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Conserved domains on  [gi|568922388|ref|XP_006501350|]
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methylcytosine dioxygenase TET2 isoform X3 [Mus musculus]

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 ...
 1048-1364 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 cd18892:

Pssm-ID: 394797  Cd Length: 398  Bit Score: 569.62  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922388 1048 CEGCNPD---KDEAPYYTHLGAGPDVAAIRTLMEERYGEKGKAIRIEKVIYTGKEGKSSQGCPIAKWVYRRSSEEEKLLC 1124
Cdd:cd18892     1 CGCFPPDespPEPGPYYTHLGAGPSLAALRELLEKRTGVTGKAIRIEKVIYTGKEGKTSQGCPIAKWIIRRSSLEEKYLV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922388 1125 LVRVRPNHTCETAVMVIAIMLWDGIPKLLASELYSELTDILGKCGICTNRRCSQNET-NCCCQGENPETCGASFSFGCSW 1203
Cdd:cd18892    81 LVKHRPGHFCHSAFIVICIVAWEGVPQSNADELYSLLTDKLNKFGLPTKRRCGTNEErTCACQGLDPETCGASFSFGCSW 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922388 1204 SMYYNGCKFARSKKPRKFRLhgAEPKEEERLGSHLQNLATVIAPIYKKLAPDAYNNQVEFEHQAPDCCLGLKEGRPFSGV 1283
Cdd:cd18892   161 SMYYNGCKFARSKTVRKFRL--SDKSEEEELEDKLQNLATHLAPLYKSLAPDSYKNQVQFEEEALDCRLGLKPGRPFSGV 238

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922388 1284 TACLDFSAHSHRDQQNMPNGSTVVVTLNREDNREvGAKPEDEQFHVLPMYIIAPEDEFGSTEGQEKKIRMGSIEVLQSFR 1363
Cdd:cd18892   239 TACVDFCAHAHKDLHNMNNGCTVVVTLTKHRNLT-KPEPEQLHVLPLYLYDMTDEDEFGSVEGQEEKVRNGSIEVLTKYP 317


                  .
gi 568922388 1364 R 1364
Cdd:cd18892   318 C 318
Tet_JBP super family cl40427
oxygenase domain of ten-eleven translocation (TET) enzymes, J-binding proteins (JBPs), and ...
 1755-1846 2.53e-42

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 cd18896:

Pssm-ID: 394797  Cd Length: 434  Bit Score: 162.06  E-value: 2.53e-42
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922388 1755 QEIEYWSDSEHNFQDPCIGGVAIAPTHGSILIECAKCEVHATTKVNDPDRNHPTRISLVLYRHKNLFLPKHCLALWEAKM 1834
Cdd:cd18896   341 LEDEVWSDSEQSFLDPDIGGVAVAPSHGSILIECAKRELHATTPLKNPNRNHPTRISLVFYQHKSMNEPKHGLALWEAKM 420

                          90
                  ....*....|...
gi 568922388 1835 AEKAR-KEEECGK 1846
Cdd:cd18896   421 AEKAReKEEECEK 433
 
Name Accession Description Interval E-value
TET cd18892
oxygenase domain of ten-eleven translocation (TET)1, TET2, and TET3 methylcytosine ...
 1048-1364 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: 569.62  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922388 1048 CEGCNPD---KDEAPYYTHLGAGPDVAAIRTLMEERYGEKGKAIRIEKVIYTGKEGKSSQGCPIAKWVYRRSSEEEKLLC 1124
Cdd:cd18892     1 CGCFPPDespPEPGPYYTHLGAGPSLAALRELLEKRTGVTGKAIRIEKVIYTGKEGKTSQGCPIAKWIIRRSSLEEKYLV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922388 1125 LVRVRPNHTCETAVMVIAIMLWDGIPKLLASELYSELTDILGKCGICTNRRCSQNET-NCCCQGENPETCGASFSFGCSW 1203
Cdd:cd18892    81 LVKHRPGHFCHSAFIVICIVAWEGVPQSNADELYSLLTDKLNKFGLPTKRRCGTNEErTCACQGLDPETCGASFSFGCSW 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922388 1204 SMYYNGCKFARSKKPRKFRLhgAEPKEEERLGSHLQNLATVIAPIYKKLAPDAYNNQVEFEHQAPDCCLGLKEGRPFSGV 1283
Cdd:cd18892   161 SMYYNGCKFARSKTVRKFRL--SDKSEEEELEDKLQNLATHLAPLYKSLAPDSYKNQVQFEEEALDCRLGLKPGRPFSGV 238

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922388 1284 TACLDFSAHSHRDQQNMPNGSTVVVTLNREDNREvGAKPEDEQFHVLPMYIIAPEDEFGSTEGQEKKIRMGSIEVLQSFR 1363
Cdd:cd18892   239 TACVDFCAHAHKDLHNMNNGCTVVVTLTKHRNLT-KPEPEQLHVLPLYLYDMTDEDEFGSVEGQEEKVRNGSIEVLTKYP 317


                  .
gi 568922388 1364 R 1364
Cdd:cd18892   318 C 318
Tet_JBP pfam12851
Oxygenase domain of the 2OGFeDO superfamily; A double-stranded beta helix (DSBH) fold domain ...
 1202-1329 2.23e-55

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: 190.29  E-value: 2.23e-55
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922388  1202 SWSMYYNGCKFARSKKPRKFRLHGAEPKEEERLGSHLQNLATVIAPIYKKLAPDAYNNQVEFEHQAPDCCLGLKEGRPFS 1281
Cdd:pfam12851    1 SWSMYYDGCKFPGPRKPRKFSFTPRNPKEEIKLEDELQELAALLGAIYKQIAPDLYENQIEYEQDAAICRLGRKWGRPFS 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 568922388  1282 GVTACLDFSAHSHRDQQNMPNGSTVVVTLnreDNREVGAKPEDEQFHV 1329
Cdd:pfam12851   81 GVTVNLNFETISHRDLGNFRNGSTLLCTL---TGRYEGGRLALPQLGV 125
TET2 cd18896
oxygenase domain of ten-eleven translocation (TET)2 methylcytosine dioxygenase and similar ...
 1755-1846 2.53e-42

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: 162.06  E-value: 2.53e-42
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922388 1755 QEIEYWSDSEHNFQDPCIGGVAIAPTHGSILIECAKCEVHATTKVNDPDRNHPTRISLVLYRHKNLFLPKHCLALWEAKM 1834
Cdd:cd18896   341 LEDEVWSDSEQSFLDPDIGGVAVAPSHGSILIECAKRELHATTPLKNPNRNHPTRISLVFYQHKSMNEPKHGLALWEAKM 420

                          90
                  ....*....|...
gi 568922388 1835 AEKAR-KEEECGK 1846
Cdd:cd18896   421 AEKAReKEEECEK 433
Tet_JBP pfam12851
Oxygenase domain of the 2OGFeDO superfamily; A double-stranded beta helix (DSBH) fold domain ...
 1774-1818 4.59e-12

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: 66.25  E-value: 4.59e-12
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 568922388  1774 GVAIAPTHGSILIECAKCEVHATTKVNDPDRNhpTRISLVLYRHK 1818
Cdd:pfam12851  124 GVAFAPTPGTVLIFCGKSLEHGVTPVKNPNRW--ERVSLVFYWHK 166
 
Name Accession Description Interval E-value
TET cd18892
oxygenase domain of ten-eleven translocation (TET)1, TET2, and TET3 methylcytosine ...
 1048-1364 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: 569.62  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922388 1048 CEGCNPD---KDEAPYYTHLGAGPDVAAIRTLMEERYGEKGKAIRIEKVIYTGKEGKSSQGCPIAKWVYRRSSEEEKLLC 1124
Cdd:cd18892     1 CGCFPPDespPEPGPYYTHLGAGPSLAALRELLEKRTGVTGKAIRIEKVIYTGKEGKTSQGCPIAKWIIRRSSLEEKYLV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922388 1125 LVRVRPNHTCETAVMVIAIMLWDGIPKLLASELYSELTDILGKCGICTNRRCSQNET-NCCCQGENPETCGASFSFGCSW 1203
Cdd:cd18892    81 LVKHRPGHFCHSAFIVICIVAWEGVPQSNADELYSLLTDKLNKFGLPTKRRCGTNEErTCACQGLDPETCGASFSFGCSW 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922388 1204 SMYYNGCKFARSKKPRKFRLhgAEPKEEERLGSHLQNLATVIAPIYKKLAPDAYNNQVEFEHQAPDCCLGLKEGRPFSGV 1283
Cdd:cd18892   161 SMYYNGCKFARSKTVRKFRL--SDKSEEEELEDKLQNLATHLAPLYKSLAPDSYKNQVQFEEEALDCRLGLKPGRPFSGV 238

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922388 1284 TACLDFSAHSHRDQQNMPNGSTVVVTLNREDNREvGAKPEDEQFHVLPMYIIAPEDEFGSTEGQEKKIRMGSIEVLQSFR 1363
Cdd:cd18892   239 TACVDFCAHAHKDLHNMNNGCTVVVTLTKHRNLT-KPEPEQLHVLPLYLYDMTDEDEFGSVEGQEEKVRNGSIEVLTKYP 317


                  .
gi 568922388 1364 R 1364
Cdd:cd18892   318 C 318
TET2 cd18896
oxygenase domain of ten-eleven translocation (TET)2 methylcytosine dioxygenase and similar ...
 1054-1377 1.37e-180

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: 552.65  E-value: 1.37e-180
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922388 1054 DKDEAPYYTHLGAGPDVAAIRTLMEERYGEKGKAIRIEKVIYTGKEGKSSQGCPIAKWVYRRSSEEEKLLCLVRVRPNHT 1133
Cdd:cd18896    13 EKDEGPYYTHLGAGPNVAAIREIMEERFGQKGKAIRIERVIYTGKEGKSSQGCPIAKWVIRRSSEEEKLLCLVRERAGHS 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922388 1134 CETAVMVIAIMLWDGIPKLLASELYSELTDILGKCGICTNRRCSQNET-NCCCQGENPETCGASFSFGCSWSMYYNGCKF 1212
Cdd:cd18896    93 CETAVIVILILVWEGIPISLADKLYSELTDTLRKYGTLTNRRCALNEErTCACQGLDPETCGASFSFGCSWSMYYNGCKF 172

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922388 1213 ARSKKPRKFRLHGAEPKEEERLGSHLQNLATVIAPIYKKLAPDAYNNQVEFEHQAPDCCLGLKEGRPFSGVTACLDFSAH 1292
Cdd:cd18896   173 ARSKIPRKFKLLGDDPKEEEKLESNLQNLSTLMAPTYKKLAPDAYNNQIEYEHRAPDCRLGLKEGRPFSGVTACLDFCAH 252

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922388 1293 SHRDQQNMPNGSTVVVTLNREDNREVGAKPEDEQFHVLPMYIIAPEDEFGSTEGQEKKIRMGSIEVLQSFrRRRVIRIGE 1372
Cdd:cd18896   253 AHRDLHNMQNGSTLVCTLTREDNREIGKIPEDEQLHVLPLYKVSDVDEFGSTEAQEEKKRNGAIQVLSSF-RRKVRMLAE 331


                  ....*
gi 568922388 1373 LPKSC 1377
Cdd:cd18896   332 PVKTC 336
TET1 cd18895
oxygenase domain of ten-eleven translocation (TET)1 methylcytosine dioxygenase and similar ...
 1054-1366 1.55e-167

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: 516.77  E-value: 1.55e-167
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922388 1054 DKDEAPYYTHLGAGPDVAAIRTLMEERYGEKGKAIRIEKVIYTGKEGKSSQGCPIAKWVYRRSSEEEKLLCLVRVRPNHT 1133
Cdd:cd18895     9 EKDEGPYYTHLGAGPSVAAVREIMENRYGEKGNAIRIEVVVYTGKEGKSSQGCPIAKWVIRRSSDEEKLLCLVRQRAGHH 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922388 1134 CETAVMVIAIMLWDGIPKLLASELYSELTDILGKCGICTNRRCSQNET-NCCCQGENPETCGASFSFGCSWSMYYNGCKF 1212
Cdd:cd18895    89 CQTAVIVILILAWEGIPRLLADRLYQELTQTLKKYGSPTSRRCALNEDrTCACQGLDPETCGASFSFGCSWSMYFNGCKF 168

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922388 1213 ARSKKPRKFRLHGAEPKEEERLGSHLQNLATVIAPIYKKLAPDAYNNQVEFEHQAPDCCLGLKEGRPFSGVTACLDFSAH 1292
Cdd:cd18895   169 ARSKYPRKFRLLTDDPKEEENLESNLQNLATDVAPVYKKLAPEAFQNQVENENVAPDCRLGSKEGRPFSGVTACIDFCAH 248

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568922388 1293 SHRDQQNMPNGSTVVVTLNREDNREVGAKPEDEQFHVLPMYIIAPEDEFGSTEGQEKKIRMGSIEVLQSFRRRR 1366
Cdd:cd18895   249 AHKDTHNMHNGSTVVCTLTKEDNRSVGVIPEDEQLHVLPLYKISDTDEFGSEEGQEAKIKNGAIQVLSAFPREV 322
TET3 cd18897
oxygenase domain of ten-eleven translocation (TET)3 methylcytosine dioxygenase and similar ...
 1054-1364 1.92e-161

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: 501.83  E-value: 1.92e-161
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922388 1054 DKDEAPYYTHLGAGPDVAAIRTLMEERYGEKGKAIRIEKVIYTGKEGKSSQGCPIAKWVYRRSSEEEKLLCLVRVRPNHT 1133
Cdd:cd18897     9 EKDEGPYYTHLGSGPTVASIRELMEERYGEKGKAIRIEKVIYTGKEGKSSRGCPIAKWVIRRSSEEEKLLCLVRHRAGHH 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922388 1134 CETAVMVIAIMLWDGIPKLLASELYSELTDILGKCGICTNRRCSQNET-NCCCQGENPETCGASFSFGCSWSMYYNGCKF 1212
Cdd:cd18897    89 CQNAVIVILILAWEGIPRALGDKLYQELTETLTKYGNPTSRRCGLNDDrTCACQGKDPNTCGASFSFGCSWSMYFNGCKY 168

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922388 1213 ARSKKPRKFRLHGAEPKEEERLGSHLQNLATVIAPIYKKLAPDAYNNQVEFEHQAPDCCLGLKEGRPFSGVTACLDFSAH 1292
Cdd:cd18897   169 ARSKTPRKFRLIGDNPKEEENLRDNFQDLATEVAPLYKRLAPQAYQNQVTNEDIAIDCRLGLKEGRPFSGVTACMDFCAH 248

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568922388 1293 SHRDQQNMPNGSTVVVTLNREDNREVGAKPEDEQFHVLPMYIIAPEDEFGSTEGQEKKIRMGSIEVLQSFRR 1364
Cdd:cd18897   249 AHKDQHNLYNGCTVVCTLTKEDNRTVGKIPEDEQLHVLPLYKMSTTDEFGSEENQNEKIGSGAIQVLTSFPR 320
Tet_JBP cd14946
oxygenase domain of ten-eleven translocation (TET) enzymes, J-binding proteins (JBPs), and ...
 1073-1346 1.60e-59

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: 206.08  E-value: 1.60e-59
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922388 1073 IRTLMEERYG-EKGKAIRIEKVIYTGKEGKSsQGCPIAKWVYRRSseeeKLLCLVRVRpnhtcetAVMVIAIMLWDGIPK 1151
Cdd:cd14946     1 LLENMLSKCGtQQSFANANITLKYEGKEGKS-QGCPKALKNVRTS----KLAYFVCDH-------DGSVILAYVPEVLPK 68

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922388 1152 LLASELYSELTDILGKCGIctnrrcsqnetncccqgENPETCGASFSFGCSWSMYYNGCKfarskkprkfRLHGAEPKEE 1231
Cdd:cd14946    69 ELVEEFTEKLESIQTKRGT-----------------LDPETKGDTGYSGILDNSMPFNYV----------TADLSQELGQ 121

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922388 1232 ERLGSHLQNLATVIAPIYKKLAPDAYNNQVEFEHQAPDCCLGLKEGRPFSGVTACLDFS-AHSHRDQQNMPNGSTVVVTL 1310
Cdd:cd14946   122 YLSEIVNPQISYYISKLLTCVSPRTINYLVEYEHRSLNDSYYALNNCLYPSTAFNSLKRiRKPHKDNLDIQNGPSSLFYF 201

                         250       260       270
                  ....*....|....*....|....*....|....*.
gi 568922388 1311 NREDNrevgakpeDEQFHVLPMYIIAPEDEFGSTEG 1346
Cdd:cd14946   202 GNFQN--------TEGYLELTLKKVIGNCAVFVQPG 229
Tet_JBP pfam12851
Oxygenase domain of the 2OGFeDO superfamily; A double-stranded beta helix (DSBH) fold domain ...
 1202-1329 2.23e-55

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: 190.29  E-value: 2.23e-55
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922388  1202 SWSMYYNGCKFARSKKPRKFRLHGAEPKEEERLGSHLQNLATVIAPIYKKLAPDAYNNQVEFEHQAPDCCLGLKEGRPFS 1281
Cdd:pfam12851    1 SWSMYYDGCKFPGPRKPRKFSFTPRNPKEEIKLEDELQELAALLGAIYKQIAPDLYENQIEYEQDAAICRLGRKWGRPFS 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 568922388  1282 GVTACLDFSAHSHRDQQNMPNGSTVVVTLnreDNREVGAKPEDEQFHV 1329
Cdd:pfam12851   81 GVTVNLNFETISHRDLGNFRNGSTLLCTL---TGRYEGGRLALPQLGV 125
TET2 cd18896
oxygenase domain of ten-eleven translocation (TET)2 methylcytosine dioxygenase and similar ...
 1755-1846 2.53e-42

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: 162.06  E-value: 2.53e-42
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922388 1755 QEIEYWSDSEHNFQDPCIGGVAIAPTHGSILIECAKCEVHATTKVNDPDRNHPTRISLVLYRHKNLFLPKHCLALWEAKM 1834
Cdd:cd18896   341 LEDEVWSDSEQSFLDPDIGGVAVAPSHGSILIECAKRELHATTPLKNPNRNHPTRISLVFYQHKSMNEPKHGLALWEAKM 420

                          90
                  ....*....|...
gi 568922388 1835 AEKAR-KEEECGK 1846
Cdd:cd18896   421 AEKAReKEEECEK 433
TET1 cd18895
oxygenase domain of ten-eleven translocation (TET)1 methylcytosine dioxygenase and similar ...
 1758-1843 1.00e-37

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: 147.75  E-value: 1.00e-37
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922388 1758 EYWSDSEHNFQDPCIGGVAIAPTHGSILIECAKCEVHATTKVNDPDRNHPTRISLVLYRHKNLFLPKHCLALWEAKMAEK 1837
Cdd:cd18895   324 EVWSDSEHNFLDEDIGGVAVAPSHGSILIECARRELHATTPIKKPNRNHPTRISLVFYQHKNLNEPKHGLALWEAKMAEK 403


                  ....*.
gi 568922388 1838 ARKEEE 1843
Cdd:cd18895   404 AKEKEK 409
TET3 cd18897
oxygenase domain of ten-eleven translocation (TET)3 methylcytosine dioxygenase and similar ...
 1739-1872 2.45e-36

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: 144.75  E-value: 2.45e-36
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568922388 1739 SQEKQPEVSGQDAAAV-----QEI-EYWSDSEHNFQDPCIGGVAIAPTHGSILIECAKCEVHATTKVNDPDRNHPTRISL 1812
Cdd:cd18897   299 SEENQNEKIGSGAIQVltsfpREVrEVWSDSEHNFLDENIGGVAVAPAHGSILIECARRELHATTPLKKPNRCHPTRISL 378

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568922388 1813 VLYRHKNLFLPKHCLALWEAKM---AEKAR-KEEECGKNGSDHvSQKNHGKQEKREPTGPQEPS 1872
Cdd:cd18897   379 VFYQHKNLNQPNHGLALWEAKMkllAERARaRQEEAARLGLQQ-EIKPYGKKRKWGGAPAAEPQ 441
TET cd18892
oxygenase domain of ten-eleven translocation (TET)1, TET2, and TET3 methylcytosine ...
 1758-1834 1.89e-32

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: 132.03  E-value: 1.89e-32
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568922388 1758 EYWSDSEHNFQDPCIGGVAIAPTHGSILIECAKCEVHATTKVNDPDRNHPTRISLVLYRHKNLFLPKHCLALWEAKM 1834
Cdd:cd18892   322 EYWSDSEECFLDPDIGGVAIALSHGSVLFECAKRELHATTPLKNPNRQHPTRISLVFYQHKNLNYSRHGLAEYEAKM 398
Tet_JBP pfam12851
Oxygenase domain of the 2OGFeDO superfamily; A double-stranded beta helix (DSBH) fold domain ...
 1774-1818 4.59e-12

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: 66.25  E-value: 4.59e-12
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 568922388  1774 GVAIAPTHGSILIECAKCEVHATTKVNDPDRNhpTRISLVLYRHK 1818
Cdd:pfam12851  124 GVAFAPTPGTVLIFCGKSLEHGVTPVKNPNRW--ERVSLVFYWHK 166
Tet_JBP cd14946
oxygenase domain of ten-eleven translocation (TET) enzymes, J-binding proteins (JBPs), and ...
 1772-1818 1.87e-09

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: 60.47  E-value: 1.87e-09
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 568922388 1772 IGGVAIAPTHGSILIECAKCEVHATTKVNDPDrNHPTRISLVLYRHK 1818
Cdd:cd14946   219 IGNCAVFVQPGDVLFFKGNEYKHVVTNITNPN-NHGWRISLVYYAHK 264
 
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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