6sf2: Difference between revisions

Revision as of 06:54, 8 April 2020

Ternary complex of human bone morphogenetic protein 9 (BMP9) growth factor domain, its prodomain and extracellular domain of activin receptor-like kinase 1 (ALK1).

Structural highlights

6sf2 is a 6 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	NAG
Related:	6sf1, 6sf3
Activity:	Receptor protein serine/threonine kinase, with EC number 2.7.11.30
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[ACVL1_HUMAN] Defects in ACVRL1 are the cause of hereditary hemorrhagic telangiectasia type 2 (HHT2) [MIM:600376]; also known as Osler-Rendu-Weber syndrome 2 (ORW2). HHT2 is an autosomal dominant multisystemic vascular dysplasia, characterized by recurrent epistaxis, muco-cutaneous telangiectases, gastro-intestinal hemorrhage, and pulmonary, cerebral and hepatic arteriovenous malformations; all secondary manifestations of the underlying vascular dysplasia.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9]

Function

[ACVL1_HUMAN] Type I receptor for TGF-beta family ligands BMP9/GDF2 and BMP10 and important regulator of normal blood vessel development. On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. May bind activin as well.^[10] ^[11] [GDF2_HUMAN] Potent circulating inhibitor of angiogenesis. Could be involved in bone formation. Signals through the type I activin receptor ACVRL1 but not other Alks.^[12] ^[13]

References

↑ Berg JN, Gallione CJ, Stenzel TT, Johnson DW, Allen WP, Schwartz CE, Jackson CE, Porteous ME, Marchuk DA. The activin receptor-like kinase 1 gene: genomic structure and mutations in hereditary hemorrhagic telangiectasia type 2. Am J Hum Genet. 1997 Jul;61(1):60-7. PMID:9245985 doi:S0002-9297(07)64277-3
↑ Johnson DW, Berg JN, Baldwin MA, Gallione CJ, Marondel I, Yoon SJ, Stenzel TT, Speer M, Pericak-Vance MA, Diamond A, Guttmacher AE, Jackson CE, Attisano L, Kucherlapati R, Porteous ME, Marchuk DA. Mutations in the activin receptor-like kinase 1 gene in hereditary haemorrhagic telangiectasia type 2. Nat Genet. 1996 Jun;13(2):189-95. PMID:8640225 doi:10.1038/ng0696-189
↑ Klaus DJ, Gallione CJ, Anthony K, Yeh EY, Yu J, Lux A, Johnson DW, Marchuk DA. Novel missense and frameshift mutations in the activin receptor-like kinase-1 gene in hereditary hemorrhagic telangiectasia. Mutations in brief no. 164. Online. Hum Mutat. 1998;12(2):137. PMID:10694922 doi:<137::AID-HUMU16>3.0.CO;2-J 10.1002/(SICI)1098-1004(1998)12:2<137::AID-HUMU16>3.0.CO;2-J
↑ Abdalla SA, Pece-Barbara N, Vera S, Tapia E, Paez E, Bernabeu C, Letarte M. Analysis of ALK-1 and endoglin in newborns from families with hereditary hemorrhagic telangiectasia type 2. Hum Mol Genet. 2000 May 1;9(8):1227-37. PMID:10767348
↑ Kjeldsen AD, Brusgaard K, Poulsen L, Kruse T, Rasmussen K, Green A, Vase P. Mutations in the ALK-1 gene and the phenotype of hereditary hemorrhagic telangiectasia in two large Danish families. Am J Med Genet. 2001 Feb 1;98(4):298-302. PMID:11170071
↑ Trembath RC, Thomson JR, Machado RD, Morgan NV, Atkinson C, Winship I, Simonneau G, Galie N, Loyd JE, Humbert M, Nichols WC, Morrell NW, Berg J, Manes A, McGaughran J, Pauciulo M, Wheeler L. Clinical and molecular genetic features of pulmonary hypertension in patients with hereditary hemorrhagic telangiectasia. N Engl J Med. 2001 Aug 2;345(5):325-34. PMID:11484689 doi:10.1056/NEJM200108023450503
↑ Harrison RE, Flanagan JA, Sankelo M, Abdalla SA, Rowell J, Machado RD, Elliott CG, Robbins IM, Olschewski H, McLaughlin V, Gruenig E, Kermeen F, Halme M, Raisanen-Sokolowski A, Laitinen T, Morrell NW, Trembath RC. Molecular and functional analysis identifies ALK-1 as the predominant cause of pulmonary hypertension related to hereditary haemorrhagic telangiectasia. J Med Genet. 2003 Dec;40(12):865-71. PMID:14684682
↑ Lesca G, Plauchu H, Coulet F, Lefebvre S, Plessis G, Odent S, Riviere S, Leheup B, Goizet C, Carette MF, Cordier JF, Pinson S, Soubrier F, Calender A, Giraud S. Molecular screening of ALK1/ACVRL1 and ENG genes in hereditary hemorrhagic telangiectasia in France. Hum Mutat. 2004 Apr;23(4):289-99. PMID:15024723 doi:10.1002/humu.20017
↑ Kuehl HK, Caselitz M, Hasenkamp S, Wagner S, El-Harith el-HA, Manns MP, Stuhrmann M. Hepatic manifestation is associated with ALK1 in hereditary hemorrhagic telangiectasia: identification of five novel ALK1 and one novel ENG mutations. Hum Mutat. 2005 Mar;25(3):320. PMID:15712270 doi:10.1002/humu.9311
↑ Mahlawat P, Ilangovan U, Biswas T, Sun LZ, Hinck AP. Structure of the Alk1 extracellular domain and characterization of its bone morphogenetic protein (BMP) binding properties. Biochemistry. 2012 Aug 14;51(32):6328-41. Epub 2012 Aug 2. PMID:22799562 doi:10.1021/bi300942x
↑ Townson SA, Martinez-Hackert E, Greppi C, Lowden P, Sako D, Liu J, Ucran JA, Liharska K, Underwood KW, Seehra J, Kumar R, Grinberg AV. Specificity and structure of a high affinity activin receptor-like kinase 1 (ALK1) signaling complex. J Biol Chem. 2012 Jun 20. PMID:22718755 doi:10.1074/jbc.M112.377960
↑ David L, Mallet C, Keramidas M, Lamande N, Gasc JM, Dupuis-Girod S, Plauchu H, Feige JJ, Bailly S. Bone morphogenetic protein-9 is a circulating vascular quiescence factor. Circ Res. 2008 Apr 25;102(8):914-22. doi: 10.1161/CIRCRESAHA.107.165530. Epub, 2008 Feb 28. PMID:18309101 doi:10.1161/CIRCRESAHA.107.165530
↑ Mahlawat P, Ilangovan U, Biswas T, Sun LZ, Hinck AP. Structure of the Alk1 extracellular domain and characterization of its bone morphogenetic protein (BMP) binding properties. Biochemistry. 2012 Aug 14;51(32):6328-41. Epub 2012 Aug 2. PMID:22799562 doi:10.1021/bi300942x

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Berg JN, Gallione CJ, Stenzel TT, Johnson DW, Allen WP, Schwartz CE, Jackson CE, Porteous ME, Marchuk DA. The activin receptor-like kinase 1 gene: genomic structure and mutations in hereditary hemorrhagic telangiectasia type 2. Am J Hum Genet. 1997 Jul;61(1):60-7. PMID:9245985 doi:S0002-9297(07)64277-3

[2] Johnson DW, Berg JN, Baldwin MA, Gallione CJ, Marondel I, Yoon SJ, Stenzel TT, Speer M, Pericak-Vance MA, Diamond A, Guttmacher AE, Jackson CE, Attisano L, Kucherlapati R, Porteous ME, Marchuk DA. Mutations in the activin receptor-like kinase 1 gene in hereditary haemorrhagic telangiectasia type 2. Nat Genet. 1996 Jun;13(2):189-95. PMID:8640225 doi:10.1038/ng0696-189

[3] Klaus DJ, Gallione CJ, Anthony K, Yeh EY, Yu J, Lux A, Johnson DW, Marchuk DA. Novel missense and frameshift mutations in the activin receptor-like kinase-1 gene in hereditary hemorrhagic telangiectasia. Mutations in brief no. 164. Online. Hum Mutat. 1998;12(2):137. PMID:10694922 doi:<137::AID-HUMU16>3.0.CO;2-J 10.1002/(SICI)1098-1004(1998)12:2<137::AID-HUMU16>3.0.CO;2-J

[4] Abdalla SA, Pece-Barbara N, Vera S, Tapia E, Paez E, Bernabeu C, Letarte M. Analysis of ALK-1 and endoglin in newborns from families with hereditary hemorrhagic telangiectasia type 2. Hum Mol Genet. 2000 May 1;9(8):1227-37. PMID:10767348

[5] Kjeldsen AD, Brusgaard K, Poulsen L, Kruse T, Rasmussen K, Green A, Vase P. Mutations in the ALK-1 gene and the phenotype of hereditary hemorrhagic telangiectasia in two large Danish families. Am J Med Genet. 2001 Feb 1;98(4):298-302. PMID:11170071

[6] Trembath RC, Thomson JR, Machado RD, Morgan NV, Atkinson C, Winship I, Simonneau G, Galie N, Loyd JE, Humbert M, Nichols WC, Morrell NW, Berg J, Manes A, McGaughran J, Pauciulo M, Wheeler L. Clinical and molecular genetic features of pulmonary hypertension in patients with hereditary hemorrhagic telangiectasia. N Engl J Med. 2001 Aug 2;345(5):325-34. PMID:11484689 doi:10.1056/NEJM200108023450503

[7] Harrison RE, Flanagan JA, Sankelo M, Abdalla SA, Rowell J, Machado RD, Elliott CG, Robbins IM, Olschewski H, McLaughlin V, Gruenig E, Kermeen F, Halme M, Raisanen-Sokolowski A, Laitinen T, Morrell NW, Trembath RC. Molecular and functional analysis identifies ALK-1 as the predominant cause of pulmonary hypertension related to hereditary haemorrhagic telangiectasia. J Med Genet. 2003 Dec;40(12):865-71. PMID:14684682

[8] Lesca G, Plauchu H, Coulet F, Lefebvre S, Plessis G, Odent S, Riviere S, Leheup B, Goizet C, Carette MF, Cordier JF, Pinson S, Soubrier F, Calender A, Giraud S. Molecular screening of ALK1/ACVRL1 and ENG genes in hereditary hemorrhagic telangiectasia in France. Hum Mutat. 2004 Apr;23(4):289-99. PMID:15024723 doi:10.1002/humu.20017

[9] Kuehl HK, Caselitz M, Hasenkamp S, Wagner S, El-Harith el-HA, Manns MP, Stuhrmann M. Hepatic manifestation is associated with ALK1 in hereditary hemorrhagic telangiectasia: identification of five novel ALK1 and one novel ENG mutations. Hum Mutat. 2005 Mar;25(3):320. PMID:15712270 doi:10.1002/humu.9311

[10] Mahlawat P, Ilangovan U, Biswas T, Sun LZ, Hinck AP. Structure of the Alk1 extracellular domain and characterization of its bone morphogenetic protein (BMP) binding properties. Biochemistry. 2012 Aug 14;51(32):6328-41. Epub 2012 Aug 2. PMID:22799562 doi:10.1021/bi300942x

[11] Townson SA, Martinez-Hackert E, Greppi C, Lowden P, Sako D, Liu J, Ucran JA, Liharska K, Underwood KW, Seehra J, Kumar R, Grinberg AV. Specificity and structure of a high affinity activin receptor-like kinase 1 (ALK1) signaling complex. J Biol Chem. 2012 Jun 20. PMID:22718755 doi:10.1074/jbc.M112.377960

[12] David L, Mallet C, Keramidas M, Lamande N, Gasc JM, Dupuis-Girod S, Plauchu H, Feige JJ, Bailly S. Bone morphogenetic protein-9 is a circulating vascular quiescence factor. Circ Res. 2008 Apr 25;102(8):914-22. doi: 10.1161/CIRCRESAHA.107.165530. Epub, 2008 Feb 28. PMID:18309101 doi:10.1161/CIRCRESAHA.107.165530

[13] Mahlawat P, Ilangovan U, Biswas T, Sun LZ, Hinck AP. Structure of the Alk1 extracellular domain and characterization of its bone morphogenetic protein (BMP) binding properties. Biochemistry. 2012 Aug 14;51(32):6328-41. Epub 2012 Aug 2. PMID:22799562 doi:10.1021/bi300942x

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6sf2 is ON HOLD
+==Ternary complex of human bone morphogenetic protein 9 (BMP9) growth factor domain, its prodomain and extracellular domain of activin receptor-like kinase 1 (ALK1).==
+<StructureSection load='6sf2' size='340' side='right'caption='[[6sf2]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
-Authors:
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6sf2]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6SF2 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6SF2 FirstGlance]. <br>
-Description:
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
-[[Category: Unreleased Structures]]
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6sf1|6sf1]], [[6sf3|6sf3]]</td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein_serine/threonine_kinase Receptor protein serine/threonine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.30 2.7.11.30] </span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6sf2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6sf2 OCA], [http://pdbe.org/6sf2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6sf2 RCSB], [http://www.ebi.ac.uk/pdbsum/6sf2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6sf2 ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[[http://www.uniprot.org/uniprot/ACVL1_HUMAN ACVL1_HUMAN]] Defects in ACVRL1 are the cause of hereditary hemorrhagic telangiectasia type 2 (HHT2) [MIM:[http://omim.org/entry/600376 600376]]; also known as Osler-Rendu-Weber syndrome 2 (ORW2). HHT2 is an autosomal dominant multisystemic vascular dysplasia, characterized by recurrent epistaxis, muco-cutaneous telangiectases, gastro-intestinal hemorrhage, and pulmonary, cerebral and hepatic arteriovenous malformations; all secondary manifestations of the underlying vascular dysplasia.<ref>PMID:9245985</ref> <ref>PMID:8640225</ref> <ref>PMID:10694922</ref> <ref>PMID:10767348</ref> <ref>PMID:11170071</ref> <ref>PMID:11484689</ref> <ref>PMID:14684682</ref> <ref>PMID:15024723</ref> <ref>PMID:15712270</ref>
+== Function ==
+[[http://www.uniprot.org/uniprot/ACVL1_HUMAN ACVL1_HUMAN]] Type I receptor for TGF-beta family ligands BMP9/GDF2 and BMP10 and important regulator of normal blood vessel development. On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. May bind activin as well.<ref>PMID:22799562</ref> <ref>PMID:22718755</ref>  [[http://www.uniprot.org/uniprot/GDF2_HUMAN GDF2_HUMAN]] Potent circulating inhibitor of angiogenesis. Could be involved in bone formation. Signals through the type I activin receptor ACVRL1 but not other Alks.<ref>PMID:18309101</ref> <ref>PMID:22799562</ref>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Receptor protein serine/threonine kinase]]
+[[Category: Guo, J]]
+[[Category: Li, W]]
+[[Category: Salmon, R M]]
+[[Category: Yu, M]]
+[[Category: Alk1]]
+[[Category: Bmp]]
+[[Category: Bmp9]]
+[[Category: Cytokine]]
+[[Category: Prodomain]]
+[[Category: Signalling]]
+[[Category: Ternary complex]]
+[[Category: Tgfbeta]]

6sf2: Difference between revisions

Revision as of 06:54, 8 April 2020

Ternary complex of human bone morphogenetic protein 9 (BMP9) growth factor domain, its prodomain and extracellular domain of activin receptor-like kinase 1 (ALK1).

Structural highlights

Disease

Function

References

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