Endoglin (ENG)
The protein contains 658 amino acids for an estimated molecular weight of 70578 Da.
Vascular endothelium glycoprotein that plays an important role in the regulation of angiogenesis (PubMed:21737454, PubMed:23300529). Required for normal structure and integrity of adult vasculature (PubMed:7894484). Regulates the migration of vascular endothelial cells (PubMed:17540773). Required for normal extraembryonic angiogenesis and for embryonic heart development (By similarity). May regulate endothelial cell shape changes in response to blood flow, which drive vascular remodeling and establishment of normal vascular morphology during angiogenesis (By similarity). May play a critical role in the binding of endothelial cells to integrins and/or other RGD receptors (PubMed:1692830). Acts as TGF-beta coreceptor and is involved in the TGF-beta/BMP signaling cascade that ultimately leads to the activation of SMAD transcription factors (PubMed:8370410, PubMed:21737454, PubMed:22347366, PubMed:23300529). Required for GDF2/BMP9 signaling through SMAD1 in endothelial cells and modulates TGFB1 signaling through SMAD3 (PubMed:21737454, PubMed:22347366, PubMed:23300529). (updated: June 20, 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.
- 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.
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, is predicted to be membranous by TOPCONS.
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Biological Process
Angiogenesis
Artery morphogenesis
Atrial cardiac muscle tissue morphogenesis
Atrioventricular canal morphogenesis
BMP signaling pathway
Bone development
Branching involved in blood vessel morphogenesis
Cardiac atrium morphogenesis
Cardiac ventricle morphogenesis
Cell adhesion
Cell chemotaxis
Cell migration
Cell migration involved in endocardial cushion formation
Cell motility
Cellular response to mechanical stimulus
Central nervous system vasculogenesis
Detection of hypoxia
Dorsal aorta morphogenesis
Endocardial cushion morphogenesis
Epithelial to mesenchymal transition
Epithelial to mesenchymal transition involved in endocardial cushion formation
Extracellular matrix constituent secretion
Extracellular matrix disassembly
Heart looping
Intracellular signal transduction
Negative regulation of cell migration
Negative regulation of endothelial cell proliferation
Negative regulation of gene expression
Negative regulation of nitric-oxide synthase activity
Negative regulation of pathway-restricted SMAD protein phosphorylation
Negative regulation of protein autophosphorylation
Negative regulation of transcription by RNA polymerase II
Negative regulation of transforming growth factor beta receptor signaling pathway
Obsolete chronological cell aging
Outflow tract septum morphogenesis
Positive regulation of angiogenesis
Positive regulation of BMP signaling pathway
Positive regulation of collagen biosynthetic process
Positive regulation of epithelial to mesenchymal transition involved in endocardial cushion formation
Positive regulation of gene expression
Positive regulation of pathway-restricted SMAD protein phosphorylation
Positive regulation of protein kinase B signaling
Positive regulation of protein phosphorylation
Positive regulation of systemic arterial blood pressure
Positive regulation of transcription by RNA polymerase II
Positive regulation of vascular associated smooth muscle cell differentiation
Regulation of cell adhesion
Regulation of cell population proliferation
Regulation of phosphorylation
Regulation of transcription, DNA-templated
Regulation of transforming growth factor beta receptor signaling pathway
Response to corticosteroid
Response to drug
Response to hypoxia
Response to statin
Response to transforming growth factor beta
Smooth muscle tissue development
Transforming growth factor beta receptor signaling pathway
Vascular associated smooth muscle cell development
Vasculogenesis
Venous blood vessel morphogenesis
Ventricular trabecula myocardium morphogenesis
Wound healing
Cellular Component
Cell surface
Cytoplasm
Endothelial microparticle
External side of plasma membrane
Extracellular space
Focal adhesion
Integral component of membrane
Nuclear body
Nucleoplasm
Obsolete transforming growth factor beta receptor complex
Plasma membrane
Receptor complex
Molecular Function
Activin binding
Coreceptor activity
Galactose binding
Glycosaminoglycan binding
Identical protein binding
Obsolete transforming growth factor beta receptor, cytoplasmic mediator activity
Protein homodimerization activity
Transforming growth factor beta binding
Transforming growth factor beta-activated receptor activity
Transmembrane signaling receptor activity
Type I transforming growth factor beta receptor binding
Type II transforming growth factor beta receptor binding
The reference OMIM entry for this protein is 131195
Endoglin; eng
Cd105
DESCRIPTION
Endoglin (ENG), also called CD105, is a homodimeric membrane glycoprotein primarily associated with human vascular endothelium. It is also found on bone marrow proerythroblasts, activated monocytes, and lymphoblasts in childhood leukemia. Endoglin is a component of the transforming growth factor-beta (TGFB) receptor complex and binds TGFB1 (190180) with high affinity (Rius et al., 1998).CLONING
Gougos and Letarte (1990) isolated a cDNA encoding ENG lacking a leader sequence from an endothelial cell cDNA library. By screening a leukemia cell cDNA library, Bellon et al. (1993) obtained full-length cDNAs encoding 2 variants of ENG. Both contain a 25-amino acid leader peptide, followed by 561 residues in the extracellular portion and a 25-amino acid transmembrane sequence. However, the long variant has a 47-amino acid cytoplasmic tail, while the tail of the short variant contains only 14 residues. Flow cytometric and immunoprecipitation analyses indicated high expression of both the 160- and 170-kD disulfide-linked homodimer ENG variants at the cell surface. RT-PCR analysis detected expression of both variants on activated monocytes, endothelial cells, and placenta, with the long form being predominant.GENE FUNCTION
Bellon et al. (1993) found that both isoforms of ENG could bind TGFB1. Rius et al. (1998) cloned and characterized the promoter region of the ENG gene. They showed that the endoglin promoter exhibits inducibility in the presence of TGFB1, suggesting possible therapeutic treatments in HHT1 (187300) patients, in which the expression level of the normal endoglin allele might not reach the threshold required for its function. Grisanti et al. (2004) analyzed endoglin expression in choroidal neovascular membranes (CNVMs) surgically excised from eyes with age-related macular degeneration (ARMD; see 153800). Endoglin expression was increased in the endothelial cells of CNVMs but was rarely associated with a concomitant expression of the proliferation marker Ki-67 (176741). The authors concluded that the elevated expression of endoglin in the surgically excised CNVMs suggested a persisting postmitotic activation in an advanced stage of neovascular tissue. Hereditary hemorrhagic telangiectasia (see 187300) and cerebral cavernous malformations (see 116860) are disorders involving disruption of normal vascular morphogenesis. The autosomal dominant mode of inheritance in both of these disorders suggested to Marchuk et al. (2003) that their underlying genes might regulate critical aspects of vascular morphogenesis. The authors summarized the roles of these genes, endoglin, KRIT1 (604214), and ALK1 (ACVRL1; 601284), in the genetic control of angiogenesis. Lebrin et al. (2004) found that mouse endothelial cells lacking endoglin did not grow because Tgfb/Alk1 signaling was reduced and Tgfb/Alk5 (190181) signaling was increased. Surviving cells adapted to the imbalance and proliferated by downregulating Alk5 expression. Lebrin et al. (2004) concluded that endoglin has a role in the balance of ALK1 and ALK5 signaling to regulate endothelial cell proliferation. GIPC1 (605072) is a scaffolding protein that regulates cell surface receptor expression and trafficking. Using predominantly embryonic mouse endothelial cell lines, Lee et al. (2008) showed that endoglin and Gipc interacted directly. The interaction enhanced TGF-beta-1-induced phosphorylation of Smad1 (601595)/Smad5 (603110)/Smad8 (SMAD9; 603295 ... More on the omim web site
July 2, 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
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 131195 was added.