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Protein

E3 ubiquitin-protein ligase NRDP1

Gene

RNF41

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

Functioni

Acts as E3 ubiquitin-protein ligase and regulates the degradation of target proteins. Polyubiquitinates MYD88. Negatively regulates MYD88-dependent production of proinflammatory cytokines. Can promote TRIF-dependent production of type I interferon and inhibits infection with vesicular stomatitis virus (By similarity). Promotes also activation of TBK1 and IRF3. Involved in the ubiquitination of erythropoietin (EPO) and interleukin-3 (IL-3) receptors. Thus, through maintaining basal levels of cytokine receptors, RNF41 is involved in the control of hematopoietic progenitor cell differentiation into myeloerythroid lineages (By similarity). Contributes to the maintenance of steady-state ERBB3 levels by mediating its growth factor-independent degradation. Involved in the degradation of the inhibitor of apoptosis BIRC6 and thus is an important regulator of cell death by promoting apoptosis. Acts also as a PARK2 modifier that accelerates its degradation, resulting in a reduction of PARK2 activity, influencing the balance of intracellular redox state. The RNF41-PARK2 pathway regulates autophagosome-lysosome fusion during late mitophagy. Mitophagy is a selective form of autophagy necessary for mitochondrial quality control (PubMed:24949970).By similarity7 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 fingeri18 – 57RING-type; degeneratePROSITE-ProRule annotationAdd BLAST40
Zinc fingeri78 – 138SIAH-type; degeneratePROSITE-ProRule annotationAdd BLAST61

GO - Molecular functioni

  • acid-amino acid ligase activity Source: InterPro
  • protein tag Source: InterPro
  • Ral GTPase binding Source: UniProtKB
  • ubiquitin protein ligase activity Source: ParkinsonsUK-UCL
  • ubiquitin-protein transferase activity Source: UniProtKB
  • zinc ion binding Source: InterPro

GO - Biological processi

  • autophagy Source: UniProtKB-KW
  • ERBB2 signaling pathway Source: Reactome
  • extrinsic apoptotic signaling pathway Source: UniProtKB
  • negative regulation of cell migration Source: MGI
  • negative regulation of cell proliferation Source: MGI
  • negative regulation of macromitophagy Source: Ensembl
  • positive regulation of reactive oxygen species metabolic process Source: ParkinsonsUK-UCL
  • positive regulation of sequence-specific DNA binding transcription factor activity Source: Ensembl
  • proteasomal protein catabolic process Source: ParkinsonsUK-UCL
  • protein autoubiquitination Source: FlyBase
  • protein polyubiquitination Source: UniProtKB
  • regulation of establishment of cell polarity Source: Ensembl
  • regulation of lymphocyte differentiation Source: Ensembl
  • regulation of MAPK cascade Source: MGI
  • regulation of myeloid cell differentiation Source: Ensembl
  • regulation of protein kinase B signaling Source: MGI
  • regulation of reactive oxygen species metabolic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Apoptosis, Autophagy, Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BRENDAi6.3.2.19. 2681.
ReactomeiR-HSA-1358803. Downregulation of ERBB2:ERBB3 signaling.
R-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase NRDP1 (EC:6.3.2.-)
Alternative name(s):
RING finger protein 41
Gene namesi
Name:RNF41
Synonyms:FLRF, NRDP1
ORF Names:SBBI03
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:18401. RNF41.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi34C → S: Loss of activity; when associated with Q-36. 2 Publications1
Mutagenesisi36H → Q: Loss of activity; when associated with S-34. 2 Publications1
Mutagenesisi56D → V: Loss of activity. 1 Publication1

Organism-specific databases

DisGeNETi10193.
OpenTargetsiENSG00000181852.
PharmGKBiPA134875033.

Polymorphism and mutation databases

BioMutaiRNF41.
DMDMi88909120.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002239541 – 317E3 ubiquitin-protein ligase NRDP1Add BLAST317

Post-translational modificationi

Autoubiquitinated. Autoubiquitination leads to proteasomal degradation. Deubiquitinated by USP8 to get stabilized which induces apoptosis.3 Publications

Keywords - PTMi

Ubl conjugation

Proteomic databases

EPDiQ9H4P4.
MaxQBiQ9H4P4.
PaxDbiQ9H4P4.
PeptideAtlasiQ9H4P4.
PRIDEiQ9H4P4.

PTM databases

iPTMnetiQ9H4P4.
PhosphoSitePlusiQ9H4P4.

Expressioni

Tissue specificityi

Detected in ovary, testis and prostate.1 Publication

Gene expression databases

BgeeiENSG00000181852.
CleanExiHS_RNF41.
ExpressionAtlasiQ9H4P4. baseline and differential.
GenevisibleiQ9H4P4. HS.

Organism-specific databases

HPAiHPA016812.
HPA052170.

Interactioni

Subunit structurei

Interacts with USP8, ERBB3, PARK2 and BIRC6. Interacts with CSF2RB, EPOR, IL3RA, MYD88 and TBK1. Interacts with CLEC16A (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
ARL6IP4Q66PJ3-33EBI-2130266,EBI-10248982
ASB6Q9NWX55EBI-2130266,EBI-6425205
C1orf109Q9NX043EBI-2130266,EBI-8643161
ENOPH1Q9UHY74EBI-2130266,EBI-726969
HOMER2Q9NSB83EBI-2130266,EBI-2126733
ISCA2Q86U283EBI-2130266,EBI-10258659
LZTS2Q9BRK43EBI-2130266,EBI-741037
RFC4P352496EBI-2130266,EBI-476655
TTC1Q9961410EBI-2130266,EBI-742074
VPS52Q8N1B45EBI-2130266,EBI-2799833

GO - Molecular functioni

  • Ral GTPase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi115488. 66 interactors.
IntActiQ9H4P4. 49 interactors.
STRINGi9606.ENSP00000342755.

Structurei

Secondary structure

1317
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi193 – 205Combined sources13
Beta strandi206 – 211Combined sources6
Helixi214 – 216Combined sources3
Beta strandi217 – 220Combined sources4
Helixi223 – 235Combined sources13
Helixi240 – 248Combined sources9
Helixi252 – 254Combined sources3
Turni257 – 259Combined sources3
Helixi262 – 267Combined sources6
Turni268 – 270Combined sources3
Helixi271 – 274Combined sources4
Beta strandi277 – 279Combined sources3
Beta strandi283 – 289Combined sources7
Helixi290 – 292Combined sources3
Turni298 – 300Combined sources3
Beta strandi303 – 312Combined sources10
Beta strandi314 – 316Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2FZPX-ray1.87A193-317[»]
2GWFX-ray2.30B/D/F193-317[»]
ProteinModelPortaliQ9H4P4.
SMRiQ9H4P4.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9H4P4.

Family & Domainsi

Sequence similaritiesi

Contains 1 RING-type zinc finger.PROSITE-ProRule annotation
Contains 1 SIAH-type zinc finger.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri18 – 57RING-type; degeneratePROSITE-ProRule annotationAdd BLAST40
Zinc fingeri78 – 138SIAH-type; degeneratePROSITE-ProRule annotationAdd BLAST61

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiENOG410ISDX. Eukaryota.
ENOG410XNN7. LUCA.
GeneTreeiENSGT00530000063647.
HOGENOMiHOG000006561.
HOVERGENiHBG053154.
InParanoidiQ9H4P4.
KOiK11981.
OMAiLMENCHE.
OrthoDBiEOG091G0BKR.
PhylomeDBiQ9H4P4.
TreeFamiTF351947.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
3.90.890.10. 1 hit.
InterProiIPR013323. SIAH-type.
IPR008974. TRAF-like.
IPR015036. USP8_interacting.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
IPR013010. Znf_SIAH.
[Graphical view]
PfamiPF08941. USP8_interact. 1 hit.
[Graphical view]
SMARTiSM00184. RING. 1 hit.
[Graphical view]
SUPFAMiSSF49599. SSF49599. 1 hit.
PROSITEiPS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
PS51081. ZF_SIAH. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q9H4P4-1) [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
MGYDVTRFQG DVDEDLICPI CSGVLEEPVQ APHCEHAFCN ACITQWFSQQ
60 70 80 90 100
QTCPVDRSVV TVAHLRPVPR IMRNMLSKLQ IACDNAVFGC SAVVRLDNLM
110 120 130 140 150
SHLSDCEHNP KRPVTCEQGC GLEMPKDELP NHNCIKHLRS VVQQQQTRIA
160 170 180 190 200
ELEKTSAEHK HQLAEQKRDI QLLKAYMRAI RSVNPNLQNL EETIEYNEIL
210 220 230 240 250
EWVNSLQPAR VTRWGGMIST PDAVLQAVIK RSLVESGCPA SIVNELIENA
260 270 280 290 300
HERSWPQGLA TLETRQMNRR YYENYVAKRI PGKQAVVVMA CENQHMGDDM
310
VQEPGLVMIF AHGVEEI
Length:317
Mass (Da):35,905
Last modified:February 21, 2006 - v2
Checksum:i46AE87AF8BE1A369
GO
Isoform 2 (identifier: Q9H4P4-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-71: Missing.

Note: No experimental confirmation available.
Show »
Length:246
Mass (Da):27,965
Checksum:iF21D7FD03FA53642
GO

Sequence cautioni

The sequence AAG01988 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0446701 – 71Missing in isoform 2. 1 PublicationAdd BLAST71

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF077599 mRNA. Translation: AAC27647.1.
AK314811 mRNA. Translation: BAG37335.1.
AC073896 Genomic DNA. No translation available.
CH471054 Genomic DNA. Translation: EAW96909.1.
CH471054 Genomic DNA. Translation: EAW96910.1.
BC024284 mRNA. No translation available.
BC032637 mRNA. Translation: AAH32637.1.
AY007109 mRNA. Translation: AAG01988.1. Different initiation.
CCDSiCCDS8909.1. [Q9H4P4-1]
CCDS8910.1. [Q9H4P4-2]
RefSeqiNP_001229755.1. NM_001242826.1. [Q9H4P4-1]
NP_005776.1. NM_005785.3. [Q9H4P4-1]
NP_919339.1. NM_194358.2. [Q9H4P4-2]
NP_919340.1. NM_194359.2. [Q9H4P4-1]
XP_005268618.1. XM_005268561.4. [Q9H4P4-2]
XP_011536036.1. XM_011537734.2. [Q9H4P4-2]
XP_011536037.1. XM_011537735.2. [Q9H4P4-2]
UniGeneiHs.524502.

Genome annotation databases

EnsembliENST00000345093; ENSP00000342755; ENSG00000181852. [Q9H4P4-1]
ENST00000394013; ENSP00000377581; ENSG00000181852. [Q9H4P4-2]
ENST00000552656; ENSP00000447303; ENSG00000181852. [Q9H4P4-1]
ENST00000615206; ENSP00000484671; ENSG00000181852. [Q9H4P4-1]
GeneIDi10193.
KEGGihsa:10193.
UCSCiuc001ske.3. human. [Q9H4P4-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF077599 mRNA. Translation: AAC27647.1.
AK314811 mRNA. Translation: BAG37335.1.
AC073896 Genomic DNA. No translation available.
CH471054 Genomic DNA. Translation: EAW96909.1.
CH471054 Genomic DNA. Translation: EAW96910.1.
BC024284 mRNA. No translation available.
BC032637 mRNA. Translation: AAH32637.1.
AY007109 mRNA. Translation: AAG01988.1. Different initiation.
CCDSiCCDS8909.1. [Q9H4P4-1]
CCDS8910.1. [Q9H4P4-2]
RefSeqiNP_001229755.1. NM_001242826.1. [Q9H4P4-1]
NP_005776.1. NM_005785.3. [Q9H4P4-1]
NP_919339.1. NM_194358.2. [Q9H4P4-2]
NP_919340.1. NM_194359.2. [Q9H4P4-1]
XP_005268618.1. XM_005268561.4. [Q9H4P4-2]
XP_011536036.1. XM_011537734.2. [Q9H4P4-2]
XP_011536037.1. XM_011537735.2. [Q9H4P4-2]
UniGeneiHs.524502.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2FZPX-ray1.87A193-317[»]
2GWFX-ray2.30B/D/F193-317[»]
ProteinModelPortaliQ9H4P4.
SMRiQ9H4P4.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115488. 66 interactors.
IntActiQ9H4P4. 49 interactors.
STRINGi9606.ENSP00000342755.

PTM databases

iPTMnetiQ9H4P4.
PhosphoSitePlusiQ9H4P4.

Polymorphism and mutation databases

BioMutaiRNF41.
DMDMi88909120.

Proteomic databases

EPDiQ9H4P4.
MaxQBiQ9H4P4.
PaxDbiQ9H4P4.
PeptideAtlasiQ9H4P4.
PRIDEiQ9H4P4.

Protocols and materials databases

DNASUi10193.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000345093; ENSP00000342755; ENSG00000181852. [Q9H4P4-1]
ENST00000394013; ENSP00000377581; ENSG00000181852. [Q9H4P4-2]
ENST00000552656; ENSP00000447303; ENSG00000181852. [Q9H4P4-1]
ENST00000615206; ENSP00000484671; ENSG00000181852. [Q9H4P4-1]
GeneIDi10193.
KEGGihsa:10193.
UCSCiuc001ske.3. human. [Q9H4P4-1]

Organism-specific databases

CTDi10193.
DisGeNETi10193.
GeneCardsiRNF41.
HGNCiHGNC:18401. RNF41.
HPAiHPA016812.
HPA052170.
neXtProtiNX_Q9H4P4.
OpenTargetsiENSG00000181852.
PharmGKBiPA134875033.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410ISDX. Eukaryota.
ENOG410XNN7. LUCA.
GeneTreeiENSGT00530000063647.
HOGENOMiHOG000006561.
HOVERGENiHBG053154.
InParanoidiQ9H4P4.
KOiK11981.
OMAiLMENCHE.
OrthoDBiEOG091G0BKR.
PhylomeDBiQ9H4P4.
TreeFamiTF351947.

Enzyme and pathway databases

UniPathwayiUPA00143.
BRENDAi6.3.2.19. 2681.
ReactomeiR-HSA-1358803. Downregulation of ERBB2:ERBB3 signaling.
R-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.

Miscellaneous databases

EvolutionaryTraceiQ9H4P4.
GeneWikiiRNF41.
GenomeRNAii10193.
PROiQ9H4P4.

Gene expression databases

BgeeiENSG00000181852.
CleanExiHS_RNF41.
ExpressionAtlasiQ9H4P4. baseline and differential.
GenevisibleiQ9H4P4. HS.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
3.90.890.10. 1 hit.
InterProiIPR013323. SIAH-type.
IPR008974. TRAF-like.
IPR015036. USP8_interacting.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
IPR013010. Znf_SIAH.
[Graphical view]
PfamiPF08941. USP8_interact. 1 hit.
[Graphical view]
SMARTiSM00184. RING. 1 hit.
[Graphical view]
SUPFAMiSSF49599. SSF49599. 1 hit.
PROSITEiPS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
PS51081. ZF_SIAH. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiRNF41_HUMAN
AccessioniPrimary (citable) accession number: Q9H4P4
Secondary accession number(s): A6NFW0, B2RBT8, O75598
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 21, 2006
Last sequence update: February 21, 2006
Last modified: November 30, 2016
This is version 120 of the entry and version 2 of the sequence. [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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  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.