4gej
From Proteopedia
N-terminal domain of VDUP-1
Structural highlights
FunctionTXNIP_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 PubMedThioredoxin-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
| ||||||||||||||||||
