这一推断是基于黑豹的同源性映射。简言之,所有涉及的物理量(输入、输出和催化剂)都有一个映射的正态/旁态(对于络合物,至少75%的组分必须有一个映射)的反应被推断为其他物种。还为这些事件推断出高级事件,以便于导航。
http://www.pantherdb.org/about.jsp“target='NEW'>http://www.pantherdb.org/about.jsp
这一推断是基于黑豹的同源性映射。简言之,所有涉及的物理量(输入、输出和催化剂)都有一个映射的正态/旁态(对于络合物,至少75%的组分必须有一个映射)的反应被推断为其他物种。还为这些事件推断出高级事件,以便于导航。
http://www.pantherdb.org/about.jsp“target='NEW'>http://www.pantherdb.org/about.jsp
这一推断是基于黑豹的同源性映射。简言之,所有涉及的物理量(输入、输出和催化剂)都有一个映射的正态/旁态(对于络合物,至少75%的组分必须有一个映射)的反应被推断为其他物种。还为这些事件推断出高级事件,以便于导航。
http://www.pantherdb.org/about.jsp“target='NEW'>http://www.pantherdb.org/about.jsp
(注:357个OR基因中的200个子集显示为OR- g蛋白反应的组成部分。其他的将在稍后添加到Reactome。
有两种型号为GPCR-G蛋白相互作用:1)配体的GPCR第一结合,然后结合至G蛋白;2)“预偶联”的GPCR和G蛋白的前配体结合(欧丹&2008哈姆)。这两种型号可能是在不同的上下文某些GPCR的真实。预耦合很可能是功能上重要的,因为受体和G蛋白的预耦合允许一旦配体结合更快速的动力学响应,这是因为配位体结合的受体是立即能够转导信号,而不是扩散周围 within the plasma membrane until it encounters a G Protein to interact with (Oldham & Hamm 2008).
The pre-coupling model is used here to characterise the reaction of the human ORs with G Proteins in the absence of ligand, because the ligands in humans are almost completely undocumented experimentally.
In model genetic systems such as mice, many candidate OR genes have been shown experimentally to function in olfactory signaling (reviewed in (Keller & Vosshall 2008). For the human OR genes, experimental analysis has been much more limited, although some specific OR genes, such as OR7D4 and OR11H7P have been confirmed to mediate olfactory response and signaling in humans for specific chemical odorants (Keller et al. 2007, Abbafy 2007). Mice and other rodents are believed to have about 1000 functional OR genes, as well as many additional pseudogenes. Based on sequence similarities, there are 960 human OR genes, but approximately half of these are pseudogenes (Keller 2008). In mice, essentially all olfactory signaling requires G-alpha-S (OLF); mouse G-OLF knockouts have been shown to lack olfactory responses (Belluscio 1998). Bona fide human OR genes identified by sequence similarity (not pseudogenes with function-blocking mutations) that are expressed in olfactory epithelium are expected to interact with G alpha S OLF containing G Protein trimers.
Of the 960 human OR genes and pseudogenes, there is experimental evidence that indicates over 430 are expressed in human olfactory epithelium, including 80 expressed OR pseudogenes (Zhang 2007).
When expressed in model cell systems mammalian odorant receptors (OR) are typically retained in the ER and degraded by the proteasome (McClintock et al. 1997). A study using Caenorhabditis elegans showed that the transport of ORs to the cilia of olfactory neurons required the expression and association of ORs with a transmembrane protein, ODR4 (Dwyer et al. 1998). Co-transfection of rat ORs with ODR4 enhanced the transport and expression of ORs at the cell-surface (Gimelbrant et al. 2001). These studies suggested that olfactory neurons might have a selective molecular machinery that promotes expression of ORs at the cells surface. Two human protein families have been identified as potential accessory proteins involved in the trafficking of ORs to the plasma membrane (Saito et al. 2004). Receptor transporting proteins 1 and 2 (RTP1, RTP2) both strongly induced expression of several ORs at the cell-surface. To a lesser extent, the receptor expression enhancing protein 1 (REEP1) also promoted cell-surface expression. These proteins are specifically expressed in olfactory neurons with no expression in testis, where a subset of ORs are expressed (Parmentier et al. 1992, Spehr et al. 2003). Other members of the RTP and REEP families have a widespread distribution. RTP3 and RTP4 have been shown to promote cell-surface expression of the bitter taste receptors, TAS2Rs (Behrens et al. 2006). REEP1 and REEP5 (also known as DP1) are involved in shaping the ER by linking microtubule fibers to the ER (Park et al. 2010, Voeltz et al. 2006). A recent study looking at the role of REEP in the trafficking of Alpha2A- and Alpha2C-adrenergic receptors showed that REEP1-2 and 6 enhance the cell-surface expression of Alpha2C, but not Alpha2A, by increasing the capacity of ER cargo, thereby allowing more receptors to reach the cell-surface (Bjork et al. 2013). Unlike RTP1, REEP1-2 and 6 are only present in the ER, do not traffic to the plasma membrane and specifically interact with the minimal/non-glycosylated forms of Alpha2C via an interaction with its C-terminus (Saito et al. 2004, Bjork et al. 2013). REEPs may function as general modulators of the ER, rather than specifically interacting with GPCRs. Loss of association of REEP2 with membranes leads to hereditary spastic paraplegia (Esteves et al. 2014).
Olfactory receptors (ORs) are present on the plasma membrane of cilia of olfactory sensory neurons located in the olfactory epithelium of the nasal sinus. Each mature neuron expresses only one OR gene (reviewed in Nagai et al. 2016) and each OR binds one particular volatile chemical or set of volatile chemicals, known as odorants. The binding of an odorant to an OR (Mainland et al. 2015) causes a conformational change in the receptor that activates the G alpha subunit (Golf, GNAL) of an associated heterotrimeric G protein complex to exchange GDP for GTP (inferred from mouse homologs in Jones et al. 1990). GNAL:GTP and the Gbeta:Ggamma subcomplex (GNB1:GNG13) dissociate from the olfactory receptor and GNAL:GTP then binds and activates adenylate cyclase 3 (ADCY3) (inferred from rat homologs in Bakalyar and Reed 1990, reviewed in Boccaccio et al. 2021). Cyclic AMP produced by ADCY3 binds and opens the olfactory cyclic nucleotide-gated channel (CNG channel) composed of CNGA2, CNGA4, and CNGB isoform 1b (inferred from rat homologs in Liman and Buck 1994). The CNG channel translocates sodium and calcium cations from the extracellular region into the cytosol. The resulting cytosolic calcium ions bind ANO2 and increase the transport of chloride ions by ANO2 from the cytosol to the extracellular region (inferred from mouse homologs in Pifferi et al. 2009, Stephan et al. 2009). The translocations of ions across the plasma membrane causes depolarization of the neuron yielding a receptor potential and action potential that is transmitted to the olfactory bulb of the brain.