PLU-1-like protein; Sequences in this family bear similarity to the central region of PLU-1. This is a nuclear protein that may have a role in DNA-binding and transcription, and is closely associated with the malignant phenotype of breast cancer. This region is found in various other Jumonji/ARID domain-containing proteins (see pfam02373, pfam01388).

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720434809  730 TWANKVRVALEveDGRKRSLEELRALESEARERRFPNSELLQRLKNCLSEAEACVSRALGLVSGQ-------EAGPDRVA 802
Cdd:pfam08429    1 TWAEKVEEALE--EEPKPSLKELRALLNEAEKIKFPLPELLQDLRAFVQRANKWVEEAQQLLSRKqqtrrknEAEEDERE 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720434809  803 GLQMTLAELRDFLGQMNNLPCAMHQIGDVKGILEQVEAYQTEAREALVSQPSSPGL--LQSLLERGQQLGVEVPEAQQLQ 880
Cdd:pfam08429   79 REKRTVEELRKLLEEADNLPFDCPEIEQLKELLEEIEEFQKRAREALSEEPPSLSIeeLEELLEEGKSFNVDLPELEELE 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720434809  881 RQVEQARWLDEVKRTLAPSarRGTLAIMRGLLVAGASVAPSPAVDKAQAELQELLTIAERWEEKAHLCLEaRQKHPPATL 960
Cdd:pfam08429  159 KVLEQLKWLEEVRETSRKK--SLTLEDVRELIEEGVELGIPPPYEDLMAELQELLTAGERWEEKAKELLS-RERVSLAQL 235

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720434809  961 EAIIHEAENIPVHLPNIQSLKEALAKARAWIADVDEI-QNGD--HYPCLDDLEGLVAVGRDLPVGLEELRQLELQVLTAH 1037
Cdd:pfam08429  236 EALSKEAQEIPVSLPNLAALDEILKKAREWQRQIEALyQRSDfgKRPTLDELEELLAKGESLPVKPEGLSDLEKEVKRAE 315

                          330       340
                   ....*....|....*....|.
gi 1720434809 1038 SWREKASKTFLKKNSCYTLLE 1058
Cdd:pfam08429  316 DWMRRGKKLFLKKNAPLHLLE 336

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1720434809   68 RIQRLNEL-EIVVEEGGYETICKDRRWARVAQRLNYPPGKNIGSLLRSHYERIVYPYEMYQSG 129
Cdd:cd16875     30 RILDLYSLsKIVQEEGGYEAICKDRRWARVAQRLGYPPGKNIGSLLRSHYERIIYPYEMYQSG 92

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1720434809 1145 ICVCGQVPAgVGALQCDLCQDWFHGRCVTVPrlLSSQRSSLPSSPLLAWWEWDTKFLCPLC 1205
Cdd:cd15608      1 VCVCGQPPR-PGMLRCHLCQDWFHGGCVSFP--RLLSSSGPHSSPSLAWWEWDTRFLCPLC 58

C5HC2 zinc finger; Predicted zinc finger with eight potential zinc ligand binding residues. This domain is found in Jumonji. This domain may have a DNA binding function.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1720434809  665 CIKCKTTCFLSALACYDCPDGLVCLSHINDLCK-CSSSRQYLRYRYTLDELPAM 717
Cdd:pfam02928    1 CSFCKAYCYLSAVTCSKCSGKVVCLRHAKELCSdCPPSKRTLLYRYTDDELEAL 54

PLU-1-like protein; Sequences in this family bear similarity to the central region of PLU-1. This is a nuclear protein that may have a role in DNA-binding and transcription, and is closely associated with the malignant phenotype of breast cancer. This region is found in various other Jumonji/ARID domain-containing proteins (see pfam02373, pfam01388).

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720434809  730 TWANKVRVALEveDGRKRSLEELRALESEARERRFPNSELLQRLKNCLSEAEACVSRALGLVSGQ-------EAGPDRVA 802
Cdd:pfam08429    1 TWAEKVEEALE--EEPKPSLKELRALLNEAEKIKFPLPELLQDLRAFVQRANKWVEEAQQLLSRKqqtrrknEAEEDERE 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720434809  803 GLQMTLAELRDFLGQMNNLPCAMHQIGDVKGILEQVEAYQTEAREALVSQPSSPGL--LQSLLERGQQLGVEVPEAQQLQ 880
Cdd:pfam08429   79 REKRTVEELRKLLEEADNLPFDCPEIEQLKELLEEIEEFQKRAREALSEEPPSLSIeeLEELLEEGKSFNVDLPELEELE 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720434809  881 RQVEQARWLDEVKRTLAPSarRGTLAIMRGLLVAGASVAPSPAVDKAQAELQELLTIAERWEEKAHLCLEaRQKHPPATL 960
Cdd:pfam08429  159 KVLEQLKWLEEVRETSRKK--SLTLEDVRELIEEGVELGIPPPYEDLMAELQELLTAGERWEEKAKELLS-RERVSLAQL 235

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720434809  961 EAIIHEAENIPVHLPNIQSLKEALAKARAWIADVDEI-QNGD--HYPCLDDLEGLVAVGRDLPVGLEELRQLELQVLTAH 1037
Cdd:pfam08429  236 EALSKEAQEIPVSLPNLAALDEILKKAREWQRQIEALyQRSDfgKRPTLDELEELLAKGESLPVKPEGLSDLEKEVKRAE 315

                          330       340
                   ....*....|....*....|.
gi 1720434809 1038 SWREKASKTFLKKNSCYTLLE 1058
Cdd:pfam08429  316 DWMRRGKKLFLKKNAPLHLLE 336

ARID/BRIGHT DNA binding domain of lysine-specific demethylase KDM5C and KDM5D; This group includes KDM5C and KDM5D, both of which belong to the JARID subfamily within the JmjC proteins. KDM5C, also called histone demethylase JARID1C, Jumonji/ARID domain-containing protein 1C, protein SmcX, or protein Xe169, 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, also called histocompatibility Y antigen (H-Y), histone demethylase JARID1D, Jumonji/ARID domain-containing protein 1D, or protein SmcY, 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. Both KDM5C and KDM5D contain 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 two plant homeodomain (PHD) fingers.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1720434809   68 RIQRLNEL-EIVVEEGGYETICKDRRWARVAQRLNYPPGKNIGSLLRSHYERIVYPYEMYQSG 129
Cdd:cd16875     30 RILDLYSLsKIVQEEGGYEAICKDRRWARVAQRLGYPPGKNIGSLLRSHYERIIYPYEMYQSG 92

PHD finger 2 found in Lysine-specific demethylase 5C (KDM5C) and 5D (KDM5D); The family includes KDM5C and KDM5D, both of which belong to the JARID subfamily within the JmjC proteins. KDM5C (also termed Histone demethylase JARID1C, Jumonji/ARIDdomain-containing protein 1C, SmcX, or Xe169) 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 (also termed Histocompatibility Y antigen (H-Y), Histone demethylase JARID1D, Jumonji/ARID domain-containing protein 1D, or SmcY) 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. Both KDM5C and KDM5D contain the catalytic JmjC domain, JmjN, the BRIGHT domain, which is an AT-rich interacting domain (ARID), and a Cys5HisCys2 zinc finger, as well as two plant homeodomain (PHD) fingers. This model corresponds to the second PHD finger.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1720434809 1145 ICVCGQVPAgVGALQCDLCQDWFHGRCVTVPrlLSSQRSSLPSSPLLAWWEWDTKFLCPLC 1205
Cdd:cd15608      1 VCVCGQPPR-PGMLRCHLCQDWFHGGCVSFP--RLLSSSGPHSSPSLAWWEWDTRFLCPLC 58

C5HC2 zinc finger; Predicted zinc finger with eight potential zinc ligand binding residues. This domain is found in Jumonji. This domain may have a DNA binding function.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1720434809  665 CIKCKTTCFLSALACYDCPDGLVCLSHINDLCK-CSSSRQYLRYRYTLDELPAM 717
Cdd:pfam02928    1 CSFCKAYCYLSAVTCSKCSGKVVCLRHAKELCSdCPPSKRTLLYRYTDDELEAL 54

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 1720434809    25 RDPLGYIAKIRPIAEKSGICKIRPPADWQppfaVEVDNFRFtpriqrlneLEIVVEEGGYETICKDRRWARVAQRLNYPP 104
Cdd:smart01014    1 RERELFLDRLRKFMEKRGTPLDKIPVIGG----KPLDLYRL---------YRAVQKRGGFDKVTKKKKWKQVARELGIPP 67

                            90       100
                    ....*....|....*....|.
gi 1720434809   105 G-KNIGSLLRSHYERIVYPYE 124
Cdd:smart01014   68 SaTSAGTSLRKHYEKYLLPYE 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
                   ....*....|....*....|....*....|....*....|....*....
gi 1720434809   77 IVVEEGGYETICKDRRWARVAQRLNYPPG-KNIGSLLRSHYERIVYPYE 124
Cdd:pfam01388   39 AVQKLGGYDKVTEKNLWREVAEKLGFPPSaASAATQLKQIYEKYLLPYE 87

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 1720434809   432 WNLNVMPvLEQSVLCHINADISGMKV-PWLYVGMVFSAFCWHIEDHWsySINYLHWGEP 489
Cdd:smart00558    3 WNLAKLP-FKLNLLSDLPEDIPGPDVgPYLYMGMAGSTTPWHIDDYD--LVNYLHQGAG 58

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1720434809 1146 CVCGQVPAGVGALQCDLCQDWFHGRCVTVPRLLSSQRsslpsspllawwewDTKFLCPLCMRS 1208
Cdd:pfam00628    3 AVCGKSDDGGELVQCDGCDDWFHLACLGPPLDPAEIP--------------SGEWLCPECKPK 51

PLU-1-like protein; Sequences in this family bear similarity to the central region of PLU-1. This is a nuclear protein that may have a role in DNA-binding and transcription, and is closely associated with the malignant phenotype of breast cancer. This region is found in various other Jumonji/ARID domain-containing proteins (see pfam02373, pfam01388).

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720434809  730 TWANKVRVALEveDGRKRSLEELRALESEARERRFPNSELLQRLKNCLSEAEACVSRALGLVSGQ-------EAGPDRVA 802
Cdd:pfam08429    1 TWAEKVEEALE--EEPKPSLKELRALLNEAEKIKFPLPELLQDLRAFVQRANKWVEEAQQLLSRKqqtrrknEAEEDERE 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720434809  803 GLQMTLAELRDFLGQMNNLPCAMHQIGDVKGILEQVEAYQTEAREALVSQPSSPGL--LQSLLERGQQLGVEVPEAQQLQ 880
Cdd:pfam08429   79 REKRTVEELRKLLEEADNLPFDCPEIEQLKELLEEIEEFQKRAREALSEEPPSLSIeeLEELLEEGKSFNVDLPELEELE 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720434809  881 RQVEQARWLDEVKRTLAPSarRGTLAIMRGLLVAGASVAPSPAVDKAQAELQELLTIAERWEEKAHLCLEaRQKHPPATL 960
Cdd:pfam08429  159 KVLEQLKWLEEVRETSRKK--SLTLEDVRELIEEGVELGIPPPYEDLMAELQELLTAGERWEEKAKELLS-RERVSLAQL 235

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720434809  961 EAIIHEAENIPVHLPNIQSLKEALAKARAWIADVDEI-QNGD--HYPCLDDLEGLVAVGRDLPVGLEELRQLELQVLTAH 1037
Cdd:pfam08429  236 EALSKEAQEIPVSLPNLAALDEILKKAREWQRQIEALyQRSDfgKRPTLDELEELLAKGESLPVKPEGLSDLEKEVKRAE 315

                          330       340
                   ....*....|....*....|.
gi 1720434809 1038 SWREKASKTFLKKNSCYTLLE 1058
Cdd:pfam08429  316 DWMRRGKKLFLKKNAPLHLLE 336

ARID/BRIGHT DNA binding domain of lysine-specific demethylase KDM5C and KDM5D; This group includes KDM5C and KDM5D, both of which belong to the JARID subfamily within the JmjC proteins. KDM5C, also called histone demethylase JARID1C, Jumonji/ARID domain-containing protein 1C, protein SmcX, or protein Xe169, 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, also called histocompatibility Y antigen (H-Y), histone demethylase JARID1D, Jumonji/ARID domain-containing protein 1D, or protein SmcY, 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. Both KDM5C and KDM5D contain 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 two plant homeodomain (PHD) fingers.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1720434809   68 RIQRLNEL-EIVVEEGGYETICKDRRWARVAQRLNYPPGKNIGSLLRSHYERIVYPYEMYQSG 129
Cdd:cd16875     30 RILDLYSLsKIVQEEGGYEAICKDRRWARVAQRLGYPPGKNIGSLLRSHYERIIYPYEMYQSG 92

PHD finger 1 found in Lysine-specific demethylase KDM5A, KDM5B, KDM5C, KDM5D and similar proteins; The JARID subfamily within the JmjC proteins 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 (H3K4me2 and H3K4me3), 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. This family also includes Drosophila melanogaster protein little imaginal discs (Lid) that functions as a JmjC-dependent H3K4me3 demethylase, which is required for dMyc-induced cell growth. It positively regulates Hox gene expression in S2 cells. Members in this family contain the catalytic JmjC domain, JmjN, the BRIGHT domain, which is an AT-rich interacting domain (ARID), and a Cys5HisCys2 zinc finger, as well as two or three plant homeodomain (PHD) fingers. This model corresponds to the first PHD finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1720434809  284 VCRMCSRGDEDDKLLLCDGCDDNYHIFCLLPPLPEIPKGVWRCPKC 329
Cdd:cd15515      1 ICQVCGRGDDEDKLLLCDGCDDSYHTFCLIPPLPDIPPGDWRCPKC 46

ARID/BRIGHT DNA binding domain of lysine-specific demethylase 5A (KDM5A); KDM5A, also called 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; 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 the 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, 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
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1720434809   76 EIVVEEGGYETICKDRRWARVAQRLNYPPGKNIGSLLRSHYERIVYPYEMYQSG 129
Cdd:cd16873     39 KIVASEGGFEMVTKEKKWSKVGSRMGYLPGKGTGSLLKSHYERILYPYELFQSG 92

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 1720434809  284 VCRMCSRGDEDDKLLLCDGCDDNYHIFCLLPPLPEIPKGVWRCPKC 329
Cdd:cd15605      1 VCHTCGRGDGEESMLLCDGCDDSYHTFCLLPPLSEVPKGDWRCPKC 46

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 1720434809    13 ECPVFEPSWAEFRDPLGYIAKIRPIAEKSGICKIRPPADWQP 54
Cdd:smart00545    1 EIPVFYPTMEEFKDPLAYISKIRPQAEKYGICKVVPPKSWKP 42

PHD finger 2 found in Lysine-specific demethylase KDM5A, KDM5B, KDM5C, KDM5D, and similar proteins; The JARID subfamily within the JmjC proteins 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 in this family contain the catalytic JmjC domain, JmjN, the BRIGHT domain, which is an AT-rich interacting domain (ARID), and a Cys5HisCys2 zinc finger, as well as two or three plant homeodomain (PHD) fingers. This model corresponds to the second PHD finger.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1720434809 1145 ICVCGQVPAGvGALQCDLCQDWFHGRCVTVPRLLSSQRSslpssplLAWWEWDTKFLCPLC 1205
Cdd:cd15516      1 ICLCGKALAA-GMLQCELCQDWFHGSCVAVPRISSSPRP-------LAWWEGDRKFLCPLC 53

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
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1720434809   71 RLNELeiVVEEGGYETICKDRRWARVAQRLNYPPGKNIGSLLRSHYERIVYPY 123
Cdd:cd16874     39 QLNKL--VAEEGGFDLVCKERKWTKIATKMGFAPGKAVGSHIRAHYERILYPY 89

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 1720434809  285 CRMCSRGDEDDKLLLCDGCDDNYHIFCLLPPLPEIPKGVWRCPKC 329
Cdd:cd15543      2 CRKCGLSDHPEWILLCDRCDAGYHTACLRPPLMIIPDGNWFCPPC 46

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 1720434809    25 RDPLGYIAKIRPIAEKSGICKIRPPADWQppfaVEVDNFRFtpriqrlneLEIVVEEGGYETICKDRRWARVAQRLNYPP 104
Cdd:smart01014    1 RERELFLDRLRKFMEKRGTPLDKIPVIGG----KPLDLYRL---------YRAVQKRGGFDKVTKKKKWKQVARELGIPP 67

                            90       100
                    ....*....|....*....|.
gi 1720434809   105 G-KNIGSLLRSHYERIVYPYE 124
Cdd:smart01014   68 SaTSAGTSLRKHYEKYLLPYE 88

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 1720434809  284 VCRMCSRGDEDDKLLLCDGCDDNYHIFCLLPPLP--EIPKGVWRCPKCV 330
Cdd:pfam00628    1 YCAVCGKSDDGGELVQCDGCDDWFHLACLGPPLDpaEIPSGEWLCPECK 49

PHD finger found in bromodomain adjacent to zinc finger domain protein 1B (BAZ1B); BAZ1B, also termed Tyrosine-protein kinase BAZ1B, or Williams syndrome transcription factor (WSTF), or Williams-Beuren syndrome chromosomal region 10 protein, Williams-Beuren syndrome chromosomal region 9 protein, or WALp2, is a multifunctional protein implicated in several nuclear processes, including replication, transcription, and the DNA damage response. BAZ1B/WSTF, together with the imitation switch (ISWI) ATPase, forms a WSTF-ISWI chromatin remodeling complex (WICH), which transiently associates with the human inactive X chromosome (Xi) during late S-phase prior to BRCA1 and gamma-H2AX. Moreover, BAZ1B/WSTF, SNF2h, and nuclear myosin 1 (NM1) forms the chromatin remodeling complex B-WICH that is involved in regulating rDNA transcription. BAZ1B contains a WAC motif, a DDT domain, 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 1720434809  285 CRMCSRGDEDDKLLLCDGCDDNYHIFCLLPPLPEIPKGVWRCPKC 329
Cdd:cd15628      2 CKVCRKKGEDDKLILCDECNQAFHLFCLRPALYEVPDGEWMCPAC 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 1720434809  284 VCRMCSRGDEDDKLLLCDGCDDNYHIFCLLPPLPEIPKGVWRCPKCV 330
Cdd:cd15513      1 VCEGCGKASDESRLLLCDDCDISYHTYCLDPPLQTVPKGGWKCKWCV 47

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 1720434809  284 VCRMCSRGDEDDKLLLCDGCDDNYHIFCLLPPLPEIPKGVWRCPKC 329
Cdd:cd15594      1 VCQTCRQPGDDNKMLVCDTCDKGYHTFCLQPVMTTIPKNGWKCKNC 46

PHD finger found in bromodomain adjacent to zinc finger domain protein 2A (BAZ2A); BAZ2A, also termed transcription termination factor I-interacting protein 5 (TTF-I-interacting protein 5, or Tip5), or WALp3, is an epigenetic regulator. It has been implicated in epigenetic rRNA gene silencing, as the large subunit of the SNF2h-containing chromatin-remodeling complex NoRC that induces nucleosome sliding in an ATP- and histone H4 tail-dependent fashion. BAZ2A has also been shown to be broadly overexpressed in prostate cancer, to regulate numerous protein-coding genes and to cooperate with EZH2 (enhancer of zeste homolog 2) to maintain epigenetic silencing at genes repressed in prostate cancer metastasis. Its overexpression is tightly associated with a prostate cancer subtype displaying CpG island methylator phenotype (CIMP) in tumors and with prostate cancer recurrence in patients. It contains a TAM (TIP5/ARBP/MBD) 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 1720434809  285 CRMCSRGDEDDKLLLCDGCDDNYHIFCLLPPLPEIPKGVWRCPKCV 330
Cdd:cd15629      2 CLVCRKGDNDEYLLLCDGCDRGCHMYCHRPKMLQVPEGDWFCPNCV 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 1720434809  285 CRMCSRGDEDDKLLLCDGCDDNYHIFCLLPPLPEIPKGVWRCPKC 329
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 1720434809   284 VCRMCSRGDEDDKLLLCDGCDDNYHIFCLLPPL-PEIPKGVWRCPKC 329
Cdd:smart00249    1 YCSVCGKPDDGGELLQCDGCDRWYHQTCLGPPLlEEEPDGKWYCPKC 47

PHD finger 2 found in Histone-lysine N-methyltransferase 2D (KMT2D); KMT2D, also termed ALL1-related protein (ALR), is encoded by the gene that was named myeloid/lymphoid or mixed-lineage leukemia 4 (MLL4), a fourth human homolog of Drosophila trithorax, located on chromosome 12. KMT2D enzymatically generates trimethylated histone H3 Lys 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 asHOXA1-3 and NESTIN. It 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 KMT2D. The ASCOM complex is critical for nuclear receptor (NR) activation of bile acid transporter genes and is down regulated in cholestasis. KMT2D contains the catalytic domain SET, five plant homeodomain (PHD) fingers, two 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 second PHD finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1720434809  284 VCRMCSRGDEDDKLLLCDGCDDNYHIFCLLPPLPEIPKGVWRCPKC 329
Cdd:cd15595      1 VCQTCRKPGEDSKMLVCEACDKGYHTFCLKPAMESLPTDSWKCKAC 46

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 1720434809  285 CRMCSRGDEDDKLLLCDGCDDNYHIFCLLPPLPEIPKGVWRCPKC 329
Cdd:cd15530      2 CSLCGTSENDDQLLFCDDCDRGYHMYCLSPPMSEPPEGSWSCHLC 46

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 1720434809  285 CRMCSRGDEDDKLLLCDGCDDNYHIFCLLPPLPEIPKGVWRCPKCV 330
Cdd:cd15630      3 CQICRKGDNEELLLLCDGCDKGCHTYCHRPKITTIPEGDWFCPACI 48

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 1720434809  284 VCRMCSRGDEDDKLLLCDGCDDNYHIFCLlpPLPEIPKGVWRCPKC 329
Cdd:cd15529      1 TCTKCGDPHDEDKMMFCDQCDRGYHTFCV--GLRSIPDGRWICPLC 44

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 1720434809  285 CRMCSRGDEddkLLLCDGCDDNYHIFCLLPPLPEIPKGVWRCPKC 329
Cdd:cd15539      2 CAVCGDGGE---LLCCDGCPRAFHLACLVPPLTLIPSGTWRCSSC 43

PHD finger found in ubiquitin-like PHD and RING finger domain-containing protein 1 (UHRF1); UHRF1 (also termed inverted CCAAT box-binding protein of 90 kDa, nuclear protein 95, nuclear zinc finger protein Np95 (Np95), RING finger protein 106, transcription factor ICBP90, or E3 ubiquitin-protein ligase 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. UHRF1 contains an N-terminal ubiquitin-like domain (UBL), a tandem Tudor domain (TTD), a plant homeodomain (PHD) finger, a SET and RING finger associated (SRA) domain, and a C-terminal RING-finger domain. It specifically binds to hemimethylated DNA, double-stranded CpG dinucleotides, and recruits the maintenance methyltransferase DNMT1 to its hemimethylated DNA substrate through its SRA domain. UHRF1-dependent H3K23 ubiquitylation has an essential role in maintaining DNA methylation and replication. The tandem Tudor domain directs UHRF1 binding to the heterochromatin mark histone H3K9me3 and the PHD finger targets UHRF1 to unmodified histone H3 in euchromatic regions. The RING-finger domain exhibit both autocatalytic E3 ubiquitin (Ub) ligase activity and activity against histone H3 and DNMT1.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1720434809  285 CRMCSRGDEDDKLLLCDGCDDNYHIFCLLPPLPEIP-KGVWRCPKC 329
Cdd:cd15616      2 CHVCGGKQDPDKQLMCDECDMAFHIYCLNPPLSSIPdDEDWYCPEC 47

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 1720434809  285 CRMCSRGDEddkLLLCDGCDDNYHIFCLLPPLPEIPKGVWRCPKC 329
Cdd:cd15524      2 CAACKRGGN---LQPCGTCPRAYHLDCLDPPLKTAPKGVWVCPKC 43

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 1720434809  285 CRMCSRGDEddkLLLCDGCDDNYHIFCLLPPLPEIPKGVWRCPKC 329
Cdd:cd15531      2 CEVCQQGGE---IILCDTCPRAYHLVCLDPELEKAPEGKWSCPHC 43

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
                   ....*....|....*....|....*....|....*....|....*....
gi 1720434809   77 IVVEEGGYETICKDRRWARVAQRLNYPPG-KNIGSLLRSHYERIVYPYE 124
Cdd:cd16872     38 EVTSRGGLEKVIKDRKWKEVAAVFNFPPTiTNASFVLRKYYLSLLHHYE 86

ARID/BRIGHT DNA binding domain of AT-rich interactive domain-containing proteins ARID5A, ARID5B, and similar proteins; This subfamily contains ARID5A and its paralog ARID5B. 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 plays an important role in the promotion of inflammatory processes and autoimmune diseases. ARID5B, also called MRF1-like protein or modulator recognition factor 2 (MRF-2), is a DNA-binding protein that directly interacts with plant homeodomain (PHD) finger 2 (PHF2) to form a protein kinase A (PKA)-dependent PHF2-ARID5B histone H3K9Me2 demethylase complex. It also functions as a transcriptional co-regulator for the transcription factor sex determining region Y (SRY)-box protein 9 (Sox9) and promotes chondrogenesis through histone modification. Moreover, ARID5B is highly expressed in the cardiovascular system and may play essential roles in the phenotypic change of smooth muscle cells (SMCs) through its regulation of SMC differentiation. Both ARID5A and ARID5B contain an AT-rich DNA-interacting domain (ARID, also known as BRIGHT).

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1720434809   59 EVDNFRFTPRIQRLneleivveeGGYETICKDRRWARVAQRLNYPPG-KNIGSLLRSHYERIVYPYE 124
Cdd:cd16869     30 QIDLYTFFKLVQKL---------GGYEQVTAKRLWKHVYDELGGNPSsTSAATCTRRHYEKLLLPYE 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 1720434809  284 VCRMCSRGD--EDDKLLLCDGCDDNYHIFCLLPP----LPEIPKGVWRCPKC 329
Cdd:cd15502      1 VCIVCQRGHspKSNRIVFCDGCNTPYHQLCHDPSiddeVVEDPDAEWFCKKC 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 1720434809  284 VCRMCSRG--DEDDKLLLCDG-CDDNYHIFCLLPPL--PEIPKG--VWRCPKC 329
Cdd:cd15504      1 FCAKCQSGeaSPDNDILLCDGgCNRAYHQKCLEPPLltEDIPPEdeGWLCPLC 53