DBN1 (drebrin 1)
2013-09-01 John Chilton AffiliationBiomedical Neuroscience Research Group, University of Exeter Medical School, Hatherly Laboratories, Prince of Wales Road, Exeter EX4 4PS, UK
DNA/RNA
Description
14 exons.
Transcription
Two alternatively spliced isoforms:
- NCBI LOCUS NM_004395 2942 bp corresponds to DBN1a variant,
- NCBI LOCUS NM_080881 3058 bp corresponds to DBN1b variant.
- NCBI LOCUS NM_004395 2942 bp corresponds to DBN1a variant,
- NCBI LOCUS NM_080881 3058 bp corresponds to DBN1b variant.
Proteins
Description
DBN1 encodes a 71 kDa protein of ~650 amino acids (DBN1a has 649 amino acids, DBN1b has 651 amino acids). The N-terminus contains an ADF/Cofilin homology domain (Poukkula et al., 2011) followed by a coiled-coil and a helical domain which each contain an actin-binding site (Worth et al., 2013). The C-terminus contains no identifiable domain structure apart from two Homer binding motifs and can provide intramolecular regulation of F-actin binding (Worth et al., 2013).
In some species (chick, rat) developmental regulation of the protein occurs such that at the earliest stages of development an embryonic E1 isoform is expressed. This is then downregulated in favour of an E2 isoform containing a 43 amino acid insertion which itself is subsequently superseded by the adult A isoform containing a further 46 amino acids insertion adjacent to the previous one (Kojima et al., 1993). In humans E2 appears to be the predominant isoform.
In some species (chick, rat) developmental regulation of the protein occurs such that at the earliest stages of development an embryonic E1 isoform is expressed. This is then downregulated in favour of an E2 isoform containing a 43 amino acid insertion which itself is subsequently superseded by the adult A isoform containing a further 46 amino acids insertion adjacent to the previous one (Kojima et al., 1993). In humans E2 appears to be the predominant isoform.
Expression
DBN1 is widely expressed in the nervous system and is also found in other organs, predominantly kidney, stomach, lung and skin (Dun and Chilton, 2010).
Localisation
DBN1 localises to actin-rich structures within cells such as the leading edge of neuronal growth cones (Geraldo et al., 2008; Dun et al., 2012) and intercellular junctions (Butkevich et al., 2004; Rehm et al., 2013).
Function
At the molecular level, DBN1 stabilises actin filaments (Mikati et al., 2013). It may provide a link between the actin and microtubule networks (Geraldo et al., 2008) and is required for neuronal migration (Dun et al., 2012).
Drebrin function can be regulated by the phosphorylation state of distinct serine residues due to the actions of Cdk5 (Worth et al., 2013) and PTEN (Kreis et al., 2013).
Drebrin function can be regulated by the phosphorylation state of distinct serine residues due to the actions of Cdk5 (Worth et al., 2013) and PTEN (Kreis et al., 2013).
Homology
Drebrin is conserved across vertebrates, especially in the first 300 amino acids containing the ADF/Cofilin homology, coiled-coil and helical domains. The closest relative in invertebrate species is actin-binding protein 1 (ABP1).
Implicated in
Entity name
Note
Drebrin is a direct target of Sox11 in primary mantle cell lymphomas (Wang et al., 2010).
Entity name
B-cell precursor acute lymphoblastic leukemia (BCP-ALL)
Note
High levels of drebrin protein expression in BCP-ALL (Vaskova et al., 2011).
Entity name
Skin tumours (varied)
Note
Drebrin levels are increased compared to control skin samples in basal cell carcinoma, squamous cell carcinoma, melanoma and leiomyosarcoma (Peitsch et al., 2005).
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 15084279 | 2004 | Drebrin is a novel connexin-43 binding partner that links gap junctions to the submembrane cytoskeleton. | Butkevich E et al |
| 22306864 | 2012 | Drebrin controls neuronal migration through the formation and alignment of the leading process. | Dun XP et al |
| 20183806 | 2010 | Control of cell shape and plasticity during development and disease by the actin-binding protein Drebrin. | Dun XP et al |
| 18806788 | 2008 | Targeting of the F-actin-binding protein drebrin by the microtubule plus-tip protein EB3 is required for neuritogenesis. | Geraldo S et al |
| 8361332 | 1993 | Molecular cloning of a developmentally regulated brain protein, chicken drebrin A and its expression by alternative splicing of the drebrin gene. | Kojima N et al |
| 23940795 | 2013 | Phosphorylation of the actin binding protein Drebrin at S647 is regulated by neuronal activity and PTEN. | Kreis P et al |
| 23696644 | 2013 | Drebrin-induced stabilization of actin filaments. | Mikati MA et al |
| 16185277 | 2005 | Drebrin, an actin-binding, cell-type characteristic protein: induction and localization in epithelial skin tumors and cultured keratinocytes. | Peitsch WK et al |
| 21850706 | 2011 | Actin-depolymerizing factor homology domain: a conserved fold performing diverse roles in cytoskeletal dynamics. | Poukkula M et al |
| 23750010 | 2013 | Drebrin preserves endothelial integrity by stabilizing nectin at adherens junctions. | Rehm K et al |
| 21497902 | 2011 | High expression of cytoskeletal protein drebrin in TEL/AML1pos B-cell precursor acute lymphoblastic leukemia identified by a novel monoclonal antibody. | Vaskova M et al |
| 21124928 | 2010 | Gene expression profiling and chromatin immunoprecipitation identify DBN1, SETMAR and HIG2 as direct targets of SOX11 in mantle cell lymphoma. | Wang X et al |
| 23979715 | 2013 | Drebrin contains a cryptic F-actin-bundling activity regulated by Cdk5 phosphorylation. | Worth DC et al |
Other Information
Locus ID:
NCBI: 1627
MIM: 126660
HGNC: 2695
Ensembl: ENSG00000113758
Variants:
dbSNP: 1627
ClinVar: 1627
TCGA: ENSG00000113758
COSMIC: DBN1
RNA/Proteins
Expression (GTEx)
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 36690273 | 2023 | The well-developed actin cytoskeleton and Cthrc1 expression by actin-binding protein drebrin in myofibroblasts promote cardiac and hepatic fibrosis. | 4 |
| 36690273 | 2023 | The well-developed actin cytoskeleton and Cthrc1 expression by actin-binding protein drebrin in myofibroblasts promote cardiac and hepatic fibrosis. | 4 |
| 36155064 | 2022 | Drebrin promotes lung adenocarcinoma cell migration through inducing integrin β1 endocytosis. | 0 |
| 36155064 | 2022 | Drebrin promotes lung adenocarcinoma cell migration through inducing integrin β1 endocytosis. | 0 |
| 33453340 | 2021 | Physical interaction between BAALC and DBN1 induces chemoresistance in leukemia. | 1 |
| 33739391 | 2021 | Effects of neuronal drebrin on actin dynamics. | 2 |
| 33453340 | 2021 | Physical interaction between BAALC and DBN1 induces chemoresistance in leukemia. | 1 |
| 33739391 | 2021 | Effects of neuronal drebrin on actin dynamics. | 2 |
| 32015686 | 2020 | TFAP2A Induced ITPKA Serves as an Oncogene and Interacts with DBN1 in Lung Adenocarcinoma. | 14 |
| 32662890 | 2020 | Drebrin expression patterns in patients with refractory temporal lobe epilepsy and hippocampal sclerosis. | 4 |
| 32015686 | 2020 | TFAP2A Induced ITPKA Serves as an Oncogene and Interacts with DBN1 in Lung Adenocarcinoma. | 14 |
| 32662890 | 2020 | Drebrin expression patterns in patients with refractory temporal lobe epilepsy and hippocampal sclerosis. | 4 |
| 30467237 | 2019 | The human phosphatase CDC14A modulates primary cilium length by regulating centrosomal actin nucleation. | 17 |
| 30880752 | 2019 | Downregulation of DBN1 is related to vincristine resistance in colon cancer cells. | 4 |
| 30467237 | 2019 | The human phosphatase CDC14A modulates primary cilium length by regulating centrosomal actin nucleation. | 17 |
Citation
John Chilton
DBN1 (drebrin 1)
Atlas Genet Cytogenet Oncol Haematol. 2013-09-01
Online version: http://atlasgeneticsoncology.org/gene/51520/dbn1-(drebrin-1)
