6VX5,4WD8


Conserved Protein Domain Family
Bestrophin

?
pfam01062: Bestrophin 
Bestrophin, RFP-TM, chloride channel
Bestrophin is a 68-kDa basolateral plasma membrane protein expressed in retinal pigment epithelial cells (RPE). It is encoded by the VMD2 gene, which is mutated in Best macular dystrophy, a disease characterized by a depressed light peak in the electrooculogram. VMD2 encodes a 585-amino acid protein with an approximate mass of 68 kDa which has been designated bestrophin. Bestrophin shares homology with the Caenorhabditis elegans RFP gene family, named for the presence of a conserved arginine (R), phenylalanine (F), proline (P), amino acid sequence motif. Bestrophin is a plasma membrane protein, localized to the basolateral surface of RPE cells consistent with a role for bestrophin in the generation or regulation of the EOG light peak. Bestrophin and other RFP family members represent a new class of chloride channels, indicating a direct role for bestrophin in generating the light peak. The VMD2 gene underlying Best disease was shown to represent the first human member of the RFP-TM protein family. More than 97% of the disease-causing mutations are located in the N-terminal RFP-TM domain implying important functional properties. The bestrophins are four-pass transmembrane chloride-channel proteins, and the RFP-TM or bestrophin domain extends from the N-terminus through approximately 350 amino acids and contains all of the TM domains as well as nearly all reported disease causing mutations. Interestingly, the RFP motif is not conserved evolutionarily back beyond Metazoa, neither is it in plant members.
Statistics
?
PSSM-Id: 460047
Aligned: 151 rows
Threshold Bit Score: 153.092
Created: 21-Mar-2022
Updated: 17-Oct-2022
Structure
?
Program:
Drawing:
Aligned Rows:
PubMed ReferencesClick to see Conserved Features Help

Sequence Alignment
?
Format: Row Display: Color Bits: Type Selection:
6VX5_A              8 RVAKARFGGFSKLLLLWRGSIYKLLWRELLCFLGLFMALSAAYRfvlteeqkRY----------FEKLVlycdryaslIP 77 
XP_003170426       28 LSHRTKPRRWPLVLRFIKGAIHGAILVPVLCHAIFTVLVVVLDK--------HVfdtvgvpptiIPSLS---------IV 90 
EFW19422           31 kSHRSKPRRWPLVLRFIKGAVHSAVLVPLICHALFTVLVVCLDK--------YVydslglpptiIPSLS---------IV 93 
CAZ83819           21 kslRQKPRKWPLVFRFIKGAIHYVILIPVLFHTLFTIAVLLVHR--------LVdvdlalpssiVPSLS---------IV 83 
jgi:Cyan7425_0608   6 VLSTAAKQSWLRLALQLQGSVFPIVLPRILMFSGLGMLVALAHdfhlpvyiqa-----lgdlsnnvacN---------LV 71 
P72926              7 HPSRSP-RIWTDILLRWQGSVIPAIASRVLVCMAFSLGVTLVDG--------WGykfsipi-qesivpS---------IV 67  Synechocys...
jgi:PCC8801_0221    7 yqDKSEGRNWFRLVYQWRGSVMKAILPRVLVCAIFSLGVTVFYQ--------CGvnlalpl-esgivpS---------IV 68 
WP_015955116        6 FSDRQQ-RLWFRLLFEWRGSVIPAILPKILFCGMFSIIIIVIDI--------SGynlslpl-esgivpS---------LV 66  Gloeothece...
Q8YSU5              1 -MTVAK-KHWFQIAFQLRGSVIGAIYKRVICCALFGVLVTLLYQ--------LKipvsqpi-lgsvipS---------IV 60  Nostoc sp....
jgi:Mic7113_5672    7 tSKKSAKNFWIKKTFSLKGSVILGVLERSFLCGAFGILISFLYL--------KKipvaqpi-lgnvipS---------IV 68 
6VX5_A             78 VSFVLGFYVTLVVHRWWNQYLSMPLTDALMCVVVGTVHG-H-----D-ERGRLYRRTLMRYAGLSGVLILRSVSTAVFKR 150
XP_003170426       91 VGLILVFRNQTSYNRFWDGRNCLTTITTALRNLTRTILVsCrnpngPlSDAEKQDIERT---IRLLIAFPYAVKCYLRAE 167
EFW19422           94 VGLILVFRNQTSYNRFWDGRNALTTIHTAIRNLARSILLnScnrnrPlTVAERQDIERT---IRVMIAFPYAVKNYLRAE 170
CAZ83819           84 VGLMLVFRNSSSYERYWGGRTALQQIVNNLRNLVRTFLVcGpl--sD--DSDRVETERT---VKTLVAMLYAVKNHLRGN 156
jgi:Cyan7425_0608  72 LGLLLVFRTNTAYEKFWEGRKAWGELVVNIRNLSREIRCsL-----P--AESEQDRQTQETLIKLLTAFAIATKLHLRQL 144
P72926             68 LGLLLVFRTNTAYERFWEGRKAWGTMVNTIRNLSRIIWVsV-----A--EPSPQAHQDKIKILHLLVAFAVATKLHLRSQ 140 Synechocys...
jgi:PCC8801_0221   69 LGLLLVFRTNTAYERFWEGRKLWGTLINTVRNLARTIWVtV-----E--ENEAQDRQEKIVTLRLLVAFSVATKLHLRGY 141
WP_015955116       67 LGLLLVFRTNTAYDRFWEGRKAWGTLINTVRNLARTIWVsI-----E--EHKPEDRNEKTATLRLLVAFAIATKLHLRSE 139 Gloeothece...
Q8YSU5             61 LGLLLVFRTNTAYDRFWEGRKAWGSIVNNTRNLARQIWVsV-----E--EVSLKDREAKISVLNLLVAFAVATKLHLRGE 133 Nostoc sp....
jgi:Mic7113_5672   69 LALLLVFRTNTAYERFWEGRKLWGSTVSTIRNLVWQIWIaV-----D--EVEQGDRESKITTLRLLSAFAISKKLYLRYE 141
6VX5_A            151 ------------------------FPTID--HVVEAGfmtREERKKFEnlnssynkYWVPCV---WfCnLaaqarREGRI 201
XP_003170426      168 wstewgsvsnpnmiadavlrqeagGPKQEflSLLPAG-----FQAHEAd------gLGLPLQltfPvEaFiqrgaKRGWF 236
EFW19422          171 wsvgwsvqpl----iengagvgggSSKEEyvDLLPTG-----FACLEDn------gLSIPLQlsfFvEgFikrglERGWF 235
CAZ83819          157 we--------------------asALQPEfaSLMPEG-----FRGHEAe------gVGLPMElafVvErYikrgvKKGAF 205
jgi:Cyan7425_0608 145 ------------------------PIEQEldELVSPD---QLPQ--LQq------sANPPLLislAiEaYlqqqyQHQNL 189
P72926            141 ------------------------PLNEEiwALLPES---GYRK--LEd------lNNPPLEiafWiSnYlqreyDQNNI 185 Synechocys...
jgi:PCC8801_0221  142 ------------------------TNYDEliDLMPNL---WHEK--LKs------mNNPPLEiafWiGdYlqeqyEKGCI 186
WP_015955116      140 ------------------------PVNEElvPFMPYG---CYEN--LKn------mNNPPLEvafWiGdYlqrqnDKGSL 184 Gloeothece...
Q8YSU5            134 ------------------------PINSEleDLISTS---RYFK--LKs------mNNPPLEvafWiGdYlqqqyTCKCL 178 Nostoc sp....
jgi:Mic7113_5672  142 ------------------------PASEElqPWVSPS---QYGI--LQn------tPNMPLEiirWiAdElhqkyKRGLL 186
6VX5_A            202 RDNG-AfkLLLEELNVFRSKCGMLFHYDWISVPLVYTQVVTIAVYSYFlaCLIGRQFLDpaqgykdhdldlcvpiftllQ 280
XP_003170426      237 DPPAaN--QLGNQVSAMIDAYGKMETIKLTPIPVAHLIHQKQVLALFG--CVLPFAMVDdmgwwa--------vpivclV 304
EFW19422          236 DPPGaS--QMGNQVSTMVDAYGKMETIKLTPIPIAHLIHQKQVLALFG--CVLPFAMVDdmgwwa--------vpivslV 303
CAZ83819          206 NAPQsA--NLNASLNAVIMAYGNMETIKLTPIPVCQQIHQKQVLALYC--CVLPFCLLDdmgwwt--------ipvitlV 273
jgi:Cyan7425_0608 190 EVNQrI--AMGERVNQLIAGLTSCERIARTPIPPAYTIYLKRLILIYC--CFLPFNLVErtqtwt--------glimavV 257
P72926            186 NAYQlT--AMLRLVDTMVDVLGSCERILKTPIPLAYAIHLRQLIFLYC--FITPFQIVNtlhwat--------afvvgiI 253 Synechocys...
jgi:PCC8801_0221  187 NPYQlT--AMFKLLDIMVDVLGGCERILKTPIPLAYSIHLKQLVFIYC--FTLPFQVVDelrwlt--------splvslI 254
WP_015955116      185 NAYQlT--SMFKLLDSLVDVLGICERILKTPIPLAYNIHLKQLILLYC--CTLPFQLVDqfrwlt--------pllvclI 252 Gloeothece...
Q8YSU5            179 NSYQlT--SIQELLNNLVDNLGSCERILRTPMPLAYSIHLKQLLLLYC--FLLPFQMVEslgwwt--------glvvglV 246 Nostoc sp....
jgi:Mic7113_5672  187 TVSQlG--DIQSLMNKLIDNVGGCERILKTPIPPAYVIHLNQLVLIYC--LILPFQFVKdlgwwt--------glfvtiV 254
6VX5_A            281 fFFYAGWLKVAEQLINPFGEDDDDFETNFL---IDR 313
XP_003170426      305 iFTLYGIEGIGSQLEDPFGYDKNDIKMDAIvederv 340
EFW19422          304 iFTLYGIEGIGSQLEDPFGYDRNDIKMDAIvedqrt 339
CAZ83819          274 cFTLYGIEGIGEELEDPFGNDRNDIKIDAIiedcrq 309
jgi:Cyan7425_0608 258 sFILFGVEEIGNQIENPFGTDPNDLPLDQIcqvIVE 293
P72926            254 aFTVFGIEEIGVEIENPFGHDANDLPLDQIcqtMQA 289 Synechocystis sp. PCC 6803 substr. Kazusa
jgi:PCC8801_0221  255 sFTVFGIEEIGEEIEDPFGYDANDLPLDKIcqtMKI 290
WP_015955116      253 sFTVFGIEEIGIEIENPFGDDPNDLPLDQIcqtMKR 288 Gloeothece citriformis
Q8YSU5            247 sFTLFGIEAIGLEIENPFGYDPNDLPLDAIcntMKR 282 Nostoc sp. PCC 7120 = FACHB-418
jgi:Mic7113_5672  255 sFALFGIEEIGVEIENPFGYDMNDLPLDGIcqlIQN 290
| Disclaimer | Privacy statement | Accessibility |
NCBI Home NCBI Search NCBI SiteMap