In biology, a Src homology domain is one of the two small protein binding domains found in the Srconcoprotein. Homologs of both the Src homology 2 and Src homology 3 domains are found in numerous other proteins. The Src homology 1 domain was an early name of the protein kinase domain.
The SH2domain is a structurally conserved protein domain contained within the Src oncoprotein and in many other intracellular signal-transducing proteins. SH2 domains allow proteins containing those domains to dock to phosphorylated tyrosine residues on other proteins. SH2 domains are commonly found in adaptor proteins that aid in the signal transduction of receptor tyrosine kinase pathways.
The SRC Homology 3 Domain is a small protein domain of about 60 amino acid residues. Initially, SH3 was described as a conserved sequence in the viral adaptor protein v-Crk. This domain is also present in the molecules of phospholipase and several cytoplasmic tyrosine kinases such as Abl and Src. It has also been identified in several other protein families such as: PI3 Kinase, Ras GTPase-activating protein, CDC24 and cdc25. SH3 domains are found in proteins of signaling pathways regulating the cytoskeleton, the Ras protein, and the Src kinase and many others. The SH3 proteins interact with adaptor proteins and tyrosine kinases. Interacting with tyrosine kinases SH3 proteins usually bind far away from the active site. Approximately 300 SH3 domains are found in proteins encoded in the human genome. In addition to that, the SH3 domain was responsible for controlling protein-protein interactions in the signal transduction pathways and regulating the interactions of proteins involved in the cytoplasmic signaling.
The protein kinase domain is a structurally conserved protein domain containing the catalytic function of protein kinases. Protein kinases are a group of enzymes that move a phosphate group onto proteins, in a process called phosphorylation. This functions as an on/off switch for many cellular processes, including metabolism, transcription, cell cycle progression, cytoskeletal rearrangement and cell movement, apoptosis, and differentiation. They also function in embryonic development, physiological responses, and in the nervous and immune system. Abnormal phosphorylation causes many human diseases, including cancer, and drugs that affect phosphorylation can treat those diseases.
In terms of initiating the cell cycle when growth factor signals are present, "Src homology domains" are found on Grb2 proteins, allowing them to bind Receptor Tyrosine Kinases (RTKs), and also on SOS proteins allowing them to interact with Grb2. This brings SOS proteins close to the membrane, where Ras-GDP is bound via a lipid "tail". SOS acts as a Guanosine exchange factor (GEF) for Ras, activating Ras to cleave a phosphate group from Raf, causing it to release the 14-3-3 proteins that are keeping it inactive, which through a downstream signalling cascade allows the release of E2F and thus, progression through the Restriction point (R point) in G1 phase of the cell cycle.
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