Interphotoreceptor retinoid-binding protein; serine protease family S41; Interphotoreceptor retinoid-binding protein (IRBP) is a homolog of the S41 protease, C-terminal processing peptidase (CTPase) family. It is thought to facilitate the compartmentalization of the visual cycle that requires poorly soluble and potentially toxic retinoids to cross the aqueous subretinal space between the photoreceptors and the retinal pigment epithelium (RPE). IRBP is secreted by photoreceptors into the interphotoreceptor matrix (IPM) where it is rapidly turned over by a combination of RPE and photoreceptor endocytosis. It is the most abundant soluble protein component of the IPM, consisting of homologous modules, each repeat structure arising through the duplication (as in teleost IRBP) or quadruplication (in tetrapods) of an ancient gene, arisen in the early evolution of the vertebrate eye. IRBP has been shown to promote the release of all-trans retinol from photoreceptors and facilitates its delivery to the RPE. Conversely, IRBP can promote the release of 11-cis-retinal from the RPE, prevent its isomerization in the subretinal space, and transfer it to photoreceptors. In vivo evidence implicates IRBP as a retinoid transporter in the visual cycle, suggesting a critical role for IRBP in cone function essential for human vision. IRBP is a dominant autoimmune antigen in the eye; IRBP proteolysis analysis has proven a useful biomarker for autoimmune uveitis (AU) disorders, a major cause of blindness. This family also includes a chlamydia-secreted protein, designated chlamydia protease-like activity factor (CPAF), known to degrade host proteins, enabling Chlamydia to evade host defenses and replicate.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68235858   1 VDTIYDRPSNTTTEIWTLPKVLGERYSAEKDVVVLTSGHTGGVAEDIAYILKQMRRAIVVGERTEGGALDLQKLRIGQsN 80
Cdd:cd07563 129 LYTIYKRPGNTTTELWTLPVVPGGRYGYTKPVYVLTSPVTFSAAEEFAYALKQLKRATVVGETTAGGASPVLPFPLPN-G 207

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 68235858  81 FFLTVPVSRSLGPLggGGQTWEGSGVLPCVGTPAEQALEKALA 123
Cdd:cd07563 208 LYLTVPTSRSVDPI--TGTNWEGVGVPPDIEVPATPGYDDALE 248

Interphotoreceptor retinoid-binding protein; serine protease family S41; Interphotoreceptor retinoid-binding protein (IRBP) is a homolog of the S41 protease, C-terminal processing peptidase (CTPase) family. It is thought to facilitate the compartmentalization of the visual cycle that requires poorly soluble and potentially toxic retinoids to cross the aqueous subretinal space between the photoreceptors and the retinal pigment epithelium (RPE). IRBP is secreted by photoreceptors into the interphotoreceptor matrix (IPM) where it is rapidly turned over by a combination of RPE and photoreceptor endocytosis. It is the most abundant soluble protein component of the IPM, consisting of homologous modules, each repeat structure arising through the duplication (as in teleost IRBP) or quadruplication (in tetrapods) of an ancient gene, arisen in the early evolution of the vertebrate eye. IRBP has been shown to promote the release of all-trans retinol from photoreceptors and facilitates its delivery to the RPE. Conversely, IRBP can promote the release of 11-cis-retinal from the RPE, prevent its isomerization in the subretinal space, and transfer it to photoreceptors. In vivo evidence implicates IRBP as a retinoid transporter in the visual cycle, suggesting a critical role for IRBP in cone function essential for human vision. IRBP is a dominant autoimmune antigen in the eye; IRBP proteolysis analysis has proven a useful biomarker for autoimmune uveitis (AU) disorders, a major cause of blindness. This family also includes a chlamydia-secreted protein, designated chlamydia protease-like activity factor (CPAF), known to degrade host proteins, enabling Chlamydia to evade host defenses and replicate.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68235858   1 VDTIYDRPSNTTTEIWTLPKVLGERYSAEKDVVVLTSGHTGGVAEDIAYILKQMRRAIVVGERTEGGALDLQKLRIGQsN 80
Cdd:cd07563 129 LYTIYKRPGNTTTELWTLPVVPGGRYGYTKPVYVLTSPVTFSAAEEFAYALKQLKRATVVGETTAGGASPVLPFPLPN-G 207

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 68235858  81 FFLTVPVSRSLGPLggGGQTWEGSGVLPCVGTPAEQALEKALA 123
Cdd:cd07563 208 LYLTVPTSRSVDPI--TGTNWEGVGVPPDIEVPATPGYDDALE 248

Interphotoreceptor retinoid-binding protein; serine protease family S41; Interphotoreceptor retinoid-binding protein (IRBP) is a homolog of the S41 protease, C-terminal processing peptidase (CTPase) family. It is thought to facilitate the compartmentalization of the visual cycle that requires poorly soluble and potentially toxic retinoids to cross the aqueous subretinal space between the photoreceptors and the retinal pigment epithelium (RPE). IRBP is secreted by photoreceptors into the interphotoreceptor matrix (IPM) where it is rapidly turned over by a combination of RPE and photoreceptor endocytosis. It is the most abundant soluble protein component of the IPM, consisting of homologous modules, each repeat structure arising through the duplication (as in teleost IRBP) or quadruplication (in tetrapods) of an ancient gene, arisen in the early evolution of the vertebrate eye. IRBP has been shown to promote the release of all-trans retinol from photoreceptors and facilitates its delivery to the RPE. Conversely, IRBP can promote the release of 11-cis-retinal from the RPE, prevent its isomerization in the subretinal space, and transfer it to photoreceptors. In vivo evidence implicates IRBP as a retinoid transporter in the visual cycle, suggesting a critical role for IRBP in cone function essential for human vision. IRBP is a dominant autoimmune antigen in the eye; IRBP proteolysis analysis has proven a useful biomarker for autoimmune uveitis (AU) disorders, a major cause of blindness. This family also includes a chlamydia-secreted protein, designated chlamydia protease-like activity factor (CPAF), known to degrade host proteins, enabling Chlamydia to evade host defenses and replicate.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68235858 134 VVLRLQEALQDYY----TLVDRVPGLLHHLAGMDYSAVVSEEDLVTKLNAGLQAVsEDPRLLVRAtgpretssrpetgdp 209
Cdd:cd07563   1 VFEALAKLLEENYafpeAKGIDWDALAARLRAQVYLDITSPEELAAVLTADLQEL-GDGHLNVSY--------------- 64

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 68235858 210 paatpevpkeedarralvdsvfqvsvlpgnVGYLRFDRFADASVlrTLGPYVLQQVWEPLQDTEHLI 276
Cdd:cd07563  65 ------------------------------IGYLRIDSFGGFEI--AAAEALLDEALDKLADTDALI 99

Peptidase family S41;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 68235858    32 VVVLTSGHTGGVAEDIAYILKQMRRAIVVGERTeGGALDLQKLRIGQSNFFLTVPVSRSLGPlggGGQTWEGSGVLP 108
Cdd:pfam03572  89 LVVLVNEGSASASEIFAGALQDNGRATLVGERT-FGKGTVQTVYPLPDGSALKLTIAKYYTP---DGRSIEGKGIEP 161

Interphotoreceptor retinoid-binding protein; serine protease family S41; Interphotoreceptor retinoid-binding protein (IRBP) is a homolog of the S41 protease, C-terminal processing peptidase (CTPase) family. It is thought to facilitate the compartmentalization of the visual cycle that requires poorly soluble and potentially toxic retinoids to cross the aqueous subretinal space between the photoreceptors and the retinal pigment epithelium (RPE). IRBP is secreted by photoreceptors into the interphotoreceptor matrix (IPM) where it is rapidly turned over by a combination of RPE and photoreceptor endocytosis. It is the most abundant soluble protein component of the IPM, consisting of homologous modules, each repeat structure arising through the duplication (as in teleost IRBP) or quadruplication (in tetrapods) of an ancient gene, arisen in the early evolution of the vertebrate eye. IRBP has been shown to promote the release of all-trans retinol from photoreceptors and facilitates its delivery to the RPE. Conversely, IRBP can promote the release of 11-cis-retinal from the RPE, prevent its isomerization in the subretinal space, and transfer it to photoreceptors. In vivo evidence implicates IRBP as a retinoid transporter in the visual cycle, suggesting a critical role for IRBP in cone function essential for human vision. IRBP is a dominant autoimmune antigen in the eye; IRBP proteolysis analysis has proven a useful biomarker for autoimmune uveitis (AU) disorders, a major cause of blindness. This family also includes a chlamydia-secreted protein, designated chlamydia protease-like activity factor (CPAF), known to degrade host proteins, enabling Chlamydia to evade host defenses and replicate.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68235858   1 VDTIYDRPSNTTTEIWTLPKVLGERYSAEKDVVVLTSGHTGGVAEDIAYILKQMRRAIVVGERTEGGALDLQKLRIGQsN 80
Cdd:cd07563 129 LYTIYKRPGNTTTELWTLPVVPGGRYGYTKPVYVLTSPVTFSAAEEFAYALKQLKRATVVGETTAGGASPVLPFPLPN-G 207

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 68235858  81 FFLTVPVSRSLGPLggGGQTWEGSGVLPCVGTPAEQALEKALA 123
Cdd:cd07563 208 LYLTVPTSRSVDPI--TGTNWEGVGVPPDIEVPATPGYDDALE 248

C-terminal processing peptidase family S41; Peptidase family S41 (C-terminal processing peptidase or CTPase family) contains very different subfamilies; it includes photosystem II D1 C-terminal processing protease (CTPase), interphotoreceptor retinoid-binding protein IRBP and tricorn protease (TRI). CTPase and TRI both contain the PDZ domain while IRBP, although being very similar to the tail-specific protease domain, lacks the PDZ insertion domain and hydrolytic activity. These serine proteases have distinctly different active sites: in CTPase, the active site consists of a serine/lysine catalytic dyad while in tricorn core protease, it is a tetrad (serine, histidine, serine, glutamate). CPases with different substrate specificities in different species include processing of D1 protein of the photosystem II reaction center in higher plants and cleavage of a peptide of 11 residues from the precursor form of penicillin-binding protein; and others such as tricorn protease (TRI) act as a carboxypeptidase, involved in the degradation of proteasomal products. CTPase homolog IRBP, secreted by photoreceptors into the interphotoreceptor matrix, having arisen in the early evolution of the vertebrate eye, promotes the release of all-trans retinol from photoreceptors and facilitates its delivery to the retinal pigment epithelium.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68235858   1 VDTIYDRPSNttteiWTLPKVLGERYSAEKDVVVLTSGHTGGVAEDIAYILKQMRRAIVVGERTEGGALDlQKLRIGQSN 80
Cdd:cd06567 121 VVTTRRRGGN-----ETEYVAPGGGSLYDGPLVVLVNEGSASASEIFAGALQDLGRATLVGERTFGKGSV-QTVFPLLDG 194

                        90       100       110
                ....*....|....*....|....*....|
gi 68235858  81 FFLTVPVSRSLGPlggGGQTWEGSGVLPCV 110
Cdd:cd06567 195 SALKLTTAKYYTP---SGRSIEGKGVEPDI 221

C-terminal processing protease CtpA/Prc, contains a PDZ domain [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68235858  32 VVVLTSGHTGGVAEDIAYILKQMRRAIVVGERTEGGAldlqklrIGQSNF------FLTVPVSRSLGPlggGGQTWEGSG 105
Cdd:COG0793 244 LVVLVNEGSASASEIFAGALQDYGRGVIVGTRTFGKG-------SVQTVFplpdggALKLTTARYYTP---SGRSIQGKG 313

                ...
gi 68235858 106 VLP 108
Cdd:COG0793 314 VEP 316

Tricorn protease; serine protease family S41; The tricorn protease (TRI), a member of the S41 peptidase family and named for its tricorn-like shape, exists only in some archaea and eubacteria. It has been shown to act as a carboxypeptidase, involved in the degradation of proteasomal products to preferentially yield di- and tripeptides, with subsequent and final degradations to free amino acid residues by tricorn interacting factors, F1, F2 and F3. Tricorn is a hexameric D3-symmetric protease of 720kD, and can self-associate further into a giant icosahedral capsid structure containing twenty copies of the complex. Each tricorn peptidase monomer consists of five structural domains: a six-bladed beta-propeller and a seven-bladed beta-propeller that limit access to the active site, the two domains (C1 and C2) that carry the active site residues, and a PDZ-like domain (proposed to be important for substrate recognition) between the C1 and C2 domains. The active site tetrad residues are distributed between the C1 and C2 domains, with serine and histidine on C1 and serine and glutamate on C2.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68235858  32 VVVLTSGHTGGVAEDIAYILKQMRRAIVVGERTEGGALDLQKLR-IGQSnfFLTVPVSRSLGPLGGGGqtwEGSGVLPCV 110
Cdd:cd07562 166 VVVLVNEGSASDAEIFAYGFRALGLGPVVGTRTAGGVIISGRYRlPDGG--SLTVPEFGVYLPDGGPL---ENRGVAPDI 240

                        90       100
                ....*....|....*....|....
gi 68235858 111 ---GTPAEQA------LEKALAIL 125
Cdd:cd07562 241 eveNTPEDVAagrdpqLEAAIEEL 264