Zinc finger protein with KRAB and SCAN domains 3 (ZKSCAN3)

Zinc finger protein with KRAB and SCAN domains 3 (ZKSCAN3) is a multifunctional transcription factor characterized by DNA-binding C2H2 zinc finger motifs, a KRAB (Krüppel-associated box) repression domain responsible for recruiting co-repressor complexes, and a SCAN domain involved in protein–protein interactions[1][2]. ZKSCAN3 acts as a master repressor of autophagy and lysosomal function by binding to promoter regions of autophagy-related genes and inhibiting their transcription, particularly under nutrient-replete conditions[1][2][3]. Under cellular stress or nutrient deprivation, ZKSCAN3 is exported from the nucleus, relieving repression and permitting autophagic activity[1][2]. It maintains genomic stability, modulates cell proliferation, and dynamically responds to post-translational modifications such as phosphorylation and ubiquitination[1]. Functionally, ZKSCAN3 displays context-dependent roles in tumorigenesis, acting as a tumor suppressor in early stages (preventing genomic instability and EMT) and an oncogene in advanced cancers (promoting metastasis and resistance)[1]. It is also implicated in controlling erythroid lineage differentiation, stem cell homeostasis, and cardiac remodeling[1]. The complexity, redundancy with related proteins, and context-specific functional duality present both opportunities and challenges for therapeutic targeting and biomarker applications.

Other names

Zinc finger protein with KRAB and SCAN domains 3ZKSCAN3ZFP47ZNF306ZNF309ZSCAN13ZSCAN35Zinc finger and SCAN domain-containing protein 13Zinc finger protein 306Zinc finger protein 309Zinc finger protein 47 homologZF47ZFP306dJ874C20.1zfp-47

No approved small-molecule inhibitors or drugs are currently known; therapeutic potential is proposed via modulation of ZKSCAN3–regulated transcriptional pathways or epigenetic networks[1].