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FLASH GENE

Symbol

FBN1

contributors: mct/npt/pgu - updated : 09-01-2018

HGNC name	fibrillin 1 (Marfan syndrome)
HGNC id	3603

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	ACMICD acromicric dysplasia ECTL ectopia lentis, isolated GLSD2 geleophysic dysplasia 2 KPSI kyphoscoliosis, isolated, progressive, of variable severity MFLS Marfan lipodystrophy syndrome MFS1 Marfan syndrome 1 SGS Shprintzen-Goldberg syndrome of marfanoid habitus craniosynostosis SSKS stiff skin syndrome TAA thoracic aortic aneurysm WMSAD Weill-Marchesani syndrome
Location	15q21.1      Physical location : 48.700.503 - 48.937.985
Synonym name	fibrillin 1 (Marfan syndrome)
	fibrillin 15
Synonym symbol(s)	FBN, MASS, OCTD, WMS

DNA

TYPE	functioning gene
STRUCTURE	237.48 kb     66 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
	cytosine-phosphate-guanine/HTF
motif	repetitive sequence
text structure	47 EGF-like motifs (43 calcium-binding EGF repeats)
	a single CpG-rich promoter which was highly conserved in mammals with potential binding sites for a number of factors implicated in mesenchyme differentiation and gene expression

MAPPING

cloned

Y

linked

Y

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000138 66 - 11695 NP_000129 - 2871 - 2009 19573590 54A-FBN1 - splicing - - - - 2011 21726527 contains a cryptic 105 basepair exon between exons 54 and 55 predicted to produce non-functional protein 57A-FBN1 - splicing - - 2217 adult brain 2011 21726527 contains a cryptic 62 basepair exon between exons 57 and 58 truncated fibrillin protein of 2217 amino acids since the 57A insertion creates a premature stop codon that mimics Marfan-associated mutations, the protein encoded by 57A-FBN1 is likely to not be functional may regulate fibrillin expression and disease severity represents a significant portion of total FBN1 expression

EXPRESSION

Type	ubiquitous

expressed in

(based on citations)

organ(s)

System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart       moderately Homo sapiens   vessel aorta     moderately Homo sapiens Digestive liver       lowly Homo sapiens Nervous brain       moderately Homo sapiens Respiratory lung       moderately Homo sapiens Skin/Tegument skin       highly Homo sapiens Urinary kidney       moderately Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose     highly Connective bone     highly Homo sapiens Adult Connective cartilage       Membrane advantitia perichondrium     Muscular smooth     highly Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Muscular myocyte not specific adipocyte

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	47 EGF-like repeats (43 with a calcium binding consensus sequence),several cysteine-rich modules
	a RGD motif, seven transforming growth factor beta 1-binding protein-like domains (LTBP)
	a proline-rich region and two FIB motifs
	unique N and C termini
	two distinct regions bound to ADAMTS10, one in the N-terminal half and another in the C-terminal half

conjugated

GlycoP

isoforms

Precursor

profibrilin-1 is a 350 Kda cysteine-rich glycoprotein

HOMOLOGY

Homologene

FAMILY

fibrillin family

CATEGORY

structural protein

SUBCELLULAR LOCALIZATION	extracellular
text	microfibrils, colocalizing with FBNL2, basement membrane

basic FUNCTION	involved in the maintenance of elastic fibers and anchoring epithelial cells to the interstitial matrix
	with FBN2, regulate lung fibroblast migration
	glycoprotein component of the extracellular microfibrils
	FBN1 and FBN2, the structural components of extracellular microfibrils, differentially regulate TGFbeta and bone morphogenetic protein (BMP) bioavailability in bone
	FBN2 exerts a greater positive influence on the mechanical properties of bone than FBN1 assemblies, and the above findings are mostly, if not exclusively, related to the differetial control of TGFbeta family signaling by fibrillin proteins 2)
	both FBN1 and FBN2 are essential for the formation of thick oxytalan fibers in the ciliary zonule and are informative for clarifying the mechanism of homeostasis of the ocular matrix
	FBN1, FBN2, FBN3, are important in maintaining the structure and integrity of the extracellular matrix and, in combination with their sequence family members the LTBPs, also contribute to the regulation of the TGFB family of major growth factors
	both FBN1 and FBN2 expression is required to form thick oxytalan fibers in the periodontal ligament (PDL)
	FBN1 regulates mesenchymal stem cells [MSCs] activity by modulating TGFB1 bioavailability within the microenvironment of marrow niches
	FBN1-microfibrils influence adult bone marrow hematopoiesis

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

sensory transduction/vision

a component

major constituent of extracellular matrix

INTERACTION

DNA

RNA

small molecule

protein	up-regulating MMP1 and MMP3 through the RGD motif (role in the progressive breakdown of microfibrils and in the pathogenesis of Marfan syndrome)
	binding THSD4
	ADAMTS10 binds to fibrillin-1
	bind to LTBPs (latent transforming growth factor beta binding proteins) to assist in this process and is thus involved in regulating the bioavailability of TGFB
	FBN1, acts at the downstream of AURKA and BRCA2, promotes ovarian cancer metastasis through the TP53 and SNAI2-associated signaling

cell & other

REGULATION

Other

furin mediated

ASSOCIATED DISORDERS

corresponding disease(s)

ECTL , MFS1 , SGS , KPSI , TAA , WMSAD , SSKS , ACMICD , GLSD2 , MFLS

related resource

Marfan Database - Fibrillin-1 gene mutations

Susceptibility

to sporadic thoracic aortic aneurysms and dissections (STAAD)

Variant & Polymorphism SNP , other	common genetic variants at 15q21.1 that probably act via FBN1 are associated with STAAD

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cardiovascular valvulopathy   decrease the proportion of FBN1 expressed as 57A-FBN1 represents a potential therapeutic modality in Marfan syndrome

ANIMAL & CELL MODELS

decreased expression of Fbn1 during morphogenesis of the fetal diaphragm may disrupt mesenchymal cell proliferation, causing malformed muscle connective tissue (MCT) and thus resulting in diaphragmatic defects in the nitrofen-induced congenital diaphragmatic hernia (CDH) model