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2kb9

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Revision as of 10:25, 18 July 2018

Human Jagged-1, exon 6

Structural highlights

2kb9 is a 1 chain structure. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	2vj2
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[JAG1_HUMAN] Defects in JAG1 are the cause of Alagille syndrome type 1 (ALGS1) [MIM:118450]. Alagille syndrome is an autosomal dominant multisystem disorder defined clinically by hepatic bile duct paucity and cholestasis in association with cardiac, skeletal, and ophthalmologic manifestations. There are characteristic facial features and less frequent clinical involvement of the renal and vascular systems.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10] ^[11] ^[12] ^[13] Defects in JAG1 are a cause of tetralogy of Fallot (TOF) [MIM:187500]. TOF is a congenital heart anomaly which consists of pulmonary stenosis, ventricular septal defect, dextroposition of the aorta (aorta is on the right side instead of the left) and hypertrophy of the right ventricle. This condition results in a blue baby at birth due to inadequate oxygenation. Surgical correction is emergent.^[14] ^[15]

Function

[JAG1_HUMAN] Ligand for multiple Notch receptors and involved in the mediation of Notch signaling. May be involved in cell-fate decisions during hematopoiesis. Seems to be involved in early and late stages of mammalian cardiovascular development. Inhibits myoblast differentiation (By similarity). Enhances fibroblast growth factor-induced angiogenesis (in vitro).^[16] ^[17]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

ABSTRACT: BACKGROUND: Notch signaling drives developmental processes in all metazoans. The receptor binding region of the human Notch ligand Jagged-1 is made of a DSL (Delta/Serrate/Lag-2) domain and two atypical epidermal growth factor (EGF) repeats encoded by two exons, exon 5 and 6, which are out of phase with respect to the EGF domain boundaries. RESULTS: We determined the 1H-NMR solution structure of the polypeptide encoded by exon 6 of JAG1 and spanning the C-terminal region of EGF1 and the entire EGF2. We show that this single, evolutionary conserved exon defines an autonomous structural unit that, despite the minimal structural context, closely matches the structure of the same region in the entire receptor binding module. CONCLUSIONS: In eukaryotic genomes, exon and domain boundaries usually coincide. We report a case study where this assertion does not hold, and show that the autonomously folding, structural unit is delimited by exon boundaries, rather than by predicted domain boundaries.

Exon 6 of human JAG1 encodes a conserved structural unit.,Pintar A, Guarnaccia C, Dhir S, Pongor S BMC Struct Biol. 2009 Jul 8;9(1):43. PMID:19586525^[18]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Li L, Krantz ID, Deng Y, Genin A, Banta AB, Collins CC, Qi M, Trask BJ, Kuo WL, Cochran J, Costa T, Pierpont ME, Rand EB, Piccoli DA, Hood L, Spinner NB. Alagille syndrome is caused by mutations in human Jagged1, which encodes a ligand for Notch1. Nat Genet. 1997 Jul;16(3):243-51. PMID:9207788 doi:10.1038/ng0797-243
↑ Oda T, Elkahloun AG, Pike BL, Okajima K, Krantz ID, Genin A, Piccoli DA, Meltzer PS, Spinner NB, Collins FS, Chandrasekharappa SC. Mutations in the human Jagged1 gene are responsible for Alagille syndrome. Nat Genet. 1997 Jul;16(3):235-42. PMID:9207787 doi:10.1038/ng0797-235
↑ Krantz ID, Colliton RP, Genin A, Rand EB, Li L, Piccoli DA, Spinner NB. Spectrum and frequency of jagged1 (JAG1) mutations in Alagille syndrome patients and their families. Am J Hum Genet. 1998 Jun;62(6):1361-9. PMID:9585603 doi:S0002-9297(07)62777-3
↑ Crosnier C, Driancourt C, Raynaud N, Dhorne-Pollet S, Pollet N, Bernard O, Hadchouel M, Meunier-Rotival M. Mutations in JAGGED1 gene are predominantly sporadic in Alagille syndrome. Gastroenterology. 1999 May;116(5):1141-8. PMID:10220506
↑ Pilia G, Uda M, Macis D, Frau F, Crisponi L, Balli F, Barbera C, Colombo C, Frediani T, Gatti R, Iorio R, Marazzi MG, Marcellini M, Musumeci S, Nebbia G, Vajro P, Ruffa G, Zancan L, Cao A, DeVirgilis S. Jagged-1 mutation analysis in Italian Alagille syndrome patients. Hum Mutat. 1999;14(5):394-400. PMID:10533065 doi:<394::AID-HUMU5>3.0.CO;2-1 10.1002/(SICI)1098-1004(199911)14:5<394::AID-HUMU5>3.0.CO;2-1
↑ Heritage ML, MacMillan JC, Colliton RP, Genin A, Spinner NB, Anderson GJ. Jagged1 (JAG1) mutation detection in an Australian Alagille syndrome population. Hum Mutat. 2000 Nov;16(5):408-16. PMID:11058898 doi:<408::AID-HUMU5>3.0.CO;2-9 10.1002/1098-1004(200011)16:5<408::AID-HUMU5>3.0.CO;2-9
↑ Morrissette JD, Colliton RP, Spinner NB. Defective intracellular transport and processing of JAG1 missense mutations in Alagille syndrome. Hum Mol Genet. 2001 Feb 15;10(4):405-13. PMID:11157803
↑ Crosnier C, Driancourt C, Raynaud N, Hadchouel M, Meunier-Rotival M. Fifteen novel mutations in the JAGGED1 gene of patients with Alagille syndrome. Hum Mutat. 2001;17(1):72-3. PMID:11139247 doi:<72::AID-HUMU11>3.0.CO;2-U 10.1002/1098-1004(2001)17:1<72::AID-HUMU11>3.0.CO;2-U
↑ Colliton RP, Bason L, Lu FM, Piccoli DA, Krantz ID, Spinner NB. Mutation analysis of Jagged1 (JAG1) in Alagille syndrome patients. Hum Mutat. 2001 Feb;17(2):151-2. PMID:11180599 doi:<151::AID-HUMU8>3.0.CO;2-T 10.1002/1098-1004(200102)17:2<151::AID-HUMU8>3.0.CO;2-T
↑ Heritage ML, MacMillan JC, Anderson GJ. DHPLC mutation analysis of Jagged1 (JAG1) reveals six novel mutations in Australian alagille syndrome patients. Hum Mutat. 2002 Dec;20(6):481. PMID:12442286 doi:10.1002/humu.9095
↑ Ropke A, Kujat A, Graber M, Giannakudis J, Hansmann I. Identification of 36 novel Jagged1 (JAG1) mutations in patients with Alagille syndrome. Hum Mutat. 2003 Jan;21(1):100. PMID:12497640 doi:10.1002/humu.9102
↑ Jurkiewicz D, Popowska E, Glaser C, Hansmann I, Krajewska-Walasek M. Twelve novel JAG1 gene mutations in Polish Alagille syndrome patients. Hum Mutat. 2005 Mar;25(3):321. PMID:15712272 doi:10.1002/humu.9313
↑ Warthen DM, Moore EC, Kamath BM, Morrissette JJ, Sanchez-Lara PA, Piccoli DA, Krantz ID, Spinner NB. Jagged1 (JAG1) mutations in Alagille syndrome: increasing the mutation detection rate. Hum Mutat. 2006 May;27(5):436-43. PMID:16575836 doi:10.1002/humu.20310
↑ Oda T, Elkahloun AG, Pike BL, Okajima K, Krantz ID, Genin A, Piccoli DA, Meltzer PS, Spinner NB, Collins FS, Chandrasekharappa SC. Mutations in the human Jagged1 gene are responsible for Alagille syndrome. Nat Genet. 1997 Jul;16(3):235-42. PMID:9207787 doi:10.1038/ng0797-235
↑ Eldadah ZA, Hamosh A, Biery NJ, Montgomery RA, Duke M, Elkins R, Dietz HC. Familial Tetralogy of Fallot caused by mutation in the jagged1 gene. Hum Mol Genet. 2001 Jan 15;10(2):163-9. PMID:11152664
↑ Li L, Milner LA, Deng Y, Iwata M, Banta A, Graf L, Marcovina S, Friedman C, Trask BJ, Hood L, Torok-Storb B. The human homolog of rat Jagged1 expressed by marrow stroma inhibits differentiation of 32D cells through interaction with Notch1. Immunity. 1998 Jan;8(1):43-55. PMID:9462510
↑ Cordle J, Johnson S, Tay JZ, Roversi P, Wilkin MB, de Madrid BH, Shimizu H, Jensen S, Whiteman P, Jin B, Redfield C, Baron M, Lea SM, Handford PA. A conserved face of the Jagged/Serrate DSL domain is involved in Notch trans-activation and cis-inhibition. Nat Struct Mol Biol. 2008 Aug;15(8):849-57. Epub 2008 Jul 27. PMID:18660822 doi:10.1038/nsmb.1457
↑ Pintar A, Guarnaccia C, Dhir S, Pongor S. Exon 6 of human JAG1 encodes a conserved structural unit. BMC Struct Biol. 2009 Jul 8;9(1):43. PMID:19586525 doi:1472-6807-9-43

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2kb9"

@@ Line 1: / Line 1: @@
 ==Human Jagged-1, exon 6==
 <StructureSection load='2kb9' size='340' side='right' caption='[[2kb9]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[2kb9]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KB9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2KB9 FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2vj2|2vj2]]</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=2kb9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kb9 OCA], [http://pdbe.org/2kb9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2kb9 RCSB], [http://www.ebi.ac.uk/pdbsum/2kb9 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=2kb9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kb9 OCA], [http://pdbe.org/2kb9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2kb9 RCSB], [http://www.ebi.ac.uk/pdbsum/2kb9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2kb9 ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 14: / Line 15: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kb/2kb9_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kb/2kb9_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 36: / Line 37: @@
 [[Category: Pintar, A]]
 [[Category: Pongor, S]]
+[[Category: Calcium]]
 [[Category: Developmental protein]]
 [[Category: Disease mutation]]
@@ Line 44: / Line 46: @@
 [[Category: Notch signaling]]
 [[Category: Notch signaling pathway]]
+[[Category: Polymorphism]]
 [[Category: Protein binding]]
 [[Category: Transmembrane]]

2kb9

From Proteopedia

Revision as of 10:25, 18 July 2018

Human Jagged-1, exon 6

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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