Cytohesin-1 (CYTH1)
The protein contains 398 amino acids for an estimated molecular weight of 46413 Da.
Promotes guanine-nucleotide exchange on ARF1, ARF5 and ARF6. Promotes the activation of ARF factors through replacement of GDP with GTP. Plays an important role in membrane trafficking, during junctional remodeling and epithelial polarization, through regulation of ARF6 activity. (updated: March 28, 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.
- 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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Biological Process
Establishment of epithelial cell polarity
Positive regulation of GTPase activity
Regulation of ARF protein signal transduction
Regulation of cell adhesion
Vesicle-mediated transport
The reference OMIM entry for this protein is 182115
Cytohesin 1; cyth1
Pleckstrin homology, sec7, and coiled-coil domains protein 1; pscd1
Sec7, yeast, homolog of; sec7
D17s811e
CLONING
One of the major mediators of the inborn or 'natural' immune system is the natural killer (NK) cell. Dixon et al. (1993) prepared a subtractive cDNA library from human NK cells and characterized 13 unique clones. A clone named B2-1 was highly expressed in both NK and T cells, but was very weakly expressed or absent in several other cell lines. The deduced protein was highly homologous to the yeast protein SEC7, which is located in the Golgi apparatus and is thought to be involved in transporting proteins through the Golgi complex. B2-1 was the only known human protein with significant homology to SEC7 and may be one of the human equivalents of the yeast secretory proteins. Using a yeast 2-hybrid screen of a T-cell leukemia cell line with the intracellular portion of CD18 (ITGB2; 600065) as bait, Kolanus et al. (1996) isolated a cDNA encoding cytohesin-1 (PSCD1) and a partial cDNA encoding PSCD2L (602488), which they designated cts18.1. PSCD1 is 88% identical to the PSCD2L fragment. The predicted 398-amino acid PSCD1 protein contains a central 200-residue SEC7 domain and a C-terminal pleckstrin homology (PH) domain. Western blot analysis showed expression of a 47-kD protein, particularly, but not exclusively, in lymphoid cells. By EST analysis, Ikenouchi and Umeda (2010) found that CYTH1 was ubiquitously expressed in epithelial tissues. In mouse intestinal epithelial cells, Cyth1 colocalized with Zo1 (TJP1; 601009) at tight junctions. In EpH4 mouse mammary epithelial cells, Cyth1 localized to both primordial adherens junctions and tight junctions.GENE FUNCTION
Kolanus et al. (1996) found that overexpression of a full-length PSCD1 protein or of the SEC7 domain only induced CD18-dependent binding to ICAM1 (147840), whereas the PSCD1 PH domain specifically inhibited adhesion. Binding analysis indicated that the SEC7 domain, but not the PH domain, interacts with the cytoplasmic domain of CD18 but not with other cell surface receptors or protein-tyrosine kinases tested. Kolanus et al. (1996) concluded that PSCD1 specifically regulates the adhesive function of beta-2 integrins in lymphocytes. The induction of a transformed cellular phenotype by viruses requires the modulation of signaling pathways through viral proteins. Kliche et al. (2001) showed that the phenotypic changes induced by the kaposin A protein of human herpesvirus-8 are mediated through its direct interaction with cytohesin-1, a guanine nucleotide exchange factor (GEF) for ARF GTPases (e.g., ARF1; 103180) and regulator of integrin-mediated cell adhesion. Focus formation, stress fiber dissolution, and activation of the ERK1 (601795)/ERK2 (176948) mitogen-activated protein kinase (MAPK) signal cascade were reverted by a cytohesin-1 glu157-to-lys mutant, which is deficient in catalyzing guanine nucleotide exchange. Furthermore, liposome-embedded kaposin A was found to specifically stimulate cytohesin-1-dependent GTP binding of myristoylated ARF1 in vitro. Hafner et al. (2006) used an aptamer displacement screen to identify SecinH3, a small Sec7 domain-specific molecular antagonist of cytohesins. The cytohesins are a class of BFA-resistant small GEFs for ADP-ribosylation factors (ARFs), which regulate cytoskeletal organization, integrin activation, or integrin signaling. The application of SecinH3 in human liver cells showed that insulin receptor complex-associated cytohesins are required for insulin signaling. SecinH3-treated mice showed increased exp ... 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
April 12, 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
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
Oct. 27, 2017: Protein entry updated
Automatic update: model status changed
March 25, 2017: Additional information
No protein expression data in P. Mayeux work for CYTH1
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 182115 was added.
Feb. 24, 2016: Protein entry updated
Automatic update: model status changed