Protein diaphanous homolog 1 (DIAPH1)
The protein contains 1272 amino acids for an estimated molecular weight of 141347 Da.
Actin nucleation and elongation factor required for the assembly of F-actin structures, such as actin cables and stress fibers (By similarity). Binds to the barbed end of the actin filament and slows down actin polymerization and depolymerization (By similarity). Required for cytokinesis, and transcriptional activation of the serum response factor (By similarity). DFR proteins couple Rho and Src tyrosine kinase during signaling and the regulation of actin dynamics (By similarity). Functions as a scaffold protein for MAPRE1 and APC to stabilize microtubules and promote cell migration (By similarity). Has neurite outgrowth promoting activity. Acts in a Rho-dependent manner to recruit PFY1 to the membrane (By similarity). In hear cells, it may play a role in the regulation of actin polymerization in hair cells (PubMed:20937854, PubMed:21834987, PubMed:26912466). The MEMO1-RHOA-DIAPH1 signaling pathway plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex (PubMed:20937854, PubMed:21834987). It controls the localization of APC and CLASP2 to the cell membrane, via the regulation of GSK3B activity (PubMed:20937854, PubMed:21834987). In turn, membrane-bound APC allows the localization of the MACF1 to the cell membrane, which is required for microtubule capture and stabilization (PubMed:20937854, PubMed:21834987). Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape (PubMed:2093785 (updated: Nov. 7, 2018)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- 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.
- 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.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- 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.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
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.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.
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| Variant | Description |
|---|---|
| DFNA1 |
Biological Process
Actin cytoskeleton organization
Actin filament polymerization
Cellular response to histamine
Cytoskeleton organization
Neuron projection development
Neutrophil degranulation
Positive regulation of cell migration
Protein localization to microtubule
Regulation of cell motility
Regulation of cell shape
Regulation of cytoskeleton organization
Regulation of microtubule-based process
Regulation of release of sequestered calcium ion into cytosol
Sensory perception of sound
The reference OMIM entry for this protein is 124900
Deafness, autosomal dominant 1; dfna1
Hereditary low frequency hearing loss; lfhl1
Deafness, progressive low tone
Konigsmark syndrome
A number sign (#) is used with this entry because autosomal dominant deafness-1 (DFNA1), a form of low frequency sensorineural hearing loss (LFSNHL), is caused by heterozygous mutation in the human homolog of the Drosophila diaphanous gene (DIAPH1; 602121) on chromosome 5q31. Low frequency hearing loss is genetically heterogeneous; see, e.g., DFNA6 (600965), which is caused by mutation in the WFS1 gene (606201).
CLINICAL FEATURES
Konigsmark et al. (1971) studied 3 families with low frequency hearing loss in an autosomal dominant pedigree pattern. In a large Costa Rican family, Leon et al. (1981) described many cases of low frequency autosomal dominant deafness which differed from that previously reported in its earlier onset (first decade) and its progression to more profound deafness. Although the audiometric results indicated an apical initiation of the pathology, as might result from endolymphatic hydrops, presumably produced by alterations in the stria vascularis or from labyrinthine otosclerosis, no bone histology was available to identify the precise structures affected. In later studies, Leon et al. (1992) indicated that the deafness was primary (i.e., nonsyndromal) and postlingual (with onset at about age 10 years, after language and speaking were learned). By age 30, intelligence, fertility, and life expectancy were normal. The family traced its ancestry to an affected founder by the name of Monge, who was born in Costa Rica in 1754. Low frequency hearing loss is said to occur in several sensorineural hearing disorders such as Meniere disease, myxedema, and inner ear malformations, and in conductive hearing disorders resulting from either fixation or partial disruption of the ossicular chain (Parving, 1984).MAPPING
Leon et al. (1992) mapped the gene for the deafness in the Costa Rican family described by Leon et al. (1981) to 5q31, between markers IL9 (146931) at 5q31-q32 and GRL (138040) at 5q31. The maximum lod score with IL9 was 13.55 at theta = 0.06. They indicated that the IL9 and GRL genes are separated by about 7 cM.MOLECULAR GENETICS
The form of autosomal dominant, fully penetrant, nonsyndromic sensorineural progressive hearing loss in the large Costa Rican kindred studied by Leon et al. (1981, 1992) was designated DFNA1. Lynch et al. (1997) mapped the DFNA1 gene in this kindred to a region of 1 cM on 5q31 by linkage analysis and constructed a complete 800-kb bacterial artificial chromosome (BAC) contig of the linked region. They compared the sequences of these BACs with known genes and expressed sequence tags (ESTs) from all available databases. A previously unidentified human gene homologous to the Drosophila gene 'diaphanous' and a mouse gene was revealed by the genomic sequence of 3 BACs. The human diaphanous gene (602121) was screened for mutations in members of the Costa Rican M family by means of SSCP analysis. Sequencing of variant bands revealed a guanine-to-thymine substitution in the splice donor of the penultimate exon of DFNA1 in affected members of the M kindred (602121.0001). The base substitution disrupted the canonical splice donor sequence AAGgtaagt and resulted in insertion of 4 nucleotides in the transcript, a frameshift, and loss of the C-terminal 32 amino acids of the protein. All 78 affected members of the M kindred were heterozygous for the mutation. The site was wildtype in 330 control individuals with normal hearing (660 chromosomes) of the following ancestrie ... More on the omim web site
Nov. 16, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 124900 was added.