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FLASH GENE

Symbol

FBLN1

contributors: mct - updated : 20-02-2019

HGNC name	fibulin 1
HGNC id	3600

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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 blood / hematopoietic spleen       highly Cardiovascular vessel       highly Homo sapiens Endocrine pancreas         Nervous brain       highly Reproductive male system prostate     highly Respiratory lung         Homo sapiens Skin/Tegument skin         Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective bone       Connective cartilage       Homo sapiens

cell lineage	during development, it is prominently expressed in the neural crest cells
cell lines
fluid/secretion

at STAGE

physiological period

fetal, pregnancy

Text	highly, in endocardium during development

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	nine extracellular, Ca2+ binding EGF-like repeats, nine tandem EGF-like domains that are present in many extracellular proteins and have crucial role in their diverse functions, and the fifth EGF-like domain is a calcium-binding domain that has been shown to have a role in the localization of the protein and its self-interaction, as well as interaction with other proteins such as hemicentin
	a signal peptide
	three anaphylatoxin-like domains (potential disulfide loop structure)

conjugated

GlycoP

HOMOLOGY

interspecies	homolog to murine Fbln1
	homolog to Drosophila CG10323
	homolog to C.elegans F56H11.1C

intraspecies

homolog to anaphylatoxins C3a,C4a,C5a

Homologene

FAMILY

growing family of extracellular glycoproteins

CATEGORY

structural protein

SUBCELLULAR LOCALIZATION	extracellular
text	extracellular matrix

basic FUNCTION	mediating platelet adhesion via binding fibrinogen
	regulator of ADAMTS1-mediated proteoglycan proteolysis and thus may play an important role in proteoglycan turnover in tissues where there is overlapping expression
	is required for the directed migration and survival of cranial neural crest cell (NCC) contributing to the development of pharyngeal glands, craniofacial skeleton, cranial nerves, aortic arch arteries, cardiac outflow tract and cephalic blood vessels
	like TNC, FBLN1 inhibits fibroblast spreading and cell-mediated contraction of a fibrin-FN matrix
	extracellular matrix protein that has an important role in the structure of elastic fibers and basement membranes of various tissues
	FBLN1 has crucial role in development of the central nervous system and various connective tissues
	involved in numerous processes including cardiovascular and lung development
	FBLN1 is a new positive modulator of the formation of membranous bone and endochondral bone in the skull, acting as a positive regulator of BMP signaling
	FBLN1 is required for bone formation and BMP2-mediated induction of SP7
	FBLN1 normally suppresses proximal cardiac outflow tract (OFT) mesenchymal transition (EMT) preventing proximal cushion hypercellularity and blood cell accumulation
	has also been implicated in embryonic development of the heart and neural crest-derived structures
	important extracellular matrix (ECM) protein involved in matrix organization, may be involved in the pathogenesis of respiratory diseases
	contributes to the structure of the extracellular matrix
	ACAN and FBLN1 have likely critical roles in determining the biomechanics of the aorta and their modification with age could underpin age-related aortic stiffening

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

constituent of extracellular matrix protein

INTERACTION

DNA

RNA

small molecule	metal binding,
	calcium Ca2+

protein	binding to laminin (LAMC2) nidogen and fibronectin
	FBLN1 regulates VCAN-dependent events in ventricular morphogenesis by promoting ADAMTS1 cleavage of VCAN leading to suppression of trabecular cardiomyocyte proliferation mediated by the ERBB2-Map kinase pathway
	CALU binds to and stabilizes FBLN1, leading to inactivation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) signaling
	MMP13 proteolyzes FBLN1 and CALU protects FBLN1 from cleavage by MMP13
	FBLN1c may be a novel driver of TGFB1-induced fibrosis involving LTBP1 and may be an upstream therapeutic target

cell & other

REGULATION

induced by

estradiol in estrogen receptor (ER) ovarian cancer cell lines

ASSOCIATED DISORDERS

corresponding disease(s)

PSDY3 , MRCLUG

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional   translocation     translocation t(12;22)(p11.2;q13.3) in a complex type of synpolydactyly constitutional         haploinsufficence of variant D in synpolydactyly tumoral     --over   of FBLN1C and FBLN1D in ovarian cancer constitutional       loss of function of variant D in autosomal-dominant giant platelet syndromes(FTNS) tumoral     --low   promoter hypermethylation of FBLN1 is associated with tumor progression in cutaneous melanoma tumoral     --low   in renal cell carcinoma through promoter hypermethylation

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	serum FBLN1 and STK31 are biomarkers of colorectal cancer, having ability to noninvasively differentiate colorectal cancer from benign polyps
	changes in VIM and FBLN1 methylation levels in cell-free DNA (cfDNA) are associated with Hepatocellular carcinoma (HCC) and could represent useful plasma-based biomarkers
	plasma levels of FBLN1 could serve as a potential indicator to monitor kidney malfunction or kidney damage
Therapy target

ANIMAL & CELL MODELS

	Fbln1c-/- mice also had reduced airway remodeling in experimental chronic asthma and pulmonary fibrosis
	Fbln1c-deficient (-/-) mice had reduced pulmonary remodeling/fibrosis and improved lung function after bleomycin challenge