1J7X,3DJA


Conserved Protein Domain Family
Peptidase_S41_IRBP

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cd07563: Peptidase_S41_IRBP 
Click on image for an interactive view with Cn3D
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.
Statistics
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PSSM-Id: 143479
View PSSM: cd07563
Aligned: 65 rows
Threshold Bit Score: 122.786
Threshold Setting Gi: 219852797
Created: 29-Apr-2009
Updated: 17-Jan-2013
Structure
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Program:
Drawing:
Aligned Rows:
 
active site
Conserved site includes 3 residues -Click on image for an interactive view with Cn3D
Feature 1:active site triad [active site]
Evidence:
  • Comment:Active site residues are inferred for IRBP from CPAF
  • Comment:Mutations of catalytic triad abolish CPAF autocleavage and proteolytic activity.
  • Structure:3DJA: Chlamydia trachomatis secreted protease CPAF
    View structure with Cn3D

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                            #           
1J7X_A         7 VLHQLCDILANNYAfser-----iptLLQHLPNldys--------tvisEEDIAAKLNYELQslteDPRLVLKSktdtlv 73
3DJA_A        12 DLSFLEHLLQVKYApktwkeqylgwdLVQSSVSaqqklr----tqenpsTSFCQQVLADFIGgl-nDFHAGVTFfaiesa 86
gi 12644488   34 DLNVIEHLISLKYAplpwkellfgwdLSQQTQQarlqlv----leekptTNYCQKVLSNYVRsl-nDYHAGITFyrtesa 108
gi 46446550   38 DLKMIKHAFDVGYAplewkk-nytglNLDEELNksidlil---snptltHKDFQRIVKNFLAst-kDYHVDVIFfsteta 112
gi 118444694  45 DFNYMYNILKENYPyfevn---krqnKVDWLNKkndyism---ikttknDKEFLNTLHNILKel-nNGHTDIMPekfysp 117
gi 157364108 110 YLMNGGKVVPIFVSfddeq--itiltDVEGKLNqpgklislngvsagdlKEEILKMVSFERAsf-gYARASLLFhlycwv 186
gi 160887775 160 NGLPYKQWIEQNEKyte------astVPHRRLRtay-----------daFRSYADTLRNYTLlr-gGDTLTVTLplkqrd 221
gi 188587087  54 DFKYMYNIMKENYVnlydi--dtdwlDMKAHFKasvk--------dtddNYEFYQQMYNSLRvi-dDLHLGIYDpkmfys 122
gi 227367015 119 DHEKLYSSANTGQIpagsailsingqDIESLFQnmkknig--gtsqfrdIISLKLFSYFLYLen-iTAPFSVKYklpegd 195
gi 227485935  97 DFEYLFKELKESYPffgvl---krkyEVDFLKNhdaylkk---vracknDGEFIKVLNEVMAdl-hNYHAKIADsayvdq 169
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                        
1J7X_A        74 xpgdsiqaeniped------------------------------------------------------------------ 87
3DJA_A        87 ylpytvqkssdgrfyfvdixtfsseirvgdellevdgapvqdvlatlygsnhkgtaaeesaalrtlfsrxaslghkvpsg 166
gi 12644488  109 yipyvlklsedghvfvvdvqtsqgdiylgdeilevdgmgireaieslrfgrgsatdysaavrsltsrsaafgdavpsgia 188
gi 46446550  113 tlpfdvkgvnnryfitwidelklppstytikvgdeiiefdgrplgdvieelkqhgsknsnpltdqalaeikltnrlgwlg 192
gi 118444694 118 faslytertdlnkawldelnkpkslery---------------------------------------------------- 145
gi 157364108 187 ifgeqesftvefltqqgqlqkiel-------------------------------------------------------- 210
gi 160887775 222 yfpdne-------------------------------------------------------------------------- 227
gi 188587087 123 kelgsgeiikfadkkyhgwkevfneeg----------------------------------------------------- 149
gi 227367015 196 ireitinegmkfrdf----------------------------------------------------------------- 210
gi 227485935 170 tlkyysqnwnqpsiyyeflnlnrqvvrnryg------------------------------------------------- 200
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                        
1J7X_A           --------------------------------------------------------------------------------
3DJA_A       167 rttlkirrpfgttrevrvkwryvpegvgdlatiapsirapqlqksmrsffpkkddafhrssslfyspmvphfwaelrnhy 246
gi 12644488  189 mlklrrpsglirstpvrwrytpehigdfslvaplipehkpqlptqscvlfrsgvnsqssssslfssymvpyfweelrvqn 268
gi 46446550  193 diipqgpvtikvhsrsk--------evplsyqliwdyrpelifspsfflqtvesffpnkkisvrspcmtmmnlthrkmms 264
gi 118444694     --------------------------------------------------------------------------------
gi 157364108     --------------------------------------------------------------------------------
gi 160887775     --------------------------------------------------------------------------------
gi 188587087     --------------------------------------------------------------------------------
gi 227367015     --------------------------------------------------------------------------------
gi 227485935     --------------------------------------------------------------------------------
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                        
1J7X_A        88 ----------------------------eaxlqalvntvfkvsilpgnIGYLRFdqfadvs---------viaklaPFIV 130
3DJA_A       247 atsglksgynigstdgflpvigpviweseglfrayissvtdgdgkshkVGFLRIptyswqdxe----dfdpsgpppWEEF 322
gi 12644488  269 kqrfdsnhhigsrngflptfgpilweqdkgpyrsyifkakdsqgnphrIGFLRIssyvwtdlegleedhkdspwelFGEI 348
gi 46446550  265 etkrdgtlcarksfiptlgprvwmfdkidkekeiswyayiykiseeekIGYIRIphyigy----------keeskeFGEL 334
gi 118444694 146 ---------------sanndninkktnpniykkptannfrteilekdkVAYLYIksfnyyn--------idsdgkmIYKF 202
gi 157364108 211 -------------------esvdfekyrakreqmnmsgklwdfsiidkTAVMTIntfssay--------ekdlkqfIKQS 263
gi 160887775 228 ------------------------------------eqtvesrilqdsIGYLTIktmmn------------pvmedFKAV 259
gi 188587087 150 ---------------ydidpeqlrdeekekryeggaanidteiieedqIAYLHInsfei------------dsseeIRNF 202
gi 227367015 211 ----------------------------lalsmpgiakpydfkiinhkLAYLDFrsmsgnm---------ddfdkfLSET 253
gi 227485935 201 ------------legvqsqsasasvkrkqekkskgdskanisledhgdLAILKIsqmgdmn--------nekdqkvLDEF 260
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                        
1J7X_A       131 NTVWEpit-iteNLIIDLRyNVGGss-taVPLLLSYFldpetKIHLFTLHnrqqnstdevysh----------------- 191
3DJA_A       323 AKIIQvfssnteALIIDQTnNPGGsv-lyLYALLSXLtd--rPLELPKHRxiltqdevvdaldwltllenvdtnvesrla 399
gi 12644488  349 IDHLEke---tdALIIDQThNPGGsv-fyLYSLLSMLtd--hPLDTPKHRmiftqdevssalhwqdlledvftdeqavav 422
gi 46446550  335 LNYLEqk---tdALVIDQVhNGGGya-sfQYELASMLal--nPLKTPKHQmkitqkdvltayqildviekiqqgiddeie 408
gi 118444694 203 LQKIKdy----kVLIIDIRnNGGGsdnywQENIVSPLln--kTVVYNTYLafrggkfsenfienrfnkkydsldniskik 276
gi 157364108 264 FEQIKked--iqNLIIDLRkNGGGss-eiGEYLYSFIsn--kPYRVYAEIhvkysddavktlkifdplllfrvkv----- 333
gi 160887775 260 YPKVKdl----pYLIIDVRrNGGGns-mnGVNICKYFir--eAQPHCVSKsyimqpe----------------------- 309
gi 188587087 203 MEEISdy----pYLIIDIRgNLGGqr-ywKDVFHNLEev--dYKSYLFSKggdlanyflehkvsedyniddikeypgyed 275
gi 227367015 254 FSTIRken--ikDLAIDLRnNSGGns-ilGDLLLSYItd--qKYSLQGSKrwkisqiykdkliadhnteseylkme---- 324
gi 227485935 261 LRNKHmy----kALVIDIRnNVGGnmeywQSFLLPKLtk--nPKQVINHMffkdsaktrlllqdntlnmenlsnvditgi 334
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                             #          
1J7X_A       192 ----------------------------------------------pkvlgkpygskkGVYVLTShqtaTAAEEFAYLXQ 225
3DJA_A       400 lgdnxegytvdlqvaeylksfgrqvlncwskgdielstpiplfgfekihphprvqyskPICVLINeqdfSCADFFPVVLK 479
gi 12644488  423 lgetmegycmdmhavaslqnfsqsvlsswvsgdinlskpmpllgfaqvrphpkhqytkPLFMLIDeddfSCGDLAPAILK 502
gi 46446550  409 egpidyqhllf-------lkafyeftiqewdgqrtltdpthlegcdwinphsdyrytkPILMLINeldfSGGDFMPAIMQ 481
gi 118444694 277 een-----------------------lsntppelenkfkyykkdvyiihpqypigfkgKIYLITNkkvfSASEAFSVFAQ 333
gi 157364108 334 ----------------------------------lnqkiivhrndfkkvrrndllfnkNVYVLVGpgtfSAAADFAAMVK 379
gi 160887775 310 ----------------------------------------------------adaykgKIYLLTDtytlSAAESFTLDMK 337
gi 188587087 276 -----------------------------lpdhiqenfedyiwkektiepedpldfsgEIFILTDrnvySSSDRLVNFAR 326
gi 227367015 325 ---------------------------------ngtvwetgnckpdfnkfkndpvfkgKVYVLTGpftfSSANLVADGMK 371
gi 227485935 335 rl------------------------dhaedlkdfayyikdtitinpdetkrdngyegPIFLLVDenvfSAAEGFASFIK 390
                        490       500       510       520       530       540       550       560
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                             #                          
1J7X_A       226 SlsRATIIGEITSGNLx---hSKVFPFGd--tQLSVTVPi-INFIDSn-GDYWLGGGVVPDAIVLa------------DE 286
3DJA_A       480 DndRALIVGTRTAGAGg---fVFNVQFPnrtgIKTCSLTg-SLAVREh-GAFIENIGVEPHIDLPftandi--rykgySE 552
gi 12644488  503 DngRATLIGKPTAGAGg---fVFQVTFPnrsgIKGLSLTg-SLAVRKd-GEFIENLGVAPHIDLGftsrdl--qtsrfTD 575
gi 46446550  482 DnqRAVLFGTRTSGAGg---fVLQASFPnnngIAAFSYTg-SIAERPetLLKIENLGVTPDIVYSltvddlqngyqgyKA 557
gi 118444694 334 StgFATLIGEPTGGDGig-fdPAICSLPn--sGYIFRFPl-DLGMISd-GTCNFEHKTIPDIKCNpkmhv----nirrDE 404
gi 157364108 380 DlkAATVVGEETGGLAssygdVLSFILPn--sKLQLGVSf-KYFVRC--GGFDDKRGVIPDIAVQipitdd--tdqlvRT 452
gi 160887775 338 EsgNVTLIGEATGGDTg----NGPRPFCtk-qRTYFRIPtrQPDVSSk-GFPMEGIGIPPHHQVSqtvad---fmkdeDT 408
gi 188587087 327 KtdLATVVGTRTRGGGmngppRLFYSLPn--sGLLIEFEg-FLGLNA--DGKNSYVGTEPDIEVEtqth-----qeliDE 396
gi 227367015 372 QykLAELVGEPTGEYTndfgeAFMFTLPn--sKIQMRSTs-SMSFGAd-CNTSSYTPVVPDILIVptlqd---kingiDK 444
gi 227485935 391 HteFATIVGTQTGGDGit-lgVINSVLPn--sGLVFTYTn-TLGYDPs-GEINEEDPTKPDIESAs-----------yRQ 454

                 ....*
Feature 1             
1J7X_A       287 ALDKA 291
3DJA_A       553 YLDKV 557
gi 12644488  576 YVEAV 580
gi 46446550  558 AVNEA 562
gi 118444694 405 PIKYI 409
gi 157364108 453 VLEAV 457
gi 160887775 409 VLNYA 413
gi 188587087 397 TVEII 401
gi 227367015 445 PLEYI 449
gi 227485935 455 SIETI 459

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