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Protein

E3 ubiquitin-protein ligase RNF146

Gene

Rnf146

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at protein leveli

Functioni

E3 ubiquitin-protein ligase that specifically binds poly-ADP-ribosylated (PARsylated) proteins and mediates their ubiquitination and subsequent degradation. May regulate many important biological processes, such as cell survival and DNA damage response. Acts as an activator of the Wnt signaling pathway by mediating the ubiquitination of PARsylated AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex. Acts in cooperation with tankyrase proteins (TNKS and TNKS2), which mediate PARsylation of target proteins AXIN1, AXIN2, BLZF1, CASC3, TNKS and TNKS2. Recognizes and binds tankyrase-dependent PARsylated proteins via its WWE domain and mediates their ubiquitination. May regulate TNKS and TNKS2 subcellular location, preventing aggregation at a centrosomal location. Neuroprotective protein. Protects the brain against N-methyl-D-aspartate (NMDA) receptor-mediated glutamate excitotoxicity and ischemia, by interfering with PAR-induced cell death, called parthanatos. Prevents nuclear translocation of AIFM1 in a PAR-binding dependent manner. Does not affect PARP1 activation. Protects against cell death induced by DNA damaging agents, such as N-methyl-N-nitro-N-nitrosoguanidine (MNNG) and rescues cells from G1 arrest. Promotes cell survival after gamma-irradiation. Facilitates DNA repair. Neuroprotective protein. Protects the brain against N-methyl-D-aspartate (NMDA) receptor-mediated glutamate excitotoxicity and ischemia, by interfering with PAR-induced cell death, called parthanatos. Prevents nuclear translocation of AIFM1 in a PAR-binding dependent manner. Does not affect PARP1 activation (By similarity).By similarity

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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei107 – 1071iso-ADP-ribose adenine ring groupBy similarity
Binding sitei110 – 1101iso-ADP-ribose 5'-phosphate groupBy similarity
Binding sitei114 – 1141iso-ADP-ribose 5'-phosphate groupBy similarity
Binding sitei144 – 1441iso-ADP-ribose 1'-phosphate groupBy similarity
Binding sitei153 – 1531iso-ADP-ribose adenine ring groupBy similarity
Binding sitei163 – 1631iso-ADP-ribose 1'-phosphate groupBy similarity
Binding sitei175 – 1751iso-ADP-ribose 5'-phosphate groupBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri36 – 7439RING-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Ubl conjugation pathway, Wnt signaling pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase RNF146 (EC:6.3.2.-)
Alternative name(s):
Iduna
RING finger protein 146
Gene namesi
Name:Rnf146
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi1306482. Rnf146.

Subcellular locationi

  • Cytoplasmcytosol By similarity
  • Nucleus By similarity

  • Note: Translocates to the nucleus after DNA damage, such as laser-induced DNA breaks, and concentrates at DNA breaks. This translocation requires PARP1 activation and PAR-binding (By similarity).By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 352352E3 ubiquitin-protein ligase RNF146PRO_0000056110Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Cross-linki84 – 84Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki94 – 94Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki130 – 130Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki175 – 175Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei288 – 2881PhosphoserineCombined sources
Modified residuei292 – 2921PhosphoserineCombined sources

Post-translational modificationi

Ubiquitinated; autoubiquitinated. Autoubiquitination is enhanced upon poly(ADP-ribose)-binding (By similarity).By similarity

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ5XIK5.
PRIDEiQ5XIK5.

PTM databases

iPTMnetiQ5XIK5.
PhosphoSiteiQ5XIK5.

Expressioni

Gene expression databases

BgeeiENSRNOG00000011588.
GenevisibleiQ5XIK5. RN.

Interactioni

Subunit structurei

Can form homooligomers. Interacts with PARsylated AXIN1, AXIN2, BLZF1, CASC3, HIST1H1C, IPO7, LIG3, NCL, PARP1, XRCC1, XRCC5 and XRCC6. Interacts with DDB1, DHX15, IQGAP1, LRPPRC, PARP2, PRKDC, RUVBL2, TNKS1 and TNKS2. Binding often leads to interactor ubiquitination, in the presence of the appropriate E1 and E2 enzymes, and proteasomal degradation (By similarity).By similarity

Protein-protein interaction databases

BioGridi258888. 1 interaction.
STRINGi10116.ENSRNOP00000015421.

Structurei

3D structure databases

ProteinModelPortaliQ5XIK5.
SMRiQ5XIK5. Positions 20-179.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini91 – 16777WWEPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni142 – 16524PAR-bindingBy similarityAdd
BLAST

Domaini

The WWE domain mediates non-covalent poly(ADP-ribose)-binding.By similarity

Sequence similaritiesi

Contains 1 RING-type zinc finger.PROSITE-ProRule annotation
Contains 1 WWE domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri36 – 7439RING-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG0824. Eukaryota.
ENOG410ZTFC. LUCA.
HOGENOMiHOG000128547.
HOVERGENiHBG057514.
InParanoidiQ5XIK5.
KOiK15700.
OrthoDBiEOG091G0Y4Y.
PhylomeDBiQ5XIK5.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR033509. RNF146.
IPR004170. WWE-dom.
IPR018123. WWE-dom_subgr.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
PANTHERiPTHR13417. PTHR13417. 1 hit.
PfamiPF02825. WWE. 1 hit.
[Graphical view]
SMARTiSM00184. RING. 1 hit.
SM00678. WWE. 1 hit.
[Graphical view]
PROSITEiPS50918. WWE. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q5XIK5-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAGCGEIDHS LNMLPTNKKA SETCSNTAPS LTVPECAICL QTCVHPVSLP
60 70 80 90 100
CKHVFCYLCV KGASWLGKRC ALCRQEIPED FLDKPTLLSP EELKAASRGN
110 120 130 140 150
GEYVWYYEGR NGWWQYDERT SRELEDAFSK GKKNTEMLIA GFLYVADLEN
160 170 180 190 200
MVQYRRNEHG RRRKIKRDII DIPKKGVAGL RLDCDSNTVN LARESSADGA
210 220 230 240 250
DSGSAHTGAS VQLPVPSSTR PLTSVDGQLT SPVTPSPDAG ASLEDSFAHL
260 270 280 290 300
QLSGDSIAER SHRGEGEEDH ESPSSGRVPD TSTEETESDA SSDIEDAPVV
310 320 330 340 350
VAQHSLTQQR LLVSSANQTV AERSDRPVAG GGTMSVNVRS RRPDGQCTVT

EV
Length:352
Mass (Da):38,224
Last modified:November 23, 2004 - v1
Checksum:iA0AE19B1F23560C1
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC083675 mRNA. Translation: AAH83675.1.
RefSeqiNP_001012060.2. NM_001012060.2.
UniGeneiRn.167060.
Rn.16849.

Genome annotation databases

GeneIDi308051.
KEGGirno:308051.
UCSCiRGD:1306482. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC083675 mRNA. Translation: AAH83675.1.
RefSeqiNP_001012060.2. NM_001012060.2.
UniGeneiRn.167060.
Rn.16849.

3D structure databases

ProteinModelPortaliQ5XIK5.
SMRiQ5XIK5. Positions 20-179.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi258888. 1 interaction.
STRINGi10116.ENSRNOP00000015421.

PTM databases

iPTMnetiQ5XIK5.
PhosphoSiteiQ5XIK5.

Proteomic databases

PaxDbiQ5XIK5.
PRIDEiQ5XIK5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi308051.
KEGGirno:308051.
UCSCiRGD:1306482. rat.

Organism-specific databases

CTDi81847.
RGDi1306482. Rnf146.

Phylogenomic databases

eggNOGiKOG0824. Eukaryota.
ENOG410ZTFC. LUCA.
HOGENOMiHOG000128547.
HOVERGENiHBG057514.
InParanoidiQ5XIK5.
KOiK15700.
OrthoDBiEOG091G0Y4Y.
PhylomeDBiQ5XIK5.

Enzyme and pathway databases

UniPathwayiUPA00143.

Miscellaneous databases

PROiQ5XIK5.

Gene expression databases

BgeeiENSRNOG00000011588.
GenevisibleiQ5XIK5. RN.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR033509. RNF146.
IPR004170. WWE-dom.
IPR018123. WWE-dom_subgr.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
PANTHERiPTHR13417. PTHR13417. 1 hit.
PfamiPF02825. WWE. 1 hit.
[Graphical view]
SMARTiSM00184. RING. 1 hit.
SM00678. WWE. 1 hit.
[Graphical view]
PROSITEiPS50918. WWE. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiRN146_RAT
AccessioniPrimary (citable) accession number: Q5XIK5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 1, 2005
Last sequence update: November 23, 2004
Last modified: September 7, 2016
This is version 88 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. 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.