Tudor domain found in PHD finger protein1 (PHF1) and similar proteins; PHF1, also called Polycomb-like protein 1 (PCL1), together with JARID2 and AEBP2, associates with 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. PHF1 is essential in epigenetic regulation and genome maintenance. It acts as a dual reader of lysine trimethylation at lysine 36 of histone H3 and lysine 27 of histone variant H3t. Moreover, PHF1 is required for efficient H3-K27 trimethylation (H3K27me3) and Hox gene silencing. It can mediate deposition of the repressive H3K27me3 mark and acts as a cofactor in early DNA-damage response. PHF1 consists of an N-terminal Tudor domain followed by two PHD domains, and a C-terminal MTF2 domain. Its Tudor domain selectively binds to histone H3K36me3.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1220209779  30 RLWEGQDVLARWTDGLLYLGTIKKVDSAREVCLVQFEDDSQFLVLWKDISPA 81
Cdd:cd20449     1 RLWEGQDVLARWTDGLLYLGTIKKVDSAREVCLVQFEDDSQFLVLWKDISPA 52

Polycomb-like MTF2 factor 2; Mammalian Polycomb-like gene MTF2/PCL2 forms a complex with Polycomb repressive complex-2 (PRC2) and collaborates with PRC1 to achieve repression of Hox gene expression. The human MTF2 gene is expressed in three splicing variants, each of them contains the short C-terminal domain defined here. The domain is subject to structure determination by the Joint Center of Structural Genomics.

                          10        20        30
                  ....*....|....*....|....*....|
gi 1220209779 504 LSRGDPVRVLARRVRPDGSVQYLVEWGGGG 533
Cdd:pfam14061  19 IACGERYAVLAKRVTPNGKVQYLVEWEGTT 48

Tudor domain found in PHD finger protein1 (PHF1) and similar proteins; PHF1, also called Polycomb-like protein 1 (PCL1), together with JARID2 and AEBP2, associates with 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. PHF1 is essential in epigenetic regulation and genome maintenance. It acts as a dual reader of lysine trimethylation at lysine 36 of histone H3 and lysine 27 of histone variant H3t. Moreover, PHF1 is required for efficient H3-K27 trimethylation (H3K27me3) and Hox gene silencing. It can mediate deposition of the repressive H3K27me3 mark and acts as a cofactor in early DNA-damage response. PHF1 consists of an N-terminal Tudor domain followed by two PHD domains, and a C-terminal MTF2 domain. Its Tudor domain selectively binds to histone H3K36me3.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1220209779  30 RLWEGQDVLARWTDGLLYLGTIKKVDSAREVCLVQFEDDSQFLVLWKDISPA 81
Cdd:cd20449     1 RLWEGQDVLARWTDGLLYLGTIKKVDSAREVCLVQFEDDSQFLVLWKDISPA 52

PHD finger 1 found in PHD finger protein1 (PHF1); PHF1, also termed polycomb-like protein 1 (PCL1), together with JARID2 and AEBP2, associates with 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. PHF1 is essential in epigenetic regulation and genome maintenance. It acts as a dual reader of Lysine trimethylation at Lysine 36 of Histone H3 and Lysine 27 of Histone variant H3t. PHF1 consists of an N-terminal Tudor domain followed by two PHD fingers, and a C-terminal MTF2 domain. Its Tudor domain selectively binds to histone H3K36me3. Moreover, PHF1 is required for efficient H3K27me3 and Hox gene silencing. It can mediate deposition of the repressive H3K27me3 mark and acts as a cofactor in early DNA-damage response. This model corresponds to the first PHD finger.

                          10        20
                  ....*....|....*....|....*..
gi 1220209779  81 AYHQDCHVPRAPAPGEGEGTSWVCRQC 107
Cdd:cd15500    25 AYHQECHVPRVPLESAGDGDSWMCRQC 51

Polycomb-like MTF2 factor 2; Mammalian Polycomb-like gene MTF2/PCL2 forms a complex with Polycomb repressive complex-2 (PRC2) and collaborates with PRC1 to achieve repression of Hox gene expression. The human MTF2 gene is expressed in three splicing variants, each of them contains the short C-terminal domain defined here. The domain is subject to structure determination by the Joint Center of Structural Genomics.

                          10        20        30
                  ....*....|....*....|....*....|
gi 1220209779 504 LSRGDPVRVLARRVRPDGSVQYLVEWGGGG 533
Cdd:pfam14061  19 IACGERYAVLAKRVTPNGKVQYLVEWEGTT 48

PHD finger 2 found in polycomb repressive complex 2 (PRC2)-associated polycomb-like (PCL) family proteins MTF2, PHF19, and similar 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 and all contain an N-terminal Tudor domain followed by two plant homeodomain (PHD) fingers, 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 finger-containing proteins, the first PHD finger of PCL proteins do not display histone H3K4 binding affinity and they do not affect the Tudor domain binding to histones. This model corresponds to the second PHD finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1220209779 156 YCYCGGPGEWNLKMLQCRSCLQWFHEACTQCLSKPLLYGDRFYEFECCVCRG 207
Cdd:cd15503     1 YCYCGGPGEWNLKMLQCCKCRQWFHEACLQCLKKPLLYGDRFYNFCCSVCNN 52

PHD finger 2 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 plant homeodomain (PHD) fingers, and a C-terminal MTF2 domain. It binds 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 second PHD finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1220209779 156 YCYCGGPGEWNLKMLQCRSCLQWFHEACTQCLSKPLLYGDRFYEFECCVC 205
Cdd:cd15581     1 YCYCGGPGEWYLKMLQCYRCRQWFHEACTQCLNDPMMFGDRFYLFFCAVC 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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1220209779  30 RLWEGQDVLARWTDGLLYLGTIKKVDSAREVCLVQFEDDSQFLVLWKDISPA 81
Cdd:cd20385     1 KFAEGQDVLARWTDGLFYLGTIKKVDSAKEKCLVIFEDDSTFWVLFKDIHKV 52

Tudor domain found in PHD finger protein1 (PHF19) and similar proteins; PHF19, also called 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 domains, 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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1220209779  31 LWEGQDVLARWTDGLLYLGTIKKVDSAREVCLVQFEDDSQFLVLWKDISPA 81
Cdd:cd20451     2 LTEGQYVLCRWTDGLYYLGKIKRVSSSKQSCLVTFEDNSKYWVLWKDIQHA 52

PHD finger 1 found in PHD finger protein1 (PHF1); PHF1, also termed polycomb-like protein 1 (PCL1), together with JARID2 and AEBP2, associates with 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. PHF1 is essential in epigenetic regulation and genome maintenance. It acts as a dual reader of Lysine trimethylation at Lysine 36 of Histone H3 and Lysine 27 of Histone variant H3t. PHF1 consists of an N-terminal Tudor domain followed by two PHD fingers, and a C-terminal MTF2 domain. Its Tudor domain selectively binds to histone H3K36me3. Moreover, PHF1 is required for efficient H3K27me3 and Hox gene silencing. It can mediate deposition of the repressive H3K27me3 mark and acts as a cofactor in early DNA-damage response. This model corresponds to the first PHD finger.

                          10        20
                  ....*....|....*....|....*..
gi 1220209779  81 AYHQDCHVPRAPAPGEGEGTSWVCRQC 107
Cdd:cd15500    25 AYHQECHVPRVPLESAGDGDSWMCRQC 51

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 1220209779   29 PRLWEGQDVLARWTDGLLYLGTIKKVDSAREvCLVQFEDD-SQFLVLWKDISP 80
Cdd:smart00333   1 PTFKVGDKVAARWEDGEWYRARIVKVDGEQL-YEVFFIDYgNEEVVPPSDLRQ 52

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        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1220209779 156 YCY-CGGPGEWNLKMLQCRSCLQWFHeacTQCLSKPLLYGDRFYEFECCVC 205
Cdd:cd15489     1 SCIvCGKGGDLGGELLQCDGCGKWFH---ADCLGPPLSSFVPNGKWICPVC 48

Tudor domain found in tumor suppressor TP53-binding protein 1 (53BP1) and similar proteins; 53BP1, also called p53-binding protein 1 (p53BP1), is a double-strand break (DSB) repair protein involved in response to DNA damage, telomere dynamics, and class-switch recombination (CSR) during antibody genesis. It plays a key role in the repair of DSBs in response to DNA damage by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs and specifically counteracting the function of the homologous recombination (HR) repair protein BRCA1. It is recruited to DSB sites by recognizing and binding histone H2A monoubiquitinated at 'Lys-15' (H2AK15Ub) and histone H4 dimethylated at 'Lys-20' (H4K20me2), two histone marks that are present at DSB sites. 53BP1 contains one 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
                  ....*....|....*....|....*....|....*....|....*.
gi 1220209779  34 GQDVLARW-TDGLLYLGTIKKVDsAREVCLVQFEDDSQFLVLWKDI 78
Cdd:cd20383     2 GTRVFAKWsSDGYYYPGIITRVL-GDGKYKVLFDDGYERDVKGKDI 46

Domain of unknown function (DUF4537); The function of this domain family is unknown. It is found in eukaryotes, and is typically between 119 and 141 amino acids in length. In humans, it is found in the chromosomal position C11orf16.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1220209779  34 GQDVLARW-TDGLLYLGTIKKVDSAReVCLVQFEDDSQFLVLWKDISPAYHQDCHV 88
Cdd:pfam15057   1 GQRVLARWdEDGFYYRGTVKKYLNGG-QYLVEFDAGDRQVVLTRDIIALEDAMEHP 55

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 1220209779  34 GQDVLARWT-DGLLYLGTIKKVDSAREVClVQFEDDSQFLVLWKDISP 80
Cdd:cd04508     1 GDRVEAKWSdDGQWYPATVVAVNDDGKYT-VLFDDGNEEEVSEDDIRP 47

PHD finger 1 found in polycomb repressive complex 2 (PRC2)-associated polycomb-like (PCL) family proteins MTF2, PHF19, and similar proteins; The family includes two PCL family proteins, metal-response element-binding transcription factor 2 (MTF2/PCL2) and PHF19/PCL3, which are homologs of PHD finger protein1 (PHF1). PCL family proteins are accessory components of the polycomb repressive complex 2 (PRC2) core complex and all contain an N-terminal Tudor domain followed by two PHD fingers, and a C-terminal MTF2 domain. They 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 finger-containing proteins, the first PHD fingers of PCL proteins do not display histone H3K4 binding affinity and they do not affect the Tudor domain binding to histones. This model corresponds to the first PHD finger.

                          10        20        30
                  ....*....|....*....|....*....|
gi 1220209779  81 AYHQDCHVPRA-PAPGEGEGtSWVCRQCVF 109
Cdd:cd15499    25 GYHQLCHSPKVrTSPLEGDE-KWFCSRCVF 53

PHD finger found in PHF2, PHF8 and KDM7; This family includes PHF2, PHF8, KDM7, and similar proteins. PHF2, also termed GRC5, or PHD finger protein 2, is a histone lysine demethylase ubiquitously expressed in various tissues. PHF8, also termed PHD finger protein 8, or KDM7B, is a monomethylated histone H4 lysine 20(H4K20me1) demethylase that transcriptionally regulates many cell cycle genes. It also preferentially acts on H3K9me2 and H3K9me1. PHF8 is modulated by CDC20-containing anaphase-promoting complex (APC (cdc20)) and plays an important role in the G2/M transition. It acts as a critical molecular sensor for mediating retinoic acid (RA) treatment response in RAR alpha-fusion-induced leukemia. Moreover, PHF8 is essential for cytoskeleton dynamics and is associated with X-linked mental retardation. KDM7, also termed JmjC domain-containing histone demethylation protein 1D (JHDM1D), or KIAA1718, is a dual histone demethylase that catalyzes demethylation of monomethylated and dimethylated H3K9 (H3K9me2/me1) and H3K27 (H3K27me2/me1), which functions as an eraser of silencing marks on chromatin during brain development. It also plays a tumor-suppressive role by regulating angiogenesis. All family members contain a plant homeodomain (PHD) finger and a JmjC domain.

                          10        20
                  ....*....|....*....|....*...
gi 1220209779 156 YCYCGGPGEWNLKMLQCRSCLQWFHEAC 183
Cdd:cd15554     1 YCICRQPYDVTRFMIECDVCKDWFHGSC 28

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
                  ....*....|....*....|....*....|....
gi 1220209779  34 GQDVLARWT-DGLLYLGTIKKVDSAREVCLVQFE 66
Cdd:cd21182     1 GDKCLAPYSdDGKYYEATIEEITEESDTATVVFD 34

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 1220209779  82 YHQDCHVPRAPAPGEGEGTSWVCRQCVF 109
Cdd:cd15579    26 YHQQCHIPVVDSSDDPPLTPWFCRRCIF 53