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 549440220   3 GMQAAIEQAMKSHEILSISDPQTLAHVLTAGVQSsLNDPRLLISYepsaleapqqapalsnlsreellaqmqrnihhevl 82
Cdd:cd07563   21 IDWDALAARLRAQVYLDITSPEELAAVLTADLQE-LGDGHLNVSY----------------------------------- 64

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 549440220  83 egnVGYLRVDDLPGQEVlsELGEFLVTHIWKQLMDTSSLVLDLRHCTGGHVSGIPYVISYLNPGNTVMHVDTIYDRPSNT 162
Cdd:cd07563   65 ---IGYLRIDSFGGFEI--AAAEALLDEALDKLADTDALIIDLRYNGGGSDSLVAYLASYFTDEDKPVHLYTIYKRPGNT 139

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 549440220 163 TTEIWTLPKVLGERYSADKDVVVLTSGRTGGV*EDIAYILKQMRRAIVV 211
Cdd:cd07563  140 TTELWTLPVVPGGRYGYTKPVYVLTSPVTFSAAEEFAYALKQLKRATVV 188

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 549440220   3 GMQAAIEQAMKSHEILSISDPQTLAHVLTAGVQSsLNDPRLLISYepsaleapqqapalsnlsreellaqmqrnihhevl 82
Cdd:cd07563   21 IDWDALAARLRAQVYLDITSPEELAAVLTADLQE-LGDGHLNVSY----------------------------------- 64

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 549440220  83 egnVGYLRVDDLPGQEVlsELGEFLVTHIWKQLMDTSSLVLDLRHCTGGHVSGIPYVISYLNPGNTVMHVDTIYDRPSNT 162
Cdd:cd07563   65 ---IGYLRIDSFGGFEI--AAAEALLDEALDKLADTDALIIDLRYNGGGSDSLVAYLASYFTDEDKPVHLYTIYKRPGNT 139

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 549440220 163 TTEIWTLPKVLGERYSADKDVVVLTSGRTGGV*EDIAYILKQMRRAIVV 211
Cdd:cd07563  140 TTELWTLPVVPGGRYGYTKPVYVLTSPVTFSAAEEFAYALKQLKRATVV 188

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 549440220  80 EVLEGNVGYLRVDDL---PGQEVLSELGEFlvthiwkQLMDTSSLVLDLRHCTGGHVSGIPYVISYLNPGNTVMhvdtiY 156
Cdd:COG0793  153 KLLEGKIGYIRIPSFgenTAEEFKRALKEL-------KKQGAKGLILDLRNNPGGLLDEAVELADLFLPKGPIV-----Y 220

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 549440220 157 DRPSNTTTEIWtlpKVLGERYSADKDVVVLTSGRTGGV*EDIAYILKQMRRAIVV 211
Cdd:COG0793  221 TRGRNGKVETY---KATPGGALYDGPLVVLVNEGSASASEIFAGALQDYGRGVIV 272

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 549440220   3 GMQAAIEQAMKSHEILSISDPQTLAHVLTAGVQSsLNDPRLLISYepsaleapqqapalsnlsreellaqmqrnihhevl 82
Cdd:cd07563   21 IDWDALAARLRAQVYLDITSPEELAAVLTADLQE-LGDGHLNVSY----------------------------------- 64

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 549440220  83 egnVGYLRVDDLPGQEVlsELGEFLVTHIWKQLMDTSSLVLDLRHCTGGHVSGIPYVISYLNPGNTVMHVDTIYDRPSNT 162
Cdd:cd07563   65 ---IGYLRIDSFGGFEI--AAAEALLDEALDKLADTDALIIDLRYNGGGSDSLVAYLASYFTDEDKPVHLYTIYKRPGNT 139

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 549440220 163 TTEIWTLPKVLGERYSADKDVVVLTSGRTGGV*EDIAYILKQMRRAIVV 211
Cdd:cd07563  140 TTELWTLPVVPGGRYGYTKPVYVLTSPVTFSAAEEFAYALKQLKRATVV 188

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 549440220  85 NVGYLRVDDLPGQEVLSELGEFLVthiwKQLMDTSSLVLDLRHCTGGHVSGIPYVISYLNPGNTVMHVDTIYDRPsnttt 164
Cdd:cd06567   60 TIGYIRIPSFSAESTAEELREALA----ELKKGVKGLILDLRNNPGGLLSAAVELASLFLPKGKIVVTTRRRGGN----- 130

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 549440220 165 eiWTLPKVLGERYSADKDVVVLTSGRTGGV*EDIAYILKQMRRAIVV 211
Cdd:cd06567  131 --ETEYVAPGGGSLYDGPLVVLVNEGSASASEIFAGALQDLGRATLV 175

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 549440220  79 HEVLEGNVGYLRVDDLpGQEVLSELgeflvthiWKQLMDTSS---LVLDLRHCTGGHVSGipYVISYLNPGNTVMHVDTI 155
Cdd:cd07562   82 EELSDGRIGYVHIPDM-GDDGFAEF--------LRDLLAEVDkdgLIIDVRFNGGGNVAD--LLLDFLSRRRYGYDIPRG 150

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 549440220 156 YDRPSNTTTEIWTLPkvlgerysadkdVVVLTSGRTGGV*EDIAYILKQMRRAIVV 211
Cdd:cd07562  151 GGKPVTYPSGRWRGP------------VVVLVNEGSASDAEIFAYGFRALGLGPVV 194

N-terminal domain of Peptidase_S41 in eukaryotic IRBP; Peptidase_S41_N is a family found at the N-terminus of the functional unit of interphotoreceptor retinoid binding proteins 3, IRBP, in eukaryotes. From the structure of PDB:1j7x, the domain forms the N-terminal end of the module which is characterized as a serine-peptidase, pfam03572. Peptidase_S41_N forms a three-helix bundle followed by a small beta strand and is termed domain A. Part of the peptidase domain folds back over domain A to create a largely hydrophobic cleft between the two domains. On binding of ligand domain A is structurally rearranged with respect to domain B.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 549440220    3 GMQAAIEQAMKSHEILSISDPQTLAHVLTAGVQSSLNDPRLLISY--------EPSALEAPQQAPALSNLSREELLAQMQ 74
Cdd:pfam11918  41 AVAAHLASLLASGDYSSVVSEEDLASKLNADLQALSGDPRLKVRYirpepasdEPEAADNIPGLVPMQPPSPEMLEALIK 120

                  ....*....
gi 549440220   75 RNIHHEVLE 83
Cdd:pfam11918 121 SSFKVDVLP 129