Drebrin-like protein (DBNL)

The protein contains 430 amino acids for an estimated molecular weight of 48207 Da.

 

Adapter protein that binds F-actin and DNM1, and thereby plays a role in receptor-mediated endocytosis. Plays a role in the reorganization of the actin cytoskeleton, formation of cell projections, such as neurites, in neuron morphogenesis and synapse formation via its interaction with WASL and COBL. Does not bind G-actin and promote actin polymerization by itself. Required for the formation of organized podosome rosettes (By similarity). May act as a common effector of antigen receptor-signaling pathways in leukocytes. Acts as a key component of the immunological synapse that regulates T-cell activation by bridging TCRs and the actin cytoskeleton to gene activation and endocytic processes. (updated: March 4, 2015)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  4. Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
  5. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  6. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete		TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.


Interpro domains
Total structural coverage: 34%
Model score: 0
MODL_I-TASSER-3.0

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The reference OMIM entry for this protein is 610106

Drebrin-like; dbnl
Hpk1-interacting protein, 55-kd; hip55

CLONING

By yeast 2-hybrid screening of a HeLa cell cDNA library using GLK (MAP4K3; 604921) as bait, followed by EST database analysis, Ensenat et al. (1999) cloned DBNL, which they called HIP55. The predicted 430-amino acid protein has a calculated molecular mass of 48 kD. The N terminus of HIP55 contains a putative actin-binding domain found in drebrins (see DBN1; 126660), which are involved in brain development, and the C terminus contains an SH3 domain. Western blot analysis detected a 55-kD protein. Northern blot analysis revealed ubiquitous expression of a 2.3-kb transcript, with highest levels in spleen and peripheral blood leukocytes.

GENE FUNCTION

By yeast 2-hybrid analysis, Ensenat et al. (1999) found that HIP55 interacted with GLK and HPK1 (MAP4K1; 601983). They confirmed the interaction with HPK1 both in vitro and in vivo. The interaction was dependent on the SH3 domain of HIP55 and the second proline-rich domain of HPK1. When cotransfected, HIP55 increased HPK1 kinase activity and JNK1 (MAPK8; 601158) kinase activity. Ensenat et al. (1999) concluded that HIP55 binds HPK1 and regulates the JNK1 signaling cascade. Using confocal microscopy, RNA interference, and overexpression experiments in mouse and human cell lines, Le Bras et al. (2004) found that HIP55 did not contribute to early formation of T cell-antigen-presenting cell (APC) conjugates. However, they identified HIP55 as a key constituent of the immunologic synapse, regulating T-cell activation by bridging T-cell receptors and the actin cytoskeleton to gene activation and endocytic processes.

MAPPING

The International Radiation Hybrid Mapping Consortium mapped the DBNL gene to chromosome 7 (TMAP D7S2634).

ANIMAL MODEL

Han et al. (2005) found that Hip55 -/- mice were viable and fertile, but they showed decreased body weight and increased frequency of death within the first 4 weeks after birth. Lymphoid organs of Hip55 -/- mice showed normal cellularity and T-cell development. However, Hip55 -/- T cells proliferated at a reduced level, with lower cytokine production and lower expression of activation markers after T-cell receptor stimulation. ... More on the omim web site

Subscribe to this protein entry history

May 12, 2019: Protein entry updated
Automatic update: model status changed

Nov. 17, 2018: Protein entry updated
Automatic update: model status changed

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

Oct. 27, 2017: Protein entry updated
Automatic update: model status changed

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 610106 was added.

Feb. 24, 2016: Protein entry updated
Automatic update: model status changed