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Conserved domains on  [gi|1907149837|ref|XP_036018905|]
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methylcytosine dioxygenase TET2 isoform X1 [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 ...
1048-1373 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: 569.23  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907149837 1048 CEGCNPD---KDEAPYYTHLGAGPDVAAIRTLMEERYGEKGKAIRIEKVIYTGKEGKSSQGCPIAKWVYRRSSEEEKLLC 1124
Cdd:cd18892      1 CGCFPPDespPEPGPYYTHLGAGPSLAALRELLEKRTGVTGKAIRIEKVIYTGKEGKTSQGCPIAKWIIRRSSLEEKYLV 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907149837 1125 LVRVRPNHTCETAVMVIAIMLWDGIPKLLASELYSELTDILGKCGICTNRRCSQNETkkkqsppsRNCCCQGENPETCGA 1204
Cdd:cd18892     81 LVKHRPGHFCHSAFIVICIVAWEGVPQSNADELYSLLTDKLNKFGLPTKRRCGTNEE--------RTCACQGLDPETCGA 152
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907149837 1205 SFSFGCSWSMYYNGCKFARSKKPRKFRLhgAEPKEEERLGSHLQNLATVIAPIYKKLAPDAYNNQVEFEHQAPDCCLGLK 1284
Cdd:cd18892    153 SFSFGCSWSMYYNGCKFARSKTVRKFRL--SDKSEEEELEDKLQNLATHLAPLYKSLAPDSYKNQVQFEEEALDCRLGLK 230
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907149837 1285 EGRPFSGVTACLDFSAHSHRDQQNMPNGSTVVVTLNREDNREvGAKPEDEQFHVLPMYIIAPEDEFGSTEGQEKKIRMGS 1364
Cdd:cd18892    231 PGRPFSGVTACVDFCAHAHKDLHNMNNGCTVVVTLTKHRNLT-KPEPEQLHVLPLYLYDMTDEDEFGSVEGQEEKVRNGS 309

                   ....*....
gi 1907149837 1365 IEVLQSFRR 1373
Cdd:cd18892    310 IEVLTKYPC 318
Tet_JBP super family cl40427
oxygenase domain of ten-eleven translocation (TET) enzymes, J-binding proteins (JBPs), and ...
1764-1855 2.88e-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: 161.68  E-value: 2.88e-42
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907149837 1764 QEIEYWSDSEHNFQDPCIGGVAIAPTHGSILIECAKCEVHATTKVNDPDRNHPTRISLVLYRHKNLFLPKHCLALWEAKM 1843
Cdd:cd18896    341 LEDEVWSDSEQSFLDPDIGGVAVAPSHGSILIECAKRELHATTPLKNPNRNHPTRISLVFYQHKSMNEPKHGLALWEAKM 420
                           90
                   ....*....|...
gi 1907149837 1844 AEKAR-KEEECGK 1855
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 ...
1048-1373 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: 569.23  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907149837 1048 CEGCNPD---KDEAPYYTHLGAGPDVAAIRTLMEERYGEKGKAIRIEKVIYTGKEGKSSQGCPIAKWVYRRSSEEEKLLC 1124
Cdd:cd18892      1 CGCFPPDespPEPGPYYTHLGAGPSLAALRELLEKRTGVTGKAIRIEKVIYTGKEGKTSQGCPIAKWIIRRSSLEEKYLV 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907149837 1125 LVRVRPNHTCETAVMVIAIMLWDGIPKLLASELYSELTDILGKCGICTNRRCSQNETkkkqsppsRNCCCQGENPETCGA 1204
Cdd:cd18892     81 LVKHRPGHFCHSAFIVICIVAWEGVPQSNADELYSLLTDKLNKFGLPTKRRCGTNEE--------RTCACQGLDPETCGA 152
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907149837 1205 SFSFGCSWSMYYNGCKFARSKKPRKFRLhgAEPKEEERLGSHLQNLATVIAPIYKKLAPDAYNNQVEFEHQAPDCCLGLK 1284
Cdd:cd18892    153 SFSFGCSWSMYYNGCKFARSKTVRKFRL--SDKSEEEELEDKLQNLATHLAPLYKSLAPDSYKNQVQFEEEALDCRLGLK 230
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907149837 1285 EGRPFSGVTACLDFSAHSHRDQQNMPNGSTVVVTLNREDNREvGAKPEDEQFHVLPMYIIAPEDEFGSTEGQEKKIRMGS 1364
Cdd:cd18892    231 PGRPFSGVTACVDFCAHAHKDLHNMNNGCTVVVTLTKHRNLT-KPEPEQLHVLPLYLYDMTDEDEFGSVEGQEEKVRNGS 309

                   ....*....
gi 1907149837 1365 IEVLQSFRR 1373
Cdd:cd18892    310 IEVLTKYPC 318
Tet_JBP pfam12851
Oxygenase domain of the 2OGFeDO superfamily; A double-stranded beta helix (DSBH) fold domain ...
1211-1338 2.12e-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: 2.12e-55
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907149837 1211 SWSMYYNGCKFARSKKPRKFRLHGAEPKEEERLGSHLQNLATVIAPIYKKLAPDAYNNQVEFEHQAPDCCLGLKEGRPFS 1290
Cdd:pfam12851    1 SWSMYYDGCKFPGPRKPRKFSFTPRNPKEEIKLEDELQELAALLGAIYKQIAPDLYENQIEYEQDAAICRLGRKWGRPFS 80
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 1907149837 1291 GVTACLDFSAHSHRDQQNMPNGSTVVVTLnreDNREVGAKPEDEQFHV 1338
Cdd:pfam12851   81 GVTVNLNFETISHRDLGNFRNGSTLLCTL---TGRYEGGRLALPQLGV 125
TET2 cd18896
oxygenase domain of ten-eleven translocation (TET)2 methylcytosine dioxygenase and similar ...
1764-1855 2.88e-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: 161.68  E-value: 2.88e-42
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907149837 1764 QEIEYWSDSEHNFQDPCIGGVAIAPTHGSILIECAKCEVHATTKVNDPDRNHPTRISLVLYRHKNLFLPKHCLALWEAKM 1843
Cdd:cd18896    341 LEDEVWSDSEQSFLDPDIGGVAVAPSHGSILIECAKRELHATTPLKNPNRNHPTRISLVFYQHKSMNEPKHGLALWEAKM 420
                           90
                   ....*....|...
gi 1907149837 1844 AEKAR-KEEECGK 1855
Cdd:cd18896    421 AEKAReKEEECEK 433
Tet_JBP pfam12851
Oxygenase domain of the 2OGFeDO superfamily; A double-stranded beta helix (DSBH) fold domain ...
1783-1827 4.61e-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: 4.61e-12
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 1907149837 1783 GVAIAPTHGSILIECAKCEVHATTKVNDPDRNhpTRISLVLYRHK 1827
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 ...
1048-1373 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: 569.23  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907149837 1048 CEGCNPD---KDEAPYYTHLGAGPDVAAIRTLMEERYGEKGKAIRIEKVIYTGKEGKSSQGCPIAKWVYRRSSEEEKLLC 1124
Cdd:cd18892      1 CGCFPPDespPEPGPYYTHLGAGPSLAALRELLEKRTGVTGKAIRIEKVIYTGKEGKTSQGCPIAKWIIRRSSLEEKYLV 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907149837 1125 LVRVRPNHTCETAVMVIAIMLWDGIPKLLASELYSELTDILGKCGICTNRRCSQNETkkkqsppsRNCCCQGENPETCGA 1204
Cdd:cd18892     81 LVKHRPGHFCHSAFIVICIVAWEGVPQSNADELYSLLTDKLNKFGLPTKRRCGTNEE--------RTCACQGLDPETCGA 152
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907149837 1205 SFSFGCSWSMYYNGCKFARSKKPRKFRLhgAEPKEEERLGSHLQNLATVIAPIYKKLAPDAYNNQVEFEHQAPDCCLGLK 1284
Cdd:cd18892    153 SFSFGCSWSMYYNGCKFARSKTVRKFRL--SDKSEEEELEDKLQNLATHLAPLYKSLAPDSYKNQVQFEEEALDCRLGLK 230
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907149837 1285 EGRPFSGVTACLDFSAHSHRDQQNMPNGSTVVVTLNREDNREvGAKPEDEQFHVLPMYIIAPEDEFGSTEGQEKKIRMGS 1364
Cdd:cd18892    231 PGRPFSGVTACVDFCAHAHKDLHNMNNGCTVVVTLTKHRNLT-KPEPEQLHVLPLYLYDMTDEDEFGSVEGQEEKVRNGS 309

                   ....*....
gi 1907149837 1365 IEVLQSFRR 1373
Cdd:cd18892    310 IEVLTKYPC 318
TET2 cd18896
oxygenase domain of ten-eleven translocation (TET)2 methylcytosine dioxygenase and similar ...
1054-1386 2.34e-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: 552.27  E-value: 2.34e-180
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907149837 1054 DKDEAPYYTHLGAGPDVAAIRTLMEERYGEKGKAIRIEKVIYTGKEGKSSQGCPIAKWVYRRSSEEEKLLCLVRVRPNHT 1133
Cdd:cd18896     13 EKDEGPYYTHLGAGPNVAAIREIMEERFGQKGKAIRIERVIYTGKEGKSSQGCPIAKWVIRRSSEEEKLLCLVRERAGHS 92
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907149837 1134 CETAVMVIAIMLWDGIPKLLASELYSELTDILGKCGICTNRRCSQNEtkkkqsppSRNCCCQGENPETCGASFSFGCSWS 1213
Cdd:cd18896     93 CETAVIVILILVWEGIPISLADKLYSELTDTLRKYGTLTNRRCALNE--------ERTCACQGLDPETCGASFSFGCSWS 164
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907149837 1214 MYYNGCKFARSKKPRKFRLHGAEPKEEERLGSHLQNLATVIAPIYKKLAPDAYNNQVEFEHQAPDCCLGLKEGRPFSGVT 1293
Cdd:cd18896    165 MYYNGCKFARSKIPRKFKLLGDDPKEEEKLESNLQNLSTLMAPTYKKLAPDAYNNQIEYEHRAPDCRLGLKEGRPFSGVT 244
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907149837 1294 ACLDFSAHSHRDQQNMPNGSTVVVTLNREDNREVGAKPEDEQFHVLPMYIIAPEDEFGSTEGQEKKIRMGSIEVLQSFrR 1373
Cdd:cd18896    245 ACLDFCAHAHRDLHNMQNGSTLVCTLTREDNREIGKIPEDEQLHVLPLYKVSDVDEFGSTEAQEEKKRNGAIQVLSSF-R 323
                          330
                   ....*....|...
gi 1907149837 1374 RRVIRIGELPKSC 1386
Cdd:cd18896    324 RKVRMLAEPVKTC 336
TET1 cd18895
oxygenase domain of ten-eleven translocation (TET)1 methylcytosine dioxygenase and similar ...
1054-1375 2.30e-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: 516.39  E-value: 2.30e-167
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907149837 1054 DKDEAPYYTHLGAGPDVAAIRTLMEERYGEKGKAIRIEKVIYTGKEGKSSQGCPIAKWVYRRSSEEEKLLCLVRVRPNHT 1133
Cdd:cd18895      9 EKDEGPYYTHLGAGPSVAAVREIMENRYGEKGNAIRIEVVVYTGKEGKSSQGCPIAKWVIRRSSDEEKLLCLVRQRAGHH 88
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907149837 1134 CETAVMVIAIMLWDGIPKLLASELYSELTDILGKCGICTNRRCSQNEtkkkqsppSRNCCCQGENPETCGASFSFGCSWS 1213
Cdd:cd18895     89 CQTAVIVILILAWEGIPRLLADRLYQELTQTLKKYGSPTSRRCALNE--------DRTCACQGLDPETCGASFSFGCSWS 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907149837 1214 MYYNGCKFARSKKPRKFRLHGAEPKEEERLGSHLQNLATVIAPIYKKLAPDAYNNQVEFEHQAPDCCLGLKEGRPFSGVT 1293
Cdd:cd18895    161 MYFNGCKFARSKYPRKFRLLTDDPKEEENLESNLQNLATDVAPVYKKLAPEAFQNQVENENVAPDCRLGSKEGRPFSGVT 240
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907149837 1294 ACLDFSAHSHRDQQNMPNGSTVVVTLNREDNREVGAKPEDEQFHVLPMYIIAPEDEFGSTEGQEKKIRMGSIEVLQSFRR 1373
Cdd:cd18895    241 ACIDFCAHAHKDTHNMHNGSTVVCTLTKEDNRSVGVIPEDEQLHVLPLYKISDTDEFGSEEGQEAKIKNGAIQVLSAFPR 320

                   ..
gi 1907149837 1374 RR 1375
Cdd:cd18895    321 EV 322
TET3 cd18897
oxygenase domain of ten-eleven translocation (TET)3 methylcytosine dioxygenase and similar ...
1054-1373 3.79e-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: 501.06  E-value: 3.79e-161
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907149837 1054 DKDEAPYYTHLGAGPDVAAIRTLMEERYGEKGKAIRIEKVIYTGKEGKSSQGCPIAKWVYRRSSEEEKLLCLVRVRPNHT 1133
Cdd:cd18897      9 EKDEGPYYTHLGSGPTVASIRELMEERYGEKGKAIRIEKVIYTGKEGKSSRGCPIAKWVIRRSSEEEKLLCLVRHRAGHH 88
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907149837 1134 CETAVMVIAIMLWDGIPKLLASELYSELTDILGKCGICTNRRCSQNEtkkkqsppSRNCCCQGENPETCGASFSFGCSWS 1213
Cdd:cd18897     89 CQNAVIVILILAWEGIPRALGDKLYQELTETLTKYGNPTSRRCGLND--------DRTCACQGKDPNTCGASFSFGCSWS 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907149837 1214 MYYNGCKFARSKKPRKFRLHGAEPKEEERLGSHLQNLATVIAPIYKKLAPDAYNNQVEFEHQAPDCCLGLKEGRPFSGVT 1293
Cdd:cd18897    161 MYFNGCKYARSKTPRKFRLIGDNPKEEENLRDNFQDLATEVAPLYKRLAPQAYQNQVTNEDIAIDCRLGLKEGRPFSGVT 240
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907149837 1294 ACLDFSAHSHRDQQNMPNGSTVVVTLNREDNREVGAKPEDEQFHVLPMYIIAPEDEFGSTEGQEKKIRMGSIEVLQSFRR 1373
Cdd:cd18897    241 ACMDFCAHAHKDQHNLYNGCTVVCTLTKEDNRTVGKIPEDEQLHVLPLYKMSTTDEFGSEENQNEKIGSGAIQVLTSFPR 320
Tet_JBP cd14946
oxygenase domain of ten-eleven translocation (TET) enzymes, J-binding proteins (JBPs), and ...
1073-1355 2.60e-58

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: 202.61  E-value: 2.60e-58
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907149837 1073 IRTLMEERYG-EKGKAIRIEKVIYTGKEGKSsQGCPIAKWVYRRSseeeKLLCLVRVRpnhtcetAVMVIAIMLWDGIPK 1151
Cdd:cd14946      1 LLENMLSKCGtQQSFANANITLKYEGKEGKS-QGCPKALKNVRTS----KLAYFVCDH-------DGSVILAYVPEVLPK 68
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907149837 1152 LLASELYSELTDILGKCGIctnrrcsqnetkkkqsppsrncccqgENPETCGASFSFGCSWSMYYNGCKfarskkprkfR 1231
Cdd:cd14946     69 ELVEEFTEKLESIQTKRGT--------------------------LDPETKGDTGYSGILDNSMPFNYV----------T 112
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907149837 1232 LHGAEPKEEERLGSHLQNLATVIAPIYKKLAPDAYNNQVEFEHQAPDCCLGLKEGRPFSGVTACLDFS-AHSHRDQQNMP 1310
Cdd:cd14946    113 ADLSQELGQYLSEIVNPQISYYISKLLTCVSPRTINYLVEYEHRSLNDSYYALNNCLYPSTAFNSLKRiRKPHKDNLDIQ 192
                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*
gi 1907149837 1311 NGSTVVVTLNREDNrevgakpeDEQFHVLPMYIIAPEDEFGSTEG 1355
Cdd:cd14946    193 NGPSSLFYFGNFQN--------TEGYLELTLKKVIGNCAVFVQPG 229
Tet_JBP pfam12851
Oxygenase domain of the 2OGFeDO superfamily; A double-stranded beta helix (DSBH) fold domain ...
1211-1338 2.12e-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: 2.12e-55
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907149837 1211 SWSMYYNGCKFARSKKPRKFRLHGAEPKEEERLGSHLQNLATVIAPIYKKLAPDAYNNQVEFEHQAPDCCLGLKEGRPFS 1290
Cdd:pfam12851    1 SWSMYYDGCKFPGPRKPRKFSFTPRNPKEEIKLEDELQELAALLGAIYKQIAPDLYENQIEYEQDAAICRLGRKWGRPFS 80
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 1907149837 1291 GVTACLDFSAHSHRDQQNMPNGSTVVVTLnreDNREVGAKPEDEQFHV 1338
Cdd:pfam12851   81 GVTVNLNFETISHRDLGNFRNGSTLLCTL---TGRYEGGRLALPQLGV 125
TET2 cd18896
oxygenase domain of ten-eleven translocation (TET)2 methylcytosine dioxygenase and similar ...
1764-1855 2.88e-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: 161.68  E-value: 2.88e-42
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907149837 1764 QEIEYWSDSEHNFQDPCIGGVAIAPTHGSILIECAKCEVHATTKVNDPDRNHPTRISLVLYRHKNLFLPKHCLALWEAKM 1843
Cdd:cd18896    341 LEDEVWSDSEQSFLDPDIGGVAVAPSHGSILIECAKRELHATTPLKNPNRNHPTRISLVFYQHKSMNEPKHGLALWEAKM 420
                           90
                   ....*....|...
gi 1907149837 1844 AEKAR-KEEECGK 1855
Cdd:cd18896    421 AEKAReKEEECEK 433
TET1 cd18895
oxygenase domain of ten-eleven translocation (TET)1 methylcytosine dioxygenase and similar ...
1767-1852 1.11e-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: 1.11e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907149837 1767 EYWSDSEHNFQDPCIGGVAIAPTHGSILIECAKCEVHATTKVNDPDRNHPTRISLVLYRHKNLFLPKHCLALWEAKMAEK 1846
Cdd:cd18895    324 EVWSDSEHNFLDEDIGGVAVAPSHGSILIECARRELHATTPIKKPNRNHPTRISLVFYQHKNLNEPKHGLALWEAKMAEK 403

                   ....*.
gi 1907149837 1847 ARKEEE 1852
Cdd:cd18895    404 AKEKEK 409
TET3 cd18897
oxygenase domain of ten-eleven translocation (TET)3 methylcytosine dioxygenase and similar ...
1748-1881 2.94e-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: 144.36  E-value: 2.94e-36
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907149837 1748 SQEKQPEVSGQDAAAV-----QEI-EYWSDSEHNFQDPCIGGVAIAPTHGSILIECAKCEVHATTKVNDPDRNHPTRISL 1821
Cdd:cd18897    299 SEENQNEKIGSGAIQVltsfpREVrEVWSDSEHNFLDENIGGVAVAPAHGSILIECARRELHATTPLKKPNRCHPTRISL 378
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907149837 1822 VLYRHKNLFLPKHCLALWEAKM---AEKAR-KEEECGKNGSDHvSQKNHGKQEKREPTGPQEPS 1881
Cdd:cd18897    379 VFYQHKNLNQPNHGLALWEAKMkllAERARaRQEEAARLGLQQ-EIKPYGKKRKWGGAPAAEPQ 441
TET cd18892
oxygenase domain of ten-eleven translocation (TET)1, TET2, and TET3 methylcytosine ...
1767-1843 1.94e-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: 1.94e-32
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907149837 1767 EYWSDSEHNFQDPCIGGVAIAPTHGSILIECAKCEVHATTKVNDPDRNHPTRISLVLYRHKNLFLPKHCLALWEAKM 1843
Cdd:cd18892    322 EYWSDSEECFLDPDIGGVAIALSHGSVLFECAKRELHATTPLKNPNRQHPTRISLVFYQHKNLNYSRHGLAEYEAKM 398
Tet_JBP pfam12851
Oxygenase domain of the 2OGFeDO superfamily; A double-stranded beta helix (DSBH) fold domain ...
1783-1827 4.61e-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: 4.61e-12
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 1907149837 1783 GVAIAPTHGSILIECAKCEVHATTKVNDPDRNhpTRISLVLYRHK 1827
Cdd:pfam12851  124 GVAFAPTPGTVLIFCGKSLEHGVTPVKNPNRW--ERVSLVFYWHK 166
Tet_JBP cd14946
oxygenase domain of ten-eleven translocation (TET) enzymes, J-binding proteins (JBPs), and ...
1781-1827 1.88e-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: 1.88e-09
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1907149837 1781 IGGVAIAPTHGSILIECAKCEVHATTKVNDPDrNHPTRISLVLYRHK 1827
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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