EFEMP2

A large number of extracellular matrix proteins have been found to contain variations of the epidermal growth factor (EGF) domain and have been implicated in functions as diverse as blood coagulation, activation of complement and determination of cell fate during development. The protein encoded by this gene contains four EGF2 domains and six calcium-binding EGF2 domains. This gene is necessary for elastic fiber formation and connective tissue development. Defects in this gene are cause of an autosomal recessive cutis laxa syndrome.

Full Name

EGF-containing fibulin-like extracellular matrix protein 2

Alternative Names

FBLN4; MBP1; UPH1

Research Area

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).

Biological Process

Aorta development Source: UniProtKB
Aorta smooth muscle tissue morphogenesis Source: UniProtKB
Elastic fiber assembly Source: UniProtKB
Negative regulation of vascular associated smooth muscle cell proliferation Source: UniProtKB
Positive regulation of aortic smooth muscle cell differentiation Source: UniProtKB
Positive regulation of collagen fibril organization Source: UniProtKB
Positive regulation of smooth muscle cell-matrix adhesion Source: UniProtKB
Regulation of collagen fibril organization Source: UniProtKB
Vascular associated smooth muscle cell development Source: UniProtKB

Cellular Location

Extracellular matrix; Basement membrane. Localizes on the microfibrils surrounding ELN cores.

Involvement in disease

Cutis laxa, autosomal recessive, 1B (ARCL1B):
A connective tissue disorder characterized by loose, hyperextensible skin with decreased resilience and elasticity leading to a premature aged appearance. Face, hands, feet, joints, and torso may be differentially affected. The clinical spectrum of autosomal recessive cutis laxa is highly heterogeneous with respect to organ involvement and severity. ARCL1B features include emphysema, lethal pulmonary artery occlusion, aortic aneurysm, cardiopulmonary insufficiency, birth fractures, arachnodactyly, and fragility of blood vessels.

PTM

N-glycosylated; contains mostly complex-type glycans (PubMed:27339457, PubMed:23782690). Not O-glycosylated (PubMed:27339457).
Cleaved by ELANE; produces a 50-55 kDa fragment (PubMed:27339457). Cleaved by MMP2 and MMP9; produces several fragments (PubMed:27339457).