Cullin-5 is a protein that in humans is encoded by the CUL5 gene. [5] [6] [7]
The mammalian gene product was originally discovered by expression cloning, due to the protein's ability to mobilize intracellular calcium in response to the peptide hormone arginine vasopressin. It was first titled VACM-1, for vasopressin-activated, calcium-mobilizing receptor. [8] Since then, VACM-1 has been shown to be homologous to the Cullin family of proteins, and was subsequently dubbed cul5.
Studies have shown that the cul5 protein is expressed at its highest levels in heart and skeletal tissue, and is specifically expressed in vascular endothelium and renal collecting tubules. [9]
Cul5 inhibits cellular proliferation, potentially through its involvement in the SOCS/ BC-box/ eloBC/ cul5/ RING E3 ligase complex, which functions as part of the ubiquitin system for protein degradation. [10]
One study have shown that Cul5 plays a role in Reelin signaling cascade, participating in the DAB1 degradation and thus ensuring the negative feedback mechanism of Reelin signaling during corticogenesis. [11]
Cullin 1, also known as CUL1, is a human protein and gene from cullin family. This protein plays an important role in protein degradation and protein ubiquitination.
NEDD8 is a protein that in humans is encoded by the NEDD8 gene. This ubiquitin-like (UBL) protein becomes covalently conjugated to a limited number of cellular proteins, in a process called NEDDylation similar to ubiquitination. Human NEDD8 shares 60% amino acid sequence identity to ubiquitin. The primary known substrates of NEDD8 modification are the cullin subunits of cullin-based E3 ubiquitin ligases, which are active only when NEDDylated. Their NEDDylation is critical for the recruitment of E2 to the ligase complex, thus facilitating ubiquitin conjugation. NEDD8 modification has therefore been implicated in cell cycle progression and cytoskeletal regulation.
Neural precursor cell expressed developmentally downregulated gene 4-like (NEDD4L) or NEDD4-2 is an enzyme of the NEDD4 family. In human the protein is encoded by the NEDD4L gene. In mouse the protein is commonly known as NEDD4-2 and the gene Nedd4-2.
RING-box protein 1 is a protein that in humans is encoded by the RBX1 gene.
Cullin-4A is a protein that in humans is encoded by the CUL4A gene. CUL4A belongs to the cullin family of ubiquitin ligase proteins and is highly homologous to the CUL4B protein. CUL4A regulates numerous key processes such as DNA repair, chromatin remodeling, spermatogenesis, haematopoiesis and the mitotic cell cycle. As a result, CUL4A has been implicated in several cancers and the pathogenesis of certain viruses including HIV. A component of a CUL4A complex, Cereblon, was discovered to be a major target of the teratogenic agent thalidomide.
The SCNN1G gene encodes for the γ subunit of the epithelial sodium channel ENaC in vertebrates. ENaC is assembled as a heterotrimer composed of three homologous subunits α, β, and γ or δ, β, and γ. The other ENAC subunits are encoded by SCNN1A, SCNN1B, and SCNN1D.
Cullin-2 is a protein that in humans is encoded by the CUL2 gene.
Autocrine motility factor receptor, isoform 2 is a protein that in humans is encoded by the AMFR gene.
Cullin-4B is a protein that in humans is encoded by the CUL4B gene which is located on the X chromosome. CUL4B has high sequence similarity with CUL4A, with which it shares certain E3 ubiquitin ligase functions. CUL4B is largely expressed in the nucleus and regulates several key functions including: cell cycle progression, chromatin remodeling and neurological and placental development in mice. In humans, CUL4B has been implicated in X-linked intellectual disability and is frequently mutated in pancreatic adenocarcinomas and a small percentage of various lung cancers. Viruses such as HIV can also co-opt CUL4B-based complexes to promote viral pathogenesis. CUL4B complexes containing Cereblon are also targeted by the teratogenic drug thalidomide.
Cullin 3 is a protein that in humans is encoded by the CUL3 gene.
RING-box protein 2 is a protein that in humans is encoded by the RNF7 gene.
NEDD8-activating enzyme E1 regulatory subunit is a protein that in humans is encoded by the NAE1 gene.
NEDD8-activating enzyme E1 catalytic subunit is a protein that in humans is encoded by the UBA3 gene.
Anaphase-promoting complex subunit 2 is an enzyme that in humans is encoded by the ANAPC2 gene.
Cullin-associated NEDD8-dissociated protein 1 is a protein that in humans is encoded by the CAND1 gene.
NEDD8-conjugating enzyme Ubc12 is a protein that in humans is encoded by the UBE2M gene.
Sentrin-specific protease 8 is an enzyme that in humans is encoded by the SENP8 gene.
Anaphase-promoting complex subunit 11 is an enzyme that in humans is encoded by the ANAPC11 gene.
Potassium voltage-gated channel subfamily A member 10 also known as Kv1.8 is a protein that in humans is encoded by the KCNA10 gene. The protein encoded by this gene is a voltage-gated potassium channel subunit.
Cullins are a family of hydrophobic scaffold proteins which provide support for ubiquitin ligases (E3). All eukaryotes appear to have cullins. They combine with RING proteins to form Cullin-RING ubiquitin ligases (CRLs) that are highly diverse and play a role in myriad cellular processes, most notably protein degradation by ubiquitination.