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Protein

E3 ubiquitin-protein ligase RNF146

Gene

Rnf146

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 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 (By similarity). 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 (By similarity). 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 similarity2 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.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei109iso-ADP-ribose adenine ring groupBy similarity1
Binding sitei112iso-ADP-ribose 5'-phosphate groupBy similarity1
Binding sitei116iso-ADP-ribose 5'-phosphate groupBy similarity1
Binding sitei146iso-ADP-ribose 1'-phosphate groupBy similarity1
Binding sitei155iso-ADP-ribose adenine ring groupBy similarity1
Binding sitei165iso-ADP-ribose 1'-phosphate groupBy similarity1
Binding sitei177iso-ADP-ribose 5'-phosphate groupBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri38 – 76RING-typePROSITE-ProRule annotationAdd BLAST39

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

ReactomeiR-MMU-201681. TCF dependent signaling in response to WNT.
R-MMU-4641257. Degradation of AXIN.
R-MMU-5689880. Ub-specific processing proteases.
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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:1915281. Rnf146.

Subcellular locationi

  • Cytoplasmcytosol 1 Publication
  • 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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi55H → A: Loss of ubiquitination activity. 1 Publication1
Mutagenesisi61C → A: Loss of ubiquitination activity. Loss of protection against DNA damage. No effect on PAR-binding. 1 Publication1
Mutagenesisi156Y → A: Loss of PAR-binding and of protection against DNA damage; when associated with A-157. 2 Publications1
Mutagenesisi157R → A: Loss of PAR-binding and of protection against DNA damage; when associated with A-156. 2 Publications1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000561081 – 359E3 ubiquitin-protein ligase RNF146Add BLAST359

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki86Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki96Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki132Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki177Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei290PhosphoserineBy similarity1
Modified residuei294PhosphoserineBy similarity1

Post-translational modificationi

Ubiquitinated; autoubiquitinated. Autoubiquitination is enhanced upon PAR-binding (By similarity).By similarity

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ9CZW6.
PaxDbiQ9CZW6.
PRIDEiQ9CZW6.

PTM databases

iPTMnetiQ9CZW6.
PhosphoSitePlusiQ9CZW6.

Expressioni

Tissue specificityi

Expressed at relatively high levels in the brain. Also present in spleen, heart, kidney, testis and liver. In the brain, expressed in the cerebellum, hippocampus, striatum, cortex, frontal cortex and, at lowest levels, in olfactory bulb (at protein level). Predominantly expressed in neurons.2 Publications

Inductioni

Up-regulated in cortical neurons by treatment with N-methyl-D-aspartate (NMDA). Toxic doses of NMDA fail to induce Iduna expression. Sublethal exposure to oxygen-glucose deprivation also induces Iduna protein expression. Also induced by treatments that result in resistance to subsequent ischemic injury, such as 5 minute bilateral common carotid artery occlusion (at protein level).1 Publication

Gene expression databases

BgeeiENSMUSG00000038876.
CleanExiMM_RNF146.
ExpressionAtlasiQ9CZW6. baseline and differential.
GenevisibleiQ9CZW6. MM.

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

Protein-protein interaction databases

DIPiDIP-61462N.
STRINGi10090.ENSMUSP00000037224.

Structurei

Secondary structure

1359
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni39 – 41Combined sources3
Beta strandi42 – 44Combined sources3
Beta strandi46 – 50Combined sources5
Beta strandi56 – 58Combined sources3
Helixi59 – 66Combined sources8
Turni67 – 69Combined sources3
Turni73 – 75Combined sources3
Turni81 – 85Combined sources5
Helixi92 – 98Combined sources7
Turni99 – 101Combined sources3
Beta strandi105 – 111Combined sources7
Beta strandi114 – 117Combined sources4
Helixi120 – 131Combined sources12
Beta strandi135 – 141Combined sources7
Beta strandi144 – 149Combined sources6
Turni150 – 153Combined sources4
Beta strandi154 – 159Combined sources6
Beta strandi163 – 174Combined sources12
Beta strandi177 – 179Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1UJRNMR-A83-179[»]
2RSFNMR-A83-179[»]
4QPLX-ray1.90A/C32-185[»]
ProteinModelPortaliQ9CZW6.
SMRiQ9CZW6.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9CZW6.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini93 – 169WWEPROSITE-ProRule annotationAdd BLAST77

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni144 – 167PAR-bindingAdd BLAST24

Domaini

The WWE domain mediates non-covalent PAR-binding.

Sequence similaritiesi

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

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri38 – 76RING-typePROSITE-ProRule annotationAdd BLAST39

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG0824. Eukaryota.
ENOG410ZTFC. LUCA.
GeneTreeiENSGT00390000000358.
HOGENOMiHOG000128547.
HOVERGENiHBG057514.
InParanoidiQ9CZW6.
KOiK15700.
OMAiRMAGCGE.
OrthoDBiEOG091G0Y4Y.
PhylomeDBiQ9CZW6.
TreeFamiTF318925.

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.

Q9CZW6-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEMAGCGEID HSINMLPTNK KANESCSNTA PSLTVPECAI CLQTCVHPVS
60 70 80 90 100
LPCKHVFCYL CVKGASWLGK RCALCRQEIP EDFLDKPTLL SPEELKAASR
110 120 130 140 150
GNGEYAWYYE GRNGWWQYDE RTSRELEDAF SKGKKNTEML IAGFLYVADL
160 170 180 190 200
ENMVQYRRNE HGRRRKIKRD IIDIPKKGVA GLRLDCDTNT VNLARESSAD
210 220 230 240 250
GADSGSAQTG ASVQLAVPSS TRPLTSVDGQ LTSPVTPSPD AGISLEDSFA
260 270 280 290 300
HLQLSGDSIA ERSHRGEGEE DHESPSSGRV PDTSVEETES DASSDSEDAP
310 320 330 340 350
VVVAQHSLTQ QRPLVPNGNQ TVADQSDRSG TDRSVAGGGT MSVNVRSRRP

DGQCTVTEV
Length:359
Mass (Da):38,934
Last modified:March 1, 2003 - v2
Checksum:iB4449DB4897A41E0
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti339G → R in BAE31587 (PubMed:16141072).Curated1
Sequence conflicti339G → R in BAE31549 (PubMed:16141072).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK012080 mRNA. Translation: BAB28015.2.
AK169237 mRNA. Translation: BAE41005.1.
AK152856 mRNA. Translation: BAE31549.1.
AK152907 mRNA. Translation: BAE31587.1.
AC153912 Genomic DNA. No translation available.
BC050795 mRNA. Translation: AAH50795.1.
CCDSiCCDS48529.1.
RefSeqiNP_001103666.1. NM_001110196.1.
NP_001103667.1. NM_001110197.1.
NP_001103668.1. NM_001110198.1.
NP_001271208.1. NM_001284279.1.
NP_080794.2. NM_026518.4.
UniGeneiMm.28930.
Mm.475694.

Genome annotation databases

EnsembliENSMUST00000037548; ENSMUSP00000037224; ENSMUSG00000038876.
ENSMUST00000160144; ENSMUSP00000124288; ENSMUSG00000038876.
ENSMUST00000160372; ENSMUSP00000124215; ENSMUSG00000038876.
ENSMUST00000162335; ENSMUSP00000124772; ENSMUSG00000038876.
GeneIDi68031.
KEGGimmu:68031.
UCSCiuc007esy.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK012080 mRNA. Translation: BAB28015.2.
AK169237 mRNA. Translation: BAE41005.1.
AK152856 mRNA. Translation: BAE31549.1.
AK152907 mRNA. Translation: BAE31587.1.
AC153912 Genomic DNA. No translation available.
BC050795 mRNA. Translation: AAH50795.1.
CCDSiCCDS48529.1.
RefSeqiNP_001103666.1. NM_001110196.1.
NP_001103667.1. NM_001110197.1.
NP_001103668.1. NM_001110198.1.
NP_001271208.1. NM_001284279.1.
NP_080794.2. NM_026518.4.
UniGeneiMm.28930.
Mm.475694.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1UJRNMR-A83-179[»]
2RSFNMR-A83-179[»]
4QPLX-ray1.90A/C32-185[»]
ProteinModelPortaliQ9CZW6.
SMRiQ9CZW6.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-61462N.
STRINGi10090.ENSMUSP00000037224.

PTM databases

iPTMnetiQ9CZW6.
PhosphoSitePlusiQ9CZW6.

Proteomic databases

MaxQBiQ9CZW6.
PaxDbiQ9CZW6.
PRIDEiQ9CZW6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000037548; ENSMUSP00000037224; ENSMUSG00000038876.
ENSMUST00000160144; ENSMUSP00000124288; ENSMUSG00000038876.
ENSMUST00000160372; ENSMUSP00000124215; ENSMUSG00000038876.
ENSMUST00000162335; ENSMUSP00000124772; ENSMUSG00000038876.
GeneIDi68031.
KEGGimmu:68031.
UCSCiuc007esy.2. mouse.

Organism-specific databases

CTDi81847.
MGIiMGI:1915281. Rnf146.

Phylogenomic databases

eggNOGiKOG0824. Eukaryota.
ENOG410ZTFC. LUCA.
GeneTreeiENSGT00390000000358.
HOGENOMiHOG000128547.
HOVERGENiHBG057514.
InParanoidiQ9CZW6.
KOiK15700.
OMAiRMAGCGE.
OrthoDBiEOG091G0Y4Y.
PhylomeDBiQ9CZW6.
TreeFamiTF318925.

Enzyme and pathway databases

UniPathwayiUPA00143.
ReactomeiR-MMU-201681. TCF dependent signaling in response to WNT.
R-MMU-4641257. Degradation of AXIN.
R-MMU-5689880. Ub-specific processing proteases.

Miscellaneous databases

ChiTaRSiRnf146. mouse.
EvolutionaryTraceiQ9CZW6.
PROiQ9CZW6.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000038876.
CleanExiMM_RNF146.
ExpressionAtlasiQ9CZW6. baseline and differential.
GenevisibleiQ9CZW6. MM.

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_MOUSE
AccessioniPrimary (citable) accession number: Q9CZW6
Secondary accession number(s): E0CX97, Q3TF93, Q3U6Y7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 1, 2005
Last sequence update: March 1, 2003
Last modified: November 2, 2016
This is version 122 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Was named Iduna after the Norse goddess of protection and eternal youth.1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. 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.