241 human active and 13 inactive phosphatases in total;
194 phosphatases have substrate data;
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336 protein substrates;
83 non-protein substrates;
1215 dephosphorylation interactions;
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299 KEGG pathways;
876 Reactome pathways;
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last scientific update: 11 Mar, 2019
last maintenance update: 01 Sep, 2023
Membrane Cellprojection, cilium, photoreceptor outer segment Note=Synthesized in the innersegment (IS) of rod photoreceptor cells before vectorial transportto disk membranes in the rod outer segment (OS) photosensorycilia
Function (UniProt annotation)
Photoreceptor required for image-forming vision at lowlight intensity (PubMed:8107847, PubMed:7846071) Required forphotoreceptor cell viability after birth (PubMed:2215617,PubMed:12566452) Light-induced isomerization of the chromophore11-cis-retinal to all-trans-retinal triggers a conformationalchange that activates signaling via G-proteins (PubMed:8107847,PubMed:28524165, PubMed:26200343, PubMed:28753425) Subsequentreceptor phosphorylation mediates displacement of the bound G-protein alpha subunit by the arrestin SAG and terminates signaling(PubMed:28524165, PubMed:26200343)
Phototransduction is a biochemical process by which the photoreceptor cells generate electrical signals in response to captured photons. The vertebrate cascade starts with the absorption of photons by the photoreceptive pigments, the rhodopsins, which consist of a membrane embedded chromophore, 11-cis-retinal, and a G-protein-coupled receptor, opsin. The photon isomerizes 11-cis-retinal to all-trans-retinal which induces a structural change that activates the opsin. This triggers hydrolysis of cGMP by activating a transducinphosphodiesterase 6 (PDE6) cascade, which results in closure of the cGMP-gated cation channels (CNG) in the plasma membrane and membrane hyperpolarization. The hyperpolarization of the membrane potential of the photoreceptor cell modulates the release of neurotransmitters to downstream cells. Recovery from light involves the deactivation of the light- activated intermediates: photolyzed rhodopsin is phosphorylated by rhodopsin kinase (RK) and subsequently capped off by arrestin; GTP-binding transducin alpha subunit deactivates through a process that is stimulated by RGS9.
The retinoid cycle (also referred to as the visual cycle) is the process by which the visual chromophore 11-cis-retinal (11cRAL) is released from light-activated opsins in the form all-trans-retinal and isomerized back to its 11-cis isomer ready for another photoisomerization reaction. This process involves oxidation, reduction and isomerization reactions and take place in the retinal pigment epithelium (RPE) and photoreceptor segments of the eye (von Lintig 2012, Blomhoff & Blomhoff 2006, von Lintig et al. 2010, D'Ambrosio et al. 2011). This section describes the retinoid cycle in rods during dark/twilight conditions
The photoreceptor cascade starts with light isomerization of 11-cis-retinal (11cRAL) of rhodopsin (RHO) to all-trans-retinal (atRAL), inducing a conformational change in RHO to the active, metarhodopsin II (MII) state. MII activates the G protein transducin (Gt) that in turn activates phosphodiesterase 6 (PDE6). Consequently, there is a fall in the intracellular concentration of cGMP that closes cGMP-dependent cation channels (CNG channels) and hyperpolarizes the rod. This has the effect of reducing or stopping glutamate release from synaptic vesicles thus signalling to the surrounding cells how many photons were absorbed (Burns & Pugh 2010, Korenbrot 2012, Pugh & Lamb 1993)
To terminate the single photon response and restore the system to its basal state, the three activated intermediates in phototransduction, rhodopsin (MII), transducin alpha subunit with GTP bound (GNAT1-GTP) and phosphodiesterase 6 (PDE6) all need to be efficiently deactivated. In addition, the cGMP concentrations must be restored to support reopening of the CNG channels. This section describes the inactivation and recovery events of the activated intermediates involved in phototransduction (Burns & Pugh 2010, Korenbrot 2012)
The classical signalling mechanism for G alpha (i) is inhibition of the cAMP dependent pathway through inhibition of adenylate cyclase (Dessauer C W et al. 2002). Decreased production of cAMP from ATP results in decreased activity of cAMP-dependent protein kinases. Other functions of G alpha (i) includes activation of the protein tyrosine kinase c-Src (Ma Y C et al. 2000). Regulator of G-protein Signalling (RGS) proteins can regulate the activity of G alpha (i) (Soundararajan et al. 2008)
Opsins are light-sensitive, 35-55 kDa membrane-bound G protein-coupled receptors of the retinylidene protein family found in photoreceptor cells of the retina. Five classical groups of opsins are involved in vision, mediating the conversion of a photon of light into an electrochemical signal, the first step in the visual transduction cascade (Terakita A, 2005; Nickle B and Robinson PR, 2007). Another opsin found in the mammalian retina, melanopsin, is involved in circadian rhythms and pupillary reflex but not in image-forming (Hankins MW et al, 2008; Kumbalasiri T and Provencio I, 2005). Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G protein transducin, encoded by GNAT genes, is one of the transducers of a visual impulse that performs the coupling between rhodopsin and cGMP-phosphodiesterase. Defects in GNAT1 are the cause of congenital stationary night blindness autosomal dominant type 3, also known as congenital stationary night blindness Nougaret type. Congenital stationary night blindness is a non-progressive retinal disorder characterized by impaired night vision (Dryja TP et al, 1996). Defects in GNAT2 are the cause of achromatopsia type 4 (ACHM4). Achromatopsia is an autosomal recessively inherited visual disorder that is present from birth and that features the absence of color discrimination (Kohl S et al, 2002)
A number of membrane proteins destined for the ciliary membrane are recognized by ARF4 in the trans-Golgi network, initiating the formation of a ciliary targeting complex that directs the passage of these cargo to the cilium (Mazelova et al, 2009; Geng et al, 2006; Jenkins et al, 2006; Ward et al, 2011; reviewed in Deretic, 2013). Although there is some support for the presence of a VxPx or related motif in the C-terminal tail of cargo destined for ARF4-mediated transport to the cilium, the details of this have not been definitively established and other ciliary targeting sequences have also been identified (reviewed in Deretic, 2013; Bhogaraju et al, 2013)
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