-
This gene encodes an E3 ubiquitin ligase. The
encoded protein plays a role in type 1 cytokine receptor signaling by
controlling the balance between JAK2-associated cytokine receptor
degradation and ectodomain shedding. Alternative splicing results in
multiple transcript variants. [provided by RefSeq, Jun 2011]
Acts as E3 ubiquitin-protein ligase and regulates the degradation of
target proteins. Polyubiquitinates MYD88. Negatively regulates
MYD88-dependent production of pro-inflammatory 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 PRKN modifier that accelerates its
degradation, resulting in a reduction of PRKN activity, influencing the
balance of intracellular redox state. The RNF41-PRKN pathway regulates
autophagosome-lysosome fusion during late mitophagy. Mitophagy is a
selective form of autophagy necessary for mitochondrial quality control
(PubMed:24949970).
(
RNF41_HUMAN,Q9H4P4 )
Aliases for RNF41 Gene
Aliases for RNF41 Gene
GeneCards Symbol:
RNF41 2
Ring Finger Protein 41 2
3
5
NRDP1 2
3
4
5
SBBI03 2
3
5
Ring Finger Protein 41, E3
Ubiquitin Protein Ligase 2
3
RING-Type E3 Ubiquitin Transferase
NRDP1 3
4
E3 Ubiquitin-Protein Ligase NRDP1 3
4
External Ids for RNF41 Gene
ERBB3 binds RN41. Kts STRING MEMO1 karttaa
ERBB3 binds RN41. Kts STRING MEMO1 karttaa
/Neuregulin; Engelsk definition
A peptide factor originally identified by its ability to stimulate the phosphorylation the erbB-2 receptor (RECEPTOR, ERBB-2). It is a ligand for the erbB-3 receptor (RECEPTOR, ERBB-3) and the erbB-4 receptor. Variant forms of NEUREGULIN-1 occur through alternative splicing of its mRNA.)
27,11, 2023
Functional genomic characterization of a synthetic anti-HER3 antibody reveals a role for ubiquitination by RNF41 in the anti-proliferative response.
Turowec JP, Lau EWT, Wang X, Brown KR, Fellouse FA, Jawanda KK, Pan J, Moffat J, Sidhu SS.
J Biol Chem. 2019 Jan 25;294(4):1396-1409. doi: 10.1074/jbc.RA118.004420. Epub 2018 Dec 6.
PMID: 30523157
Free PMC article.
Using an shRNA library targeting enzymes in the ubiquitin
proteasome system, we screened for genes that effect response to IgG 95
and uncovered the E3 ubiquitin ligase
RNF41 as a driver of IgG 95 anti-proliferative activity.
RNF41 has been shown previously to regula …
Dysregulation of the ErbB family of receptor tyrosine kinases is
involved in the progression of many cancers. Antibodies targeting the
dimerization domains of family members EGFR and HER2 are approved cancer
therapeutics, but efficacy is restricted to a subset of tumors and
resistance often develops in response to treatment. A third family
member, HER3, heterodimerizes with both EGFR and HER2 and has also been
implicated in cancer. Consequently, there is strong interest in
developing antibodies that target HER3, but to date, no therapeutics
have been approved. To aid the development of anti-HER3 antibodies as
cancer therapeutics, we combined antibody engineering and functional
genomics screens to identify putative mechanisms of resistance or
synthetic lethality with antibody-mediated anti-proliferative effects.
We developed a synthetic antibody called IgG 95, which binds to HER3 and
promotes ubiquitination, internalization, and receptor down-regulation.
Using an shRNA library targeting enzymes in the ubiquitin proteasome
system, we screened for genes that effect response to IgG 95 and
uncovered the E3 ubiquitin ligase RNF41 as a driver of IgG 95
anti-proliferative activity. RNF41 has been shown previously to regulate
HER3 levels under normal conditions and we now show that it is also
responsible for down-regulation of HER3 upon treatment with IgG 95.
Moreover, our findings suggest that down-regulation of RNF41 itself may
be a mechanism for acquired resistance to treatment with IgG 95 and
perhaps other anti-HER3 antibodies. Our work deepens our understanding
of HER3 signaling by uncovering the mechanistic basis for the
anti-proliferative effects of potential anti-HER3 antibody therapeutics.
Keywords:
E3 ubiquitin ligase; HER3; RNF41; antibody; antibody engineering;
cancer; cell signaling; functional genomics; protein engineering; short
hairpin RNA (shRNA); ubiquitylation (ubiquitination).
© 2019 Turowec et al.
- Protein Symbol:
- Q9H4P4-RNF41_HUMAN
- Recommended name:
- E3 ubiquitin-protein ligase NRDP1
- Protein Accession:
- Q9H4P4
- Secondary Accessions:
-
Protein attributes for RNF41 Gene
- Size:
- 317 amino acids
- Molecular mass:
- 35905 Da
- Protein existence level:
- PE1
- Quaternary structure:
-
- Interacts with USP8, ERBB3, PRKN and BIRC6.
Interacts with CSF2RB, EPOR, IL3RA, MYD88 and TBK1.
Interacts with CLEC16A (By similarity).
- Sequence caution:
-
-
The sequence AAG01988.1 differs from that shown. Reason: Erroneous initiation Truncated N-terminus
Post-translational modifications for RNF41 Gene
-
Autoubiquitinated.
Autoubiquitination leads to proteasomal degradation.
Deubiquitinated by USP8 to get stabilized which induces apoptosis.
(
Q9H4P4-RNF41_HUMAN )
-
Ubiquitination at Lys174
(
NX_Q9H4P4 [NX_Q9H4P4-1]
)
-
Modification sites at PhosphoSitePlus
(
Q9H4P4 )
