Literature summary for 2.3.2.26 extracted from

Li, Y.; Kong, Y.; Zhou, Z.; Chen, H.; Wang, Z.; Hsieh, Y.C.; Zhao, D.; Zhi, X.; Huang, J.; Zhang, J.; Li, H.; Chen, C.
The HECTD3 E3 ubiquitin ligase facilitates cancer cell survival by promoting K63-linked polyubiquitination of caspase-8 (2013), Cell Death Dis., 4, e935.

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Protein Variants

Protein Variants	Comment	Organism
medicine	isoform HECTD3 is frequently overexpressed in breast carcinomas suggesting that caspase-8 ubiquitination by HECTD3 confers cancer cell survival	Homo sapiens

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	Q5T447	-	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
HEK-293T cell	-	Homo sapiens	-
MDA-MB-231 cell	-	Homo sapiens	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [caspase-8]-L-lysine	-	Homo sapiens	[E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[caspase-8]-L-lysine	isoform HECTD3 ubiquitinates caspase-8 with K63-linked polyubiquitin chains that do not target caspase-8 for degradation but decrease the caspase-8 activation	?

Synonyms

Synonyms	Comment	Organism
HECTD3	-	Homo sapiens

General Information

General Information	Comment	Organism
physiological function	HECTD3 depletion can sensitize cancer cells to extrinsic apoptotic stimuli. HECTD3 inhibits TNF-related apoptosis-inducing ligand-induced caspase-8 cleavage in an E3 ligase activity-dependent manner. Mutation of the caspase-8 ubiquitination site at K215 abolishes the HECTD3 protection from TNF-related apoptosis-inducing ligand-induced cleavage	Homo sapiens

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Release 2026.1 (March 2026)