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FLASH GENE

Symbol

EFEMP2

contributors: npt/shn - updated : 25-04-2017

HGNC name	EGF-containing fibulin-like extracellular matrix protein 2
HGNC id	3219

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	CLAR1B cutis laxa, type 1B
Location	11q13.2      Physical location : 65.633.912 - 65.640.340
Synonym name	fibulin 4
	mutant p53 binding protein 1
	fibulin-like extracellular matrix protein
	protein UPH1
Synonym symbol(s)	UPH1, FBLN4, FIBL-4, MBP1

DNA

TYPE	functioning gene
STRUCTURE	6.43 kb     12 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

Map	cen - D11S4205 - D11S1883 - EFEMP2 - D11S913 - D11S1889 - qter
Authors	Katsanis (00)
Text	[EFEMP2 ]

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_016938 12 - 2031 NP_058634 - 443 - Chen (2009)

EXPRESSION

Type

widely

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       highly Digestive liver       lowly Endocrine pancreas       moderately Nervous brain       lowly Reproductive female system placenta     moderately Respiratory lung       lowly Urinary kidney       moderately Visual eye retina     moderately

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum skeletal   moderately

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal, pregnancy

Text	brain, kidney, heart and retina

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	six Ca2+ binging EGF-like domains
	four EGF2 domains
	a C-terminal fibulin domain

conjugated

GlycoP

HOMOLOGY

interspecies	ortholog to Efemp2, Mus musculus
	ortholog to Efemp2, Rattus norvegicus
	ortholog to efemp2, Danio rerio
	ortholog to EFEMP2, Pan troglodytes

intraspecies

homolog to EFEMP1

Homologene

FAMILY

fibulin family

CATEGORY

structural protein , signaling

SUBCELLULAR LOCALIZATION	extracellular
text	extracellular matrix
	secreted

basic FUNCTION	an elastic-fibre-associated glycoprotein indispensable for elastic-fibre formation and connective tissue evelopment
	playing an essential role in elastogenesis
	elastic-fibre-associated glycoprotein that is indispensable for elastic-fibre formation (Chen 2009)
	structural protein, that may also participate in regulating elastic-fibre formation in human cells through an unanticipated mechanism, namely the regulation of tropoelastin expression (Chen 2009)
	distinct roles of EFEMP2 and FBLN5 in elastic fiber assembly and how they act in concert to chaperone cross-linked elastin onto microfibrils (Choudhury 2009)
	dose-dependent requirement for FBLN4 in the development of the elastic fibers in arteries, and have a specific role in recruiting the elastin-cross-linking enzyme, lysyl oxidase (LOX) (Horiguchi 2009)
	acts as an indispensible adaptor between proLOX and elastin to facilitate proper maturation of elastic fibers (Horiguchi 2009)

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

constituent of extracellular matrix

INTERACTION

DNA

RNA

small molecule	metal binding,
	Ca2+

protein	p53 (Gallagher et al, 1999)
	strong binding between EFEMP2 and lysyl oxidase enhanced the interaction of EFEMP2 with tropoelastin, forming ternary complexes that may direct elastin cross-linking (Choudhury 2009)
	specific interaction between EFEMP2 and LOX, which efficiently promotes assembly of LOX onto tropoelastin( suggest a mechanism of elastogenesis, in which a sufficient amount of EFEMP2 is essential for tethering LOX to tropoelastin to facilitate cross-linking) (Horiguchi 2009)
	participate in regulating elastic-fibre formation in human cells through an unanticipated mechanism, namely the regulation of tropoelastin expression (Chen et al, 2009)
	EMILIN1 interacts directly with EFEMP2 (also known as fibulin-4) and is required for proper extracellular matrix (ECM) deposition of EFEMP2
	EMILIN1 not only assists in EFEMP2 and tropoelastin deposition onto the fibrillin microfibril (FMF) scaffold during elastogenesis, but also targets LOX via EFEMP2 to collagen fibers in order to establish critical collagen crosslinks

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

CLAR1B

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --other   dysregulated expression of associated with colon carcinoma

Susceptibility

recognized as an autoantigen mainly in osteoarthritis

Variant & Polymorphism

Candidate gene	retinal dystrophy
Marker
Therapy target

ANIMAL & CELL MODELS

	Fbln4-deficient mice have tortuous aortae and emphysematous lungs, with severe disruption in elastic tissues (Horiguchi 2009)
	knocked down of fibulin-4 in human foreskin fibroblasts using siRNA leads to impairment of elastic-fibre formation (Chen et al, 2009)
	Knocking down or knocking out fibulin-4 in mice lead to a decrease in tropoelastin expression in the aorta (Chen et al, 2009)