HSR domain; The Sp100 protein is a constituent of nuclear domains, also known as nuclear dots (NDs). An ND-targeting region that coincides with a homodimerization domain was mapped in Sp100. Sequences similar to the Sp100 homodimerization/ND-targeting region occur in several other proteins and constitute a novel protein motif, termed HSR domain (for homogeneously-staining region). The HSR domain has also been named ASS (AIRE, Sp-100 and Sp140). This domain is usually found at the amino terminus of proteins that contain a SAND domain pfam01342.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907069675  25 YQLMFKHFKENKVEIASAITKPFPFLMSLRDRDFISEQKFQEYQETCKNLVPVERVVYDILSNVQKKFSRDLLKVIFSKT 104
Cdd:pfam03172   2 EEALFQHFKENKVEIAYAIKKPFPFLEGLRDHSFITEKMYKESLEACRNLVPVQRVVYNVLSELEKTFSLSLLEALFSDV 81

                          90
                  ....*....|....*
gi 1907069675 105 HLKAYPDLKETLKHF 119
Cdd:pfam03172  82 NLKEYPDLIEILKSF 96

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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1907069675 360 KCEVCRDGGLLFCCDTCFRAFHEDCHIPTVEAEITPWSCIFC 401
Cdd:cd15626     1 KCEVCGQEGKLFCCCTCSRVFHEDCHIPPVEAQRSPWSCTFC 42

HSR domain; The Sp100 protein is a constituent of nuclear domains, also known as nuclear dots (NDs). An ND-targeting region that coincides with a homodimerization domain was mapped in Sp100. Sequences similar to the Sp100 homodimerization/ND-targeting region occur in several other proteins and constitute a novel protein motif, termed HSR domain (for homogeneously-staining region). The HSR domain has also been named ASS (AIRE, Sp-100 and Sp140). This domain is usually found at the amino terminus of proteins that contain a SAND domain pfam01342.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907069675  25 YQLMFKHFKENKVEIASAITKPFPFLMSLRDRDFISEQKFQEYQETCKNLVPVERVVYDILSNVQKKFSRDLLKVIFSKT 104
Cdd:pfam03172   2 EEALFQHFKENKVEIAYAIKKPFPFLEGLRDHSFITEKMYKESLEACRNLVPVQRVVYNVLSELEKTFSLSLLEALFSDV 81

                          90
                  ....*....|....*
gi 1907069675 105 HLKAYPDLKETLKHF 119
Cdd:pfam03172  82 NLKEYPDLIEILKSF 96

SAND domain;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907069675  256 ELLPVTCGNLKGVLHKEKFKQGISVKSIQcQNGNWFTPSEFEMMGGYGKSKNWKLSLRCHNWPLKLLIQRNFLP 329
Cdd:smart00258   1 SELPVTCGTVKGILYKKKFKCGISVKCIQ-YEDKWFTPKEFEIEGGKGKSKDWKRSIRCGGSSLRTLMENGTLD 73

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
                  ....*....|....*....|....*....|....*....|....*...
gi 1907069675 361 CEVCR---DGGLLFCCDTCFRAFHEDCHIPTVEAE---ITPWSCIFCR 402
Cdd:pfam00628   2 CAVCGksdDGGELVQCDGCDDWFHLACLGPPLDPAeipSGEWLCPECK 49

HSR domain; The Sp100 protein is a constituent of nuclear domains, also known as nuclear dots (NDs). An ND-targeting region that coincides with a homodimerization domain was mapped in Sp100. Sequences similar to the Sp100 homodimerization/ND-targeting region occur in several other proteins and constitute a novel protein motif, termed HSR domain (for homogeneously-staining region). The HSR domain has also been named ASS (AIRE, Sp-100 and Sp140). This domain is usually found at the amino terminus of proteins that contain a SAND domain pfam01342.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907069675  25 YQLMFKHFKENKVEIASAITKPFPFLMSLRDRDFISEQKFQEYQETCKNLVPVERVVYDILSNVQKKFSRDLLKVIFSKT 104
Cdd:pfam03172   2 EEALFQHFKENKVEIAYAIKKPFPFLEGLRDHSFITEKMYKESLEACRNLVPVQRVVYNVLSELEKTFSLSLLEALFSDV 81

                          90
                  ....*....|....*
gi 1907069675 105 HLKAYPDLKETLKHF 119
Cdd:pfam03172  82 NLKEYPDLIEILKSF 96

SAND domain;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907069675  256 ELLPVTCGNLKGVLHKEKFKQGISVKSIQcQNGNWFTPSEFEMMGGYGKSKNWKLSLRCHNWPLKLLIQRNFLP 329
Cdd:smart00258   1 SELPVTCGTVKGILYKKKFKCGISVKCIQ-YEDKWFTPKEFEIEGGKGKSKDWKRSIRCGGSSLRTLMENGTLD 73

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 1907069675 361 CEVCRDGGLLFCCDTCFRAFHEDCHIPTV-EAEITPWSCIFC 401
Cdd:cd15541     2 CAVCQNGGELLCCDKCPRVFHLDCHIPPIpEFPSGEWSCSLC 43

PHD finger 1 found in PHD finger protein 12 (PHF12); PHF12, also termed PHD factor 1 (Pf1), is a plant homeodomain (PHD) zinc finger-containing protein that bridges the transducin-like enhancer of split (TLE) corepressor to the mSin3A-histone deacetylase (HDAC)-complex, and further represses transcription at targeted genes. PHF12 also interacts with MRG15 (mortality factor-related genes on chromosome 15), a member of the mortality factor (MORF) family of proteins implicated in regulating cellular senescence. PHF12 contains two plant-homeodomain (PHD) zinc fingers followed by a polybasic region. The PHD fingers function downstream of phosphoinositide signaling triggered by the interaction between polybasic regions and phosphoinositides. This model corresponds to the first PHD finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1907069675 361 CEVCRDGGLLFCCDTCFRAFHEDCHIPTVEAEITP---WSCIFC 401
Cdd:cd15533     2 CDSCGEGGDLLCCDRCPASFHLQCCNPPLDEEDLPpgeWLCHRC 45

PHD finger found in transcriptional intermediary factor 1 gamma (TIF1gamma); TIF1gamma, also termed tripartite motif-containing 33 (trim33), or ectodermin, or RFG7, or PTC7, is an E3-ubiquitin ligase that functions as a regulator of transforming growth factor beta (TGFbeta) signaling; it inhibits the Smad4-mediated TGFbeta response by interaction with Smad2/3 or ubiquitylation of Smad4. Moreover, TIF1gamma is an important regulator of transcription during hematopoiesis, as well as a key factor of tumorigenesis. Like other TIF1 family members, TIF1gamma also contains an intrinsic transcriptional silencing function. It can control erythroid cell fate by regulating transcription elongation. It can bind to the anaphase-promoting complex/cyclosome (APC/C) and promotes mitosis. TIF1gamma contains an N-terminal RBCC (RING finger, B-box zinc-fingers, coiled-coil), a plant homeodomain (PHD) finger, followed by a bromodomain in the C-terminal region.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1907069675 361 CEVCRDGGLLFCCDTCFRAFHEDCHIPTVEAEIT-PWSCIFCR 402
Cdd:cd15624     2 CAVCQNGGDLLCCEKCPKVFHLTCHVPTLLSFPSgDWICTFCR 44

PHD finger found in transcription intermediary factor 1-alpha (TIF1-alpha); TIF1-alpha, also termed tripartite motif-containing protein 24 (TRIM24), or E3 ubiquitin-protein ligase TRIM24, or RING finger protein 82, belongs to the TRIM/RBCC protein family. It interacts specifically and in a ligand-dependent manner with the ligand binding domain (LBD) of several nuclear receptors (NRs), including retinoid X (RXR), retinoic acid (RAR), vitamin D3 (VDR), estrogen (ER), and progesterone (PR) receptors. It also associates with heterochromatin-associated factors HP1alpha, MOD1 (HP1beta) and MOD2 (HP1gamma), as well as vertebrate Kruppel-type (C2H2) zinc finger proteins that contain transcriptional silencing domain KRAB. TIF1-alpha is a ligand-dependent co-repressor of retinoic acid receptor (RAR) that interacts with multiple nuclear receptors in vitro via an LXXLL motif, and further acts as a gatekeeper of liver carcinogenesis. It also functions as an E3-ubiquitin ligase targeting p53 and is broadly associated with chromatin silencing. Moreover, it is a chromatin regulator that recognizes specific, combinatorial histone modifications through its C-terminal plant homeodomain (PHD)-Bromodomain (Bromo) region. In addition, it interacts with chromatin and estrogen receptor to activate estrogen-dependent genes associated with cellular proliferation and tumor development. TIF1-alpha contains an N-terminal RBCC (RING finger, B-box zinc-fingers, coiled-coil), a plant homeodomain (PHD) finger, followed by a bromodomain in the C-terminal region.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1907069675 361 CEVCRDGGLLFCCDTCFRAFHEDCHIPTVEAEIT-PWSCIFC 401
Cdd:cd15622     2 CAVCQNGGELLCCEKCPKVFHLSCHVPTLMNFPSgEWICTFC 43

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 1907069675  361 CEVCR---DGGLLFCCDTCFRAFHEDCHIPTVEAEITP--WSCIFC 401
Cdd:smart00249   2 CSVCGkpdDGGELLQCDGCDRWYHQTCLGPPLLEEEPDgkWYCPKC 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 1907069675 360 KCEVCRDGG----LLFCcDTCFRAFHEDCHIPTV-EAEITPWSCIFC 401
Cdd:cd15527     1 TCSVCQDSGnadnLLFC-DACDKGFHMECHDPPLtRMPKGKWVCQIC 46

PHD finger found in transcription intermediary factor 1-beta (TIF1-beta); TIF1-beta, also termed Kruppel-associated Box (KRAB)-associated protein 1 (KAP-1), or KRAB-interacting protein 1 (KRIP-1), or nuclear co-repressor KAP-1, or RING finger protein 96, or tripartite motif-containing protein 28 (TRIM28), or E3 SUMO-protein ligase TRIM28, acts as a nuclear co-repressor that plays a role in transcription and in DNA damage response. Upon DNA damage, the phosphorylation of KAP-1 on serine 824 by the ataxia telangiectasia-mutated (ATM) kinase enhances cell survival and facilitates chromatin relaxation and heterochromatic DNA repair. It also regulates CHD3 nucleosome remodeling during DNA double-strand break (DSB) response. Meanwhile, KAP-1 can be dephosphorylated by protein phosphatase PP4C in the DNA damage response. In addition, KAP-1 is a co-activator of the orphan nuclear receptor NGFI-B (or Nur77) and is involved in NGFI-B-dependent transcription. It is also a coiled-coil binding partner, substrate and activator of the c-Fes protein tyrosine kinase. TIF1-beta contains an N-terminal RBCC (RING finger, B-box zinc-fingers, coiled-coil), which can interact with KRAB zinc finger proteins (KRAB-ZFPs), MDM2, MM1, C/EBPbeta, and mediates homo- and heterodimerization, a plant homeodomain (PHD) finger followed by a bromodomain in the C-terminal region, which interact with SETDB1, Mi-2alpha and other proteins to form complexes with histone deacetylase or methyltransferase activity.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1907069675 361 CEVCRDGGLLFCCDTCFRAFHEDCHIPTVEaEITP--WSCIFC 401
Cdd:cd15623     2 CRVCQKAGALVMCDQCEFCFHLDCHLPALQ-EVPGedWKCLLC 43

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 1907069675 361 CEVCRDGG----LLFCCDTCFRAFHEDCHIPTVEAEITP--WSCIFC 401
Cdd:cd15489     2 CIVCGKGGdlggELLQCDGCGKWFHADCLGPPLSSFVPNgkWICPVC 48

PHD finger 1 found in polycomb repressive complex 2 (PRC2)-associated polycomb-like (PCL) family proteins MTF2, PHF19, and similar proteins; The family includes two PCL family proteins, metal-response element-binding transcription factor 2 (MTF2/PCL2) and PHF19/PCL3, which are homologs of PHD finger protein1 (PHF1). PCL family proteins are accessory components of the polycomb repressive complex 2 (PRC2) core complex and all contain an N-terminal Tudor domain followed by two PHD fingers, and a C-terminal MTF2 domain. They specifically recognize tri-methylated H3K36 (H3K36me3) through their N-terminal Tudor domains. The interaction between their Tudor domains and H3K36me3 is critical for both the targeting and spreading of PRC2 into active chromatin regions and for the maintenance of optimal repression of poised developmental genes where PCL proteins, H3K36me3, and H3K27me3 coexist. Moreover, unlike other PHD finger-containing proteins, the first PHD fingers of PCL proteins do not display histone H3K4 binding affinity and they do not affect the Tudor domain binding to histones. This model corresponds to the first PHD finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1907069675 360 KCEVC-----RDGGLLFCCDTCFRAFHEDCHIPTVEAEI----TPWSCIFC 401
Cdd:cd15499     1 TCSICggaeaRDGNEILICDKCDKGYHQLCHSPKVRTSPlegdEKWFCSRC 51

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1907069675 360 KCEVCRD-----GGLLFCCDTCFRAFHEDCHIPTVEAE----ITPWSCIFC 401
Cdd:cd15579     1 KCNVCLGkssgpLNEILICGKCGLGYHQQCHIPVVDSSddppLTPWFCRRC 51

PHD finger 4 found in nuclear SET domain-containing protein 2 (NSD2); NSD2, also termed histone-lysine N-methyltransferase NSD2, or multiple myeloma SET domain-containing protein (MMSET), or protein trithorax-5 Wolf-Hirschhorn syndrome candidate 1 protein (WHSC1), is overexpressed frequently in the t(4;14) translocation in 15% to 20% of multiple myeloma. It plays important roles in cancer cell proliferation, survival, and tumor growth, by mediating constitutive NF-kappaB signaling via the cytokine autocrine loop. It also enhances androgen receptor (AR)-mediated transcription. The principal chromatin-regulatory activity of NSD2 is dimethylation of histone H3 at lysine 36 (H3K36me2). NSD2 contains a catalytic suppressor of variegation, enhancer of zeste and trithorax (SET) domain, two proline-tryptophan-tryptophan-prolin motif (PWWP) domains, a high mobility group (HMG) box, five PHD (plant-homeodomain) zinc fingers, and an NSD-specific Cys-His rich domain (Cys5HisCysHis). The SET domain is responsible for histone methyltransferase activity. The PWWP, HMG, and PHD fingers mediate chromatin interaction and recognition of histone marks. This model corresponds to the fourth PHD finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1907069675 361 CEVCRDGGLLFCCDTCFRAFHEDCHipTVEAEITPWSCIFCR 402
Cdd:cd15657     2 CFVCSKGGSLLCCESCPAAFHPDCL--NIEMPDGSWFCNDCR 41

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
                  ....*....|....*....|....*....|....*....|.
gi 1907069675 366 DGGLLFCCDTCFRAFHEDCHIPTVEAEITP-----WSCIFC 401
Cdd:cd15504    13 DNDILLCDGGCNRAYHQKCLEPPLLTEDIPpedegWLCPLC 53

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 1907069675 360 KCEVCRDG-----GLLFCCDTCFRAFHEDCHIPTVEAEI-----TPWSCIFC 401
Cdd:cd15502     1 VCIVCQRGhspksNRIVFCDGCNTPYHQLCHDPSIDDEVvedpdAEWFCKKC 52

PHD finger 4 found in nuclear receptor-binding SET domain-containing protein 1 (NSD1); NSD1, also termed H3 Lysine-36 and H4 Lysine-20 specific histone-lysine N-methyltransferase, or androgen receptor coactivator 267 kDa protein, or androgen receptor-associated protein of 267 kDa, or H3-K36-HMTase H4-K20-HMTase, or Lysine N-methyltransferase 3B (KMT3B), or NR-binding SET domain-containing protein, is a lysine methyltransferase that preferentially methylates H3 on Lysine36 (H3-K36) and H4 on Lysine20 (H4-K20), which is primarily associated with active transcription. It plays a role in several pathologies, including but not limited to Sotos and Weaver syndromes, acute myeloid leukemia, breast cancer, neuroblastoma, and glioblastoma formation. It can alter transcription by interacting with the protein NSD1-interacting zinc finger protein 1 (NIZP1). It also mitigates caspase-1 activation by listeriolysin o (LLO) in macrophages, and requires functional LLO for the regulation of IL-1beta secretion. Moreover, NSD1 regulates RNA polymerase II (RNAP II) recruitment to bone morphogenetic protein 4 (BMP4). NSD1 contains a catalytic suppressor of variegation, enhancer of zeste and trithorax (SET) domain, two proline-tryptophan-tryptophan-proline (PWWP) domains, five plant homeodomain (PHD) fingers, and an NSD-specific Cys-His rich domain (Cys5HisCysHis). The SET domain is responsible for histone methyltransferase activity. The PWWP and PHD fingers are involved in protein-protein interactions. This model corresponds to the fourth PHD finger.

                          10        20
                  ....*....|....*....|....
gi 1907069675 361 CEVCRDGGLLFCCDTCFRAFHEDC 384
Cdd:cd15656     2 CFVCSEGGSLLCCESCPAAFHREC 25