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Conserved domains on  [gi|187761317|ref|NP_001120680|]
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methylcytosine dioxygenase TET2 isoform a [Homo sapiens]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
TET2 cd18896
oxygenase domain of ten-eleven translocation (TET)2 methylcytosine dioxygenase and similar ...
 1129-1472 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: 746.41  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187761317 1129 DFPSCRCVEQIIEKDEGPFYTHLGAGPNVAAIREIMEERFGQKGKAIRIERVIYTGKEGKSSQGCPIAKWVVRRSSSEEK 1208
Cdd:cd18896     1 DFPSCSCVEQIIEKDEGPYYTHLGAGPNVAAIREIMEERFGQKGKAIRIERVIYTGKEGKSSQGCPIAKWVIRRSSEEEK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187761317 1209 LLCLVRERAGHTCEAAVIVILILVWEGIPLSLADKLYSELTETLRKYGTLTNRRCALNEERTCACQGLDPETCGASFSFG 1288
Cdd:cd18896    81 LLCLVRERAGHSCETAVIVILILVWEGIPISLADKLYSELTDTLRKYGTLTNRRCALNEERTCACQGLDPETCGASFSFG 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187761317 1289 CSWSMYYNGCKFARSKIPRKFKLLGDDPKEEEKLESHLQNLSTLMAPTYKKLAPDAYNNQIEYEHRAPECRLGLKEGRPF 1368
Cdd:cd18896   161 CSWSMYYNGCKFARSKIPRKFKLLGDDPKEEEKLESNLQNLSTLMAPTYKKLAPDAYNNQIEYEHRAPDCRLGLKEGRPF 240

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187761317 1369 SGVTACLDFCAHAHRDLHNMQNGSTLVCTLTREDNREFGGKPEDEQLHVLPLYKVSDVDEFGSVEAQEEKKRSGAIQVLS 1448
Cdd:cd18896   241 SGVTACLDFCAHAHRDLHNMQNGSTLVCTLTREDNREIGKIPEDEQLHVLPLYKVSDVDEFGSTEAQEEKKRNGAIQVLS 320

                         330       340
                  ....*....|....*....|....
gi 187761317 1449 SFRRKVRMLAEPVKTCRQRKLEAK 1472
Cdd:cd18896   321 SFRRKVRMLAEPVKTCRQRKLEDE 344
Tet_JBP super family cl40427
oxygenase domain of ten-eleven translocation (TET) enzymes, J-binding proteins (JBPs), and ...
 1844-1921 2.25e-49

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: 182.86  E-value: 2.25e-49
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 187761317 1844 DEVWSDSEQSFLDPDIGGVAVAPTHGSILIECAKRELHATTPLKNPNRNHPTRISLVFYQHKSMNEPKHGLALWEAKM 1921
Cdd:cd18896   343 DEVWSDSEQSFLDPDIGGVAVAPSHGSILIECAKRELHATTPLKNPNRNHPTRISLVFYQHKSMNEPKHGLALWEAKM 420
 
Name Accession Description Interval E-value
TET2 cd18896
oxygenase domain of ten-eleven translocation (TET)2 methylcytosine dioxygenase and similar ...
 1129-1472 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: 746.41  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187761317 1129 DFPSCRCVEQIIEKDEGPFYTHLGAGPNVAAIREIMEERFGQKGKAIRIERVIYTGKEGKSSQGCPIAKWVVRRSSSEEK 1208
Cdd:cd18896     1 DFPSCSCVEQIIEKDEGPYYTHLGAGPNVAAIREIMEERFGQKGKAIRIERVIYTGKEGKSSQGCPIAKWVIRRSSEEEK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187761317 1209 LLCLVRERAGHTCEAAVIVILILVWEGIPLSLADKLYSELTETLRKYGTLTNRRCALNEERTCACQGLDPETCGASFSFG 1288
Cdd:cd18896    81 LLCLVRERAGHSCETAVIVILILVWEGIPISLADKLYSELTDTLRKYGTLTNRRCALNEERTCACQGLDPETCGASFSFG 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187761317 1289 CSWSMYYNGCKFARSKIPRKFKLLGDDPKEEEKLESHLQNLSTLMAPTYKKLAPDAYNNQIEYEHRAPECRLGLKEGRPF 1368
Cdd:cd18896   161 CSWSMYYNGCKFARSKIPRKFKLLGDDPKEEEKLESNLQNLSTLMAPTYKKLAPDAYNNQIEYEHRAPDCRLGLKEGRPF 240

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187761317 1369 SGVTACLDFCAHAHRDLHNMQNGSTLVCTLTREDNREFGGKPEDEQLHVLPLYKVSDVDEFGSVEAQEEKKRSGAIQVLS 1448
Cdd:cd18896   241 SGVTACLDFCAHAHRDLHNMQNGSTLVCTLTREDNREIGKIPEDEQLHVLPLYKVSDVDEFGSTEAQEEKKRNGAIQVLS 320

                         330       340
                  ....*....|....*....|....
gi 187761317 1449 SFRRKVRMLAEPVKTCRQRKLEAK 1472
Cdd:cd18896   321 SFRRKVRMLAEPVKTCRQRKLEDE 344
Tet_JBP pfam12851
Oxygenase domain of the 2OGFeDO superfamily; A double-stranded beta helix (DSBH) fold domain ...
 1290-1426 1.17e-58

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: 199.92  E-value: 1.17e-58
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187761317  1290 SWSMYYNGCKFARSKIPRKFKLLGDDPKEEEKLESHLQNLSTLMAPTYKKLAPDAYNNQIEYEHRAPECRLGLKEGRPFS 1369
Cdd:pfam12851    1 SWSMYYDGCKFPGPRKPRKFSFTPRNPKEEIKLEDELQELAALLGAIYKQIAPDLYENQIEYEQDAAICRLGRKWGRPFS 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 187761317  1370 GVTACLDFCAHAHRDLHNMQNGSTLVCTLTredNREFGGKPEDEQLHVLPLYKVSDV 1426
Cdd:pfam12851   81 GVTVNLNFETISHRDLGNFRNGSTLLCTLT---GRYEGGRLALPQLGVAFAPTPGTV 134
TET2 cd18896
oxygenase domain of ten-eleven translocation (TET)2 methylcytosine dioxygenase and similar ...
 1844-1921 2.25e-49

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: 182.86  E-value: 2.25e-49
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 187761317 1844 DEVWSDSEQSFLDPDIGGVAVAPTHGSILIECAKRELHATTPLKNPNRNHPTRISLVFYQHKSMNEPKHGLALWEAKM 1921
Cdd:cd18896   343 DEVWSDSEQSFLDPDIGGVAVAPSHGSILIECAKRELHATTPLKNPNRNHPTRISLVFYQHKSMNEPKHGLALWEAKM 420
Tet_JBP pfam12851
Oxygenase domain of the 2OGFeDO superfamily; A double-stranded beta helix (DSBH) fold domain ...
 1853-1905 2.25e-13

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: 70.10  E-value: 2.25e-13
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 187761317  1853 SFLDPDIGgVAVAPTHGSILIECAKRELHATTPLKNPNRNhpTRISLVFYQHK 1905
Cdd:pfam12851  117 RLALPQLG-VAFAPTPGTVLIFCGKSLEHGVTPVKNPNRW--ERVSLVFYWHK 166
 
Name Accession Description Interval E-value
TET2 cd18896
oxygenase domain of ten-eleven translocation (TET)2 methylcytosine dioxygenase and similar ...
 1129-1472 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: 746.41  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187761317 1129 DFPSCRCVEQIIEKDEGPFYTHLGAGPNVAAIREIMEERFGQKGKAIRIERVIYTGKEGKSSQGCPIAKWVVRRSSSEEK 1208
Cdd:cd18896     1 DFPSCSCVEQIIEKDEGPYYTHLGAGPNVAAIREIMEERFGQKGKAIRIERVIYTGKEGKSSQGCPIAKWVIRRSSEEEK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187761317 1209 LLCLVRERAGHTCEAAVIVILILVWEGIPLSLADKLYSELTETLRKYGTLTNRRCALNEERTCACQGLDPETCGASFSFG 1288
Cdd:cd18896    81 LLCLVRERAGHSCETAVIVILILVWEGIPISLADKLYSELTDTLRKYGTLTNRRCALNEERTCACQGLDPETCGASFSFG 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187761317 1289 CSWSMYYNGCKFARSKIPRKFKLLGDDPKEEEKLESHLQNLSTLMAPTYKKLAPDAYNNQIEYEHRAPECRLGLKEGRPF 1368
Cdd:cd18896   161 CSWSMYYNGCKFARSKIPRKFKLLGDDPKEEEKLESNLQNLSTLMAPTYKKLAPDAYNNQIEYEHRAPDCRLGLKEGRPF 240

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187761317 1369 SGVTACLDFCAHAHRDLHNMQNGSTLVCTLTREDNREFGGKPEDEQLHVLPLYKVSDVDEFGSVEAQEEKKRSGAIQVLS 1448
Cdd:cd18896   241 SGVTACLDFCAHAHRDLHNMQNGSTLVCTLTREDNREIGKIPEDEQLHVLPLYKVSDVDEFGSTEAQEEKKRNGAIQVLS 320

                         330       340
                  ....*....|....*....|....
gi 187761317 1449 SFRRKVRMLAEPVKTCRQRKLEAK 1472
Cdd:cd18896   321 SFRRKVRMLAEPVKTCRQRKLEDE 344
TET cd18892
oxygenase domain of ten-eleven translocation (TET)1, TET2, and TET3 methylcytosine ...
 1133-1502 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: 647.43  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187761317 1133 CRCVEQII-EKDEGPFYTHLGAGPNVAAIREIMEERFGQKGKAIRIERVIYTGKEGKSSQGCPIAKWVVRRSSSEEKLLC 1211
Cdd:cd18892     1 CGCFPPDEsPPEPGPYYTHLGAGPSLAALRELLEKRTGVTGKAIRIEKVIYTGKEGKTSQGCPIAKWIIRRSSLEEKYLV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187761317 1212 LVRERAGHTCEAAVIVILILVWEGIPLSLADKLYSELTETLRKYGTLTNRRCALNEERTCACQGLDPETCGASFSFGCSW 1291
Cdd:cd18892    81 LVKHRPGHFCHSAFIVICIVAWEGVPQSNADELYSLLTDKLNKFGLPTKRRCGTNEERTCACQGLDPETCGASFSFGCSW 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187761317 1292 SMYYNGCKFARSKIPRKFKLLgdDPKEEEKLESHLQNLSTLMAPTYKKLAPDAYNNQIEYEHRAPECRLGLKEGRPFSGV 1371
Cdd:cd18892   161 SMYYNGCKFARSKTVRKFRLS--DKSEEEELEDKLQNLATHLAPLYKSLAPDSYKNQVQFEEEALDCRLGLKPGRPFSGV 238

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187761317 1372 TACLDFCAHAHRDLHNMQNGSTLVCTLTREDNREfGGKPEDEQLHVLPLYKVSDVDEFGSVEAQEEKKRSGAIQVLSSFR 1451
Cdd:cd18892   239 TACVDFCAHAHKDLHNMNNGCTVVVTLTKHRNLT-KPEPEQLHVLPLYLYDMTDEDEFGSVEGQEEKVRNGSIEVLTKYP 317

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 187761317 1452 RKVRMLAEPVKTCRQRKLEAKKAAAEKLSSLENSSNKNEKEKS----APSRTKQT 1502
Cdd:cd18892   318 CEVREYWSDSEECFLDPDIGGVAIALSHGSVLFECAKRELHATtplkNPNRQHPT 372
TET1 cd18895
oxygenase domain of ten-eleven translocation (TET)1 methylcytosine dioxygenase and similar ...
 1133-1455 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: 618.85  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187761317 1133 CRCVEQIIEKDEGPFYTHLGAGPNVAAIREIMEERFGQKGKAIRIERVIYTGKEGKSSQGCPIAKWVVRRSSSEEKLLCL 1212
Cdd:cd18895     1 CDCVEQIIEKDEGPYYTHLGAGPSVAAVREIMENRYGEKGNAIRIEVVVYTGKEGKSSQGCPIAKWVIRRSSDEEKLLCL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187761317 1213 VRERAGHTCEAAVIVILILVWEGIPLSLADKLYSELTETLRKYGTLTNRRCALNEERTCACQGLDPETCGASFSFGCSWS 1292
Cdd:cd18895    81 VRQRAGHHCQTAVIVILILAWEGIPRLLADRLYQELTQTLKKYGSPTSRRCALNEDRTCACQGLDPETCGASFSFGCSWS 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187761317 1293 MYYNGCKFARSKIPRKFKLLGDDPKEEEKLESHLQNLSTLMAPTYKKLAPDAYNNQIEYEHRAPECRLGLKEGRPFSGVT 1372
Cdd:cd18895   161 MYFNGCKFARSKYPRKFRLLTDDPKEEENLESNLQNLATDVAPVYKKLAPEAFQNQVENENVAPDCRLGSKEGRPFSGVT 240

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187761317 1373 ACLDFCAHAHRDLHNMQNGSTLVCTLTREDNREFGGKPEDEQLHVLPLYKVSDVDEFGSVEAQEEKKRSGAIQVLSSFRR 1452
Cdd:cd18895   241 ACIDFCAHAHKDTHNMHNGSTVVCTLTKEDNRSVGVIPEDEQLHVLPLYKISDTDEFGSEEGQEAKIKNGAIQVLSAFPR 320


                  ...
gi 187761317 1453 KVR 1455
Cdd:cd18895   321 EVR 323
TET3 cd18897
oxygenase domain of ten-eleven translocation (TET)3 methylcytosine dioxygenase and similar ...
 1133-1455 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: 583.87  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187761317 1133 CRCVEQIIEKDEGPFYTHLGAGPNVAAIREIMEERFGQKGKAIRIERVIYTGKEGKSSQGCPIAKWVVRRSSSEEKLLCL 1212
Cdd:cd18897     1 CDCVEQILEKDEGPYYTHLGSGPTVASIRELMEERYGEKGKAIRIEKVIYTGKEGKSSRGCPIAKWVIRRSSEEEKLLCL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187761317 1213 VRERAGHTCEAAVIVILILVWEGIPLSLADKLYSELTETLRKYGTLTNRRCALNEERTCACQGLDPETCGASFSFGCSWS 1292
Cdd:cd18897    81 VRHRAGHHCQNAVIVILILAWEGIPRALGDKLYQELTETLTKYGNPTSRRCGLNDDRTCACQGKDPNTCGASFSFGCSWS 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187761317 1293 MYYNGCKFARSKIPRKFKLLGDDPKEEEKLESHLQNLSTLMAPTYKKLAPDAYNNQIEYEHRAPECRLGLKEGRPFSGVT 1372
Cdd:cd18897   161 MYFNGCKYARSKTPRKFRLIGDNPKEEENLRDNFQDLATEVAPLYKRLAPQAYQNQVTNEDIAIDCRLGLKEGRPFSGVT 240

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187761317 1373 ACLDFCAHAHRDLHNMQNGSTLVCTLTREDNREFGGKPEDEQLHVLPLYKVSDVDEFGSVEAQEEKKRSGAIQVLSSFRR 1452
Cdd:cd18897   241 ACMDFCAHAHKDQHNLYNGCTVVCTLTKEDNRTVGKIPEDEQLHVLPLYKMSTTDEFGSEENQNEKIGSGAIQVLTSFPR 320


                  ...
gi 187761317 1453 KVR 1455
Cdd:cd18897   321 EVR 323
Tet_JBP cd14946
oxygenase domain of ten-eleven translocation (TET) enzymes, J-binding proteins (JBPs), and ...
 1160-1423 2.13e-80

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: 266.17  E-value: 2.13e-80
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187761317 1160 IREIMEERFG-QKGKAIRIERVIYTGKEGKSsQGCPIAKWVVRRSsseeKLLCLVRERAGhtceaavIVILILVWEGIPL 1238
Cdd:cd14946     1 LLENMLSKCGtQQSFANANITLKYEGKEGKS-QGCPKALKNVRTS----KLAYFVCDHDG-------SVILAYVPEVLPK 68

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187761317 1239 SLADKLYSELTETLRKYGTLtnrrcalneertcacqglDPETCGASFSFGCSWSMYYNGCKfarskiprkfKLLGDDPKE 1318
Cdd:cd14946    69 ELVEEFTEKLESIQTKRGTL------------------DPETKGDTGYSGILDNSMPFNYV----------TADLSQELG 120

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187761317 1319 EEKLESHLQNLSTLMAPTYKKLAPDAYNNQIEYEHRAPECRLGLKEGRPFSGVTACLD-FCAHAHRDLHNMQNGSTLVCT 1397
Cdd:cd14946   121 QYLSEIVNPQISYYISKLLTCVSPRTINYLVEYEHRSLNDSYYALNNCLYPSTAFNSLkRIRKPHKDNLDIQNGPSSLFY 200

                         250       260
                  ....*....|....*....|....*.
gi 187761317 1398 LTREDNrefggkpeDEQLHVLPLYKV 1423
Cdd:cd14946   201 FGNFQN--------TEGYLELTLKKV 218
Tet_JBP pfam12851
Oxygenase domain of the 2OGFeDO superfamily; A double-stranded beta helix (DSBH) fold domain ...
 1290-1426 1.17e-58

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: 199.92  E-value: 1.17e-58
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187761317  1290 SWSMYYNGCKFARSKIPRKFKLLGDDPKEEEKLESHLQNLSTLMAPTYKKLAPDAYNNQIEYEHRAPECRLGLKEGRPFS 1369
Cdd:pfam12851    1 SWSMYYDGCKFPGPRKPRKFSFTPRNPKEEIKLEDELQELAALLGAIYKQIAPDLYENQIEYEQDAAICRLGRKWGRPFS 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 187761317  1370 GVTACLDFCAHAHRDLHNMQNGSTLVCTLTredNREFGGKPEDEQLHVLPLYKVSDV 1426
Cdd:pfam12851   81 GVTVNLNFETISHRDLGNFRNGSTLLCTLT---GRYEGGRLALPQLGVAFAPTPGTV 134
TET2 cd18896
oxygenase domain of ten-eleven translocation (TET)2 methylcytosine dioxygenase and similar ...
 1844-1921 2.25e-49

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: 182.86  E-value: 2.25e-49
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 187761317 1844 DEVWSDSEQSFLDPDIGGVAVAPTHGSILIECAKRELHATTPLKNPNRNHPTRISLVFYQHKSMNEPKHGLALWEAKM 1921
Cdd:cd18896   343 DEVWSDSEQSFLDPDIGGVAVAPSHGSILIECAKRELHATTPLKNPNRNHPTRISLVFYQHKSMNEPKHGLALWEAKM 420
TET1 cd18895
oxygenase domain of ten-eleven translocation (TET)1 methylcytosine dioxygenase and similar ...
 1816-1921 1.15e-43

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: 165.47  E-value: 1.15e-43
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187761317 1816 LHKLSDAN------GQE-KQPLALVQGVASGAEDNDEVWSDSEQSFLDPDIGGVAVAPTHGSILIECAKRELHATTPLKN 1888
Cdd:cd18895   288 LYKISDTDefgseeGQEaKIKNGAIQVLSAFPREVREVWSDSEHNFLDEDIGGVAVAPSHGSILIECARRELHATTPIKK 367

                          90       100       110
                  ....*....|....*....|....*....|...
gi 187761317 1889 PNRNHPTRISLVFYQHKSMNEPKHGLALWEAKM 1921
Cdd:cd18895   368 PNRNHPTRISLVFYQHKNLNEPKHGLALWEAKM 400
TET3 cd18897
oxygenase domain of ten-eleven translocation (TET)3 methylcytosine dioxygenase and similar ...
 1820-1921 6.32e-43

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: 164.39  E-value: 6.32e-43
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 187761317 1820 SDANGQEKQPLALVQGVASGAEDNDEVWSDSEQSFLDPDIGGVAVAPTHGSILIECAKRELHATTPLKNPNRNHPTRISL 1899
Cdd:cd18897   299 SEENQNEKIGSGAIQVLTSFPREVREVWSDSEHNFLDENIGGVAVAPAHGSILIECARRELHATTPLKKPNRCHPTRISL 378

                          90       100
                  ....*....|....*....|..
gi 187761317 1900 VFYQHKSMNEPKHGLALWEAKM 1921
Cdd:cd18897   379 VFYQHKNLNQPNHGLALWEAKM 400
TET cd18892
oxygenase domain of ten-eleven translocation (TET)1, TET2, and TET3 methylcytosine ...
 1845-1921 4.91e-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: 4.91e-40
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 187761317 1845 EVWSDSEQSFLDPDIGGVAVAPTHGSILIECAKRELHATTPLKNPNRNHPTRISLVFYQHKSMNEPKHGLALWEAKM 1921
Cdd:cd18892   322 EYWSDSEECFLDPDIGGVAIALSHGSVLFECAKRELHATTPLKNPNRQHPTRISLVFYQHKNLNYSRHGLAEYEAKM 398
Tet_JBP cd14946
oxygenase domain of ten-eleven translocation (TET) enzymes, J-binding proteins (JBPs), and ...
 1839-1905 1.07e-14

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: 76.27  E-value: 1.07e-14
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 187761317 1839 GAEDNDEVWsdsEQSFLDPDIGGVAVAPTHGSILIECAKRELHATTPLKNPNrNHPTRISLVFYQHK 1905
Cdd:cd14946   202 GNFQNTEGY---LELTLKKVIGNCAVFVQPGDVLFFKGNEYKHVVTNITNPN-NHGWRISLVYYAHK 264
Tet_JBP pfam12851
Oxygenase domain of the 2OGFeDO superfamily; A double-stranded beta helix (DSBH) fold domain ...
 1853-1905 2.25e-13

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: 70.10  E-value: 2.25e-13
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 187761317  1853 SFLDPDIGgVAVAPTHGSILIECAKRELHATTPLKNPNRNhpTRISLVFYQHK 1905
Cdd:pfam12851  117 RLALPQLG-VAFAPTPGTVLIFCGKSLEHGVTPVKNPNRW--ERVSLVFYWHK 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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