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FLASH GENE

Symbol

EDA

contributors: npt/mct - updated : 10-10-2014

HGNC name	ectodysplasin A
HGNC id	3157

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	ED1 ectodermal dysplasia 1, anhidrotic HYDX X-linked hypodontia
Location	Xq13.1      Physical location : 68.835.910 - 69.259.319
Synonym name	ectodysplasin-A, membrane form
	ectodysplasin-A, secreted form
	ectodermal dysplasia 1, anhidrotic
	EDA protein
	oligodontia 1
Synonym symbol(s)	HED, EDA1, EDA2, XLHED, XHED, ED1-A1, ED1-A2
EC.number	3.5.-.-

DNA

TYPE	functioning gene
STRUCTURE	423.41 kb     8 Exon(s)

regulatory sequence	Promoter
	Binding site   enhancer
text structure	exons include alternative 1a, to 1e, 2a, 2b, 3a, 3b, 8a, 8b
	a binding site for lymphoid enhancer-binding factor-1
	target of Wnt signaling

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

text	including six truncated transcripts O, B, C, D, E, F.

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001399 8 - 5296 NP_001390 41.3 391 differentially expressed 1998 9736768 also called EDA-A1 binding only to EDAR NM_001005609 8 splicing 5290 NP_001005609 40.9 389 differentially expressed 1998 9736768 also called EDA-A2 using an alternate in-frame splice site binding only to XEDAR NM_001005610 2 splicing 1089 NP_001005610 19 178 - 1998 9736768 also called EDA-B including exons 1a, 3a, 3b truncated form differing in the 3' UTR and coding region compared to variant 1 NM_001005611 1 splicing 1233 NP_001005611 14.9 147 restricted to heart, liver, muscle 1998 9736768 also called EDA-C exons 1a, 1b differing in the 3' UTR and coding region compared to variant 1 NM_001005612 3 splicing 1140 NP_001005612 14.6 142 very weakly expressed 1998 9736768 also called EDA-D stop in exon 1d differing in the 3' UTR and coding region compared to variant 1 NM_001005615 2 splicing 840 NP_001005615 13.9 135 keratinocytes, hair follicles, sweat glands, and in other adult and fetal tissues 1998 9736768 also called EDA-O two exons 1a, stop in exon 2a differing in the 3' UTR and coding region compared to variant 1 NM_001005613 3 - 942 NP_001005613 - 148 - 1998 9736768

EXPRESSION

Type

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         Digestive intestine small intestine         liver           tooth         Endocrine pancreas         Reproductive female system uterus         male system prostate       Skin/Tegument skin appendages hair follicle       skin appendages skin gland sweat gland eccrine sweat gland

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial barrier/lining       Epithelial secretory glandular exocrine   Epithelial sensory olfactory

cells

System Cell Pubmed Species Stage Rna symbol Skin/Tegument keratinocyte

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

embryo, fetal, pregnancy

Text	placenta (isoform D), developing epithelium, tooth bud, umbilical chord, fetal liver

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a collagen-like domain comprising 19 GXX triplets and a EC1 domain composing with a triple helical domain, activating EDA1 by multimerization, whereas the proteoglycan-binding domain may restrict the distribution of endogeneous EDA1
	a stalk region including two consecutive consensus furin cleavage sequences
	a proteolytic processing site responsible for its conversion to a soluble form
	a C terminal extracellular EC2 with three cysteine residues, a trimeric TNF homology domain (THD) that binds the receptor EDAR

conjugated

GlycoP

mono polymer

homomer , trimer

HOMOLOGY

interspecies

ortholog to murine Eda

intraspecies

homolog to TNF ligand

Homologene

FAMILY

tumor necrosis factor family

CATEGORY

adhesion , regulatory , signaling

SUBCELLULAR LOCALIZATION	extracellular
	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,cytoplasm,cytoskeleton
text	type 2 membrane protein that can be cleaved by furin to produce a secreted form and that binds to EDAR

basic FUNCTION	regulating the function of epithelial signaling centers
	involved in regulation of cell-cell or cell-matrix interaction
	paracrine signaling role in hair, tooth and skin sweat gland development
	a regulatory role in both the NF-kappa-B and JNK pathways
	may be involved in development of the human dentition, especially of anterior teeth, but not posterior teeth
	EDA signaling is needed for the determination and development of various skin appendages at spatiotemporally restricted intervals
	EDA and WNT pathways are required for salivary gland branching morphogenesis
	is a unique regulator of embryonic and prepubertal ductal morphogenesis
	is a unique mesenchymal factor regulating embryonic and prepubertal mammary gland morphogenesis through activation of EDAR/NFKB in the epithelium

CELLULAR PROCESS

cell communication

PHYSIOLOGICAL PROCESS

development , immunity/defense

text	skin and appendages

PATHWAY

metabolism

signaling

signal transduction

	TNF signaling to the target cells through activation of the NF-kappa B system of transcriptional regulation through IKB
	EDA/EDAR/NF-kappaB signaling pathways in initiation and maintenance of primary hair follicle placodes
	ectodysplasin (EDA) pathway is essential for the formation and function of several ectodermal organs

a component

INTERACTION

DNA

RNA

small molecule

protein	EDAR (isoform EDA-A1)
	EDA regulates growth and branching of the submandibular salivary gland (SMG) via transcription factor NFKB in the epithelium, and the hedgehog pathway is an important mediator of EDA/NFKB
	NFKB regulates embryonic and prepubertal ductal development and is essential for EDA-induced accelerated branching morphogenesis
	FOXI3 is a likely transcriptional target of EDA in ectodermal appendage placodes suggesting that hypohidrotic ectodermal dysplasia (HED) phenotype may in part be produced by compromised FOXI3 activity

cell & other

REGULATION

induced by

Wnt6 (in mice)

Other

regulated by WNT signaling

ASSOCIATED DISORDERS

corresponding disease(s)

ED1 , HYDX

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

murine Tabby (Ta) phenopypically identical to murine downless and crinked