Glutaredoxin (GRX) family, PKC-interacting cousin of TRX (PICOT)-like subfamily; composed of PICOT and GRX-PICOT-like proteins. The non-PICOT members of this family contain only the GRX-like domain, whereas PICOT contains an N-terminal TRX-like domain followed by one to three GRX-like domains. It is interesting to note that PICOT from plants contain three repeats of the GRX-like domain, metazoan proteins (except for insect) have two repeats, while fungal sequences contain only one copy of the domain. PICOT is a protein that interacts with protein kinase C (PKC) theta, a calcium independent PKC isoform selectively expressed in skeletal muscle and T lymphocytes. PICOT inhibits the activation of c-Jun N-terminal kinase and the transcription factors, AP-1 and NF-kB, induced by PKC theta or T-cell activating stimuli. Both GRX and TRX domains of PICOT are required for its activity. Characterized non-PICOT members of this family include CXIP1, a CAX-interacting protein in Arabidopsis thaliana, and PfGLP-1, a GRX-like protein from Plasmodium falciparum.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958649024 191 LKVLTNKASVMLFMKGNKQEAKCGFSKQILEILNSTGVEYETFDILEDEEVRQGLKTFSNWPTYPQLYVRGDLVGGLDIV 270
Cdd:cd03028     1 IKKLIKENPVVLFMKGTPEEPRCGFSRKVVQILNQLGVDFGTFDILEDEEVRQGLKEYSNWPTFPQLYVNGELVGGCDIV 80

                  ....*....
gi 1958649024 271 KELKDNGEL 279
Cdd:cd03028    81 KEMHESGEL 89

Glutaredoxin (GRX) family, PKC-interacting cousin of TRX (PICOT)-like subfamily; composed of PICOT and GRX-PICOT-like proteins. The non-PICOT members of this family contain only the GRX-like domain, whereas PICOT contains an N-terminal TRX-like domain followed by one to three GRX-like domains. It is interesting to note that PICOT from plants contain three repeats of the GRX-like domain, metazoan proteins (except for insect) have two repeats, while fungal sequences contain only one copy of the domain. PICOT is a protein that interacts with protein kinase C (PKC) theta, a calcium independent PKC isoform selectively expressed in skeletal muscle and T lymphocytes. PICOT inhibits the activation of c-Jun N-terminal kinase and the transcription factors, AP-1 and NF-kB, induced by PKC theta or T-cell activating stimuli. Both GRX and TRX domains of PICOT are required for its activity. Characterized non-PICOT members of this family include CXIP1, a CAX-interacting protein in Arabidopsis thaliana, and PfGLP-1, a GRX-like protein from Plasmodium falciparum.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958649024 191 LKVLTNKASVMLFMKGNKQEAKCGFSKQILEILNSTGVEYETFDILEDEEVRQGLKTFSNWPTYPQLYVRGDLVGGLDIV 270
Cdd:cd03028     1 IKKLIKENPVVLFMKGTPEEPRCGFSRKVVQILNQLGVDFGTFDILEDEEVRQGLKEYSNWPTFPQLYVNGELVGGCDIV 80

                  ....*....
gi 1958649024 271 KELKDNGEL 279
Cdd:cd03028    81 KEMHESGEL 89

monothiol glutaredoxin, Grx4 family; The gene for the member of this glutaredoxin family in E. coli, originally designated ydhD, is now designated grxD. Its protein, Grx4, is a monothiol glutaredoxin similar to Grx5 of yeast, which is involved in iron-sulfur cluster formation. [Energy metabolism, Electron transport]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958649024 188 EERLKVLTNKASVMLFMKGNKQEAKCGFSKQILEILNSTGVEYETFDILEDEEVRQGLKTFSNWPTYPQLYVRGDLVGGL 267
Cdd:TIGR00365   2 IERIKEQIAENPVVLYMKGTPQFPQCGFSARAVQILNACGVPFAYVNVLEDPEIRQGIKEYSNWPTIPQLYVKGEFVGGC 81

                          90
                  ....*....|....*.
gi 1958649024 268 DIVKELKDNGELLPIL 283
Cdd:TIGR00365  82 DIIMEMYQSGELQTLL 97

monothiol glutaredoxin, Grx4 family; The gene for the member of this glutaredoxin family in E. coli, originally designated ydhD, is now designated grxD. Its protein, Grx4, is a monothiol glutaredoxin similar to Grx5 of yeast, which is involved in iron-sulfur cluster formation. [Energy metabolism, Electron transport]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958649024  88 RLKKLTHAAPCMLFMKGTPQEPRCGFSKQMVEILHKHNIQFSSFDIFSDEEVRQGLKTYSNWPTYPQLYVSGELIGGLDI 167
Cdd:TIGR00365   4 RIKEQIAENPVVLYMKGTPQFPQCGFSARAVQILNACGVPFAYVNVLEDPEIRQGIKEYSNWPTIPQLYVKGEFVGGCDI 83

                          90
                  ....*....|...
gi 1958649024 168 IKELEASEELDTI 180
Cdd:TIGR00365  84 IMEMYQSGELQTL 96

glutaredoxin; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958649024 189 ERLKVLTNKASVMLFMKGNKQEAKCGFSKQILEILNSTGVEYETFDILEDEEVRQGLKTFSNWPTYPQLYVRGDLVGGLD 268
Cdd:PTZ00062  104 EKIERLIRNHKILLFMKGSKTFPFCRFSNAVVNMLNSSGVKYETYNIFEDPDLREELKVYSNWPTYPQLYVNGELIGGHD 183

                          90
                  ....*....|.
gi 1958649024 269 IVKELKDNGEL 279
Cdd:PTZ00062  184 IIKELYESNSL 194

Grx4 family monothiol glutaredoxin;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958649024  97 PCMLFMKGTPQEPRCGFSKQMVEILHKHNIQFSSFDIFSDEEVRQGLKTYSNWPTYPQLYVSGELIGGLDIIKELEASEE 176
Cdd:PRK10824   16 PILLYMKGSPKLPSCGFSAQAVQALSACGERFAYVDILQNPDIRAELPKYANWPTFPQLWVDGELVGGCDIVIEMYQRGE 95

                  ....
gi 1958649024 177 LDTI 180
Cdd:PRK10824   96 LQQL 99

Glutaredoxin;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958649024  99 MLFMKgtpqePRCGFSKQMVEILHKHNIQFSSFDIFSDEEVRQGLKTYSNWPTYPQLYVSGELI 162
Cdd:pfam00462   2 VLYTK-----PTCPFCKRAKRLLKSLGVDFEEIDVDEDPEIREELKELSGWPTVPQVFIDGEHI 60

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958649024   4 VMAELAKEHPH-VSFVKLEAEAVPEVSEKYEISSVPTFLFFKNSQKVDRLDGAHAPE-LTKKVQRHV 68
Cdd:TIGR01068  35 ILEELAKEYEGkVKFVKLNVDENPDIAAKYGIRSIPTLLLFKNGKEVDRSVGALPKAaLKQLINKNL 101

Glutaredoxin (GRX) family, PKC-interacting cousin of TRX (PICOT)-like subfamily; composed of PICOT and GRX-PICOT-like proteins. The non-PICOT members of this family contain only the GRX-like domain, whereas PICOT contains an N-terminal TRX-like domain followed by one to three GRX-like domains. It is interesting to note that PICOT from plants contain three repeats of the GRX-like domain, metazoan proteins (except for insect) have two repeats, while fungal sequences contain only one copy of the domain. PICOT is a protein that interacts with protein kinase C (PKC) theta, a calcium independent PKC isoform selectively expressed in skeletal muscle and T lymphocytes. PICOT inhibits the activation of c-Jun N-terminal kinase and the transcription factors, AP-1 and NF-kB, induced by PKC theta or T-cell activating stimuli. Both GRX and TRX domains of PICOT are required for its activity. Characterized non-PICOT members of this family include CXIP1, a CAX-interacting protein in Arabidopsis thaliana, and PfGLP-1, a GRX-like protein from Plasmodium falciparum.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958649024 191 LKVLTNKASVMLFMKGNKQEAKCGFSKQILEILNSTGVEYETFDILEDEEVRQGLKTFSNWPTYPQLYVRGDLVGGLDIV 270
Cdd:cd03028     1 IKKLIKENPVVLFMKGTPEEPRCGFSRKVVQILNQLGVDFGTFDILEDEEVRQGLKEYSNWPTFPQLYVNGELVGGCDIV 80

                  ....*....
gi 1958649024 271 KELKDNGEL 279
Cdd:cd03028    81 KEMHESGEL 89

monothiol glutaredoxin, Grx4 family; The gene for the member of this glutaredoxin family in E. coli, originally designated ydhD, is now designated grxD. Its protein, Grx4, is a monothiol glutaredoxin similar to Grx5 of yeast, which is involved in iron-sulfur cluster formation. [Energy metabolism, Electron transport]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958649024 188 EERLKVLTNKASVMLFMKGNKQEAKCGFSKQILEILNSTGVEYETFDILEDEEVRQGLKTFSNWPTYPQLYVRGDLVGGL 267
Cdd:TIGR00365   2 IERIKEQIAENPVVLYMKGTPQFPQCGFSARAVQILNACGVPFAYVNVLEDPEIRQGIKEYSNWPTIPQLYVKGEFVGGC 81

                          90
                  ....*....|....*.
gi 1958649024 268 DIVKELKDNGELLPIL 283
Cdd:TIGR00365  82 DIIMEMYQSGELQTLL 97

monothiol glutaredoxin, Grx4 family; The gene for the member of this glutaredoxin family in E. coli, originally designated ydhD, is now designated grxD. Its protein, Grx4, is a monothiol glutaredoxin similar to Grx5 of yeast, which is involved in iron-sulfur cluster formation. [Energy metabolism, Electron transport]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958649024  88 RLKKLTHAAPCMLFMKGTPQEPRCGFSKQMVEILHKHNIQFSSFDIFSDEEVRQGLKTYSNWPTYPQLYVSGELIGGLDI 167
Cdd:TIGR00365   4 RIKEQIAENPVVLYMKGTPQFPQCGFSARAVQILNACGVPFAYVNVLEDPEIRQGIKEYSNWPTIPQLYVKGEFVGGCDI 83

                          90
                  ....*....|...
gi 1958649024 168 IKELEASEELDTI 180
Cdd:TIGR00365  84 IMEMYQSGELQTL 96

glutaredoxin; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958649024 189 ERLKVLTNKASVMLFMKGNKQEAKCGFSKQILEILNSTGVEYETFDILEDEEVRQGLKTFSNWPTYPQLYVRGDLVGGLD 268
Cdd:PTZ00062  104 EKIERLIRNHKILLFMKGSKTFPFCRFSNAVVNMLNSSGVKYETYNIFEDPDLREELKVYSNWPTYPQLYVNGELIGGHD 183

                          90
                  ....*....|.
gi 1958649024 269 IVKELKDNGEL 279
Cdd:PTZ00062  184 IIKELYESNSL 194

Glutaredoxin (GRX) family; composed of GRX, approximately 10 kDa in size, and proteins containing a GRX or GRX-like domain. GRX is a glutathione (GSH) dependent reductase, catalyzing the disulfide reduction of target proteins such as ribonucleotide reductase. It contains a redox active CXXC motif in a TRX fold and uses a similar dithiol mechanism employed by TRXs for intramolecular disulfide bond reduction of protein substrates. Unlike TRX, GRX has preference for mixed GSH disulfide substrates, in which it uses a monothiol mechanism where only the N-terminal cysteine is required. The flow of reducing equivalents in the GRX system goes from NADPH -> GSH reductase -> GSH -> GRX -> protein substrates. By altering the redox state of target proteins, GRX is involved in many cellular functions including DNA synthesis, signal transduction and the defense against oxidative stress. Different classes are known including human GRX1 and GRX2, as well as E. coli GRX1 and GRX3, which are members of this family. E. coli GRX2, however, is a 24-kDa protein that belongs to the GSH S-transferase (GST) family.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958649024  97 PCMLFMKGTpqeprCGFSKQMVEILHKHNIQFSSFDIFSDEEVRQGLKTYSNWPTYPQLYVSGELIGGLDIIKELE 172
Cdd:cd02066     1 KVVVFSKST-----CPYCKRAKRLLESLGIEFEEIDILEDGELREELKELSGWPTVPQIFINGEFIGGYDDLKALH 71

Grx4 family monothiol glutaredoxin;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958649024  97 PCMLFMKGTPQEPRCGFSKQMVEILHKHNIQFSSFDIFSDEEVRQGLKTYSNWPTYPQLYVSGELIGGLDIIKELEASEE 176
Cdd:PRK10824   16 PILLYMKGSPKLPSCGFSAQAVQALSACGERFAYVDILQNPDIRAELPKYANWPTFPQLWVDGELVGGCDIVIEMYQRGE 95

                  ....
gi 1958649024 177 LDTI 180
Cdd:PRK10824   96 LQQL 99

Glutaredoxin;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1958649024 200 VMLFMKgnkqeAKCGFSKQILEILNSTGVEYETFDILEDEEVRQGLKTFSNWPTYPQLYVRGDLV 264
Cdd:pfam00462   1 VVLYTK-----PTCPFCKRAKRLLKSLGVDFEEIDVDEDPEIREELKELSGWPTVPQVFIDGEHI 60

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958649024   1 MNDVMAELAKEHPHVSFVKLEAEAVPEVSEKYEISSVPTFLFFKNSQKVDRLDGAHAP-ELTKKVQ 65
Cdd:cd02947    28 IAPVLEELAEEYPKVKFVKVDVDENPELAEEYGVRSIPTFLFFKNGKEVDRVVGADPKeELEEFLE 93

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958649024   4 VMAELAKEHPH-VSFVKLEAEAVPEVSEKYEISSVPTFLFFKNSQKVDRLDGAHAPE-LTKKVQRHV 68
Cdd:TIGR01068  35 ILEELAKEYEGkVKFVKLNVDENPDIAAKYGIRSIPTLLLFKNGKEVDRSVGALPKAaLKQLINKNL 101

Glutaredoxin (GRX) family, GRX human class 1 and 2 (h_1_2)-like subfamily; composed of proteins similar to human GRXs, approximately 10 kDa in size, and proteins containing a GRX or GRX-like domain. GRX is a glutathione (GSH) dependent reductase, catalyzing the disulfide reduction of target proteins such as ribonucleotide reductase. It contains a redox active CXXC motif in a TRX fold and uses a similar dithiol mechanism employed by TRXs for intramolecular disulfide bond reduction of protein substrates. Unlike TRX, GRX has preference for mixed GSH disulfide substrates, in which it uses a monothiol mechanism where only the N-terminal cysteine is required. The flow of reducing equivalents in the GRX system goes from NADPH -> GSH reductase -> GSH -> GRX -> protein substrates. By altering the redox state of target proteins, GRX is involved in many cellular functions including DNA synthesis, signal transduction and the defense against oxidative stress. Different classes are known including human GRX1 and GRX2, which are members of this subfamily. Also included in this subfamily are the N-terminal GRX domains of proteins similar to human thioredoxin reductase 1 and 3.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958649024 213 CGFSKQILEILNSTGVEYETF--DILED-EEVRQGLKTFSNWPTYPQLYVRGDLVGGLDIVKELKDNGELLPI 282
Cdd:cd03419    10 CPYCKRAKSLLKELGVKPAVVelDQHEDgSEIQDYLQELTGQRTVPNVFIGGKFIGGCDDLMALHKSGKLVKL 82

thioredoxin 2; Provisional

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1958649024   3 DVMAELAKEhphVSFVKLEAEAVPEVSEKYEISSVPTFLFFKNSQKVDRLDGA 55
Cdd:PRK10996   76 DVAAERSGK---VRFVKVNTEAERELSARFRIRSIPTIMIFKNGQVVDMLNGA 125

Glutaredoxin [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1958649024 213 CGFSKQILEILNSTGVEYETFDILEDEEVRQGLKTFSNWPTYPQLYVRGDLVGGLD 268
Cdd:COG0695    10 CPYCARAKRLLDEKGIPYEEIDVDEDPEAREELRERSGRRTVPVIFIGGEHLGGFD 65

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
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1958649024   1 MNDVMAELAKEHPHVSFVKLEAEAVpEVSEKYEISSVPTFLFFKNSQKVDRL 52
Cdd:cd02957    42 LDSHLEELAAKYPETKFVKINAEKA-FLVNYLDIKVLPTLLVYKNGELIDNI 92

Glutaredoxin [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1958649024 109 PRCGFSKQMVEILHKHNIQFSSFDIFSDEEVRQGLKTYSNWPTYPQLYVSGELIGGLD 166
Cdd:COG0695     8 PGCPYCARAKRLLDEKGIPYEEIDVDEDPEAREELRERSGRRTVPVIFIGGEHLGGFD 65

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
                  ....*....|....*....|....*....|....*....|....
gi 1958649024   5 MAELAKEHPHVSFVKLEAEAVPEVSEKYEISSVPTFLFFKNSQK 48
Cdd:cd02961    40 LAKELKGDGKVVVAKVDCTANNDLCSEYGVRGYPTIKLFPNGSK 83

Glutaredoxin (GRX) family, GRX-like domain containing protein subfamily; composed of uncharacterized eukaryotic proteins containing a GRX-like domain having only one conserved cysteine, aligning to the C-terminal cysteine of the CXXC motif of GRXs. This subfamily is predominantly composed of plant proteins. GRX is a glutathione (GSH) dependent reductase, catalyzing the disulfide reduction of target proteins via a redox active CXXC motif using a similar dithiol mechanism employed by TRXs. GRX has preference for mixed GSH disulfide substrates, in which it uses a monothiol mechanism where only the N-terminal cysteine is required. Proteins containing only the C-terminal cysteine are generally redox inactive.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958649024 120 ILHKHNIQFSSFDIFSD----EEVRQGLKTYSNWPTYPQLYVSGELIGGLDIIKELEASEELDTICPKAPKLE 188
Cdd:cd03031    25 ILESFRVKFDERDVSMDsgfrEELRELLGAELKAVSLPRVFVDGRYLGGAEEVLRLNESGELRKLLKGIRARA 97

Phosducin (Phd)-like family, Phd subfamily; Phd is a cytosolic regulator of G protein functions. It specifically binds G protein betagamma (Gbg)-subunits with high affinity, resulting in the solubilization of Gbg from the plasma membrane. This impedes the formation of a functional G protein trimer (G protein alphabetagamma), thereby inhibiting G protein-mediated signal transduction. 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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1958649024   1 MNDVMAELAKEHPHVSFVKLEAEAVpEVSEKYEISSVPTFLFFKN 45
Cdd:cd02987   101 LNSSLLCLAAEYPAVKFCKIRASAT-GASDEFDTDALPALLVYKG 144

disulphide isomerase; Provisional

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1958649024   6 AELAKEHPHVSFVKLEAEAVPEVSEKYEISSVPTFLFFKNSQKVD 50
Cdd:PTZ00102   76 KMLKEKKSEIVLASVDATEEMELAQEFGVRGYPTIKFFNKGNPVN 120