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Protein

E3 ubiquitin-protein ligase RNF146

Gene

Rnf146

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

Miscellaneous

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

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.

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

Keywordsi

Molecular functionTransferase
Biological processUbl conjugation pathway, Wnt signaling pathway
LigandMetal-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
R-MMU-8948751 Regulation of PTEN stability and activity
UniPathwayi
UPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase RNF146 (EC:2.3.2.27)
Alternative name(s):
Iduna
RING finger protein 146
RING-type E3 ubiquitin transferase RNF146Curated
Gene namesi
Name:Rnf146
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:1915281 Rnf146

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

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 Expressed in 286 organ(s), highest expression level in visual cortex
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

Binary interactionsi

WithEntry#Exp.IntActNotes
UBE2D1P516682EBI-16124494,EBI-743540From Homo sapiens.

Protein-protein interaction databases

DIPiDIP-61462N
IntActiQ9CZW6, 1 interactor
STRINGi10090.ENSMUSP00000037224

Structurei

Secondary structure

1359
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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.

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
3.30.720.50, 1 hit
InterProiView protein in InterPro
IPR033509 RNF146
IPR004170 WWE-dom
IPR018123 WWE-dom_subgr
IPR037197 WWE_dom_sf
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
IPR017907 Znf_RING_CS
PANTHERiPTHR13417:SF2 PTHR13417:SF2, 1 hit
PfamiView protein in Pfam
PF02825 WWE, 1 hit
SMARTiView protein in SMART
SM00184 RING, 1 hit
SM00678 WWE, 1 hit
SUPFAMiSSF117839 SSF117839, 1 hit
PROSITEiView protein in PROSITE
PS50918 WWE, 1 hit
PS00518 ZF_RING_1, 1 hit
PS50089 ZF_RING_2, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.iShow all

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

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H9KV17H9KV17_MOUSE
E3 ubiquitin-protein ligase RNF146
Rnf146
223Annotation score:
A0A1L1SSN4A0A1L1SSN4_MOUSE
E3 ubiquitin-protein ligase RNF146
Rnf146
168Annotation score:

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

Similar proteinsi

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
IntActiQ9CZW6, 1 interactor
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

UniPathwayi
UPA00143

ReactomeiR-MMU-201681 TCF dependent signaling in response to WNT
R-MMU-4641257 Degradation of AXIN
R-MMU-5689880 Ub-specific processing proteases
R-MMU-8948751 Regulation of PTEN stability and activity

Miscellaneous databases

ChiTaRSiRnf146 mouse
EvolutionaryTraceiQ9CZW6
PROiPR:Q9CZW6
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000038876 Expressed in 286 organ(s), highest expression level in visual cortex
CleanExiMM_RNF146
ExpressionAtlasiQ9CZW6 baseline and differential
GenevisibleiQ9CZW6 MM

Family and domain databases

Gene3Di3.30.40.10, 1 hit
3.30.720.50, 1 hit
InterProiView protein in InterPro
IPR033509 RNF146
IPR004170 WWE-dom
IPR018123 WWE-dom_subgr
IPR037197 WWE_dom_sf
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
IPR017907 Znf_RING_CS
PANTHERiPTHR13417:SF2 PTHR13417:SF2, 1 hit
PfamiView protein in Pfam
PF02825 WWE, 1 hit
SMARTiView protein in SMART
SM00184 RING, 1 hit
SM00678 WWE, 1 hit
SUPFAMiSSF117839 SSF117839, 1 hit
PROSITEiView protein in PROSITE
PS50918 WWE, 1 hit
PS00518 ZF_RING_1, 1 hit
PS50089 ZF_RING_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiRN146_MOUSE
AccessioniPrimary (citable) accession number: Q9CZW6
Secondary accession number(s): E0CX97, Q3TF93, Q3U6Y7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 1, 2005
Last sequence update: March 1, 2003
Last modified: September 12, 2018
This is version 132 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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