Structural highlights
Function
[RFFL_HUMAN] Has E3 ubiquitin protein ligase activity. Regulates the levels of CASP8 and CASP10 by targeting them for proteasomal degradation. Has anti-apoptotic activity. May bind phosphatidylinositol phosphates.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The caspase-associated ring proteins (CARP1 and CARP2) are distinguished from other caspase regulators by the presence of a FYVE-type zinc finger domain. FYVE-type domains are divided into two known classes: FYVE domains that specifically bind to phosphatidylinositol 3-phosphate in lipid bilayers and FYVE-related domains of undetermined function. Here, we report the crystal structure of the N-terminal region of CARP2 (44-139) including the FYVE-type domain and its associated helical bundle at 1.7 A resolution. The structure reveals a cramped phosphoinositide binding pocket and a blunted membrane insertion loop. These structural features indicate that the domain is not optimized to bind to phosphoinositides or insert into lipid bilayers. The CARP2 FYVE-like domain thus defines a third subfamily of FYVE-type domains that are functionally and structurally distinct. Structural analyses provide insights into the possible function of this unique subfamily of FYVE-type domains.
Crystal structure of a FYVE-type zinc finger domain from the caspase regulator CARP2.,Tibbetts MD, Shiozaki EN, Gu L, McDonald ER 3rd, El-Deiry WS, Shi Y Structure. 2004 Dec;12(12):2257-63. PMID:15576038[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ McDonald ER 3rd, El-Deiry WS. Suppression of caspase-8- and -10-associated RING proteins results in sensitization to death ligands and inhibition of tumor cell growth. Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):6170-5. Epub 2004 Apr 6. PMID:15069192 doi:http://dx.doi.org/10.1073/pnas.0307459101
- ↑ Tibbetts MD, Shiozaki EN, Gu L, McDonald ER 3rd, El-Deiry WS, Shi Y. Crystal structure of a FYVE-type zinc finger domain from the caspase regulator CARP2. Structure. 2004 Dec;12(12):2257-63. PMID:15576038 doi:10.1016/j.str.2004.10.007
