BPTF

Developmental stage

Abundantly expressed in the fetal brain. Present throughout the gray and white matter of the developing spinal cord at 18-22 gestational weeks. Expressed at low levels in adult brain and spinal cord and reexpressed in neurodegenerative diseases (at protein level).

Domain

The second PHD-type zinc finger mediates binding to histone H3K4Me3. Has specificity for trimethyllysine; introducing a mutation in the Tyr-2876 residue can induce binding to dimethyllysine.

Function

Regulatory subunit of the ATP-dependent NURF-1 and NURF-5 ISWI chromatin remodeling complexes, which form ordered nucleosome arrays on chromatin and facilitate access to DNA during DNA-templated processes such as DNA replication, transcription, and repair (PubMed:14609955, PubMed:28801535). The NURF-1 ISWI chromatin remodeling complex has a lower ATP hydrolysis rate than the NURF-5 ISWI chromatin remodeling complex (PubMed:28801535). Within the NURF-1 ISWI chromatin-remodeling complex, binds to the promoters of En1 and En2 to positively regulate their expression and promote brain development (PubMed:14609955). Histone-binding protein which binds to H3 tails trimethylated on 'Lys-4' (H3K4me3), which mark transcription start sites of active genes (PubMed:16728976, PubMed:16728978). Binds to histone H3 tails dimethylated on 'Lys-4' (H3K4Me2) to a lesser extent (PubMed:16728976, PubMed:16728978, PubMed:18042461). May also regulate transcription through direct binding to DNA or transcription factors (PubMed:10575013).

Involvement in disease

Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies

NEDDFL

An autosomal dominant neurodevelopmental disorder characterized by variable degrees of developmental delay, intellectual disability, speech delay, postnatal microcephaly, dysmorphic features, and mild abnormalities of the hands and feet.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

Phosphorylation enhances DNA-binding.

Highly susceptible to proteolysis.

Sequence Similarities

Belongs to the PBTF family.

Tissue Specificity

Ubiquitously expressed, with highest levels in testis. Present in kidney, liver and brain. In the brain, highest levels are found in motor cortex (at protein level).

Cellular localization

• Cytoplasm
• Nucleus
• Localizes to sites of DNA damage (PubMed:25593309). In brains of Alzheimer disease patients, present in a subset of amyloid-containing plaques (PubMed:10727212).

Alternative names

FAC1, FALZ, BPTF, Nucleosome-remodeling factor subunit BPTF, Bromodomain and PHD finger-containing transcription factor, Fetal Alz-50 clone 1 protein, Fetal Alzheimer antigen

Database links

swissprot:Q12830 entrezGene:2186 omim:601819

Other research areas

• Neuroscience