RNF41 E3 ubikitiiniligaasi hajoittaa neureguliinireseptoriproteiinia 1,

 

NCBI Gene Summary for RNF41 Gene

• 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]

GeneCards Summary for RNF41 Gene

RNF41 (Ring Finger Protein 41) is a Protein Coding gene. Among its related pathways are Class I MHC mediated antigen processing and presentation and Signaling by ERBB2. Gene Ontology (GO) annotations related to this gene include ubiquitin-protein transferase activity and acid-amino acid ligase activity. An important paralog of this gene is RNF151.

UniProtKB/Swiss-Prot Summary for RNF41 Gene

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}

• FLRF ^{3 4}

• Neuregulin Receptor Degradation Protein-1 ³

• Fetal Liver Ring Finger ³

• RING Finger Protein 41 ⁴

• EC 2.3.2.27 ⁴

• EC 6.3.2 ⁴⁸

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 details for RNF41 Gene (UniProtKB/Swiss-Prot)

Protein Symbol:

Q9H4P4-RNF41_HUMAN

Recommended name:

E3 ubiquitin-protein ligase NRDP1

Protein Accession:

Q9H4P4

Secondary Accessions:

• A6NFW0
• B2RBT8
• O75598

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 )