DBN1 (drebrin 1)

2013-09-01   John Chilton 

Biomedical Neuroscience Research Group, University of Exeter Medical School, Hatherly Laboratories, Prince of Wales Road, Exeter EX4 4PS, UK

Identity

HGNC
LOCATION
5q35.3
LOCUSID
ALIAS
D0S117E
FUSION GENES

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.

Proteins

Atlas Image

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This is then downregulated in favour of an E2 isoform containing a 43 amino acid insertion which itself is subsequently superseded by the adult A isoform containing a further 46 amino acids insertion adjacent to the previous one (Kojima et al., 1993).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.

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).

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

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).

Bibliography

Pubmed IDLast YearTitleAuthors

Other Information

Locus ID:

NCBI: 1627
MIM: 126660
HGNC: 2695
Ensembl: ENSG00000113758

Variants:

dbSNP: 1627
ClinVar: 1627
TCGA: ENSG00000113758
COSMIC: DBN1

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000113758ENST00000292385Q16643
ENSG00000113758ENST00000309007Q16643
ENSG00000113758ENST00000393565Q16643
ENSG00000113758ENST00000477391D6R9W4
ENSG00000113758ENST00000506117D6RCR4
ENSG00000113758ENST00000512501D6R9Q9
ENSG00000113758ENST00000514833D6RFI1

Expression (GTEx)

0
50
100
150

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
188067882008Targeting of the F-actin-binding protein drebrin by the microtubule plus-tip protein EB3 is required for neuritogenesis.92
120095252002Drebrin, a dendritic spine protein, is manifold decreased in brains of patients with Alzheimer's disease and Down syndrome.56
211249282010Gene expression profiling and chromatin immunoprecipitation identify DBN1, SETMAR and HIG2 as direct targets of SOX11 in mantle cell lymphoma.24
201838062010Control of cell shape and plasticity during development and disease by the actin-binding protein Drebrin.17
232011352013The role of drebrin in glioma migration and invasion.14
258391642015A novel role for drebrin in regulating progranulin bioactivity in bladder cancer.14
284166662017Drebrin restricts rotavirus entry by inhibiting dynamin-mediated endocytosis.12
183388032008Decreased drebrin mRNA expression in Alzheimer disease: correlation with tau pathology.11
222754342012Apico-basal elongation requires a drebrin-E-EB3 complex in columnar human epithelial cells.11
246106772014iTRAQ analysis of colorectal cancer cell lines suggests Drebrin (DBN1) is overexpressed during liver metastasis.10

Citation

John Chilton

DBN1 (drebrin 1)

Atlas Genet Cytogenet Oncol Haematol. 2013-09-01

Online version: http://atlasgeneticsoncology.org/gene/51520/js/web-card-gene.js