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4gei

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Revision as of 18:30, 25 December 2014

N-terminal domain of VDUP-1

Structural highlights

4gei is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	4gej
Gene:	TXNIP, VDUP1 (Homo sapiens)
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[TXNIP_HUMAN] May act as an oxidative stress mediator by inhibiting thioredoxin activity or by limiting its bioavailability. Interacts with COPS5 and restores COPS5-induced suppression of CDKN1B stability, blocking the COPS5-mediated translocation of CDKN1B from the nucleus to the cytoplasm. Functions as a transcriptional repressor, possibly by acting as a bridge molecule between transcription factors and corepressor complexes, and over-expression will induce G0/G1 cell cycle arrest. Required for the maturation of natural killer cells. Acts as a suppressor of tumor cell growth. Inhibits the proteasomal degradation of DDIT4, and thereby contributes to the inhibition of the mammalian target of rapamycin complex 1 (mTORC1).^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

Thioredoxin-interacting protein (TXNIP) is one of the six known alpha-arrestins and has recently received considerable attention owing to its involvement in redox signalling and metabolism. Various stress stimuli such as high glucose, heat shock, UV, H2O2 and mechanical stress among others robustly induce the expression of TXNIP, resulting in the sequestration and inactivation of thioredoxin, which in turn leads to cellular oxidative stress. While TXNIP is the only alpha-arrestin known to bind thioredoxin, TXNIP and two other alpha-arrestins, Arrdc4 and Arrdc3, have been implicated in metabolism. Furthermore, owing to its roles in the pathologies of diabetes and cardiovascular disease, TXNIP is considered to be a promising drug target. Based on their amino-acid sequences, TXNIP and the other alpha-arrestins are remotely related to beta-arrestins. Here, the crystal structure of the N-terminal domain of TXNIP is reported. It provides the first structural information on any of the alpha-arrestins and reveals that although TXNIP adopts a beta-arrestin fold as predicted, it is structurally more similar to Vps26 proteins than to beta-arrestins, while sharing below 15% pairwise sequence identity with either.

Structure of the N-terminal domain of human thioredoxin-interacting protein.,Polekhina G, Ascher DB, Kok SF, Beckham S, Wilce M, Waltham M Acta Crystallogr D Biol Crystallogr. 2013 Mar;69(Pt 3):333-44. doi:, 10.1107/S0907444912047099. Epub 2013 Feb 16. PMID:23519408^[5]

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

References

↑ Liyanage NP, Fernando MR, Lou MF. Regulation of the bioavailability of thioredoxin in the lens by a specific thioredoxin-binding protein (TBP-2). Exp Eye Res. 2007 Aug;85(2):270-9. Epub 2007 May 21. PMID:17603038 doi:S0014-4835(07)00133-9
↑ Han SH, Jeon JH, Ju HR, Jung U, Kim KY, Yoo HS, Lee YH, Song KS, Hwang HM, Na YS, Yang Y, Lee KN, Choi I. VDUP1 upregulated by TGF-beta1 and 1,25-dihydorxyvitamin D3 inhibits tumor cell growth by blocking cell-cycle progression. Oncogene. 2003 Jun 26;22(26):4035-46. PMID:12821938 doi:10.1038/sj.onc.1206610
↑ Shin KH, Kim RH, Kim RH, Kang MK, Park NH. hnRNP G elicits tumor-suppressive activity in part by upregulating the expression of Txnip. Biochem Biophys Res Commun. 2008 Aug 8;372(4):880-5. doi:, 10.1016/j.bbrc.2008.05.175. Epub 2008 Jun 9. PMID:18541147 doi:10.1016/j.bbrc.2008.05.175
↑ Jin HO, Seo SK, Kim YS, Woo SH, Lee KH, Yi JY, Lee SJ, Choe TB, Lee JH, An S, Hong SI, Park IC. TXNIP potentiates Redd1-induced mTOR suppression through stabilization of Redd1. Oncogene. 2011 Sep 1;30(35):3792-801. doi: 10.1038/onc.2011.102. Epub 2011 Apr 4. PMID:21460850 doi:10.1038/onc.2011.102
↑ Polekhina G, Ascher DB, Kok SF, Beckham S, Wilce M, Waltham M. Structure of the N-terminal domain of human thioredoxin-interacting protein. Acta Crystallogr D Biol Crystallogr. 2013 Mar;69(Pt 3):333-44. doi:, 10.1107/S0907444912047099. Epub 2013 Feb 16. PMID:23519408 doi:10.1107/S0907444912047099

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4gei"

@@ Line 7: / Line 7: @@
 <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=4gei FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gei OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4gei RCSB], [http://www.ebi.ac.uk/pdbsum/4gei PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/TXNIP_HUMAN TXNIP_HUMAN]] May act as an oxidative stress mediator by inhibiting thioredoxin activity or by limiting its bioavailability. Interacts with COPS5 and restores COPS5-induced suppression of CDKN1B stability, blocking the COPS5-mediated translocation of CDKN1B from the nucleus to the cytoplasm. Functions as a transcriptional repressor, possibly by acting as a bridge molecule between transcription factors and corepressor complexes, and over-expression will induce G0/G1 cell cycle arrest. Required for the maturation of natural killer cells. Acts as a suppressor of tumor cell growth. Inhibits the proteasomal degradation of DDIT4, and thereby contributes to the inhibition of the mammalian target of rapamycin complex 1 (mTORC1).<ref>PMID:17603038</ref> <ref>PMID:12821938</ref> <ref>PMID:18541147</ref> <ref>PMID:21460850</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

4gei

From Proteopedia

Revision as of 18:30, 25 December 2014

N-terminal domain of VDUP-1

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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