E3 ubiquitin-protein ligase RNF123 (RNF123)

The protein contains 1314 amino acids for an estimated molecular weight of 148515 Da.

 

Catalytic subunit of the KPC complex that acts as E3 ubiquitin-protein ligase. Promotes the ubiquitination and proteasome-mediated degradation of CDKN1B which is the cyclin-dependent kinase inhibitor at the G0-G1 transition of the cell cycle (PubMed:15531880, PubMed:16227581). Functions also as an inhibitor of innate antiviral signaling mediated by DDX58 and IFIH1 independently of its E3 ligase activity (PubMed:27312109). Interacts with the N-terminal CARD domains of DDX58 and IFIH1 and competes with the downstream adapter MAVS (PubMed:27312109). (updated: Oct. 16, 2019)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  4. Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
  5. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  6. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  7. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

Interpro domains
Total structural coverage: 6%
Model score: 0

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VariantDescription
dbSNP:rs2960546
dbSNP:rs35620248
dbSNP:rs35726701
dbSNP:rs34823813

The reference OMIM entry for this protein is 614472

Ring finger protein 123; rnf123
Kip1 ubiquitination-promoting complex 1; kpc1

DESCRIPTION

RNF123 is a cytoplasmic E3 ubiquitin ligase with a role in cell cycle progression (Kamura et al., 2004).

CLONING

By searching an EST database for sequences similar to rabbit Kpc1, Kamura et al. (2004) identified human RNF123, which they called KPC1. The deduced 1,314-amino acid protein has an N-terminal SPRY domain and a C-terminal RING finger domain. Epitope-tagged KPC1 was expressed as a cytoplasmic protein in transfected NIH-3T3 cells.

GENE FUNCTION

By immunoprecipitation analysis, Kamura et al. (2004) found that epitope-tagged KPC1 interacted directly with KPC2 (UBAC1; 608129) and exhibited pronounced E3 ubiquitin ligase activity toward p27(KIP1) (CDKN1B; 600778), but not other substrates, in the presence of E1 (UBA1; 314370) and E2 (UBCH5A, or UBE2D1; 602961) enzymes. Both mono- and polyubiquitinated forms of p27(KIP1) were detected, and polyubiquitination required either UBC4 (UBE2D2; 602962) or UBCH5A. The E3 activity of KPC1 toward p27(KIP1) was greater in the absence of PKC2. Overexpression and knockdown studies with mouse fibroblasts revealed that the KPC complex functioned in the cytoplasm, ubiquitinated p27(KIP1) during G1 phase of the cell cycle, and required nuclear export of p27(KIP1) by Crm1 (XPO1; 602559). Ubiquitination of p27(KIP1) at S phase was performed by Skp2 (601436). Depletion of endogenous Kpc1 from Skp2 -/- mouse embryonic fibroblasts resulted in p27(KIP1) accumulation and a delay in cell cycle progression. Using rat myoblast and fibroblast cell lines, Lu et al. (2009) showed that the ubiquitin-specific protease Usp19 (614471) regulated p27(KIP1) levels by deubiquitinating and stabilizing Kpc1 against proteasomal degradation. Immunoprecipitation analysis revealed that Usp19 interacted directly with Kpc1. Knockdown of Usp19 resulted in loss of Kpc1, accumulation of p27(KIP1), inhibition of cell proliferation, and slower progression from G0/G1 to S phase.

MAPPING

Hartz (2011) mapped the RPF123 gene to chromosome 3p21.31 based on an alignment of the RPF123 sequence (GenBank GENBANK AK022627) with the genomic sequence (GRCh37). ... More on the omim web site

Subscribe to this protein entry history

Oct. 27, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.

May 12, 2019: Protein entry updated
Automatic update: model status changed

Nov. 17, 2018: Protein entry updated
Automatic update: model status changed

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

Oct. 27, 2017: Protein entry updated
Automatic update: model status changed

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 614472 was added.

Feb. 24, 2016: Protein entry updated
Automatic update: model status changed