2f4m

Structural highlights

Function

[RD23B_MOUSE] Multiubiquitin chain receptor involved in modulation of proteasomal degradation. Binds to polyubiquitin chains. Proposed to be capable to bind simultaneously to the 26S proteasome and to polyubiquitinated substrates and to deliver ubiquitinated proteins to the proteasome. May play a role in endoplasmic reticulum-associated degradation (ERAD) of misfolded glycoproteins by association with PNGase and delivering deglycosylated proteins to the proteasome.^{[1] [2] [3]} Involved in global genome nucleotide excision repair (GG-NER) by acting as component of the XPC complex. Cooperatively with Cetn2 appears to stabilize Xpc. May protect Xpc from proteasomal degradation (By similarity).^{[4] [5] [6]} The XPC complex is proposed to represent the first factor bound at the sites of DNA damage and together with other core recognition factors, Xpa, RPA and the TFIIH complex, is part of the pre-incision (or initial recognition) complex. The XPC complex recognizes a wide spectrum of damaged DNA characterized by distortions of the DNA helix such as single-stranded loops, mismatched bubbles or single stranded overhangs. The orientation of XPC complex binding appears to be crucial for inducing a productive NER. XPC complex is proposed to recognize and to interact with unpaired bases on the undamaged DNA strand which is followed by recruitment of the TFIIH complex and subsequent scanning for lesions in the opposite strand in a 5'-to-3' direction by the NER machinery. Cyclobutane pyrimidine dimers (CPDs) which are formed upon UV-induced DNA damage esacpe detection by the XPC complex due to a low degree of structural perurbation. Instead they are detected by the UV-DDB complex which in turn recruits and cooperates with the XPC complex in the respective DNA repair. In vitro, the Xpc:Rad23b dimer is sufficient to initiate NER; it preferentially binds to cisplatin and UV-damaged double-stranded DNA and also binds to a variety of chemically and structurally diverse DNA adducts. Xpc:Rad23b contacts DNA both 5' and 3' of a cisplatin lesion with a preference for the 5' side. Xpc:Rad23bB induces a bend in DNA upon binding. Xpc:Rad23b stimulates the activity of DNA glycosylases Tdg and Smug1 (By similarity).^{[7] [8] [9]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

1. ↑ Ng JM, Vermeulen W, van der Horst GT, Bergink S, Sugasawa K, Vrieling H, Hoeijmakers JH. A novel regulation mechanism of DNA repair by damage-induced and RAD23-dependent stabilization of xeroderma pigmentosum group C protein. Genes Dev. 2003 Jul 1;17(13):1630-45. Epub 2003 Jun 18. PMID:12815074 doi:http://dx.doi.org/10.1101/gad.260003
2. ↑ Okuda Y, Nishi R, Ng JM, Vermeulen W, van der Horst GT, Mori T, Hoeijmakers JH, Hanaoka F, Sugasawa K. Relative levels of the two mammalian Rad23 homologs determine composition and stability of the xeroderma pigmentosum group C protein complex. DNA Repair (Amst). 2004 Oct 5;3(10):1285-95. PMID:15336624 doi:http://dx.doi.org/10.1016/j.dnarep.2004.06.010
3. ↑ Li G, Zhao G, Zhou X, Schindelin H, Lennarz WJ. The AAA ATPase p97 links peptide N-glycanase to the endoplasmic reticulum-associated E3 ligase autocrine motility factor receptor. Proc Natl Acad Sci U S A. 2006 May 30;103(22):8348-53. Epub 2006 May 18. PMID:16709668 doi:http://dx.doi.org/10.1073/pnas.0602747103
4. ↑ Ng JM, Vermeulen W, van der Horst GT, Bergink S, Sugasawa K, Vrieling H, Hoeijmakers JH. A novel regulation mechanism of DNA repair by damage-induced and RAD23-dependent stabilization of xeroderma pigmentosum group C protein. Genes Dev. 2003 Jul 1;17(13):1630-45. Epub 2003 Jun 18. PMID:12815074 doi:http://dx.doi.org/10.1101/gad.260003
5. ↑ Okuda Y, Nishi R, Ng JM, Vermeulen W, van der Horst GT, Mori T, Hoeijmakers JH, Hanaoka F, Sugasawa K. Relative levels of the two mammalian Rad23 homologs determine composition and stability of the xeroderma pigmentosum group C protein complex. DNA Repair (Amst). 2004 Oct 5;3(10):1285-95. PMID:15336624 doi:http://dx.doi.org/10.1016/j.dnarep.2004.06.010
6. ↑ Li G, Zhao G, Zhou X, Schindelin H, Lennarz WJ. The AAA ATPase p97 links peptide N-glycanase to the endoplasmic reticulum-associated E3 ligase autocrine motility factor receptor. Proc Natl Acad Sci U S A. 2006 May 30;103(22):8348-53. Epub 2006 May 18. PMID:16709668 doi:http://dx.doi.org/10.1073/pnas.0602747103
7. ↑ Ng JM, Vermeulen W, van der Horst GT, Bergink S, Sugasawa K, Vrieling H, Hoeijmakers JH. A novel regulation mechanism of DNA repair by damage-induced and RAD23-dependent stabilization of xeroderma pigmentosum group C protein. Genes Dev. 2003 Jul 1;17(13):1630-45. Epub 2003 Jun 18. PMID:12815074 doi:http://dx.doi.org/10.1101/gad.260003
8. ↑ Okuda Y, Nishi R, Ng JM, Vermeulen W, van der Horst GT, Mori T, Hoeijmakers JH, Hanaoka F, Sugasawa K. Relative levels of the two mammalian Rad23 homologs determine composition and stability of the xeroderma pigmentosum group C protein complex. DNA Repair (Amst). 2004 Oct 5;3(10):1285-95. PMID:15336624 doi:http://dx.doi.org/10.1016/j.dnarep.2004.06.010
9. ↑ Li G, Zhao G, Zhou X, Schindelin H, Lennarz WJ. The AAA ATPase p97 links peptide N-glycanase to the endoplasmic reticulum-associated E3 ligase autocrine motility factor receptor. Proc Natl Acad Sci U S A. 2006 May 30;103(22):8348-53. Epub 2006 May 18. PMID:16709668 doi:http://dx.doi.org/10.1073/pnas.0602747103
10. ↑ Zhao G, Zhou X, Wang L, Li G, Kisker C, Lennarz WJ, Schindelin H. Structure of the mouse peptide N-glycanase-HR23 complex suggests co-evolution of the endoplasmic reticulum-associated degradation and DNA repair pathways. J Biol Chem. 2006 May 12;281(19):13751-61. Epub 2006 Feb 24. PMID:16500903 doi:10.1074/jbc.M600137200