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Cullin-5

Core component of multiple cullin-5-RING E3 ubiquitin-protein ligase complexes (ECS complexes, also named CRL5 complexes), which mediate the ubiquitination and subsequent proteasomal degradation of target proteins^{1,2,3,4,5,6,7,8,9,10,11}. Acts a scaffold protein that contributes to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme^12,13,14. The functional specificity of the E3 ubiquitin-protein ligase complex depends on the variable SOCS box-containing substrate recognition component^15,16,17. Acts as a key regulator of neuron positioning during cortex development: component of various SOCS-containing ECS complexes, such as the ECS(SOCS7) complex, that regulate reelin signaling by mediating ubiquitination and degradation of DAB1 (By similarity). ECS(SOCS1) seems to direct ubiquitination of JAK2¹⁸. The ECS(SOCS2) complex mediates the ubiquitination and subsequent proteasomal degradation of phosphorylated EPOR and GHR^19,20. The ECS(SPSB3) complex catalyzes ubiquitination of nuclear CGAS²¹. ECS(KLHDC1) complex is part of the DesCEND (destruction via C-end degrons) pathway and mediates ubiquitination and degradation of truncated SELENOS selenoprotein produced by failed UGA/Sec decoding, which ends with a glycine²². The ECS(ASB9) complex mediates ubiquitination and degradation of CKB²³. As part of some ECS complex, promotes 'Lys-11'-linked ubiquitination and degradation of BTRC²⁴. As part of a multisubunit ECS complex, polyubiquitinates monoubiquitinated POLR2A²⁵. As part of the ECS(RAB40C) complex, mediates ANKRD28 ubiquitination and degradation, thereby inhibiting protein phosphatase 6 (PP6) complex activity and focal adhesion assembly during cell migration²⁶. As part of the ECS(RAB40A) complex, mediates RHOU 'Lys-48'-linked ubiquitination and degradation, thus inhibiting focal adhesion disassembly during cell migration²⁷. As part of the ECS(RAB40B) complex, mediates LIMA1/EPLIN and RAP2 ubiquitination, thereby regulating actin cytoskeleton dynamics and stress fiber formation during cell migration^28,29. The ECS(ASB7) complex acts a negative regulator of H3K9me3 histone mark by mediating ubiquitination and degradation of SUV39H1³⁰. May form a cell surface vasopressin receptor³¹. (Microbial infection) Following infection by HIV-1 virus, CUL5 associates with HIV-1 Vif proteins and forms a cullin-5-RING E3 ubiquitin-protein ligase complex (ECS complex) that catalyzes ubiquitination and degradation of APOBEC3F and APOBEC3G^32,33. The complex can also ubiquitinate APOBEC3H to some extent³⁴. (Microbial infection) Seems to be involved in proteasomal degradation of p53/TP53 stimulated by adenovirus E1B-55 kDa protein.

AlphaFold DB , UniProt , Accession Q93034, Species HUMAN (Homo sapiens, Human), Gene CUL5, Length 780 aa.