4a9z - Revision history

OCA at 10:48, 9 May 2024

OCA — Thu, 09 May 2024 10:48:50 GMT

←Older revision		Revision as of 10:48, 9 May 2024
Line 3:		Line 3:
	<StructureSection load='4a9z' size='340' side='right'caption='[[4a9z]], [[Resolution\|resolution]] 2.29Å' scene=''>		<StructureSection load='4a9z' size='340' side='right'caption='[[4a9z]], [[Resolution\|resolution]] 2.29Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4a9z]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4A9Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4A9Z FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4a9z]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4A9Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4A9Z FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=PE4:2-{2~~-[~~2-(2-{2-~~[~~2-(2-ETHOXY-ETHOXY)-ETHOXY~~]~~-ETHOXY}-ETHOXY)-ETHOXY~~]~~-ETHOXY}-ETHANOL'>PE4</scene>~~</td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.29Å</td></tr>
-	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"><~~div style~~='~~overflow~~: ~~auto; max~~-~~height: 3em;'>~~[[~~2y9t\|2y9t]], [[3zy0\|3zy0]], [[3zy1\|3zy1]], [[1rg6\|1rg6]], [[2y9u\|2y9u~~]]</~~div~~></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PE4:2-{2-[2-(2-{2-[2-(2-ETHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHOXY]-ETHOXY}-ETHANOL'>PE4</scene></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4a9z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a9z OCA], [https://pdbe.org/4a9z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4a9z RCSB], [https://www.ebi.ac.uk/pdbsum/4a9z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4a9z ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4a9z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a9z OCA], [https://pdbe.org/4a9z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4a9z RCSB], [https://www.ebi.ac.uk/pdbsum/4a9z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4a9z ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[https://www.uniprot.org/uniprot/P63_HUMAN P63_HUMAN]] Defects in TP63 are the cause of acro-dermato-ungual-lacrimal-tooth syndrome (ADULT syndrome) [MIM:[https://omim.org/entry/103285 103285]]; a form of ectodermal dysplasia. Ectodermal dysplasias (EDs) constitute a heterogeneous group of developmental disorders affecting tissues of ectodermal origin. EDs are characterized by abnormal development of two or more ectodermal structures such as hair, teeth, nails and sweat glands, with or without any additional clinical sign. Each combination of clinical features represents a different type of ectodermal dysplasia. ADULT syndrome involves ectrodactyly, syndactyly, finger- and toenail dysplasia, hypoplastic breasts and nipples, intensive freckling, lacrimal duct atresia, frontal alopecia, primary hypodontia, and loss of permanent teeth. ADULT differs significantly from EEC3 syndrome by the absence of facial clefting. Defects in TP63 are the cause of ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) [MIM:[https://omim.org/entry/106260 106260]]. AEC is an autosomal dominant condition characterized by congenital ectodermal dysplasia with coarse, wiry, sparse hair, dystrophic nails, slight hypohidrosis, scalp infections, ankyloblepharon filiform adnatum, maxillary hypoplasia, hypodontia and cleft lip/palate.<ref>PMID:11159940</ref> Defects in TP63 are the cause of ectrodactyly-ectodermal dysplasia-cleft lip/palate syndrome type 3 (EEC3) [MIM:[https://omim.org/entry/604292 604292]]. EEC3 is an autosomal dominant syndrome characterized by ectrodactyly of hands and feet, ectodermal dysplasia and facial clefting.<ref>PMID:10535733</ref> <ref>PMID:10839977</ref> <ref>PMID:11462173</ref> <ref>PMID:12838557</ref> Defects in TP63 are the cause of split-hand/foot malformation type 4 (SHFM4) [MIM:[https://omim.org/entry/605289 605289]]. Split-hand/split-foot malformation is a limb malformation involving the central rays of the autopod and presenting with syndactyly, median clefts of the hands and feet, and aplasia and/or hypoplasia of the phalanges, metacarpals, and metatarsals. There is restricted overlap between the mutational spectra of EEC3 and SHFM4.<ref>PMID:10839977</ref> <ref>PMID:11462173</ref> Defects in TP63 are the cause of limb-mammary syndrome (LMS) [MIM:[https://omim.org/entry/603543 603543]]. LMS is characterized by ectrodactyly, cleft palate and mammary-gland abnormalities.<ref>PMID:11462173</ref> Note=Defects in TP63 are a cause of cervical, colon, head and neck, lung and ovarian cancers. Defects in TP63 are a cause of ectodermal dysplasia Rapp-Hodgkin type (EDRH) [MIM:[https://omim.org/entry/129400 129400]]; also called Rapp-Hodgkin syndrome or anhidrotic ectodermal dysplasia with cleft lip/palate. Ectodermal dysplasia defines a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. EDRH is characterized by the combination of anhidrotic ectodermal dysplasia, cleft lip, and cleft palate. The clinical syndrome is comprised of a characteristic facies (narrow nose and small mouth), wiry, slow-growing, and uncombable hair, sparse eyelashes and eyebrows, obstructed lacrimal puncta/epiphora, bilateral stenosis of external auditory canals, microsomia, hypodontia, cone-shaped incisors, enamel hypoplasia, dystrophic nails, and cleft lip/cleft palate.<ref>PMID:12939657</ref> <ref>PMID:12766194</ref> <ref>PMID:15200513</ref> <ref>PMID:16740912</ref> Defects in TP63 are the cause of non-syndromic orofacial cleft type 8 (OFC8) [MIM:[https://omim.org/entry/129400 129400]]. Non-syndromic orofacial cleft is a common birth defect consisting of cleft lips with or without cleft palate. Cleft lips are associated with cleft palate in two-third of cases. A cleft lip can occur on one or both sides and range in severity from a simple notch in the upper lip to a complete opening in the lip extending into the floor of the nostril and involving the upper gum.	+	[https://www.uniprot.org/uniprot/P63_HUMAN P63_HUMAN] Defects in TP63 are the cause of acro-dermato-ungual-lacrimal-tooth syndrome (ADULT syndrome) [MIM:[https://omim.org/entry/103285 103285]; a form of ectodermal dysplasia. Ectodermal dysplasias (EDs) constitute a heterogeneous group of developmental disorders affecting tissues of ectodermal origin. EDs are characterized by abnormal development of two or more ectodermal structures such as hair, teeth, nails and sweat glands, with or without any additional clinical sign. Each combination of clinical features represents a different type of ectodermal dysplasia. ADULT syndrome involves ectrodactyly, syndactyly, finger- and toenail dysplasia, hypoplastic breasts and nipples, intensive freckling, lacrimal duct atresia, frontal alopecia, primary hypodontia, and loss of permanent teeth. ADULT differs significantly from EEC3 syndrome by the absence of facial clefting. Defects in TP63 are the cause of ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) [MIM:[https://omim.org/entry/106260 106260]. AEC is an autosomal dominant condition characterized by congenital ectodermal dysplasia with coarse, wiry, sparse hair, dystrophic nails, slight hypohidrosis, scalp infections, ankyloblepharon filiform adnatum, maxillary hypoplasia, hypodontia and cleft lip/palate.<ref>PMID:11159940</ref> Defects in TP63 are the cause of ectrodactyly-ectodermal dysplasia-cleft lip/palate syndrome type 3 (EEC3) [MIM:[https://omim.org/entry/604292 604292]. EEC3 is an autosomal dominant syndrome characterized by ectrodactyly of hands and feet, ectodermal dysplasia and facial clefting.<ref>PMID:10535733</ref> <ref>PMID:10839977</ref> <ref>PMID:11462173</ref> <ref>PMID:12838557</ref> Defects in TP63 are the cause of split-hand/foot malformation type 4 (SHFM4) [MIM:[https://omim.org/entry/605289 605289]. Split-hand/split-foot malformation is a limb malformation involving the central rays of the autopod and presenting with syndactyly, median clefts of the hands and feet, and aplasia and/or hypoplasia of the phalanges, metacarpals, and metatarsals. There is restricted overlap between the mutational spectra of EEC3 and SHFM4.<ref>PMID:10839977</ref> <ref>PMID:11462173</ref> Defects in TP63 are the cause of limb-mammary syndrome (LMS) [MIM:[https://omim.org/entry/603543 603543]. LMS is characterized by ectrodactyly, cleft palate and mammary-gland abnormalities.<ref>PMID:11462173</ref> Note=Defects in TP63 are a cause of cervical, colon, head and neck, lung and ovarian cancers. Defects in TP63 are a cause of ectodermal dysplasia Rapp-Hodgkin type (EDRH) [MIM:[https://omim.org/entry/129400 129400]; also called Rapp-Hodgkin syndrome or anhidrotic ectodermal dysplasia with cleft lip/palate. Ectodermal dysplasia defines a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. EDRH is characterized by the combination of anhidrotic ectodermal dysplasia, cleft lip, and cleft palate. The clinical syndrome is comprised of a characteristic facies (narrow nose and small mouth), wiry, slow-growing, and uncombable hair, sparse eyelashes and eyebrows, obstructed lacrimal puncta/epiphora, bilateral stenosis of external auditory canals, microsomia, hypodontia, cone-shaped incisors, enamel hypoplasia, dystrophic nails, and cleft lip/cleft palate.<ref>PMID:12939657</ref> <ref>PMID:12766194</ref> <ref>PMID:15200513</ref> <ref>PMID:16740912</ref> Defects in TP63 are the cause of non-syndromic orofacial cleft type 8 (OFC8) [MIM:[https://omim.org/entry/129400 129400]. Non-syndromic orofacial cleft is a common birth defect consisting of cleft lips with or without cleft palate. Cleft lips are associated with cleft palate in two-third of cases. A cleft lip can occur on one or both sides and range in severity from a simple notch in the upper lip to a complete opening in the lip extending into the floor of the nostril and involving the upper gum.
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/P63_HUMAN P63_HUMAN]] Acts as a sequence specific DNA binding transcriptional activator or repressor. The isoforms contain a varying set of transactivation and auto-regulating transactivation inhibiting domains thus showing an isoform specific activity. Isoform 2 activates RIPK4 transcription. May be required in conjunction with TP73/p73 for initiation of p53/TP53 dependent apoptosis in response to genotoxic insults and the presence of activated oncogenes. Involved in Notch signaling by probably inducing JAG1 and JAG2. Plays a role in the regulation of epithelial morphogenesis. The ratio of DeltaN-type and TA*-type isoforms may govern the maintenance of epithelial stem cell compartments and regulate the initiation of epithelial stratification from the undifferentiated embryonal ectoderm. Required for limb formation from the apical ectodermal ridge. Activates transcription of the p21 promoter.<ref>PMID:9774969</ref> <ref>PMID:11641404</ref> <ref>PMID:12446779</ref> <ref>PMID:12446784</ref> <ref>PMID:12374749</ref> <ref>PMID:20123734</ref> <ref>PMID:22197488</ref>	+	[https://www.uniprot.org/uniprot/P63_HUMAN P63_HUMAN] Acts as a sequence specific DNA binding transcriptional activator or repressor. The isoforms contain a varying set of transactivation and auto-regulating transactivation inhibiting domains thus showing an isoform specific activity. Isoform 2 activates RIPK4 transcription. May be required in conjunction with TP73/p73 for initiation of p53/TP53 dependent apoptosis in response to genotoxic insults and the presence of activated oncogenes. Involved in Notch signaling by probably inducing JAG1 and JAG2. Plays a role in the regulation of epithelial morphogenesis. The ratio of DeltaN-type and TA*-type isoforms may govern the maintenance of epithelial stem cell compartments and regulate the initiation of epithelial stratification from the undifferentiated embryonal ectoderm. Required for limb formation from the apical ectodermal ridge. Activates transcription of the p21 promoter.<ref>PMID:9774969</ref> <ref>PMID:11641404</ref> <ref>PMID:12446779</ref> <ref>PMID:12446784</ref> <ref>PMID:12374749</ref> <ref>PMID:20123734</ref> <ref>PMID:22197488</ref>

	==See Also==		==See Also==
Line 19:		Line 19:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Arrowsmith~~, C H~~]]	+	[[Category: Arrowsmith CH]]
-	[[Category: Bountra, C]]	+	[[Category: Bountra C]]
-	[[Category: Chaikuad, A]]	+	[[Category: Chaikuad A]]
-	[[Category: Coutandin, D]]	+	[[Category: Coutandin D]]
-	~~[[Category: Delft, F von~~]]	+	[[Category: Dotsch V]]
-	[[Category: Dotsch, V]]	+	[[Category: Edwards AM]]
-	[[Category: Edwards~~, A M~~]]	+	[[Category: Knapp S]]
-	[[Category: Knapp, S]]	+	[[Category: Muniz JRC]]
-	[[Category: Muniz~~, J R.C~~]]	+	[[Category: Salah E]]
-	[[Category: Salah, E]]	+	[[Category: Vollmar M]]
-	[[Category: Vollmar, M]]	+	[[Category: Weigelt J]]
-	[[Category: Weigelt, J]]	+	[[Category: Von Delft F]]
-	[[Category: ~~Transcription~~]]	+

OCA at 07:54, 18 August 2022

OCA — Thu, 18 Aug 2022 07:54:58 GMT

←Older revision		Revision as of 07:54, 18 August 2022
Line 3:		Line 3:
	<StructureSection load='4a9z' size='340' side='right'caption='[[4a9z]], [[Resolution\|resolution]] 2.29Å' scene=''>		<StructureSection load='4a9z' size='340' side='right'caption='[[4a9z]], [[Resolution\|resolution]] 2.29Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4a9z]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4A9Z OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4A9Z FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4a9z]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4A9Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4A9Z FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PE4:2-{2-[2-(2-{2-[2-(2-ETHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHOXY]-ETHOXY}-ETHANOL'>PE4</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PE4:2-{2-[2-(2-{2-[2-(2-ETHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHOXY]-ETHOXY}-ETHANOL'>PE4</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2y9t\|2y9t]], [[3zy0\|3zy0]], [[3zy1\|3zy1]], [[1rg6\|1rg6]], [[2y9u\|2y9u]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2y9t\|2y9t]], [[3zy0\|3zy0]], [[3zy1\|3zy1]], [[1rg6\|1rg6]], [[2y9u\|2y9u]]</div></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4a9z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a9z OCA], [~~http~~://pdbe.org/4a9z PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4a9z RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4a9z PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4a9z ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4a9z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a9z OCA], [https://pdbe.org/4a9z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4a9z RCSB], [https://www.ebi.ac.uk/pdbsum/4a9z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4a9z ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[~~http~~://www.uniprot.org/uniprot/P63_HUMAN P63_HUMAN]] Defects in TP63 are the cause of acro-dermato-ungual-lacrimal-tooth syndrome (ADULT syndrome) [MIM:[~~http~~://omim.org/entry/103285 103285]]; a form of ectodermal dysplasia. Ectodermal dysplasias (EDs) constitute a heterogeneous group of developmental disorders affecting tissues of ectodermal origin. EDs are characterized by abnormal development of two or more ectodermal structures such as hair, teeth, nails and sweat glands, with or without any additional clinical sign. Each combination of clinical features represents a different type of ectodermal dysplasia. ADULT syndrome involves ectrodactyly, syndactyly, finger- and toenail dysplasia, hypoplastic breasts and nipples, intensive freckling, lacrimal duct atresia, frontal alopecia, primary hypodontia, and loss of permanent teeth. ADULT differs significantly from EEC3 syndrome by the absence of facial clefting. Defects in TP63 are the cause of ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) [MIM:[~~http~~://omim.org/entry/106260 106260]]. AEC is an autosomal dominant condition characterized by congenital ectodermal dysplasia with coarse, wiry, sparse hair, dystrophic nails, slight hypohidrosis, scalp infections, ankyloblepharon filiform adnatum, maxillary hypoplasia, hypodontia and cleft lip/palate.<ref>PMID:11159940</ref> Defects in TP63 are the cause of ectrodactyly-ectodermal dysplasia-cleft lip/palate syndrome type 3 (EEC3) [MIM:[~~http~~://omim.org/entry/604292 604292]]. EEC3 is an autosomal dominant syndrome characterized by ectrodactyly of hands and feet, ectodermal dysplasia and facial clefting.<ref>PMID:10535733</ref> <ref>PMID:10839977</ref> <ref>PMID:11462173</ref> <ref>PMID:12838557</ref> Defects in TP63 are the cause of split-hand/foot malformation type 4 (SHFM4) [MIM:[~~http~~://omim.org/entry/605289 605289]]. Split-hand/split-foot malformation is a limb malformation involving the central rays of the autopod and presenting with syndactyly, median clefts of the hands and feet, and aplasia and/or hypoplasia of the phalanges, metacarpals, and metatarsals. There is restricted overlap between the mutational spectra of EEC3 and SHFM4.<ref>PMID:10839977</ref> <ref>PMID:11462173</ref> Defects in TP63 are the cause of limb-mammary syndrome (LMS) [MIM:[~~http~~://omim.org/entry/603543 603543]]. LMS is characterized by ectrodactyly, cleft palate and mammary-gland abnormalities.<ref>PMID:11462173</ref> Note=Defects in TP63 are a cause of cervical, colon, head and neck, lung and ovarian cancers. Defects in TP63 are a cause of ectodermal dysplasia Rapp-Hodgkin type (EDRH) [MIM:[~~http~~://omim.org/entry/129400 129400]]; also called Rapp-Hodgkin syndrome or anhidrotic ectodermal dysplasia with cleft lip/palate. Ectodermal dysplasia defines a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. EDRH is characterized by the combination of anhidrotic ectodermal dysplasia, cleft lip, and cleft palate. The clinical syndrome is comprised of a characteristic facies (narrow nose and small mouth), wiry, slow-growing, and uncombable hair, sparse eyelashes and eyebrows, obstructed lacrimal puncta/epiphora, bilateral stenosis of external auditory canals, microsomia, hypodontia, cone-shaped incisors, enamel hypoplasia, dystrophic nails, and cleft lip/cleft palate.<ref>PMID:12939657</ref> <ref>PMID:12766194</ref> <ref>PMID:15200513</ref> <ref>PMID:16740912</ref> Defects in TP63 are the cause of non-syndromic orofacial cleft type 8 (OFC8) [MIM:[~~http~~://omim.org/entry/129400 129400]]. Non-syndromic orofacial cleft is a common birth defect consisting of cleft lips with or without cleft palate. Cleft lips are associated with cleft palate in two-third of cases. A cleft lip can occur on one or both sides and range in severity from a simple notch in the upper lip to a complete opening in the lip extending into the floor of the nostril and involving the upper gum.	+	[[https://www.uniprot.org/uniprot/P63_HUMAN P63_HUMAN]] Defects in TP63 are the cause of acro-dermato-ungual-lacrimal-tooth syndrome (ADULT syndrome) [MIM:[https://omim.org/entry/103285 103285]]; a form of ectodermal dysplasia. Ectodermal dysplasias (EDs) constitute a heterogeneous group of developmental disorders affecting tissues of ectodermal origin. EDs are characterized by abnormal development of two or more ectodermal structures such as hair, teeth, nails and sweat glands, with or without any additional clinical sign. Each combination of clinical features represents a different type of ectodermal dysplasia. ADULT syndrome involves ectrodactyly, syndactyly, finger- and toenail dysplasia, hypoplastic breasts and nipples, intensive freckling, lacrimal duct atresia, frontal alopecia, primary hypodontia, and loss of permanent teeth. ADULT differs significantly from EEC3 syndrome by the absence of facial clefting. Defects in TP63 are the cause of ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) [MIM:[https://omim.org/entry/106260 106260]]. AEC is an autosomal dominant condition characterized by congenital ectodermal dysplasia with coarse, wiry, sparse hair, dystrophic nails, slight hypohidrosis, scalp infections, ankyloblepharon filiform adnatum, maxillary hypoplasia, hypodontia and cleft lip/palate.<ref>PMID:11159940</ref> Defects in TP63 are the cause of ectrodactyly-ectodermal dysplasia-cleft lip/palate syndrome type 3 (EEC3) [MIM:[https://omim.org/entry/604292 604292]]. EEC3 is an autosomal dominant syndrome characterized by ectrodactyly of hands and feet, ectodermal dysplasia and facial clefting.<ref>PMID:10535733</ref> <ref>PMID:10839977</ref> <ref>PMID:11462173</ref> <ref>PMID:12838557</ref> Defects in TP63 are the cause of split-hand/foot malformation type 4 (SHFM4) [MIM:[https://omim.org/entry/605289 605289]]. Split-hand/split-foot malformation is a limb malformation involving the central rays of the autopod and presenting with syndactyly, median clefts of the hands and feet, and aplasia and/or hypoplasia of the phalanges, metacarpals, and metatarsals. There is restricted overlap between the mutational spectra of EEC3 and SHFM4.<ref>PMID:10839977</ref> <ref>PMID:11462173</ref> Defects in TP63 are the cause of limb-mammary syndrome (LMS) [MIM:[https://omim.org/entry/603543 603543]]. LMS is characterized by ectrodactyly, cleft palate and mammary-gland abnormalities.<ref>PMID:11462173</ref> Note=Defects in TP63 are a cause of cervical, colon, head and neck, lung and ovarian cancers. Defects in TP63 are a cause of ectodermal dysplasia Rapp-Hodgkin type (EDRH) [MIM:[https://omim.org/entry/129400 129400]]; also called Rapp-Hodgkin syndrome or anhidrotic ectodermal dysplasia with cleft lip/palate. Ectodermal dysplasia defines a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. EDRH is characterized by the combination of anhidrotic ectodermal dysplasia, cleft lip, and cleft palate. The clinical syndrome is comprised of a characteristic facies (narrow nose and small mouth), wiry, slow-growing, and uncombable hair, sparse eyelashes and eyebrows, obstructed lacrimal puncta/epiphora, bilateral stenosis of external auditory canals, microsomia, hypodontia, cone-shaped incisors, enamel hypoplasia, dystrophic nails, and cleft lip/cleft palate.<ref>PMID:12939657</ref> <ref>PMID:12766194</ref> <ref>PMID:15200513</ref> <ref>PMID:16740912</ref> Defects in TP63 are the cause of non-syndromic orofacial cleft type 8 (OFC8) [MIM:[https://omim.org/entry/129400 129400]]. Non-syndromic orofacial cleft is a common birth defect consisting of cleft lips with or without cleft palate. Cleft lips are associated with cleft palate in two-third of cases. A cleft lip can occur on one or both sides and range in severity from a simple notch in the upper lip to a complete opening in the lip extending into the floor of the nostril and involving the upper gum.
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/P63_HUMAN P63_HUMAN]] Acts as a sequence specific DNA binding transcriptional activator or repressor. The isoforms contain a varying set of transactivation and auto-regulating transactivation inhibiting domains thus showing an isoform specific activity. Isoform 2 activates RIPK4 transcription. May be required in conjunction with TP73/p73 for initiation of p53/TP53 dependent apoptosis in response to genotoxic insults and the presence of activated oncogenes. Involved in Notch signaling by probably inducing JAG1 and JAG2. Plays a role in the regulation of epithelial morphogenesis. The ratio of DeltaN-type and TA*-type isoforms may govern the maintenance of epithelial stem cell compartments and regulate the initiation of epithelial stratification from the undifferentiated embryonal ectoderm. Required for limb formation from the apical ectodermal ridge. Activates transcription of the p21 promoter.<ref>PMID:9774969</ref> <ref>PMID:11641404</ref> <ref>PMID:12446779</ref> <ref>PMID:12446784</ref> <ref>PMID:12374749</ref> <ref>PMID:20123734</ref> <ref>PMID:22197488</ref>	+	[[https://www.uniprot.org/uniprot/P63_HUMAN P63_HUMAN]] Acts as a sequence specific DNA binding transcriptional activator or repressor. The isoforms contain a varying set of transactivation and auto-regulating transactivation inhibiting domains thus showing an isoform specific activity. Isoform 2 activates RIPK4 transcription. May be required in conjunction with TP73/p73 for initiation of p53/TP53 dependent apoptosis in response to genotoxic insults and the presence of activated oncogenes. Involved in Notch signaling by probably inducing JAG1 and JAG2. Plays a role in the regulation of epithelial morphogenesis. The ratio of DeltaN-type and TA*-type isoforms may govern the maintenance of epithelial stem cell compartments and regulate the initiation of epithelial stratification from the undifferentiated embryonal ectoderm. Required for limb formation from the apical ectodermal ridge. Activates transcription of the p21 promoter.<ref>PMID:9774969</ref> <ref>PMID:11641404</ref> <ref>PMID:12446779</ref> <ref>PMID:12446784</ref> <ref>PMID:12374749</ref> <ref>PMID:20123734</ref> <ref>PMID:22197488</ref>

	==See Also==		==See Also==

OCA at 12:41, 1 January 2020

OCA — Wed, 01 Jan 2020 12:41:53 GMT

←Older revision		Revision as of 12:41, 1 January 2020
Line 1:		Line 1:

	==CRYSTAL STRUCTURE OF HUMAN P63 TETRAMERIZATION DOMAIN==		==CRYSTAL STRUCTURE OF HUMAN P63 TETRAMERIZATION DOMAIN==
-	<StructureSection load='4a9z' size='340' side='right' caption='[[4a9z]], [[Resolution\|resolution]] 2.29Å' scene=''>	+	<StructureSection load='4a9z' size='340' side='right'caption='[[4a9z]], [[Resolution\|resolution]] 2.29Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4a9z]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4A9Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4A9Z FirstGlance]. <br>		<table><tr><td colspan='2'>[[4a9z]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4A9Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4A9Z FirstGlance]. <br>
Line 12:		Line 12:
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/P63_HUMAN P63_HUMAN]] Acts as a sequence specific DNA binding transcriptional activator or repressor. The isoforms contain a varying set of transactivation and auto-regulating transactivation inhibiting domains thus showing an isoform specific activity. Isoform 2 activates RIPK4 transcription. May be required in conjunction with TP73/p73 for initiation of p53/TP53 dependent apoptosis in response to genotoxic insults and the presence of activated oncogenes. Involved in Notch signaling by probably inducing JAG1 and JAG2. Plays a role in the regulation of epithelial morphogenesis. The ratio of DeltaN-type and TA*-type isoforms may govern the maintenance of epithelial stem cell compartments and regulate the initiation of epithelial stratification from the undifferentiated embryonal ectoderm. Required for limb formation from the apical ectodermal ridge. Activates transcription of the p21 promoter.<ref>PMID:9774969</ref> <ref>PMID:11641404</ref> <ref>PMID:12446779</ref> <ref>PMID:12446784</ref> <ref>PMID:12374749</ref> <ref>PMID:20123734</ref> <ref>PMID:22197488</ref>		[[http://www.uniprot.org/uniprot/P63_HUMAN P63_HUMAN]] Acts as a sequence specific DNA binding transcriptional activator or repressor. The isoforms contain a varying set of transactivation and auto-regulating transactivation inhibiting domains thus showing an isoform specific activity. Isoform 2 activates RIPK4 transcription. May be required in conjunction with TP73/p73 for initiation of p53/TP53 dependent apoptosis in response to genotoxic insults and the presence of activated oncogenes. Involved in Notch signaling by probably inducing JAG1 and JAG2. Plays a role in the regulation of epithelial morphogenesis. The ratio of DeltaN-type and TA*-type isoforms may govern the maintenance of epithelial stem cell compartments and regulate the initiation of epithelial stratification from the undifferentiated embryonal ectoderm. Required for limb formation from the apical ectodermal ridge. Activates transcription of the p21 promoter.<ref>PMID:9774969</ref> <ref>PMID:11641404</ref> <ref>PMID:12446779</ref> <ref>PMID:12446784</ref> <ref>PMID:12374749</ref> <ref>PMID:20123734</ref> <ref>PMID:22197488</ref>
		+
		+	==See Also==
		+	*[[P63\|P63]]
	== References ==		== References ==
	<references/>		<references/>
Line 17:		Line 20:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Arrowsmith, C H]]		[[Category: Arrowsmith, C H]]
	[[Category: Bountra, C]]		[[Category: Bountra, C]]

OCA at 19:44, 24 January 2018

OCA — Wed, 24 Jan 2018 19:44:38 GMT

←Older revision		Revision as of 19:44, 24 January 2018
Line 12:		Line 12:
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/P63_HUMAN P63_HUMAN]] Acts as a sequence specific DNA binding transcriptional activator or repressor. The isoforms contain a varying set of transactivation and auto-regulating transactivation inhibiting domains thus showing an isoform specific activity. Isoform 2 activates RIPK4 transcription. May be required in conjunction with TP73/p73 for initiation of p53/TP53 dependent apoptosis in response to genotoxic insults and the presence of activated oncogenes. Involved in Notch signaling by probably inducing JAG1 and JAG2. Plays a role in the regulation of epithelial morphogenesis. The ratio of DeltaN-type and TA*-type isoforms may govern the maintenance of epithelial stem cell compartments and regulate the initiation of epithelial stratification from the undifferentiated embryonal ectoderm. Required for limb formation from the apical ectodermal ridge. Activates transcription of the p21 promoter.<ref>PMID:9774969</ref> <ref>PMID:11641404</ref> <ref>PMID:12446779</ref> <ref>PMID:12446784</ref> <ref>PMID:12374749</ref> <ref>PMID:20123734</ref> <ref>PMID:22197488</ref>		[[http://www.uniprot.org/uniprot/P63_HUMAN P63_HUMAN]] Acts as a sequence specific DNA binding transcriptional activator or repressor. The isoforms contain a varying set of transactivation and auto-regulating transactivation inhibiting domains thus showing an isoform specific activity. Isoform 2 activates RIPK4 transcription. May be required in conjunction with TP73/p73 for initiation of p53/TP53 dependent apoptosis in response to genotoxic insults and the presence of activated oncogenes. Involved in Notch signaling by probably inducing JAG1 and JAG2. Plays a role in the regulation of epithelial morphogenesis. The ratio of DeltaN-type and TA*-type isoforms may govern the maintenance of epithelial stem cell compartments and regulate the initiation of epithelial stratification from the undifferentiated embryonal ectoderm. Required for limb formation from the apical ectodermal ridge. Activates transcription of the p21 promoter.<ref>PMID:9774969</ref> <ref>PMID:11641404</ref> <ref>PMID:12446779</ref> <ref>PMID:12446784</ref> <ref>PMID:12374749</ref> <ref>PMID:20123734</ref> <ref>PMID:22197488</ref>
-
-	==See Also==
-	*[[P63\|P63]]
	== References ==		== References ==
	<references/>		<references/>
Line 24:		Line 21:
	[[Category: Chaikuad, A]]		[[Category: Chaikuad, A]]
	[[Category: Coutandin, D]]		[[Category: Coutandin, D]]
-	[[Category: Delft, F ~~Von~~]]	+	[[Category: Delft, F von]]
	[[Category: Dotsch, V]]		[[Category: Dotsch, V]]
	[[Category: Edwards, A M]]		[[Category: Edwards, A M]]

OCA at 09:45, 4 August 2016

OCA — Thu, 04 Aug 2016 09:45:54 GMT

←Older revision		Revision as of 09:45, 4 August 2016
Line 1:		Line 1:
		+
	==CRYSTAL STRUCTURE OF HUMAN P63 TETRAMERIZATION DOMAIN==		==CRYSTAL STRUCTURE OF HUMAN P63 TETRAMERIZATION DOMAIN==
	<StructureSection load='4a9z' size='340' side='right' caption='[[4a9z]], [[Resolution\|resolution]] 2.29Å' scene=''>		<StructureSection load='4a9z' size='340' side='right' caption='[[4a9z]], [[Resolution\|resolution]] 2.29Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4a9z]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4A9Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4A9Z FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4a9z]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4A9Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4A9Z FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PE4:2-{2-[2-(2-{2-[2-(2-ETHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHOXY]-ETHOXY}-ETHANOL'>PE4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PE4:2-{2-[2-(2-{2-[2-(2-ETHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHOXY]-ETHOXY}-ETHANOL'>PE4</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2y9t\|2y9t]], [[3zy0\|3zy0]], [[3zy1\|3zy1]], [[1rg6\|1rg6]], [[2y9u\|2y9u]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2y9t\|2y9t]], [[3zy0\|3zy0]], [[3zy1\|3zy1]], [[1rg6\|1rg6]], [[2y9u\|2y9u]]</td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4a9z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a9z OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4a9z RCSB], [http://www.ebi.ac.uk/pdbsum/4a9z PDBsum]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4a9z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a9z OCA], [http://pdbe.org/4a9z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4a9z RCSB], [http://www.ebi.ac.uk/pdbsum/4a9z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4a9z ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 11:		Line 12:
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/P63_HUMAN P63_HUMAN]] Acts as a sequence specific DNA binding transcriptional activator or repressor. The isoforms contain a varying set of transactivation and auto-regulating transactivation inhibiting domains thus showing an isoform specific activity. Isoform 2 activates RIPK4 transcription. May be required in conjunction with TP73/p73 for initiation of p53/TP53 dependent apoptosis in response to genotoxic insults and the presence of activated oncogenes. Involved in Notch signaling by probably inducing JAG1 and JAG2. Plays a role in the regulation of epithelial morphogenesis. The ratio of DeltaN-type and TA*-type isoforms may govern the maintenance of epithelial stem cell compartments and regulate the initiation of epithelial stratification from the undifferentiated embryonal ectoderm. Required for limb formation from the apical ectodermal ridge. Activates transcription of the p21 promoter.<ref>PMID:9774969</ref> <ref>PMID:11641404</ref> <ref>PMID:12446779</ref> <ref>PMID:12446784</ref> <ref>PMID:12374749</ref> <ref>PMID:20123734</ref> <ref>PMID:22197488</ref>		[[http://www.uniprot.org/uniprot/P63_HUMAN P63_HUMAN]] Acts as a sequence specific DNA binding transcriptional activator or repressor. The isoforms contain a varying set of transactivation and auto-regulating transactivation inhibiting domains thus showing an isoform specific activity. Isoform 2 activates RIPK4 transcription. May be required in conjunction with TP73/p73 for initiation of p53/TP53 dependent apoptosis in response to genotoxic insults and the presence of activated oncogenes. Involved in Notch signaling by probably inducing JAG1 and JAG2. Plays a role in the regulation of epithelial morphogenesis. The ratio of DeltaN-type and TA*-type isoforms may govern the maintenance of epithelial stem cell compartments and regulate the initiation of epithelial stratification from the undifferentiated embryonal ectoderm. Required for limb formation from the apical ectodermal ridge. Activates transcription of the p21 promoter.<ref>PMID:9774969</ref> <ref>PMID:11641404</ref> <ref>PMID:12446779</ref> <ref>PMID:12446784</ref> <ref>PMID:12374749</ref> <ref>PMID:20123734</ref> <ref>PMID:22197488</ref>
		+
		+	==See Also==
		+	*[[P63\|P63]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Arrowsmith, C H]]		[[Category: Arrowsmith, C H]]
	[[Category: Bountra, C]]		[[Category: Bountra, C]]

OCA at 08:47, 21 December 2014

OCA — Sun, 21 Dec 2014 08:47:13 GMT

←Older revision		Revision as of 08:47, 21 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_4a9z~~\| ~~PDB~~=4a9z \| ~~SCENE~~= }}	+	==CRYSTAL STRUCTURE OF HUMAN P63 TETRAMERIZATION DOMAIN==
-	===~~CRYSTAL STRUCTURE OF HUMAN P63 TETRAMERIZATION DOMAIN~~===	+	<StructureSection load='4a9z' size='340' side='right' caption='[[4a9z]], [[Resolution\|resolution]] 2.29Å' scene=''>
-		+	== Structural highlights ==
-	==Disease==	+	<table><tr><td colspan='2'>[[4a9z]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4A9Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4A9Z FirstGlance]. <br>
-	[[http://www.uniprot.org/uniprot/P63_HUMAN P63_HUMAN]] Defects in TP63 are the cause of acro-dermato-ungual-lacrimal-tooth syndrome (ADULT syndrome) [MIM:[http://omim.org/entry/103285 103285]]; a form of ectodermal dysplasia. Ectodermal dysplasias (EDs) constitute a heterogeneous group of developmental disorders affecting tissues of ectodermal origin. EDs are characterized by abnormal development of two or more ectodermal structures such as hair, teeth, nails and sweat glands, with or without any additional clinical sign. Each combination of clinical features represents a different type of ectodermal dysplasia. ADULT syndrome involves ectrodactyly, syndactyly, finger- and toenail dysplasia, hypoplastic breasts and nipples, intensive freckling, lacrimal duct atresia, frontal alopecia, primary hypodontia, and loss of permanent teeth. ADULT differs significantly from EEC3 syndrome by the absence of facial clefting. Defects in TP63 are the cause of ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) [MIM:[http://omim.org/entry/106260 106260]]. AEC is an autosomal dominant condition characterized by congenital ectodermal dysplasia with coarse, wiry, sparse hair, dystrophic nails, slight hypohidrosis, scalp infections, ankyloblepharon filiform adnatum, maxillary hypoplasia, hypodontia and cleft lip/palate.<ref>PMID:11159940</ref> Defects in TP63 are the cause of ectrodactyly-ectodermal dysplasia-cleft lip/palate syndrome type 3 (EEC3) [MIM:[http://omim.org/entry/604292 604292]]. EEC3 is an autosomal dominant syndrome characterized by ectrodactyly of hands and feet, ectodermal dysplasia and facial clefting.<ref>PMID:10535733</ref><ref>PMID:10839977</ref><ref>PMID:11462173</ref><ref>PMID:12838557</ref> Defects in TP63 are the cause of split-hand/foot malformation type 4 (SHFM4) [MIM:[http://omim.org/entry/605289 605289]]. Split-hand/split-foot malformation is a limb malformation involving the central rays of the autopod and presenting with syndactyly, median clefts of the hands and feet, and aplasia and/or hypoplasia of the phalanges, metacarpals, and metatarsals. There is restricted overlap between the mutational spectra of EEC3 and SHFM4.<ref>PMID:10839977</ref><ref>PMID:11462173</ref> Defects in TP63 are the cause of limb-mammary syndrome (LMS) [MIM:[http://omim.org/entry/603543 603543]]. LMS is characterized by ectrodactyly, cleft palate and mammary-gland abnormalities.<ref>PMID:11462173</ref> Note=Defects in TP63 are a cause of cervical, colon, head and neck, lung and ovarian cancers. Defects in TP63 are a cause of ectodermal dysplasia Rapp-Hodgkin type (EDRH) [MIM:[http://omim.org/entry/129400 129400]]; also called Rapp-Hodgkin syndrome or anhidrotic ectodermal dysplasia with cleft lip/palate. Ectodermal dysplasia defines a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. EDRH is characterized by the combination of anhidrotic ectodermal dysplasia, cleft lip, and cleft palate. The clinical syndrome is comprised of a characteristic facies (narrow nose and small mouth), wiry, slow-growing, and uncombable hair, sparse eyelashes and eyebrows, obstructed lacrimal puncta/epiphora, bilateral stenosis of external auditory canals, microsomia, hypodontia, cone-shaped incisors, enamel hypoplasia, dystrophic nails, and cleft lip/cleft palate.<ref>PMID:12939657</ref><ref>PMID:12766194</ref><ref>PMID:15200513</ref><ref>PMID:16740912</ref> Defects in TP63 are the cause of non-syndromic orofacial cleft type 8 (OFC8) [MIM:[http://omim.org/entry/129400 129400]]. Non-syndromic orofacial cleft is a common birth defect consisting of cleft lips with or without cleft palate. Cleft lips are associated with cleft palate in two-third of cases. A cleft lip can occur on one or both sides and range in severity from a simple notch in the upper lip to a complete opening in the lip extending into the floor of the nostril and involving the upper gum.	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PE4:2-{2-[2-(2-{2-[2-(2-ETHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHOXY]-ETHOXY}-ETHANOL'>PE4</scene></td></tr>
-		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2y9t\|2y9t]], [[3zy0\|3zy0]], [[3zy1\|3zy1]], [[1rg6\|1rg6]], [[2y9u\|2y9u]]</td></tr>
-	==Function==	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4a9z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a9z OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4a9z RCSB], [http://www.ebi.ac.uk/pdbsum/4a9z PDBsum]</span></td></tr>
-	[[http://www.uniprot.org/uniprot/P63_HUMAN P63_HUMAN]] Acts as a sequence specific DNA binding transcriptional activator or repressor. The isoforms contain a varying set of transactivation and auto-regulating transactivation inhibiting domains thus showing an isoform specific activity. Isoform 2 activates RIPK4 transcription. May be required in conjunction with TP73/p73 for initiation of p53/TP53 dependent apoptosis in response to genotoxic insults and the presence of activated oncogenes. Involved in Notch signaling by probably inducing JAG1 and JAG2. Plays a role in the regulation of epithelial morphogenesis. The ratio of DeltaN-type and TA*-type isoforms may govern the maintenance of epithelial stem cell compartments and regulate the initiation of epithelial stratification from the undifferentiated embryonal ectoderm. Required for limb formation from the apical ectodermal ridge. Activates transcription of the p21 promoter.<ref>PMID:9774969</ref><ref>PMID:11641404</ref><ref>PMID:12446779</ref><ref>PMID:12446784</ref><ref>PMID:12374749</ref><ref>PMID:20123734</ref><ref>PMID:22197488</ref>	+	</table>
-		+	== Disease ==
-	==~~About this Structure==~~	+	[[http://www.uniprot.org/uniprot/P63_HUMAN P63_HUMAN]] Defects in TP63 are the cause of acro-dermato-ungual-lacrimal-tooth syndrome (ADULT syndrome) [MIM:[http://omim.org/entry/103285 103285]]; a form of ectodermal dysplasia. Ectodermal dysplasias (EDs) constitute a heterogeneous group of developmental disorders affecting tissues of ectodermal origin. EDs are characterized by abnormal development of two or more ectodermal structures such as hair, teeth, nails and sweat glands, with or without any additional clinical sign. Each combination of clinical features represents a different type of ectodermal dysplasia. ADULT syndrome involves ectrodactyly, syndactyly, finger- and toenail dysplasia, hypoplastic breasts and nipples, intensive freckling, lacrimal duct atresia, frontal alopecia, primary hypodontia, and loss of permanent teeth. ADULT differs significantly from EEC3 syndrome by the absence of facial clefting. Defects in TP63 are the cause of ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) [MIM:[http://omim.org/entry/106260 106260]]. AEC is an autosomal dominant condition characterized by congenital ectodermal dysplasia with coarse, wiry, sparse hair, dystrophic nails, slight hypohidrosis, scalp infections, ankyloblepharon filiform adnatum, maxillary hypoplasia, hypodontia and cleft lip/palate.<ref>PMID:11159940</ref> Defects in TP63 are the cause of ectrodactyly-ectodermal dysplasia-cleft lip/palate syndrome type 3 (EEC3) [MIM:[http://omim.org/entry/604292 604292]]. EEC3 is an autosomal dominant syndrome characterized by ectrodactyly of hands and feet, ectodermal dysplasia and facial clefting.<ref>PMID:10535733</ref> <ref>PMID:10839977</ref> <ref>PMID:11462173</ref> <ref>PMID:12838557</ref> Defects in TP63 are the cause of split-hand/foot malformation type 4 (SHFM4) [MIM:[http://omim.org/entry/605289 605289]]. Split-hand/split-foot malformation is a limb malformation involving the central rays of the autopod and presenting with syndactyly, median clefts of the hands and feet, and aplasia and/or hypoplasia of the phalanges, metacarpals, and metatarsals. There is restricted overlap between the mutational spectra of EEC3 and SHFM4.<ref>PMID:10839977</ref> <ref>PMID:11462173</ref> Defects in TP63 are the cause of limb-mammary syndrome (LMS) [MIM:[http://omim.org/entry/603543 603543]]. LMS is characterized by ectrodactyly, cleft palate and mammary-gland abnormalities.<ref>PMID:11462173</ref> Note=Defects in TP63 are a cause of cervical, colon, head and neck, lung and ovarian cancers. Defects in TP63 are a cause of ectodermal dysplasia Rapp-Hodgkin type (EDRH) [MIM:[http://omim.org/entry/129400 129400]]; also called Rapp-Hodgkin syndrome or anhidrotic ectodermal dysplasia with cleft lip/palate. Ectodermal dysplasia defines a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. EDRH is characterized by the combination of anhidrotic ectodermal dysplasia, cleft lip, and cleft palate. The clinical syndrome is comprised of a characteristic facies (narrow nose and small mouth), wiry, slow-growing, and uncombable hair, sparse eyelashes and eyebrows, obstructed lacrimal puncta/epiphora, bilateral stenosis of external auditory canals, microsomia, hypodontia, cone-shaped incisors, enamel hypoplasia, dystrophic nails, and cleft lip/cleft palate.<ref>PMID:12939657</ref> <ref>PMID:12766194</ref> <ref>PMID:15200513</ref> <ref>PMID:16740912</ref> Defects in TP63 are the cause of non-syndromic orofacial cleft type 8 (OFC8) [MIM:[http://omim.org/entry/129400 129400]]. Non-syndromic orofacial cleft is a common birth defect consisting of cleft lips with or without cleft palate. Cleft lips are associated with cleft palate in two-third of cases. A cleft lip can occur on one or both sides and range in severity from a simple notch in the upper lip to a complete opening in the lip extending into the floor of the nostril and involving the upper gum.
-	[[4a9z]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4A9Z OCA].	+	== Function ==
-		+	[[http://www.uniprot.org/uniprot/P63_HUMAN P63_HUMAN]] Acts as a sequence specific DNA binding transcriptional activator or repressor. The isoforms contain a varying set of transactivation and auto-regulating transactivation inhibiting domains thus showing an isoform specific activity. Isoform 2 activates RIPK4 transcription. May be required in conjunction with TP73/p73 for initiation of p53/TP53 dependent apoptosis in response to genotoxic insults and the presence of activated oncogenes. Involved in Notch signaling by probably inducing JAG1 and JAG2. Plays a role in the regulation of epithelial morphogenesis. The ratio of DeltaN-type and TA*-type isoforms may govern the maintenance of epithelial stem cell compartments and regulate the initiation of epithelial stratification from the undifferentiated embryonal ectoderm. Required for limb formation from the apical ectodermal ridge. Activates transcription of the p21 promoter.<ref>PMID:9774969</ref> <ref>PMID:11641404</ref> <ref>PMID:12446779</ref> <ref>PMID:12446784</ref> <ref>PMID:12374749</ref> <ref>PMID:20123734</ref> <ref>PMID:22197488</ref>
-	~~==Reference~~==	+	== References ==
-	<references ~~group="xtra"~~/><~~references~~/>	+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Arrowsmith, C H.]]	+	[[Category: Arrowsmith, C H]]
-	[[Category: Bountra, C.]]	+	[[Category: Bountra, C]]
-	[[Category: Chaikuad, A.]]	+	[[Category: Chaikuad, A]]
-	[[Category: Coutandin, D.]]	+	[[Category: Coutandin, D]]
-	[[Category: Delft, F Von.]]	+	[[Category: Delft, F Von]]
-	[[Category: Dotsch, V.]]	+	[[Category: Dotsch, V]]
-	[[Category: Edwards, A M.]]	+	[[Category: Edwards, A M]]
-	[[Category: Knapp, S.]]	+	[[Category: Knapp, S]]
-	[[Category: Muniz, J R.C.]]	+	[[Category: Muniz, J R.C]]
-	[[Category: Salah, E.]]	+	[[Category: Salah, E]]
-	[[Category: Vollmar, M.]]	+	[[Category: Vollmar, M]]
-	[[Category: Weigelt, J.]]	+	[[Category: Weigelt, J]]
	[[Category: Transcription]]		[[Category: Transcription]]

OCA: Protected "4a9z" [edit=sysop:move=sysop]

OCA — Sun, 24 Mar 2013 12:01:49 GMT

Protected "4a9z" [edit=sysop:move=sysop]

←Older revision

Revision as of 12:01, 24 March 2013

OCA: New page: {{STRUCTURE_4a9z| PDB=4a9z | SCENE= }} ===CRYSTAL STRUCTURE OF HUMAN P63 TETRAMERIZATION DOMAIN=== ==Disease== http://www.uniprot.org/uniprot/P63_HUMAN P63_HUMAN Defects in TP63 ...

OCA — Sun, 24 Mar 2013 12:01:47 GMT

New page: {{STRUCTURE_4a9z| PDB=4a9z | SCENE= }} ===CRYSTAL STRUCTURE OF HUMAN P63 TETRAMERIZATION DOMAIN=== ==Disease== http://www.uniprot.org/uniprot/P63_HUMAN P63_HUMAN Defects in TP63 ...

New page

{{STRUCTURE_4a9z| PDB=4a9z | SCENE= }}
===CRYSTAL STRUCTURE OF HUMAN P63 TETRAMERIZATION DOMAIN===

==Disease==
[[http://www.uniprot.org/uniprot/P63_HUMAN P63_HUMAN]] Defects in TP63 are the cause of acro-dermato-ungual-lacrimal-tooth syndrome (ADULT syndrome) [MIM:[http://omim.org/entry/103285 103285]]; a form of ectodermal dysplasia. Ectodermal dysplasias (EDs) constitute a heterogeneous group of developmental disorders affecting tissues of ectodermal origin. EDs are characterized by abnormal development of two or more ectodermal structures such as hair, teeth, nails and sweat glands, with or without any additional clinical sign. Each combination of clinical features represents a different type of ectodermal dysplasia. ADULT syndrome involves ectrodactyly, syndactyly, finger- and toenail dysplasia, hypoplastic breasts and nipples, intensive freckling, lacrimal duct atresia, frontal alopecia, primary hypodontia, and loss of permanent teeth. ADULT differs significantly from EEC3 syndrome by the absence of facial clefting. Defects in TP63 are the cause of ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) [MIM:[http://omim.org/entry/106260 106260]]. AEC is an autosomal dominant condition characterized by congenital ectodermal dysplasia with coarse, wiry, sparse hair, dystrophic nails, slight hypohidrosis, scalp infections, ankyloblepharon filiform adnatum, maxillary hypoplasia, hypodontia and cleft lip/palate.<ref>PMID:11159940</ref> Defects in TP63 are the cause of ectrodactyly-ectodermal dysplasia-cleft lip/palate syndrome type 3 (EEC3) [MIM:[http://omim.org/entry/604292 604292]]. EEC3 is an autosomal dominant syndrome characterized by ectrodactyly of hands and feet, ectodermal dysplasia and facial clefting.<ref>PMID:10535733</ref><ref>PMID:10839977</ref><ref>PMID:11462173</ref><ref>PMID:12838557</ref> Defects in TP63 are the cause of split-hand/foot malformation type 4 (SHFM4) [MIM:[http://omim.org/entry/605289 605289]]. Split-hand/split-foot malformation is a limb malformation involving the central rays of the autopod and presenting with syndactyly, median clefts of the hands and feet, and aplasia and/or hypoplasia of the phalanges, metacarpals, and metatarsals. There is restricted overlap between the mutational spectra of EEC3 and SHFM4.<ref>PMID:10839977</ref><ref>PMID:11462173</ref> Defects in TP63 are the cause of limb-mammary syndrome (LMS) [MIM:[http://omim.org/entry/603543 603543]]. LMS is characterized by ectrodactyly, cleft palate and mammary-gland abnormalities.<ref>PMID:11462173</ref> Note=Defects in TP63 are a cause of cervical, colon, head and neck, lung and ovarian cancers. Defects in TP63 are a cause of ectodermal dysplasia Rapp-Hodgkin type (EDRH) [MIM:[http://omim.org/entry/129400 129400]]; also called Rapp-Hodgkin syndrome or anhidrotic ectodermal dysplasia with cleft lip/palate. Ectodermal dysplasia defines a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. EDRH is characterized by the combination of anhidrotic ectodermal dysplasia, cleft lip, and cleft palate. The clinical syndrome is comprised of a characteristic facies (narrow nose and small mouth), wiry, slow-growing, and uncombable hair, sparse eyelashes and eyebrows, obstructed lacrimal puncta/epiphora, bilateral stenosis of external auditory canals, microsomia, hypodontia, cone-shaped incisors, enamel hypoplasia, dystrophic nails, and cleft lip/cleft palate.<ref>PMID:12939657</ref><ref>PMID:12766194</ref><ref>PMID:15200513</ref><ref>PMID:16740912</ref> Defects in TP63 are the cause of non-syndromic orofacial cleft type 8 (OFC8) [MIM:[http://omim.org/entry/129400 129400]]. Non-syndromic orofacial cleft is a common birth defect consisting of cleft lips with or without cleft palate. Cleft lips are associated with cleft palate in two-third of cases. A cleft lip can occur on one or both sides and range in severity from a simple notch in the upper lip to a complete opening in the lip extending into the floor of the nostril and involving the upper gum.

==Function==
[[http://www.uniprot.org/uniprot/P63_HUMAN P63_HUMAN]] Acts as a sequence specific DNA binding transcriptional activator or repressor. The isoforms contain a varying set of transactivation and auto-regulating transactivation inhibiting domains thus showing an isoform specific activity. Isoform 2 activates RIPK4 transcription. May be required in conjunction with TP73/p73 for initiation of p53/TP53 dependent apoptosis in response to genotoxic insults and the presence of activated oncogenes. Involved in Notch signaling by probably inducing JAG1 and JAG2. Plays a role in the regulation of epithelial morphogenesis. The ratio of DeltaN-type and TA*-type isoforms may govern the maintenance of epithelial stem cell compartments and regulate the initiation of epithelial stratification from the undifferentiated embryonal ectoderm. Required for limb formation from the apical ectodermal ridge. Activates transcription of the p21 promoter.<ref>PMID:9774969</ref><ref>PMID:11641404</ref><ref>PMID:12446779</ref><ref>PMID:12446784</ref><ref>PMID:12374749</ref><ref>PMID:20123734</ref><ref>PMID:22197488</ref>

==About this Structure==
[[4a9z]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4A9Z OCA].

==Reference==
<references group="xtra"/><references/>
[[Category: Homo sapiens]]
[[Category: Arrowsmith, C H.]]
[[Category: Bountra, C.]]
[[Category: Chaikuad, A.]]
[[Category: Coutandin, D.]]
[[Category: Delft, F Von.]]
[[Category: Dotsch, V.]]
[[Category: Edwards, A M.]]
[[Category: Knapp, S.]]
[[Category: Muniz, J R.C.]]
[[Category: Salah, E.]]
[[Category: Vollmar, M.]]
[[Category: Weigelt, J.]]
[[Category: Transcription]]