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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156139122 1422 CSCLDRVIQKDKGPYYTHLGAGPSVAAVREIMENRYGQKGNAIRIEIVVYTGKEGKSSHGCPIAKWVLRRSSDEEKVLCL 1501
Cdd:cd18895     1 CDCVEQIIEKDEGPYYTHLGAGPSVAAVREIMENRYGEKGNAIRIEVVVYTGKEGKSSQGCPIAKWVIRRSSDEEKLLCL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156139122 1502 VRQRTGHHCPTAVMVVLIMVWDGIPLPMADRLYTELTENLKSYnGHPTDRRCTLNENRTCTCQGIDPETCGASFSFGCSW 1581
Cdd:cd18895    81 VRQRAGHHCQTAVIVILILAWEGIPRLLADRLYQELTQTLKKY-GSPTSRRCALNEDRTCACQGLDPETCGASFSFGCSW 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156139122 1582 SMYFNGCKFGRSPSPRRFRIDPSSPLHEKNLEDNLQSLATRLAPIYKQYAPVAYQNQVEYENVARECRLGSKEGRPFSGV 1661
Cdd:cd18895   160 SMYFNGCKFARSKYPRKFRLLTDDPKEEENLESNLQNLATDVAPVYKKLAPEAFQNQVENENVAPDCRLGSKEGRPFSGV 239

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156139122 1662 TACLDFCAHPHRDIHNMNNGSTVVCTLTREDNRSLGVIPQDEQLHVLPLYKLSDTDEFGSKEGMEAKIKSGAIEVLAPRR 1741
Cdd:cd18895   240 TACIDFCAHAHKDTHNMHNGSTVVCTLTKEDNRSVGVIPEDEQLHVLPLYKISDTDEFGSEEGQEAKIKNGAIQVLSAFP 319

                  ....
gi 156139122 1742 KKRT 1745
Cdd:cd18895   320 REVR 323

CXXC zinc finger domain; This domain contains eight conserved cysteine residues that bind to two zinc ions. The CXXC domain is found in a variety of chromatin-associated proteins. This domain binds to nonmethyl-CpG dinucleotides. The domain is characterized by two repeats, and shows a peculiar internal duplication in which the second unit is inserted into the first one. Each of these units is characterized by four conserved cysteines, displaying a CXXCXXCX(n)C motif that chelate a Zn+2 ion. The DNA binding interface has been identified by NMR. In eukaryotes, the CXXC domain is found in stramenopiles, plants and metazoans. Plants possess a mono-CXXC domain that is present in distinct chromatin proteins. Structural comparisons show that the mono-CXXC is homologous to the structural-zinc binding domain of medium chain dehydrogenases.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 156139122   585 KKKRKRCGVCEPCQQKTNCGECTYCKNRK------NSHQICKKRKC 624
Cdd:pfam02008    3 RRKRRRCGVCEGCQRPEDCGQCSFCLDMPkfggpgKKKQKCRLRRC 48

PET ((Prickle Espinas Testin) domain is involved in protein-protein interactions; PET domain is involved in protein-protein interactions and is usually found in conjunction with LIM domain, which is also a protein-protein interaction domain. The PET containing proteins serve as adaptors or scaffolds to support the assembly of multimeric protein complexes. The PET domain has been found at the N-terminal of four known groups of proteins: prickle, testin, LIMPETin/LIM-9 and overexpressed breast tumor protein (OEBT). Prickle has been implicated in regulation of cell movement through its association with the Dishevelled (Dsh) protein in the planar cell polarity (PCP) pathway. Testin is a cytoskeleton associated focal adhesion protein that localizes along actin stress fibers, at cell contact areas, and at focal adhesion plaques. It interacts with a variety of cytoskeletal proteins, including zyxin, mena, VASP, talin, and actin, and is involved in cell motility and adhesion events. Knockout mice experiments reveal tumor repressor function of Testin. LIMPETin/LIM-9 contains an N-terminal PET domain and 6 LIM domains at the C-terminal. In Schistosoma mansoni, where LIMPETin was first identified, it is down regulated in sexually mature adult females compared to sexually immature adult females and adult males. Its differential expression indicates that it is a transcription regulator. In C. elegans, LIM-9 may play a role in regulating the assembly and maintenance of the muscle A-band by forming a protein complex with SCPL-1 and UNC-89 and other proteins. OEBT displays a PET domain with two LIM domains, and is predicted to be localized in the nucleus with a possible role in cancer differentiation.

                          10        20
                  ....*....|....*....|...
gi 156139122 1035 LHQLPPRNNEVEYCNQLLDSSKK 1057
Cdd:cd09827    52 LHQLPPHDNEVRYCNSLSEEEKR 74

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156139122 1422 CSCLDRVIQKDKGPYYTHLGAGPSVAAVREIMENRYGQKGNAIRIEIVVYTGKEGKSSHGCPIAKWVLRRSSDEEKVLCL 1501
Cdd:cd18895     1 CDCVEQIIEKDEGPYYTHLGAGPSVAAVREIMENRYGEKGNAIRIEVVVYTGKEGKSSQGCPIAKWVIRRSSDEEKLLCL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156139122 1502 VRQRTGHHCPTAVMVVLIMVWDGIPLPMADRLYTELTENLKSYnGHPTDRRCTLNENRTCTCQGIDPETCGASFSFGCSW 1581
Cdd:cd18895    81 VRQRAGHHCQTAVIVILILAWEGIPRLLADRLYQELTQTLKKY-GSPTSRRCALNEDRTCACQGLDPETCGASFSFGCSW 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156139122 1582 SMYFNGCKFGRSPSPRRFRIDPSSPLHEKNLEDNLQSLATRLAPIYKQYAPVAYQNQVEYENVARECRLGSKEGRPFSGV 1661
Cdd:cd18895   160 SMYFNGCKFARSKYPRKFRLLTDDPKEEENLESNLQNLATDVAPVYKKLAPEAFQNQVENENVAPDCRLGSKEGRPFSGV 239

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156139122 1662 TACLDFCAHPHRDIHNMNNGSTVVCTLTREDNRSLGVIPQDEQLHVLPLYKLSDTDEFGSKEGMEAKIKSGAIEVLAPRR 1741
Cdd:cd18895   240 TACIDFCAHAHKDTHNMHNGSTVVCTLTKEDNRSVGVIPEDEQLHVLPLYKISDTDEFGSEEGQEAKIKNGAIQVLSAFP 319

                  ....
gi 156139122 1742 KKRT 1745
Cdd:cd18895   320 REVR 323

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156139122 1946 LTSPQDLASSPMEEDEQ-H-------SEADEPPSDEPLSDDPLSPAEEKLP----HIDEYWSDSEHIFLDANIGGVAIAP 2013
Cdd:cd18895   266 LTKEDNRSVGVIPEDEQlHvlplykiSDTDEFGSEEGQEAKIKNGAIQVLSafprEVREVWSDSEHNFLDEDIGGVAVAP 345

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 156139122 2014 AHGSVLIECARRELHATTPVEHPNRNHPTRLSLVFYQHKNLNKPQHGFELNKIKFEAKEAKNKKM 2078
Cdd:cd18895   346 SHGSILIECARRELHATTPIKKPNRNHPTRISLVFYQHKNLNEPKHGLALWEAKMAEKAKEKEKE 410

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 156139122  2008 GVAIAPAHGSVLIECARRELHATTPVEHPNRNhpTRLSLVFYQHK 2052
Cdd:pfam12851  124 GVAFAPTPGTVLIFCGKSLEHGVTPVKNPNRW--ERVSLVFYWHK 166

The PET domain of Prickle; The PET domain of Prickle: Prickle contains an N-terminal PET domain and three C-terminal LIM domains. Prickle has been implicated in regulation of cell movement in the planar cell polarity (PCP) pathway which requires the conserved Frizzled/Dishevelled (Dsh); Prickle interacts with Dishevelled, thereby modulating the activity of Frizzled/Dishevelled and the PCP signaling. Two forms of Prickle have been identified, namely Prickle 1 and Prickle 2. These are differentially expressed; Prickle 1 is found in fetal heart and hematological malignancies, while Prickle 2 is expressed in fetal brain, adult cartilage, pancreatic islet, and some types of timorous cells. The PET domain is a protein-protein interaction domain, usually found in conjunction with the LIM domain, which is also involved in protein-protein interactions. The PET containing proteins serve as adaptors or scaffolds to support the assembly of multimeric protein complexes.

                          10        20
                  ....*....|....*....|...
gi 156139122 1035 LHQLPPRNNEVEYCNQLLDSSKK 1057
Cdd:cd09827    52 LHQLPPHDNEVRYCNSLSEEEKR 74

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156139122 1422 CSCLDRVIQKDKGPYYTHLGAGPSVAAVREIMENRYGQKGNAIRIEIVVYTGKEGKSSHGCPIAKWVLRRSSDEEKVLCL 1501
Cdd:cd18895     1 CDCVEQIIEKDEGPYYTHLGAGPSVAAVREIMENRYGEKGNAIRIEVVVYTGKEGKSSQGCPIAKWVIRRSSDEEKLLCL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156139122 1502 VRQRTGHHCPTAVMVVLIMVWDGIPLPMADRLYTELTENLKSYnGHPTDRRCTLNENRTCTCQGIDPETCGASFSFGCSW 1581
Cdd:cd18895    81 VRQRAGHHCQTAVIVILILAWEGIPRLLADRLYQELTQTLKKY-GSPTSRRCALNEDRTCACQGLDPETCGASFSFGCSW 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156139122 1582 SMYFNGCKFGRSPSPRRFRIDPSSPLHEKNLEDNLQSLATRLAPIYKQYAPVAYQNQVEYENVARECRLGSKEGRPFSGV 1661
Cdd:cd18895   160 SMYFNGCKFARSKYPRKFRLLTDDPKEEENLESNLQNLATDVAPVYKKLAPEAFQNQVENENVAPDCRLGSKEGRPFSGV 239

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156139122 1662 TACLDFCAHPHRDIHNMNNGSTVVCTLTREDNRSLGVIPQDEQLHVLPLYKLSDTDEFGSKEGMEAKIKSGAIEVLAPRR 1741
Cdd:cd18895   240 TACIDFCAHAHKDTHNMHNGSTVVCTLTKEDNRSVGVIPEDEQLHVLPLYKISDTDEFGSEEGQEAKIKNGAIQVLSAFP 319

                  ....
gi 156139122 1742 KKRT 1745
Cdd:cd18895   320 REVR 323

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156139122 1418 ELPTCSCLDRVIQKDKGPYYTHLGAGPSVAAVREIMENRYGQKGNAIRIEIVVYTGKEGKSSHGCPIAKWVLRRSSDEEK 1497
Cdd:cd18896     1 DFPSCSCVEQIIEKDEGPYYTHLGAGPNVAAIREIMEERFGQKGKAIRIERVIYTGKEGKSSQGCPIAKWVIRRSSEEEK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156139122 1498 VLCLVRQRTGHHCPTAVMVVLIMVWDGIPLPMADRLYTELTENLKSYNGHpTDRRCTLNENRTCTCQGIDPETCGASFSF 1577
Cdd:cd18896    81 LLCLVRERAGHSCETAVIVILILVWEGIPISLADKLYSELTDTLRKYGTL-TNRRCALNEERTCACQGLDPETCGASFSF 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156139122 1578 GCSWSMYFNGCKFGRSPSPRRFRIDPSSPLHEKNLEDNLQSLATRLAPIYKQYAPVAYQNQVEYENVARECRLGSKEGRP 1657
Cdd:cd18896   160 GCSWSMYYNGCKFARSKIPRKFKLLGDDPKEEEKLESNLQNLSTLMAPTYKKLAPDAYNNQIEYEHRAPDCRLGLKEGRP 239

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156139122 1658 FSGVTACLDFCAHPHRDIHNMNNGSTVVCTLTREDNRSLGVIPQDEQLHVLPLYKLSDTDEFGSKEGMEAKIKSGAIEVL 1737
Cdd:cd18896   240 FSGVTACLDFCAHAHRDLHNMQNGSTLVCTLTREDNREIGKIPEDEQLHVLPLYKVSDVDEFGSTEAQEEKKRNGAIQVL 319

                         330       340
                  ....*....|....*....|.
gi 156139122 1738 APRRKKRTCFTQPVpRSGKKR 1758
Cdd:cd18896   320 SSFRRKVRMLAEPV-KTCRQR 339

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156139122  1580 SWSMYFNGCKFGRSPSPRRFRIDPSSPLHEKNLEDNLQSLATRLAPIYKQYAPVAYQNQVEYENVARECRLGSKEGRPFS 1659
Cdd:pfam12851    1 SWSMYYDGCKFPGPRKPRKFSFTPRNPKEEIKLEDELQELAALLGAIYKQIAPDLYENQIEYEQDAAICRLGRKWGRPFS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156139122  1660 GVTACLDFCAHPHRDIHNMNNGSTVVCTLTredNRSLGVIPQDEQLHVLPLYKLSDTDEFGSKegmeaKIKSGAIEVLAP 1739
Cdd:pfam12851   81 GVTVNLNFETISHRDLGNFRNGSTLLCTLT---GRYEGGRLALPQLGVAFAPTPGTVLIFCGK-----SLEHGVTPVKNP 152

                   ....*..
gi 156139122  1740 RRKKRTC 1746
Cdd:pfam12851  153 NRWERVS 159

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156139122 1946 LTSPQDLASSPMEEDEQ-H-------SEADEPPSDEPLSDDPLSPAEEKLP----HIDEYWSDSEHIFLDANIGGVAIAP 2013
Cdd:cd18895   266 LTKEDNRSVGVIPEDEQlHvlplykiSDTDEFGSEEGQEAKIKNGAIQVLSafprEVREVWSDSEHNFLDEDIGGVAVAP 345

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 156139122 2014 AHGSVLIECARRELHATTPVEHPNRNHPTRLSLVFYQHKNLNKPQHGFELNKIKFEAKEAKNKKM 2078
Cdd:cd18895   346 SHGSILIECARRELHATTPIKKPNRNHPTRISLVFYQHKNLNEPKHGLALWEAKMAEKAKEKEKE 410

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156139122 1991 DEYWSDSEHIFLDANIGGVAIAPAHGSVLIECARRELHATTPVEHPNRNHPTRLSLVFYQHKNLNKPQHGFELnkikFEA 2070
Cdd:cd18896   343 DEVWSDSEQSFLDPDIGGVAVAPSHGSILIECAKRELHATTPLKNPNRNHPTRISLVFYQHKSMNEPKHGLAL----WEA 418

                          90
                  ....*....|....*..
gi 156139122 2071 KEAKnkkmKASEQKDQA 2087
Cdd:cd18896   419 KMAE----KAREKEEEC 431

CXXC zinc finger domain; This domain contains eight conserved cysteine residues that bind to two zinc ions. The CXXC domain is found in a variety of chromatin-associated proteins. This domain binds to nonmethyl-CpG dinucleotides. The domain is characterized by two repeats, and shows a peculiar internal duplication in which the second unit is inserted into the first one. Each of these units is characterized by four conserved cysteines, displaying a CXXCXXCX(n)C motif that chelate a Zn+2 ion. The DNA binding interface has been identified by NMR. In eukaryotes, the CXXC domain is found in stramenopiles, plants and metazoans. Plants possess a mono-CXXC domain that is present in distinct chromatin proteins. Structural comparisons show that the mono-CXXC is homologous to the structural-zinc binding domain of medium chain dehydrogenases.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 156139122   585 KKKRKRCGVCEPCQQKTNCGECTYCKNRK------NSHQICKKRKC 624
Cdd:pfam02008    3 RRKRRRCGVCEGCQRPEDCGQCSFCLDMPkfggpgKKKQKCRLRRC 48

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 156139122 2006 IGGVAIAPAHGSVLIECARRELHATTPVEHPNrNHPTRLSLVFYQHK 2052
Cdd:cd14946   219 IGNCAVFVQPGDVLFFKGNEYKHVVTNITNPN-NHGWRISLVYYAHK 264

The PET domain of Prickle; The PET domain of Prickle: Prickle contains an N-terminal PET domain and three C-terminal LIM domains. Prickle has been implicated in regulation of cell movement in the planar cell polarity (PCP) pathway which requires the conserved Frizzled/Dishevelled (Dsh); Prickle interacts with Dishevelled, thereby modulating the activity of Frizzled/Dishevelled and the PCP signaling. Two forms of Prickle have been identified, namely Prickle 1 and Prickle 2. These are differentially expressed; Prickle 1 is found in fetal heart and hematological malignancies, while Prickle 2 is expressed in fetal brain, adult cartilage, pancreatic islet, and some types of timorous cells. The PET domain is a protein-protein interaction domain, usually found in conjunction with the LIM domain, which is also involved in protein-protein interactions. The PET containing proteins serve as adaptors or scaffolds to support the assembly of multimeric protein complexes.

                          10        20
                  ....*....|....*....|...
gi 156139122 1035 LHQLPPRNNEVEYCNQLLDSSKK 1057
Cdd:cd09827    52 LHQLPPHDNEVRYCNSLSEEEKR 74