EGF-containing fibulin-like extracellular matrix protein 2 (EFEMP2)
The protein contains 443 amino acids for an estimated molecular weight of 49405 Da.
Plays a crucial role in elastic fiber formation in tissue, and in the formation of ultrastructural connections between elastic laminae and smooth muscle cells in the aorta, therefore participates in terminal differentiation and maturation of smooth muscle cell (SMC) and in the mechanical properties and wall integrity maintenance of the aorta (PubMed:27339457). In addition, is involved in the control of collagen fibril assembly in tissue throught proteolytic activation of LOX leading to cross- linking of collagen and elastin (By similarity). Also promotes ELN coacervation and participates in the deposition of ELN coacervates on to microfibrils but also regulates ELN cross- linking through LOX interaction (PubMed:18973305, PubMed:19570982). Moreover adheres to the cells through heparin binding in a calcium-dependent manner and regulates vascularlar smooth muscle cells proliferation through angiotensin signaling (PubMed:23782690). (updated: Feb. 10, 2021)
Protein identification was indicated in the following studies:
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
Aorta development
Aorta smooth muscle tissue morphogenesis
Elastic fiber assembly
Negative regulation of vascular associated smooth muscle cell proliferation
Positive regulation of aortic smooth muscle cell differentiation
Positive regulation of collagen fibril organization
Positive regulation of smooth muscle cell-matrix adhesion
Regulation of collagen fibril organization
Vascular associated smooth muscle cell development
The reference OMIM entry for this protein is 604633
Egf-containing fibulin-like extracellular matrix protein 2; efemp2
Fibulin 4; fbln4
DESCRIPTION
Members of the fibulin family of proteins, like EFEMP2, are extracellular matrix proteins characterized by tandem arrays of EGF (131530)-like domains and a C-terminal fibulin (see FBLN1; 135820)-type module (Kobayashi et al., 2007).CLONING
A large number of extracellular matrix proteins contain variations of the EGF domain, e.g., fibrillin (FBN1; 134797) and Notch (190198). As part of their efforts in transcriptional mapping of the human 11q13.1-q13.2 genomic region, Katsanis et al. (2000) identified a novel partial cDNA from a human brain cDNA library. They called the cDNA 'EGF-containing fibulin-like extracellular matrix protein-2' (EFEMP2) because of its significant homology to EFEMP1 (601548). Sequence analysis detected 6 putative calcium-binding EGF domains and 4 EGF modules. Katsanis et al. (2000) observed expression of a 2.0-kb EFEMP2 transcript in all adult tissues tested by Northern blot analysis, with highest levels in heart. RT-PCR detected a 105-bp amplicon from the 3-prime untranslated region in fetal brain, kidney, and heart, but not in lung. EFEMP1 is likewise expressed in a wide range of adult and fetal tissues. In contrast to EFEMP1, however, EFEMP2 was not significantly overexpressed in senescent or quiescent fibroblasts, suggesting a diversity of function within this EGF-like domain subfamily. Katsanis et al. (2000) also cloned the mouse Efemp2 homolog. Using radioimmunoassays, Kobayashi et al. (2007) found variable Fbln4 expression in all 14 mouse tissues examined, with highest expression in aorta, and lowest expression in heart and thymus. Immunohistochemical analysis localized Fbln4 in perichondrium of developing bone in day-15 mouse embryos and in lung parenchyma in day-14 mouse embryos. Electron microscopy after rotary shadowing revealed that recombinant mouse Fbln4, like Fbln3 (EFEMP1; 601548) and Fbln5 (604580), appeared as a 20-nm rod with a globular domain at one end, which represented the N-terminal EGF modules.MAPPING
By analysis of a somatic cell hybrid panel and by placement on a series of genomic clones by PCR, Katsanis et al. (2000) mapped the EFEMP2 gene to chromosome 11q13, in an area where several retinopathies have shown genetic linkage.GENE FUNCTION
Kobayashi et al. (2007) found that mouse Fbln3 and Fbln4 and both mouse and human FBLN5 were secreted into the culture media of transfected HEK293 cells. Solid-phase binding assays showed that these proteins bound differentially to extracellular proteins. Mouse Fbln4 bound to collagen XIV (see 120324), nidogen-2 (NID2; 605399), tropoelastin (ELN; 130160), and collagen XV (see 120325)-derived endostatin, but not to fibronectin (135600) or most basement membrane proteins examined.MOLECULAR GENETICS
- Doyne Honeycomb Retinal Dystrophy Given that EFEMP1 is the site of mutations causing Doyne honeycomb retinal dystrophy (126600), Katsanis et al. (2000) suggested EFEMP2 as a candidate for retinal dystrophies. Toto et al. (2002) studied linkage of both the EFEMP2 and EFEMP1 genes to malattia leventinese in a 3-generation Swiss-Italian family. Linkage was found only to EFEMP1 in 2 of 5 affected family members. - Autosomal Recessive Cutis Laxa Type IB Cutis laxa is a condition characterized by redundant, pendulous, and inelastic skin. A severe autosomal recessive form of cutis laxa (ARCL1A; 219100) is caused by mutation in the fibulin-5 gene (FBLN5; 604580). Hucthagowder et al. (2006) hypothe ... More on the omim web site
Feb. 16, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 604633 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).