Drebrin 1: Products
Drebrin 1, also known as Developmentally-regulated Brain Protein, is a member of the ADF-H family of actin-binding proteins. Human Drebrin 1 is 649 amino acids (aa) in length and shares 82% aa sequence identity with the mouse and rat orthologs. It contains an N-terminal actin depolymerizing homology domain (aa 3-134), an actin-binding region (aa 150-300), and two C-terminal HOMER binding motifs (aa 539-543 and 617-621). It has a predicted molecular weight of approximately 72 kDa, but runs anomalously at 115-116 kDa in SDS-PAGE as Drebrin 1 can undergo phosphorylation at 10 different Ser/Thr sites and one Tyr residue. Additionally, alternative splicing generates several isoform variants.
One isoform, Drebrin-A, contains a 46 aa insert after Gly319. Other isoforms include one that utilizes an alternative start site at Met64, one that shows a 60 aa substitution for aa 1-110, and one that contains a 28 aa substitution for aa 4-29. Drebrin 1 is expressed by neurons, gastric Parietal cells, astrocytes, cells of the distal convoluted tubule epithelium, and proton-secreting intercalated cells of the renal collecting duct. In neurons, it is found in dendritic spines at postsynaptic excitatory synapses and is thought to play an important role in regulating dendritic spine morphology.
Drebrin 1 has also been shown to interact with multiple partners near the membrane and link Connexin-43 and F-actin to stabilize membrane gap junctions. It has also been shown to bind to EB3 (End-binding Protein 3) on microtubules, facilitating actin-microtubule interactions. Drebrin 1 expression has been shown to be high during embryogenesis and decrease with normal aging. Low Drebrin 1 levels have been detected in the cortex of patients with Alzheimer's disease and has been correlated with cognitive impairment in these individuals.
