FH1/FH2 domain-containing protein 1 (FHOD1)
The protein contains 1164 amino acids for an estimated molecular weight of 126551 Da.
Required for the assembly of F-actin structures, such as stress fibers. Depends on the Rho-ROCK cascade for its activity. Contributes to the coordination of microtubules with actin fibers and plays a role in cell elongation. Acts synergistically with ROCK1 to promote SRC-dependent non-apoptotic plasma membrane blebbing. (updated: March 4, 2015)
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.
- 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.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
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.
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Biological Process
Actin filament network formation
Cortical actin cytoskeleton organization
Establishment of centrosome localization
Nuclear migration
Positive regulation of stress fiber assembly
Positive regulation of transcription by RNA polymerase II
Regulation of stress fiber assembly
Cellular Component
Bleb
Cytoplasm
Cytoskeleton
Cytosol
Intercalated disc
Membrane
Nucleoplasm
Nucleus
Obsolete cell
The reference OMIM entry for this protein is 606881
Formin homology-2 domain-containing protein 1; fhod1
Fh1/fh2 domain-containing protein; fhos
DESCRIPTION
FHOD1 belongs to the formin protein family, whose members are defined by formin homology-1 (FH1) and FH2 domains and are required for cell organization and limb development. The first members of the family were termed formins because mutations caused improper limb and renal formation in mice (summary by Westendorf et al., 1999). For additional background information on formins, see FMN1 (136535).CLONING
Using a portion of the AML-1B (RUNX1; 151385) transcription factor as bait in a yeast-2 hybrid screen of a B-cell cDNA library, Westendorf et al. (1999) identified a partial cDNA clone for FHOD1. The full-length clone was obtained by screening a Burkitt lymphoma cell line and human fetal and adult spleen cDNA libraries with the partial cDNA. The deduced 1,165-amino acid protein has a calculated molecular mass of 128 kD and shows sequence homology to Diaphanous (see 300108) and FMN1 within the FH1 and FH2 domains. It also contains a coiled-coil, a collagen-like domain, 2 nuclear localization signals, and several potential PKC and PKA phosphorylation sites. Westendorf et al. (1999) identified a 4-kb transcript in several human erythroid leukemia cell lines and in all tissues tested, with highest expression in spleen. Immunolocalization of endogenous FHOD1 showed predominant cytoplasmic localization with expression in a variety of human cell lines.GENE FUNCTION
Using in vitro capture of FHOD1 with several recombinant Rho family GST fusion proteins, Westendorf (2001) determined that FHOD1 interacts specifically with Rac1 (602048) in a guanine nucleotide-independent manner, and that FHOD1 does not interact with other members of the Rho subfamily of GTPases. Immunoprecipitation studies confirmed direct interaction between endogenous FHOD1 and Rac1. Using a yeast 2-hybrid screen with a human bone marrow cDNA expression library, Westendorf and Koka (2004) found that FHOD1 interacted with PRKCBP1 (ZMYND8; 615713), cyclophilin B (PPIB; 123841), and the B isoform of WISH (NCKIPSD; 606671). Coimmunoprecipitation analysis confirmed the interaction between FHOD1 and WISH-B. Domain analysis revealed that the N-terminal SH3 and PST domains of WISH-B interacted predominantly with the FH1 domain of FHOD1. The N-terminal domains of WISH-B, but not the full-length protein, inhibited FHOD1-induced stress fiber formation in transfected HEK293T cells. However, full-length WISH-B altered the solubility of FHOD1, suggesting that WISH-B may influence the subcellular localization of FHOD1 or recruit it to larger protein complexes.MAPPING
By radiation hybrid analysis, Westendorf et al. (1999) mapped the FHOD1 gene to chromosome 16q22. ... More on the omim web site
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 606881 was added.
Feb. 24, 2016: Protein entry updated
Automatic update: model status changed