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Conserved domains on  [gi|295635811|emb|CAZ83819|]
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unnamed protein product [Tuber melanosporum]

Protein Classification

bestrophin family protein( domain architecture ID 10471023)

bestrophin family protein is a member of a family of Ca(2+)-regulated homo-tetrameric anion channels; similar to bestrophin, which functions as a calcium-activated anion channel

Gene Ontology:  GO:0005254
PubMed:  12907679|18400985
TCDB:  1.A.46

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
Bestrophin pfam01062
Bestrophin, RFP-TM, chloride channel; Bestrophin is a 68-kDa basolateral plasma membrane ...
24-305 1.90e-82

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.


:

Pssm-ID: 460047  Cd Length: 272  Bit Score: 250.55  E-value: 1.90e-82
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 295635811   24 RQKPRKWPLVFRFIKGAIHYVILIPVLFHTLFTIAVLLVHRLvdvdlalpssIVPSLSIVVGLMLVFRNSSSYERYWGGR 103
Cdd:pfam01062   4 RSRLRGFLKLLFRWRGSIYKLILPELLVFLLLYALVSLIYRR----------IFELLGIPLSFFLGFRVNAVYDRWWEGR 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 295635811  104 TALQQIVNNLRNLVRTFLVCGPLSDDSDRVETERTVKTLVAMLYAVKNHLRGNWeasalqPEFASLMPEGF---RGHEAE 180
Cdd:pfam01062  74 KLWGWPDNLARSLARQVLGLDEEGRLARRTILRYLVLSLVAFFRALSAHLRKRF------PTLDHLLPAGMeeeRKILEN 147
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 295635811  181 GVGLPMELAFVVERYIKRGVKKGAFNAPQSAnLNASLNAVIMAYGNMETIKLTPIPVCQQIHQKQVLALYCCVLPFCLLD 260
Cdd:pfam01062 148 KYWVPIAWLRRLAARLARLRREGRIRDDQAQ-LDEELNAFRGVLGGCERIDWTPIPLAYTQLVHRAVYLYCLLLPFTLLQ 226
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*
gi 295635811  261 DMGWWTIPVITLVCFTLYGIEGIGEELEDPFGNDRNDIKIDAIIE 305
Cdd:pfam01062 227 TLGWWTPLVVAIFAFFFFGWLKVAEELENPFGEDDDDLELNALID 271
 
Name Accession Description Interval E-value
Bestrophin pfam01062
Bestrophin, RFP-TM, chloride channel; Bestrophin is a 68-kDa basolateral plasma membrane ...
24-305 1.90e-82

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.


Pssm-ID: 460047  Cd Length: 272  Bit Score: 250.55  E-value: 1.90e-82
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 295635811   24 RQKPRKWPLVFRFIKGAIHYVILIPVLFHTLFTIAVLLVHRLvdvdlalpssIVPSLSIVVGLMLVFRNSSSYERYWGGR 103
Cdd:pfam01062   4 RSRLRGFLKLLFRWRGSIYKLILPELLVFLLLYALVSLIYRR----------IFELLGIPLSFFLGFRVNAVYDRWWEGR 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 295635811  104 TALQQIVNNLRNLVRTFLVCGPLSDDSDRVETERTVKTLVAMLYAVKNHLRGNWeasalqPEFASLMPEGF---RGHEAE 180
Cdd:pfam01062  74 KLWGWPDNLARSLARQVLGLDEEGRLARRTILRYLVLSLVAFFRALSAHLRKRF------PTLDHLLPAGMeeeRKILEN 147
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 295635811  181 GVGLPMELAFVVERYIKRGVKKGAFNAPQSAnLNASLNAVIMAYGNMETIKLTPIPVCQQIHQKQVLALYCCVLPFCLLD 260
Cdd:pfam01062 148 KYWVPIAWLRRLAARLARLRREGRIRDDQAQ-LDEELNAFRGVLGGCERIDWTPIPLAYTQLVHRAVYLYCLLLPFTLLQ 226
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*
gi 295635811  261 DMGWWTIPVITLVCFTLYGIEGIGEELEDPFGNDRNDIKIDAIIE 305
Cdd:pfam01062 227 TLGWWTPLVVAIFAFFFFGWLKVAEELENPFGEDDDDLELNALID 271
YneE COG3781
Predicted membrane chloride channel, bestrophin family [Inorganic ion transport and metabolism] ...
26-309 1.15e-62

Predicted membrane chloride channel, bestrophin family [Inorganic ion transport and metabolism];


Pssm-ID: 442995  Cd Length: 306  Bit Score: 201.15  E-value: 1.15e-62
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 295635811  26 KPRKWPLVFRFIKGAIHYVILIPVLFHTLFTIAVLLVH-RLVDVDLALPSSIVPSLSIVVGLMLVFRNSSSYERYWGGRT 104
Cdd:COG3781    5 KRPNWFRLLFVLRGSVLPKILPRLLLLLLLSVLVVLLYqVLFGLWVSLPIAPFTLLGTALALFLGFRNNAAYDRWWEARK 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 295635811 105 ALQQIVNNLRNLVRTFLVCgpLSDDSDRVETERTVKTLVAMLYAVKNHLRGNWEASALQP-----EFASLMPEGFRghea 179
Cdd:COG3781   85 LWGALVNDSRNLARQVLAL--LPDEEDREERRRLVRRLIAFAHALRHHLRGEDPWEELERllpaeELERLKAAKNP---- 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 295635811 180 egvglPMELAFVVERYIKRGVKKGAFNAPQSANLNASLNAVIMAYGNMETIKLTPIPVCQQIHQKQVLALYCCVLPFCLL 259
Cdd:COG3781  159 -----PNAILLLIGRELAELRRRGRIDDIQLLALDRTLNELSDIQGGCERIKNTPIPFAYSLLLHRFVYLFCLLLPFGLV 233
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....
gi 295635811 260 DDMGWWTIPVITLVCFTLYGIEGIGEELEDPFGNDRNDIKIDAI---IE-DCRQ 309
Cdd:COG3781  234 DSLGWLTPPVVALIAYTFFGLEAIGEELEDPFGNDPNDLPLDAIcrtIEiNLLE 287
 
Name Accession Description Interval E-value
Bestrophin pfam01062
Bestrophin, RFP-TM, chloride channel; Bestrophin is a 68-kDa basolateral plasma membrane ...
24-305 1.90e-82

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.


Pssm-ID: 460047  Cd Length: 272  Bit Score: 250.55  E-value: 1.90e-82
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 295635811   24 RQKPRKWPLVFRFIKGAIHYVILIPVLFHTLFTIAVLLVHRLvdvdlalpssIVPSLSIVVGLMLVFRNSSSYERYWGGR 103
Cdd:pfam01062   4 RSRLRGFLKLLFRWRGSIYKLILPELLVFLLLYALVSLIYRR----------IFELLGIPLSFFLGFRVNAVYDRWWEGR 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 295635811  104 TALQQIVNNLRNLVRTFLVCGPLSDDSDRVETERTVKTLVAMLYAVKNHLRGNWeasalqPEFASLMPEGF---RGHEAE 180
Cdd:pfam01062  74 KLWGWPDNLARSLARQVLGLDEEGRLARRTILRYLVLSLVAFFRALSAHLRKRF------PTLDHLLPAGMeeeRKILEN 147
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 295635811  181 GVGLPMELAFVVERYIKRGVKKGAFNAPQSAnLNASLNAVIMAYGNMETIKLTPIPVCQQIHQKQVLALYCCVLPFCLLD 260
Cdd:pfam01062 148 KYWVPIAWLRRLAARLARLRREGRIRDDQAQ-LDEELNAFRGVLGGCERIDWTPIPLAYTQLVHRAVYLYCLLLPFTLLQ 226
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*
gi 295635811  261 DMGWWTIPVITLVCFTLYGIEGIGEELEDPFGNDRNDIKIDAIIE 305
Cdd:pfam01062 227 TLGWWTPLVVAIFAFFFFGWLKVAEELENPFGEDDDDLELNALID 271
YneE COG3781
Predicted membrane chloride channel, bestrophin family [Inorganic ion transport and metabolism] ...
26-309 1.15e-62

Predicted membrane chloride channel, bestrophin family [Inorganic ion transport and metabolism];


Pssm-ID: 442995  Cd Length: 306  Bit Score: 201.15  E-value: 1.15e-62
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 295635811  26 KPRKWPLVFRFIKGAIHYVILIPVLFHTLFTIAVLLVH-RLVDVDLALPSSIVPSLSIVVGLMLVFRNSSSYERYWGGRT 104
Cdd:COG3781    5 KRPNWFRLLFVLRGSVLPKILPRLLLLLLLSVLVVLLYqVLFGLWVSLPIAPFTLLGTALALFLGFRNNAAYDRWWEARK 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 295635811 105 ALQQIVNNLRNLVRTFLVCgpLSDDSDRVETERTVKTLVAMLYAVKNHLRGNWEASALQP-----EFASLMPEGFRghea 179
Cdd:COG3781   85 LWGALVNDSRNLARQVLAL--LPDEEDREERRRLVRRLIAFAHALRHHLRGEDPWEELERllpaeELERLKAAKNP---- 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 295635811 180 egvglPMELAFVVERYIKRGVKKGAFNAPQSANLNASLNAVIMAYGNMETIKLTPIPVCQQIHQKQVLALYCCVLPFCLL 259
Cdd:COG3781  159 -----PNAILLLIGRELAELRRRGRIDDIQLLALDRTLNELSDIQGGCERIKNTPIPFAYSLLLHRFVYLFCLLLPFGLV 233
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....
gi 295635811 260 DDMGWWTIPVITLVCFTLYGIEGIGEELEDPFGNDRNDIKIDAI---IE-DCRQ 309
Cdd:COG3781  234 DSLGWLTPPVVALIAYTFFGLEAIGEELEDPFGNDPNDLPLDAIcrtIEiNLLE 287
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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