TRX family; composed of two groups: Group I, which includes proteins that exclusively encode a TRX domain; and Group II, which are composed of fusion proteins of TRX and additional domains. Group I TRX is a small ancient protein that alter the redox state of target proteins via the reversible oxidation of an active site dithiol, present in a CXXC motif, partially exposed at the protein's surface. TRX reduces protein disulfide bonds, resulting in a disulfide bond at its active site. Oxidized TRX is converted to the active form by TRX reductase, using reducing equivalents derived from either NADPH or ferredoxins. By altering their redox state, TRX regulates the functions of at least 30 target proteins, some of which are enzymes and transcription factors. It also plays an important role in the defense against oxidative stress by directly reducing hydrogen peroxide and certain radicals, and by serving as a reductant for peroxiredoxins. At least two major types of functional TRXs have been reported in most organisms; in eukaryotes, they are located in the cytoplasm and the mitochondria. Higher plants contain more types (at least 20 TRX genes have been detected in the genome of Arabidopsis thaliana), two of which (types f amd m) are located in the same compartment, the chloroplast. Also included in the alignment are TRX-like domains which show sequence homology to TRX but do not contain the redox active CXXC motif. Group II proteins, in addition to either a redox active TRX or a TRX-like domain, also contain additional domains, which may or may not possess homology to known proteins.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345100816  22 FQEALDAAgdKLVVVDFSATWCGPSKMIKPFFHSLSEKYSNVIFLEVDVDDCQDVASECEVKSMPTFQFFKKGQKVGEFS 101
Cdd:cd02947    3 FEELIKSA--KPVVVDFWAPWCGPCKAIAPVLEELAEEYPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDRVV 80

                         90
                 ....*....|...
gi 345100816 102 GAN-KEKLEATIN 113
Cdd:cd02947   81 GADpKEELEEFLE 93

TRX family; composed of two groups: Group I, which includes proteins that exclusively encode a TRX domain; and Group II, which are composed of fusion proteins of TRX and additional domains. Group I TRX is a small ancient protein that alter the redox state of target proteins via the reversible oxidation of an active site dithiol, present in a CXXC motif, partially exposed at the protein's surface. TRX reduces protein disulfide bonds, resulting in a disulfide bond at its active site. Oxidized TRX is converted to the active form by TRX reductase, using reducing equivalents derived from either NADPH or ferredoxins. By altering their redox state, TRX regulates the functions of at least 30 target proteins, some of which are enzymes and transcription factors. It also plays an important role in the defense against oxidative stress by directly reducing hydrogen peroxide and certain radicals, and by serving as a reductant for peroxiredoxins. At least two major types of functional TRXs have been reported in most organisms; in eukaryotes, they are located in the cytoplasm and the mitochondria. Higher plants contain more types (at least 20 TRX genes have been detected in the genome of Arabidopsis thaliana), two of which (types f amd m) are located in the same compartment, the chloroplast. Also included in the alignment are TRX-like domains which show sequence homology to TRX but do not contain the redox active CXXC motif. Group II proteins, in addition to either a redox active TRX or a TRX-like domain, also contain additional domains, which may or may not possess homology to known proteins.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345100816  22 FQEALDAAgdKLVVVDFSATWCGPSKMIKPFFHSLSEKYSNVIFLEVDVDDCQDVASECEVKSMPTFQFFKKGQKVGEFS 101
Cdd:cd02947    3 FEELIKSA--KPVVVDFWAPWCGPCKAIAPVLEELAEEYPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDRVV 80

                         90
                 ....*....|...
gi 345100816 102 GAN-KEKLEATIN 113
Cdd:cd02947   81 GADpKEELEEFLE 93

thioredoxin; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345100816  13 VKQIESKTAFQEALdaAGDKLVVVDFSATWCGPSKMIKPFFHSLSEKYSNVIFLEVDVDDCQDVASECEVKSMPTFQFFK 92
Cdd:PTZ00051   2 VHIVTSQAEFESTL--SQNELVIVDFYAEWCGPCKRIAPFYEECSKEYTKMVFVKVDVDELSEVAEKENITSMPTFKVFK 79

                         90
                 ....*....|....*....
gi 345100816  93 KGQKVGEFSGANKEKLEAT 111
Cdd:PTZ00051  80 NGSVVDTLLGANDEALKQL 98

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 345100816   22 FQEALdAAGDKLVVVDFSATWCGPSKMIKPFFHSLSEKYSN-VIFLEVDVDDCQDVASECEVKSMPTFQFFKKGQKVGEF 100
Cdd:TIGR01068   6 FDETI-ASSDKPVLVDFWAPWCGPCKMIAPILEELAKEYEGkVKFVKLNVDENPDIAAKYGIRSIPTLLLFKNGKEVDRS 84

                          90
                  ....*....|....*..
gi 345100816  101 SGAN-KEKLEATINELV 116
Cdd:TIGR01068  85 VGALpKAALKQLINKNL 101

TRX family; composed of two groups: Group I, which includes proteins that exclusively encode a TRX domain; and Group II, which are composed of fusion proteins of TRX and additional domains. Group I TRX is a small ancient protein that alter the redox state of target proteins via the reversible oxidation of an active site dithiol, present in a CXXC motif, partially exposed at the protein's surface. TRX reduces protein disulfide bonds, resulting in a disulfide bond at its active site. Oxidized TRX is converted to the active form by TRX reductase, using reducing equivalents derived from either NADPH or ferredoxins. By altering their redox state, TRX regulates the functions of at least 30 target proteins, some of which are enzymes and transcription factors. It also plays an important role in the defense against oxidative stress by directly reducing hydrogen peroxide and certain radicals, and by serving as a reductant for peroxiredoxins. At least two major types of functional TRXs have been reported in most organisms; in eukaryotes, they are located in the cytoplasm and the mitochondria. Higher plants contain more types (at least 20 TRX genes have been detected in the genome of Arabidopsis thaliana), two of which (types f amd m) are located in the same compartment, the chloroplast. Also included in the alignment are TRX-like domains which show sequence homology to TRX but do not contain the redox active CXXC motif. Group II proteins, in addition to either a redox active TRX or a TRX-like domain, also contain additional domains, which may or may not possess homology to known proteins.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345100816  22 FQEALDAAgdKLVVVDFSATWCGPSKMIKPFFHSLSEKYSNVIFLEVDVDDCQDVASECEVKSMPTFQFFKKGQKVGEFS 101
Cdd:cd02947    3 FEELIKSA--KPVVVDFWAPWCGPCKAIAPVLEELAEEYPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDRVV 80

                         90
                 ....*....|...
gi 345100816 102 GAN-KEKLEATIN 113
Cdd:cd02947   81 GADpKEELEEFLE 93

thioredoxin; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345100816  13 VKQIESKTAFQEALdaAGDKLVVVDFSATWCGPSKMIKPFFHSLSEKYSNVIFLEVDVDDCQDVASECEVKSMPTFQFFK 92
Cdd:PTZ00051   2 VHIVTSQAEFESTL--SQNELVIVDFYAEWCGPCKRIAPFYEECSKEYTKMVFVKVDVDELSEVAEKENITSMPTFKVFK 79

                         90
                 ....*....|....*....
gi 345100816  93 KGQKVGEFSGANKEKLEAT 111
Cdd:PTZ00051  80 NGSVVDTLLGANDEALKQL 98

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 345100816   22 FQEALdAAGDKLVVVDFSATWCGPSKMIKPFFHSLSEKYSN-VIFLEVDVDDCQDVASECEVKSMPTFQFFKKGQKVGEF 100
Cdd:TIGR01068   6 FDETI-ASSDKPVLVDFWAPWCGPCKMIAPILEELAKEYEGkVKFVKLNVDENPDIAAKYGIRSIPTLLLFKNGKEVDRS 84

                          90
                  ....*....|....*..
gi 345100816  101 SGAN-KEKLEATINELV 116
Cdd:TIGR01068  85 VGALpKAALKQLINKNL 101

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345100816  25 ALDAAGDKLVVVDFSATWCGPSKMIKPFFHSLSEKYSNVIFLEVDVDD----------------------CQDVASECEV 82
Cdd:COG0526   22 SLADLKGKPVLVNFWATWCPPCRAEMPVLKELAEEYGGVVFVGVDVDEnpeavkaflkelglpypvlldpDGELAKAYGV 101

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 345100816  83 KSMPTFQFF-KKGQKVGEFSGA-NKEKLEATINELV 116
Cdd:COG0526  102 RGIPTTVLIdKDGKIVARHVGPlSPEELEEALEKLL 137

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345100816  22 FQEALdaAGDKLVVVDFSATWCGPSKMIKPFFHSLSEKY---SNVIFLEVDVDDCQDVASECEVKSMPTFQFFKKG-QKV 97
Cdd:cd02961    8 FDELV--KDSKDVLVEFYAPWCGHCKALAPEYEKLAKELkgdGKVVVAKVDCTANNDLCSEYGVRGYPTIKLFPNGsKEP 85

                         90
                 ....*....|
gi 345100816  98 GEFSGANKEK 107
Cdd:cd02961   86 VKYEGPRTLE 95

TRX domain, novel NADPH thioredoxin reductase (NTR) family; composed of fusion proteins found only in oxygenic photosynthetic organisms containing both TRX and NTR domains. The TRX domain functions as a protein disulfide reductase via the reversible oxidation of an active center dithiol present in a CXXC motif, while the NTR domain functions as a reductant to oxidized TRX. The fusion protein is bifunctional, showing both TRX and NTR activities, but it is not an independent NTR/TRX system. In plants, the protein is found exclusively in shoots and mature leaves and is localized in the chloroplast. It is involved in plant protection against oxidative stress.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 345100816  31 DKLVVVDFSATWCGPSKMIKPFFHSLSEKYSNVI-FLEVDVDDCQDVASECEVKSMPTFQFFKKGQKVGEFSGANKEK 107
Cdd:cd02949   13 DRLILVLYTSPTCGPCRTLKPILNKVIDEFDGAVhFVEIDIDEDQEIAEAAGIMGTPTVQFFKDKELVKEISGVKMKS 90

thioredoxin TrxA;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345100816  30 GDKLVVVDFSATWCGPSKMIKPFFHSLSEKYS-NVIFLEVDVDDCQDVASECEVKSMPTFQFFKKGQ----KVGEFS-GA 103
Cdd:PRK09381  20 ADGAILVDFWAEWCGPCKMIAPILDEIADEYQgKLTVAKLNIDQNPGTAPKYGIRGIPTLLLFKNGEvaatKVGALSkGQ 99

                 ....*....
gi 345100816 104 NKEKLEATI 112
Cdd:PRK09381 100 LKEFLDANL 108

disulphide isomerase; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 345100816  31 DKLVVVDFSATWCGPSKMIKPFFHS----LSEKYSNVIFLEVDVDDCQDVASECEVKSMPTFQFFKKGQKVgEFSGA 103
Cdd:PTZ00102  49 NEIVLVKFYAPWCGHCKRLAPEYKKaakmLKEKKSEIVLASVDATEEMELAQEFGVRGYPTIKFFNKGNPV-NYSGG 124

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345100816  12 SVKQIESKTAFQEALDaaGDKLVVVDFSATWCGPSKMIKPFFHSLSEKYS---NVIFLEVDVDDcQDVASECEVKSMPTF 88
Cdd:cd02995    1 PVKVVVGKNFDEVVLD--SDKDVLVEFYAPWCGHCKALAPIYEELAEKLKgddNVVIAKMDATA-NDVPSEFVVDGFPTI 77

                 ....*...
gi 345100816  89 QFFKKGQK 96
Cdd:cd02995   78 LFFPAGDK 85

Thioredoxin (TRX) superfamily; a large, diverse group of proteins containing a TRX-fold. Many members contain a classic TRX domain with a redox active CXXC motif. They function as protein disulfide oxidoreductases (PDOs), altering the redox state of target proteins via the reversible oxidation of their active site dithiol. The PDO members of this superfamily include TRX, protein disulfide isomerase (PDI), tlpA-like, glutaredoxin, NrdH redoxin, and the bacterial Dsb (DsbA, DsbC, DsbG, DsbE, DsbDgamma) protein families. Members of the superfamily that do not function as PDOs but contain a TRX-fold domain include phosducins, peroxiredoxins and glutathione (GSH) peroxidases, SCO proteins, GSH transferases (GST, N-terminal domain), arsenic reductases, TRX-like ferredoxins and calsequestrin, among others.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 345100816  35 VVDFSATWCGPSKMIKPFFHSLSEKYSNVIFLEVDVDDC---QDVASECEVKSMPTFQFFKKGQKV 97
Cdd:cd01659    1 LVLFYAPWCPFCQALRPVLAELALLNKGVKFEAVDVDEDpalEKELKRYGVGGVPTLVVFGPGIGV 66

TRX-like protein A (TxlA) family; TxlA was originally isolated from the cyanobacterium Synechococcus. It is found only in oxygenic photosynthetic organisms. TRX is a small enzyme that participate in redox reactions, via the reversible oxidation of an active site dithiol present in a CXXC motif. Disruption of the txlA gene suggests that the protein is involved in the redox regulation of the structure and function of photosynthetic apparatus. The plant homolog (designated as HCF164) is localized in the chloroplast and is involved in the assembly of the cytochrome b6f complex, which takes a central position in photosynthetic electron transport.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345100816  14 KQIESKTAFQEALdaAGDKLVVVDFSATWCGPSKMIKPFFHSLSEKYS---NVIFLEVDVDDCQDVASECEVKSMPTFQF 90
Cdd:cd02950    5 QLAASSTPPEVAL--SNGKPTLVEFYADWCTVCQEMAPDVAKLKQKYGdqvNFVMLNVDNPKWLPEIDRYRVDGIPHFVF 82

                         90       100
                 ....*....|....*....|....*...
gi 345100816  91 F-KKGQKVGEFSGA-NKEKLEATINELV 116
Cdd:cd02950   83 LdREGNEEGQSIGLqPKQVLAQNLDALV 110

TlpA-like family; composed of TlpA, ResA, DsbE and similar proteins. TlpA, ResA and DsbE are bacterial protein disulfide reductases with important roles in cytochrome maturation. They are membrane-anchored proteins with a soluble TRX domain containing a CXXC motif located in the periplasm. The TRX domains of this family contain an insert, approximately 25 residues in length, which correspond to an extra alpha helix and a beta strand when compared with TRX. TlpA catalyzes an essential reaction in the biogenesis of cytochrome aa3, while ResA and DsbE are essential proteins in cytochrome c maturation. Also included in this family are proteins containing a TlpA-like TRX domain with domain architectures similar to E. coli DipZ protein, and the N-terminal TRX domain of PilB protein from Neisseria which acts as a disulfide reductase that can recylce methionine sulfoxide reductases.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 345100816  26 LDAAGDKLVVVDFSATWCGPSKMIKPFFHSLSEKYS--NVIFLEVDVDD 72
Cdd:cd02966   14 LSDLKGKVVLVNFWASWCPPCRAEMPELEALAKEYKddGVEVVGVNVDD 62

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 345100816  35 VVDFSATWCGPSKMIKPFFHSLSE---KYSNVifLEVDVDDC-----QDVASECEVKSMPTFQFFK---KGQKVGEfsga 103
Cdd:cd02992   23 LVEFYASWCGHCRAFAPTWKKLARdlrKWRPV--VRVAAVDCadeenVALCRDFGVTGYPTLRYFPpfsKEATDGL---- 96

                         90
                 ....*....|..
gi 345100816 104 NKEKLEATINEL 115
Cdd:cd02992   97 KQEGPERDVNEL 108

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 345100816  26 LDAAGDKLVVVDFSATWCGPSKMIKPFF----HSLSEKYSNVIFLEVDVDDCQDVASECEVKSMPTFQFFKKG 94
Cdd:cd03000   10 KDVRKEDIWLVDFYAPWCGHCKKLEPVWnevgAELKSSGSPVRVGKLDATAYSSIASEFGVRGYPTIKLLKGD 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 345100816  35 VVDFSATWCGPSKMIKPFFhslsEKYSNVIFLEVDVD--DCQDVASECE---VKSMPTFQFFKKGQK 96
Cdd:cd03004   23 LVDFYAPWCGPCQALLPEL----RKAARALKGKVKVGsvDCQKYESLCQqanIRAYPTIRLYPGNAS 85

Phosducin (Phd)-like family; composed of Phd and Phd-like proteins (PhLP), characterized as cytosolic regulators of G protein functions. Phd and PhLPs specifically bind G protein betagamma (Gbg)-subunits with high affinity, resulting in the solubilization of Gbg from the plasma membrane and impeding G protein-mediated signal transduction by inhibiting the formation of a functional G protein trimer (G protein alphabetagamma). Phd also inhibits the GTPase activity of G protein alpha. Phd can be phosphorylated by protein kinase A and G protein-coupled receptor kinase 2, leading to its inactivation. Phd was originally isolated from the retina, where it is highly expressed and has been implicated to play an important role in light adaptation. It is also found in the pineal gland, liver, spleen, striated muscle and the brain. The C-terminal domain of Phd adopts a thioredoxin fold, but it does not contain a CXXC motif. Phd interacts with G protein beta mostly through the N-terminal helical domain. Also included in this family is a PhLP characterized as a viral inhibitor of apoptosis (IAP)-associated factor, named VIAF, that functions in caspase activation during apoptosis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 345100816  11 GSVKQIESKTAFQEALDAAGDKLVVVDFSATWCGPSKMIKPFFHSLSEKYSNVIFLEVDVDDCqDVASECEVKSMPTFQF 90
Cdd:cd02957    4 GEVREISSKEFLEEVTKASKGTRVVVHFYEPGFPRCKILDSHLEELAAKYPETKFVKINAEKA-FLVNYLDIKVLPTLLV 82

                         90
                 ....*....|..
gi 345100816  91 FKKGQKVGEFSG 102
Cdd:cd02957   83 YKNGELIDNIVG 94

thioredoxin-like protein

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 345100816  38 FSATWCGPSKMIKPFFHSLSEKYsnvifLEVDVDDCQDVASECEVKSMPT 87
Cdd:PHA02125   5 FGAEWCANCKMVKPMLANVEYTY-----VDVDTDEGVELTAKHHIRSLPT 49

Thioredoxin-like; Thioredoxins are small enzymes that participate in redox reactions, via the reversible oxidation of an active centre disulfide bond.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 345100816   31 DKLVVVDFSATWCGPSKMIKPFFHSLSEKYS-----NVIFLEVDVD 71
Cdd:pfam13905   1 GKVVLLYFGASWCKPCRRFTPLLKELYEKLKkkknvEIVFVSLDRD 46