Ubiquitin activating enzyme

Function

Ubiquitin activating enzyme (Uba) or E1 enzyme catalyzes the first step in the ubiquitination of a protein tagged to be degraded by the proteasome. Ubiquitin activating enzyme (E1) and ATP produce a C-terminal acyl adenylated ubiquitin molecule which binds to ubiquitin conjugating enzyme (E2) (Ubc) cysteine^[1]. The Ubc then binds to ubiquitin ligase (E3) via a conserved binding region. E3 catalyzes the transfer of ubiquitin from the Ubc-ubiquitin complex to a lysine residue of the target protein.

• Uba1 see Uba1.
  
• Uba3 is the catalytic subunit of NEDD8 activating enzyme and APPB1 is its regulatory subunit. Similar to ubiquitin and SUMO, NEDD8 binds to proteins after processing of its C-terminal.
  
• Uba6 regulates the interferon-gamma production of T-cells by modulating NF-κB activation pathway^[2].
• Uba7 is involved in interferon-stimulated gene 15 conjugation^[3].
• Ubiquitin-like 1 activating enzyme E1A and Ubiquitin-like modifier-activating enzyme 2 are involved in SUMOylation^[4],^[5].

For ubiquitin-like modifier-activating enzyme Atg7 see Autophagy-related protein

(PDB entry 1y8x). .

3D structures of Ubiquitin activating enzyme

References

1. ↑ Nagai Y, Kaneda S, Nomura K, Yasuda H, Seno T, Yamao F. Ubiquitin-activating enzyme, E1, is phosphorylated in mammalian cells by the protein kinase Cdc2. J Cell Sci. 1995 Jun;108 ( Pt 6):2145-52. PMID:7673335
2. ↑ Lee JY, An EK, Hwang J, Jin JO, Lee PCW. Ubiquitin Activating Enzyme UBA6 Regulates Th1 and Tc1 Cell Differentiation. Cells. 2021 Dec 29;11(1):105. PMID:35011668 doi:10.3390/cells11010105
3. ↑ Lin M, Li Y, Qin S, Jiao Y, Hua F. Ubiquitin-like modifier-activating enzyme 7 as a marker for the diagnosis and prognosis of breast cancer. Oncol Lett. 2020 Apr;19(4):2773-2784. PMID:32218830 doi:10.3892/ol.2020.11406
4. ↑ Ong JR, Bamodu OA, Khang NV, Lin YK, Yeh CT, Lee WH, Cherng YG. SUMO-Activating Enzyme Subunit 1 (SAE1) Is a Promising Diagnostic Cancer Metabolism Biomarker of Hepatocellular Carcinoma. Cells. 2021 Jan 17;10(1):178. PMID:33477333 doi:10.3390/cells10010178
5. ↑ Zhang G, Zou J, Shi J, Qian B, Qiu K, Liu Q, Xie T, He Z, Xu H, Liao Y, Wu Y, Li Y, Xiao G, Yuan Y, Xiao R, Wu G, Zou X. Correction: Knockdown of ubiquitin-like modifier-activating enzyme 2 promotes apoptosis of clear cell renal cell carcinoma cells. Cell Death Dis. 2024 Jan 3;15(1):1. PMID:38172132 doi:10.1038/s41419-023-06384-w