UBE2D1 (UBCH5)

UBE2D1 (Ubiquitin-conjugating enzyme E2D 1), also known as UBCH5, or UBCH5A, is a member of the ubiquitin-conjugating enzyme UBE2D family. UBE2D family (UBE2D1-4) as E2 partners for IDOL that support both autoubiquitination and IDOL-dependent ubiquitination of the LDLR in a cell-free system. Analysis of the IDOL-UBE2D1 interface also defined the stereochemical basis for the selectivity of IDOL for UBE2Ds over other E2 ligases. The IDOL-UBE2D complex as an important determinant of LDLR activity, and provide insight into molecular mechanisms underlying the regulation of cholesterol uptake. UBCH5 regulates Zipper-interacting protein kinase (ZIPK) accumulation in PML-NBs by interacting with ZIPK and stimulating its ubiquitination. Cadmium (Cd) markedly decreased the expression of UBE2D1, UBE2D2, UBE2D3 and UBE2D4 prior to the appearance of cytotoxicity in the NRK-52E cells. UBE2D family members may be one of the critical targets of renal toxicity caused by Cd. UBCH5A is involved in the iron-dependent ubiquitination of the hypoxia-inducible factor (HIF) by the von Hippel-Lindau tumor suppressor (pVHL) E3 ligase complex.

UBE2D1 (UBCH5) Alternative Names

UBE2D1, UBCH5, E2(17)KB1, SFT, UBC4/5, UBCH5A [Homo sapiens]

Ube2d1, UBCH5, MGC28550 [Mus musculus]

Summaries for UBE2D1 (UBCH5)

Entrez Gene summary for UBE2D1 (UBCH5):

The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. UBE2D1 gene encodes a member of the E2 ubiquitin-conjugating enzyme family. This enzyme is closely related to a stimulator of iron transport (SFT), and is up-regulated in hereditary hemochromatosis. It also functions in the ubiquitination of the tumor-suppressor protein p53 and the hypoxia-inducible transcription factor HIF1alpha by interacting with the E1 ubiquitin-activating enzyme and the E3 ubiquitin-protein ligases. Two transcript variants encoding different isoforms have been found for UBE2D1 gene. [provided by RefSeq, Mar 2011]

OMIM - description for UBE2D1 (UBCH5):

The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation by the 26S proteasome. At least 3 classes of enzymes are involved in the conjugation of ubiquitin to proteins. Ubiquitin-activating enzymes (e.g., UBE1 ), or E1s, are responsible for ATP-dependent charging of ubiquitin through formation of a high-energy thiol ester bond between the C terminus of ubiquitin and a cysteine within itself. The thiol ester-linked ubiquitin is transferred from E1 to a cysteine residue in a ubiquitin-conjugating enzyme, or E2. E2 enzymes, either by themselves or in combination with ubiquitin-protein ligases (e.g., UBE3A ), or E3s, then transfer ubiquitin monomers or multiubiquitin chains to target proteins, where stable isopeptide linkages are formed. The genome of S. cerevisiae contains at least 10 different E2s, including the closely related UBC4 and UBC5. UBE2D1 encodes a human homolog of S. cerevisiae UBC4 and UBC5. E2s that are highly similar to yeast UBC4 and UBC5 have also been identified in such diverse organisms as Arabidopsis thaliana (UBC8), Drosophila (UbcD1), and C. elegans (ubc2) (Scheffner et al., 1994).

Wikipedia summary for UBE2D1 (UBCH5):

Ubiquitin-conjugating enzyme E2 D1 is a protein that in humans is encoded by the UBE2D1 gene.
The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes a member of the E2 ubiquitin-conjugating enzyme family. This enzyme is closely related to a stimulator of iron transport (SFT), and is up-regulated in hereditary hemochromatosis. It also functions in the ubiquitination of the tumor-suppressor protein p53 and the hypoxia-inducible transcription factor HIF1alpha by interacting with the E1 ubiquitin-activating enzyme and the E3 ubiquitin-protein ligases.

Human UBE2D1 (UBCH5) Protein General Information

 

• Protein names: Ubiquitin-conjugating enzyme E2 D1
  Short name=UBE2D1
• Sequence length: 147 AA.
• Pathway: Protein modification; protein ubiquitination.
• Sequence similarities: Belongs to the ubiquitin-conjugating enzyme family.
• Catalytic activity: ATP + ubiquitin + protein lysine = AMP + diphosphate + protein N-ubiquityllysine.
• Subunit structure: Component of a E3 ubiquitin ligase complex containing UBE2D1, SIAH1, CACYBP/SIP, SKP1, APC and TBL1X. Interacts with RNF11.
• Subcellular location: Cytoplasm
• Tissue specificity: Ubiquitous. Up-regulated in livers of iron-overloaded patients with hereditary hemochromatosis.
• Caution: cloned and sequenced SFT which consisted of UBE2D1 last coding exon along with intronic sequences on the 5'-end of this exon. A function in iron transport has been described.

General information above from UniProt

Function for UBE2D1 (UBCH5) Protein

UniProtKB:

UBE2D1 accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-48'-linked polyubiquitination. UBE2D1 mediates the selective degradation of short-lived and abnormal proteins. UBE2D1 functions in the E6/E6-AP-induced ubiquitination of p53/TP53. UBE2D1 mediates ubiquitination of PEX5 and auto-ubiquitination of STUB1, TRAF6 and TRIM63/MURF1. UBE2D1 ubiquitinates STUB1-associated HSP90AB1 in vitro. UBE2D1 lacks inherent specificity for any particular lysine residue of ubiquitin. UBE2D1 is essential for viral activation of IRF3. UBE2D1 mediates polyubiquitination of CYP3A4.

Genatlas:

• UBE2D1 is involved in the degradation of cellular proteins
• UBE2D1 mediates the E6-AP dependent ubiquitination of TP53
• UBE2D1 regulates DAPK3 accumulation in promyelocytic leukemia protein nuclear body (PML-NB)by interacting with DAPK3 and stimulating its ubiquitination
• Catalytically active UBE2D1 is required for IRF3 activation by viral infection
• UBE2D1 is critical regulators of the stability of BIRC2 protein following destabilizing stimuli such as TNFSF12 or CD40 signalling or IAP antagonists
• UBE2D1 is promiscuous E2 enzyme with an innate preference for forming polyubiquitin chains through lysine 11 (K11), lysine 48 (K48), and lysine 63 (K63) of Ubiquitin
• BIRC2 and UBE2D1 promote K11-linked polyubiquitination of RIPK1 in TNF signalling

Homology for human UBE2D1 (UBCH5)

• homolog to yeast UBC4/5