oxygenase domain of ten-eleven translocation (TET) enzymes, J-binding proteins (JBPs), and similar proteins; TET proteins are involved in DNA demethylation through iteratively oxidizing 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). TET proteins contain a C-terminal catalytic domain which consists of a cysteine-rich region and a double-stranded beta-helix (DSBH) fold. Alterations in TET protein function have been linked to cancer, and TETs influence many cell differentiation processes. J binding protein (JBP) 1 and JBP2 are thymidine hydroxylases that catalyze the first step of base J biosynthesis: the hydroxylation of thymine in DNA to form 5-hydroxymethyluracil (hmU). Base J (beta-d-glucopyranosyloxymethyluracil) is a hyper-modified DNA base found in the DNA of kinetoplastids (Trypanosoma brucei, Trypanosoma cruzi, and Leishmania). JBP1 and JBP2 each contain a J-DNA binding domain and a thymidine hydroxylase domain. Members of this TET/JBP family of dioxygenases require Fe2+ and alpha-ketoglutarate (also known as 2-oxoglutarate) for activity.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 386770421 1802 AEINENIEAFQDPQMGGVAIALNHGSVLIECAKHEMHATTAVRRPDRHHPTRMTLIFYQHRNLNRCRHGIDEWEEKM 1878
Cdd:cd18892   322 EYWSDSEECFLDPDIGGVAIALSHGSVLFECAKRELHATTPLKNPNRQHPTRISLVFYQHKNLNYSRHGLAEYEAKM 398

oxygenase domain of ten-eleven translocation (TET)1, TET2, and TET3 methylcytosine dioxygenases and similar proteins; TET proteins are involved in DNA demethylation through iteratively oxidizing 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). TET proteins contain a C-terminal catalytic domain which consists of a cysteine-rich region and a double-stranded beta-helix (DSBH) fold. Alterations in TET protein function have been linked to cancer, and TETs influence many cell differentiation processes. TET family genes have been implicated as tumor suppressors, for example mutations/deletions of the TET2 gene frequently occur in multiple spectra of myeloid malignancies. TET3 acts as a suppressor of ovarian cancer by demethylating the miR-30d precursor gene promoter to block TGF-beta1 induced epithelial-mesenchymal transition (EMT). TET3 (and TET2) promoters are silenced in melanoma cells by mechanisms triggered by TGF-beta and mediated by DNA methyltransferase 3 alpha (DNMT3A). TET genes are downregulated in endometriosis. TET proteins belong to the TET/JBP family of dioxygenases that require Fe2+ and alpha-ketoglutarate (also known as 2-oxoglutarate) for activity.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 386770421 1802 AEINENIEAFQDPQMGGVAIALNHGSVLIECAKHEMHATTAVRRPDRHHPTRMTLIFYQHRNLNRCRHGIDEWEEKM 1878
Cdd:cd18892   322 EYWSDSEECFLDPDIGGVAIALSHGSVLFECAKRELHATTPLKNPNRQHPTRISLVFYQHKNLNYSRHGLAEYEAKM 398

Oxygenase domain of the 2OGFeDO superfamily; A double-stranded beta helix (DSBH) fold domain of the 2-oxoglutarate (2OG)-Fe(II)-dependent dioxygenase (2OGFeDO) superfamily found in various eukaryotes, bacteria and bacteriophages. Members of this family catalyze nucleic acid modifications, such as thymidine hydroxylation during base J synthesis in kinetoplastids, and the conversion of 5 methyl-cytosine (5-mC) to 5-hydroxymethyl-cytosine (hmC), or further oxidation to 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). Metazoan TET proteins contain a cysteine-rich region inserted into the core of the DSBH fold. Vertebrate TET proteins are oncogenes that are mutated in various myeloid cancers. Fungal and algal versions of this family are linked to a predicted transposase and show lineage-specific expansions.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 386770421  1811 FQDPQMGgVAIALNHGSVLIECAKHEMHATTAVRRPDRHhpTRMTLIFYQHR 1862
Cdd:pfam12851  118 LALPQLG-VAFAPTPGTVLIFCGKSLEHGVTPVKNPNRW--ERVSLVFYWHK 166

oxygenase domain of ten-eleven translocation (TET)2 methylcytosine dioxygenase and similar proteins; TET2 is involved in DNA demethylation through iteratively oxidizing 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). Human TET2 (and TET1) have been shown to be more active on 5mC-DNA than 5hmC/5fC-DNA substrates. TET proteins contain a C-terminal catalytic domain which consists of a cysteine-rich region and a double-stranded beta-helix (DSBH) fold. TET2 acts as a tumor suppressor in hematopoiesis; mutations/deletions of the TET2 gene frequently occur in multiple spectra of myeloid malignancies. TET2 (and TET3) promoters are silenced in melanoma cells by mechanisms triggered by TGF-beta and mediated by DNA methyltransferase 3 alpha (DNMT3A), which play a functional role in the epithelial-mesenchymal transition process and metastasis. In addition, TET2 (and TET3) may be guardians of regulatory T cell stability and immune homeostasis. TET2 belongs to the TET/JBP family of dioxygenases that require Fe2+ and alpha-ketoglutarate (also known as 2-oxoglutarate) for activity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386770421  830 EIPECECFQSDKNPPEpGTYYTHLGTASSLMDLRREFEERCNLTGRQLRIEKIVYTGKEGKTSQGCPVAKWVIRRADLEE 909
Cdd:cd18896     1 DFPSCSCVEQIIEKDE-GPYYTHLGAGPNVAAIREIMEERFGQKGKAIRIERVIYTGKEGKSSQGCPIAKWVIRRSSEEE 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386770421  910 KILVVVKKRPGHRCIAAYIVVCMVAWDGMPRLEADNAYKNLIPKLNKYGLPTTRRCATNENRTCACQGLDPESSGASYSF 989
Cdd:cd18896    80 KLLCLVRERAGHSCETAVIVILILVWEGIPISLADKLYSELTDTLRKYGTLTNRRCALNEERTCACQGLDPETCGASFSF 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386770421  990 GCSWSMYYNGCKYARSKTVRKFRLSVK--SEEAAIEDHMNLIATLLAPVFKQVCPRSYDNQTKYEHEASDCRLGLEPGKP 1067
Cdd:cd18896   160 GCSWSMYYNGCKFARSKIPRKFKLLGDdpKEEEKLESNLQNLSTLMAPTYKKLAPDAYNNQIEYEHRAPDCRLGLKEGRP 239

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386770421 1068 FSGVTACLDFCAHSHRDLHNMQDGCTVHVALLKPGNRDT-RLPDDEQFHVLPLYTMDGTDEFESVEGQRDKHRTGAVQML 1146
Cdd:cd18896   240 FSGVTACLDFCAHAHRDLHNMQNGSTLVCTLTREDNREIgKIPEDEQLHVLPLYKVSDVDEFGSTEAQEEKKRNGAIQVL 319

                         330
                  ....*....|....*....
gi 386770421 1147 DKFPCEVRVRSTPLIPCRR 1165
Cdd:cd18896   320 SSFRRKVRMLAEPVKTCRQ 338

oxygenase domain of ten-eleven translocation (TET)3 methylcytosine dioxygenase and similar proteins; TET3 is involved in DNA demethylation through iteratively oxidizing 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). TET proteins contain a C-terminal catalytic domain which consists of a cysteine-rich region and a double-stranded beta-helix (DSBH) fold. TET3 serves as a tumor suppressor; it acts as a suppressor of ovarian cancer by demethylating the miR-30d precursor gene promoter to block TGF-beta1 induced epithelial-mesenchymal transition (EMT). TET3 (and TET2) promoters are silenced in melanoma cells by mechanisms triggered by TGF-beta and mediated by DNA methyltransferase 3 alpha (DNMT3A), which play a functional role in the EMT process and metastasis. In addition, TET3 (and TET2) may be guardians of regulatory T cell stability and immune homeostasis. TET3 has been shown to prevent terminal differentiation of adult neural stem cells by a mechanism involving direct binding and repression of TET3 to the imprinted gene Snrpn. TET3 has also been shown to mediate the activation of hepatic stellate cells via modulation of the long non-coding RNA HIF1A-AS1 expression. TET1 belongs to the TET/JBP family of dioxygenases that require Fe2+ and alpha-ketoglutarate (also known as 2-oxoglutarate) for activity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386770421  834 CECFQSDKNPPEpGTYYTHLGTASSLMDLRREFEERCNLTGRQLRIEKIVYTGKEGKTSQGCPVAKWVIRRADLEEKILV 913
Cdd:cd18897     1 CDCVEQILEKDE-GPYYTHLGSGPTVASIRELMEERYGEKGKAIRIEKVIYTGKEGKSSRGCPIAKWVIRRSSEEEKLLC 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386770421  914 VVKKRPGHRCIAAYIVVCMVAWDGMPRLEADNAYKNLIPKLNKYGLPTTRRCATNENRTCACQGLDPESSGASYSFGCSW 993
Cdd:cd18897    80 LVRHRAGHHCQNAVIVILILAWEGIPRALGDKLYQELTETLTKYGNPTSRRCGLNDDRTCACQGKDPNTCGASFSFGCSW 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386770421  994 SMYYNGCKYARSKTVRKFRLSVKS--EEAAIEDHMNLIATLLAPVFKQVCPRSYDNQTKYEHEASDCRLGLEPGKPFSGV 1071
Cdd:cd18897   160 SMYFNGCKYARSKTPRKFRLIGDNpkEEENLRDNFQDLATEVAPLYKRLAPQAYQNQVTNEDIAIDCRLGLKEGRPFSGV 239

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386770421 1072 TACLDFCAHSHRDLHNMQDGCTVHVALLKPGNRDT-RLPDDEQFHVLPLYTMDGTDEFESVEGQRDKHRTGAVQMLDKFP 1150
Cdd:cd18897   240 TACMDFCAHAHKDQHNLYNGCTVVCTLTKEDNRTVgKIPEDEQLHVLPLYKMSTTDEFGSEENQNEKIGSGAIQVLTSFP 319

                  ....
gi 386770421 1151 CEVR 1154
Cdd:cd18897   320 REVR 323

oxygenase domain of ten-eleven translocation (TET)1, TET2, and TET3 methylcytosine dioxygenases and similar proteins; TET proteins are involved in DNA demethylation through iteratively oxidizing 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). TET proteins contain a C-terminal catalytic domain which consists of a cysteine-rich region and a double-stranded beta-helix (DSBH) fold. Alterations in TET protein function have been linked to cancer, and TETs influence many cell differentiation processes. TET family genes have been implicated as tumor suppressors, for example mutations/deletions of the TET2 gene frequently occur in multiple spectra of myeloid malignancies. TET3 acts as a suppressor of ovarian cancer by demethylating the miR-30d precursor gene promoter to block TGF-beta1 induced epithelial-mesenchymal transition (EMT). TET3 (and TET2) promoters are silenced in melanoma cells by mechanisms triggered by TGF-beta and mediated by DNA methyltransferase 3 alpha (DNMT3A). TET genes are downregulated in endometriosis. TET proteins belong to the TET/JBP family of dioxygenases that require Fe2+ and alpha-ketoglutarate (also known as 2-oxoglutarate) for activity.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 386770421 1802 AEINENIEAFQDPQMGGVAIALNHGSVLIECAKHEMHATTAVRRPDRHHPTRMTLIFYQHRNLNRCRHGIDEWEEKM 1878
Cdd:cd18892   322 EYWSDSEECFLDPDIGGVAIALSHGSVLFECAKRELHATTPLKNPNRQHPTRISLVFYQHKNLNYSRHGLAEYEAKM 398

oxygenase domain of ten-eleven translocation (TET)2 methylcytosine dioxygenase and similar proteins; TET2 is involved in DNA demethylation through iteratively oxidizing 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). Human TET2 (and TET1) have been shown to be more active on 5mC-DNA than 5hmC/5fC-DNA substrates. TET proteins contain a C-terminal catalytic domain which consists of a cysteine-rich region and a double-stranded beta-helix (DSBH) fold. TET2 acts as a tumor suppressor in hematopoiesis; mutations/deletions of the TET2 gene frequently occur in multiple spectra of myeloid malignancies. TET2 (and TET3) promoters are silenced in melanoma cells by mechanisms triggered by TGF-beta and mediated by DNA methyltransferase 3 alpha (DNMT3A), which play a functional role in the epithelial-mesenchymal transition process and metastasis. In addition, TET2 (and TET3) may be guardians of regulatory T cell stability and immune homeostasis. TET2 belongs to the TET/JBP family of dioxygenases that require Fe2+ and alpha-ketoglutarate (also known as 2-oxoglutarate) for activity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386770421 1809 EAFQDPQMGGVAIALNHGSVLIECAKHEMHATTAVRRPDRHHPTRMTLIFYQHRNLNRCRHGIDEWEEKMRvkkintdld 1888
Cdd:cd18896   351 QSFLDPDIGGVAVAPSHGSILIECAKRELHATTPLKNPNRNHPTRISLVFYQHKSMNEPKHGLALWEAKMA--------- 421

                  ....*...
gi 386770421 1889 NKAKEERE 1896
Cdd:cd18896   422 EKAREKEE 429

oxygenase domain of ten-eleven translocation (TET)3 methylcytosine dioxygenase and similar proteins; TET3 is involved in DNA demethylation through iteratively oxidizing 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). TET proteins contain a C-terminal catalytic domain which consists of a cysteine-rich region and a double-stranded beta-helix (DSBH) fold. TET3 serves as a tumor suppressor; it acts as a suppressor of ovarian cancer by demethylating the miR-30d precursor gene promoter to block TGF-beta1 induced epithelial-mesenchymal transition (EMT). TET3 (and TET2) promoters are silenced in melanoma cells by mechanisms triggered by TGF-beta and mediated by DNA methyltransferase 3 alpha (DNMT3A), which play a functional role in the EMT process and metastasis. In addition, TET3 (and TET2) may be guardians of regulatory T cell stability and immune homeostasis. TET3 has been shown to prevent terminal differentiation of adult neural stem cells by a mechanism involving direct binding and repression of TET3 to the imprinted gene Snrpn. TET3 has also been shown to mediate the activation of hepatic stellate cells via modulation of the long non-coding RNA HIF1A-AS1 expression. TET1 belongs to the TET/JBP family of dioxygenases that require Fe2+ and alpha-ketoglutarate (also known as 2-oxoglutarate) for activity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386770421 1800 EVAEINENIE-AFQDPQMGGVAIALNHGSVLIECAKHEMHATTAVRRPDRHHPTRMTLIFYQHRNLNRCRHGIDEWEEKM 1878
Cdd:cd18897   321 EVREVWSDSEhNFLDENIGGVAVAPAHGSILIECARRELHATTPLKKPNRCHPTRISLVFYQHKNLNQPNHGLALWEAKM 400

                          90       100
                  ....*....|....*....|...
gi 386770421 1879 RVkkintdLDNKAK---EERERL 1898
Cdd:cd18897   401 KL------LAERARarqEEAARL 417

oxygenase domain of ten-eleven translocation (TET) enzymes, J-binding proteins (JBPs), and similar proteins; TET proteins are involved in DNA demethylation through iteratively oxidizing 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). TET proteins contain a C-terminal catalytic domain which consists of a cysteine-rich region and a double-stranded beta-helix (DSBH) fold. Alterations in TET protein function have been linked to cancer, and TETs influence many cell differentiation processes. J binding protein (JBP) 1 and JBP2 are thymidine hydroxylases that catalyze the first step of base J biosynthesis: the hydroxylation of thymine in DNA to form 5-hydroxymethyluracil (hmU). Base J (beta-d-glucopyranosyloxymethyluracil) is a hyper-modified DNA base found in the DNA of kinetoplastids (Trypanosoma brucei, Trypanosoma cruzi, and Leishmania). JBP1 and JBP2 each contain a J-DNA binding domain and a thymidine hydroxylase domain. Members of this TET/JBP family of dioxygenases require Fe2+ and alpha-ketoglutarate (also known as 2-oxoglutarate) for activity.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 386770421 1817 GGVAIALNHGSVLIECAKHEMHATTAVRRPDrHHPTRMTLIFYQHR 1862
Cdd:cd14946   220 GNCAVFVQPGDVLFFKGNEYKHVVTNITNPN-NHGWRISLVYYAHK 264