PHD finger 2 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 plant homeodomain (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 second PHD finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2462608851 254 YCYCGGPGEWNLKMLQCRSCLQWFHEACTQCLSKPLLYGDRFYEFECCVCRG 305
Cdd:cd15582     1 YCYCGGPGEWNLKMLQCCSCLQWFHEACTQCLSKPLLYGDRFYVFECSVCTG 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        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2462608851 155 LCCVCRSETVVPGNRLVSCEKCRHAYHQDCHVPRAPAPGEGEGTSWVCRQC 205
Cdd:cd15500     1 ICCVCDSETVSPKNPLVNCEKCHHAYHQECHVPRVPLESAGDGDSWMCRQC 51

PHD finger 2 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 plant homeodomain (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 second PHD finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2462608851 254 YCYCGGPGEWNLKMLQCRSCLQWFHEACTQCLSKPLLYGDRFYEFECCVCRG 305
Cdd:cd15582     1 YCYCGGPGEWNLKMLQCCSCLQWFHEACTQCLSKPLLYGDRFYVFECSVCTG 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        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2462608851 155 LCCVCRSETVVPGNRLVSCEKCRHAYHQDCHVPRAPAPGEGEGTSWVCRQC 205
Cdd:cd15500     1 ICCVCDSETVSPKNPLVNCEKCHHAYHQECHVPRVPLESAGDGDSWMCRQC 51

PHD-finger; PHD folds into an interleaved type of Zn-finger chelating 2 Zn ions in a similar manner to that of the RING and FYVE domains. Several PHD fingers have been identified as binding modules of methylated histone H3.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 2462608851 156 CCVCRSETvvPGNRLVSCEKCRHAYHQDCHVPRAPAPGEGEGtSWVCRQCVFA 208
Cdd:pfam00628   2 CAVCGKSD--DGGELVQCDGCDDWFHLACLGPPLDPAEIPSG-EWLCPECKPK 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 2462608851 601 LSRGDPVRVLARRVRPDGSVQYLVEWGGGG 630
Cdd:pfam14061  19 IACGERYAVLAKRVTPNGKVQYLVEWEGTT 48

PHD finger 2 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 plant homeodomain (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 second PHD finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2462608851 254 YCYCGGPGEWNLKMLQCRSCLQWFHEACTQCLSKPLLYGDRFYEFECCVCRG 305
Cdd:cd15582     1 YCYCGGPGEWNLKMLQCCSCLQWFHEACTQCLSKPLLYGDRFYVFECSVCTG 52

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 2462608851  96 RLWEGQDVLARWTDGLLYLGTIKKVDSAREVCLVQFEDDSQFLVLWKDISPAA 148
Cdd:cd20449     1 RLWEGQDVLARWTDGLLYLGTIKKVDSAREVCLVQFEDDSQFLVLWKDISPAA 53

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 2462608851 254 YCYCGGPGEWNLKMLQCRSCLQWFHEACTQCLSKPLLYGDRFYEFECCVC 303
Cdd:cd15581     1 YCYCGGPGEWYLKMLQCYRCRQWFHEACTQCLNDPMMFGDRFYLFFCAVC 50

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        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2462608851 155 LCCVCRSETVVPGNRLVSCEKCRHAYHQDCHVPRAPAPGEGEGTSWVCRQC 205
Cdd:cd15500     1 ICCVCDSETVSPKNPLVNCEKCHHAYHQECHVPRVPLESAGDGDSWMCRQC 51

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 2462608851  99 EGQDVLARWTDGLLYLGTIKKVDSAREVCLVQFEDDSQFLVLWKDISPAA 148
Cdd:cd20450     4 EGQDVLARWSDGLFYLGTIKKINKLKQSCFIIFEDSSKSWVLWKDIQTGA 53

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).

                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 2462608851 100 GQDVLARWTDGLLYLGTIKKVDSArEVCLVQFEDDS 135
Cdd:pfam18104   1 GQDVIARWTDGRYYLGKFIGIHTQ-TFYEVEFEDGS 35

PHD finger found in integrator complex subunit 12 (Int12) and similar proteins; Int12, also termed IntS12, or PHD finger protein 22, is a component of integrator, a multi-protein mediator of small nuclear RNA processing. The integrator complex directly interacts with the C-terminal domain of RNA polymerase II (RNAPII) largest subunit and mediates the 3' end processing of small nuclear RNAs (snRNAs) U1 and U2. Different from other components of integrator, Int12 contains a PHD finger, which is not required for snRNA 3' end cleavage. Instead, Int12 harbors a small microdomain at its N-terminus which is necessary and sufficient for Int12 function; this microdomain facilitates Int12 binding to Int1 and promotes snRNA 3' end formation.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2462608851 156 CCVCRSETVVPGNRLVSCEKCRHAYHQDCHVPRAP-APGEGEGTSWVCRQC 205
Cdd:cd15501     2 CVVCKQMDVTSGNQLVECQECHNLYHQECHKPPVTdKDVNDPRLVWYCSRC 52

PHD-finger; PHD folds into an interleaved type of Zn-finger chelating 2 Zn ions in a similar manner to that of the RING and FYVE domains. Several PHD fingers have been identified as binding modules of methylated histone H3.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 2462608851 156 CCVCRSETvvPGNRLVSCEKCRHAYHQDCHVPRAPAPGEGEGtSWVCRQCVFA 208
Cdd:pfam00628   2 CAVCGKSD--DGGELVQCDGCDDWFHLACLGPPLDPAEIPSG-EWLCPECKPK 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 2462608851   95 PRLWEGQDVLARWTDGLLYLGTIKKVDSAREvCLVQFEDD-SQFLVLWKDISP 146
Cdd:smart00333   1 PTFKVGDKVAARWEDGEWYRARIVKVDGEQL-YEVFFIDYgNEEVVPPSDLRQ 52

PHD zinc finger; The plant homeodomain (PHD) finger is a C4HC3 zinc-finger-like motif found in nuclear proteins thought to be involved in epigenetics and chromatin-mediated transcriptional regulation. The PHD finger binds two zinc ions using the so-called 'cross-brace' motif and is thus structurally related to the RING finger and the FYVE finger. It is not yet known if PHD fingers have a common molecular function. Several reports suggest that it can function as a protein-protein interacton domain and it was recently demonstrated that the PHD finger of p300 can cooperate with the adjacent BROMO domain in nucleosome binding in vitro. Other reports suggesting that the PHD finger is a ubiquitin ligase have been refuted as these domains were RING fingers misidentified as PHD fingers.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2462608851  156 CCVCRSEtvVPGNRLVSCEKCRHAYHQDCHVPraPAPGEGEGTSWVCRQC 205
Cdd:smart00249   2 CSVCGKP--DDGGELLQCDGCDRWYHQTCLGP--PLLEEEPDGKWYCPKC 47

PHD finger found in BRPF proteins, Jade proteins, protein AF-10, AF-17, and similar proteins; The family includes BRPF proteins, Jade proteins, protein AF-10 and AF-17. BRPF proteins are scaffold proteins that form monocytic leukemic zinc-finger protein (MOZ)/MOZ-related factor (MORF) H3 histone acetyltransferase (HAT) complexes with other regulatory subunits, such as inhibitor of growth 5 (ING5) and Esa1-associated factor 6 ortholog (EAF6). BRPF proteins have multiple domains, including a canonical Cys4HisCys3 plant homeodomain (PHD) zinc finger followed by a non-canonical extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, a bromodomain and a proline-tryptophan-tryptophan-proline (PWWP) domain. PHD and ePHD fingers both bind to lysine 4 of histone H3 (K4H3), bromodomains interact with acetylated lysines on N-terminal tails of histones and other proteins, and PWWP domains show histone-binding and chromatin association properties. Jade proteins are required for ING4 and ING5 to associate with histone acetyltransferase (HAT) HBO1 and EAF6, to form a HBO1 complex that has a histone H4-specific acetyltransferase activity, a reduced activity toward histone H3, and is responsible for the bulk of histone H4 acetylation in vivo. AF-10, also termed ALL1 (acute lymphoblastic leukemia)-fused gene from chromosome 10 protein, is a transcription factor that has been implicated in the development of leukemia following chromosomal rearrangements between the AF10 gene and one of at least two other genes, MLL and CALM. AF-17, also termed ALL1-fused gene from chromosome 17 protein, is a putative transcription factor that may play a role in multiple signaling pathways. All Jade proteins, AF-10, and AF-17 contain a canonical PHD finger followed by a non-canonical ePHD finger. This model corresponds to the canonical PHD finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2462608851 155 LCCVCRSETVVPGNRLVSCEKCRHAYHQDCH-VPRAPapgEGegtSWVCRQC 205
Cdd:cd15492     1 VCDVCLDGESEDDNEIVFCDGCNVAVHQSCYgIPLIP---EG---DWFCRKC 46

PHD finger found in Arabidopsis thaliana histone-lysine N-methyltransferase arabidopsis trithorax-like protein ATX3, ATX4, ATX5, and similar proteins; The family includes A. thaliana ATX3 (also termed protein SET domain group 14, or trithorax-homolog protein 3), ATX4 (also termed protein SET domain group 16, or trithorax-homolog protein 4) and ATX5 (also termed protein SET domain group 29, or trithorax-homolog protein 5), which belong to the histone-lysine methyltransferase family. They show distinct phylogenetic origins from the ATX1 and ATX2 family. They are multi-domain containing proteins that consist of an N-terminal PWWP domain, a canonical Cys4HisCys3 plant homeodomain (PHD) finger, a non-canonical extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, and a C-terminal SET domain; this model corresponds to the Cys4HisCys3 canonical PHD finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 2462608851 156 CCVCRSETVVPGNRLVSCEKCRHAYHQDCHVPRAPAPGEgegtSWVCRQC 205
Cdd:cd15495     2 CAVCNEGEDDDNNPLITCNRCQISVHQKCYGIREVDPDG----SWVCRAC 47

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 2462608851 156 CCVCRsETVVPGNRLVSCEKCRHAYHQDCHVPRAPAPGEGEgtSWVCRQC 205
Cdd:cd15489     2 CIVCG-KGGDLGGELLQCDGCGKWFHADCLGPPLSSFVPNG--KWICPVC 48

PHD finger found in protein Jade-3 and similar proteins; Jade-3, also termed PHD finger protein 16 (PHF16), is a plant homeodomain (PHD) zinc finger protein that is closely related to Jade-1, which functions as an essential regulator of multiple cell signaling pathways. Like Jade-1, Jade-3 is required for ING4 and ING5 to associate with histone acetyl transferase (HAT) HBO1 and Eaf6 to form a HBO1 complex that has a histone H4-specific acetyltransferase activity, a reduced activity toward histone H3, and is responsible for the bulk of histone H4 acetylation in vivo. Jade-3 contains a canonical Cys4HisCys3 PHD domain followed by a non-canonical extended PHD (ePHD) domain, Cys2HisCys5HisCys2His, both of which are zinc-binding motifs. This model corresponds to the canonical Cys4HisCys3 PHD finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 2462608851 155 LCCVCRSETVVPGNRLVSCEKCRHAYHQDCH-VPRAPapgEGegtSWVCRQCVFAI 209
Cdd:cd15681     1 ICDVCRSPDSEEGNDMVFCDKCNICVHQACYgILKVP---EG---SWLCRTCVLGI 50

PHD finger found in the transcriptional intermediary factor 1 (TIF1) family and similar proteins; The TIF1 family of transcriptional cofactors includes TIF1alpha (TRIM24), TIF1beta (TRIM28), TIF1gamma (TRIM33), and TIF1delta (TRIM66), which are characterized by an N-terminal RING-finger B-box coiled-coil (RBCC/TRIM) motif and plant homeodomain (PHD) finger followed by a bromodomain in the C-terminal region. TIF1 proteins couple chromatin modifications to transcriptional regulation, signaling, and tumor suppression. They exert a deacetylase-dependent silencing effect when tethered to a promoter region. TIF1alpha, TIF1beta, and TIF1delta can homodimerize and contain a PXVXL motif necessary and sufficient for heterochromatin protein 1(HP1) binding. TIF1alpha and TIF1beta bind nuclear receptors and Kruppel-associated boxes (KRAB) specifically and respectively. In contrast, TIF1delta appears to lack nuclear receptor- and KRAB-binding activity. Moreover, TIF1delta is specifically involved in heterochromatin-mediated gene silencing during postmeiotic phases of spermatogenesis. TIF1gamma is structurally closely related to TIF1alpha and TIF1beta, but has very little functional features in common with them. It does not interact with the KRAB silencing domain of KOX1 or the heterochromatinic proteins HP1alpha, beta, and gamma. It cannot bind to nuclear receptors (NRs). This family also includes Sp100/Sp140 family proteins, the nuclear body SP100 and SP140. Sp110 is a leukocyte-specific component of the nuclear body. It may function as a nuclear hormone receptor transcriptional coactivator that may play a role in inducing differentiation of myeloid cells. It is also involved in resisting intracellular pathogens and functions as an important drug target for preventing intracellular pathogen diseases, such as tuberculosis, hepatic veno-occlusive disease, and intracellular cancers. SP140 is an interferon inducible nuclear leukocyte-specific protein involved in primary biliary cirrhosis and a risk factor in chronic lymphocytic leukemia. It is also implicated in innate immune response to human immunodeficiency virus type 1 (HIV-1) by binding to the virus viral infectivity factor (Vif) protein. Both Sp110 and Sp140 contain a SAND domain, a plant homeodomain (PHD) finger, and a bromodomain (BRD).

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 2462608851 156 CCVCRSetvvpGNRLVSCEKCRHAYHQDCHVPRAPAPGEGEgtsWVCRQC 205
Cdd:cd15541     2 CAVCQN-----GGELLCCDKCPRVFHLDCHIPPIPEFPSGE---WSCSLC 43

PHD finger found in bromodomain and PHD finger-containing (BRPF) proteins; The family of BRPF proteins includes BRPF1, BRD1/BRPF2, and BRPF3. They are scaffold proteins that form monocytic leukemic zinc-finger protein (MOZ)/MOZ-related factor (MORF) H3 histone acetyltransferase (HAT) complexes with other regulatory subunits, such as inhibitor of growth 5 (ING5) and Esa1-associated factor 6 ortholog (EAF6). BRPF proteins have multiple domains, including a canonical Cys4HisCys3 plant homeodomain (PHD) zinc finger followed by a non-canonical extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, a bromodomain and a proline-tryptophan-tryptophan-proline (PWWP) domain. PHD and ePHD fingers both bind to lysine 4 of histone H3 (K4H3), bromodomains interact with acetylated lysines on N-terminal tails of histones and other proteins, and PWWP domains show histone-binding and chromatin association properties. This model corresponds to the canonical Cys4HisCys3 PHD finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 2462608851 155 LCCVCRSETVVPGNRLVSCEKCRHAYHQDCH-VPRAPapgEGEgtsWVCRQCV 206
Cdd:cd15572     3 VCCICLDGECQNSNVILFCDMCNLAVHQECYgVPYIP---EGQ---WLCRRCL 49

PHD finger found in bromodomain and PHD finger-containing protein 2 (BRPF2) and similar proteins; BRPF2, also termed bromodomain-containing protein 1 (BRD1), or BR140-like protein, is encoded by BRL (BR140 Like gene). It is responsible for the bulk of the acetylation of H3K14 and forms a novel monocytic leukemic zinc-finger protein (MOZ)/MOZ-related factor (MORF) H3 histone acetyltransferase (HAT) complex with HBO1 and ING4. The complex is required for full transcriptional activation of the erythroid-specific regulator genes essential for terminal differentiation and survival of erythroblasts in fetal liver. BRPF2 shows widespread expression and localizes to the nucleus within spermatocytes. It contains a cysteine rich region harboring a canonical Cys4HisCys3 plant homeodomain (PHD) finger followed by a non-canonical extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, a bromodomain, and a proline-tryptophan-tryptophan-proline (PWWP) domain. This model corresponds to the canonical Cys4HisCys3 PHD finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 2462608851 155 LCCVCRSETVVPGNRLVSCEKCRHAYHQDCH-VPRAPapgEGEgtsWVCRQCV 206
Cdd:cd15677     3 VCCICMDGECQNSNVILFCDMCNLAVHQECYgVPYIP---EGQ---WLCRHCL 49

PHD finger found in Arabidopsis thaliana pathogenesis-related homeodomain protein (PRHA) and similar proteins; PRHA is a homeodomain protein encoded by a single-copy Arabidopsis thaliana homeobox gene, prha. It shows the capacity to bind to TAATTG core sequence elements but requires additional adjacent bases for high-affinity binding. PRHA contains a plant homeodomain (PHD) finger, a homeodomain, peptide repeats and a putative leucine zipper dimerization domain.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 2462608851 155 LCCVCRSETVVPGNRLVSCE-KCRHAYHQDCHVPR-APAPGEGEGTSWVCRQC 205
Cdd:cd15504     1 FCAKCQSGEASPDNDILLCDgGCNRAYHQKCLEPPlLTEDIPPEDEGWLCPLC 53

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.

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gi 2462608851 100 GQDVLARWT-DGLLYLGTIKKVDSAREVClVQFEDDSQFLVLWKDISP 146
Cdd:cd04508     1 GDRVEAKWSdDGQWYPATVVAVNDDGKYT-VLFDDGNEEEVSEDDIRP 47

PHD finger found in putative E3 ubiquitin-protein ligase UBR7; UBR7, also termed N-recognin-7, is a UBR box-containing protein that belongs to the E3 ubiquitin ligase family that recognizes N-degrons or structurally related molecules for ubiquitin-dependent proteolysis or related processes through the UBR box motif. In addition to the UBR box, UBR7 also harbors a plant homeodomain (PHD) finger. The biochemical properties of UBR7 remain unclear.

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                  ....*....|....*....|....*....|....*....|....*....|....*
gi 2462608851 254 YCYCGGP-----GEWNLKMLQCRSCLQWFHEACTQcLSKPLLYGDRFYEFECCVC 303
Cdd:cd15542     1 YCTCDRPypdpeDEVEDEMIQCVLCEDWFHGRHLG-LTPPEPDPDEFDEMICSGC 54

PHD finger 2 found in histone-lysine N-methyltransferase 2A (KMT2A); KMT2A (also termed ALL-1, CXXC-type zinc finger protein 7, myeloid/lymphoid or mixed-lineage leukemia protein 1 (MLL1), trithorax-like protein (Htrx), or zinc finger protein HRX) is a histone methyltransferase that belongs to the MLL subfamily of H3K4-specific histone lysine methyltransferases (KMT2). It regulates chromatin-mediated transcription through the catalysis of methylation of histone 3 lysine 4 (H3K4), and is frequently rearranged in acute leukemia. KMT2A functions as the catalytic subunit in the MLL1 complex, which also contains WDR5, RbBP5, ASH2L and DPY30 as integral core subunits required for the efficient methylation activity of the complex. The MLL1 complex is highly active and specific for H3K4 methylation. KMT2A contains a CxxC (x for any residue) zinc finger domain, three plant homeodomain (PHD) fingers, a Bromodomain domain, an extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, two FY (phenylalanine tyrosine)-rich domains, and a SET (Suppressor of variegation, Enhancer of zeste, Trithorax) domain. This model corresponds to the second PHD finger.

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gi 2462608851 169 RLVSCEKCRHAYHQDCHVPRAPAPGEGEGTSWVCRQC 205
Cdd:cd15590    14 QLLECNKCRNSYHPECLGPNYPTKPTKKKRVWICTKC 50

PHD finger found in the Sp100/Sp140 family of nuclear body components; The Sp100/Sp140 family includes nuclear body proteins SP100, SP140, and similar proteins. Sp110, also termed interferon-induced protein 41/75, or speckled 110 kDa, or transcriptional coactivator Sp110, is a leukocyte-specific component of the nuclear body. It may function as a nuclear hormone receptor transcriptional coactivator that may play a role in inducing differentiation of myeloid cells. It is also involved in resisting intracellular pathogens and functions as an important drug target for preventing intracellular pathogen diseases, such as tuberculosis, hepatic veno-occlusive disease, and intracellular cancers. Sp110 gene polymorphisms may be associated with susceptibility to tuberculosis in Chinese population. Sp110 contains a Sp100-like domain, a SAND domain, a plant homeodomain (PHD) finger, and a bromodomain (BRD). SP140, also termed lymphoid-restricted homolog of Sp100 (LYSp100), or nuclear autoantigen Sp-140, or speckled 140 kDa, is an interferon inducible nuclear leukocyte-specific protein involved in primary biliary cirrhosis and a risk factor in chronic lymphocytic leukemia. It is also implicated in innate immune response to human immunodeficiency virus type 1 (HIV-1) by binding to the virus's viral infectivity factor (Vif) protein. Sp140 contains a nuclear localization signal, a dimerization domain (HSR or CARD domain), a SAND domain, a PHD finger, and a BRD.

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gi 2462608851 156 CCVCRSEtvvpgNRLVSCEKCRHAYHQDCHVPrapaPGEGEGTSWVCRQC 205
Cdd:cd15626     2 CEVCGQE-----GKLFCCCTCSRVFHEDCHIP----PVEAQRSPWSCTFC 42

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.

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gi 2462608851 100 GQDVLARWT-DGLLYLGTIKKVDSAREVCLVQFE 132
Cdd:cd21182     1 GDKCLAPYSdDGKYYEATIEEITEESDTATVVFD 34

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.

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gi 2462608851 254 YCYCGGPGEWNLKMLQCRSCLQWFHEAC 281
Cdd:cd15554     1 YCICRQPYDVTRFMIECDVCKDWFHGSC 28

PHD finger found in Arabidopsis thaliana histone-lysine N-methyltransferase arabidopsis trithorax-like protein ATX1, ATX2, and similar proteins; The family includes A. thaliana ATX1 and ATX2, both of which are sister paralogs originating from a segmental chromosomal duplication. They are plant counterparts of the Drosophila melanogaster trithorax (TRX) and mammalian mixed-lineage leukemia (MLL1) proteins. ATX1, also termed protein SET domain group 27, or trithorax-homolog protein 1 (TRX-homolog protein 1), is a methyltransferase that trimethylates histone H3 at lysine 4 (H3K4me3). It also acts as a histone modifier and as a positive effector of gene expression. ATX1regulates transcription from diverse classes of genes implicated in biotic and abiotic stress responses. It is involved in dehydration stress signaling in both abscisic acid (ABA)-dependent and ABA-independent pathways. ATX2, also termed protein SET domain group 30, or trithorax-homolog protein 2 (TRX-homolog protein 2), is involved in dimethylating histone H3 at lysine 4 (H3K4me2). Both ATX1 and ATX2 are multi-domain containing proteins that consist of an N-terminal PWWP domain, FYRN- and FYRC (DAST, domain associated with SET in trithorax) domains, a canonical Cys4HisCys3 plant homeodomain (PHD) finger, a non-canonical extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, and a C-terminal SET domain; this model corresponds to the Cys4HisCys3 canonical PHD finger.

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gi 2462608851 156 CCVCRSETVVPGNRLVSCEKCRHAYHQDCHVPRAPAPGEgegtSWVCRQC 205
Cdd:cd15494     2 CSVCGEDEEYEDNLLLQCDKCRMMVHMRCYGVLEPPPGA----LWLCNLC 47

PHD finger 2 found in monocytic leukemia zinc-finger protein (MOZ) and its factor (MORF); MOZ, also termed histone acetyltransferase KAT6A, YBF2/SAS3, SAS2 and TIP60 protein 3 (MYST-3), or runt-related transcription factor-binding protein 2, or zinc finger protein 220, is a MYST-type histone acetyltransferase (HAT) that functions as a coactivator for acute myeloid leukemia 1 protein (AML1)- and p53-dependent transcription. It possesses intrinsic HAT activity to acetylate both itself and lysine (K) residues on histone H2B, histone H3 (K14) and histone H4 (K5, K8, K12 and K16) in vitro and H3K9 in vivo. MOZ-related factor (MORF), also termed MOZ2, or histone acetyltransferase KAT6B, or MOZ, YBF2/SAS3, SAS2 and TIP60 protein 4 (MYST4), is a ubiquitously expressed transcriptional regulator with intrinsic HAT activity. It can interact with the Runt-domain transcription factor Runx2 and form a tetrameric complex with BRPFs, ING5, and EAF6. Both MOZ and MORF are catalytic subunits of HAT complexes that are required for normal developmental programs, such as hematopoiesis, neurogenesis, and skeletogenesis, and are also implicated in human leukemias. MOZ is also the catalytic subunit of a tetrameric inhibitor of growth 5 (ING5) complex, which specifically acetylates nucleosomal histone H3K14. Moreover, MOZ and MORF are involved in regulating transcriptional activation mediated by Runx2 (or Cbfa1), a Runt-domain transcription factor known to play important roles in T cell lymphomagenesis and bone development, and its homologs. MOZ contains a linker histone 1 and histone 5 domains and two plant homeodomain (PHD) fingers. In contrast, MORF contains an N-terminal region containing two PHD fingers, a putative HAT domain, an acidic region, and a C-terminal Ser/Met-rich domain. The family corresponds to the first PHD finger.

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                  ....*....|....*....|....*....|....*....|....*....|
gi 2462608851 156 CCVCRsETVVPGNRLVsCEKCRHAYHQDCHVPRAPAPGEGEgtsWVCRQC 205
Cdd:cd15527     2 CSVCQ-DSGNADNLLF-CDACDKGFHMECHDPPLTRMPKGK---WVCQIC 46