Drosophila melanogaster RdgC and related proteins, metallophosphatase domain; RdgC (retinal degeneration C) is a vertebrate serine-threonine protein phosphatase that is required to prevent light-induced retinal degeneration. In addition to its catalytic domain, RdgC has two C-terminal EF hands. Homologs of RdgC include the human phosphatases protein phosphatase with EF hands 1 and -2 (PPEF-1 and -2). PPEF-1 transcripts are present at low levels in the retina, PPEF-2 transcripts and PPEF-2 protein are present at high levels in photoreceptors. The PPP (phosphoprotein phosphatase) family, to which RdgC belongs, is one of two known protein phosphatase families specific for serine and threonine. The PPP family also includes: PP1, PP2A, PP2B (calcineurin), PP4, PP5, PP6, PP7, Bsu1, PrpE, PrpA/PrpB, and ApA4 hydrolase. The PPP catalytic domain is defined by three conserved motifs (-GDXHG-, -GDXVDRG- and -GNHE-). The PPP enzyme family is ancient with members found in all eukaryotes, and in most bacterial and archeal genomes. Dephosphorylation of phosphoserines and phosphothreonines on target proteins plays a central role in the regulation of many cellular processes. PPPs belong to the metallophosphatase (MPP) superfamily. MPPs are functionally diverse, but all share a conserved domain with an active site consisting of two metal ions (usually manganese, iron, or zinc) coordinated with octahedral geometry by a cage of histidine, aspartate, and asparagine residues. The MPP superfamily includes: Mre11/SbcD-like exonucleases, Dbr1-like RNA lariat debranching enzymes, YfcE-like phosphodiesterases, purple acid phosphatases (PAPs), YbbF-like UDP-2,3-diacylglucosamine hydrolases, and acid sphingomyelinases (ASMases). The conserved domain is a double beta-sheet sandwich with a di-metal active site made up of residues located at the C-terminal side of the sheets. This domain is thought to allow for productive metal coordination.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755566531 144 PLTFTDIHILLQAFKQQQILHAHYVLEVLFEARKVLKQMPNFSHVKTFPAKEITICGDLHGKLDDLMLIFYKNGLPSENN 223
Cdd:cd07420    1 PLTKTHIDLLIEAFKLKQRLHAKYVLLILREARKSLKQLPNISRVSTSYSKEVTICGDLHGKLDDLLLIFYKNGLPSPEN 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755566531 224 PYVFNGDFVDRGNNSMEILMILLVCFLVYPSDLHLNRGNHEDFMMNLRYGFTKEILQKYKLHGRKILQVLEEVYTWLPIG 303
Cdd:cd07420   81 PYVFNGDFVDRGKRSIEILMILFAFVLVYPNAVHLNRGNHEDHIMNLRYGFTKEVMQKYKDHGKKILRLLEDVFSWLPLA 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755566531 304 TIIDNEILVIHGGISESTDLNTLHQLQRNKMKSvlmppvlgnqetgekrnksasnyveprkvepdktpsedlTKQEWEQI 383
Cdd:cd07420  161 TIIDNKVLVVHGGISDSTDLDLLDKIDRHKYVS---------------------------------------TKTEWQQV 201

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755566531 384 VDILWSDPRGKKGCYPNTSRGGGCYFGPDVTSKVLSKNQLKMLIRSHECKPDGYEVSHDGKVITVFSASNYYEEGSNRGA 463
Cdd:cd07420  202 VDILWSDPKATKGCKPNTFRGGGCYFGPDVTSQFLQKHGLSLLIRSHECKPEGYEFCHNNKVITIFSASNYYEEGSNRGA 281

                        330
                 ....*....|....*.
gi 755566531 464 YIRLSYGTMPQFFQYQ 479
Cdd:cd07420  282 YVKLGPQLTPHFVQYQ 297

Drosophila melanogaster RdgC and related proteins, metallophosphatase domain; RdgC (retinal degeneration C) is a vertebrate serine-threonine protein phosphatase that is required to prevent light-induced retinal degeneration. In addition to its catalytic domain, RdgC has two C-terminal EF hands. Homologs of RdgC include the human phosphatases protein phosphatase with EF hands 1 and -2 (PPEF-1 and -2). PPEF-1 transcripts are present at low levels in the retina, PPEF-2 transcripts and PPEF-2 protein are present at high levels in photoreceptors. The PPP (phosphoprotein phosphatase) family, to which RdgC belongs, is one of two known protein phosphatase families specific for serine and threonine. The PPP family also includes: PP1, PP2A, PP2B (calcineurin), PP4, PP5, PP6, PP7, Bsu1, PrpE, PrpA/PrpB, and ApA4 hydrolase. The PPP catalytic domain is defined by three conserved motifs (-GDXHG-, -GDXVDRG- and -GNHE-). The PPP enzyme family is ancient with members found in all eukaryotes, and in most bacterial and archeal genomes. Dephosphorylation of phosphoserines and phosphothreonines on target proteins plays a central role in the regulation of many cellular processes. PPPs belong to the metallophosphatase (MPP) superfamily. MPPs are functionally diverse, but all share a conserved domain with an active site consisting of two metal ions (usually manganese, iron, or zinc) coordinated with octahedral geometry by a cage of histidine, aspartate, and asparagine residues. The MPP superfamily includes: Mre11/SbcD-like exonucleases, Dbr1-like RNA lariat debranching enzymes, YfcE-like phosphodiesterases, purple acid phosphatases (PAPs), YbbF-like UDP-2,3-diacylglucosamine hydrolases, and acid sphingomyelinases (ASMases). The conserved domain is a double beta-sheet sandwich with a di-metal active site made up of residues located at the C-terminal side of the sheets. This domain is thought to allow for productive metal coordination.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755566531 144 PLTFTDIHILLQAFKQQQILHAHYVLEVLFEARKVLKQMPNFSHVKTFPAKEITICGDLHGKLDDLMLIFYKNGLPSENN 223
Cdd:cd07420    1 PLTKTHIDLLIEAFKLKQRLHAKYVLLILREARKSLKQLPNISRVSTSYSKEVTICGDLHGKLDDLLLIFYKNGLPSPEN 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755566531 224 PYVFNGDFVDRGNNSMEILMILLVCFLVYPSDLHLNRGNHEDFMMNLRYGFTKEILQKYKLHGRKILQVLEEVYTWLPIG 303
Cdd:cd07420   81 PYVFNGDFVDRGKRSIEILMILFAFVLVYPNAVHLNRGNHEDHIMNLRYGFTKEVMQKYKDHGKKILRLLEDVFSWLPLA 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755566531 304 TIIDNEILVIHGGISESTDLNTLHQLQRNKMKSvlmppvlgnqetgekrnksasnyveprkvepdktpsedlTKQEWEQI 383
Cdd:cd07420  161 TIIDNKVLVVHGGISDSTDLDLLDKIDRHKYVS---------------------------------------TKTEWQQV 201

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755566531 384 VDILWSDPRGKKGCYPNTSRGGGCYFGPDVTSKVLSKNQLKMLIRSHECKPDGYEVSHDGKVITVFSASNYYEEGSNRGA 463
Cdd:cd07420  202 VDILWSDPKATKGCKPNTFRGGGCYFGPDVTSQFLQKHGLSLLIRSHECKPEGYEFCHNNKVITIFSASNYYEEGSNRGA 281

                        330
                 ....*....|....*.
gi 755566531 464 YIRLSYGTMPQFFQYQ 479
Cdd:cd07420  282 YVKLGPQLTPHFVQYQ 297

serine/threonine-protein phosphatase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755566531 196 ITICGDLHGKLDDLMLIFYKNGLPSENNpYVFNGDFVDRGNNSMEILMILLVCFLVYPSDLHLNRGNHEDFMMNLRYGFT 275
Cdd:PTZ00480  61 LKICGDVHGQYFDLLRLFEYGGYPPESN-YLFLGDYVDRGKQSLETICLLLAYKIKYPENFFLLRGNHECASINRIYGFY 139

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755566531 276 KEILQKYKLhgrKILQVLEEVYTWLPIGTIIDNEILVIHGGIseSTDLNTLHQLQrnkmksvlmppvlgnqetgekrnks 355
Cdd:PTZ00480 140 DECKRRYTI---KLWKTFTDCFNCLPVAALIDEKILCMHGGL--SPELSNLEQIR------------------------- 189

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755566531 356 asnyvepRKVEPDKTPSEDLtkqeweqIVDILWSDPRGKKGCYPNTSRGGGCYFGPDVTSKVLSKNQLKMLIRSHECKPD 435
Cdd:PTZ00480 190 -------RIMRPTDVPDTGL-------LCDLLWSDPDKDVQGWADNERGVSYVFSQEIVQVFLKKHELDLICRAHQVVED 255

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|
gi 755566531 436 GYEVSHDGKVITVFSASNYYEEGSNRGAYIRLSYGTMPQF 475
Cdd:PTZ00480 256 GYEFFSKRQLVTLFSAPNYCGEFDNAGSMMTIDESLMCSF 295

Calcineurin-like phosphoesterase; This family includes a diverse range of phosphoesterases, including protein phosphoserine phosphatases, nucleotidases, sphingomyelin phosphodiesterases and 2'-3' cAMP phosphodiesterases as well as nucleases such as bacterial SbcD or yeast MRE11. The most conserved regions in this superfamily centre around the metal chelating residues.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755566531  196 ITICGDLH--GKLDDLMLIFykNGLPSENNPYVF--NGDFVDRGNNSMEILmiLLVCFLVYPSDLHLNRGNHEDFMMNLr 271
Cdd:pfam00149   3 ILVIGDLHlpGQLDDLLELL--KKLLEEGKPDLVlhAGDLVDRGPPSEEVL--ELLERLIKYVPVYLVRGNHDFDYGEC- 77

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 755566531  272 ygftkEILQKYKLHGRKILQVLEEVYTWLPIGTII 306
Cdd:pfam00149  78 -----LRLYPYLGLLARPWKRFLEVFNFLPLAGIL 107

EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to the activation or inactivation of target proteins. EF-hands tend to occur in pairs or higher copy numbers.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 755566531 597 DLKIIFNIIDSDQSGLISMDEFRTMWKLFNAHYkahiDDSQIDELASIVDFNKDGNIDFNEFLKAF 662
Cdd:cd00051    1 ELREAFRLFDKDGDGTISADELKAALKSLGEGL----SEEEIDEMIREVDKDGDGKIDFEEFLELM 62

Eps15 homology domain; Pair of EF hand motifs that recognise proteins containing Asn-Pro-Phe (NPF) sequences.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 755566531   601 IFNIIDSDQSGLISMDEFRTMWklfnahYKAHIDDSQIDELASIVDFNKDGNIDFNEFLKAFYVV 665
Cdd:smart00027  15 IFRSLDKNQDGTVTGAQAKPIL------LKSGLPQTLLAKIWNLADIDNDGELDKDEFALAMHLI 73

Drosophila melanogaster RdgC and related proteins, metallophosphatase domain; RdgC (retinal degeneration C) is a vertebrate serine-threonine protein phosphatase that is required to prevent light-induced retinal degeneration. In addition to its catalytic domain, RdgC has two C-terminal EF hands. Homologs of RdgC include the human phosphatases protein phosphatase with EF hands 1 and -2 (PPEF-1 and -2). PPEF-1 transcripts are present at low levels in the retina, PPEF-2 transcripts and PPEF-2 protein are present at high levels in photoreceptors. The PPP (phosphoprotein phosphatase) family, to which RdgC belongs, is one of two known protein phosphatase families specific for serine and threonine. The PPP family also includes: PP1, PP2A, PP2B (calcineurin), PP4, PP5, PP6, PP7, Bsu1, PrpE, PrpA/PrpB, and ApA4 hydrolase. The PPP catalytic domain is defined by three conserved motifs (-GDXHG-, -GDXVDRG- and -GNHE-). The PPP enzyme family is ancient with members found in all eukaryotes, and in most bacterial and archeal genomes. Dephosphorylation of phosphoserines and phosphothreonines on target proteins plays a central role in the regulation of many cellular processes. PPPs belong to the metallophosphatase (MPP) superfamily. MPPs are functionally diverse, but all share a conserved domain with an active site consisting of two metal ions (usually manganese, iron, or zinc) coordinated with octahedral geometry by a cage of histidine, aspartate, and asparagine residues. The MPP superfamily includes: Mre11/SbcD-like exonucleases, Dbr1-like RNA lariat debranching enzymes, YfcE-like phosphodiesterases, purple acid phosphatases (PAPs), YbbF-like UDP-2,3-diacylglucosamine hydrolases, and acid sphingomyelinases (ASMases). The conserved domain is a double beta-sheet sandwich with a di-metal active site made up of residues located at the C-terminal side of the sheets. This domain is thought to allow for productive metal coordination.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755566531 144 PLTFTDIHILLQAFKQQQILHAHYVLEVLFEARKVLKQMPNFSHVKTFPAKEITICGDLHGKLDDLMLIFYKNGLPSENN 223
Cdd:cd07420    1 PLTKTHIDLLIEAFKLKQRLHAKYVLLILREARKSLKQLPNISRVSTSYSKEVTICGDLHGKLDDLLLIFYKNGLPSPEN 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755566531 224 PYVFNGDFVDRGNNSMEILMILLVCFLVYPSDLHLNRGNHEDFMMNLRYGFTKEILQKYKLHGRKILQVLEEVYTWLPIG 303
Cdd:cd07420   81 PYVFNGDFVDRGKRSIEILMILFAFVLVYPNAVHLNRGNHEDHIMNLRYGFTKEVMQKYKDHGKKILRLLEDVFSWLPLA 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755566531 304 TIIDNEILVIHGGISESTDLNTLHQLQRNKMKSvlmppvlgnqetgekrnksasnyveprkvepdktpsedlTKQEWEQI 383
Cdd:cd07420  161 TIIDNKVLVVHGGISDSTDLDLLDKIDRHKYVS---------------------------------------TKTEWQQV 201

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755566531 384 VDILWSDPRGKKGCYPNTSRGGGCYFGPDVTSKVLSKNQLKMLIRSHECKPDGYEVSHDGKVITVFSASNYYEEGSNRGA 463
Cdd:cd07420  202 VDILWSDPKATKGCKPNTFRGGGCYFGPDVTSQFLQKHGLSLLIRSHECKPEGYEFCHNNKVITIFSASNYYEEGSNRGA 281

                        330
                 ....*....|....*.
gi 755566531 464 YIRLSYGTMPQFFQYQ 479
Cdd:cd07420  282 YVKLGPQLTPHFVQYQ 297

PP5, C-terminal metallophosphatase domain; Serine/threonine protein phosphatase-5 (PP5) is a member of the PPP gene family of protein phosphatases that is highly conserved among eukaryotes and widely expressed in mammalian tissues. PP5 has a C-terminal phosphatase domain and an extended N-terminal TPR (tetratricopeptide repeat) domain containing three TPR motifs. The PPP (phosphoprotein phosphatase) family, to which PP5 belongs, is one of two known protein phosphatase families specific for serine and threonine. The PPP family also includes: PP1, PP2A, PP2B (calcineurin), PP4, PP6, PP7, Bsu1, RdgC, PrpE, PrpA/PrpB, and ApA4 hydrolase. The PPP catalytic domain is defined by three conserved motifs (-GDXHG-, -GDXVDRG- and -GNHE-). The PPP enzyme family is ancient with members found in all eukaryotes, and in most bacterial and archeal genomes. Dephosphorylation of phosphoserines and phosphothreonines on target proteins plays a central role in the regulation of many cellular processes. PPPs belong to the metallophosphatase (MPP) superfamily. MPPs are functionally diverse, but all share a conserved domain with an active site consisting of two metal ions (usually manganese, iron, or zinc) coordinated with octahedral geometry by a cage of histidine, aspartate, and asparagine residues. The MPP superfamily includes: Mre11/SbcD-like exonucleases, Dbr1-like RNA lariat debranching enzymes, YfcE-like phosphodiesterases, purple acid phosphatases (PAPs), YbbF-like UDP-2,3-diacylglucosamine hydrolases, and acid sphingomyelinases (ASMases). The conserved domain is a double beta-sheet sandwich with a di-metal active site made up of residues located at the C-terminal side of the sheets. This domain is thought to allow for productive metal coordination.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755566531 136 YDGPRLQF-PLTFTDIHILLQAFKQQQILHAHYVLEVLFEARKVLKQMPNFSHVKTFPAKEITICGDLHGKLDDLMLIFY 214
Cdd:cd07417    1 YSGPKLEDgKVTLEFVKEMMEWFKDQKKLHKKYAYQILLQVKEILKKLPSLVEITIPEGEKITVCGDTHGQFYDLLNIFE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755566531 215 KNGLPSENNPYVFNGDFVDRGNNSMEILMILLVCFLVYPSDLHLNRGNHEDFMMNLRYGFTKEILQKYklhGRKILQVLE 294
Cdd:cd07417   81 LNGLPSETNPYLFNGDFVDRGSFSVEVILTLFAFKLLYPNHFHLNRGNHETDNMNKIYGFEGEVKAKY---NEQMFNLFS 157

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755566531 295 EVYTWLPIGTIIDNEILVIHGGISeSTDLNTLHQLqrnkmksvlmppvlgnqetgekrnksasnyvepRKVEPDKTPSED 374
Cdd:cd07417  158 EVFNWLPLAHLINGKVLVVHGGLF-SDDGVTLDDI---------------------------------RKIDRFRQPPDS 203

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755566531 375 ltkqewEQIVDILWSDPRGKKGCYPnTSRGGGCYFGPDVTSKVLSKNQLKMLIRSHECKPDGYEVSHDGKVITVFSASNY 454
Cdd:cd07417  204 ------GLMCELLWSDPQPQPGRGP-SKRGVGCQFGPDVTKRFLEENNLDYIIRSHEVKDEGYEVEHDGKCITVFSAPNY 276

                        330       340
                 ....*....|....*....|....*.
gi 755566531 455 YEEGSNRGAYIRLSYGTM-PQFFQYQ 479
Cdd:cd07417  277 CDQMGNKGAFIRFKGSDLkPKFTQFE 302

PP7, metallophosphatase domain; PP7 is a plant phosphoprotein phosphatase that is highly expressed in a subset of stomata and thought to play an important role in sensory signaling. PP7 acts as a positive regulator of signaling downstream of cryptochrome blue light photoreceptors. PP7 also controls amplification of phytochrome signaling, and interacts with nucleotidediphosphate kinase 2 (NDPK2), a positive regulator of phytochrome signalling. In addition, PP7 interacts with heat shock transcription factor HSF and up-regulates protective heat shock proteins. PP7 may also play a role in salicylic acid-dependent defense signaling. The PPP (phosphoprotein phosphatase) family, to which PP7 belongs, is one of two known protein phosphatase families specific for serine and threonine. The PPP family also includes: PP2A, PP2B (calcineurin), PP4, PP5, PP6, Bsu1, RdgC, PrpE, PrpA/PrpB, and ApA4 hydrolase. The PPP catalytic domain is defined by three conserved motifs (-GDXHG-, -GDXVDRG- and -GNHE-). The PPP enzyme family is ancient with members found in all eukaryotes, and in most bacterial and archeal genomes. Dephosphorylation of phosphoserines and phosphothreonines on target proteins plays a central role in the regulation of many cellular processes. PPPs belong to the metallophosphatase (MPP) superfamily. MPPs are functionally diverse, but all share a conserved domain with an active site consisting of two metal ions (usually manganese, iron, or zinc) coordinated with octahedral geometry by a cage of histidine, aspartate, and asparagine residues. The MPP superfamily includes: Mre11/SbcD-like exonucleases, Dbr1-like RNA lariat debranching enzymes, YfcE-like phosphodiesterases, purple acid phosphatases (PAPs), YbbF-like UDP-2,3-diacylglucosamine hydrolases, and acid sphingomyelinases (ASMases). The conserved domain is a double beta-sheet sandwich with a di-metal active site made up of residues located at the C-terminal side of the sheets. This domain is thought to allow for productive metal coordination.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755566531 170 EVLFEARKVLKQMPNFSHVKTFPAKEITICGDLHGKLDDLMLIFYKNGLPSENNPYVFNGDFVDRGNNSMEILMILLVCF 249
Cdd:cd07418   42 SLVLTAHKILHREPNCVRIDVEDVCEVVVVGDVHGQLHDVLFLLEDAGFPDQNRFYVFNGDYVDRGAWGLETFLLLLSWK 121

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755566531 250 LVYPSDLHLNRGNHEDFMMNLRYGFTKEILQKYKLHGRKILQVLEEVYTWLPIGTIIDNEILVIHGGI------------ 317
Cdd:cd07418  122 VLLPDRVYLLRGNHESKFCTSMYGFEQEVLTKYGDKGKHVYRKCLGCFEGLPLASIIAGRVYTAHGGLfrspslpkrkkq 201

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755566531 318 -------------SESTDLNTLHQLQRNKmKSVLMPPvlgnqetGEKRNKSASnyveprkvepdktpsedltkqeweqiv 384
Cdd:cd07418  202 kgknrrvlllepeSESLKLGTLDDLMKAR-RSVLDPP-------GEGSNLIPG--------------------------- 246

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755566531 385 DILWSDPRGKKGCYPNTSRGGGCYFGPDVTSKVLSKNQLKMLIRSHEcKPD-------------GYEVSHD---GKVITV 448
Cdd:cd07418  247 DVLWSDPSLTPGLSPNKQRGIGLLWGPDCTEEFLEKNNLKLIIRSHE-GPDarekrpglagmnkGYTVDHDvesGKLITL 325

                        330       340       350
                 ....*....|....*....|....*....|....*....
gi 755566531 449 FSASNY------YEEGSNRGAYIRLSYGTM--PQFFQYQ 479
Cdd:cd07418  326 FSAPDYpqfqatEERYNNKGAYIILQPPDFsdPQFHTFE 364

Arabidopsis thaliana Bsu1 phosphatase and related proteins, C-terminal metallophosphatase domain; Bsu1 encodes a nuclear serine-threonine protein phosphatase found in plants and protozoans. Bsu1 has a C-terminal phosphatase domain and an N-terminal Kelch-repeat domain. Bsu1 is preferentially expressed in elongating plant cells. It modulates the phosphorylation state of Bes1, a transcriptional regulator phosphorylated by the glycogen synthase kinase Bin2, as part of a steroid hormone signal transduction pathway. The PPP (phosphoprotein phosphatase) family, to which Bsu1 belongs, is one of two known protein phosphatase families specific for serine and threonine. The PPP family also includes: PP1, PP2A, PP2B (calcineurin), PP4, PP5, PP6, PP7, Bsu1, RdgC, PrpE, PrpA/PrpB, and ApA4 hydrolase. The PPP catalytic domain is defined by three conserved motifs (-GDXHG-, -GDXVDRG- and -GNHE-). The PPP enzyme family is ancient with members found in all eukaryotes, and in most bacterial and archeal genomes. Dephosphorylation of phosphoserines and phosphothreonines on target proteins plays a central role in the regulation of many cellular processes. PPPs belong to the metallophosphatase (MPP) superfamily. MPPs are functionally diverse, but all share a conserved domain with an active site consisting of two metal ions (usually manganese, iron, or zinc) coordinated with octahedral geometry by a cage of histidine, aspartate, and asparagine residues. The MPP superfamily includes: Mre11/SbcD-like exonucleases, Dbr1-like RNA lariat debranching enzymes, YfcE-like phosphodiesterases, purple acid phosphatases (PAPs), YbbF-like UDP-2,3-diacylglucosamine hydrolases, and acid sphingomyelinases (ASMases). The conserved domain is a double beta-sheet sandwich with a di-metal active site made up of residues located at the C-terminal side of the sheets. This domain is thought to allow for productive metal coordination.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755566531 158 KQQQILHAHYVLEVLFEARKVLKQMPNFSHVKTfPAKeitICGDLHGKLDDLMLIFYKNGLPSEN-------NPYVFNGD 230
Cdd:cd07419   16 ERRFFFDCQEIAELCDEAERIFRQEPSVLRLRA-PIK---IFGDIHGQFGDLMRLFDEYGSPVTEeagdieyIDYLFLGD 91

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755566531 231 FVDRGNNSMEILMILLVCFLVYPSDLHLNRGNHEDFMMNLRYGFTKEILQKYKLHGRK---ILQVLEEVYTWLPIGTIID 307
Cdd:cd07419   92 YVDRGSHSLETICLLLALKVKYPNQIHLIRGNHEAADINALFGFREECIERLGEDIRDgdsVWQRINRLFNWLPLAALIE 171

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755566531 308 NEILVIHGGISES-TDLNTLHQLQRnkmkSVLMPPvlGNQetgekrnksasnyveprkvepdktpsedltkqeweQIVDI 386
Cdd:cd07419  172 DKIICVHGGIGRSiNHIHQIENLKR----PITMEA--GSP-----------------------------------VVMDL 210

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755566531 387 LWSDPRGK---KGCYPNT--SRGGGCY--FGPDVTSKVLSKNQLKMLIRSHECKPDGYEVSHDGKVITVFSASNYYEEGS 459
Cdd:cd07419  211 LWSDPTENdsvLGLRPNAidPRGTGLIvkFGPDRVMEFLEENDLQMIIRAHECVMDGFERFAQGHLITLFSATNYCGTAG 290

                 ....*...
gi 755566531 460 NRGAYIRL 467
Cdd:cd07419  291 NAGAILVL 298

PP2B, metallophosphatase domain; PP2B (calcineurin) is a unique serine/threonine protein phosphatase in its regulation by a second messenger (calcium and calmodulin). PP2B is involved in many biological processes including immune responses, the second messenger cAMP pathway, sodium/potassium ion transport in the nephron, cell cycle progression in lower eukaryotes, cardiac hypertrophy, and memory formation. PP2B is highly conserved from yeast to humans, but is absent from plants. PP2B is a heterodimer consisting of a catalytic subunit (CnA) and a regulatory subunit (CnB); CnB contains four Ca2+ binding motifs referred to as EF hands. The PPP (phosphoprotein phosphatase) family, to which PP2B belongs, is one of two known protein phosphatase families specific for serine and threonine. The PPP family also includes: PP1, PP2A, PP4, PP5, PP6, PP7, Bsu1, RdgC, PrpE, PrpA/PrpB, and ApA4 hydrolase. The PPP catalytic domain is defined by three conserved motifs (-GDXHG-, -GDXVDRG- and -GNHE-). The PPP enzyme family is ancient with members found in all eukaryotes, and in most bacterial and archeal genomes. Dephosphorylation of phosphoserines and phosphothreonines on target proteins plays a central role in the regulation of many cellular processes. PPPs belong to the metallophosphatase (MPP) superfamily. MPPs are functionally diverse, but all share a conserved domain with an active site consisting of two metal ions (usually manganese, iron, or zinc) coordinated with octahedral geometry by a cage of histidine, aspartate, and asparagine residues. The MPP superfamily includes: Mre11/SbcD-like exonucleases, Dbr1-like RNA lariat debranching enzymes, YfcE-like phosphodiesterases, purple acid phosphatases (PAPs), YbbF-like UDP-2,3-diacylglucosamine hydrolases, and acid sphingomyelinases (ASMases). The conserved domain is a double beta-sheet sandwich with a di-metal active site made up of residues located at the C-terminal side of the sheets. This domain is thought to allow for productive metal coordination.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755566531 149 DIHILLQAFKQQQILHAHYVLEVLFEARKVLKQMPNFSHVKTfpakEITICGDLHGKLDDLMLIFYKNGLPSENNpYVFN 228
Cdd:cd07416    2 RVDILKAHFMREGRLSEEDALRIITEGAEILRQEPNLLRIEA----PVTVCGDIHGQFYDLLKLFEVGGSPANTR-YLFL 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755566531 229 GDFVDRGNNSMEILMILLVCFLVYPSDLHLNRGNHEDFMMNLRYGFTKEILQKYklhGRKILQVLEEVYTWLPIGTIIDN 308
Cdd:cd07416   77 GDYVDRGYFSIECVLYLWALKILYPKTLFLLRGNHECRHLTEYFTFKQECKIKY---SERVYDACMEAFDCLPLAALMNQ 153

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755566531 309 EILVIHGGIseSTDLNTLHQLqrNKMKSVLMPPVLGnqetgekrnksasnyveprkvepdktpsedltkqeweQIVDILW 388
Cdd:cd07416  154 QFLCVHGGL--SPELKTLDDI--RKLDRFREPPSYG-------------------------------------PMCDLLW 192

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755566531 389 SDPRGKKG-------CYPNTSRGGGCYFGPDVTSKVLSKNQLKMLIRSHECKPDGYEV--SHDGK----VITVFSASNYY 455
Cdd:cd07416  193 SDPLEDFGnektqehFVHNTVRGCSYFYSYRAVCEFLQKNNLLSIIRAHEAQDAGYRMyrKSQTTgfpsLITIFSAPNYL 272

                        330
                 ....*....|....*..
gi 755566531 456 EEGSNRGAYIRLSYGTM 472
Cdd:cd07416  273 DVYNNKAAVLKYENNVM 289

serine/threonine-protein phosphatase PP1; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755566531 156 AFKQQQILHAHYVLEVLFEARKVLKQMPNFSHVKtfpaKEITICGDLHGKLDDLMLIFYKNGLPSENNpYVFNGDFVDRG 235
Cdd:PTZ00244  18 RTQRQILIREEDIRAVLTEVREIFMSQPMLLEIR----PPVRVCGDTHGQYYDLLRIFEKCGFPPYSN-YLFLGDYVDRG 92

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755566531 236 NNSMEILmILLVCF-LVYPSDLHLNRGNHEDFMMNLRYGFTKEILQKYKLhgrKILQVLEEVYTWLPIGTIIDNEILVIH 314
Cdd:PTZ00244  93 KHSVETI-TLQFCYkIVYPENFFLLRGNHECASINKMYGFFDDVKRRYNI---KLFKAFTDVFNTMPVCCVISEKIICMH 168

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755566531 315 GGIS-ESTDLNTLHQLQRnkmksvlmppvlgnqetgekrnksasnyveprkvePDKTPSEDLtkqeweqIVDILWSDPRG 393
Cdd:PTZ00244 169 GGLSpDLTSLASVNEIER-----------------------------------PCDVPDRGI-------LCDLLWADPED 206

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755566531 394 KKGCYPNTSRGGGCYFGPDVTSKVLSKNQLKMLIRSHECKPDGYEVSHDGKVITVFSASNYYEEGSNRGA 463
Cdd:PTZ00244 207 EVRGFLESDRGVSYLFGEDIVNDFLDMVDMDLIVRAHQVMERGYGFFASRQLVTVFSAPNYCGEFDNDAA 276

Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755566531 511 RKTDLINAFELRDHSRSGRISLAEWAFSMENIlglnlpWRSLSSHLVTiDSSGSVdymsSFDDIRiekptKDMKSNLTET 590
Cdd:COG5126    3 QRRKLDRRFDLLDADGDGVLERDDFEALFRRL------WATLFSEADT-DGDGRI----SREEFV-----AGMESLFEAT 66

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755566531 591 MyryRSDLKIIFNIIDSDQSGLISMDEFRTMWKLFNahykahIDDSQIDELASIVDFNKDGNIDFNEFLKAfyvVHKYDK 670
Cdd:COG5126   67 V---EPFARAAFDLLDTDGDGKISADEFRRLLTALG------VSEEEADELFARLDTDGDGKISFEEFVAA---VRDYYT 134

                 .
gi 755566531 671 P 671
Cdd:COG5126  135 P 135

EF-hand domain pair;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 755566531  595 RSDLKIIFNIIDSDQSGLISMDEFRTMwkLFNAHYKAHIDDSQIDELASIVDFNKDGNIDFNEFLKAFY 663
Cdd:pfam13499   1 EEKLKEAFKLLDSDGDGYLDVEELKKL--LRKLEEGEPLSDEEVEELFKEFDLDKDGRISFEEFLELYS 67

PPP5 TPR repeat region; This region is specific to the PPP5 subfamily of serine/threonine phosphatases and contains TPR repeats.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 755566531  130 IEVPDSYDGPRLQFP---LTFtdIHILLQAFKQQQILHAHYVLEVLFEARKVLKQMPNF 185
Cdd:pfam08321  34 IVVEDSYDGPRLEDEkitLEF--VKDMIERFKKGKKLHKKYAYQILLKVKEILKKEPSL 90

centrin; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755566531 518 AFELRDHSRSGRISLAEWAFSMENiLGLNLPWRSLSSHLVTID--SSGSVDYMSSFDDIRIEKPTKDMKsnltETMYRyr 595
Cdd:PTZ00183  22 AFDLFDTDGSGTIDPKELKVAMRS-LGFEPKKEEIKQMIADVDkdGSGKIDFEEFLDIMTKKLGERDPR----EEILK-- 94

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 755566531 596 sdlkiIFNIIDSDQSGLISMDEFRTMWKlfnaHYKAHIDDSQIDELASIVDFNKDGNIDFNEFLK 660
Cdd:PTZ00183  95 -----AFRLFDDDKTGKISLKNLKRVAK----ELGETITDEELQEMIDEADRNGDGEISEEEFYR 150

calmodulin; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755566531 518 AFELRDHSRSGRISLAEWAFSMENiLGLNLPWRSLSSHLVTIDSSGSvdYMSSFDDIRIEKPTKdMKSNLTEtmyryrSD 597
Cdd:PTZ00184  16 AFSLFDKDGDGTITTKELGTVMRS-LGQNPTEAELQDMINEVDADGN--GTIDFPEFLTLMARK-MKDTDSE------EE 85

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 755566531 598 LKIIFNIIDSDQSGLISMDEFRTMwkLFNAHYKahIDDSQIDELASIVDFNKDGNIDFNEFLK 660
Cdd:PTZ00184  86 IKEAFKVFDRDGNGFISAAELRHV--MTNLGEK--LTDEEVDEMIREADVDGDGQINYEEFVK 144

Shewanella-like phosphatases, metallophosphatase domain; This family includes bacterial, eukaryotic, and archeal proteins orthologous to the Shewanella cold-active protein-tyrosine phosphatase, CAPTPase. CAPTPase is an uncharacterized protein that belongs to the Shelph (Shewanella-like phosphatase) family of PPP (phosphoprotein phosphatases). The PPP family is one of two known protein phosphatase families specific for serine and threonine. In addition to Shelps, the PPP family also includes: PP1, PP2A, PP2B (calcineurin), PP4, PP5, PP6, PP7, Bsu1, RdgC, PrpE, PrpA/PrpB, and ApA4 hydrolase. The PPP catalytic domain is defined by three conserved motifs (-GDXHG-, -GDXVDRG- and -GNHE-). The PPP enzyme family is ancient with members found in all eukaryotes, and in most bacterial and archeal genomes. Dephosphorylation of phosphoserines and phosphothreonines on target proteins plays a central role in the regulation of many cellular processes. PPPs belong to the metallophosphatase (MPP) superfamily. MPPs are functionally diverse, but all share a conserved domain with an active site consisting of two metal ions (usually manganese, iron, or zinc) coordinated with octahedral geometry by a cage of histidine, aspartate, and asparagine residues. The MPP superfamily includes: Mre11/SbcD-like exonucleases, Dbr1-like RNA lariat debranching enzymes, YfcE-like phosphodiesterases, purple acid phosphatases (PAPs), YbbF-like UDP-2,3-diacylglucosamine hydrolases, and acid sphingomyelinases (ASMases). The conserved domain is a double beta-sheet sandwich with a di-metal active site made up of residues located at the C-terminal side of the sheets. This domain is thought to allow for productive metal coordination.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755566531 200 GDLHGKLDDLMLIFYKNGLPSENNPYVFN-------GDFVDRGNNSMEILMILLvcfLVYP------SDLHLNRGNHEdf 266
Cdd:cd07425    4 GDLHGDLDRLRTILKLAGVIDSNDRWIGGdtvvvqtGDILDRGDDEIEILKLLE---KLKRqarkagGKVILLLGNHE-- 78

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 755566531 267 MMNL----RY-------GFTKEILQKYKLHGRKilqvlEEVYTWL-PIGTIID-NEILVIHGGIS 318
Cdd:cd07425   79 LMNLcgdfRYvhprglnEFGGVAKRRYALLSDG-----GYIGRYLrTHPVVLVvNDILFVHGGLG 138

EF-hand, calcium binding motif, found in beta-parvalbumin; Beta-parvalbumin, also termed Oncomodulin-1 (OM), is a small calcium-binding protein that is expressed in hepatomas, as well as in the blastocyst and the cytotrophoblasts of the placenta. It is also found to be expressed in the cochlear outer hair cells of the organ of Corti and frequently expressed in neoplasms. Mammalian beta-parvalbumin is secreted by activated macrophages and neutrophils. It may function as a tissue-specific Ca2+-dependent regulatory protein, and may also serve as a specialized cytosolic Ca2+ buffer. Beta-parvalbumin acts as a potent growth-promoting signal between the innate immune system and neurons in vivo. It has high and specific affinity for its receptor on retinal ganglion cells (RGC) and functions as the principal mediator of optic nerve regeneration. It exerts its effects in a cyclic adenosine monophosphate (cAMP)-dependent manner and can further elevate intracellular cAMP levels. Moreover, beta-parvalbumin is associated with efferent function and outer hair cell electromotility, and can identify different hair cell types in the mammalian inner ear. Beta-parvalbumin is characterized by the presence of three consecutive EF-hand motifs (helix-loop-helix) called AB, CD, and EF, but only CD and EF can chelate metal ions, such as Ca2+ and Mg2+. The EF site displays a high-affinity for Ca2+/Mg2+, and the CD site is a low-affinity Ca2+-specific site. In addition, beta-parvalbumin is distinguished from other parvalbumins by its unusually low isoelectric point (pI = 3.1) and sequence eccentricities (e.g., Y57-L58-D59 instead of F57-I58-E59).

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 755566531 597 DLKIIFNIIDSDQSGLISMDEFRTMWKLFNAHYKAhIDDSQIDELASIVDFNKDGNIDFNEFLK 660
Cdd:cd16255   35 DVKKVFEIIDQDKSGFIEEEELKLFLQNFSSGARE-LTDAETKAFLKAGDSDGDGKIGVEEFQA 97

EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11) isozymes; PI-PLC isozymes are signaling enzymes that hydrolyze the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. This family corresponds to the four EF-hand motifs containing PI-PLC isozymes, including PI-PLC-beta (1-4), -gamma (1-2), -delta (1,3,4), -epsilon (1), -zeta (1), eta (1-2). Lower eukaryotes such as yeast and slime molds contain only delta-type isozymes. In contrast, other types of isoforms present in higher eukaryotes. This family also includes 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase 1 (PLC1) from fungi. Some homologs from plants contain only two atypical EF-hand motifs and they are not included. All PI-PLC isozymes except sperm-specific PI-PLC-zeta share a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. PI-PLC-zeta lacks the PH domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Most of EF-hand motifs found in PI-PLCs consist of a helix-loop-helix structure, but lack residues critical to metal binding. Moreover, the EF-hand region of most of PI-PLCs may have an important regulatory function, but it has yet to be identified. However, PI-PLC-zeta is a key exception. It is responsible for Ca2+ oscillations in fertilized oocytes and exhibits a high sensitivity to Ca2+ mediated through its EF-hand domain. In addition, PI-PLC-eta2 shows a canonical EF-loop directing Ca2+-sensitivity and thus can amplify transient Ca2+ signals. Also it appears that PI-PLC-delta1 can regulate the binding of PH domain to PIP2 in a Ca2+-dependent manner through its functionally important EF-hand domains. PI-PLCs can be activated by a variety of extracellular ligands, such as growth factors, hormones, cytokines and lipids. Their activation has been implicated in tumorigenesis and/or metastasis linked to migration, proliferation, growth, inflammation, angiogenesis and actin cytoskeleton reorganization. PI-PLC-beta isozymes are activated by G-protein coupled receptor (GPCR) through different mechanisms. However, PI-PLC-gamma isozymes are activated by receptor tyrosine kinase (RTK), such as Rho and Ras GTPases. In contrast, PI-PLC-epsilon are activated by both GPCR and RTK. PI-PLC-delta1 and PLC-eta 1 are activated by GPCR-mediated calcium mobilization. The activation mechanism for PI-PLC-zeta remains unclear.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 755566531 598 LKIIFNIIDSDQSGLISMDEFRTMWKLFNAHykahIDDSQIDELASIVDFNKDGNIDFNEFLKAF 662
Cdd:cd15898    2 LRRQWIKADKDGDGKLSLKEIKKLLKRLNIR----VSEKELKKLFKEVDTNGDGTLTFDEFEELY 62