9fot: Difference between revisions

Latest revision as of 07:26, 3 July 2025

Human monocarboxylate transporter 8 bound to Silychristin

Structural highlights

9fot is a 2 chain structure with sequence from Homo sapiens and Vicugna pacos. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3Å
Ligands:	A1IET
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

MOT8_HUMAN Allan-Herndon-Dudley syndrome. The disease is caused by variants affecting the gene represented in this entry.

Function

MOT8_HUMAN Specific thyroid hormone transmembrane transporter, that mediates both uptake and efflux of thyroid hormones across the cell membrane independently of pH or a Na(+) gradient. Major substrates are the iodothyronines T3 and T4 and to a lesser extent rT3 and 3,3-diiodothyronine (3,3'-T2) (PubMed:16887882, PubMed:18337592, PubMed:20628049, PubMed:23550058, PubMed:26426690, PubMed:27805744, PubMed:31436139). Acts as an important mediator of thyroid hormone transport, especially T3, through the blood-brain barrier (Probable) (PubMed:28526555).^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9]

References

↑ Friesema EC, Kuiper GG, Jansen J, Visser TJ, Kester MH. Thyroid hormone transport by the human monocarboxylate transporter 8 and its rate-limiting role in intracellular metabolism. Mol Endocrinol. 2006 Nov;20(11):2761-72. PMID:16887882 doi:10.1210/me.2005-0256
↑ Friesema EC, Jansen J, Jachtenberg JW, Visser WE, Kester MH, Visser TJ. Effective cellular uptake and efflux of thyroid hormone by human monocarboxylate transporter 10. Mol Endocrinol. 2008 Jun;22(6):1357-69. PMID:18337592 doi:10.1210/me.2007-0112
↑ Kinne A, Kleinau G, Hoefig CS, Grüters A, Köhrle J, Krause G, Schweizer U. Essential molecular determinants for thyroid hormone transport and first structural implications for monocarboxylate transporter 8. J Biol Chem. 2010 Sep 3;285(36):28054-63. PMID:20628049 doi:10.1074/jbc.M110.129577
↑ Kersseboom S, Kremers GJ, Friesema EC, Visser WE, Klootwijk W, Peeters RP, Visser TJ. Mutations in MCT8 in patients with Allan-Herndon-Dudley-syndrome affecting its cellular distribution. Mol Endocrinol. 2013 May;27(5):801-13. PMID:23550058 doi:10.1210/me.2012-1356
↑ Armour CM, Kersseboom S, Yoon G, Visser TJ. Further Insights into the Allan-Herndon-Dudley Syndrome: Clinical and Functional Characterization of a Novel MCT8 Mutation. PLoS One. 2015 Oct 1;10(10):e0139343. PMID:26426690 doi:10.1371/journal.pone.0139343
↑ Novara F, Groeneweg S, Freri E, Estienne M, Reho P, Matricardi S, Castellotti B, Visser WE, Zuffardi O, Visser TJ. Clinical and Molecular Characteristics of SLC16A2 (MCT8) Mutations in Three Families with the Allan-Herndon-Dudley Syndrome. Hum Mutat. 2017 Mar;38(3):260-264. PMID:27805744 doi:10.1002/humu.23140
↑ Vatine GD, Al-Ahmad A, Barriga BK, Svendsen S, Salim A, Garcia L, Garcia VJ, Ho R, Yucer N, Qian T, Lim RG, Wu J, Thompson LM, Spivia WR, Chen Z, Van Eyk J, Palecek SP, Refetoff S, Shusta EV, Svendsen CN. Modeling Psychomotor Retardation using iPSCs from MCT8-Deficient Patients Indicates a Prominent Role for the Blood-Brain Barrier. Cell Stem Cell. 2017 Jun 1;20(6):831-843.e5. PMID:28526555 doi:10.1016/j.stem.2017.04.002
↑ Groeneweg S, Kersseboom S, van den Berge A, Dolcetta-Capuzzo A, van Geest FS, van Heerebeek REA, Arjona FJ, Meima ME, Peeters RP, Visser WE, Visser TJ. In Vitro Characterization of Human, Mouse, and Zebrafish MCT8 Orthologues. Thyroid. 2019 Oct;29(10):1499-1510. PMID:31436139 doi:10.1089/thy.2019.0009
↑ Visser WE, Jansen J, Friesema EC, Kester MH, Mancilla E, Lundgren J, van der Knaap MS, Lunsing RJ, Brouwer OF, Visser TJ. Novel pathogenic mechanism suggested by ex vivo analysis of MCT8 (SLC16A2) mutations. Hum Mutat. 2009 Jan;30(1):29-38. PMID:18636565 doi:10.1002/humu.20808

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Friesema EC, Kuiper GG, Jansen J, Visser TJ, Kester MH. Thyroid hormone transport by the human monocarboxylate transporter 8 and its rate-limiting role in intracellular metabolism. Mol Endocrinol. 2006 Nov;20(11):2761-72. PMID:16887882 doi:10.1210/me.2005-0256

[2] Friesema EC, Jansen J, Jachtenberg JW, Visser WE, Kester MH, Visser TJ. Effective cellular uptake and efflux of thyroid hormone by human monocarboxylate transporter 10. Mol Endocrinol. 2008 Jun;22(6):1357-69. PMID:18337592 doi:10.1210/me.2007-0112

[3] Kinne A, Kleinau G, Hoefig CS, Grüters A, Köhrle J, Krause G, Schweizer U. Essential molecular determinants for thyroid hormone transport and first structural implications for monocarboxylate transporter 8. J Biol Chem. 2010 Sep 3;285(36):28054-63. PMID:20628049 doi:10.1074/jbc.M110.129577

[4] Kersseboom S, Kremers GJ, Friesema EC, Visser WE, Klootwijk W, Peeters RP, Visser TJ. Mutations in MCT8 in patients with Allan-Herndon-Dudley-syndrome affecting its cellular distribution. Mol Endocrinol. 2013 May;27(5):801-13. PMID:23550058 doi:10.1210/me.2012-1356

[5] Armour CM, Kersseboom S, Yoon G, Visser TJ. Further Insights into the Allan-Herndon-Dudley Syndrome: Clinical and Functional Characterization of a Novel MCT8 Mutation. PLoS One. 2015 Oct 1;10(10):e0139343. PMID:26426690 doi:10.1371/journal.pone.0139343

[6] Novara F, Groeneweg S, Freri E, Estienne M, Reho P, Matricardi S, Castellotti B, Visser WE, Zuffardi O, Visser TJ. Clinical and Molecular Characteristics of SLC16A2 (MCT8) Mutations in Three Families with the Allan-Herndon-Dudley Syndrome. Hum Mutat. 2017 Mar;38(3):260-264. PMID:27805744 doi:10.1002/humu.23140

[7] Vatine GD, Al-Ahmad A, Barriga BK, Svendsen S, Salim A, Garcia L, Garcia VJ, Ho R, Yucer N, Qian T, Lim RG, Wu J, Thompson LM, Spivia WR, Chen Z, Van Eyk J, Palecek SP, Refetoff S, Shusta EV, Svendsen CN. Modeling Psychomotor Retardation using iPSCs from MCT8-Deficient Patients Indicates a Prominent Role for the Blood-Brain Barrier. Cell Stem Cell. 2017 Jun 1;20(6):831-843.e5. PMID:28526555 doi:10.1016/j.stem.2017.04.002

[8] Groeneweg S, Kersseboom S, van den Berge A, Dolcetta-Capuzzo A, van Geest FS, van Heerebeek REA, Arjona FJ, Meima ME, Peeters RP, Visser WE, Visser TJ. In Vitro Characterization of Human, Mouse, and Zebrafish MCT8 Orthologues. Thyroid. 2019 Oct;29(10):1499-1510. PMID:31436139 doi:10.1089/thy.2019.0009

[9] Visser WE, Jansen J, Friesema EC, Kester MH, Mancilla E, Lundgren J, van der Knaap MS, Lunsing RJ, Brouwer OF, Visser TJ. Novel pathogenic mechanism suggested by ex vivo analysis of MCT8 (SLC16A2) mutations. Hum Mutat. 2009 Jan;30(1):29-38. PMID:18636565 doi:10.1002/humu.20808

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 9fot is ON HOLD
+==Human monocarboxylate transporter 8 bound to Silychristin==
+<StructureSection load='9fot' size='340' side='right'caption='[[9fot]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
-Authors:
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9fot]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Vicugna_pacos Vicugna pacos]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9FOT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9FOT FirstGlance]. <br>
-Description:
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3&#8491;</td></tr>
-[[Category: Unreleased Structures]]
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1IET:(2~{R},3~{R})-2-[(2~{S},3~{R})-3-(hydroxymethyl)-2-(3-methoxy-4-oxidanyl-phenyl)-7-oxidanyl-2,3-dihydro-1-benzofuran-5-yl]-3,5,7-tris(oxidanyl)-2,3-dihydrochromen-4-one'>A1IET</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=9fot FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9fot OCA], [https://pdbe.org/9fot PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9fot RCSB], [https://www.ebi.ac.uk/pdbsum/9fot PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9fot ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/MOT8_HUMAN MOT8_HUMAN] Allan-Herndon-Dudley syndrome. The disease is caused by variants affecting the gene represented in this entry.
+== Function ==
+[https://www.uniprot.org/uniprot/MOT8_HUMAN MOT8_HUMAN] Specific thyroid hormone transmembrane transporter, that mediates both uptake and efflux of thyroid hormones across the cell membrane independently of pH or a Na(+) gradient. Major substrates are the iodothyronines T3 and T4 and to a lesser extent rT3 and 3,3-diiodothyronine (3,3'-T2) (PubMed:16887882, PubMed:18337592, PubMed:20628049, PubMed:23550058, PubMed:26426690, PubMed:27805744, PubMed:31436139). Acts as an important mediator of thyroid hormone transport, especially T3, through the blood-brain barrier (Probable) (PubMed:28526555).<ref>PMID:16887882</ref> <ref>PMID:18337592</ref> <ref>PMID:20628049</ref> <ref>PMID:23550058</ref> <ref>PMID:26426690</ref> <ref>PMID:27805744</ref> <ref>PMID:28526555</ref> <ref>PMID:31436139</ref> <ref>PMID:18636565</ref>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Vicugna pacos]]
+[[Category: Coscia F]]
+[[Category: Tassinari M]]

9fot: Difference between revisions

Latest revision as of 07:26, 3 July 2025

Human monocarboxylate transporter 8 bound to Silychristin

Structural highlights

Disease

Function

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools