G2E3

Official Full Name

G2/M-phase specific E3 ubiquitin protein ligase

Organism

Homo sapiens

Gene ID

55632

Background

Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in apoptotic process and protein ubiquitination. Predicted to act upstream of or within blastocyst development; negative regulation of intrinsic apoptotic signaling pathway; and protein polyubiquitination. Located in Golgi apparatus and cytosol. [provided by Alliance of Genome Resources, Feb 2025]

Synonyms

PHF7B; KIAA1333

Cat.No.	Product Name	Price
CSC-DC005996	Panoply™ Human G2E3 Knockdown Stable Cell Line	Inquiry
CSC-SC005996	Panoply™ Human G2E3 Over-expressing Stable Cell Line	Inquiry

Cat.No.	Product Name	Price
AD06500Z	Human G2E3 adenoviral particles	Inquiry
LV13238L	human G2E3 (NM_017769) lentivirus particles	Inquiry

Cat.No.	Product Name	Price
SHH298193	shRNA set against Human G2E3 (NM_017769.3)	Inquiry
SHH298197	shRNA set against Mouse G2E3 (NM_001015099.2)	Inquiry
SHH298201	shRNA set against Rat G2E3 (NM_001106726.1)	Inquiry
SHW001057	shRNA set against Chicken G2E3 (NM_001012900)	Inquiry
SHW007004	shRNA set against Danio rerio G2E3 (NM_001003822)	Inquiry

Cat.No.	Product Name	Price
CDFG021064	Mouse G2e3 cDNA Clone(NM_001167963.1)	Inquiry
CDFG021068	Mouse G2e3 cDNA Clone(NM_001167964.1)	Inquiry
CDFR006460	Rat G2e3 cDNA Clone(NM_001106726.1)	Inquiry
MiUTR4H-TG03685	G2E3 miRNA 3'UTR clone	Inquiry
CDCB162532	Chicken G2E3 ORF Clone (NM_001012900)	Inquiry
CDCB168479	Danio rerio G2E3 ORF Clone (NM_001003822)	Inquiry
CDCB187320	Rabbit G2E3 ORF clone (XM_008269464.1)	Inquiry
CDCG004733	Mouse G2E3 ORF clone(NM_001015099.2)	Inquiry
CDCL110051	Human G2e3 ORF clone (NM_001167963.1)	Inquiry
CDCL110053	Human G2e3 ORF clone (NM_001167964.1)	Inquiry
CDCR302358	Human G2E3 ORF Clone(NM_017769.3)	Inquiry
CDCR373470	Rat G2e3 ORF Clone(NM_001106726.1)	Inquiry
CDCS418625	Human G2E3 ORF Clone (BC000973)	Inquiry

Detailed Information

G2-specific E3 ligase (G2E3) was originally identified in a global gene expressing profiling with the GenBank reference KIAA1333 when Crawford et al. investigated transcriptional control of gene expression in G2/M-phase. In addition, they studied gene expression after DNA damage treatment using γ-irradiation. They conducted a microarray analysis of HeLa cells after double thymidine block and identified genes with maximal expression in G2- and M-phase. Interestingly, a number of genes were down-regulated in response to γ-irradiation. One of the genes showing a maximal mRNA expression in G2/M-phase and decreased mRNA levels on γ-irradiation was G2E3.

G2E3 was proposed to have ubiquitin ligase activity since it consists of four domains which can act as E3 ligases. Three of these domains have similarity to both RING and PHD domains and the fourth C-terminal domain is a HECT domain. Nevertheless, HECT is catalytically inactive, but controls subcellular localization of G2E3. Reasons for lack of activity of the HECT domain are numerous: not matching amino acids in the E2 binding site and at the C-terminus of the HECT domain and poorly conserved residues surrounding the active site. Through an in vitro ubiquitination assay, PHD/RING2 and PHD/RING3 domain have been reported to possess ubiquitin ligase activity and catalyze Lys48-linked poly-ubiquitination.

Studies have found G2E3 to modulate cellular proliferation, survival and the DNA damage response (DDR). They show that G2E3 is regulated in a DNA damage responsive manner since G2E3 mRNA and protein levels are decreased upon DNA damage treatment. Knockdown of G2E3 resulted in p53-independent apoptosis and decreased proliferation. Moreover, researchers verified prior findings that G2E3 levels are maximal in G2-phase, arguing for a cell cycle-dependent regulation of G2E3. Therefore, they propose a model in which G2E3 acts as a pro-survival factor that protects normal cells against cell death. Upon DNA damage, G2E3 supports cells to go into apoptosis by its down-regulation (Figure 1).

G2E3 Figure 1. Model of G2E3 affecting cellular survival.

The finding that apoptosis induced by G2E3 depletion is p53-independent raises the question of how G2E3 protects cells against apoptosis. The ubiquitin ligase was localized predominantly in the nucleus. Thus, G2E3 might not play a role in cytoplasmic and mitochondrial apoptotic processes. Conversely, G2E3 could influence transcription of apoptotic genes. Three domains of G2E3 have similarity to both PHD and RING domains. PHD domains infrequently have E3 activity, but bind methylated histones and are involved in chromatin-mediated gene regulation. It is not known whether G2E3 can bind chromatin and hence affect gene expression. This could be tested by performing a chromatin fractionation and exploring if G2E3 is enhanced in the chromatin-bound fraction. Furthermore, G2E3 could influence proteins which regulate the expression of apoptotic genes. The impact of p73 on translocation of Bax seems to be indirect as p73 localizes to the nucleus while inducing cell death. G2E3 is also a nuclear protein that could conduct its pro-survival role by inhibition of p73 or other nuclear proteins which indirectly affect apoptotic signaling in the cytoplasm.

References:

Schmidt F, et al. G2E3 attenuating replicative stress. Aging, 2015, 7(8):527-528.
Schmidt F, et al. Screening analysis of ubiquitin ligases reveals G2E3 as a potential target for chemosensitizing cancer cells. Oncotarget, 2015, 6(2):617.
Schmidt F. The ubiquitin ligase G2E3 modulates cell proliferation, survival and the DNA damage response. Göttingen, 2013.
Brooks W S, et al. G2E3 is a dual function ubiquitin ligase required for early embryonic development. Journal of Biological Chemistry, 2008, 283(32):22304-22315.

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