IPR003879. Butyrophylin.
IPR013320. ConA-like_dom.
IPR006574. PRY.
IPR003877. SPRY_dom.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
PfamiPF00622. SPRY. 1 hit.
[Graphical view]
PRINTSiPR01407. BUTYPHLNCDUF.
SMARTiSM00589. PRY. 1 hit.
SM00184. RING. 1 hit.
SM00449. SPRY. 1 hit.
[Graphical view]
SUPFAMiSSF49899. SSF49899. 1 hit.
PROSITEiPS50188. B302_SPRY. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiRN135_HUMAN
AccessioniPrimary (citable) accession number: Q8IUD6
Secondary accession number(s): A0AVM5
, B2R7G9, B6ZLM5, F5GX60, Q9BSE9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 20, 2007
Last sequence update: November 24, 2009
Last modified: November 30, 2016
This is version 124 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.