| General information | | DisProt: | DP00460 | | Name: | Ectodysplasin-A [Isoform 1] | | Synonym(s): | EDA_HUMAN
Ectodysplasin-A [Isoform A1]
Ectodysplasin-A [Isoform II]
Ectodermal dysplasia protein
EDA-A1
Ectodysplasin-A, membrane form [cleavage product 1]
Ectodysplasin-A, secreted form [cleavage product 2]
| | First appeared in release: | Release 3.0 (02/17/2006) | | UniProt: | Q92838 | | UniGene: | Hs.105407 | | SwissProt: | EDA_HUMAN | | TrEMBL: | | | NCBI (GI): | 6166135 | | Source organism: | Homo sapiens (Human) | | Sequence length: | 391 | | Percent disordered: | 2% | | Homologues: | |
| Native sequence |
10 20 30 40 50 60
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MGYPEVERRE LLPAAAPRER GSQGCGCGGA PARAGEGNSC LLFLGFFGLS LALHLLTLCC - 60
YLELRSELRR ERGAESRLGG SGTPGTSGTL SSLGGLDPDS PITSHLGQPS PKQQPLEPGE - 120
AALHSDSQDG HQMALLNFFF PDEKPYSEEE SRRVRRNKRS KSNEGADGPV KNKKKGKKAG - 180
PPGPNGPPGP PGPPGPQGPP GIPGIPGIPG TTVMGPPGPP GPPGPQGPPG LQGPSGAADK - 240
AGTRENQPAV VHLQGQGSAI QVKNDLSGGV LNDWSRITMN PKVFKLHPRS GELEVLVDGT - 300
YFIYSQVEVY YINFTDFASY EVVVDEKPFL QCTRSIETGK TNYNTCYTAG VCLLKARQKI - 360
AVKMVHADIS INMSKHTTFF GAIRLGEAPA S
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| Functional narrative |
Seems to be involved in epithelial-mesenchymal signaling during morphogenesis of ectodermal organs. Isoform 1 binds only to the receptor EDAR, while isoform 3 binds exclusively to the receptor XEDAR. Two cleavage products exist: cleavage product 1 is Ectodysplasin-A, membrane form (aa 1-391) and cleavage product 2 is Ectodysplasin-A, secreted form (aa 160-391). At least eight isoforms are also known to exist.
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| Map of ordered and disordered regions |
Note: 'Mouse' over a region to see the start and stop residues. Click on a region to see detailed information.
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| Region 1 | | Type: | Disordered | | Name: | turn loop C-D | | Location: | 312 - 317 | | Length: | 6 | | Region sequence: |
INFTDF | | Modification type: | Fragment
| | PDB: | 1RJ7:A | | Structural/functional type: | Function arises from the disordered state
| | Functional classes: | Modification site
Entropic chain
| | Functional subclasses: | Glycosylation
Flexible linkers/spacers
| Detection methods:
- X-ray crystallography (292 K; pH: 7.5; HEPES (pH 7.5) 0.1 M; NaCl 0.2 M; PEG3350 25 %)
- X-ray crystallography (292 K; di-sodium hydrogen phosphate 0.2 M; PEG3350 20 %)
| References:
- Hymowitz SG, Compaan DM, Yan M, Wallweber HJ, Dixit VM, Starovasnik MA, de Vos AM. "The crystal structures of EDA-A1 and EDA-A2: splice variants with distinct receptor specificity." Structure. 2003; 11(12): 1513-20. PubMed: 14656435
| Comments:Hymovitz et al (2003) notes, "this turn was well ordered in some cases, but poorly ordered in other copies."
In Isoform 1, receptor specificity is for EDAR. At the C-terminal end of {beta}strand C, aa E308 and V309 form the receptor specificity switch, followed by a {beta}bulge formed by Y310 and Y311. An extended loop at aa 312-317 leads to {beta}strand D. Within this extended loop, residue N313 is a glycosylation site. In Isoform 3, aa E308-V309 are missing, changing the nature of the receptor specificity switch and consequently the receptor specificity--to XEDAR. (Hymovitz et al., 2003)
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| References |
- Monreal AW, Zonana J, Ferguson B. "Identification of a new splice form of the EDA1 gene permits detection of nearly all X-linked hypohidrotic ectodermal dysplasia mutations." Am J Hum Genet. 1998; 63(2): 380-9. PubMed: 9683615
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| Comments |
Hymowitz et al (2003) performed their crystallography on the TNF domain fragment of EDA-A1 comprised of aa 233-391, and on the similar fragment for EDA-A2 of aa 233-289. the authors use Isoform 1 aa numbering for both isoforms. The DP records number each sequence individually.
UniProt lists the missing aa for Isoform 3 as V307 and E308. Hymowitz et al (2003) discuss missing aa E308 and V309. In either case, the resulting stretch from 307 to 310 reads, VYYI.
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