UBOX2, UBED4A, UBOX2A, UFD2 (11q23.2), E4 ubikitiiniligaasi on E1-, E2-, E3-koordinaattori

https://www.ncbi.nlm.nih.gov/gene/9354

UBE4A ubiquitination factor E4A [ Homo sapiens (human) ]

E4 ubikitiiniligaasi eli U-box ubikitiiniligaasiperhetta, joka osallistuu jmultiubikitiiniketjujen koostamiseen ja on tärkeä kromosomiaineksen tiivistymisessä ja erkanemisissa sekuriinin poluyubikitinaation  avulla.  Autovasta-aineet  ovat merkkareita sklerodermasta ja Crohnin taudista.
Geeni  UBOX2A ( 11q23.2).
Muita nimiä E4, UFD2 ja UBOX2.  Tätä ilmenee aivossa ja umpisuolenlisäkkeessä.  

Also known as

E4A; ( UFD2 holomog yest); UBOX2

Summary This gene encodes a member of the U-box ubiquitin ligase family. The encoded protein is involved in multiubiquitin chain assembly and plays a critical role in chromosome condensation and separation through the polyubiquitination of securin. Autoantibodies against the encoded protein may be markers for scleroderma and Crohn's disease. A pseudogene of this gene is located on the long arm of chromosome 3. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2011]

Expression Ubiquitous expression in brain (RPKM 15.5), appendix (RPKM 14.1) and 25 other tissues See more Orthologs  mouse all

 

 

Preferred Names

ubiquitin conjugation factor E4 A

Names

RING-type E3 ubiquitin transferase E4 A

ubiquitination factor E4A (UFD2 homolog, yeast)

Conserved Domains (2) summary

pfam10408
Location:330 → 971

Ufd2P_core; Ubiquitin elongating factor core . This is the most conserved part of the core region of Ufd2P ubiquitin elongating factor or E4, running from helix alpha-11 to alpha-38. It consists of 31 helices of variable length connected by loops of variable size forming a compact unit; the helical packing pattern of the compact unit consists of five structural repeats that resemble tandem Armadillo (ARM) repeats. This domain is involved in ubiquitination as it binds Cdc48p and escorts ubiquitinated proteins from Cdc48p to the proteasome for degradation. The core is structurally similar to the nuclear transporter protein importin-alpha. The core is associated with the U-box at the C-terminus, pfam04564, which has ligase activity

cd16657
Location:990 → 1059

RING-Ubox_UBE4A;

U-box domain, a modified RING finger, found in ubiquitin conjugation factor E4 A (UBE4A) and similar proteins

The family includes yeast ubiquitin fusion degradation protein 2 (UFD2p) and its mammalian homolog, UBE4A. Yeast UFD2p, also known as ubiquitin conjugation factor E4 or UB fusion protein 2, is a polyubiquitin chain conjugation factor (E4) in the ubiquitin fusion degradation (UFD) pathway which catalyzes elongation of the ubiquitin chain through Lys48 linkage. It binds to substrates conjugated with one to three ubiquitin molecules and catalyzes the addition of further ubiquitin moieties in the presence of ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2) and ubiquitin ligase (E3), yielding multiubiquitylated substrates that are targets for the 26S proteasome. UFD2p is implicated in cell survival under stress conditions and is essential for homoeostasis of unsaturated fatty acids. It interacts with UBL-UBA proteins Rad23 and Dsk2, which are involved in the endoplasmic reticulum-associated degradation, ubiquitin fusion degradation, and OLE-1 gene induction pathway. UBE4A is a U-box-type ubiquitin-protein ligase that is located in common neuroblastoma deletion regions and may be subject to mutations in tumors. It may have a specific role in different biochemical processes other than ubiquitination, including growth or differentiation. Members in this family contain an N-terminal ubiquitin elongating factor core and a RING-like U-box domain at the C-terminus.

 

Related articles in PubMed

1. Autoantibodies against ubiquitination factor E4A (UBE4A) are associated with severity of Crohn's disease. Sakiyama T, et al. Inflamm Bowel Dis, 2008 Mar. PMID 18069675
2. Expression analysis of the gene encoding for the U-box-type ubiquitin ligase UBE4A in human tissues. Contino G, et al. Gene, 2004 Mar 17. PMID 15019985
3. The ubiquitin ligase UBE4A inhibits prostate cancer progression by targeting interleukin-like EMT inducer (ILEI). Sun Y, et al. IUBMB Life, 2017 Jan. PMID 27862841
4. SLAP displays tumour suppressor functions in colorectal cancer via destabilization of the SRC substrate EPHA2. Naudin C, et al. Nat Commun, 2014. PMID 24457997
5. [Differential expression of USP2, USP14 and UBE4A between ovarian serous cystadenocarcinoma and adjacent normal tissues]. Yang Y, et al. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi, 2007 Jun. PMID 17553343

See all (34) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

 

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

1. UBE4A's recruitment to sites of DNA damage is dependent on primary E3 ligases in the DDR and promotes enhancement and sustainment of K48- and K63-linked ubiquitin chains at these sites. This step is required for timely recruitment of the RAP80 and BRCA1 proteins and proper organization of RAP80- and BRCA1-associated protein complexes at DSB sites.
2. UBE4A targets PCBP1 for proteasomal degradation and that UBE4A expression can serve as a novel biomarker in thyroid cancer patients.
3. Ectopic overexpression of UBE4A, but not UBE3C, in cells was downregulated in vitro migration and invasion in these cells. Cumulatively, our data reveals a novel post-translational regulatory mechanism of regulating ILEI1 expression, a protein required for metastatic progression in prostate cancer cells
4. Identified an intestinal cDNA clone encoding ubiquitination factor E4A (UBE4A), a U-box-type ubiquitin-protein ligase. The prevalence of anti-UBE4A IgG in patients with CD was significantly higher than that in patients with UC or healthy controls
5. UBE4A was over-expressed in ovarian serous cystadenocarcinoma tissues, suggesting that the activity of ubiquitin-proteasome system is enhanced in ovarian cancer.
6. In these studies, we define Ufd2 (a novel E4 polyubiquitylating enzyme) as a new autoantigen in scleroderma, and show that it regulates chromosome condensation and separation during mitosis in human cells.
7. UBE4A is expressed in different tissues in a pattern that seems to be dependent from cell type and cell cycle and that UBE4A might have a specific role in different biochemical processes other than ubiquitination, including growth or differentiation.

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