Anterior Gradient (AGR) family; members of this family are similar to secreted proteins encoded by the cement gland-specific genes XAG-1 and XAG-2, expressed in the anterior region of dorsal ectoderm of Xenopus. They are implicated in the formation of the cement gland and the induction of forebrain fate. The human homologs, hAG-2 and hAG-3, are secreted proteins associated with estrogen-positive breast tumors. Yeast two-hybrid studies identified the metastasis-associated C4.4a protein and dystroglycan as binding partners, indicating possible roles in the development and progression of breast cancer. hAG-2 has also been implicated in prostate cancer. Its gene was cloned as an androgen-inducible gene and it was shown to be overexpressed in prostate cancer cells at the mRNA and protein levels. AGR proteins contain one conserved cysteine corresponding to the first cysteine in the CXXC motif of TRX. They show high sequence similarity to ERp19.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453541   47 GWGDQLIWTQTYEEALYKSKTSNKPLMIIHHLDECPHSQALKKVFAENKEIQKLA-EQFVLLNLVYETTDKHLSPDGQYV 125
Cdd:cd02960   1 GWGDDIIWVQTYEEGLYKAKKSNKPLMVIHHLEDCPHSQALKKAFAEHKEIQKLAqEDFIMLNLVHETTDKNLSPDGQYV 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|
gi 5453541  126 PRIMFVDPSLTVRADITGRYSNRLYAYEPADTALLLDNMKKALKLLKTEL 175
Cdd:cd02960  81 PRIMFVDPSLTVRADITGRYSNRLYTYEPADIPLLIENMKKALKLLKTEL 130

Anterior Gradient (AGR) family; members of this family are similar to secreted proteins encoded by the cement gland-specific genes XAG-1 and XAG-2, expressed in the anterior region of dorsal ectoderm of Xenopus. They are implicated in the formation of the cement gland and the induction of forebrain fate. The human homologs, hAG-2 and hAG-3, are secreted proteins associated with estrogen-positive breast tumors. Yeast two-hybrid studies identified the metastasis-associated C4.4a protein and dystroglycan as binding partners, indicating possible roles in the development and progression of breast cancer. hAG-2 has also been implicated in prostate cancer. Its gene was cloned as an androgen-inducible gene and it was shown to be overexpressed in prostate cancer cells at the mRNA and protein levels. AGR proteins contain one conserved cysteine corresponding to the first cysteine in the CXXC motif of TRX. They show high sequence similarity to ERp19.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453541   47 GWGDQLIWTQTYEEALYKSKTSNKPLMIIHHLDECPHSQALKKVFAENKEIQKLA-EQFVLLNLVYETTDKHLSPDGQYV 125
Cdd:cd02960   1 GWGDDIIWVQTYEEGLYKAKKSNKPLMVIHHLEDCPHSQALKKAFAEHKEIQKLAqEDFIMLNLVHETTDKNLSPDGQYV 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|
gi 5453541  126 PRIMFVDPSLTVRADITGRYSNRLYAYEPADTALLLDNMKKALKLLKTEL 175
Cdd:cd02960  81 PRIMFVDPSLTVRADITGRYSNRLYTYEPADIPLLIENMKKALKLLKTEL 130

Thioredoxin-related protein SoxW [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453541   54 WTQTYEEALYKSKTSNKPLMIIHHLDECPHSQALKKVFAENKEIQK-LAEQFVLLNLVYETTDKHLSPDGQ--------- 123
Cdd:COG2143  25 FLLDLEEDLALAKAEGKPILLFFESDWCPYCKKLHKEVFSDPEVAAyLKENFVVVQLDAEGDKEVTDFDGEtltekelar 104

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*...
gi 5453541  124 -----YVPRIMFVDPSLTVRADITGrysnrlyAYEPADTALLLDNMKK 166
Cdd:COG2143 105 kygvrGTPTLVFFDAEGKEIARIPG-------YLKPETFLALLKYVAE 145

Anterior Gradient (AGR) family; members of this family are similar to secreted proteins encoded by the cement gland-specific genes XAG-1 and XAG-2, expressed in the anterior region of dorsal ectoderm of Xenopus. They are implicated in the formation of the cement gland and the induction of forebrain fate. The human homologs, hAG-2 and hAG-3, are secreted proteins associated with estrogen-positive breast tumors. Yeast two-hybrid studies identified the metastasis-associated C4.4a protein and dystroglycan as binding partners, indicating possible roles in the development and progression of breast cancer. hAG-2 has also been implicated in prostate cancer. Its gene was cloned as an androgen-inducible gene and it was shown to be overexpressed in prostate cancer cells at the mRNA and protein levels. AGR proteins contain one conserved cysteine corresponding to the first cysteine in the CXXC motif of TRX. They show high sequence similarity to ERp19.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453541   47 GWGDQLIWTQTYEEALYKSKTSNKPLMIIHHLDECPHSQALKKVFAENKEIQKLA-EQFVLLNLVYETTDKHLSPDGQYV 125
Cdd:cd02960   1 GWGDDIIWVQTYEEGLYKAKKSNKPLMVIHHLEDCPHSQALKKAFAEHKEIQKLAqEDFIMLNLVHETTDKNLSPDGQYV 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|
gi 5453541  126 PRIMFVDPSLTVRADITGRYSNRLYAYEPADTALLLDNMKKALKLLKTEL 175
Cdd:cd02960  81 PRIMFVDPSLTVRADITGRYSNRLYTYEPADIPLLIENMKKALKLLKTEL 130

Endoplasmic reticulum protein 19 (ERp19) family; ERp19 is also known as ERp18, a protein located in the ER containing one redox active TRX domain. Denaturation studies indicate that the reduced form is more stable than the oxidized form, suggesting that the protein is involved in disulfide bond formation. In vitro, ERp19 has been shown to possess thiol-disulfide oxidase activity which is dependent on the presence of both active site cysteines. Although described as protein disulfide isomerase (PDI)-like, the protein does not complement for PDI activity. ERp19 shows a wide tissue distribution but is most abundant in liver, testis, heart and kidney.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453541   50 DQLIWtQTYEEALYKSKTSNKPLMIIHHLDECPHSQALKKVFAENKEIQKLAEQFVLLNLV--YETTDKHLSPDGQYVPR 127
Cdd:cd02959   1 DHIHW-VTLEDGIKEAKDSGKPLMLLIHKTWCGACKALKPKFAESKEISELSHNFVMVNLEddEEPKDEEFSPDGGYIPR 79

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 5453541  128 IMFVDPSLTVRADITGRYSNRLYAYEPADTALLLDNMK 165
Cdd:cd02959  80 ILFLDPSGDVHPEIINKKGNPNYKYFYSSAAQVTESMK 117

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 5453541   73 MIIHHLDECPHSQALKKVFAENKEIQKLAeQFVLLNLVYETTDKH--LSPDGQYVPRIMFVDPSLTVR 138
Cdd:cd01659   1 LVLFYAPWCPFCQALRPVLAELALLNKGV-KFEAVDVDEDPALEKelKRYGVGGVPTLVVFGPGIGVK 67