Deoxyhypusine synthase

Function

Deoxyhypusine synthase (DHS) plays an important role in promoting cell migration by regulating Rac-1-mediated epithelial polarity and formation of adherens junctions through Rac guanine nucleotide exchange factors^[1]. Rdx is part of the ERM (Ezrin/Radixin/Moesin) which is linked to cell shape change. Phosphorylation of the C-terminal Thr residues of ERM inhibits cell adhesion and induces formation of spherical cell shape^[2].

Disease

Rdx deficiency causes increase in bilirubin in serum, a phenotype similar to that of Dubin-Johnson syndrome in human^[3].

Structural highlights

The hydrophobic groove of the FERM domain of Rdx binds the N-terminal peptide of the adhesion molecule P-selectin glycoprotein ligand 1 with multiple hydrogen bonds^[4]. Hydrophobic, Polar

Mouse radixin FERM domain (green) complex with N-terminal peptide of the adhesion molecule PSGL-1 (yellow) (PDB code 2emt)

Drag the structure with the mouse to rotate

3D Structures of deoxyhypusine synthase3D Structures of deoxyhypusine synthase

Updated on 04-February-2021

6xxh – hDHS – human
1dhs, 1rlz, 1roz, 6dft, 6xxi – hDHS + NAD
6xxm – hDHS + putrescine
6pgr, 6wkz, 6wl6 – hDHS + inhibitor
6xxl – hDHS + spermine
6xxk – hDHS + spermidine
6xxj – hDHS + NAD + spermidine
1rqd, 6prv – hDHS + NAD + inhibitor
7cmc – DHS + NAD - Pyrococcus horikishii
6w3z – DHS + NAD – Brugia malayi

ReferencesReferences

↑ Valderrama F, Thevapala S, Ridley AJ. Radixin regulates cell migration and cell-cell adhesion through Rac1. J Cell Sci. 2012 Jul 15;125(Pt 14):3310-9. doi: 10.1242/jcs.094383. Epub 2012 Mar, 30. PMID:22467863 doi:http://dx.doi.org/10.1242/jcs.094383
↑ Tachibana K, Haghparast SM, Miyake J. Inhibition of cell adhesion by phosphorylated Ezrin/Radixin/Moesin. Cell Adh Migr. 2015;9(6):502-12. doi: 10.1080/19336918.2015.1113366. PMID:26555866 doi:http://dx.doi.org/10.1080/19336918.2015.1113366
↑ Kikuchi S, Hata M, Fukumoto K, Yamane Y, Matsui T, Tamura A, Yonemura S, Yamagishi H, Keppler D, Tsukita S, Tsukita S. Radixin deficiency causes conjugated hyperbilirubinemia with loss of Mrp2 from bile canalicular membranes. Nat Genet. 2002 Jul;31(3):320-5. doi: 10.1038/ng905. Epub 2002 Jun 17. PMID:12068294 doi:http://dx.doi.org/10.1038/ng905
↑ . PMID:18706570

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky

[1] Valderrama F, Thevapala S, Ridley AJ. Radixin regulates cell migration and cell-cell adhesion through Rac1. J Cell Sci. 2012 Jul 15;125(Pt 14):3310-9. doi: 10.1242/jcs.094383. Epub 2012 Mar, 30. PMID:22467863 doi:http://dx.doi.org/10.1242/jcs.094383

[2] Tachibana K, Haghparast SM, Miyake J. Inhibition of cell adhesion by phosphorylated Ezrin/Radixin/Moesin. Cell Adh Migr. 2015;9(6):502-12. doi: 10.1080/19336918.2015.1113366. PMID:26555866 doi:http://dx.doi.org/10.1080/19336918.2015.1113366

[3] Kikuchi S, Hata M, Fukumoto K, Yamane Y, Matsui T, Tamura A, Yonemura S, Yamagishi H, Keppler D, Tsukita S, Tsukita S. Radixin deficiency causes conjugated hyperbilirubinemia with loss of Mrp2 from bile canalicular membranes. Nat Genet. 2002 Jul;31(3):320-5. doi: 10.1038/ng905. Epub 2002 Jun 17. PMID:12068294 doi:http://dx.doi.org/10.1038/ng905

[4] . PMID:18706570

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