ANKZF1 (Ankyrin Repeat and Zinc Finger Domain Containing 1), also known historically as Anguish or ZNF674, is a protein encoded by the ANKZF1 gene located on chromosome 4. This protein contains both ankyrin repeat domains and a C2H2-type zinc finger domain, suggesting roles in protein-protein interactions and DNA/RNA binding. Critically, pathogenic variants in ANKZF1 have been identified as a cause of familial amyotrophic lateral sclerosis (ALS), establishing it as a disease-causing gene in motor neuron disease.
Structure
ANKZF1 is a 632-amino acid protein with a molecular weight of approximately 68 kDa. The protein contains several distinct structural domains:
ANKZF1 (Ankyrin Repeat and Zinc Finger Domain Containing 1), also known historically as Anguish or ZNF674, is a protein encoded by the ANKZF1 gene located on chromosome 4. This protein contains both ankyrin repeat domains and a C2H2-type zinc finger domain, suggesting roles in protein-protein interactions and DNA/RNA binding. Critically, pathogenic variants in ANKZF1 have been identified as a cause of familial amyotrophic lateral sclerosis (ALS), establishing it as a disease-causing gene in motor neuron disease.
Structure
ANKZF1 is a 632-amino acid protein with a molecular weight of approximately 68 kDa. The protein contains several distinct structural domains:
Each repeat consists of approximately 33 amino acids forming a helix-turn-helix structure
Mediates protein-protein interactions with various cellular factors
May interact with transcription factors and signaling molecules
Zinc Finger Domain (C-terminal region)
C2H2-type zinc finger motif
Coordinates zinc ion through conserved cysteine and histidine residues
Enables DNA or RNA binding capability
May function as a transcriptional regulator
Linker Regions
Flexible regions connecting ankyrin and zinc finger domains
May contain nuclear localization signals (NLS)
The predicted structure suggests ANKZF1 could function as a dual-function protein with both scaffold (via ankyrin repeats) and nucleic acid binding (via zinc finger) capabilities.
Normal Function
Transcriptional Regulation
ANKZF1 is predicted to function as a transcription factor or transcriptional co-regulator:
DNA binding: The C2H2 zinc finger domain may bind to specific DNA sequences
Transcriptional activation: Ankyrin repeats may interact with transcriptional coactivators