Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q8IUD6 (RN135_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 98. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:RNF135
ORF Names:L13
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length432 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.3 Ref.9

Pathway

Protein modification; protein ubiquitination.

Subunit structure

Interacts with DDX58. Interacts with PCBP2. Ref.3 Ref.8 Ref.9

Subcellular location

Cytoplasm Ref.9.

Tissue specificity

Expressed in skeletal muscle, spleen, kidney, placenta, prostate, stomach, thyroid and tongue. Also weakly expressed in heart, thymus, liver and lung. Ref.3

Involvement in disease

Macrocephaly, macrosomia, facial dysmorphism syndrome (MMFD) [MIM:614192]: An autosomal dominant disorder characterized by the association of macrothrombocytopathy and progressive sensorineural hearing loss without renal dysfunction.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10

Sequence similarities

Contains 1 B30.2/SPRY domain.

Contains 1 RING-type zinc finger.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8IUD6-1)

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.
Isoform 2 (identifier: Q8IUD6-2)

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.
Isoform 3 (identifier: Q8IUD6-3)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 432432E3 ubiquitin-protein ligase RNF135
PRO_0000280557

Regions

Domain241 – 432192B30.2/SPRY
Zinc finger21 – 6343RING-type
Coiled coil121 – 15636 Potential
Coiled coil191 – 21626 Potential

Natural variations

Alternative sequence173 – 21038AFSSG…EIQEK → ENSWKPRLPPHAHCLTRATL HSGELLGLLSGPSIQPLT in isoform 2.
VSP_023785
Alternative sequence211 – 432222Missing in isoform 2.
VSP_023786
Alternative sequence228 – 28659ELLEA…TVSHR → SLLPRLECSGTITAASISQA QENSWKPRLPPHAHCLTRAT LHSGELLGLLSGPSIQPLT in isoform 3.
VSP_045359
Alternative sequence287 – 432146Missing in isoform 3.
VSP_045360
Natural variant711H → Q. Ref.11
Corresponds to variant rs7225888 [ dbSNP | Ensembl ].
VAR_031165
Natural variant1081S → P. Ref.11
Corresponds to variant rs7211440 [ dbSNP | Ensembl ].
VAR_031166
Natural variant1151R → K. Ref.11
Corresponds to variant rs111902263 [ dbSNP | Ensembl ].
VAR_063495
Natural variant2861R → H in MMFD; an individual with overgrowth, learning disability and dysmorphic features. Ref.10
VAR_037652
Natural variant4151W → C. Ref.11
Corresponds to variant rs61749868 [ dbSNP | Ensembl ].
VAR_063496

Experimental info

Sequence conflict2741V → G in CAD43140. Ref.1
Sequence conflict2741V → G in AAT06743. Ref.2
Sequence conflict2931S → N in CAD43140. Ref.1
Sequence conflict2931S → N in AAT06743. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 24, 2009. Version 2.
Checksum: 488F05406996311D

FASTA43247,888
        10         20         30         40         50         60 
MAGLGLGSAV PVWLAEDDLG CIICQGLLDW PATLPCGHSF CRHCLEALWG ARDARRWACP 

        70         80         90        100        110        120 
TCRQGAAQQP HLRKNTLLQD LADKYRRAAR EIQAGSDPAH CPCPGSSSLS SAAARPRRRP 

       130        140        150        160        170        180 
ELQRVAVEKS ITEVAQELTE LVEHLVDIVR SLQNQRPLSE SGPDNELSIL GKAFSSGVDL 

       190        200        210        220        230        240 
SMASPKLVTS DTAAGKIRDI LHDLEEIQEK LQESVTWKEA PEAQMQGELL EAPSSSSCPL 

       250        260        270        280        290        300 
PDQSHPALRR ASRFAQWAIH PTFNLKSLSC SLEVSKDSRT VTVSHRPQPY RWSCERFSTS 

       310        320        330        340        350        360 
QVLCSQALSS GKHYWEVDTR NCSHWAVGVA SWEMSRDQVL GRTMDSCCVE WKGTSQLSAW 

       370        380        390        400        410        420 
HMVKETVLGS DRPGVVGIWL NLEEGKLAFY SVDNQEKLLY ECTISASSPL YPAFWLYGLH 

       430 
PGNYLIIKQV KV 

« Hide

Isoform 2 [UniParc].

Checksum: 8E57034E5F6DF444
Show »

FASTA21022,891
Isoform 3 [UniParc].

Checksum: C08F98D2BBF6544E
Show »

FASTA28630,989

References

« Hide 'large scale' references
[1]"Complete physical map and gene content of the human NF1 tumor suppressor region in human and mouse."
Jenne D.E., Tinschert S., Dorschner M.O., Hameister H., Stephens K., Kehrer-Sawatzki H.
Genes Chromosomes Cancer 37:111-120(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Suppression subtractive hybridization and expression profiling identifies a unique set of genes overexpressed in non-small-cell lung cancer."
Petroziello J., Yamane A., Westendorf L., Thompson M., McDonagh C., Cerveny C., Law C.-L., Wahl A., Carter P.
Oncogene 23:7734-7745(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]"Riplet/RNF135, a RING finger protein, ubiquitinates RIG-I to promote interferon-beta induction during the early phase of viral infection."
Oshiumi H., Matsumoto M., Hatakeyama S., Seya T.
J. Biol. Chem. 284:807-817(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH DDX58, TISSUE SPECIFICITY.
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Mammary gland and Urinary bladder.
[5]"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. expand/collapse author list , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
Tissue: Brain, Lung carcinoma and Placenta.
[8]"PCBP2 mediates degradation of the adaptor MAVS via the HECT ubiquitin ligase AIP4."
You F., Sun H., Zhou X., Sun W., Liang S., Zhai Z., Jiang Z.
Nat. Immunol. 10:1300-1308(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PCBP2.
[9]"REUL is a novel E3 ubiquitin ligase and stimulator of retinoic-acid-inducible gene-I."
Gao D., Yang Y.K., Wang R.P., Zhou X., Diao F.C., Li M.D., Zhai Z.H., Jiang Z.F., Chen D.Y.
PLoS ONE 4:E5760-E5760(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH DDX58, SUBCELLULAR LOCATION.
[10]"Mutations in RNF135, a gene within the NF1 microdeletion region, cause phenotypic abnormalities including overgrowth."
Douglas J., Cilliers D., Coleman K., Tatton-Brown K., Barker K., Bernhard B., Burn J., Huson S., Josifova D., Lacombe D., Malik M., Mansour S., Reid E., Cormier-Daire V., Cole T., Rahman N.
Nat. Genet. 39:963-965(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MMFD HIS-286.
[11]"RNF135 mutations are not present in patients with Sotos syndrome-like features."
Visser R., Koelma N., Vijfhuizen L., van der Wielen M.J., Kant S.G., Breuning M.H., Wit J.M., Losekoot M.
Am. J. Med. Genet. A 149:806-808(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GLN-71; PRO-108; LYS-115 AND CYS-415.
+Additional computationally mapped references.

Web resources

Leiden Open Variation Database

Ring finger protein 135 (RNF135)

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS11262.1. [Q8IUD6-1]
CCDS11263.1. [Q8IUD6-2]
CCDS54104.1. [Q8IUD6-3]
RefSeqNP_001171921.1. NM_001184992.1. [Q8IUD6-3]
NP_115698.3. NM_032322.3. [Q8IUD6-1]
NP_922921.1. NM_197939.1. [Q8IUD6-2]
UniGeneHs.29874.

3D structure databases

ProteinModelPortalQ8IUD6.
SMRQ8IUD6. Positions 16-85, 252-417.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid124009. 3 interactions.
STRING9606.ENSP00000328340.

Polymorphism databases

DMDM269849639.

Proteomic databases

MaxQBQ8IUD6.
PaxDbQ8IUD6.
PRIDEQ8IUD6.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000324689; ENSP00000323693; ENSG00000181481. [Q8IUD6-2]
ENST00000328381; ENSP00000328340; ENSG00000181481. [Q8IUD6-1]
ENST00000535306; ENSP00000440470; ENSG00000181481. [Q8IUD6-3]
GeneID84282.
KEGGhsa:84282.
UCSCuc002hfz.3. human. [Q8IUD6-1]
uc002hga.3. human. [Q8IUD6-2]

Organism-specific databases

CTD84282.
GeneCardsGC17P029297.
HGNCHGNC:21158. RNF135.
HPAHPA021576.
MIM611358. gene.
614192. phenotype.
neXtProtNX_Q8IUD6.
Orphanet97685. 17q11 microdeletion syndrome.
137634. Overgrowth - macrocephaly - facial dysmorphism.
PharmGKBPA134978537.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG308427.
HOGENOMHOG000059562.
HOVERGENHBG056606.
InParanoidQ8IUD6.
KOK16272.
OMAWLYGLHP.
OrthoDBEOG79KPFR.
PhylomeDBQ8IUD6.
TreeFamTF351089.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.
UniPathwayUPA00143.

Gene expression databases

ArrayExpressQ8IUD6.
BgeeQ8IUD6.
CleanExHS_RNF135.
GenevestigatorQ8IUD6.

Family and domain databases

Gene3D3.30.40.10. 1 hit.
InterProIPR001870. B30.2/SPRY.
IPR003879. Butyrophylin.
IPR008985. ConA-like_lec_gl_sf.
IPR006574. PRY.
IPR003877. SPRY_rcpt.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
PfamPF00622. SPRY. 1 hit.
[Graphical view]
PRINTSPR01407. BUTYPHLNCDUF.
SMARTSM00589. PRY. 1 hit.
SM00184. RING. 1 hit.
[Graphical view]
SUPFAMSSF49899. SSF49899. 1 hit.
PROSITEPS50188. B302_SPRY. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSRNF135. human.
GeneWikiRNF135.
GenomeRNAi84282.
NextBio73884.
PROQ8IUD6.
SOURCESearch...

Entry information

Entry nameRN135_HUMAN
AccessionPrimary (citable) accession number: Q8IUD6
Secondary accession number(s): A0AVM5 expand/collapse secondary AC list , B2R7G9, B6ZLM5, F5GX60, Q9BSE9
Entry history
Integrated into UniProtKB/Swiss-Prot: March 20, 2007
Last sequence update: November 24, 2009
Last modified: July 9, 2014
This is version 98 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM