A short protein description with the molecular wheight, isoforms, etc...
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CHEMICAL STRUCTURE AND IMAGES
When relevant for the function
- Primary structure
- Secondary structure
- Tertiary structure
- Quaternary structure
Protein Aminoacids Percentage
The Protein Aminoacids Percentage gives useful information on the local environment and the metabolic status of the cell (starvation, lack of essential AA, hypoxia)
Protein Aminoacids Percentage (Width 700 px)
SYNTHESIS AND TURNOVER
Glycoprotein involved in the important process of elastogenesis in order to ensuring the extracellular elasticity matrix
Fibulin is a glycoprotein, known in seven isoforms, each of which is encoded by a different gene; This protein belongs to the components of the extracellular matrix where it contributes to the correct elastogenesis. such glycoprotein has several binding sites for calcium, its interaction with components of the extracellular matrix ECM is in fact calcium dependent.
Concerning the first three isoforms: Fibulin-1, Fibulin-2 and Fibulin-3 are directly involved in the interaction with components such as Laminin, Fibrillin and Fironectin.
Family members of fibulin are:
# Fibulina-1, whose gene is FBLN1;
# Fibulina-2, FBNL2;
# Fibulina-3, FBNL3;
# Fibulina-4, FBNL4;
# Fibulina-5, FBNL5;
# Fibulina-6, FBNL6 or HMCN1 (hemicentin-1);
# Fibulina-7, FBNL7
The various isoforms are involved in many pathological processes characterized by alterations of the ECM and can play the role of specific markers:
Fibulin-1 is a marker employed to study cardiovascular damage; but it is also correlated with the progression of idiopathic pulmonary fibrosis.
The fibulina-3 was used as a marker of pleural mesothelioma, allowing early detection of the growth of this neoplasm in patients long exposed to Asbestos. The levels of fibulina-3 did not appear modified by patient parameters: sex, age, duration of exposure to asbestos or degree of radiographic changes. In tumors of the uterine cervix was found an increase of fibulin-4.
It's probably the best known isoform, is a glycoprotein of 52 Kd with domain calcium-binding EGF-like (cbEGF), abundantly present in the ECM and is essential in the formation of elastic tissue.
Two monomers FBNL5 associate to form a dimer with a central cavity, the equilibrium dimer/monomer is influenced by NaCl and Ca2+, whose concentrations are higher in body fluids, especially in the extracellular fluid that absorbe the ECM. However, is still not clear which of the two forms is the active and the precise role of fibulin. The sites of dimerization employ cbEGF, this phenomenon suggests a particular role of this domain in the dimerization. It is likely that Fibulin-5 works as a dimer during the elastinogenesis or that the dimerization represents a switch to limit the interaction with the tropoelastin.
The gene of fibulin-5, FBNL-5, is located on chromosome 14 and is highly presence during arteries formation, while in the adult vessels its presence is significantly reduced. This suggests that fibulin-5 has a particular role in the processes of vascular injury and atherosclerosis. The presence of fibulin-5 has been confirmed in other parts of the body rich in elastic fibers: aorta, skin, uterus, lung, heart, ovary, colon. The extensibility of these fabrics is due to the presence of elastic fibers, which decrease with age, leading to a loss of elasticity. Fibulin-5 is essential for elastinogenesis. Experimentation have been reached using Knock-out mice as trial. ending up that the gene FBNL5 shows disorders of elastic fibers with severe elastopatia. Mutations in the gene cause disorders of elastic fibers, such as cutis laxa, associated with age-related macular degeneration. It has been shown that fibulin-5 links elastic fibers and interacts with the tropoelastin, fibrillin-1, lysyl oxidase-1, lysyl oxidase-2, lysyl oxidase-4, with protein-2 binding TGFβ, Emilin-1, apolipoprotein-a and superoxide dismutase. Moreover, the presence of an RGD domain suggests that the fibulin-5 interacts with integrin too.
The chaining of elastic fibers is a complex hierarchical process. One model proposes that fibulin-5 interacts with the elastic fibers by means of fibrillin-1; the tropoelastin molecule binds itself to fibulin-5 this process allows to recruit the lysyl oxidase, which through the formation of cross-links, leads to the formation of elastic fibers. So fibulin-5 increases the recruitment of tropoelastin, increasing the formation of elastic fibers. However, other data suggest that fibulin-5 slows down the aging of elastic fibers. This, of course, is to be put in relation with the dual nature of fibulin-5 which has a monomeric form and a dimeric.
In addition, a study conducted by a Japanese team of thoracic surgeons showed a deficit of the such protein in samples of lung tissue obtained during bullectomy in young patients with recidive pneumothorax, this study although it has not been validated by further studies, it is still a first attempt etiopathogenic research in a molecular point of view relating to a pathology which has been always defined as idiopathic as pneumothorax in youth patients and for which were highlighted exclusively extrinsic risk factors for the involved organ as the phenotype or BMI (body mass index). It is therefore not surprising that a similar study conducted on women having uterine prolapse has found a deficit of the same glycoprotein.
In addition, a mutation in the genes coding for isoforms 4 and 5 are considered to be the cause of the pathology known as "Cutis Laxa"; rare condition characterized by abnormalities of the connective tissue, responsible for the association between types of skin; wrinkled, redundant and inelastic and severe systemic involvement (pulmonary atelectasis and emphysema, vascular anomalies and diverticula).
This disease is genetically heterogeneous and although the etiology is not known in most cases, in some patients, mutations have been identified in the genes FBLN5 (14q31) and EFEMP2 (11q13), which encode respectively for fibulin-5 and the fibulin-4, extracellular matrix proteins. Mutations in the gene EFEMP2 are usually associated with arachnodactyly, bone fragility, vascular tortuosity and aortic aneurysms.
Finally, a study of post myocardial infarction cells showed the correlation between expression of fibulin-6 and activity of cardiac remodeling under the influence of the factor TGF-B.
*Robbins e Cotran, Le basi patologiche delle malattie. Patologia generale Ed.8, Elsevier, 2010,
*Chowdhury A, Herzog C, Hasselbach L, Loghmani H, Zhang J, Hammerschmidt M, Rudat C, Kispert A, Gaestel M, Menon MB, Tudorache I, Hilfiker-Kleiner D, Mühlfeld C, Schmitto JD, Müller M, Theilmeier G, Expression of fibulin-6 in failing hearts and its role for cardiac fibroblast migration, Cardiovasc Res. 2014
*Khadzhieva MB, Kamoeva SV, Chumachenko AG, Ivanova AV, Volodin IV, Vladimirov IS, Abilev SK, Salnikova LE, Fibulin-5 (FBLN5) gene polymorphism is associated with pelvic organ prolapse, Maturitas, 2014
*Jaffar J, Unger S, Corte TJ, Keller M, Wolters PJ, Richeldi L, Cerri S, Prêle CM, Hansbro PM, Argraves WS, Oliver RA, Oliver BG, Black JL, Burgess JK, Fibulin-1 predicts disease progression in patients with idiopathic pulmonary fibrosis, Chest. 2014
*Chen J, Zhang J, Liu X, Fang R, Zhao Y, Ma D, Overexpression of fibulin-4 is associated with tumor progression and poor prognosis in patients with cervical carcinoma, Oncol Rep, 2014
*Brandsma CA, van den Berge M, Postma DS, Jonker MR, Brouwer S, Paré PD, Sin DD, Bossé Y, Laviolette M, Karjalainen J, Fehrmann RS, Nickle DC, Hao K, Spanjer AI, Timens W, Franke L, A large lung gene expression study identifying fibulin-5 as a novel player in tissue repair in COPD, Thorax. 2014
*Papke CL, Yanagisawa H, Fibulin-4 and fibulin-5 in elastogenesis and beyond: Insights from mouse and human studies, Matrix Biol. 2014
*Yoshimitsu Hirai, MD,1,2 Yasuteru Muragaki, MD, PhD,2 Shunji Itoh, PhD,2 Kosuke Oikawa, PhD,2 Masanobu Juri, MD, PhD,3 Tomohiro Kondo, MD, PhD,4 and Yoshitaka Okamura, MD, PhD, Fibulin-5 Protein Is Reduced in the Lung of Patients with Spontaneous Pneumothorax Who Are Under 25 Years Old, Ann Thorac Cardiovasc Surg 2012; 18: 200–205