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 60279653  42 GWGDQLIWAQTYEEALFWSRSKNKPLMVIFHLEDCPHSQALKKAFAEDKEIQKLADEDFVILNLVYETTDKHLSPDGQYV 121
Cdd:cd02960   1 GWGDDIIWVQTYEEGLYKAKKSNKPLMVIHHLEDCPHSQALKKAFAEHKEIQKLAQEDFIMLNLVHETTDKNLSPDGQYV 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|
gi 60279653 122 PRIIFVDPSMTVRADITGRYSNRMYAYEPADMKLLLSNMQRALKFLKTEL 171
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 60279653  42 GWGDQLIWAQTYEEALFWSRSKNKPLMVIFHLEDCPHSQALKKAFAEDKEIQKLADEDFVILNLVYETTDKHLSPDGQYV 121
Cdd:cd02960   1 GWGDDIIWVQTYEEGLYKAKKSNKPLMVIHHLEDCPHSQALKKAFAEHKEIQKLAQEDFIMLNLVHETTDKNLSPDGQYV 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|
gi 60279653 122 PRIIFVDPSMTVRADITGRYSNRMYAYEPADMKLLLSNMQRALKFLKTEL 171
Cdd:cd02960  81 PRIMFVDPSLTVRADITGRYSNRLYTYEPADIPLLIENMKKALKLLKTEL 130

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 60279653  49 WAQTYEEALFWSRSKNKPLMVIFHLEDCPHSQALKKAFAEDKEIQKLADEDFVILNLVYETTDKHLSPDGQ--------- 119
Cdd:COG2143  25 FLLDLEEDLALAKAEGKPILLFFESDWCPYCKKLHKEVFSDPEVAAYLKENFVVVQLDAEGDKEVTDFDGEtltekelar 104

                        90       100
                ....*....|....*....|....*
gi 60279653 120 -----YVPRIIFVDPSMTVRADITG 139
Cdd:COG2143 105 kygvrGTPTLVFFDAEGKEIARIPG 129

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 60279653  42 GWGDQLIWAQTYEEALFWSRSKNKPLMVIFHLEDCPHSQALKKAFAEDKEIQKLADEDFVILNLVYETTDKHLSPDGQYV 121
Cdd:cd02960   1 GWGDDIIWVQTYEEGLYKAKKSNKPLMVIHHLEDCPHSQALKKAFAEHKEIQKLAQEDFIMLNLVHETTDKNLSPDGQYV 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|
gi 60279653 122 PRIIFVDPSMTVRADITGRYSNRMYAYEPADMKLLLSNMQRALKFLKTEL 171
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 60279653  45 DQLIWAqTYEEALFWSRSKNKPLMVIFHLEDCPHSQALKKAFAEDKEIQKLAdEDFVILNLV--YETTDKHLSPDGQYVP 122
Cdd:cd02959   1 DHIHWV-TLEDGIKEAKDSGKPLMLLIHKTWCGACKALKPKFAESKEISELS-HNFVMVNLEddEEPKDEEFSPDGGYIP 78

                        90       100
                ....*....|....*....|....*.
gi 60279653 123 RIIFVDPSMTVRADITGRYSNRMYAY 148
Cdd:cd02959  79 RILFLDPSGDVHPEIINKKGNPNYKY 104

SoxW family; SoxW is a bacterial periplasmic TRX, containing a redox active CXXC motif, encoded by a genetic locus (sox operon) involved in thiosulfate oxidation. Sulfur bacteria oxidize sulfur compounds to provide reducing equivalents for carbon dioxide fixation during autotrophic growth and the respiratory electron transport chain. It is unclear what the role of SoxW is, since it has been found to be dispensable in the oxidation of thiosulfate to sulfate. SoxW is specifically kept in the reduced state by SoxV, which is essential in thiosulfate oxidation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 60279653  63 KNKPLMVIFHLEDCPHSQALKKAFAEDKEIQKLADEDFVILNLVYETTDKHLSPDGQ--------------YVPRIIFVD 128
Cdd:cd02951  13 GKKPLLLLFSQPGCPYCDKLKRDYLNDPAVQAYIRAHFVVVYINIDGDKEVTDFDGEalsekelarkyrvrFTPTVIFLD 92

                ..
gi 60279653 129 PS 130
Cdd:cd02951  93 PE 94

UAS family; UAS is a domain of unknown function. Most members of this family are uncharacterized proteins with similarity to FAS-associated factor 1 (FAF1) and ETEA because of the presence of a UAS domain N-terminal to a ubiquitin-associated UBX domain. FAF1 is a longer protein, compared to the other members of this family, having additional N-terminal domains, a ubiquitin-associated UBA domain and a nuclear targeting domain. FAF1 is an apoptotic signaling molecule that acts downstream in the Fas signal transduction pathway. It interacts with the cytoplasmic domain of Fas, but not to a Fas mutant that is deficient in signal transduction. ETEA is the protein product of a highly expressed gene in T-cells and eosinophils of atopic dermatitis patients. The presence of the ubiquitin-associated UBX domain in the proteins of this family suggests the possibility of their involvement in ubiquitination. Recently, FAF1 has been shown to interact with valosin-containing protein (VCP), which is involved in the ubiquitin-proteosome pathway. Some members of this family are uncharacterized proteins containing only a UAS domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 60279653  52 TYEEALFWSRSKNKPLMVIFHLEDCPHSQALKKAFAEDKEIQKLADEDFVIlnLVYETTdkhlSPDGQYV---------P 122
Cdd:cd02958   5 SFEDAKQEAKSEKKWLLVYLQSEDEFDSQVLNRDLWSNESVKEFIRENFIF--WQCDID----SSEGQRFlqsykvdkyP 78

                        90
                ....*....|....*....
gi 60279653 123 RIIFVDP-SMTVRADITGR 140
Cdd:cd02958  79 HIAIIDPrTGEVLKVWSGN 97