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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958757166 398 CVLCPNKGGAFKQTSDGHWAHVVCAIWIPEVCFANTVFLEPIEGIDSIPPARWKLTCYICKQKGLGAAIQCHKVNCYTAF 477
Cdd:cd15703     1 CVLCPNKGGAFKQTSDGRWAHVVCAIWIPEVCFANTVFLEPVEGVNNIPPARWKLTCYLCKQKGRGAAIQCHKVNCYTAF 80

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1958757166 478 HVTCAQRAGLFMKIEPMRETSLNGTIFTVRKTAYCEAH 515
Cdd:cd15703    81 HVTCAQRAGLFMKIEPVRETGLNGTTFTVRKTAYCENH 118

Extended PHD finger found in bromodomain and PHD finger-containing protein 3 (BRPF3) and similar proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of BRPF3. BRF3 is a homolog of BRPF1 and BRPF2. It is a scaffold protein that forms a novel monocytic leukemic zinc finger protein (MOZ)/MOZ-related factor (MORF) H3 histone acetyltransferase (HAT) complex with other regulatory subunits. BRPF3 contains a plant homeodomain (PHD) finger followed by this non-canonical ePHD finger, a bromodomain, and a proline-tryptophan-tryptophan-proline (PWWP) domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958757166 398 CVLCPNKGGAFKQTSDGHWAHVVCAIWIPEVCFANTVFLEPIEGIDSIPPARWKLTCYICKQKGLGAAIQCHKVNCYTAF 477
Cdd:cd15703     1 CVLCPNKGGAFKQTSDGRWAHVVCAIWIPEVCFANTVFLEPVEGVNNIPPARWKLTCYLCKQKGRGAAIQCHKVNCYTAF 80

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1958757166 478 HVTCAQRAGLFMKIEPMRETSLNGTIFTVRKTAYCEAH 515
Cdd:cd15703    81 HVTCAQRAGLFMKIEPVRETGLNGTTFTVRKTAYCENH 118

PHD-zinc-finger like domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958757166 396 VDCVLCPNKGGAFKQTSDGHWAHVVCAIWIPEVCFANTVFLEPIeGIDSIPPARWKLTCYICKQKGlGAAIQCHKVNCYT 475
Cdd:pfam13832   1 VRCCLCPLRGGALKQTSDGRWVHVLCAIFVPEVRFGNVATMEPI-DVSRIPPERWKLKCVFCKKRS-GACIQCSKGRCTT 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1958757166 476 AFHVTCAQRAGLFMKIEpmretslngTIFTVRKTAYCEAH 515
Cdd:pfam13832  79 AFHVTCAQAAGVYMEPE---------DWPNVVVIAYCQKH 109

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 1958757166 341 DAFCCVCLDDECHNSNVILFCDICNLAVHQECYGVPYIPEGQWLCRCCLQSPSR 394
Cdd:cd15572     1 DAVCCICLDGECQNSNVILFCDMCNLAVHQECYGVPYIPEGQWLCRRCLQSPSR 54

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
                   ....*....|....*....|....*....|....*.
gi 1958757166  453 TCYICKQKGLGAA-IQCHKvnCYTAFHVTCAQRAGL 487
Cdd:smart00249   1 YCSVCGKPDDGGElLQCDG--CDRWYHQTCLGPPLL 34

Extended PHD finger found in bromodomain and PHD finger-containing protein 3 (BRPF3) and similar proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of BRPF3. BRF3 is a homolog of BRPF1 and BRPF2. It is a scaffold protein that forms a novel monocytic leukemic zinc finger protein (MOZ)/MOZ-related factor (MORF) H3 histone acetyltransferase (HAT) complex with other regulatory subunits. BRPF3 contains a plant homeodomain (PHD) finger followed by this non-canonical ePHD finger, a bromodomain, and a proline-tryptophan-tryptophan-proline (PWWP) domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958757166 398 CVLCPNKGGAFKQTSDGHWAHVVCAIWIPEVCFANTVFLEPIEGIDSIPPARWKLTCYICKQKGLGAAIQCHKVNCYTAF 477
Cdd:cd15703     1 CVLCPNKGGAFKQTSDGRWAHVVCAIWIPEVCFANTVFLEPVEGVNNIPPARWKLTCYLCKQKGRGAAIQCHKVNCYTAF 80

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1958757166 478 HVTCAQRAGLFMKIEPMRETSLNGTIFTVRKTAYCEAH 515
Cdd:cd15703    81 HVTCAQRAGLFMKIEPVRETGLNGTTFTVRKTAYCENH 118

Extended PHD finger found in BRPF proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model corresponds to the ePHD finger of the family of BRPF proteins, which includes BRPF1, BRD1/BRPF2, and BRPF3. These 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 plant homeodomain (PHD) zinc finger followed by a non-canonical ePHD finger, a bromodomain and a proline-tryptophan-tryptophan-proline (PWWP) domain. This PHD finger binds to lysine 4 of histone H3 (K4H3), the bromodomain interacts with acetylated lysines on N-terminal tails of histones and other proteins, and the PWWP domain shows histone-binding and chromatin association properties.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958757166 398 CVLCPNKGGAFKQTSDGHWAHVVCAIWIPEVCFANTVFLEPIEGIDSIPPARWKLTCYICKQKGlGAAIQCHKVNCYTAF 477
Cdd:cd15670     1 CVLCPNKGGAFKQTDDGRWAHVVCALWIPEVSFANTVFLEPIDGIQNIPKARWKLTCYICKKRM-GACIQCHKKNCYTAF 79

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1958757166 478 HVTCAQRAGLFMKIEPMREtSLNGTIFTVRKTAYCEAH 515
Cdd:cd15670    80 HVTCAQQAGLYMKIEPVKD-PGNGTSDSVRKEAYCDKH 116

Extended PHD finger found in bromodomain and PHD finger-containing protein 2 (BRPF2) and similar proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of BRPF2. BRPF2 also termed bromodomain-containing protein 1 (BRD1), or BR140-likeprotein, 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 plant homeodomain (PHD) finger followed by a non-canonical ePHD finger, a bromodomain, and a proline-tryptophan-tryptophan-proline (PWWP) domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958757166 398 CVLCPNKGGAFKQTSDGHWAHVVCAIWIPEVCFANTVFLEPIEGIDSIPPARWKLTCYICKQKGLGAAIQCHKVNCYTAF 477
Cdd:cd15702     1 CVLCPNKGGAFKKTDDDRWGHVVCALWIPEVGFANTVFIEPIDGVRNIPPARWKLTCYLCKQKGVGACIQCHKANCYTAF 80

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1958757166 478 HVTCAQRAGLFMKIEPMRETSLNGTIFTVRKTAYCEAH 515
Cdd:cd15702    81 HVTCAQKAGLYMKMEPVKEVTGGGTTFSVRKTAYCDAH 118

Enhancer of polycomb-like; This is a family of EPL1 (Enhancer of polycomb-like) proteins. The EPL1 protein is a member of a histone acetyltransferase complex which is involved in transcriptional activation of selected genes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958757166 177 RLHRISIYDPLKIITEDEL-------TAQDITECNSNKENSEQPQF------------------PAKSKKPSSKGKKKES 231
Cdd:pfam10513   1 RHRRISIKQPLPIISEDEVdgldtspDEDEPSECNSNKENSLHAVEtgvdkeeedevhlkvinaAKKALSSSKKSQNTSE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958757166 232 CSKHAPGTSF-HLPQP---SFRVVDTGsqpeapplPAAYYRYIEKPPEDLDAEVEYDMDEEDMAWLDMVNEKRRADGHSS 307
Cdd:pfam10513  81 SSVPAPNKERlYLPTPdagKFREFERP--------PASYIRFSETVEEELDEGVEYDMDEEDEAWLEELNEKRKSEGVEK 152

                         170
                  ....*....|....*.
gi 1958757166 308 VSADTFELLVDRLEKE 323
Cdd:pfam10513 153 ISEDEFEILMDRFEKE 168

Extended plant homeodomain (PHD) finger, characterized by Cys2HisCys5HisCys2His; PHD finger is also termed LAP (leukemia-associated protein) motif or TTC (trithorax consensus) domain. The extended PHD finger is characterized as Cys2HisCys5HisCys2His, which has 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958757166 398 CVLCPNKGGAFKQ------TSDGHWAHVVCAIWIPEVCFANTVFLEpIEGIDSIPPARWKLTCYICKQKGlGAAIQCHKV 471
Cdd:cd15571     1 CALCPRSGGALKGggalktTSDGLWVHVVCALWSPEVYFDDGTLLE-VEGVSKIPKRRKKLKCSICGKRG-GACIQCSYP 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1958757166 472 NCYTAFHVTCAQRAGLFMKIEPMREtslngtiftvRKTAYCEAH 515
Cdd:cd15571    79 GCPRSFHVSCAIRAGCLFEFEDGPG----------NFVVYCPKH 112

PHD finger found in bromodomain and PHD finger-containing protein 3 (BRPF3) and similar proteins; BRPF3 is a homolog of BRPF1 and BRPF2. It is a scaffold protein that forms a novel monocytic leukemic zinc finger protein (MOZ)/MOZ-related factor (MORF) H3 histone acetyltransferase (HAT) complex with other regulatory subunits. BRPF3 contains 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 1958757166 341 DAFCCVCLDDECHNSNVILFCDICNLAVHQECYGVPYIPEGQWLCRCCLQSPSRP 395
Cdd:cd15678     1 DAFCCVCLDDECHNSNVILFCDICNLAVHQECYGVPYIPEGQWLCRCCLQSPSRP 55

PHD-like zinc-binding domain; The members of this family are annotated as containing PHD domain, but the zinc-binding region here is not typical of PHD domains. The conformation here is a well-conserved cysteine-histidine rich region spanning 90 residues, where the Cys and His are arranged as HxxC(31)CxxC(6)CxxCxxxxCxxxxHxxC (21)CxxH.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958757166 418 HVVCAIWIPEVCFANTVFL-EPIEGIDSIPPARWKLTCYICKQKGlGAAIQCHKVNCYTAFHVTCAQRAGLFMKIEPMRE 496
Cdd:pfam13771   1 HVVCALWSPELVQRGNDSMgFPIEDIEKIPKRRWKLKCYLCKKKG-GACIQCSKKNCRRAFHVTCALEAGLLMQFDEDNG 79

                          90
                  ....*....|....*....
gi 1958757166 497 TslngtiftvrKTAYCEAH 515
Cdd:pfam13771  80 T----------FKSYCKKH 88

PHD finger found in bromodomain and PHD finger-containing protein 1 (BRPF1) and similar proteins; BRPF1, also termed peregrin or protein Br140, is a multi-domain protein that binds histones, mediates monocytic leukemic zinc-finger protein (MOZ)-dependent histone acetylation, and is required for Hox gene expression and segmental identity. It is a close partner of the MOZ histone acetyltransferase (HAT) complex and a novel Trithorax group (TrxG) member with a central role during development. BRPF1 is primarily a nuclear protein that has a broad tissue distribution and is abundant in testes and spermatogonia. It contains 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. BRPF1 may be involved in chromatin remodeling. This model corresponds to the canonical Cys4HisCys3 PHD finger.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1958757166 335 QSLIDEDAFCCVCLDDECHNSNVILFCDICNLAVHQECYGVPYIPEGQWLCRCCLQSPSRPV 396
Cdd:cd15676     1 NALIDEDAVCCICNDGECQNSNVILFCDMCNLAVHQECYGVPYIPEGQWLCRRCLQSPSRAV 62

Extended PHD finger found in Jumonji domain-containing protein 2 (JMJD2) family of histone demethylases; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of JMJD2 proteins. JMJD2 proteins, also termed lysine-specific demethylase 4 histone demethylases (KDM4), have been implicated in various cellular processes including DNA damage response, transcription, cell cycle regulation, cellular differentiation, senescence, and carcinogenesis. They selectively catalyze the demethylation of di- and trimethylated H3K9 and H3K36. This model contains three JMJD2 proteins, JMJD2A-C, which all contain jmjN and jmjC domains in the N-terminal region, followed by a canonical PHD finger, this non-canonical ePHD finger, and a Tudor domain. JMJD2D is not included in this family, since it lacks both PHD and Tudor domains and has a different substrate specificity. JMJD2A-C are required for efficient cancer cell growth.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958757166 398 CVLCPNKGGAFKQTSDGHWAHVVCAIWIPEVCFANTVFLEPIEgIDSIPPARWKLTCYICKQ-----KGLGAAIQCHKVN 472
Cdd:cd15675     1 CCLCCLRGGALKPTTDGRWAHVVCAIAIPEVRFSNVPERGPID-ISKIPPARLKLKCIYCSKitksmSHMGACIQCSTGK 79

                          90       100
                  ....*....|....*....|.
gi 1958757166 473 CYTAFHVTCAQRAGlfMKIEP 493
Cdd:cd15675    80 CTTSFHVTCAHAAG--VQMEP 98

Extended PHD finger found in protein AF-10 and AF-17; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of AF-10 and AF-17. AF-10, also termed ALL1 (acute lymphoblastic leukaemia)-fused gene from chromosome 10 protein, is a transcription factor encoded by gene AF10, a translocation partner of the MLL (mixed-lineage leukaemia) oncogene in leukaemia. AF-10 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. It plays a key role in the survival of uncommitted hematopoietic cells. Moreover, AF-10 functions as a follistatin-related gene (FLRG)-interacting protein. The interaction with FLRG enhances AF10-dependent transcription. It interacts with the human counterpart of yeast Dot1, hDOT1L, and may act as a bridge for the recruitment of hDOT1L to the genes targeted by MLL-AF10. It also interacts with the synovial sarcoma associated protein SYT protein and may play a role in synovial sarcomas and acute leukemias. AF-17, also termed ALL1-fused gene from chromosome 17 protein, is encoded by gene AF17 that has been identified in hematological malignancies as translocation partners of the mixed lineage leukemia gene MLL. It is a putative transcription factor that may play a role in multiple signaling pathways. It is involved in chromatin-mediated gene regulation mechanisms. It functions as a component of the multi-subunit Dot1 complex (Dotcom) and plays a role in the Wnt/Wingless signaling pathway. It also seems to be a downstream target of the beta-catenin/T-cell factor pathway, and participates in G2-M progression. Moreover, it may function as an important regulator of ENaC-mediated Na+ transport and thus blood pressure. Both AF-10 and AF-17 contain an N-terminal plant homeodomain (PHD) finger followed by this non-canonical ePHD finger. The PHD finger is involved in their homo-oligomerization. In the C-terminal region, they possess a leucine zipper domain and a glutamine-rich region. This family also includes ZFP-1, the Caenorhabditis elegans AF10 homolog. It was originally identified as a factor promoting RNAi interference in C. elegans. It also acts as Dot1-interacting protein that opposes H2B ubiquitination to reduce polymerase II (Pol II) transcription.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958757166 398 CVLCPNKGGAFKQTSDGHWAHVVCAIWIPEVCFANTVFLEPIEgIDSIPPARWKLTCYICKQKG------LGAAIQCHKV 471
Cdd:cd15672     1 CELCPHKDGALKRTDNGGWAHVVCALYIPEVRFGNVATMEPII-LQDVPQDRFNKTCYICEEQGreskasTGACMQCNKS 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1958757166 472 NCYTAFHVTCAQRAGLFMkiepmrETSLNGTIfTVRKTAYCEAH 515
Cdd:cd15672    80 GCKQSFHVTCAQMAGLLC------EEAGNYSD-NVKYCGYCSYH 116

Extended PHD finger found in Jumonji domain-containing protein 2B (JMJD2B); The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of JMJD2B. JMJD2B, also termed lysine-specific demethylase 4B (KDM4B), or JmjC domain-containing histone demethylation protein 3B (JHDM3B), specifically antagonizes the trimethyl group from H3K9 in pericentric heterochromatin and reduces H3K36 methylation in mammalian cells. It plays an essential role in the growth regulation of cancer cells by modulating the G1-S transition and promotes cell-cycle progression through the regulation of cyclin-dependent kinase 6 (CDK6). It interacts with heat shock protein 90 (Hsp90) and its stability can be regulated by Hsp90. JMJD2B also functions as a direct transcriptional target of p53, which induces its expression through promoter binding. Moreover, JMJD2B expression can be controlled by hypoxia-inducible factor 1alpha (HIF1alpha) in colorectal cancer and estrogen receptor alpha (ERalpha) in breast cancer. It is also involved in bladder, lung, and gastric cancer. JMJD2B contains jmjN and jmjC domains in the N-terminal region, followed by a canonical PHD finger, this non-canonical ePHD finger, and a Tudor domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958757166 398 CVLCPNKGGAFKQTSDGHWAHVVCAIWIPEVCFANTVFLEPIEgIDSIPPARWKLTCYICK---QKGLGAAIQCHKVNCY 474
Cdd:cd15714     1 CCLCNLRGGALQMTTDERWVHVICAIAVPEARFLNVIERHPVD-VSAIPEQRWKLKCVYCRkrmKKVSGACIQCSYDHCS 79

                          90
                  ....*....|....*.
gi 1958757166 475 TAFHVTCAQRAGLFMK 490
Cdd:cd15714    80 TSFHVTCAHAAGVVME 95

Extended PHD finger found in PHD finger protein 14 (PHF14) and similar proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of PHF14. PHF14 is a novel nuclear transcription factor that controls the proliferation of mesenchymal cells by directly repressing platelet-derived growth factor receptor-alpha (PDGFRalpha) expression. It also acts as an epigenetic regulator and plays an important role in the development of multiple organs in mammals. PHF14 contains three canonical plant homeodomain (PHD) fingers and this non-canonical ePHD finger. It can interact with histones through its PHD fingers.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958757166 398 CVLCPNKGGAFKQTSDGHWAHVVCAIWIPEVCFANTVFLEPIEgIDSIPPARW-KLTCYICKQKGL---GAAIQCHKVNC 473
Cdd:cd15674     1 CELCPNRGGIFKETDTGRWVHLVCALYTPGVAFGDVDKLSPVT-LTEMNYSKWgARECSLCEDPRFartGVCISCDAGMC 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1958757166 474 YTAFHVTCAQRAGLFmkIEPMRETSLNGTIFtvrktAYCEAH 515
Cdd:cd15674    80 KSYFHVTCAQREGLL--SEATDEEDIADPFY-----AYCKQH 114

Extended PHD finger found in protein Jade-1 and similar proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of Jade-1. Jade-1, also termed PHD finger protein 17 (PHF17), is a novel binding partner of von Hippel-Lindau (VHL) tumor suppressor Pvhl, a key regulator of cellular oxygen sensing pathway. It is highly expressed in renal proximal tubules. Jade-1 functions as an essential regulator of multiple cell signaling pathways. It may be involved in the Serine/threonine kinase AKT/AKT1 pathway during renal cancer pathogenesis and normally prevents renal epithelial cell proliferation and transformation. It also acts as a pro-apoptotic and growth suppressive ubiquitin ligase to inhibit canonical Wnt downstream effector beta-catenin for proteasomal degradation and ASA transcription factor associated with histone acetyltransferase activity and with increased abundance of cyclin-dependent kinase inhibitor p21. Moreover, Jade-1 is required for ING4 and ING5 to associate with histone acetyltransferase (HAT) HBO1 and Eaf6 to form a HBO1 complex, and plays a role in epithelial cell regeneration. It has also been identified as a novel component of the nephrocystin protein (NPHP) complex and interacts with the ciliary protein nephrocystin-4 (NPHP4). Jade-1 contains a canonical plant homeodomain (PHD) finger followed by this non-canonical ePHD finger, both of which are zinc-binding motifs.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958757166 398 CVLCPNKGGAFKQTSDG-HWAHVVCAIWIPEVCFANTVFLEPIEGIDSIPPARWKLTCYICKQKgLGAAIQCHKVNCYTA 476
Cdd:cd15704     4 CLLCPKKGGAMKPTRSGtKWVHVSCALWIPEVSIGSPEKMEPITKVSHIPSSRWALVCSLCNEK-VGASIQCSVKNCRTA 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1958757166 477 FHVTCAQRAGLFMKIEPMRETSlngtiftVRKTAYCEAHS 516
Cdd:cd15704    83 FHVTCAFDRGLEMKTILAENDE-------VKFKSYCPKHS 115

Extended PHD finger found in protein AF-17 and similar proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of AF-17. AF-17, also termed ALL1-fused gene from chromosome 17 protein, is encoded by gene AF17 that has been identified in hematological malignancies as a translocation partner of the mixed lineage leukemia gene MLL. It is a putative transcription factor that may play a role in multiple signaling pathways. It is involved in chromatin-mediated gene regulation mechanisms. It functions as a component of the multi-subunit Dot1 complex (Dotcom) and plays a role in the Wnt/Wingless signaling pathway. It also seems to be a downstream target of the beta-catenin/T-cell factor pathway, and participates in G2-M progression. Moreover, it may function as an important regulator of ENaC-mediated Na+ transport and thus blood pressure. AF-17 contains an N-terminal plant homeodomain (PHD) finger followed by a non-canonical ePHD finger.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958757166 396 VDCVLCPNKGGAFKQTSDGHWAHVVCAIWIPEVCFANTVFLEPIEgIDSIPPARWKLTCYICKQKGL------GAAIQCH 469
Cdd:cd15709     3 VRCELCPHKDGALKRTDNGGWAHVVCALYIPEVQFANVLTMEPIV-LQYVPHDRFNKTCYICEEQGReskaasGACMTCN 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1958757166 470 KVNCYTAFHVTCAQRAGLFMKIEPMRetslngtIFTVRKTAYCEAH 515
Cdd:cd15709    82 RHGCRQAFHVTCAQMAGLLCEEEVLE-------VDNVKYCGYCKYH 120

Extended PHD finger (ePHD) found in Jumonji domain-containing protein 2A (JMJD2A); The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of JMJD2A. JMJD2A, also termed lysine-specific demethylase 4A (KDM4A), or JmjC domain-containing histone demethylation protein 3A (JHDM3A), catalyzes the demethylation of di- and trimethylated H3K9 and H3K36. It is involved in carcinogenesis and functions as a transcription regulator that may either stimulate or repress gene transcription. It associates with nuclear receptor co-repressor complex or histone deacetylases. Moreover, JMJD2A forms complexes with both the androgen and estrogen receptor (ER) and plays an essential role in growth of both ER-positive and -negative breast tumors. It is also involved in prostate, colon, and lung cancer progression. JMJD2A contains jmjN and jmjC domains in the N-terminal region, followed by a canonical PHD finger, this non-canonical ePHD finger, and a Tudor domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958757166 398 CVLCPNKGGAFKQTSDGHWAHVVCAIWIPEVCFANTVFLEPIEgIDSIPPARWKLTCYICK---QKGLGAAIQCHKVNCY 474
Cdd:cd15713     1 CCLCSLRGGALQRANDDKWVHVMCAVAVLEARFVNIAERSPVD-VSKIPLQRFKLKCIFCKkrrKRTAGCCVQCSHGRCP 79

                          90
                  ....*....|....*.
gi 1958757166 475 TAFHVTCAQRAGLFMK 490
Cdd:cd15713    80 TSFHASCAQAAGVMMQ 95

PHD finger found in proteins Jade-1, Jade-2, Jade-3, and similar proteins; This family includes proteins Jade-1 (PHF17), Jade-2 (PHF15), and Jade-3 (PHF16), each of which is 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. This family also contains Drosophila melanogaster PHD finger protein rhinoceros (RNO). It is a novel plant homeodomain (PHD)-containing nuclear protein that may function as a transcription factor that antagonizes Ras signaling by regulating transcription of key EGFR/Ras pathway regulators in the Drosophila eye. All Jade proteins contain a canonical Cys4HisCys3 PHD finger followed by a non-canonical extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, both of which are zinc-binding motifs. This model corresponds to the canonical Cys4HisCys3 PHD finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1958757166 344 CCVCLDDECHNSNVILFCDICNLAVHQECYGVPYIPEGQWLCRCC 388
Cdd:cd15573     2 CDVCRSPDSEEGNEMVFCDKCNICVHQACYGIQKIPEGSWLCRTC 46

PHD finger found in protein Jade-1 and similar proteins; Jade-1, also termed PHD finger protein 17 (PHF17), is a novel binding partner of von Hippel-Lindau (VHL) tumor suppressor Pvhl, a key regulator of the cellular oxygen sensing pathway. It is highly expressed in renal proximal tubules. Jade-1 functions as an essential regulator of multiple cell signaling pathways. It may be involved in the serine/threonine kinase AKT/AKT1 pathway during renal cancer pathogenesis and normally prevents renal epithelial cell proliferation and transformation. It also acts as a pro-apoptotic and growth suppressive ubiquitin ligase to inhibit canonical Wnt downstream effector beta-catenin for proteasomal degradation, and as a transcription factor associated with histone acetyltransferase activity and with increased abundance of cyclin-dependent kinase inhibitor p21. Moreover, Jade-1 is required for ING4 and ING5 to associate with histone acetyltransferase (HAT) HBO1 and Eaf6 to form a HBO1 complex, and plays a role in epithelial cell regeneration. It has also been identified as a novel component of the nephrocystin protein (NPHP) complex and interacts with the ciliary protein nephrocystin-4 (NPHP4). Jade-1 contains a canonical Cys4HisCys3 plant homeodomain (PHD) finger followed by a non-canonical extended PHD (ePHD) finger, Cys2HisCys5HisCys2His, both of which are zinc-binding motifs. This model corresponds to the canonical Cys4HisCys3 PHD finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1958757166 344 CCVCLDDECHNSNVILFCDICNLAVHQECYGVPYIPEGQWLCRCC 388
Cdd:cd15679     2 CDVCQSPDGEDGNEMVFCDKCNICVHQACYGILKVPEGSWLCRTC 46

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
                  ....*....|....*....|....*....|....*....|....*.
gi 1958757166 344 CCVCLDDECHNSNVILFCDICNLAVHQECYGVPYIPEGQWLCRCCL 389
Cdd:cd15681     2 CDVCRSPDSEEGNDMVFCDKCNICVHQACYGILKVPEGSWLCRTCV 47

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
                  ....*....|....*....|....*....|....*
gi 1958757166 355 SNVILFCDICNLAVHQECYGVPYIPEG-QWLCRCC 388
Cdd:pfam13831   1 TSPLVYCSKCSVQVHASCYGVPPIPDGdGWKCRRC 35

Extended PHD finger 2 found in histone-lysine N-methyltransferase 2C (KMT2C) and 2D (KMT2D); The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model corresponds to the second ePHD finger of KMT2C, and 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 PHD fingers, two ePHD fingers, a RING finger, an HMG (high-mobilitygroup)-binding motif, and two FY-rich regions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958757166 398 CVLCpnkggafKQTSDGH--------------WAHVVCAIWIPEV------CFANtvflepiegIDSIPPARWKLTCYIC 457
Cdd:cd15666     1 CVLC-------GGEGDGDtdgpgrllnldvdkWVHLNCALWSYEVyetqngALMN---------VEEALRRALTTTCSHC 64

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1958757166 458 KQkgLGAAIQCHKVNCYTAFHVTCAqraglfMKiepmretslNGTIFTVRKTAYCEAH 515
Cdd:cd15666    65 GR--TGATVPCFKPRCANVYHLPCA------IK---------DGCMFFKDKTMLCPSH 105

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 1958757166 343 FCCVClDDECHNSNVILFCDICNLAVHQECYGVPY---IPEGQWLCRCC 388
Cdd:cd15489     1 SCIVC-GKGGDLGGELLQCDGCGKWFHADCLGPPLssfVPNGKWICPVC 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 1958757166 344 CCVCLDDECHNSNVILFCDICNLAVHQECY-----GVPYIPEGQWLCRCCL 389
Cdd:cd15499     2 CSICGGAEARDGNEILICDKCDKGYHQLCHspkvrTSPLEGDEKWFCSRCV 52

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 1958757166 343 FCCVCLDDECHNSNVILFCD-ICNLAVHQECYGVPYIPE------GQWLCRCC 388
Cdd:cd15504     1 FCAKCQSGEASPDNDILLCDgGCNRAYHQKCLEPPLLTEdippedEGWLCPLC 53

Extended PHD finger found in retinoic acid-induced protein 1 (RAI1), transcription factor 20 (TCF-20) and similar proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the C-terminal ePHD/ADD (ATRX-DNMT3-DNMT3L) domain of RAI1 and TCF-20. RAI1, a homolog of stromelysin-1 PDGF (platelet-derived growth factor)-responsive element-binding protein (SPBP, also termed TCF-20), is a chromatin-binding protein implicated in the regulation of gene expression. TCF-20 is involved in transcriptional activation of the MMP3 (matrix metalloprotease 3) promoter. It also functions as a transcriptional co-regulator that enhances or represses the transcriptional activity of certain transcription factors/cofactors, such as specificity protein 1 (Sp1), E twenty-six 1 (Ets1), paired box protein 6 (Pax6), small nuclear RING-finger (SNURF)/RNF4, c-Jun, androgen receptor (AR) and estrogen receptor alpha (ERalpha). Both RAI1 and TCF-20 are strongly enriched in chromatin in interphase HeLa cells, and display low nuclear mobility, and have been implicated in Smith-Magenis syndrome and Potocki-Lupski syndrome.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958757166 398 CVLCpNKGGAFKQTSD------GHWAHVVCAIWIPEVCFANTvflePIEGIDSippARW---KLTCYICKQKGlgAAIQC 468
Cdd:cd15668     1 CVFC-KRGPHYKGLGDlfgpyyEVWVHEDCAVWAPGVYLVGG----KLYGLEE---AVWvakQSVCSSCQQTG--ATIGC 70

                          90
                  ....*....|....*...
gi 1958757166 469 HKVNCYTAFHVTCAQRAG 486
Cdd:cd15668    71 LHKGCKAKYHYPCAVESG 88