E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of NKD2 (By similarity). Stimulates transcription mediated by NF-kappa-B.
RING finger protein 43 (RNF43) is a 90 kDa member of the ZNRF3 family of ubiquitin ligase proteins. Human RNF43 is synthesized as a 783 amino acid (aa) protein that contains a putative 23 aa signal sequence, a 174 aa extracellular domain (ECD), a transmembrane domain, and a cytoplasmic domain with an atypical RING-type zinc finger. RNF43 is expressed in stem cells at the bottom of colon crypts, where it limits the ability of Wnts to induce proliferation. RNF43 and ZNRF3, another transmembrane E3 ubiquitin ligase, ubiquitinate and promote the turnover of Frizzled Wnt receptors to antagonize Wnt signaling. RNF43 has been shown to suppress both canonical and non-canonical Wnt signaling pathways by distinct mechanisms. RNF43/ZNRF3-mediated turnover of Frizzled receptors is inhibited by R-Spondin. Dishevelled, a positive regulator of Wnt signaling, interacts with RNF43/ZNRF3 to mediate turnover of Frizzled receptors. RNF43 may promote cell survival by binding to NEDL1 and by suppressing the transcriptional activity of p53. RNF43 has been shown both to inhibit and promote cancer. Deletion of RNF43, as well as mutations found in colorectal and other cancers, allows hypersensitivity to Wnts and promotes adenoma formation. Furthermore, RNF43 down-regulation in gliomas is associated with poor prognosis. However, RNF43 is frequently over-expressed in cancers, correlating with growth-promoting activity and colorectal and hepatocellular cancer pathogenesis.
ROBO2 belongs to the ROBO family. Members of the ROBO family are a group of highly conserved transmembrane glycoproteins that make up a small subgroup of the immunoglobulin (Ig) superfamily. They are best known for their roles as receptors for the Slit family of repellent axon guidance cues. In structure, ROBOs are characterized by five C2-type Ig-like repeats, three fibronectin type III domains, a transmembrane region, and an intracellular domain with three (ROBO3) or four (ROBO1, 2) CC (conserved cytoplasmic) motifs. ROBO2 is a receptor for SLIT2, and probably SLIT1, which are thought to act as molecular guidance cue in cellular migration, including axonal navigation at the ventral midline of the neural tube and projection of axons to different regions during neuronal development. ROBO2 also abrogates SLIT-ROBO signaling in vitro.
Roundabout homolog 4(ROBO4) contains 2 fibronectin type-III domains; 2 Ig-like C2-type (immunoglobulin-like) domains and belongs to the immunoglobulin superfamily.The protein is a receptor for slit proteins; at least for SLIT2; and seems to be involved in angiogenesis and vascular patterning. ROBO4 may mediate the inhibition of primary endothelial cell migration by Slit proteins.
Roundabout homolog 4; also known as magic roundabout and ROBO4 is a member of theimmunoglobulin superfamily and ROBO family. ROBO4 is specifically expressed in endothelial cells. It is expressed at sites of angiogenesis in different tumor types. ROBO4 contains twofibronectin type-III domains and twoIg-like C2-type (immunoglobulin-like) domains. ROBO4 is the fourth identified member of the roundabout receptor family. It is the only Robo family member expressed in primary endothelial cells and that application of Slit inhibits their migration. ROBO4 is predominantly expressed in embryonic or tumor vascular endothelium and is considered important for vascular development and as a candidate tumor endothelial marker. ROBO4 is a bona fide member of the Robo family and may provide a repulsive cue to migrating endothelial cells during vascular development. ROBO4 is a receptor for Slit proteins; at least for SLIT2; and seems to be involved in angiogenesis and vascular patterning. ROBO4 may mediate the inhibition of primary endothelial cell migration by Slit proteins. Activating ROBO4 may have broad therapeutic application in diseases characterized by excessive angiogenesis and/or vascular leak.
The protein encoded by this gene is a serine/threonine kinase that regulates cytokinesis, smooth muscle contraction, the formation of actin stress fibers and focal adhesions, and the activation of the c-fos serum response element. This protein, which is an isozyme of ROCK1 is a target for the small GTPase Rho.
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