Flavin adenine dinucleotide (FAD)-dependent sulfhydryl oxidase; This is a flavin adenine dinucleotide (FAD) binding domain found in Quiescin sulfhydryl oxidases (QSOX) (EC:1.8.3.2). QSOX is a multi-domain disulfide catalyst that is localized primarily to the Golgi apparatus and secreted fluids and has attracted attention due to its over-production in tumors. Structural studies indicate that the closure of the Trx1 domain over the FAD-binding site may enhance the active-site chemistry for disulfide formation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12836398   298 DRSKIYMADLESALHYILRVEVGKFSVLEGQRLVALKKFVAVLAKYFPGQPLVQNFLHSINDWLQKQQKKRIPYSFFKAA 377
Cdd:pfam18371   1 DRSKVYMADLESALHYSLRVELAKHSVLEGEELKALKDYVTVLAKYFPGRPSVKNLLQSLDSWLQSQPETKISYSALLDA 80

                          90       100
                  ....*....|....*....|....
gi 12836398   378 LDSRKE--DAVLTEKVNWVGCQGS 399
Cdd:pfam18371  81 LDNKKEapGAVLPEEVRWVGCQGS 104

PDIa family, Quiescin-sulfhydryl oxidase (QSOX) subfamily; QSOX is a eukaryotic protein containing an N-terminal redox active TRX domain, similar to that of PDI, and a small C-terminal flavin adenine dinucleotide (FAD)-binding domain homologous to the yeast ERV1p protein. QSOX oxidizes thiol groups to disulfides like PDI, however, unlike PDI, this oxidation is accompanied by the reduction of oxygen to hydrogen peroxide. QSOX is localized in high concentrations in cells with heavy secretory load and prefers peptides and proteins as substrates, not monothiols like glutathione. Inside the cell, QSOX is found in the endoplasmic reticulum and Golgi. The flow of reducing equivalents in a QSOX-catalyzed reaction goes from the dithiol substrate -> dithiol of the QSOX TRX domain -> dithiols of the QSOX ERV1p domain -> FAD -> oxygen.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12836398  43 DPLTLLDADSVRPTVLGSSSAWAVEFFASWCGHCIAFAPTWKELANDVKDWRPALNLAVLDCAEETNSAVCREFNIAGFP 122
Cdd:cd02992   1 DPVIVLDAASFNSALLGSPSAWLVEFYASWCGHCRAFAPTWKKLARDLRKWRPVVRVAAVDCADEENVALCRDFGVTGYP 80

                        90       100       110
                ....*....|....*....|....*....|....
gi 12836398 123 TVRFFQAFTKNGS-GATLPGAGANVQTLRMRLID 155
Cdd:cd02992  81 TLRYFPPFSKEATdGLKQEGPERDVNELREALIL 114

Flavin adenine dinucleotide (FAD)-dependent sulfhydryl oxidase; This is a flavin adenine dinucleotide (FAD) binding domain found in Quiescin sulfhydryl oxidases (QSOX) (EC:1.8.3.2). QSOX is a multi-domain disulfide catalyst that is localized primarily to the Golgi apparatus and secreted fluids and has attracted attention due to its over-production in tumors. Structural studies indicate that the closure of the Trx1 domain over the FAD-binding site may enhance the active-site chemistry for disulfide formation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12836398   298 DRSKIYMADLESALHYILRVEVGKFSVLEGQRLVALKKFVAVLAKYFPGQPLVQNFLHSINDWLQKQQKKRIPYSFFKAA 377
Cdd:pfam18371   1 DRSKVYMADLESALHYSLRVELAKHSVLEGEELKALKDYVTVLAKYFPGRPSVKNLLQSLDSWLQSQPETKISYSALLDA 80

                          90       100
                  ....*....|....*....|....
gi 12836398   378 LDSRKE--DAVLTEKVNWVGCQGS 399
Cdd:pfam18371  81 LDNKKEapGAVLPEEVRWVGCQGS 104

PDIa family, Quiescin-sulfhydryl oxidase (QSOX) subfamily; QSOX is a eukaryotic protein containing an N-terminal redox active TRX domain, similar to that of PDI, and a small C-terminal flavin adenine dinucleotide (FAD)-binding domain homologous to the yeast ERV1p protein. QSOX oxidizes thiol groups to disulfides like PDI, however, unlike PDI, this oxidation is accompanied by the reduction of oxygen to hydrogen peroxide. QSOX is localized in high concentrations in cells with heavy secretory load and prefers peptides and proteins as substrates, not monothiols like glutathione. Inside the cell, QSOX is found in the endoplasmic reticulum and Golgi. The flow of reducing equivalents in a QSOX-catalyzed reaction goes from the dithiol substrate -> dithiol of the QSOX TRX domain -> dithiols of the QSOX ERV1p domain -> FAD -> oxygen.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12836398  43 DPLTLLDADSVRPTVLGSSSAWAVEFFASWCGHCIAFAPTWKELANDVKDWRPALNLAVLDCAEETNSAVCREFNIAGFP 122
Cdd:cd02992   1 DPVIVLDAASFNSALLGSPSAWLVEFYASWCGHCRAFAPTWKKLARDLRKWRPVVRVAAVDCADEENVALCRDFGVTGYP 80

                        90       100       110
                ....*....|....*....|....*....|....
gi 12836398 123 TVRFFQAFTKNGS-GATLPGAGANVQTLRMRLID 155
Cdd:cd02992  81 TLRYFPPFSKEATdGLKQEGPERDVNELREALIL 114

Thioredoxin; Thioredoxins are small enzymes that participate in redox reactions, via the reversible oxidation of an active centre disulfide bond. Some members with only the active site are not separated from the noise.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 12836398    66 VEFFASWCGHCIAFAPTWKELANDVKDwrpALNLAVLDCAEetNSAVCREFNIAGFPTVRFFqaftKNG 134
Cdd:pfam00085  23 VDFYAPWCGPCKMLAPEYEELAQEYKG---NVVFAKVDVDE--NPDLASKYGVRGYPTLIFF----KNG 82

disulphide isomerase; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 12836398   66 VEFFASWCGHCIAFAPTWKELANDVKDWRPALNLAVLDCAEETNSAvcREFNIAGFPTVRFFQAFTK-NGSGA 137
Cdd:PTZ00102  54 VKFYAPWCGHCKRLAPEYKKAAKMLKEKKSEIVLASVDATEEMELA--QEFGVRGYPTIKFFNKGNPvNYSGG 124

Mitochondrial sulfhydryl oxidase involved in the biogenesis of cytosolic Fe/S proteins [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12836398 409 SLWVLFHflTVQANryseaHPQEPADGQEvlQAMRSYVQFF---FGCRDCADHFEQMAAASMHQVRSPSNAILWLWTSHN 485
Cdd:COG5054  85 SSWTLLH--TVAAN-----YPARPTPQQR--DDLRSFLFLFsitYPCGECSKHFQKLLDVYPPQVSSREAATTWACEVHN 155

                ....*.
gi 12836398 486 RVNARL 491
Cdd:COG5054 156 KVNEKL 161

Flavin adenine dinucleotide (FAD)-dependent sulfhydryl oxidase; This is a flavin adenine dinucleotide (FAD) binding domain found in Quiescin sulfhydryl oxidases (QSOX) (EC:1.8.3.2). QSOX is a multi-domain disulfide catalyst that is localized primarily to the Golgi apparatus and secreted fluids and has attracted attention due to its over-production in tumors. Structural studies indicate that the closure of the Trx1 domain over the FAD-binding site may enhance the active-site chemistry for disulfide formation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12836398   298 DRSKIYMADLESALHYILRVEVGKFSVLEGQRLVALKKFVAVLAKYFPGQPLVQNFLHSINDWLQKQQKKRIPYSFFKAA 377
Cdd:pfam18371   1 DRSKVYMADLESALHYSLRVELAKHSVLEGEELKALKDYVTVLAKYFPGRPSVKNLLQSLDSWLQSQPETKISYSALLDA 80

                          90       100
                  ....*....|....*....|....
gi 12836398   378 LDSRKE--DAVLTEKVNWVGCQGS 399
Cdd:pfam18371  81 LDNKKEapGAVLPEEVRWVGCQGS 104

PDIa family, Quiescin-sulfhydryl oxidase (QSOX) subfamily; QSOX is a eukaryotic protein containing an N-terminal redox active TRX domain, similar to that of PDI, and a small C-terminal flavin adenine dinucleotide (FAD)-binding domain homologous to the yeast ERV1p protein. QSOX oxidizes thiol groups to disulfides like PDI, however, unlike PDI, this oxidation is accompanied by the reduction of oxygen to hydrogen peroxide. QSOX is localized in high concentrations in cells with heavy secretory load and prefers peptides and proteins as substrates, not monothiols like glutathione. Inside the cell, QSOX is found in the endoplasmic reticulum and Golgi. The flow of reducing equivalents in a QSOX-catalyzed reaction goes from the dithiol substrate -> dithiol of the QSOX TRX domain -> dithiols of the QSOX ERV1p domain -> FAD -> oxygen.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12836398  43 DPLTLLDADSVRPTVLGSSSAWAVEFFASWCGHCIAFAPTWKELANDVKDWRPALNLAVLDCAEETNSAVCREFNIAGFP 122
Cdd:cd02992   1 DPVIVLDAASFNSALLGSPSAWLVEFYASWCGHCRAFAPTWKKLARDLRKWRPVVRVAAVDCADEENVALCRDFGVTGYP 80

                        90       100       110
                ....*....|....*....|....*....|....
gi 12836398 123 TVRFFQAFTKNGS-GATLPGAGANVQTLRMRLID 155
Cdd:cd02992  81 TLRYFPPFSKEATdGLKQEGPERDVNELREALIL 114

Protein Disulfide Isomerase (PDIa) family, redox active TRX domains; composed of eukaryotic proteins involved in oxidative protein folding in the endoplasmic reticulum (ER) by acting as catalysts and folding assistants. Members of this family include PDI and PDI-related proteins like ERp72, ERp57 (or ERp60), ERp44, P5, PDIR, ERp46 and the transmembrane PDIs. PDI, ERp57, ERp72, P5, PDIR and ERp46 are all oxidases, catalyzing the formation of disulfide bonds of newly synthesized polypeptides in the ER. They also exhibit reductase activity in acting as isomerases to correct any non-native disulfide bonds, as well as chaperone activity to prevent protein aggregation and facilitate the folding of newly synthesized proteins. These proteins usually contain multiple copies of a redox active TRX (a) domain containing a CXXC motif, and may also contain one or more redox inactive TRX-like (b) domains. Only one a domain is required for the oxidase function but multiple copies are necessary for the isomerase function. The different types of PDIs may show different substrate specificities and tissue-specific expression, or may be induced by stress. PDIs are in their reduced form at steady state and are oxidized to the active form by Ero1, which is localized in the ER through ERp44. Some members of this family also contain a DnaJ domain in addition to the redox active a domains; examples are ERdj5 and Pfj2. Also included in the family is the redox inactive N-terminal TRX-like domain of ERp29.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 12836398  57 VLGSSSAWAVEFFASWCGHCIAFAPTWKELANDVKdWRPALNLAVLDCAEetNSAVCREFNIAGFPTVRFFQAFTKNG 134
Cdd:cd02961  11 LVKDSKDVLVEFYAPWCGHCKALAPEYEKLAKELK-GDGKVVVAKVDCTA--NNDLCSEYGVRGYPTIKLFPNGSKEP 85

PDI family, MPD1-like subfamily; composed of eukaryotic proteins similar to Saccharomyces cerevisiae MPD1 protein, which contains a single redox active TRX domain located at the N-terminus, and an ER retention signal at the C-terminus indicative of an ER-resident protein. MPD1 has been shown to suppress the maturation defect of carboxypeptidase Y caused by deletion of the yeast PDI1 gene. Other characterized members of this subfamily include the Aspergillus niger prpA protein and Giardia PDI-1. PrpA is non-essential to strain viability, however, its transcript level is induced by heterologous protein expression suggesting a possible role in oxidative protein folding during high protein production. Giardia PDI-1 has the ability to refold scrambled RNase and exhibits transglutaminase activity.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12836398  44 PLTLLDADSVRPTVLGSSSAWAVEFFASWCGHCIAFAPTWKELAndvKDWRPALNLAVLDCAEETNSAVCREFNIAGFPT 123
Cdd:cd03002   1 PVYELTPKNFDKVVHNTNYTTLVEFYAPWCGHCKNLKPEYAKAA---KELDGLVQVAAVDCDEDKNKPLCGKYGVQGFPT 77

                        90       100
                ....*....|....*....|.
gi 12836398 124 VRFFQAFTKNGSGATLPGAGA 144
Cdd:cd03002  78 LKVFRPPKKASKHAVEDYNGE 98

Thioredoxin; Thioredoxins are small enzymes that participate in redox reactions, via the reversible oxidation of an active centre disulfide bond. Some members with only the active site are not separated from the noise.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 12836398    66 VEFFASWCGHCIAFAPTWKELANDVKDwrpALNLAVLDCAEetNSAVCREFNIAGFPTVRFFqaftKNG 134
Cdd:pfam00085  23 VDFYAPWCGPCKMLAPEYEELAQEYKG---NVVFAKVDVDE--NPDLASKYGVRGYPTLIFF----KNG 82

PDIa family, C-terminal ERdj5 subfamily; ERdj5, also known as JPDI and macrothioredoxin, is a protein containing an N-terminal DnaJ domain and four redox active TRX domains. This subfamily is composed of the three TRX domains located at the C-terminal half of the protein. ERdj5 is a ubiquitous protein localized in the endoplasmic reticulum (ER) and is abundant in secretory cells. It's transcription is induced during ER stress. It interacts with BiP through its DnaJ domain in an ATP-dependent manner. BiP, an ER-resident member of the Hsp70 chaperone family, functions in ER-associated degradation and protein translocation. Also included in the alignment is the single complete TRX domain of an uncharacterized protein from Tetraodon nigroviridis, which also contains a DnaJ domain at its N-terminus.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12836398  48 LDADSVRPTVLGSSSAWAVEFFASWCGHCIAFAPTWKELANDVKdwrPALNLAVLDCaeETNSAVCREFNIAGFPTVRFF 127
Cdd:cd03004   6 LTPEDFPELVLNRKEPWLVDFYAPWCGPCQALLPELRKAARALK---GKVKVGSVDC--QKYESLCQQANIRAYPTIRLY 80

                ....*..
gi 12836398 128 QAFTKNG 134
Cdd:cd03004  81 PGNASKY 87

PDIa family, TMX3 subfamily; composed of eukaryotic proteins similar to human TMX3, a TRX related transmembrane protein containing one redox active TRX domain at the N-terminus and a classical ER retrieval sequence for type I transmembrane proteins at the C-terminus. The TMX3 transcript is found in a variety of tissues with the highest levels detected in skeletal muscle and the heart. In vitro, TMX3 showed oxidase activity albeit slightly lower than that of protein disulfide isomerase.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 12836398  64 WAVEFFASWCGHCIAFAPTWKELANDVKDWRPALNLAVLDCAeeTNSAVCREFNIAGFPTVRFFQ---AFTKNG 134
Cdd:cd03000  18 WLVDFYAPWCGHCKKLEPVWNEVGAELKSSGSPVRVGKLDAT--AYSSIASEFGVRGYPTIKLLKgdlAYNYRG 89

PDIa family, PDIR subfamily; composed of proteins similar to human PDIR (for Protein Disulfide Isomerase Related). PDIR is composed of three redox active TRX (a) domains and an N-terminal redox inactive TRX-like (b) domain. Similar to PDI, it is involved in oxidative protein folding in the endoplasmic reticulum (ER) through its isomerase and chaperone activities. These activities are lower compared to PDI, probably due to PDIR acting only on a subset of proteins. PDIR is preferentially expressed in cells actively secreting proteins and its expression is induced by stress. Similar to PDI, the isomerase and chaperone activities of PDIR are independent; CXXC mutants lacking isomerase activity retain chaperone activity.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12836398  48 LDADSVRPTVLGSSSAwAVEFFASWCGHCIAFAPTWKELANDVKDWRPALnLAVLDCAEETNSAVCREFNIAGFPTVRFF 127
Cdd:cd02997   5 LTDEDFRKFLKKEKHV-LVMFYAPWCGHCKKMKPEFTKAATELKEDGKGV-LAAVDCTKPEHDALKEEYNVKGFPTFKYF 82

PDIa family, C-terminal TRX domain (a') subfamily; composed of the C-terminal redox active a' domains of PDI, ERp72, ERp57 (or ERp60) and EFP1. PDI, ERp72 and ERp57 are endoplasmic reticulum (ER)-resident eukaryotic proteins involved in oxidative protein folding. They are oxidases, catalyzing the formation of disulfide bonds of newly synthesized polypeptides in the ER. They also exhibit reductase activity in acting as isomerases to correct any non-native disulfide bonds, as well as chaperone activity to prevent protein aggregation and facilitate the folding of newly synthesized proteins. PDI and ERp57 have the abb'a' domain structure (where a and a' are redox active TRX domains while b and b' are redox inactive TRX-like domains). PDI also contains an acidic region (c domain) after the a' domain that is absent in ERp57. ERp72 has an additional a domain at the N-terminus (a"abb'a' domain structure). ERp57 interacts with the lectin chaperones, calnexin and calreticulin, and specifically promotes the oxidative folding of glycoproteins, while PDI shows a wider substrate specificity. ERp72 associates with several ER chaperones and folding factors to form complexes in the ER that bind nascent proteins. EFP1 is a binding partner protein of thyroid oxidase, which is responsible for the generation of hydrogen peroxide, a crucial substrate of thyroperoxidase, which functions to iodinate thyroglobulin and synthesize thyroid hormones.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 12836398  66 VEFFASWCGHCIAFAPTWKELANDVKDwRPALNLAVLDCaeeTNSAVCREFNIAGFPTVRFFQAFTKN 133
Cdd:cd02995  23 VEFYAPWCGHCKALAPIYEELAEKLKG-DDNVVIAKMDA---TANDVPSEFVVDGFPTILFFPAGDKS 86

Chaperedoxin CnoX, contains thioredoxin-like and TPR-like domains, YbbN/TrxSC family [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12836398  48 LDADSVRPTVLGSSSAWAVEFFASWCGHCIAFAPTWKELAndvKDWRPALNLAVLDCaeETNSAVCREFNIAGFPTVRFF 127
Cdd:COG3118   5 LTDENFEEEVLESDKPVLVDFWAPWCGPCKMLAPVLEELA---AEYGGKVKFVKVDV--DENPELAAQFGVRSIPTLLLF 79

                ....*..
gi 12836398 128 qaftKNG 134
Cdd:COG3118  80 ----KDG 82

thioredoxin; Several proteins, such as protein disulfide isomerase, have two or more copies of a domain closely related to thioredoxin. This model is designed to recognize authentic thioredoxin, a small protein that should be hit exactly once by this model. Any protein that hits once with a score greater than the second (per domain) trusted cutoff may be taken as thioredoxin. [Energy metabolism, Electron transport]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12836398    48 LDADSVRPTVLGSSSAWAVEFFASWCGHCIAFAPTWKELAndvKDWRPALNLAVLDCAEETNSAvcREFNIAGFPTVRFF 127
Cdd:TIGR01068   1 LTDANFDETIASSDKPVLVDFWAPWCGPCKMIAPILEELA---KEYEGKVKFVKLNVDENPDIA--AKYGIRSIPTLLLF 75

                  ....*..
gi 12836398   128 qaftKNG 134
Cdd:TIGR01068  76 ----KNG 78

Thiol-disulfide isomerase or thioredoxin [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12836398  66 VEFFASWCGHCIAFAPTWKELANDVKD--------------WRPALNLAVLD--CAEETNSAVCREFNIAGFPTVrFFqa 129
Cdd:COG0526  33 VNFWATWCPPCRAEMPVLKELAEEYGGvvfvgvdvdenpeaVKAFLKELGLPypVLLDPDGELAKAYGVRGIPTT-VL-- 109

                ....*
gi 12836398 130 FTKNG 134
Cdd:COG0526 110 IDKDG 114

Mitochondrial sulfhydryl oxidase involved in the biogenesis of cytosolic Fe/S proteins [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12836398 409 SLWVLFHflTVQANryseaHPQEPADGQEvlQAMRSYVQFF---FGCRDCADHFEQMAAASMHQVRSPSNAILWLWTSHN 485
Cdd:COG5054  85 SSWTLLH--TVAAN-----YPARPTPQQR--DDLRSFLFLFsitYPCGECSKHFQKLLDVYPPQVSSREAATTWACEVHN 155

                ....*.
gi 12836398 486 RVNARL 491
Cdd:COG5054 156 KVNEKL 161

thioredoxin; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12836398   57 VLGSSSAWAVEFFASWCGHCIAFAPTWKELANDvkdwRPALNLAVLDCAEEtnSAVCREFNIAGFPTVRFFqaftKNGSG 136
Cdd:PTZ00051  14 TLSQNELVIVDFYAEWCGPCKRIAPFYEECSKE----YTKMVFVKVDVDEL--SEVAEKENITSMPTFKVF----KNGSV 83

                 ....*....
gi 12836398  137 A-TLPGAGA 144
Cdd:PTZ00051  84 VdTLLGAND 92

PDIa family, endoplasmic reticulum protein 44 (ERp44) subfamily; ERp44 is an ER-resident protein, induced during stress, involved in thiol-mediated ER retention. It contains an N-terminal TRX domain, similar to that of PDIa, with a CXFS motif followed by two redox inactive TRX-like domains, homologous to the b and b' domains of PDI. The CXFS motif in the N-terminal domain allows ERp44 to form stable reversible mixed disulfides with its substrates. Through this activity, ERp44 mediates the ER localization of Ero1alpha, a protein that oxidizes protein disulfide isomerases into their active form. ERp44 also prevents the secretion of unassembled cargo protein with unpaired cysteines. It also modulates the activity of inositol 1,4,5-triphosphate type I receptor (IP3R1), an intracellular channel protein that mediates calcium release from the ER to the cytosol.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 12836398  57 VLGSSSAWAVEFFASWCGHCIAFAPTWKELANDVKDWRPALNLAVL---DCAEETNSAvcREFNIAGFPTVRFF 127
Cdd:cd02996  14 ILQSAELVLVNFYADWCRFSQMLHPIFEEAAAKIKEEFPDAGKVVWgkvDCDKESDIA--DRYRINKYPTLKLF 85

TMX2 family; composed of proteins similar to human TMX2, a 372-amino acid TRX-related transmembrane protein, identified and characterized through the cloning of its cDNA from a human fetal library. It contains a TRX domain but the redox active CXXC motif is replaced with SXXC. Sequence analysis predicts that TMX2 may be a Type I membrane protein, with its C-terminal half protruding on the luminal side of the endoplasmic reticulum (ER). In addition to the TRX domain, transmembrane region and ER-retention signal, TMX2 also contains a Myb DNA-binding domain repeat signature and a dileucine motif in the tail.

                        10        20
                ....*....|....*....|....*
gi 12836398  64 WAVEFFASWCGHCIAFAPTWKELAN 88
Cdd:cd02962  50 WLVEFFTTWSPECVNFAPVFAELSL 74

thioredoxin 2; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 12836398   66 VEFFASWCGHCIAFAPTWKELANDVKDwrpalNLAVLDCAEETNSAVCREFNIAGFPTVRFFqaftKNG 134
Cdd:PRK10996  57 IDFWAPWCGPCRNFAPIFEDVAAERSG-----KVRFVKVNTEAERELSARFRIRSIPTIMIF----KNG 116