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FLASH GENE

Symbol

ECE1

contributors: shn/npt - updated : 01-03-2010

HGNC name	endothelin converting enzyme 1
HGNC id	3146

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	HSCR5 Hirschsprung disease 5
Location	1p36.12      Physical location : 21.543.739 - 21.672.034
Synonym name	Hirschsprung disease, cardiac defects, and autonomic dysfunction, included
Synonym symbol(s)	ECE, ECE-1
EC.number	3.4.24.71

DNA

TYPE	functioning gene
STRUCTURE	128.29 kb     19 Exon(s)

Genomic sequence alignment details
10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

Map	pter - D1S2732 - D1S3720 - ECE1 - D1S334 - D1S2828 - cen

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001397 (transcript variant 1) 19 splicing 5114 NP_001388 - 770 . abundantly in endothelial cells . perinuclear region and in Weibel-Palade bodies of the human umbilical vein endothelial cells . endothelium and smooth muscle, retinal arterioles Xu et al, 1994; Russel et al, 1998? Hein 2009 NM_001113347 (transcript variant 3) 17 splicing 5259 NP_001106818 - 758 . abundantly in endothelial cells . perinuclear region and in Weibel-Palade bodies of the human umbilical vein endothelial cells . endothelium and smooth muscle, retinal arterioles Xu et al, 1994; Russell et al, 1998, Hein 2009 NM_001113349 (transcript variant 2) 18 splicing 5105 NP_001106820 - 767 . abundantly in endothelial cells . . perinuclear region and in Weibel-Palade bodies of the human umbilical vein endothelial cells . endothelium and smooth muscle, retinal arterioles Xu et al, 1994; Russell et al, 1998; Hein 2009 NM_001113348 (transcript variant 4) 19 splicing 5154 NP_001106819 - 754 . abundantly in endothelial cells . perinuclear region and in Weibel-Palade bodies of the human umbilical vein endothelial cells . endothelium and smooth muscle, retinal arterioles Xu 1994; Russell 1998; Hein 2009

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       highly Digestive intestine large intestine colon   highly   intestine small intestine     moderately   liver       moderately Endocrine pancreas       highly Lymphoid/Immune spleen       moderately   thymus       lowly Reproductive female system ovary     highly   female system placenta     moderately   male system testis     moderately   male system prostate     moderately Respiratory lung       moderately Urinary kidney       lowly Visual eye retina     lowly

tissue

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

cells

System Cell Pubmed Species Stage Rna symbol Cardiovascular endothelial cell

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal

Text	olfactory mucosa and FNC-B4 cells

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	two peptidase domains
	a conserved pentapeptide zinc binding motif near the C terminus
	a HEXXH (HELTH) motif

secondary structure

structurally related to neutral endopeptidase 24.11 and Kell blood group protein

conjugated

PhosphoP

mono polymer

homomer , dimer

HOMOLOGY

interspecies	ortholog to ECE1, Pan troglodytes
	ortholog to Ece1, Rattus norvegicus
	ortholog to Ece1, Mus musculus

Homologene

FAMILY

neutral endopeptidase family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular,cytoplasm,organelle,Golgi
	intracellular,cytoplasm,organelle,endosome
text	type II integral membrane glycoprotein

basic FUNCTION	involved in proteolytic processing of endothelin precursors to biologically active peptides
	involved in the development of distinct subsets of neural crest cell lineages (Yanagisawa et al, 1998)
	generates endothelin-1 (ET-1) by specific proteolytic processing of a precursor peptide, big ET-1 (Fahnoe et al, 2000)
	a physiological role in limiting Abeta accumulation in the brain (Eckman et al, 2003)
	in early endosomes degrades neuropeptides, regulates post-endocytic sorting of receptors and degrades Calcitonin gene-related peptide (Padilla et al, 2007)

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

development

text	Hydrolysis of the 21-Trp-
	-Val-22 bond in big endothelin to form endothelin 1

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule	metal binding,
	Zn2+

protein

endothelin-1 (ET-1)

cell & other

shear stress attenuates endothelin and endothelin-converting enzyme expression through oxidative stress

REGULATION

inhibited by	inhibited by treatment with estrogen, genistein, or daidzein
	phosphoramidon

Other

localization of isoforms modulated by the ECE1-b targetting signal

ASSOCIATED DISORDERS

corresponding disease(s)

HSCR5

Susceptibility

Variant & Polymorphism SNP	polymorphisms in the 5-prime flanking region of the ECE1 gene, -338C-A and -839T-G, are associated with ambulatory blood pressure values (Funke-Kaiser et al, 2003)

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

	ECE-1-/- term mouse embryos exhibited craniofacial and cardiac abnormalities virtually identical to the defects seen in ET-1 and endothelin A receptor (ETA)-deficient embryos, epidermal melanocytes and enteric neurons of the distal gut are absent (Yanagisawa et al, 1998)
	brains of mice deficient for ECE-1 display significant increases in the levels of both Abeta40 and Abeta42 (Eckman et al, 2003)