PHD finger superfamily; The PHD finger superfamily includes a canonical plant homeodomain (PHD) finger typically characterized as Cys4HisCys3, and a non-canonical extended PHD finger, characterized as Cys2HisCys5HisCys2His. Variations include the RAG2 PHD finger characterized by Cys3His2Cys2His and the PHD finger 5 found in nuclear receptor-binding SET domain-containing proteins characterized by Cys4HisCys2His. The PHD finger is also termed LAP (leukemia-associated protein) motif or TTC (trithorax consensus) domain. Single or multiple copies of PHD fingers have been found in a variety of eukaryotic proteins involved in the control of gene transcription and chromatin dynamics. PHD fingers can recognize the unmodified and modified histone H3 tail, and some have been found to interact with non-histone proteins. They also function as epigenome readers controlling gene expression through molecular recruitment of multi-protein complexes of chromatin regulators and transcription factors. The PHD finger domain SF is structurally similar to the RING and FYVE_like superfamilies.

                         10        20
                 ....*....|....*....|....*..
gi 558472779  98 KCNICLGKTSGPLNEILICGKCGLVPH 124
Cdd:cd15579    1 KCNVCLGKSSGPLNEILICGKCGLGYH 27

Jumonji domain-containing protein 2A Tudor domain; This is the tudor domain found in histone demethylase Jumonji domain-containing protein 2A (JMJD2A). Structure and function analysis indicate that this domain can recognize equally well two unrelated histone peptides, H3K4me3 and H4K20me3, by means of two very different binding mechanisms. JMJD2 also known as KDM4, is a conserved iron (II)-dependent jumonji-domain demethylase subfamily that is essential during development. Vertebrate KDM4A-C proteins contain a conserved double tudor domain (DTD).

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                  ....*....|....*....|....*....|....*.
gi 558472779   43 GQYVLCRWTDGLYYLGKIKRVsSSKQSCLVTFEDNS 78
Cdd:pfam18104   1 GQDVIARWTDGRYYLGKFIGI-HTQTFYEVEFEDGS 35

Tudor domain; Domain of unknown function present in several RNA-binding proteins. 10 copies in the Drosophila Tudor protein. Initial proposal that the survival motor neuron gene product contain a Tudor domain are corroborated by more recent database search techniques such as PSI-BLAST (unpublished).

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 558472779    38 SKLTEGQYVLCRWTDGLYYLGKIKRVSSSkQSCLVTFEDNSKY-WVLWKDI 87
Cdd:smart00333   1 PTFKVGDKVAARWEDGEWYRARIVKVDGE-QLYEVFFIDYGNEeVVPPSDL 50

Tudor domain found in polycomb repressive complex 2 (PRC2)-associated polycomb-like (PCL) family proteins; The PCL family includes PHD finger protein1 (PHF1) and its homologs, metal-response element-binding transcription factor 2 (MTF2/PCL2) and PHF19/PCL3, which are accessory components of the Polycomb repressive complex 2 (PRC2) core complex. Members contain an N-terminal Tudor domain followed by two PHD domains, and a C-terminal MTF2 domain. PCL proteins specifically recognize tri-methylated H3K36 (H3K36me3) through their N-terminal Tudor domains. The interaction between their Tudor domains and H3K36me3 is critical for both the targeting and spreading of PRC2 into active chromatin regions and for the maintenance of optimal repression of poised developmental genes where PCL proteins, H3K36me3, and H3K27me3 coexist. Moreover, unlike other PHD domain-containing proteins, the first PHD domains of PCL proteins do not display histone H3K4 binding affinity and they do not affect the binding of the Tudor domain to histones.

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                 ....*....|....*....|....*....|....*....|....*....|...
gi 558472779  39 KLTEGQYVLCRWTDGLYYLGKIKRVSSSKQSCLVTFEDNSKYWVLWKDIQHAG 91
Cdd:cd20385    1 KFAEGQDVLARWTDGLFYLGTIKKVDSAKEKCLVIFEDDSTFWVLFKDIHKVP 53

Tudor domain found in metal-response element-binding transcription factor 2 (MTF2) and similar proteins; MTF2, also called metal regulatory transcription factor 2, metal-response element DNA-binding protein M96, or Polycomb-like protein 2 (PCL2), complexes with the Polycomb repressive complex-2 (PRC2) in embryonic stem cells and regulates the transcriptional networks during embryonic stem cell self-renewal and differentiation. It recruits the PRC2 complex to the inactive X chromosome and target loci in embryonic stem cells. Moreover, MTF2 is required for PRC2-mediated Hox cluster repression. It activates the Cdkn2a gene and promotes cellular senescence, thus suppressing the catalytic activity of PRC2 locally. MTF2, like other PCL family proteins, consists of an N-terminal Tudor domain followed by two PHD domains, and a C-terminal MTF2 domain. PCL proteins specifically recognize tri-methylated H3K36 (H3K36me3) through their N-terminal Tudor domains.

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                 ....*....|....*....|....*....|....*....|....*....|
gi 558472779  39 KLTEGQYVLCRWTDGLYYLGKIKRVSSSKQSCLVTFEDNSKYWVLWKDIQ 88
Cdd:cd20450    1 KFEEGQDVLARWSDGLFYLGTIKKINKLKQSCFIIFEDSSKSWVLWKDIQ 50

PHD finger 1 found in PHD finger protein 19 (PHF19); PHF19, also termed Polycomb-like protein 3 (PCL3), is a component of the polycomb repressive complex 2 (PRC2), which is the major H3K27 methyltransferase that regulates pluripotency, differentiation, and tumorigenesis through catalysis of histone H3 lysine 27 trimethylation (H3K27me3) on chromatin. PHF19 consists of an N-terminal Tudor domain followed by two PHD fingers, and a C-terminal MTF2 domain. It binds trimethylated histone H3 Lys36 (H3K36me3) through its Tudor domain and recruits the PRC2 complex and the H3K36me3 demethylase NO66 to embryonic stem cell genes during differentiation. Moreover, PHF19 and its upstream regulator, Akt, play roles in the phenotype switch of melanoma cells from proliferative to invasive states. This model corresponds to the first PHD finger.

                         10        20
                 ....*....|....*....|....*..
gi 558472779  98 KCNICLGKTSGPLNEILICGKCGLVPH 124
Cdd:cd15579    1 KCNVCLGKSSGPLNEILICGKCGLGYH 27

Tudor domain; Domain of unknown function present in several RNA-binding proteins. 10 copies in the Drosophila Tudor protein. Initial proposal that the survival motor neuron gene product contain a Tudor domain are corroborated by more recent database search techniques such as PSI-BLAST (unpublished).

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 558472779    38 SKLTEGQYVLCRWTDGLYYLGKIKRVSSSkQSCLVTFEDNSKY-WVLWKDI 87
Cdd:smart00333   1 PTFKVGDKVAARWEDGEWYRARIVKVDGE-QLYEVFFIDYGNEeVVPPSDL 50

Tudor domain superfamily; The Tudor domain is a conserved structural domain, originally identified in the Tudor protein of Drosophila, that adopts a beta-barrel-like core structure containing four short beta-strands followed by an alpha-helical region. It binds to proteins with dimethylated arginine or lysine residues, and may also bind methylated histone tails to facilitate protein-protein interactions. Tudor domain-containing proteins may mediate protein-protein interactions required for various DNA-templated biological processes, such as RNA metabolism, as well as histone modification and the DNA damage response. Members of this superfamily contain one or more copies of the Tudor domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 558472779  43 GQYVLCRWT-DGLYYLGKIKRVSSSkQSCLVTFEDNSKYWVLWKDIQ 88
Cdd:cd04508    1 GDRVEAKWSdDGQWYPATVVAVNDD-GKYTVLFDDGNEEEVSEDDIR 46

Tudor domain found in survival motor neuron protein (SMN), motor neuron-related-splicing factor 30 (SPF30), and similar proteins; This group contains SMN, SPF30, Tudor domain-containing protein 3 (TDRD3), DNA excision repair protein ERCC-6-like 2 (ERCC6L2), and similar proteins. SMN, also called component of gems 1, or Gemin-1, is part of a multimeric SMN complex that includes spliceosomal Sm core proteins and plays a catalyst role in the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome. SPF30, also called 30 kDa splicing factor SMNrp, SMN-related protein, or survival motor neuron domain-containing protein 1 (SMNDC1), is an essential pre-mRNA splicing factor required for assembly of the U4/U5/U6 tri-small nuclear ribonucleoprotein into the spliceosome. TDRD3 is a scaffolding protein that specifically recognizes and binds dimethylarginine-containing proteins. ERCC6L2, also called DNA repair and recombination protein RAD26-like (RAD26L), may be involved in early DNA damage response. It regulates RNA Pol II-mediated transcription via its interaction with DNA-dependent protein kinase (DNA-PK) to resolve R loops and minimize transcription-associated genome instability. Members of this group contain a single Tudor domain. The Tudor domain binds to proteins with dimethylated arginine or lysine residues, and may also bind methylated histone tails to facilitate protein-protein interactions.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 558472779  43 GQYVLCRWT-DGLYYLGKIKRVSSSKQSCLVTFEDNSKY-WVLWKDIQHA 90
Cdd:cd21182    1 GDKCLAPYSdDGKYYEATIEEITEESDTATVVFDGYGNSeEVPLSDLKPL 50

Tudor domain found in PHD finger protein 20 (PHF20), PHF20-like protein 1 (PHF20L1), and similar proteins; PHF20, also called Glioma-expressed antigen 2, hepatocellular carcinoma-associated antigen 58, novel zinc finger protein, or transcription factor TZP (referring to Tudor and zinc finger domain containing protein), is a regulator of NF-kappaB activation by disrupting recruitment of PP2A to p65. It also functions as a transcription factor that binds to Akt and plays a role in Akt cell survival/growth signaling. Moreover, it transcriptionally regulates p53. The phosphorylation of PHF20 on Ser291 mediated by protein kinase B (PKB) is essential in tumorigenesis via the regulation of p53-mediated signaling. PHF20L1 is an active malignant brain tumor (MBT) domain-containing protein that binds to monomethylated lysine 142 on DNA (cytosine-5) Methyltransferase 1 (DNMT1) (DNMT1K142me1) and colocalizes at the perinucleolar space in a SET7-dependent manner. Both PHF20 and PHF20L1 contain an N-terminal malignant brain tumor (MBT) domain, a Tudor domain, a plant homeodomain (PHD) finger and putative DNA-binding domains AT hook and C2H2-type zinc finger. The Tudor domain binds to proteins with dimethylated arginine or lysine residues, and may also bind methylated histone tails to facilitate protein-protein interactions.

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                 ....*....|....*....|....*....|....*....|....*....|
gi 558472779  43 GQYVLCRWTDGLYYLGKIKRVSSSkQSCLVTFEDNSKywvlwKDIQHAGV 92
Cdd:cd20386    4 GEEVLARWSDCKFYPAKILKVLDN-GTYEVLFYDGFK-----KTVKASNL 47

first Tudor domain found in Jumonji domain-containing protein 2 (JMJD2) family of histone demethylases; JMJD2 proteins, also called lysine-specific demethylase 4 histone demethylases (KDM4), have been implicated in various cellular processes including DNA damage response, transcription, cell cycle regulation, cellular differentiation, senescence, and carcinogenesis. They selectively catalyze the demethylation of di- and trimethylated H3K9 and H3K36. This model contains only three JMJD2 proteins, JMJD2A-C, which all contain jmjN and jmjC domains in the N-terminal region, followed by a canonical PHD domain, a noncanonical extended PHD domain, and tandem Tudor domains. The model corresponds to the first Tudor domain. The Tudor domain binds to proteins with dimethylated arginine or lysine residues, and may also bind methylated histone tails to facilitate protein-protein interactions. JMJD2D is not included in this model, since it lacks both the PHD and Tudor domains and has a different substrate specificity. JMJD2A-C are required for efficient cancer cell growth.

                         10        20        30
                 ....*....|....*....|....*....|....*....
gi 558472779  40 LTEGQYVLCRWTDGLYYLGKIKRVsSSKQSCLVTFEDNS 78
Cdd:cd20391    1 ISVGQRVIAKHKNGRYYEAEVVDL-TTQTFYEVNFDDGS 38