InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: FBN1

Summary

InnateDB Protein

IDBP-10991.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

FBN1

Protein Name

fibrillin 1

Synonyms

ACMICD; ECTOL1; FBN; GPHYSD2; MASS; MFS1; OCTD; SGS; SSKS; WMS; WMS2;

Species

Homo sapiens

Ensembl Protein

ENSP00000325527

InnateDB Gene

IDBG-10989 (FBN1)

Protein Structure

UniProt Annotation

Function

Fibrillins are structural components of 10-12 nm extracellular calcium-binding microfibrils, which occur either in association with elastin or in elastin-free bundles. Fibrillin-1- containing microfibrils provide long-term force bearing structural support. Regulates osteoblast maturation by controlling TGF-beta bioavailability and calibrating TGF-beta and BMP levels, respectively. {ECO:0000269PubMed:15062093}.

Subcellular Localization

Secreted, extracellular space, extracellular matrix {ECO:0000269PubMed:21989719}.

Disease Associations

Marfan syndrome (MFS) [MIM:154700]: A hereditary disorder of connective tissue that affects the skeletal, ocular, and cardiovascular systems. A wide variety of skeletal abnormalities occurs with Marfan syndrome, including scoliosis, chest wall deformity, tall stature, abnormal joint mobility. Ectopia lentis occurs in most of the patients and is almost always bilateral. The leading cause of premature death is progressive dilation of the aortic root and ascending aorta, causing aortic incompetence and dissection. Neonatal Marfan syndrome is the most severe form resulting in death from cardiorespiratory failure in the first few years of life. {ECO:0000269PubMed:10425041, ECO:0000269PubMed:10441597, ECO:0000269PubMed:10694921, ECO:0000269PubMed:11700157, ECO:0000269PubMed:11826022, ECO:0000269PubMed:12203992, ECO:0000269PubMed:1301946, ECO:0000269PubMed:14695540, ECO:0000269PubMed:15221638, ECO:0000269PubMed:1569206, ECO:0000269PubMed:16220557, ECO:0000269PubMed:16222657, ECO:0000269PubMed:1852208, ECO:0000269PubMed:20803651, ECO:0000269PubMed:21542060, ECO:0000269PubMed:7611299, ECO:0000269PubMed:7738200, ECO:0000269PubMed:7870075, ECO:0000269PubMed:7977366, ECO:0000269PubMed:8004112, ECO:0000269PubMed:8040326, ECO:0000269PubMed:8071963, ECO:0000269PubMed:8136837, ECO:0000269PubMed:8281141, ECO:0000269PubMed:8406497, ECO:0000269PubMed:8504310, ECO:0000269PubMed:8863159, ECO:0000269PubMed:8882780, ECO:0000269PubMed:9254848, ECO:0000269PubMed:9338581, ECO:0000269PubMed:9452085, ECO:0000269PubMed:9837823, ECO:0000269Ref.42}. Note=The disease is caused by mutations affecting the gene represented in this entry. The majority of the more than 600 mutations in FBN1 currently known are point mutations, the rest are frameshifts and splice site mutations. Marfan syndrome has been suggested in at least 2 historical figures, Abraham Lincoln and Paganini.Ectopia lentis 1, isolated, autosomal dominant (ECTOL1) [MIM:129600]: An ocular abnormality characterized by partial or complete displacement of the lens from its space resulting from defective zonule formation. {ECO:0000269PubMed:11700157, ECO:0000269PubMed:11826022, ECO:0000269PubMed:12203992, ECO:0000269PubMed:8188302}. Note=The disease is caused by mutations affecting the gene represented in this entry.Weill-Marchesani syndrome 2 (WMS2) [MIM:608328]: A rare connective tissue disorder characterized by short stature, brachydactyly, joint stiffness, and eye abnormalities including microspherophakia, ectopia lentis, severe myopia and glaucoma. {ECO:0000269PubMed:12525539}. Note=The disease is caused by mutations affecting the gene represented in this entry.Overlap connective tissue disease (OCTD) [MIM:604308]: Heritable disorder of connective tissue characterized by involvement of the mitral valve, aorta, skeleton, and skin. MASS syndrome is closely resembling both the Marfan syndrome and the Barlow syndrome. However, no dislocation of the lenses or aneurysmal changes occur in the aorta, and the mitral valve prolapse is by no means invariable. {ECO:0000269PubMed:2739055}. Note=The disease is caused by mutations affecting the gene represented in this entry.Stiff skin syndrome (SSKS) [MIM:184900]: A syndrome characterized by hard, thick skin, usually over the entire body, which limits joint mobility and causes flexion contractures. Other occasional findings include lipodystrophy and muscle weakness. {ECO:0000269PubMed:20375004}. Note=The disease is caused by mutations affecting the gene represented in this entry.Geleophysic dysplasia 2 (GPHYSD2) [MIM:614185]: An autosomal dominant disorder characterized by severe short stature, short hands and feet, joint limitations, and skin thickening. Radiologic features include delayed bone age, cone-shaped epiphyses, shortened long tubular bones, and ovoid vertebral bodies. Affected individuals have characteristic facial features including a 'happy' face with full cheeks, shortened nose, hypertelorism, long and flat philtrum, and thin upper lip. Other distinctive features include progressive cardiac valvular thickening often leading to an early death, toe walking, tracheal stenosis, respiratory insufficiency, and lysosomal-like storage vacuoles in various tissues. {ECO:0000269PubMed:21683322}. Note=The disease is caused by mutations affecting the gene represented in this entry.Acromicric dysplasia (ACMICD) [MIM:102370]: An autosomal dominant disorder characterized by severe short stature, short hands and feet, joint limitations, and skin thickening. Radiologic features include delayed bone age, cone-shaped epiphyses, shortened long tubular bones, and ovoid vertebral bodies. Affected individuals have distinct facial features, including round face, well-defined eyebrows, long eyelashes, bulbous nose with anteverted nostrils, long and prominent philtrum, and thick lips with a small mouth. Other characteristic features include hoarse voice and pseudomuscular build, and there are distinct skeletal features as well, including an internal notch of the femoral head, internal notch of the second metacarpal, and external notch of the fifth metacarpal. {ECO:0000269PubMed:21683322}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 15 experimentally validated interaction(s) in this database.
They are also associated with 3 interaction(s) predicted by orthology.

Experimentally validated
Total	15 [view]
Protein-Protein	15 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	3 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005201	extracellular matrix structural constituent
GO:0005509	calcium ion binding
GO:0005515	protein binding

Biological Process

GO:0001501	skeletal system development
GO:0001656	metanephros development
GO:0001822	kidney development
GO:0007507	heart development
GO:0022617	extracellular matrix disassembly
GO:0030198	extracellular matrix organization
GO:0035582	sequestering of BMP in extracellular matrix
GO:0035583	sequestering of TGFbeta in extracellular matrix
GO:0071560	cellular response to transforming growth factor beta stimulus

Cellular Component

GO:0001527	microfibril
GO:0005576	extracellular region
GO:0005578	proteinaceous extracellular matrix
GO:0005604	basement membrane
GO:0005615	extracellular space
GO:0031012	extracellular matrix
GO:0070062	extracellular vesicular exosome

Protein Structure and Domains

PDB ID

InterPro

IPR000742 Epidermal growth factor-like domain
IPR001881 EGF-like calcium-binding domain
IPR009030 Insulin-like growth factor binding protein, N-terminal
IPR011398 Fibrillin/Microneme protein4
IPR017878 TB domain

PFAM

PF00008
PF07645
PF00683

PRINTS

PIRSF

PIRSF036312

SMART

SM00181
SM00179

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt