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Protein

E3 ubiquitin-protein ligase RNF185

Gene

RNF185

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

Functioni

E3 ubiquitin-protein ligase that regulates selective mitochondrial autophagy by mediating 'Lys-63'-linked polyubiquitination of BNIP1 (PubMed:21931693). Acts in the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway, which targets misfolded proteins that accumulate in the endoplasmic reticulum (ER) for ubiquitination and subsequent proteasome-mediated degradation (PubMed:27485036). Protects cells from ER stress-induced apoptosis (PubMed:27485036). Responsible for the cotranslational ubiquitination and degradation of CFTR in the ERAD pathway (PubMed:24019521). Preferentially associates with the E2 enzymes UBE2J1 and UBE2J2 (PubMed:24019521).3 Publications

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.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 fingeri39 – 80RING-typePROSITE-ProRule annotationAdd BLAST42

GO - Molecular functioni

  • metal ion binding Source: UniProtKB-KW
  • ubiquitin-like protein conjugating enzyme binding Source: ParkinsonsUK-UCL
  • ubiquitin protein ligase activity involved in ERAD pathway Source: ParkinsonsUK-UCL

GO - Biological processi

  • autophagy Source: UniProtKB-KW
  • endoplasmic reticulum mannose trimming Source: Reactome
  • ERAD pathway Source: ParkinsonsUK-UCL
  • ER-associated misfolded protein catabolic process Source: GO_Central
  • protein autoubiquitination Source: ParkinsonsUK-UCL
  • protein ubiquitination involved in ubiquitin-dependent protein catabolic process Source: GO_Central
  • transmembrane transport Source: Reactome
  • ubiquitin-dependent ERAD pathway Source: ParkinsonsUK-UCL

Keywordsi

Molecular functionTransferase
Biological processAutophagy, Ubl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-382556. ABC-family proteins mediated transport.
R-HSA-5678895. Defective CFTR causes cystic fibrosis.
R-HSA-901032. ER Quality Control Compartment (ERQC).
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase RNF185 (EC:2.3.2.272 Publications)
Alternative name(s):
RING finger protein 185
RING-type E3 ubiquitin transferase RNF185Curated
Gene namesi
Name:RNF185
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

EuPathDBiHostDB:ENSG00000138942.15.
HGNCiHGNC:26783. RNF185.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 130Cytoplasmic1 PublicationAdd BLAST130
Transmembranei131 – 151HelicalSequence analysisAdd BLAST21
Topological domaini152 – 171Mitochondrial intermembrane1 PublicationAdd BLAST20
Transmembranei172 – 192HelicalSequence analysisAdd BLAST21

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Mitochondrion, Mitochondrion outer membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi39C → S: Decreased ubiquitin ligase activity. 1 Publication1

Organism-specific databases

OpenTargetsiENSG00000138942.
PharmGKBiPA142671056.

Polymorphism and mutation databases

BioMutaiRNF185.
DMDMi74751883.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002475201 – 192E3 ubiquitin-protein ligase RNF185Add BLAST192

Proteomic databases

EPDiQ96GF1.
MaxQBiQ96GF1.
PaxDbiQ96GF1.
PeptideAtlasiQ96GF1.
PRIDEiQ96GF1.
TopDownProteomicsiQ96GF1-1. [Q96GF1-1]
Q96GF1-2. [Q96GF1-2]

PTM databases

iPTMnetiQ96GF1.
PhosphoSitePlusiQ96GF1.

Expressioni

Tissue specificityi

Ubiquitously expressed.1 Publication

Inductioni

Up-regulated by unfolded protein response (UPR) and endoplasmic reticulum (ER) stress triggered by thapsigargin or tunicamycin.2 Publications

Gene expression databases

BgeeiENSG00000138942.
CleanExiHS_RNF185.
ExpressionAtlasiQ96GF1. baseline and differential.
GenevisibleiQ96GF1. HS.

Interactioni

Subunit structurei

Interacts with ATG5 and BNIP1.1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

  • ubiquitin-like protein conjugating enzyme binding Source: ParkinsonsUK-UCL

Protein-protein interaction databases

BioGridi124834. 67 interactors.
IntActiQ96GF1. 30 interactors.
STRINGi9606.ENSP00000320508.

Structurei

3D structure databases

ProteinModelPortaliQ96GF1.
SMRiQ96GF1.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni29 – 80Required for ubiquitin ligase activity and protection against ER stress-induced cell death1 PublicationAdd BLAST52

Domaini

The RING-type zinc finger domain is responsible for E3 ubiquitin ligase activity.1 Publication

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri39 – 80RING-typePROSITE-ProRule annotationAdd BLAST42

Keywords - Domaini

Transmembrane, Transmembrane helix, Zinc-finger

Phylogenomic databases

eggNOGiKOG0823. Eukaryota.
ENOG4111IHV. LUCA.
GeneTreeiENSGT00760000119075.
HOGENOMiHOG000238304.
HOVERGENiHBG054495.
InParanoidiQ96GF1.
KOiK10666.
OMAiDGGFHMS.
OrthoDBiEOG091G0W2I.
PhylomeDBiQ96GF1.
TreeFamiTF317334.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiView protein in InterPro
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
SMARTiView protein in SMART
SM00184. RING. 1 hit.
PROSITEiView protein in PROSITE
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q96GF1-1) [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
MASKGPSASA SPENSSAGGP SGSSNGAGES GGQDSTFECN ICLDTAKDAV
60 70 80 90 100
ISLCGHLFCW PCLHQWLETR PNRQVCPVCK AGISRDKVIP LYGRGSTGQQ
110 120 130 140 150
DPREKTPPRP QGQRPEPENR GGFQGFGFGD GGFQMSFGIG AFPFGIFATA
160 170 180 190
FNINDGRPPP AVPGTPQYVD EQFLSRLFLF VALVIMFWLL IA
Length:192
Mass (Da):20,459
Last modified:December 1, 2001 - v1
Checksum:iF24B49EA566740B3
GO
Isoform 2 (identifier: Q96GF1-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     66-121: Missing.

Note: No experimental confirmation available.
Show »
Length:136
Mass (Da):14,139
Checksum:i00AAB3A853E80773
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_02000466 – 121Missing in isoform 2. 2 PublicationsAdd BLAST56

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
DQ296559 mRNA. Translation: ABB97506.1.
DQ296561 mRNA. Translation: ABB97508.1.
DQ296562 mRNA. Translation: ABB97509.1.
DQ296565 mRNA. Translation: ABB97512.1.
CR456349 mRNA. Translation: CAG30235.1.
AK095947 mRNA. Translation: BAC04659.1.
AK291236 mRNA. Translation: BAF83925.1.
AC002073 Genomic DNA. No translation available.
AC005005 Genomic DNA. No translation available.
CH471095 Genomic DNA. Translation: EAW59947.1.
CH471095 Genomic DNA. Translation: EAW59949.1.
BC009504 mRNA. Translation: AAH09504.1.
BC026040 mRNA. Translation: AAH26040.1.
BC033166 mRNA. Translation: AAH33166.1.
BC012817 mRNA. Translation: AAH12817.1.
BC035684 mRNA. Translation: AAH35684.1.
CCDSiCCDS13890.1. [Q96GF1-1]
CCDS46689.1. [Q96GF1-2]
RefSeqiNP_001129297.1. NM_001135825.1. [Q96GF1-2]
NP_689480.2. NM_152267.3. [Q96GF1-1]
UniGeneiHs.517553.

Genome annotation databases

EnsembliENST00000266252; ENSP00000266252; ENSG00000138942. [Q96GF1-2]
ENST00000326132; ENSP00000320508; ENSG00000138942. [Q96GF1-1]
ENST00000518626; ENSP00000427755; ENSG00000138942. [Q96GF1-1]
GeneIDi91445.
KEGGihsa:91445.
UCSCiuc003akb.4. human. [Q96GF1-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiRN185_HUMAN
AccessioniPrimary (citable) accession number: Q96GF1
Secondary accession number(s): A8K5C1, A9X3T8, Q8N900
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 25, 2006
Last sequence update: December 1, 2001
Last modified: October 25, 2017
This is version 130 of the entry and version 1 of the sequence. See 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 22
    Human chromosome 22: entries, gene names and cross-references to MIM
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways