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 1072321627 221 IGYIRFNNNLGNSETV--RAFKEALESLESTQGLVIDLRNTPSGGNTGVAEpILGHFVNAKTAYQGYKIQNaGKPYQEAE 298
Cdd:cd07563    65 IGYLRIDSFGGFEIAAaeALLDEALDKLADTDALIIDLRYNGGGSDSLVAY-LASYFTDEDKPVHLYTIYK-RPGNTTTE 142

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1072321627 299 LHLAYVTPSLPY-YSKPVVVLVGHWTGSMGEGMAIGFDAIGAKAVIGTPMADLLGGINQFQLPE 361
Cdd:cd07563   143 LWTLPVVPGGRYgYTKPVYVLTSPVTFSAAEEFAYALKQLKRATVVGETTAGGASPVLPFPLPN 206

tail specific protease; tail specific protease

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072321627  221 IGYIR---FNNNLGNsetvrAFKEALESLEST--QGLVIDLRNTPSGGNTGVAEpILGHFVNAktayqGYKIQNAGKPYQ 295
Cdd:smart00245  30 IGYIRipeFSEHTSN-----LVEKAWKKLEKTnvEGLILDLRNNPGGLLSAAID-VSSLFLDK-----GVIVYTVYRRTG 98

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1072321627  296 EaelHLAYVTPSLPYYSKPVVVLVGHWTGSMGEGMAIGFDAIGAKAVIGTP 346
Cdd:smart00245  99 E---LWTYPANLGRKYSKPLVVLVNKGTASASEIFAGALKDLGRATIVGER 146

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 1072321627 221 IGYIRFNNNLGNSETV--RAFKEALESLESTQGLVIDLRNTPSGGNTGVAEpILGHFVNAKTAYQGYKIQNaGKPYQEAE 298
Cdd:cd07563    65 IGYLRIDSFGGFEIAAaeALLDEALDKLADTDALIIDLRYNGGGSDSLVAY-LASYFTDEDKPVHLYTIYK-RPGNTTTE 142

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1072321627 299 LHLAYVTPSLPY-YSKPVVVLVGHWTGSMGEGMAIGFDAIGAKAVIGTPMADLLGGINQFQLPE 361
Cdd:cd07563   143 LWTLPVVPGGRYgYTKPVYVLTSPVTFSAAEEFAYALKQLKRATVVGETTAGGASPVLPFPLPN 206

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 1072321627 220 GIGYIRFNNNLGNSetVRAFKEALESLESTQGLVIDLRNTPsGGNTGvaePILGHFVNAKtAYQGYKIQNAGKPYQeael 299
Cdd:cd07562    88 RIGYVHIPDMGDDG--FAEFLRDLLAEVDKDGLIIDVRFNG-GGNVA---DLLLDFLSRR-RYGYDIPRGGGKPVT---- 156

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072321627 300 hlayvTPSLpYYSKPVVVLVGHWTGSMGEGMAIGFDAIGAKAVIGTPMADLLGGINQFQLP-ESTITL-ELGFerlYHVN 377
Cdd:cd07562   157 -----YPSG-RWRGPVVVLVNEGSASDAEIFAYGFRALGLGPVVGTRTAGGVIISGRYRLPdGGSLTVpEFGV---YLPD 227

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 1072321627 378 GSYRED--FVP-QAVSWD--GHTAS-DSELNAAIALLKA 410
Cdd:cd07562   228 GGPLENrgVAPdIEVENTpeDVAAGrDPQLEAAIEELLK 266

C-terminal processing peptidase; serine protease family S41; The C-terminal processing peptidase (CPP, EC 3.4.21.102) also known as tail-specific protease (tsp), the photosystem II D1 C-terminal processing protease (D1P), and other related S41 protease family members are present in this CD. CPP is synthesized as a precursor form with a carboxyl-terminal extension. It specifically recognizes a C-terminal tripeptide, Xaa-Yaa-Zaa, in which Xaa is preferably Ala or Leu, Yaa is preferably Ala or Tyr and Zaa is preferably Ala, but then cleaves at a variable distance from the C-terminus. The C-terminal carboxylate group is essential, and proteins where this group is amidated are not substrates. This family of proteases contains the PDZ domain that promotes protein-protein interactions and is important for substrate recognition. The active site consists of a serine/lysine catalytic dyad. The bacterial CCP-1 is believed to be important for the degradation of incorrectly synthesized proteins as well as protection from thermal and osmotic stresses. In E. coli, it is involved in the cleavage of a C-terminal peptide of 11 residues from the precursor form of penicillin-binding protein 3 (PBP3). In the plant chloroplast, the enzyme removes the C-terminal extension of the D1 polypeptide of photosystem II, allowing the light-driven assembly of the tetranuclear manganese cluster, which is responsible for photosynthetic water oxidation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072321627 221 IGYIR---FNNNlgnseTVRAFKEALESLEST--QGLVIDLRNTPsGG--NTGVAepILGHFVNAKTAYQgykIQNAGKP 293
Cdd:cd07560    50 IGYIRitsFSEN-----TAEELKKALKELKKQgmKGLILDLRNNP-GGllDEAVE--IADLFLPGGPIVS---TKGRNGK 118

                          90       100
                  ....*....|....*....|....*.
gi 1072321627 294 YQeaelhlAYVTPSLPYYSKPVVVLV 319
Cdd:cd07560   119 RE------AYASDDGGLYDGPLVVLV 138

tail specific protease; tail specific protease

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1072321627  221 IGYIR---FNNNLGNsetvrAFKEALESLEST--QGLVIDLRNTPSGGNTGVAEpILGHFVNAktayqGYKIQNAGKPYQ 295
Cdd:smart00245  30 IGYIRipeFSEHTSN-----LVEKAWKKLEKTnvEGLILDLRNNPGGLLSAAID-VSSLFLDK-----GVIVYTVYRRTG 98

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1072321627  296 EaelHLAYVTPSLPYYSKPVVVLVGHWTGSMGEGMAIGFDAIGAKAVIGTP 346
Cdd:smart00245  99 E---LWTYPANLGRKYSKPLVVLVNKGTASASEIFAGALKDLGRATIVGER 146

Tricorn protease C1 domain; This domain is the C1 core domain of tricorn protease. This is a mixed alpha-beta domain.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1072321627  27 KESWQafvqTVEDNYAYLDTAPTDWEALKAYYQPLAINATTQEEFVDVLQ 76
Cdd:pfam14684   9 DEAWR----LLRDNFYDPDMHGVDWEAVRERYRPLLPRIATRDDLSDLLS 54

PDZ domain; PDZ domains are found in diverse signaling proteins.

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 1072321627 116 VITRIKAGSAAANSQLALGDVIVGIDGESTEAAIH 150
Cdd:pfam00595  28 FVSEVLPGGAAEAGGLKVGDRILSINGQDVENMTH 62

PDZ domain of syntrophins, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of syntrophins (including alpha-1-syntrophin, beta-1-syntrophin, beta-2-syntrophin, gamma-1-syntrophin, and gamma-2-syntrophin), and related domains. Syntrophins play a role in recruiting various signaling molecules into signaling complexes and help provide appropriate spatiotemporal regulation of signaling pathways. They function in cytoskeletal organization and maintenance; as components of the dystrophin-glycoprotein complex (DGC), they help maintain structural integrity of skeletal muscle fibers. They link voltage-gated sodium channels to the actin cytoskeleton and the extracellular matrix, and control the localization and activity of the actin reorganizing proteins such as PI3K, PI(3,4)P2 and TAPP1. Through association with various cytoskeletal proteins within the cells, they are involved in processes such as regulation of focal adhesions, myogenesis, calcium homeostasis, and cell migration. They also have roles in synapse formation and in the organization of utrophin, acetylcholine receptor, and acetylcholinesterase at the neuromuscular synapse. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This syntrophin-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 1072321627 116 VITRIKAGSAAANS-QLALGDVIVGIDGESTEAAIH 150
Cdd:cd06801    28 LISKIFKGQAADQTgQLFVGDAILSVNGENLEDATH 63