Ubiquitin conjugation factor E4 B (UBE4B)

The protein contains 1302 amino acids for an estimated molecular weight of 146185 Da.

 

Ubiquitin-protein ligase that probably functions as an E3 ligase in conjunction with specific E1 and E2 ligases (By similarity). May also function as an E4 ligase mediating the assembly of polyubiquitin chains on substrates ubiquitinated by another E3 ubiquitin ligase (By similarity). May regulate myosin assembly in striated muscles together with STUB1 and VCP/p97 by targeting myosin chaperone UNC45B for proteasomal degradation (PubMed:17369820). (updated: Sept. 12, 2018)

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. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  5. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.

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.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

Interpro domains
Total structural coverage: 8%
Model score: 72
MODL_I-TASSER-3.0
MODL_I-TASSER-3.0

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VariantDescription
dbSNP:rs17034499

The reference OMIM entry for this protein is 613565

Ubiquitination factor e4b; ube4b
Ufd2, s. cerevisiae, homolog of, a; ufd2a
Kiaa0684

CLONING

By sequencing clones obtained from a size-fractionated human brain cDNA library, Ishikawa et al. (1998) cloned UBE4B, which they designated KIAA0684. The deduced 903-amino acid protein shares weak similarity with Dictyostelium NOSA, a developmental regulator involved in proteasomal degradation of ubiquitinated proteins (Koegl et al., 1999). See also UBE4A, 603753. Using RT-PCR, Ishikawa et al. (1998) found uniformly high KIAA0684 expression in all 10 human tissues examined. In vitro translation resulted in a protein with an apparent molecular mass of 92 kD by SDS-PAGE. Kaneko et al. (2003) cloned mouse Ube4b, which they called Ufd2a, from testis and T cell cDNA libraries. The deduced 1,174-amino acid protein has a C-terminal U-box domain including a proline residue perfectly conserved among U-box proteins. Western blot analysis detected Ufd2a at an apparent molecular mass of 140 kD in most mouse tissues examined, with highest abundance in cerebrum, cerebellum, and skeletal muscle. Immunohistochemical analysis revealed localization of Ufd2a in the cytoplasm of cortical pyramidal cells and cerebellar Purkinje cells.

GENE FUNCTION

By expressing epitope-tagged mouse proteins in human embryonic kidney cells, Kaneko et al. (2003) showed that Ufd2a interacted with Vcp (601023), a AAA-family ATPase implicated in protein folding. Using an in vitro ubiquitination assay with mouse and human UBE4B and MDM2 (164785), Wu et al. (2011) showed that either UBE4B or MDM2 alone led to monoubiquitination of the tumor suppressor p53 (TP53; 191170), while UBE4B in combination with MDM2 promoted p53 polyubiquitination. Reciprocal immunoprecipitation analysis and protein pull-down assays revealed that UBE4B interacted directly with MDM2. Overexpression and knockdown studies in mouse and human cell lines revealed that interaction of UBE4B with MDM2 reduced the half-life of p53 via proteasome-mediated degradation and caused repression of p53-dependent transactivation and apoptosis.

GENE STRUCTURE

Krona et al. (2003) determined that the UBE4B gene contains 28 exons. Kaneko et al. (2003) found that the mouse Ube4b gene contains 27 coding exons. The promoter region has a CpG island that contains a functional cis-acting element, but no TATA or CAAT boxes.

MAPPING

Using radiation hybrid analysis, Ishikawa et al. (1998) mapped the UBE4B gene to chromosome 1. By genomic sequence analysis, Krona et al. (2003) mapped the UBE4B gene to chromosome 1p36.3-p36.2. ... More on the omim web site

Subscribe to this protein entry history

Oct. 2, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.

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

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

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 613565 was added.

Jan. 25, 2016: Protein entry updated
Automatic update: model status changed