2e31

Structural highlights

Function

[FBX2_MOUSE] Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Involved in the endoplasmic reticulum-associated degradation pathway (ERAD) for misfolded lumenal proteins by recognizing and binding sugar chains on unfolded glycoproteins that are retrotranslocated into the cytosol and promoting their ubiquitination and subsequent degradation. Prevents formation of cytosolic aggregates of unfolded glycoproteins that have been retrotranslocated into the cytosol. Able to recognize and bind denatured glycoproteins, preferentially those of the high-mannose type.^{[1] [2] [3] [4] [5]} [SKP1_HUMAN] Essential component of the SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complex, which mediates the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. In the SCF complex, serves as an adapter that links the F-box protein to CUL1. SCF(BTRC) mediates the ubiquitination of NFKBIA at 'Lys-21' and 'Lys-22'; the degradation frees the associated NFKB1-RELA dimer to translocate into the nucleus and to activate transcription. SCF(Cyclin F) directs ubiquitination of CP110.^{[6] [7]}

Evolutionary Conservation

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

References

1. ↑ Yoshida Y, Chiba T, Tokunaga F, Kawasaki H, Iwai K, Suzuki T, Ito Y, Matsuoka K, Yoshida M, Tanaka K, Tai T. E3 ubiquitin ligase that recognizes sugar chains. Nature. 2002 Jul 25;418(6896):438-42. PMID:12140560 doi:10.1038/nature00890
2. ↑ Yoshida Y, Adachi E, Fukiya K, Iwai K, Tanaka K. Glycoprotein-specific ubiquitin ligases recognize N-glycans in unfolded substrates. EMBO Rep. 2005 Mar;6(3):239-44. PMID:15723043 doi:http://dx.doi.org/10.1038/sj.embor.7400351
3. ↑ Yamaguchi Y, Hirao T, Sakata E, Kamiya Y, Kurimoto E, Yoshida Y, Suzuki T, Tanaka K, Kato K. Fbs1 protects the malfolded glycoproteins from the attack of peptide:N-glycanase. Biochem Biophys Res Commun. 2007 Oct 26;362(3):712-6. Epub 2007 Aug 20. PMID:17720138 doi:http://dx.doi.org/10.1016/j.bbrc.2007.08.056
4. ↑ Yoshida Y, Murakami A, Iwai K, Tanaka K. A neural-specific F-box protein Fbs1 functions as a chaperone suppressing glycoprotein aggregation. J Biol Chem. 2007 Mar 9;282(10):7137-44. Epub 2007 Jan 10. PMID:17215248 doi:http://dx.doi.org/10.1074/jbc.M611168200
5. ↑ Mizushima T, Hirao T, Yoshida Y, Lee SJ, Chiba T, Iwai K, Yamaguchi Y, Kato K, Tsukihara T, Tanaka K. Structural basis of sugar-recognizing ubiquitin ligase. Nat Struct Mol Biol. 2004 Apr;11(4):365-70. Epub 2004 Feb 29. PMID:14990996 doi:http://dx.doi.org/10.1038/nsmb732
6. ↑ Hao B, Zheng N, Schulman BA, Wu G, Miller JJ, Pagano M, Pavletich NP. Structural basis of the Cks1-dependent recognition of p27(Kip1) by the SCF(Skp2) ubiquitin ligase. Mol Cell. 2005 Oct 7;20(1):9-19. PMID:16209941 doi:10.1016/j.molcel.2005.09.003
7. ↑ Li Y, Hao B. Structural basis of dimerization-dependent ubiquitination by the SCF(Fbx4) ubiquitin ligase. J Biol Chem. 2010 Apr 30;285(18):13896-906. Epub 2010 Feb 24. PMID:20181953 doi:10.1074/jbc.M110.111518
8. ↑ Mizushima T, Yoshida Y, Kumanomidou T, Hasegawa Y, Suzuki A, Yamane T, Tanaka K. Structural basis for the selection of glycosylated substrates by SCF(Fbs1) ubiquitin ligase. Proc Natl Acad Sci U S A. 2007 Apr 3;104(14):5777-81. Epub 2007 Mar 26. PMID:17389369