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Conserved domains on  [gi|767914146|ref|XP_011530992|]
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methylcytosine dioxygenase TET3 isoform X9 [Homo sapiens]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
Tet_JBP super family cl40427
oxygenase domain of ten-eleven translocation (TET) enzymes, J-binding proteins (JBPs), and ...
 1-310 0e+00

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.


The actual alignment was detected with superfamily member cd18897:

Pssm-ID: 394797  Cd Length: 452  Bit Score: 651.28  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914146   1 MEERYGEKGKAIRIEKVIYTGKEGKSSRGCPIAKWVIRRHTLEEKLLCLVRHRAGHHCQNAVIVILILAWEGIPRSLGDT 80
Cdd:cd18897   32 MEERYGEKGKAIRIEKVIYTGKEGKSSRGCPIAKWVIRRSSEEEKLLCLVRHRAGHHCQNAVIVILILAWEGIPRALGDK 111

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914146  81 LYQELTDTLRKYGNPTSRRCGLNDDRTCACQGKDPNTCGASFSFGCSWSMYFNGCKYARSKTPRKFRLAGDNPKEEEVLR 160
Cdd:cd18897  112 LYQELTETLTKYGNPTSRRCGLNDDRTCACQGKDPNTCGASFSFGCSWSMYFNGCKYARSKTPRKFRLIGDNPKEEENLR 191

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914146 161 KSFQDLATEVAPLYKRLAPQAYQNQlgplsqktsllqskgkVTNEEIAIDCRLGLKEGRPFAGVTACMDFCAHAHKDQHN 240
Cdd:cd18897  192 DNFQDLATEVAPLYKRLAPQAYQNQ----------------VTNEDIAIDCRLGLKEGRPFSGVTACMDFCAHAHKDQHN 255

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914146 241 LYNGCTVVCTLTKEDNRCVGKIPEDEQLHVLPLYKMANTDEFGSEENQNAKVGSGAIQVLTAFPREVRRL 310
Cdd:cd18897  256 LYNGCTVVCTLTKEDNRTVGKIPEDEQLHVLPLYKMSTTDEFGSEENQNEKIGSGAIQVLTSFPREVREV 325
Tet_JBP super family cl40427
oxygenase domain of ten-eleven translocation (TET) enzymes, J-binding proteins (JBPs), and ...
 796-924 1.35e-83

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.


The actual alignment was detected with superfamily member cd18897:

Pssm-ID: 394797  Cd Length: 452  Bit Score: 276.87  E-value: 1.35e-83
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914146 796 LWSDSEHNFLDENIGGVAVAPAHGSILIECARRELHATTPLKKPNRCHPTRISLVFYQHKNLNQPNHGLALWEAKMKQLA 875
Cdd:cd18897  325 VWSDSEHNFLDENIGGVAVAPAHGSILIECARRELHATTPLKKPNRCHPTRISLVFYQHKNLNQPNHGLALWEAKMKLLA 404

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 767914146 876 ERARARQEEAARLGLgQQEAKLYGKKRKWGGTVVAEPQQKEKKGVVPTR 924
Cdd:cd18897  405 ERARARQEEAARLGL-QQEIKPYGKKRKWGGAPAAEPQPKEKKDKIPTR 452
 
Name Accession Description Interval E-value
TET3 cd18897
oxygenase domain of ten-eleven translocation (TET)3 methylcytosine dioxygenase and similar ...
 1-310 0e+00

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.


Pssm-ID: 380676  Cd Length: 452  Bit Score: 651.28  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914146   1 MEERYGEKGKAIRIEKVIYTGKEGKSSRGCPIAKWVIRRHTLEEKLLCLVRHRAGHHCQNAVIVILILAWEGIPRSLGDT 80
Cdd:cd18897   32 MEERYGEKGKAIRIEKVIYTGKEGKSSRGCPIAKWVIRRSSEEEKLLCLVRHRAGHHCQNAVIVILILAWEGIPRALGDK 111

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914146  81 LYQELTDTLRKYGNPTSRRCGLNDDRTCACQGKDPNTCGASFSFGCSWSMYFNGCKYARSKTPRKFRLAGDNPKEEEVLR 160
Cdd:cd18897  112 LYQELTETLTKYGNPTSRRCGLNDDRTCACQGKDPNTCGASFSFGCSWSMYFNGCKYARSKTPRKFRLIGDNPKEEENLR 191

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914146 161 KSFQDLATEVAPLYKRLAPQAYQNQlgplsqktsllqskgkVTNEEIAIDCRLGLKEGRPFAGVTACMDFCAHAHKDQHN 240
Cdd:cd18897  192 DNFQDLATEVAPLYKRLAPQAYQNQ----------------VTNEDIAIDCRLGLKEGRPFSGVTACMDFCAHAHKDQHN 255

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914146 241 LYNGCTVVCTLTKEDNRCVGKIPEDEQLHVLPLYKMANTDEFGSEENQNAKVGSGAIQVLTAFPREVRRL 310
Cdd:cd18897  256 LYNGCTVVCTLTKEDNRTVGKIPEDEQLHVLPLYKMSTTDEFGSEENQNEKIGSGAIQVLTSFPREVREV 325
TET3 cd18897
oxygenase domain of ten-eleven translocation (TET)3 methylcytosine dioxygenase and similar ...
 796-924 1.35e-83

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.


Pssm-ID: 380676  Cd Length: 452  Bit Score: 276.87  E-value: 1.35e-83
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914146 796 LWSDSEHNFLDENIGGVAVAPAHGSILIECARRELHATTPLKKPNRCHPTRISLVFYQHKNLNQPNHGLALWEAKMKQLA 875
Cdd:cd18897  325 VWSDSEHNFLDENIGGVAVAPAHGSILIECARRELHATTPLKKPNRCHPTRISLVFYQHKNLNQPNHGLALWEAKMKLLA 404

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 767914146 876 ERARARQEEAARLGLgQQEAKLYGKKRKWGGTVVAEPQQKEKKGVVPTR 924
Cdd:cd18897  405 ERARARQEEAARLGL-QQEIKPYGKKRKWGGAPAAEPQPKEKKDKIPTR 452
Tet_JBP pfam12851
Oxygenase domain of the 2OGFeDO superfamily; A double-stranded beta helix (DSBH) fold domain ...
 127-270 1.03e-39

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.


Pssm-ID: 372343  Cd Length: 166  Bit Score: 144.45  E-value: 1.03e-39
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914146  127 SWSMYFNGCKYARSKTPRKFRLAGDNPKEEEVLRKSFQDLATEVAPLYKRLAPQAYQNQlgplsqktsllqskgkVTNEE 206
Cdd:pfam12851   1 SWSMYYDGCKFPGPRKPRKFSFTPRNPKEEIKLEDELQELAALLGAIYKQIAPDLYENQ----------------IEYEQ 64

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767914146  207 IAIDCRLGLKEGRPFAGVTACMDFCAHAHKDQHNLYNGCTVVCTLTkedNRCVGKIPEDEQLHV 270
Cdd:pfam12851  65 DAAICRLGRKWGRPFSGVTVNLNFETISHRDLGNFRNGSTLLCTLT---GRYEGGRLALPQLGV 125
Tet_JBP pfam12851
Oxygenase domain of the 2OGFeDO superfamily; A double-stranded beta helix (DSBH) fold domain ...
 811-855 1.98e-11

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.


Pssm-ID: 372343  Cd Length: 166  Bit Score: 63.17  E-value: 1.98e-11
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 767914146  811 GVAVAPAHGSILIECARRELHATTPLKKPNRchPTRISLVFYQHK 855
Cdd:pfam12851 124 GVAFAPTPGTVLIFCGKSLEHGVTPVKNPNR--WERVSLVFYWHK 166
 
Name Accession Description Interval E-value
TET3 cd18897
oxygenase domain of ten-eleven translocation (TET)3 methylcytosine dioxygenase and similar ...
 1-310 0e+00

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.


Pssm-ID: 380676  Cd Length: 452  Bit Score: 651.28  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914146   1 MEERYGEKGKAIRIEKVIYTGKEGKSSRGCPIAKWVIRRHTLEEKLLCLVRHRAGHHCQNAVIVILILAWEGIPRSLGDT 80
Cdd:cd18897   32 MEERYGEKGKAIRIEKVIYTGKEGKSSRGCPIAKWVIRRSSEEEKLLCLVRHRAGHHCQNAVIVILILAWEGIPRALGDK 111

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914146  81 LYQELTDTLRKYGNPTSRRCGLNDDRTCACQGKDPNTCGASFSFGCSWSMYFNGCKYARSKTPRKFRLAGDNPKEEEVLR 160
Cdd:cd18897  112 LYQELTETLTKYGNPTSRRCGLNDDRTCACQGKDPNTCGASFSFGCSWSMYFNGCKYARSKTPRKFRLIGDNPKEEENLR 191

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914146 161 KSFQDLATEVAPLYKRLAPQAYQNQlgplsqktsllqskgkVTNEEIAIDCRLGLKEGRPFAGVTACMDFCAHAHKDQHN 240
Cdd:cd18897  192 DNFQDLATEVAPLYKRLAPQAYQNQ----------------VTNEDIAIDCRLGLKEGRPFSGVTACMDFCAHAHKDQHN 255

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914146 241 LYNGCTVVCTLTKEDNRCVGKIPEDEQLHVLPLYKMANTDEFGSEENQNAKVGSGAIQVLTAFPREVRRL 310
Cdd:cd18897  256 LYNGCTVVCTLTKEDNRTVGKIPEDEQLHVLPLYKMSTTDEFGSEENQNEKIGSGAIQVLTSFPREVREV 325
TET cd18892
oxygenase domain of ten-eleven translocation (TET)1, TET2, and TET3 methylcytosine ...
 1-320 0e+00

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.


Pssm-ID: 380671  Cd Length: 398  Bit Score: 596.20  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914146   1 MEERYGEKGKAIRIEKVIYTGKEGKSSRGCPIAKWVIRRHTLEEKLLCLVRHRAGHHCQNAVIVILILAWEGIPRSLGDT 80
Cdd:cd18892   33 LEKRTGVTGKAIRIEKVIYTGKEGKTSQGCPIAKWIIRRSSLEEKYLVLVKHRPGHFCHSAFIVICIVAWEGVPQSNADE 112

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914146  81 LYQELTDTLRKYGNPTSRRCGLNDDRTCACQGKDPNTCGASFSFGCSWSMYFNGCKYARSKTPRKFRLAGdnPKEEEVLR 160
Cdd:cd18892  113 LYSLLTDKLNKFGLPTKRRCGTNEERTCACQGLDPETCGASFSFGCSWSMYYNGCKFARSKTVRKFRLSD--KSEEEELE 190

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914146 161 KSFQDLATEVAPLYKRLAPQAYQNQlgplsqktsllqskgkVTNEEIAIDCRLGLKEGRPFAGVTACMDFCAHAHKDQHN 240
Cdd:cd18892  191 DKLQNLATHLAPLYKSLAPDSYKNQ----------------VQFEEEALDCRLGLKPGRPFSGVTACVDFCAHAHKDLHN 254

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914146 241 LYNGCTVVCTLTKEDNRCvGKIPEDEQLHVLPLYKMANTDEFGSEENQNAKVGSGAIQVLTAFPREVRRLPEPAKSCRQR 320
Cdd:cd18892  255 MNNGCTVVVTLTKHRNLT-KPEPEQLHVLPLYLYDMTDEDEFGSVEGQEEKVRNGSIEVLTKYPCEVREYWSDSEECFLD 333
TET1 cd18895
oxygenase domain of ten-eleven translocation (TET)1 methylcytosine dioxygenase and similar ...
 1-310 0e+00

oxygenase domain of ten-eleven translocation (TET)1 methylcytosine dioxygenase and similar proteins; TET1 is involved in DNA demethylation through iteratively oxidizing 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). Human TET1 (and TET2) are 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. TET1 plays multiple roles in in tumor development and progression. TET1 serves as a tumor suppressor gene; loss of TET1 is associated with tumorigenesis and can be used as a potential biomarker for cancer therapy. In addition to its dioxygenase activity, it can induce epithelial-mesenchymal transition and act as a coactivator to regulate gene transcription. The regulation of TET1 is also correlated with microRNA in a posttranscriptional modification process. TET1 belongs to the TET/JBP family of dioxygenases that require Fe2+ and alpha-ketoglutarate (also known as 2-oxoglutarate) for activity.


Pssm-ID: 380674  Cd Length: 410  Bit Score: 546.05  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914146   1 MEERYGEKGKAIRIEKVIYTGKEGKSSRGCPIAKWVIRRHTLEEKLLCLVRHRAGHHCQNAVIVILILAWEGIPRSLGDT 80
Cdd:cd18895   32 MENRYGEKGNAIRIEVVVYTGKEGKSSQGCPIAKWVIRRSSDEEKLLCLVRQRAGHHCQTAVIVILILAWEGIPRLLADR 111

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914146  81 LYQELTDTLRKYGNPTSRRCGLNDDRTCACQGKDPNTCGASFSFGCSWSMYFNGCKYARSKTPRKFRLAGDNPKEEEVLR 160
Cdd:cd18895  112 LYQELTQTLKKYGSPTSRRCALNEDRTCACQGLDPETCGASFSFGCSWSMYFNGCKFARSKYPRKFRLLTDDPKEEENLE 191

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914146 161 KSFQDLATEVAPLYKRLAPQAYQNQlgplsqktsllqskgkVTNEEIAIDCRLGLKEGRPFAGVTACMDFCAHAHKDQHN 240
Cdd:cd18895  192 SNLQNLATDVAPVYKKLAPEAFQNQ----------------VENENVAPDCRLGSKEGRPFSGVTACIDFCAHAHKDTHN 255

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914146 241 LYNGCTVVCTLTKEDNRCVGKIPEDEQLHVLPLYKMANTDEFGSEENQNAKVGSGAIQVLTAFPREVRRL 310
Cdd:cd18895  256 MHNGSTVVCTLTKEDNRSVGVIPEDEQLHVLPLYKISDTDEFGSEEGQEAKIKNGAIQVLSAFPREVREV 325
TET2 cd18896
oxygenase domain of ten-eleven translocation (TET)2 methylcytosine dioxygenase and similar ...
 1-322 0e+00

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.


Pssm-ID: 380675  Cd Length: 434  Bit Score: 538.40  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914146   1 MEERYGEKGKAIRIEKVIYTGKEGKSSRGCPIAKWVIRRHTLEEKLLCLVRHRAGHHCQNAVIVILILAWEGIPRSLGDT 80
Cdd:cd18896   36 MEERFGQKGKAIRIERVIYTGKEGKSSQGCPIAKWVIRRSSEEEKLLCLVRERAGHSCETAVIVILILVWEGIPISLADK 115

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914146  81 LYQELTDTLRKYGNPTSRRCGLNDDRTCACQGKDPNTCGASFSFGCSWSMYFNGCKYARSKTPRKFRLAGDNPKEEEVLR 160
Cdd:cd18896  116 LYSELTDTLRKYGTLTNRRCALNEERTCACQGLDPETCGASFSFGCSWSMYYNGCKFARSKIPRKFKLLGDDPKEEEKLE 195

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914146 161 KSFQDLATEVAPLYKRLAPQAYQNQlgplsqktsllqskgkVTNEEIAIDCRLGLKEGRPFAGVTACMDFCAHAHKDQHN 240
Cdd:cd18896  196 SNLQNLSTLMAPTYKKLAPDAYNNQ----------------IEYEHRAPDCRLGLKEGRPFSGVTACLDFCAHAHRDLHN 259

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914146 241 LYNGCTVVCTLTKEDNRCVGKIPEDEQLHVLPLYKMANTDEFGSEENQNAKVGSGAIQVLTAFPREVRRLPEPAKSCRQR 320
Cdd:cd18896  260 MQNGSTLVCTLTREDNREIGKIPEDEQLHVLPLYKVSDVDEFGSTEAQEEKKRNGAIQVLSSFRRKVRMLAEPVKTCRQR 339


                 ..
gi 767914146 321 QL 322
Cdd:cd18896  340 KL 341
TET3 cd18897
oxygenase domain of ten-eleven translocation (TET)3 methylcytosine dioxygenase and similar ...
 796-924 1.35e-83

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.


Pssm-ID: 380676  Cd Length: 452  Bit Score: 276.87  E-value: 1.35e-83
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914146 796 LWSDSEHNFLDENIGGVAVAPAHGSILIECARRELHATTPLKKPNRCHPTRISLVFYQHKNLNQPNHGLALWEAKMKQLA 875
Cdd:cd18897  325 VWSDSEHNFLDENIGGVAVAPAHGSILIECARRELHATTPLKKPNRCHPTRISLVFYQHKNLNQPNHGLALWEAKMKLLA 404

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 767914146 876 ERARARQEEAARLGLgQQEAKLYGKKRKWGGTVVAEPQQKEKKGVVPTR 924
Cdd:cd18897  405 ERARARQEEAARLGL-QQEIKPYGKKRKWGGAPAAEPQPKEKKDKIPTR 452
Tet_JBP cd14946
oxygenase domain of ten-eleven translocation (TET) enzymes, J-binding proteins (JBPs), and ...
 1-275 1.50e-52

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.


Pssm-ID: 380670  Cd Length: 264  Bit Score: 184.89  E-value: 1.50e-52
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914146   1 MEERYG-EKGKAIRIEKVIYTGKEGKSsRGCPIAKWVIRRhtleEKLLCLVRHRAGhhcqnavIVILILAWEGIPRSLGD 79
Cdd:cd14946    5 MLSKCGtQQSFANANITLKYEGKEGKS-QGCPKALKNVRT----SKLAYFVCDHDG-------SVILAYVPEVLPKELVE 72

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914146  80 TLYQELTDTLRKYGNptsrrcglnddrtcacqgKDPNTCGASFSFGCSWSMYFNGCKyarsktprkfRLAGDNPKEEEVL 159
Cdd:cd14946   73 EFTEKLESIQTKRGT------------------LDPETKGDTGYSGILDNSMPFNYV----------TADLSQELGQYLS 124

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914146 160 RKSFQDLATEVAPLYKRLAPQAYQNQlgplsqktsllqskgkVTNEEIAIDCRLGLKEGRPFAGVTACMD-FCAHAHKDQ 238
Cdd:cd14946  125 EIVNPQISYYISKLLTCVSPRTINYL----------------VEYEHRSLNDSYYALNNCLYPSTAFNSLkRIRKPHKDN 188

                        250       260       270
                 ....*....|....*....|....*....|....*..
gi 767914146 239 HNLYNGCTVVCTLTKEDNrcvgkipeDEQLHVLPLYK 275
Cdd:cd14946  189 LDIQNGPSSLFYFGNFQN--------TEGYLELTLKK 217
TET2 cd18896
oxygenase domain of ten-eleven translocation (TET)2 methylcytosine dioxygenase and similar ...
 796-888 1.01e-47

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.


Pssm-ID: 380675  Cd Length: 434  Bit Score: 176.31  E-value: 1.01e-47
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914146 796 LWSDSEHNFLDENIGGVAVAPAHGSILIECARRELHATTPLKKPNRCHPTRISLVFYQHKNLNQPNHGLALWEAKMkqlA 875
Cdd:cd18896  345 VWSDSEQSFLDPDIGGVAVAPSHGSILIECAKRELHATTPLKNPNRNHPTRISLVFYQHKSMNEPKHGLALWEAKM---A 421

                         90
                 ....*....|...
gi 767914146 876 ERARARQEEAARL 888
Cdd:cd18896  422 EKAREKEEECEKY 434
TET1 cd18895
oxygenase domain of ten-eleven translocation (TET)1 methylcytosine dioxygenase and similar ...
 796-884 4.64e-47

oxygenase domain of ten-eleven translocation (TET)1 methylcytosine dioxygenase and similar proteins; TET1 is involved in DNA demethylation through iteratively oxidizing 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). Human TET1 (and TET2) are 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. TET1 plays multiple roles in in tumor development and progression. TET1 serves as a tumor suppressor gene; loss of TET1 is associated with tumorigenesis and can be used as a potential biomarker for cancer therapy. In addition to its dioxygenase activity, it can induce epithelial-mesenchymal transition and act as a coactivator to regulate gene transcription. The regulation of TET1 is also correlated with microRNA in a posttranscriptional modification process. TET1 belongs to the TET/JBP family of dioxygenases that require Fe2+ and alpha-ketoglutarate (also known as 2-oxoglutarate) for activity.


Pssm-ID: 380674  Cd Length: 410  Bit Score: 173.95  E-value: 4.64e-47
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914146 796 LWSDSEHNFLDENIGGVAVAPAHGSILIECARRELHATTPLKKPNRCHPTRISLVFYQHKNLNQPNHGLALWEAKMkqlA 875
Cdd:cd18895  325 VWSDSEHNFLDEDIGGVAVAPSHGSILIECARRELHATTPIKKPNRNHPTRISLVFYQHKNLNEPKHGLALWEAKM---A 401


                 ....*....
gi 767914146 876 ERARARQEE 884
Cdd:cd18895  402 EKAKEKEKE 410
TET cd18892
oxygenase domain of ten-eleven translocation (TET)1, TET2, and TET3 methylcytosine ...
 797-871 1.69e-40

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.


Pssm-ID: 380671  Cd Length: 398  Bit Score: 154.37  E-value: 1.69e-40
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 767914146 797 WSDSEHNFLDENIGGVAVAPAHGSILIECARRELHATTPLKKPNRCHPTRISLVFYQHKNLNQPNHGLALWEAKM 871
Cdd:cd18892  324 WSDSEECFLDPDIGGVAIALSHGSVLFECAKRELHATTPLKNPNRQHPTRISLVFYQHKNLNYSRHGLAEYEAKM 398
Tet_JBP pfam12851
Oxygenase domain of the 2OGFeDO superfamily; A double-stranded beta helix (DSBH) fold domain ...
 127-270 1.03e-39

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.


Pssm-ID: 372343  Cd Length: 166  Bit Score: 144.45  E-value: 1.03e-39
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767914146  127 SWSMYFNGCKYARSKTPRKFRLAGDNPKEEEVLRKSFQDLATEVAPLYKRLAPQAYQNQlgplsqktsllqskgkVTNEE 206
Cdd:pfam12851   1 SWSMYYDGCKFPGPRKPRKFSFTPRNPKEEIKLEDELQELAALLGAIYKQIAPDLYENQ----------------IEYEQ 64

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767914146  207 IAIDCRLGLKEGRPFAGVTACMDFCAHAHKDQHNLYNGCTVVCTLTkedNRCVGKIPEDEQLHV 270
Cdd:pfam12851  65 DAAICRLGRKWGRPFSGVTVNLNFETISHRDLGNFRNGSTLLCTLT---GRYEGGRLALPQLGV 125
Tet_JBP cd14946
oxygenase domain of ten-eleven translocation (TET) enzymes, J-binding proteins (JBPs), and ...
 809-855 4.50e-13

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.


Pssm-ID: 380670  Cd Length: 264  Bit Score: 70.49  E-value: 4.50e-13
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 767914146 809 IGGVAVAPAHGSILIECARRELHATTPLKKPNRcHPTRISLVFYQHK 855
Cdd:cd14946  219 IGNCAVFVQPGDVLFFKGNEYKHVVTNITNPNN-HGWRISLVYYAHK 264
Tet_JBP pfam12851
Oxygenase domain of the 2OGFeDO superfamily; A double-stranded beta helix (DSBH) fold domain ...
 811-855 1.98e-11

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.


Pssm-ID: 372343  Cd Length: 166  Bit Score: 63.17  E-value: 1.98e-11
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 767914146  811 GVAVAPAHGSILIECARRELHATTPLKKPNRchPTRISLVFYQHK 855
Cdd:pfam12851 124 GVAFAPTPGTVLIFCGKSLEHGVTPVKNPNR--WERVSLVFYWHK 166
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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