JmjC domain, hydroxylase; The JmjC domain belongs to the Cupin superfamily. JmjC-domain proteins may be protein hydroxylases that catalyze a novel histone modification. This is confirmed to be a hydroxylase: the human JmjC protein named Tyw5p unexpectedly acts in the biosynthesis of a hypermodified nucleoside, hydroxy-wybutosine, in tRNA-Phe by catalysing hydroxylation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 464397143  470 WLYVGMCFSSFCWHIEDHWSYSINYLHWGEPKTWYGVPSHAAEQLEEVMRelaPELFESQPDLLHQLVTIMNPNVLMEHG 549
Cdd:pfam02373   1 WLYLGMPFSTTPWHIEDQGLYSINYLHFGAPKVWYIIPPEYAEKFEKVLS---DHFGGEQPDDLLHLNTIISPKQLRENG 77

                  ...
gi 464397143  550 VPV 552
Cdd:pfam02373  78 IPV 80

Small domain found in the jumonji family of transcription factors; To date, this domain always co-occurs with the JmjC domain (although the reverse is not true).

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 464397143    18 ECPVFEPSWEEFTDPLSFIGRIRPLAEKTGICKIRPPKDWQP 59
Cdd:smart00545   1 EIPVFYPTMEEFKDPLAYISKIRPQAEKYGICKVVPPKSWKP 42

JmjC domain, hydroxylase; The JmjC domain belongs to the Cupin superfamily. JmjC-domain proteins may be protein hydroxylases that catalyze a novel histone modification. This is confirmed to be a hydroxylase: the human JmjC protein named Tyw5p unexpectedly acts in the biosynthesis of a hypermodified nucleoside, hydroxy-wybutosine, in tRNA-Phe by catalysing hydroxylation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 464397143  470 WLYVGMCFSSFCWHIEDHWSYSINYLHWGEPKTWYGVPSHAAEQLEEVMRelaPELFESQPDLLHQLVTIMNPNVLMEHG 549
Cdd:pfam02373   1 WLYLGMPFSTTPWHIEDQGLYSINYLHFGAPKVWYIIPPEYAEKFEKVLS---DHFGGEQPDDLLHLNTIISPKQLRENG 77

                  ...
gi 464397143  550 VPV 552
Cdd:pfam02373  78 IPV 80

ARID/BRIGHT DNA binding domain; Members of the recently discovered ARID (AT-rich interaction domain) family of DNA-binding proteins are found in fungi and invertebrate and vertebrate metazoans. ARID-encoding genes are involved in a variety of biological processes including embryonic development, cell lineage gene regulation and cell cycle control. Although the specific roles of this domain and of ARID-containing proteins in transcriptional regulation are yet to be elucidated, they include both positive and negative transcriptional regulation and a likely involvement in the modification of chromatin structure. The basic structure of the ARID domain domain appears to be a series of six alpha-helices separated by beta-strands, loops, or turns, but the structured region may extend to an additional helix at either or both ends of the basic six. Based on primary sequence homology, they can be partitioned into three structural classes: Minimal ARID proteins that consist of a core domain formed by six alpha helices; ARID proteins that supplement the core domain with an N-terminal alpha-helix; and Extended-ARID proteins, which contain the core domain and additional alpha-helices at their N- and C-termini.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 464397143    85 RVRLDFLDQLAKFWELQGSTL-KIPVVERKILDLYALSKIVASKGGFEIVTKEKKWSKVGSRLGYLPG-KGTGSLLKSHY 162
Cdd:smart01014   1 RERELFLDRLRKFMEKRGTPLdKIPVIGGKPLDLYRLYRAVQKRGGFDKVTKKKKWKQVARELGIPPSaTSAGTSLRKHY 80

                   ....*...
gi 464397143   163 ERILYPYE 170
Cdd:smart01014  81 EKYLLPYE 88

Small domain found in the jumonji family of transcription factors; To date, this domain always co-occurs with the JmjC domain (although the reverse is not true).

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 464397143    18 ECPVFEPSWEEFTDPLSFIGRIRPLAEKTGICKIRPPKDWQP 59
Cdd:smart00545   1 EIPVFYPTMEEFKDPLAYISKIRPQAEKYGICKVVPPKSWKP 42

A domain family that is part of the cupin metalloenzyme superfamily; Probable enzymes, but of unknown functions, that regulate chromatin reorganisation processes (Clissold and Ponting, in press).

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 464397143   443 WNLNNMPvLEQSVLAHINVDISGMKV-PWLYVGMCFSSFCWHIEDHwsYSINYLHWGEP 500
Cdd:smart00558   3 WNLAKLP-FKLNLLSDLPEDIPGPDVgPYLYMGMAGSTTPWHIDDY--DLVNYLHQGAG 58

jmjN domain;

                          10        20        30
                  ....*....|....*....|....*....|....
gi 464397143   20 PVFEPSWEEFTDPLSFIGRIRPLAEKTGICKIRP 53
Cdd:pfam02375   1 PVFYPTEEEFKDPLKYIEKIRPLGEKYGICKIVP 34

ARID/BRIGHT DNA binding domain of JARID proteins; The JARID subfamily within the JmjC protein family includes lysine-specific demethylase KDM5A, KDM5B, KDM5C, KDM5D and a Drosophila homolog, protein little imaginal discs (Lid). KDM5A was originally identified as a retinoblastoma protein (Rb)-binding partner and its inactivation may be important for Rb to promote differentiation. It is involved in transcription through interacting with TBP, p107, nuclear receptors, Myc, Sin3/HDAC, Mad1, RBP-J, CLOCK and BMAL1. KDM5B has a restricted expression pattern in the testis, ovary, and transiently in the mammary gland of the pregnant female and has been shown to be upregulated in breast cancer, prostate cancer, and lung cancer, suggesting a potential role in tumorigenesis. Both KDM5A and KDM5B function as trimethylated histone H3 lysine 4 (H3K4me3) demethylases. KDM5C is a H3K4 trimethyl-histone demethylase that catalyzes demethylation of H3K4me3 and H3K4me2 to H3K4me1. It plays a role in neuronal survival and dendrite development. KDM5C defects are associated with X-linked mental retardation (XLMR). KDM5D is a male-specific antigen that shows a demethylase activity specific for di- and tri-methylated histone H3K4 (H3K4me3 and H3K4me2), and has a male-specific function as a histone H3K4 demethylase by recruiting a meiosis-regulatory protein, MSH5, to condensed DNA. KDM5D directly interacts with a polycomb-like protein Ring6a/MBLR, and plays a role in regulation of transcriptional initiation through H3K4 demethylation. The family also includes Drosophila melanogaster protein little imaginal discs (Lid) that functions as a JmjC-dependent trimethyl histone H3K4 (H3K4me3) demethylase, which is required for dMyc-induced cell growth. It positively regulates Hox gene expression in S2 cells. Members of this subfamily contain the catalytic JmjC domain, JmjN, the AT-rich domain interacting domain (ARID)/BRIGHT domain, a C5HC2 zinc finger, as well as two or three plant homeodomain (PHD) fingers.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 464397143  84 TRVRLDFLDQLAKFWELQGSTLKIPVVERKILDLYALSKIVASKGGFEIVTKEKKWSKVGSRLGYLPGKGTGSLLKSHYE 163
Cdd:cd16864    1 TRVKLNFLDQIAKFWELQGSSLKIPNVERKALDLFTLHKIVQEEGGFEEVTKERKWSKVARRLGYPPGKGVGSLLRGHYE 80

                 ....*..
gi 464397143 164 RILYPYE 170
Cdd:cd16864   81 RILYPYD 87

ARID/BRIGHT DNA binding domain of lysine-specific demethylase 5B (KDM5B); KDM5B, also called cancer/testis antigen 31 (CT31), histone demethylase JARID1B, Jumonji/ARID domain-containing protein 1B (JARID1B), PLU-1, or retinoblastoma-binding protein 2 homolog 1 (RBP2-H1 or RBBP2H1A), is a member of the JARID subfamily within the JmjC proteins. It has a restricted expression pattern in the testis, ovary, and transiently in the mammary gland of the pregnant female and has been shown to be upregulated in breast cancer, prostate cancer, and lung cancer, suggesting a potential role in tumorigenesis. KDM5B acts as a histone demethylase that catalyzes the removal of trimethylation of lysine 4 on histone H3 (H3K4me3), induced by polychlorinated biphenyls (PCBs). It also mediates demethylation of H3K4me2 and H3K4me1. Moreover, KDM5B functions as a negative regulator of hematopoietic stem cell (HSC) self-renewal and progenitor cell activity. KDM5B has also been shown to interact with the DNA binding transcription factors BF-1 and PAX9, as well as TIEG1/KLF10 (transforming growth factor-beta inducible earlygene-1/Kruppel-like transcription factor 10), and possibly function as a transcriptional corepressor. KDM5B contains the catalytic JmjC domain, a JmjN domain, an AT-rich DNA-interacting domain (ARID, also known as BRIGHT), a C5HC2 zinc finger, as well as three plant homeodomain (PHD) fingers.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 464397143  81 EAMTRVRLDFLDQLAKFWELQGSTLKIPVVERKILDLYALSKIVASKGGFEIVTKEKKWSKVGSRLGYLPGKGTGSLLKS 160
Cdd:cd16874    1 EAQTRVKLNFLDQIAKFWELQGCTLKIPHVERKILDLFQLNKLVAEEGGFDLVCKERKWTKIATKMGFAPGKAVGSHIRA 80

                 ....*....
gi 464397143 161 HYERILYPY 169
Cdd:cd16874   81 HYERILYPY 89

PHD finger 1 found in Lysine-specific demethylase 5A (KDM5A); KDM5A (also termed Histone demethylase JARID1A, Jumonji/ARID domain-containing protein 1A, or Retinoblastoma-binding protein 2 (RBBP-2 or RBP2)) was originally identified as a retinoblastoma protein (Rb)-binding partner and its inactivation may be important for Rb to promote differentiation. It is involved in transcription through interacting with TBP, p107, nuclear receptors, Myc, Sin3/HDAC, Mad1, RBP-J, CLOCK and BMAL1. KDM5A functions as a trimethylated histone H3 lysine 4 (H3K4me3) demethylase that belongs to the JARID subfamily within the JmjC proteins. It also displays DNA-binding activities that can recognize the specific DNA sequence CCGCCC. KDM5A contains the catalytic JmjC domain, JmjN, the BRIGHT domain, which is an AT-rich interacting domain (ARID), and a Cys5HisCys2 zinc finger, as well as three plant homeodomain (PHD) fingers. This model corresponds to the first PHD finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 464397143 295 VCMFCGRGNNEDKLLLCDGCDDSYHTFCLLPPLPDVPKGDWRCPKCVAE 343
Cdd:cd15602    1 VCLFCGRGNNEDKLLLCDGCDDSYHTFCLIPPLPDVPKGDWRCPKCVAE 49

ARID/BRIGHT DNA binding domain; Members of the recently discovered ARID (AT-rich interaction domain) family of DNA-binding proteins are found in fungi and invertebrate and vertebrate metazoans. ARID-encoding genes are involved in a variety of biological processes including embryonic development, cell lineage gene regulation and cell cycle control. Although the specific roles of this domain and of ARID-containing proteins in transcriptional regulation are yet to be elucidated, they include both positive and negative transcriptional regulation and a likely involvement in the modification of chromatin structure. The basic structure of the ARID domain domain appears to be a series of six alpha-helices separated by beta-strands, loops, or turns, but the structured region may extend to an additional helix at either or both ends of the basic six. Based on primary sequence homology, they can be partitioned into three structural classes: Minimal ARID proteins that consist of a core domain formed by six alpha helices; ARID proteins that supplement the core domain with an N-terminal alpha-helix; and Extended-ARID proteins, which contain the core domain and additional alpha-helices at their N- and C-termini.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 464397143    85 RVRLDFLDQLAKFWELQGSTL-KIPVVERKILDLYALSKIVASKGGFEIVTKEKKWSKVGSRLGYLPG-KGTGSLLKSHY 162
Cdd:smart01014   1 RERELFLDRLRKFMEKRGTPLdKIPVIGGKPLDLYRLYRAVQKRGGFDKVTKKKKWKQVARELGIPPSaTSAGTSLRKHY 80

                   ....*...
gi 464397143   163 ERILYPYE 170
Cdd:smart01014  81 EKYLLPYE 88

ARID/BRIGHT DNA binding domain; This domain is know as ARID for AT-Rich Interaction Domain, and also known as the BRIGHT domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 464397143   87 RLDFLDQLAKFWELQGSTLK-IPVVERKILDLYALSKIVASKGGFEIVTKEKKWSKVGSRLGYLPGKGT-GSLLKSHYER 164
Cdd:pfam01388   2 KELFLKSLRKFHEKRGTPLKqIPVIGGKPVDLYKLYKAVQKLGGYDKVTEKNLWREVAEKLGFPPSAASaATQLKQIYEK 81

                  ....*.
gi 464397143  165 ILYPYE 170
Cdd:pfam01388  82 YLLPYE 87

PHD finger 1 found in Drosophila melanogaster protein little imaginal discs (Lid) and similar proteins; Drosophila melanogaster Lid, also termed Retinoblastoma-binding protein 2 homolog, is identified genetically as a trithorax group (trxG) protein that is a Drosophila homolog of the human protein JARID1A/kdm5A, a member of the JARID subfamily within the JmjC proteins. Lid functions as a JmjC-dependent trimethyl histone H3K4 (H3K4me3) demethylase, which is required for dMyc-induced cell growth. It positively regulates Hox gene expression in S2 cells. Lid contains the catalytic JmjC domain, JmjN, the BRIGHT domain, which is an AT-rich interacting domain (ARID), and a Cys5HisCys2 zinc finger, as well as three plant homeodomain (PHD) fingers. This model corresponds to the first PHD finger of Lid.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 464397143 295 VCMFCGRGNNEDKLLLCDGCDDSYHTFCLLPPLPDVPKGDWRCPKC 340
Cdd:cd15605    1 VCHTCGRGDGEESMLLCDGCDDSYHTFCLLPPLSEVPKGDWRCPKC 46

ARID/BRIGHT DNA binding domain family; The AT-rich interaction domain (ARID) family of transcription factors, found in a broad array of organisms from fungi to mammals, is characterized by a highly conserved, helix-turn-helix DNA binding domain that binds to the major groove of DNA. The ARID domain, also called BRIGHT, was first identified in the mouse B-cell-specific transcription factor Bright and in the product of the dead ringer (dri) gene of Drosophila melanogaster. ARID family members are implicated in normal development, differentiation, cell cycle regulation, transcriptional activation and chromatin remodeling. Different family members exhibit different DNA-binding properties. Drosophila Dri, mammalian ARID3A/3B/3C and ARID5A/5B, selectively bind AT-rich sites. However, ARID1A/1B, Drosophila Osa, yeast SWI1, ARID2, ARID4A/4B, JARID1A/1B/1C/1D, and JARID2, bind DNA without sequence specificity.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 464397143  87 RLDFLDQLAKFWELQGSTL-KIPVVERKILDLYALSKIVASKGGFEIVTKEKKWSKVGSRLGY-LPGKGTGSLLKSHYER 164
Cdd:cd16100    2 REEFLEQLRAFLESRGTPLlKPPTIGGKPLDLYKLYRAVVSRGGYEKVTEKKLWKEVARKLGLpTSSTSAAQALKRIYEK 81

                 ....*.
gi 464397143 165 ILYPYE 170
Cdd:cd16100   82 YLLPFE 87

PHD finger found in Remodeling and spacing factor 1 (Rsf-1); Rsf-1, also termed HBV pX-associated protein 8, or Hepatitis B virus X-associated protein alpha (HBxAPalpha), or p325 subunit of RSF chromatin-remodeling complex, is a novel nuclear protein with histone chaperon function. It is a subunit of an ISWI chromatin remodeling complex, remodeling and spacing factor (RSF), and plays a role in mediating ATPase-dependent chromatin remodeling and conferring tumor aggressiveness in common carcinomas. As an ataxia-telangiectasia mutated (ATM)-dependent chromatin remodeler, Rsf-1 facilitates DNA damage checkpoints and homologous recombination repair. It regulates the mitotic spindle checkpoint and chromosome instability through the association with serine/threonine kinase BubR1 (BubR1) and Hepatitis B virus (HBV) X protein (HBx) in the chromatin fraction during mitosis. It also interacts with cyclin E1 and promotes tumor development. Rsf-1 contains a plant homeodomain (PHD) finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 464397143 296 CMFCGRGNNEDKLLLCDGCDDSYHTFCLLPPLPDVPKGDWRCPKC 340
Cdd:cd15543    2 CRKCGLSDHPEWILLCDRCDAGYHTACLRPPLMIIPDGNWFCPPC 46

PHD finger 1 found in Schizosaccharomyces pombe Lid2 complex component Lid2p and similar proteins; Lid2p is a trimethyl H3K4 (H3K4me3) demethylase responsible for H3K4 hypomethylation in heterochromatin. It interacts with the histone lysine-9 methyltransferase, Clr4, through the Dos1/Clr8-Rik1 complex, and mediates H3K9 methylation and small RNA production. It also acts cooperatively with the histone modification enzymes Set1 and Lsd1 and plays an essential role in cross-talk between H3K4 and H3K9 methylation in euchromatin. Lid2p contains a JmjC domain, three PHD fingers and a JmjN domain. This model corresponds to the first PHD finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 464397143 295 VCMFCGRGNNEDKLLLCDGCDDSYHTFCLLPPLPDVPKGDWRCPKC 340
Cdd:cd15519    1 GCEVCGLDDNEGEVLLCDGCDAEYHTSCLDPPLGEIPPGTWFCPSC 46

PHD finger 5 found in Histone-lysine N-methyltransferase 2C (KMT2C) and PHD finger 4 found in KMT2D; KMT2C, also termed myeloid/lymphoid or mixed-lineage leukemia protein 3 (MLL3), or homologous to ALR protein, is a histone H3 lysine 4 (H3K4) lysine methyltransferase that functions as a circadian factor contributing to genome-scale circadian transcription. It is a component of a large complex that acts as a coactivator of multiple transcription factors, including the bile acid (BA)-activated nuclear receptor, farnesoid X receptor (FXR), a critical player in BA homeostasis. The MLL3 complex is essential for p53 transactivation of small heterodimer partner (SHP). KMT2C is also a part of activating signal cointegrator-2 (ASC-2)-containing complex (ASCOM) that contains the transcriptional coactivator nuclear receptor coactivator 6 (NCOA6), KMT2C and its paralog MLL4. The ASCOM complex is critical for nuclear receptor (NR) activation of bile acid transporter genes and is down regulated in cholestasis. KMT2D, also termed ALL1-related protein (ALR), is encoded by the gene that was named MLL4, a fourth human homolog of Drosophila trithorax, located on chromosome 12. It enzymatically generates trimethylated histone H3 Lysine 4 (H3K4me3). It plays an essential role in differentiating the human pluripotent embryonal carcinoma cell line NTERA-2 clone D1 (NT2/D1) stem cells by activating differentiation-specific genes, such as HOXA1-3 and NESTIN. KMT2D is also a part of ASCOM. Both KMT2C and KMT2D contain the catalytic domain SET, several plant homeodomain (PHD) fingers, extended PHD (ePHD) fingers, Cys2HisCys5HisCys2His, a RING finger, an HMG (high-mobility group)-binding motif, and two FY-rich regions. This model corresponds to the fifth PHD finger of KMT2C and the fourth PHD finger of KMT2D.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 464397143 295 VCMFCGRGNNEDKLLLCDGCDDSYHTFCLLPPLPDVPKGDWRCPKCV 341
Cdd:cd15513    1 VCEGCGKASDESRLLLCDDCDISYHTYCLDPPLQTVPKGGWKCKWCV 47

PHD finger found in PHD and RING finger domain-containing protein 1 (PHRF1); PHRF1, also termed KIAA1542, or CTD-binding SR-like protein rA9, is a ubiquitin ligase that induces the ubiquitination of TGIF (TG-interacting factor) at lysine 130. It acts as a tumor suppressor that promotes the transforming growth factor (TGF)-beta cytostatic program through selective release of TGIF-driven promyelocytic leukemia protein (PML) inactivation. PHRF1 contains a plant homeodomain (PHD) finger and a RING finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 464397143 296 CMFCGRGNNEDKLLLCDGCDDSYHTFCLLPPLPDVPKGDWRCPKC 340
Cdd:cd15536    2 CEVCGRSDREDRLLLCDGCDAGYHMECLTPPLDEVPIEEWFCPEC 46

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
                   ....*....|....*....|....*....|....*....|....*..
gi 464397143   295 VCMFCGRGNNEDKLLLCDGCDDSYHTFCLLPPLPD-VPKGDWRCPKC 340
Cdd:smart00249   1 YCSVCGKPDDGGELLQCDGCDRWYHQTCLGPPLLEeEPDGKWYCPKC 47

ARID/BRIGHT DNA binding domain of Arabidopsis thaliana high mobility group B proteins HMGB9, HMGB10, HMGB11, HMGB15 and similar proteins; This subfamily includes a group of conserved plant DNA-binding proteins, including HMGB9 (or ARID-HMG1), HMGB10 (or ARID-HMG2), HMGB11, and HMGB15. They have been termed ARID-HMG proteins, due to containing two DNA-binding domains, an N-terminal AT-rich DNA-interacting domain (ARID, also known as BRIGHT), and a C-terminal high mobility group (HMG)-box domain. They are widely expressed in Arabidopsis and localize primarily to the nucleus. HMGB9/ARID-HMG1 binds specifically to A/T-rich DNA. HMGB15 is a transcription factor predominantly expressed in mature pollen grains and pollen tubes. It may work in the form of a homodimer, or interact with HMGB9, HMGB10 and HMGB11 to form heteromultimers in plant cells. HMGB15 is required for pollen tube growth in Arabidopsis and is involved in transcriptional regulation through the interaction with AGL66 and AGL104.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 464397143  90 FLDQLAKFWELQGSTLKIPVVERKILDLYALSKIVASKGGFEIVTKEKKWSKVGSRLGYLPGKGTGS-LLKSHYERILYP 168
Cdd:cd16872    5 FWETLRKFHESLGTKFRIPIVGGKELDLHRLYKEVTSRGGLEKVIKDRKWKEVAAVFNFPPTITNASfVLRKYYLSLLHH 84

                 ..
gi 464397143 169 YE 170
Cdd:cd16872   85 YE 86

PHD finger 2 found in class II Chromodomain-Helicase-DNA binding (CHD) proteins; Class II CHD proteins includes chromodomain-helicase-DNA-binding protein CHD3, CHD4, and CHD5, which are nuclear and ubiquitously expressed chromatin remodelling ATPases generally associated with histone deacetylases (HDACs). They are involved in DNA Double Strand Break (DSB) signaling, DSB repair and/or p53-dependent pathways such as apoptosis and senescence, as well as in the maintenance of genomic stability, and/or cancer prevention. They function as subunits of the Nucleosome Remodelling and Deacetylase (NuRD) complex, which is generally associated with gene repression, heterochromatin formation, and overall chromatin compaction. In contrast to the class I CHD enzymes (CHD1 and CHD2), class II CHD proteins lack identifiable DNA-binding domains, but possess a C-terminal coiled-coil region. Moreover, in addition to the tandem chromodomains and a helicase domain, they all harbor tandem plant homeodomain (PHD) zinc fingers involved in the recognition of methylated histone tails. This model corresponds to the second PHD finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 464397143 295 VCMFCGRGNNedkLLLCDGCDDSYHTFCLLPPLPDVPKGDWRCPKC 340
Cdd:cd15532    1 FCRVCKDGGE---LLCCDGCPSSYHLHCLNPPLAEIPDGDWFCPRC 43

PHD finger found in bromodomain adjacent to zinc finger domain protein 2B (BAZ2B); BAZ2B, also termed WALp4, is a bromodomain-containing protein whose biological role is still elusive. It shows high sequence similarly with BAZ2A, which is the large subunit of the SNF2h-containing chromatin-remodeling complex NoRC that induces nucleosome sliding in an ATP-and histone H4 tail-dependent fashion. BAZ2B contains a TAM (TIP5/ARBP/MBD) domain, an Apolipophorin-III like domain, a DDT domain, four AT-hooks, BAZ 1 and BAZ 2 motifs, a WAKZ (WSTF/Acf1/KIAA0314/ZK783.4) motif, a plant homeodomain (PHD) finger, and a bromodomain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 464397143 296 CMFCGRGNNEDKLLLCDGCDDSYHTFCLLPPLPDVPKGDWRCPKCVA 342
Cdd:cd15630    3 CQICRKGDNEELLLLCDGCDKGCHTYCHRPKITTIPEGDWFCPACIA 49

PHD finger found in ubiquitin-like PHD and RING finger domain-containing protein UHRF1 and UHRF2; UHRF1 is a unique chromatin effector protein that integrates the recognition of both histone PTMs and DNA methylation. It is essential for cell proliferation and plays a critical role in the development and progression of many human carcinomas, such as laryngeal squamous cell carcinoma (LSCC), gastric cancer (GC), esophageal squamous cell carcinoma (ESCC), colorectal cancer, prostate cancer, and breast cancer. UHRF1 acts as a transcriptional repressor through its binding to histone H3 when it is unmodified at Arg2. Its overexpression in human lung fibroblasts results in downregulation of expression of the tumour suppressor pRB. It also plays a role in transcriptional repression of the cell cycle regulator p21. Moreover, UHRF1-dependent repression of transcription factors can facilitate the G1-S transition. It interacts with Tat-interacting protein of 60 kDa (TIP60) and induces degradation-independent ubiquitination of TIP60. It is also an N-methylpurine DNA glycosylase (MPG)-interacting protein that binds MPG in a p53 status-independent manner in the DNA base excision repair (BER) pathway. In addition, UHRF1 functions as an epigenetic regulator that is important for multiple aspects of epigenetic regulation, including maintenance of DNA methylation patterns and recognition of various histone modifications. UHRF2 was originally identified as a ubiquitin ligase acting as a small ubiquitin-like modifier (SUMO) E3 ligase that enhances zinc finger protein 131 (ZNF131) SUMOylation but does not enhance ZNF131 ubiquitination. It also ubiquitinates PCNP, a PEST-containing nuclear protein. Moreover, UHRF2 functions as a nuclear protein involved in cell-cycle regulation and has been implicated in tumorigenesis. It interacts with cyclins, CDKs, p53, pRB, PCNA, HDAC1, DNMTs, G9a, methylated histone H3 lysine 9, and methylated DNA. It interacts with the cyclin E-CDK2 complex, ubiquitinates cyclins D1 and E1, induces G1 arrest, and is involved in the G1/S transition regulation. Furthermore, UHRF2 is a direct transcriptional target of the transcription factor E2F-1 in the induction of apoptosis. It recruits HDAC1 and binds to methyl-CpG. UHRF2 also participates in the maturation of Hepatitis B virus (HBV) by interacting with the HBV core protein and promoting its degradation. Both UHRF1 and UHRF2 contain an N-terminal ubiquitin-like domain (UBL), a tandem Tudor domain (TTD), a plant homeodomain (PHD) finger, a SET- and RING-associated (SRA) domain, and a C-terminal RING finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 464397143 296 CMFCGRGNNEDKLLLCDGCDDSYHTFCLLPPLPDVPKGD-WRCPKC 340
Cdd:cd15525    2 CHVCGGKQDPEKQLLCDECDMAYHLYCLDPPLTSLPDDDeWYCPDC 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.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 464397143 296 CMFCGRGNNEDKLLLCDGCDDSYHTFCLLPPLPDVPKGDWRCPKC 340
Cdd:cd15527    2 CSVCQDSGNADNLLFCDACDKGFHMECHDPPLTRMPKGKWVCQIC 46

PHD finger 2 found in Histone-lysine N-methyltransferase 2C (KMT2C); KMT2C, also termed myeloid/lymphoid or mixed-lineage leukemia protein 3 (MLL3) or homologous to ALR protein, is a histone H3 lysine 4 (H3K4) lysine methyltransferase that functions as a circadian factor contributing to genome-scale circadian transcription. It is a component of a large complex that acts as a coactivator of multiple transcription factors, including the bile acid (BA)-activated nuclear receptor, farnesoid X receptor (FXR), a critical player in BA homeostasis. The MLL3 complex is essential for p53 transactivation of small heterodimer partner (SHP). KMT2C is also a part of activating signal cointegrator-2 (ASC-2)-containing complex (ASCOM) that contains the transcriptional coactivator nuclear receptor coactivator 6 (NCOA6), KMT2C and its paralog MLL4. The ASCOM complex is critical for nuclear receptor (NR) activation of bile acid transporter genes and is down regulated in cholestasis. KMT2C contains several plant homeodomain (PHD) fingers, two extended PHD (ePHD) fingers, Cys2HisCys5HisCys2His, an ATPase alpha beta signature, a high mobility group (HMG)-1 box, a SET (Suppressor of variegation, Enhancer of zeste, Trithorax) domain and two FY (phenylalanine tyrosine)-rich domains. This model corresponds to the second PHD finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 464397143 295 VCMFCGRGNNEDKLLLCDGCDDSYHTFCLLPPLPDVPKGDWRCPKC 340
Cdd:cd15594    1 VCQTCRQPGDDNKMLVCDTCDKGYHTFCLQPVMTTIPKNGWKCKNC 46

PHD finger 2 found in Histone-lysine N-methyltransferase 2C (KMT2C) and 2D (KMT2D); KMT2C, also termed myeloid/lymphoid or mixed-lineage leukemia protein 3 (MLL3) or homologous to ALR protein, is a histone H3 lysine 4 (H3K4) lysine methyltransferase that functions as a circadian factor contributing to genome-scale circadian transcription. It is a component of a large complex that acts as a coactivator of multiple transcription factors, including the bile acid (BA)-activated nuclear receptor, farnesoid X receptor (FXR), a critical player in BA homeostasis. The MLL3 complex is essential for p53 transactivation of small heterodimer partner (SHP). KMT2C is also a part of activating signal cointegrator-2 (ASC-2)-containing complex (ASCOM) that contains the transcriptional coactivator nuclear receptor coactivator 6 (NCOA6), KMT2C and its paralog MLL4. The ASCOM complex is critical for nuclear receptor (NR) activation of bile acid transporter genes and is down regulated in cholestasis. KMT2D, also termed ALL1-related protein (ALR), is encoded by the gene that was named MLL4, a fourth human homolog of Drosophila trithorax, located on chromosome 12. It enzymatically generates trimethylated histone H3 Lysine 4 (H3K4me3). It plays an essential role in differentiating the human pluripotent embryonal carcinoma cell line NTERA-2 clone D1 (NT2/D1) stem cells by activating differentiation-specific genes, such as HOXA1-3 and NESTIN. KMT2D is also a part of ASCOM. Both KMT2C and KMT2D contain the catalytic domain SET, five plant homeodomain (PHD) fingers, two extended PHD (ePHD) fingers, Cys2HisCys5HisCys2His, a RING finger, an HMG (high-mobilitygroup)-binding motif, and two FY-rich regions. This model corresponds to the second PHD finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 464397143 295 VCMFCGRGNNEDKLLLCDGCDDSYHTFCLLPPLPDVPKGDWRCPKC 340
Cdd:cd15510    1 VCQACRQPGDDTKMLVCETCDKGYHTSCLRPVMSSIPKYGWKCKNC 46

PHD finger 1 found in autoimmune regulator (AIRE); AIRE, also termed autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) protein, functions as a regulator of gene transcription in the thymus. It is essential for prevention of autoimmunity. AIRE plays a critical role in the induction of central tolerance. It promotes self-tolerance through tissue-specific antigen (TSA) expression. It also acts as an active regulator of chondrocyte differentiation. AIRE contains a homogeneously-staining region (HSR) or caspase-recruitment domain (CARD), a nuclear localization signal (NLS), a SAND (for Sp100, AIRE, nuclear phosphoprotein 41/75 or NucP41/75, and deformed epidermal auto regulatory factor 1 or Deaf1) domain, two plant homeodomain (PHD) fingers, and four LXXLL (where L stands for leucine) motifs. This model corresponds to the first PHD finger that recognizes the unmethylated tail of histone H3 and targets AIRE-dependent genes.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 464397143 296 CMFCGRGNNedkLLLCDGCDDSYHTFCLLPPLPDVPKGDWRCPKC 340
Cdd:cd15539    2 CAVCGDGGE---LLCCDGCPRAFHLACLVPPLTLIPSGTWRCSSC 43

PHD finger 2 found in d4 gene family proteins; The family includes proteins coded by three members of the d4 gene family, DPF1 (neuro-d4), DPF2 (ubi-d4/Requiem), and DPF3 (cer-d4), which function as transcription factors and are involved in transcriptional regulation of genes by changing the condensed/decondensed state of chromatin in the nucleus. DPF2 is ubiquitously expressed and it acts as a transcription factor that may participate in developmentally programmed cell death. DPF1 and DPF3 are expressed predominantly in neural tissues, and they may be involved in the transcription regulation of neuro-specific gene clusters. The d4 family proteins show distinct domain organization with domain 2/3 in the N-terminal region, a Cys2His2 (C2H2) zinc finger or Kruppel-type zinc finger in the central part and two adjacent plant homeodomain (PHD) fingers (d4-domain) in the C-terminal part of the molecule. This model corresponds to the second PHD finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 464397143 296 CMFCGRGNNEDKLLLCDGCDDSYHTFCLLPPLPDVPKGDWRCPKC 340
Cdd:cd15530    2 CSLCGTSENDDQLLFCDDCDRGYHMYCLSPPMSEPPEGSWSCHLC 46

PHD finger 2 found in PHD finger protein 10 (PHF10) and similar proteins; PHF10, also termed BRG1-associated factor 45a (BAF45a), or XAP135, is a ubiquitously expressed transcriptional regulator that is required for maintaining the undifferentiated status of neuroblasts. It contains a SAY (supporter of activation of yellow) domain and two adjacent plant homeodomain (PHD) fingers. This model corresponds to the second PHD finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 464397143 295 VCMFCGRGNNEDKLLLCDGCDDSYHTFCLlpPLPDVPKGDWRCPKC 340
Cdd:cd15529    1 TCTKCGDPHDEDKMMFCDQCDRGYHTFCV--GLRSIPDGRWICPLC 44

ARID/BRIGHT DNA binding domain of yeast SWI/SNF chromatin-remodeling complex subunit Swi1p and similar proteins; Saccharomyces cerevisiae Swi1p, also called SWI/SNF chromatin-remodeling complex subunit SWI1, regulatory protein GAM3, or transcription regulatory protein ADR6, is a transcription regulatory protein that is a subunit of the SWI/SNF complex, which plays critical roles in the regulation of gene transcription and expression. It can exist as a prion, [SWI(+)], which demonstrates a link between prionogenesis and global transcriptional regulation. Swi1p contains an AT-rich DNA-interacting domain (ARID, also known as BRIGHT) that binds DNA nonspecifically. This subfamily also includes Schizosaccharomyces pombe SWI/SNF chromatin-remodeling complex subunit sol1 (sol1p, also known as switch one-like protein). sol1p is a homolog of S. cerevisiae Swi1p and is also a part of SWI/SNF chromatin-remodeling complex.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 464397143  90 FLDQLAKFWELQGSTLK-IPVVERKILDLYALSKIVASKGGFEIVTKEKKWSKVGSRLGYLPGKGT--GSLLKSHYERIL 166
Cdd:cd16871    6 FMKSLREFMAKRGTPIEqQPVIGGRPVNLFRLYQLVQKLGGSRQVTQNNQWPRVAQKLGFPPEQNPqvAQQLAQIYQRYL 85

                 ....*
gi 464397143 167 YPYEL 171
Cdd:cd16871   86 LPYEE 90

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
                 ....*....|....*....|....*....|....*....|....*...
gi 464397143 295 VCMFCGR-GNNEDKLLLCDGCDDSYHTFCLLPPLPD-VPKGDWRCPKC 340
Cdd:cd15489    1 SCIVCGKgGDLGGELLQCDGCGKWFHADCLGPPLSSfVPNGKWICPVC 48

ARID/BRIGHT DNA binding domain of AT-rich interactive domain-containing protein 3A (ARID3A) and similar proteins; ARID3A, also called B-cell regulator of IgH transcription (Bright), dead ringer-like protein 1 (Dril1), or E2F-binding protein 1 (E2FBP1), is an ubiquitously expressed DNA-binding protein that has been implicated in embryonic patterning, cell lineage gene regulation, and cell cycle control, chromatin remodeling and transcriptional regulation. It was originally identified as a B cell-specific trans-activator of immunoglobulin heavy-chain (IgH) transcription, which increases immunoglobulin transcription in antigen-activated B cells and plays regulatory roles in hematopoiesis. It also functions as an E2F transcription regulator, inducing promyelocytic leukemia protein (PML) reduction and suppressing the formation of PML-nuclear bodies. It antagonizes the p16(INK4A)-Rb tumor suppressor machinery by regulating PML stability. ARID3A transcriptional activity can be modulated by SUMO (Small Ubiquitin-related Modifier) modification through the interaction with the SUMO-conjugating enzyme Ubc9. ARID3A also plays an important role in marginal zone B lymphocyte development and autoantibody production. Furthermore, ARID3A is a direct p53 target gene. It controls cell growth in a p53-dependent manner. ARID3A contains an AT-rich DNA-interacting domain (ARID, also known as BRIGHT), a SUMO-I conjugation (SUMO) motif and a multifunctional homomerization/nuclear export REKLES domain, which consists of two subdomains: a modestly conserved N-terminal REKLES alpha and a highly conserved (among ARID3 orthologous proteins) C-terminal REKLES beta.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 464397143  70 FTPRVQRLNELEAMTRvRLDFLDQLAKFWELQGSTL-KIPVVERKILDLYALSKIVASKGGFEIVTKEKKWSKVGSRLGy 148
Cdd:cd16878    7 YEEQFKQLYELDGDPK-RKEFLDDLFSFMQKRGTPVnRIPIMAKQVLDLYMLYVLVTEKGGLVEVINKKLWREITKGLN- 84

                         90       100       110
                 ....*....|....*....|....*....|.
gi 464397143 149 LPGKGTGS--LLKSHYERILYPYELFQSGVS 177
Cdd:cd16878   85 LPTSITSAafTLRTQYMKYLYPYECEKRGLS 115

PHD finger found in ubiquitin-like PHD and RING finger domain-containing protein 2 (UHRF2); UHRF2 (also termed Np95/ICBP90-like RING finger protein (NIRF), Np95-like RING finger protein, nuclear protein 97, nuclear zinc finger protein Np97, RING finger protein 107, or E3 ubiquitin-protein ligase UHRF2) was originally identified as a ubiquitin ligase acting as a small ubiquitin-like modifier (SUMO) E3 ligase that enhances zinc finger protein 131 (ZNF131) SUMOylation but does not enhance ZNF131 ubiquitination. It also ubiquitinates PCNP, a PEST-containing nuclear protein. Moreover, UHRF2 functions as a nuclear protein involved in cell-cycle regulation and has been implicated in tumorigenesis. It interacts with cyclins, CDKs,p53, pRB, PCNA, HDAC1, DNMTs, G9a, methylated histone H3 lysine 9, and methylated DNA. It interacts with the cyclin E-CDK2 complex, ubiquitinates cyclins D1 and E1, induces G1 arrest, and is involved in the G1/S transition regulation. Furthermore, UHRF2 is a direct transcriptional target of the transcription factor E2F-1 in the induction of apoptosis. It recruits HDAC1 and binds to methyl-CpG. UHRF2 also participates in the maturation of Hepatitis B virus (HBV) by interacting with the HBV core protein and promoting its degradation. UHRF2 contains an N-terminal ubiquitin-like domain (UBL), a tandem Tudor domain (TTD), a plant homeodomain (PHD) finger, a SET- and RING-associated (SRA) domain, and a C-terminal RING finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 464397143 296 CMFCGRGNNEDKLLLCDGCDDSYHTFCLLPPLPDVPKG-DWRCPKC 340
Cdd:cd15617    2 CYVCGGKQDAHMQLLCDECNMAYHIYCLNPPLDKIPEDeDWYCPSC 47

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
                 ....*....|....*....|....*....|....*....|...
gi 464397143 298 FCGRGNNEDKLLLCDGCDDSYHTFCLLPPLPDVPKGDWRCPKC 340
Cdd:cd15541    1 WCAVCQNGGELLCCDKCPRVFHLDCHIPPIPEFPSGEWSCSLC 43

PHD finger found in PHD finger protein 21B (PHF21B); PHF21B is a plant homeodomain (PHD) finger-containing protein whose biological function remains unclear. It shows high sequence similarity with PHF21A, which is associated with LSD1, a lysine (K)-specific histone demethylase and inhibits LSD1-mediated histone demethylation in vitro. PHD fingers can recognize the unmodified and modified histone H3 tail, and some have been found to interact with non-histone proteins.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 464397143 296 CMFCGRGNNedkLLLCDGCDDSYHTFCLLPPLPDVPKGDWRCPKC 340
Cdd:cd15524    2 CAACKRGGN---LQPCGTCPRAYHLDCLDPPLKTAPKGVWVCPKC 43

ARID/BRIGHT DNA binding domain of AT-rich interactive domain-containing protein 5A (ARID5A) and similar proteins; ARID5A, also called modulator recognition factor 1 (MRF-1), is an estrogen receptor alpha (ER alpha)-interacting protein that is expressed abundantly in cardiovascular tissues and suppresses ER alpha-induced transactivation. It also associates with thyroid receptor alpha (TR alpha) and retinoid X receptor alpha (RXR alpha) in a ligand-dependent manner, and with ER beta, androgen receptor (AR), and the retinoic acid receptor (RAR) in a ligand-independent manner. ARID5A functions as a negative regulator of RORgamma-induced Th17 cell differentiation and may be involved in the pathogenesis of rheumatoid arthritis (RA). Moreover, it is an important transcriptional partner of the transcription factor sex determining region Y (SRY)-box protein 9 (Sox9) in stimulation of chondrocyte-specific transcription. Meanwhile, ARID5A plays an important role in promotion of inflammatory processes and autoimmune diseases. It works as a unique RNA binding protein, which stabilizes interleukin-6 (IL-6) but not tumor necrosis factor-alpha (TNF-alpha) mRNA through binding to the 3' untranslated region (UTR) of IL-6 mRNA, and inhibits the destabilizing effect of regnase-1 on IL-6 mRNA. ARID5A contains an AT-rich DNA-interacting domain (ARID, also known as BRIGHT).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 464397143  90 FLDQLAKFWELQGSTL-KIPVVERKILDLYALSKIVASKGGFEIVTKEKKWSKVGSRLGYLPGKGT-GSLLKSHYERILY 167
Cdd:cd16884    5 FLVNLYKFMKERNTPIeRIPHLGFKQINLWKIYKAVEKLGGYELVTARRLWKNVYDELGGSPGSTSaATCTRRHYERLVL 84

                 ...
gi 464397143 168 PYE 170
Cdd:cd16884   85 PYV 87

PHD finger 1 found in class II Chromodomain-Helicase-DNA binding (CHD) proteins; Class II CHD proteins includes chromodomain-helicase-DNA-binding protein CHD3, CHD4, and CHD5, which are nuclear and ubiquitously expressed chromatin remodelling ATPases generally associated with histone deacetylases (HDACs). They are involved in DNA Double Strand Break (DSB) signaling, DSB repair and/or p53-dependent pathways such as apoptosis and senescence, as well as in the maintenance of genomic stability, and/or cancer prevention. They function as subunits of the Nucleosome Remodelling and Deacetylase (NuRD) complex, which is generally associated with gene repression, heterochromatin formation, and overall chromatin compaction. In contrast to the class I CHD enzymes (CHD1 and CHD2), class II CHD proteins lack identifiable DNA-binding domains, but possess a C-terminal coiled-coil region. Moreover, in addition to the tandem chromodomains and a helicase domain, they all harbor tandem plant homeodomain (PHD) zinc fingers involved in the recognition of methylated histone tails. This model corresponds to the first PHD finger.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 464397143 296 CMFCGRGNnedKLLLCDGCDDSYHTFCLLPPLPDVPKGDWRCPKC 340
Cdd:cd15531    2 CEVCQQGG---EIILCDTCPRAYHLVCLDPELEKAPEGKWSCPHC 43

ARID/BRIGHT DNA binding domain of AT-rich interactive domain-containing protein 1A (ARID1A) and similar proteins; ARID1A, also called B120, BRG1-associated factor 250a (BAF250A), Osa homolog 1(OSA1), SWI-like protein, SWI/SNF complex protein p270, or SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin subfamily F member 1 (SWI1), has been identified as a novel tumor suppressor in various tumor types. It interacts with BRG1 adenosine triphosphatase to form a SWItch/Sucrose NonFermentable (SWI/SNF) chromatin remodeling protein complex, which plays a critical role in transcriptional control and gene expression. ARID1A contains an AT-rich DNA-interacting domain (ARID, also known as BRIGHT), and Eld/Osa homology domains (EHD) 1 and 2 within the C-terminus. The ARID in ARID1A binds nonspecific DNA in general and plays an important role in targeting SWI/SNF to chromatin. The EHD1 may be capable of mediating an intramolecular association with EHD2, and/or an intermolecular association resulting in homo- or hetero-dimerization. The EHD2 binds Swi2/Brahma homologue Brahma-related gene 1 (BRG1, also known as Snf2b), a human homologue of yeast Swi2.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 464397143  90 FLDQLAKFWELQGSTL-KIPVVERKILDLYALSKIVASKGGFEIVTKEKKWSKVGSRLGYLPGKGTGSLLKSHYERILYP 168
Cdd:cd16876    6 WVDRYLAFTEEKAMGMtNLPAVGRKPLDLYRLYVSVKEIGGLTQVNKNKKWRELATNLNVGTSSSAASSLKKQYIQCLYA 85

                 ..
gi 464397143 169 YE 170
Cdd:cd16876   86 FE 87

PHD finger found in Schizosaccharomyces pombe SWM histone demethylase complex subunits Phf1 (Phf1p) and Phf2 (Phf2p); Phf1p and Phf2p are components of the SWM histone demethylase complex that specifically demethylates histone H3 at lysine 9 (H3K9me2), a specific tag for epigenetic transcriptional activation. They function as corepressors and play roles in regulating heterochromatin propagation and euchromatic transcription. Both Phf1p and Phf2p contain a plant homeodomain (PHD) finger.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 464397143 295 VCMFCGRGNNEDK--LLLCDGCDDSYHTFCLLPPLPD----VPKGDWRCPKC 340
Cdd:cd15502    1 VCIVCQRGHSPKSnrIVFCDGCNTPYHQLCHDPSIDDevveDPDAEWFCKKC 52

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
                 ....*....|....*....|....*....|....*....|....*...
gi 464397143 295 VCMFC--GRGNNEDKLLLCDGCDDSYHTFCLlpPLPDVPKGDWRCPKC 340
Cdd:cd15492    1 VCDVCldGESEDDNEIVFCDGCNVAVHQSCY--GIPLIPEGDWFCRKC 46