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 557440837  184 FCEVCGRSDREDRLLLCDGCDAGYHMECLDPPLQEVPVDEWFCPEC 229
Cdd:cd15536     1 YCEVCGRSDREDRLLLCDGCDAGYHMECLTPPLDEVPIEEWFCPEC 46

DNA polymerase phi; This family includes the fifth essential DNA polymerase in yeast EC:2.7.7.7. Pol5p is localized exclusively to the nucleolus and binds near or at the enhancer region of rRNA-encoding DNA repeating units.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 557440837    48 EHGDGTDGEDEGASEEEDLEDRSGSEDSEDDGET----------LLEVAGTQGKLEAAGSfnSDDDAE 105
Cdd:pfam04931  647 DEEEDDDDEDDEDSEEDDDEDDDDEDEEDDDDEDvdeidelrakLAEALGEHGDDADDDD--SDSDED 712

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 557440837  184 FCEVCGRSDREDRLLLCDGCDAGYHMECLDPPLQEVPVDEWFCPEC 229
Cdd:cd15536     1 YCEVCGRSDREDRLLLCDGCDAGYHMECLTPPLDEVPIEEWFCPEC 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 557440837    184 FCEVCGRSDREDRLLLCDGCDAGYHMECLDPPL-QEVPVDEWFCPEC 229
Cdd:smart00249    1 YCSVCGKPDDGGELLQCDGCDRWYHQTCLGPPLlEEEPDGKWYCPKC 47

N1R/p28-like protein; Provisional

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 557440837   98 FNSDDDAEsCPICLNAFRDQAV-----GTPENCAHYFCLDCIVEWSKNANSCPVDRTLF 151
Cdd:PHA02929  169 YNRSKDKE-CAICMEKVYDKEIknmyfGILSNCNHVFCIECIDIWKKEKNTCPVCRTPF 226

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 557440837 1287 PPSPESTDSSPERDFPLKPALPPASLAVA---AIQREVSLMHDEDPSQPPPLPEGTQEPHLLRPDAAEKAEAPSSPDVAP 1363
Cdd:PHA03247 2577 PSEPAVTSRARRPDAPPQSARPRAPVDDRgdpRGPAPPSPLPPDTHAPDPPPPSPSPAANEPDPHPPPTVPPPERPRDDP 2656

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 557440837 1364 AGKEDSPSAsgRVQEAARPEEVVSQTPLLRSRALVKRVtwnlqesessAPAEDRAPRAPLHRPQKPREGAWDMEDVAPTG 1443
Cdd:PHA03247 2657 APGRVSRPR--RARRLGRAAQASSPPQRPRRRAARPTV----------GSLTSLADPPPPPPTPEPAPHALVSATPLPPG 2724

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 557440837 1444 VRQVFSELPFPSHVLPEPGFPDTD--PSQVYSPGLPPAPAQP-SSIPPCALVSQPTVQFILQGSLPLVGCGAAQTLAPVP 1520
Cdd:PHA03247 2725 PAAARQASPALPAAPAPPAVPAGPatPGGPARPARPPTTAGPpAPAPPAAPAAGPPRRLTRPAVASLSESRESLPSPWDP 2804

                         250       260       270
                  ....*....|....*....|....*....|...
gi 557440837 1521 AALTPASEPASQATAASNSEEKTPAPRLAAEKT 1553
Cdd:PHA03247 2805 ADPPAAVLAPAAALPPAASPAGPLPPPTSAQPT 2837

PHD zinc finger-containing protein [General function prediction only];

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 557440837  179 EEDPTFCEVCGR-----SDREDRLLLCDGCDAGYHMECLDppLQEVPVDEWFCPEC 229
Cdd:COG5141   187 EPSDEFDDICTKctsthNENSNAIVFCDGCEICVHQSCYG--IQFLPEGFWLCRKC 240

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 557440837  184 FCEVCGRSDREDRLLLCDGCDAGYHMECLDPPLQEVPVDEWFCPEC 229
Cdd:cd15536     1 YCEVCGRSDREDRLLLCDGCDAGYHMECLTPPLDEVPIEEWFCPEC 46

PHD finger found in bromodomain adjacent to zinc finger domain protein 2A (BAZ2A) and 2B (BAZ2B); 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. BAZ2B, also termed WALp4, is a bromodomain-containing protein whose biological role is still elusive. It shows high sequence similarly with BAZ2A. Both BAZ2A and BAZ2B contain 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. BAZ2B also harbors an extra Apolipophorin-III like domain in its N-terminal region.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 557440837  184 FCEVCGRSDREDRLLLCDGCDAGYHMECLDPPLQEVPVDEWFCPEC 229
Cdd:cd15545     1 SCQICRSGDNEDQLLLCDGCDRGYHTYCFKPKMTNVPEGDWFCPEC 46

PHD finger found in bromodomain adjacent to zinc finger domain protein 1A (BAZ1A); BAZ1A, also termed ATP-dependent chromatin-remodeling protein, or ATP-utilizing chromatin assembly and remodeling factor 1 (ACF1), or CHRAC subunit ACF1, or Williams syndrome transcription factor-related chromatin-remodeling factor 180 (WCRF180), or WALp1, is a subunit of the conserved imitation switch (ISWI)-family ATP-dependent chromatin assembly and remodeling factor (ACF)/chromatin accessibility complex (CHRAC) chromatin remodeling complex, which is required for DNA replication through heterochromatin. It alters the remodeling properties of the ATPase motor protein sucrose nonfermenting-2 homolog (SNF2H). Moreover, BAZ1A and its complexes play important roles in DNA double-strand break (DSB) repair. It is essential for averting improper gene expression during spermatogenesis. It also regulates transcriptional repression of vitamin D3 receptor-regulated genes. BAZ1A 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 557440837  185 CEVCGRSDREDRLLLCDGCDAGYHMECLDPPLQEVPVDEWFCPEC 229
Cdd:cd15627     2 CRICRRKGDAEKMLLCDGCDRGHHMYCLRPPLKKVPEGDWFCPDC 46

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 557440837   184 FCEVCGRSDREDRLLLCDGCDAGYHMECLDPPLQ--EVPVDEWFCPEC 229
Cdd:pfam00628    1 YCAVCGKSDDGGELVQCDGCDDWFHLACLGPPLDpaEIPSGEWLCPEC 48

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 557440837  185 CEVCGRSDREDRLLLCDGCDAGYHMECLDPPLQEVP-VDEWFCPEC 229
Cdd:cd15525     2 CHVCGGKQDPEKQLLCDECDMAYHLYCLDPPLTSLPdDDEWYCPDC 47

Modified RING finger, HC subclass (C3HC3D-type), found in SR-related and CTD-associated factor 11 (SCAF11) and similar proteins; SCAF11, also known as CTD-associated SR protein 11 (CASP11), renal carcinoma antigen NY-REN-40, SC35-interacting protein 1 (Sip1), Serine/arginine-rich splicing factor 2 (SRSF2)-interacting protein, or splicing regulatory protein 129 (SRrp129), is a novel arginine-serine-rich (RS) domain-containing protein essential for pre-mRNA splicing. It functions as an auxiliary splice factor interacting with the spliceosomal component SC35, promoting RNAPII elongation. In addition to SR proteins, such as SC35, ASF/SF2, SRp75, and SRp20, SCAF11 also associates with U1-70K and U2AF65, proteins associated with 5' and 3' splice sites, respectively. SCAF11 contains an N-terminal modified C3HC3D-type RING-HC finger, an internal serine-arginine rich domain (SR domain), and a C-terminal SRI domain.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 557440837  105 ESCPICLNAFRDQAVGTPENCAHYFCLDCIVEWSKNANSCPVDRTLFKCIC 155
Cdd:cd16636     1 DRCPICLNCLLEQEVAFPENCSHVFCLTCILKWAETVTSCPIDRKPFQAVY 51

PHD finger 1 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/ARID domain-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 andH3K4me2), 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 first PHD finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 557440837  185 CEVCGRSDREDRLLLCDGCDAGYHMECLDPPLQEVPVDEWFCPEC 229
Cdd:cd15604     2 CRMCSRGDEDDKLLLCDGCDDNYHTFCLLPPLPEPPKGIWRCPKC 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 557440837  185 CEVCGRSDREDRLLLCDGCDAGYHMECLDPPLQEVPVDEWFCPECA 230
Cdd:cd15513     2 CEGCGKASDESRLLLCDDCDISYHTYCLDPPLQTVPKGGWKCKWCV 47

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 557440837  184 FCEVCGRSDRedrLLLCDGCDAGYHMECLDPPLQEVPVDEWFCPEC 229
Cdd:cd15532     1 FCRVCKDGGE---LLCCDGCPSSYHLHCLNPPLAEIPDGDWFCPRC 43

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 557440837  185 CEVCGRSDREDRLLLCDGCDAGYHMECLDPPLQEVPVDEWFCPEC 229
Cdd:cd15530     2 CSLCGTSENDDQLLFCDDCDRGYHMYCLSPPMSEPPEGSWSCHLC 46

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 557440837  185 CEVCGRSDREDRLLLCDGCDAGYHMECLDPPLQEVPV-DEWFCPEC 229
Cdd:cd15616     2 CHVCGGKQDPDKQLMCDECDMAFHIYCLNPPLSSIPDdEDWYCPEC 47

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 557440837  185 CEVCGRSDREDRLLLCDGCDAGYHMECLDPPLQEVPVDEWFCPEC 229
Cdd:cd15628     2 CKVCRKKGEDDKLILCDECNQAFHLFCLRPALYEVPDGEWMCPAC 46

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 557440837  185 CEVCGRSDREDRLLLCDGCDAGYHMECLDPPLQEVPVDE-WFCPEC 229
Cdd:cd15617     2 CYVCGGKQDAHMQLLCDECNMAYHIYCLNPPLDKIPEDEdWYCPSC 47

PHD finger 1 found in Saccharomyces cerevisiae transcriptional regulatory protein Rco1 and similar proteins; Rco1 is a component of the Rpd3S histone deacetylase complex that plays an important role at actively transcribed genes. Rco1 contains two plant homeodomain (PHD) fingers, which are required for the methylation of histone H3 lysine 36 (H3K36) nucleosome recognition by Rpd3S. This model corresponds to the first PHD finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 557440837  184 FCEVCGRSDRedrLLLCDGCDAGYHMECLDPPLQE--VPVDEWFCPEC 229
Cdd:cd15535     1 FCSACGGYGS---FLCCDGCPRSFHFSCLDPPLEEdnLPDDEWFCNEC 45

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 557440837  184 FCEVC--GRSDREDRLLLCDGCDAGYHMECLDPPLQ----EVPVDEWFCPEC 229
Cdd:cd15502     1 VCIVCqrGHSPKSNRIVFCDGCNTPYHQLCHDPSIDdevvEDPDAEWFCKKC 52

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 557440837  185 CEVCGRSDREDRLLLCDGCDAGYHMECLDPPLQEVPVDEWFCPEC 229
Cdd:cd15595     2 CQTCRKPGEDSKMLVCEACDKGYHTFCLKPAMESLPTDSWKCKAC 46

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 557440837  185 CEVCGRSDRedrLLLCDGCDAGYHMECLDPPLQEVPVDEWFCPEC 229
Cdd:cd15539     2 CAVCGDGGE---LLCCDGCPRAFHLACLVPPLTLIPSGTWRCSSC 43

PHD finger 1 found in bromodomain and PHD finger-containing transcription factor (BPTF); BPTF, also termed nucleosome-remodeling factor subunit BPTF, or fetal Alz-50 clone 1 protein (FAC1), or fetal Alzheimer antigen, functions as a transcriptional regulator that exhibits altered expression and subcellular localization during neuronal development and neurodegenerative diseases such as Alzheimer's disease. It interacts with the human orthologue of the Kelch-like Ech-associated protein (Keap1). Its function and subcellular localization can be regulated by Keap1. Moreover, BPTF is a novel DNA-binding protein that recognizes the DNA sequence CACAACAC and represses transcription through this site in a phosphorylation-dependent manner. Furthermore, BPTF interacts with the Myc-associated zinc finger protein (ZF87/MAZ) and alters its transcriptional activity, which has been implicated in gene regulation in neurodegeneration. Some family members contain two or three plant homeodomain (PHD) fingers, which may be involved in complex formation with histone H3 trimethylated at K4 (H3K4me3). This family corresponds to the first PHD finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 557440837  185 CEVCGRsdREDrLLLCDGCDAGYHMECLDPPLQEVPVDEWFCPEC 229
Cdd:cd15559     2 CRVCHK--LGD-LLCCETCSAVYHLECVDPPLEEVPEEDWQCEVC 43

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 557440837  185 CEVCGRSDREDRLLLCDGCDAGYHMECLDPPLQEVPVDEWFCPEC 229
Cdd:cd15594     2 CQTCRQPGDDNKMLVCDTCDKGYHTFCLQPVMTTIPKNGWKCKNC 46

PHD finger 2 found in PHD finger protein 12 (PHF12), yeast Rco1, and similar proteins; PHF12, also termed PHD factor 1 (Pf1), is a plant homeodomain (PHD) zinc finger-containing protein that bridges the transducin-like enhancer of split (TLE) corepressor to the mSin3A-histone deacetylase (HDAC)-complex, and further represses transcription at targeted genes. PHF12 also interacts with MRG15 (mortality factor-related genes on chromosome 15), a member of the mortality factor (MORF) family of proteins implicated in regulating cellular senescence. PHF12 contains two plant homeodomain (PHD) zinc fingers followed by a polybasic region. The PHD fingers function downstream of phosphoinositide signaling triggered by the interaction between polybasic regions and phosphoinositides. This subfamily also includes yeast transcriptional regulatory protein Rco1 and similar proteins. Rco1 is a component of the Rpd3S histone deacetylase complex that plays an important role at actively transcribed genes. Rco1 contains two PHD fingers, which are required for the methylation of histone H3 lysine 36 (H3K36) nucleosome recognition by Rpd3S. This model corresponds to the second PHD finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 557440837  184 FCEVCGRSDREDRLLLCDGCDAGYHMECLDPPLQEVPV-DEWFCP 227
Cdd:cd15534     1 VCFKCNRSCRVAPLIQCDYCPLLFHLDCLDPPLTHPPAtGRWMCP 45

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 557440837  184 FCEVCGRSDRedrLLLCDGCDAGYHMECLDPPLQEVPVDEWFCPEC 229
Cdd:cd15531     1 YCEVCQQGGE---IILCDTCPRAYHLVCLDPELEKAPEGKWSCPHC 43

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 557440837  184 FCEVC--GRSDREDRLLLCDGCDAGYHMECLDppLQEVPVDEWFCPEC 229
Cdd:cd15492     1 VCDVCldGESEDDNEIVFCDGCNVAVHQSCYG--IPLIPEGDWFCRKC 46

N1R/p28-like protein; Provisional

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 557440837   98 FNSDDDAEsCPICLNAFRDQAV-----GTPENCAHYFCLDCIVEWSKNANSCPVDRTLF 151
Cdd:PHA02929  169 YNRSKDKE-CAICMEKVYDKEIknmyfGILSNCNHVFCIECIDIWKKEKNTCPVCRTPF 226

PHD finger 3 found in PHD finger protein 14 (PHF14) and similar proteins; 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 a non-canonical extended PHD (ePHD) finger, Cys2HisCys5HisCys2His. It can interact with histones through its PHD fingers. The model corresponds to the third PHD finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 557440837  185 CEVCGRSDREDRLLLCDGCDAGYHMECLDPPLQEVPVDE---WFCPEC 229
Cdd:cd15563     2 CCVCKQTGDNSQLVRCDECKLCYHFGCLDPPLKKSPKQRgygWVCEEC 49

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 557440837  184 FCEVCgrsDREDRLLLCDGCDAGYHMECLDPPLQEVPVDEWFCPEC 229
Cdd:cd15541     1 WCAVC---QNGGELLCCDKCPRVFHLDCHIPPIPEFPSGEWSCSLC 43

RING finger, HC subclass, found in RING finger protein 141 (RNF141) and similar proteins; RNF141, also known as zinc finger protein 230 (ZNF230), is a RING finger protein present primarily in the nuclei of spermatogonia, the acrosome, and the tail of spermatozoa. It may have a broad function during early development of vertebrates. It plays an important role in spermatogenesis, including spermatogenic cell proliferation and sperm maturation, as well as motility and fertilization. It also exhibits DNA binding activity. RNF141/ZNF230 gene mutations may be associated with azoospermia. RNF141 contains a C3HC4-type RING finger domain that may function as an activator module in transcription.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 557440837  105 ESCPICLnafrDQAVGTPENCAHYFCLDCIVEWSKNANSCPVDR 148
Cdd:cd16545     1 EECCICM----DRKADLILPCAHSYCQKCIDKWSDRHRTCPICR 40

HC subclass of RING (RING-HC) finger and its variants; The RING finger is a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc. It is defined by the "cross-brace" motif that chelates zinc atoms by eight amino acid residues, typically Cys or His, arranged in a characteristic spacing. Canonical RING motifs have been categorized into two major subclasses, RING-HC (C3HC4-type) and RING-H2 (C3H2C3-type), according to their Cys/His content. There are also many variants of RING fingers. Some have a different Cys/His pattern. Some lack a single Cys or His residue at typical Zn ligand positions, especially, the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can chelate Zn in a RING finger as well. This family corresponds to the HC subclass of RING (RING-HC) fingers that are characterized by containing C3HC4-type canonical RING-HC fingers or noncanonical RING-HC finger variants, including C4C4-, C3HC3D-, C2H2C4-, and C3HC5-type modified RING-HC fingers. The canonical RING-HC finger has been defined as C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-C-X2-C-X(4-48)-C-X2-C. It binds two Zn ions in a unique "cross-brace" arrangement, which distinguishes it from tandem zinc fingers and other similar motifs. RING-HC fingers can be found in a group of diverse proteins with a variety of cellular functions, including oncogenesis, development, viral replication, signal transduction, the cell cycle, and apoptosis. Many of them are ubiquitin-protein ligases (E3s) that serve as scaffolds for binding to ubiquitin-conjugating enzymes (E2s, also referred to as ubiquitin carrier proteins or UBCs) in close proximity to substrate proteins, which enables efficient transfer of ubiquitin from E2 to the substrates.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 557440837  105 ESCPICLNAFRDqAVGTPenCAHYFCLDCIVEWSKNAN-SCPVD 147
Cdd:cd16449     1 LECPICLERLKD-PVLLP--CGHVFCRECIRRLLESGSiKCPIC 41

RING finger, HC subclass, found in Saccharomyces cerevisiae increased recombination centers protein 20 (IRC20) and similar proteins; IRC20 is an uncharacterized ATP-dependent helicase that is probably involved in a pathway contributing to genomic integrity. IRC20 contains a typical C3HC4-type RING-HC finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 557440837  106 SCPICLNAFRdqaVGTPENCAHYFCLDCIVEWSKNANSCPV 146
Cdd:cd23135     5 SCSICFSEIR---SGAILKCGHFFCLSCIASWLREKSTCPL 42

RING finger, H2 subclass, found in RING finger protein 181 (RNF181) and similar proteins; RNF181, also known as HSPC238, is a platelet E3 ubiquitin-protein ligase containing a C3H2C3-type RING-H2 finger. It interacts with the KVGFFKR motif of platelet integrin alpha(IIb)beta3, suggesting a role for RNF181-mediated ubiquitination in integrin and platelet signaling. It also suppresses the tumorigenesis of hepatocellular carcinoma (HCC) through the inhibition of extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signaling in the liver.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 557440837  106 SCPICLNAFRDQAVGTPENCAHYFCLDCIVEWSKNANSCPVDR 148
Cdd:cd16669     1 KCPICLLEFEEGETVKQLPCKHSFHSDCILPWLGKTNSCPLCR 43

RING finger, H2 subclass, found in the PA-TM-RING ubiquitin ligase family; The PA-TM-RING family represents a group of transmembrane-type E3 ubiquitin ligases, which has been characterized by an N-terminal transient signal peptide, a PA (protease-associated) domain, a TM (transmembrane) domain, as well as a C-terminal C3H2C3-type RING-H2 finger domain. It includes RNF13, RNF167, ZNRF4 (zinc and RING finger 4), GRAIL (gene related to anergy in lymphocytes)/RNF128, RNF130, RNF133, RNF148, RNF149 and RNF150 (which are more closely related), as well as RNF43 and ZNRF3, which have substantially longer C-terminal tail extensions compared with the others. PA-TM-RING proteins are expressed at low levels in all mammalian tissues and species, but they are not present in yeast. They play a common regulatory role in intracellular trafficking/sorting, suggesting that abrogation of their function may result in dysregulation of cellular signaling events in cancer.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 557440837  106 SCPICLNAFRDQAVGTPENCAHYFCLDCIVEWSKNANSCPV 146
Cdd:cd16454     1 TCAICLEEFKEGEKVRVLPCNHLFHKDCIDPWLEQHNTCPL 41

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 557440837 1143 RPDRKESVAWPRDRRKRRSRSPSSEHRAREHRRPRSREKWPQTRSHSPERKGAVREASP-----APLAQGEPGREDLPTR 1217
Cdd:PHA03247 2632 SPAANEPDPHPPPTVPPPERPRDDPAPGRVSRPRRARRLGRAAQASSPPQRPRRRAARPtvgslTSLADPPPPPPTPEPA 2711

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 557440837 1218 LPALGEAHVSPEVATADKAPLQAPPvLEVAAECEPDDLDLDYGDSveaghvfddfssdavfiqlddmsSPPSPESTDSSP 1297
Cdd:PHA03247 2712 PHALVSATPLPPGPAAARQASPALP-AAPAPPAVPAGPATPGGPA-----------------------RPARPPTTAGPP 2767

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 557440837 1298 ERDFPLKPALPPASLAVAAIQREVSLMHDEDPSQPPPLPEgtqephllrPDAAEKAEAPSSPDVAPAGKEDSPSASGRVQ 1377
Cdd:PHA03247 2768 APAPPAAPAAGPPRRLTRPAVASLSESRESLPSPWDPADP---------PAAVLAPAAALPPAASPAGPLPPPTSAQPTA 2838

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 557440837 1378 EAARPEEVVSQTPLLRSRA----LVKRVTWNLQESESSAPAEDRAPRAPLHRPQKPREGAWDMEDVAPtgvRQVFSELPF 1453
Cdd:PHA03247 2839 PPPPPGPPPPSLPLGGSVApggdVRRRPPSRSPAAKPAAPARPPVRRLARPAVSRSTESFALPPDQPE---RPPQPQAPP 2915

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 557440837 1454 PSHVLPEPGFPDTDPSQVYSPGLPPAPAQPSSIPPCALVSQPTVQFILQGSLPLVGCGAAQTLAPVPAALTPASEPasqa 1533
Cdd:PHA03247 2916 PPQPQPQPPPPPQPQPPPPPPPRPQPPLAPTTDPAGAGEPSGAVPQPWLGALVPGRVAVPRFRVPQPAPSREAPAS---- 2991

                         410
                  ....*....|....*..
gi 557440837 1534 taASNSEEKTPAPRLAA 1550
Cdd:PHA03247 2992 --STPPLTGHSLSRVSS 3006

Modified RING finger, HC subclass (C3HC3D-type), found in neuregulin receptor degradation protein-1 (Nrdp1) and similar proteins; Nrdp1 (referred to as FLRF in mice), also known as RING finger protein 41 (RNF41), is an E3 ubiquitin-protein ligase that plays a critical role in the regulation of cell growth and apoptosis, inflammation and production of reactive oxygen species (ROS), as well as in doxorubicin (DOX)-induced cardiac injury. It promotes the degradation of the epidermal growth factor receptor (EGFR/ErbB) family member, ErbB3, which is independent of growth factor stimulation. It also promotes M2 macrophage polarization by ubiquitinating and activating transcription factor CCAAT/enhancer-binding protein beta (C/EBPbeta) via Lys-63-linked ubiquitination. Moreover, Nrdp1 interacts with and modulates the activity of Parkin, a causative protein for early onset recessive juvenile parkinsonism (AR-JP). It also interacts with ubiquitin-specific protease 8 (USP8), which is involved in trafficking of various transmembrane proteins. Furthermore, Nrdp1 inhibits basal lysosomal degradation and enhances ectodomain shedding of JAK2-associated cytokine receptors. Its phosphorylation by the kinase Par-1b (also known as MARK2) is required for epithelial cell polarity. Nrdp1 contains an N-terminal modified C3HC3D-type RING-HC finger required for enhancing ErbB3 degradation, a B-box, a coiled-coil domain responsible for Nrdp1 oligomerization, and a C-terminal ErbB3-binding domain.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 557440837  107 CPIClNAFRDQAVGTPeNCAHYFCLDCIVEWSKNANSCPVDR 148
Cdd:cd16634     4 CPIC-SGVLEEPLQAP-HCEHAFCNACITEWLSRQQTCPVDR 43

PHD finger 4 found in nuclear receptor-binding SET domain-containing (NSD) proteins; The nuclear receptor binding SET domain (NSD) protein is a family of three HMTases, NSD1, NSD2/MMSET/WHSC1, and NSD3/WHSC1L1, that are critical in maintaining chromatin integrity. Reducing NSD activity through specific lysine-HMTase inhibitors appears promising to help suppress cancer growth. NSD proteins have specific mono- and dimethylase activities for H3K36, and they play non-redundant roles during development. NSD1 plays a role in several pathologies, including but not limited to Sotos and Weaver syndromes, acute myeloid leukemia, breast cancer, neuroblastoma, and glioblastoma formation. NSD2 is involved in cancer cell proliferation, survival, and tumor growth, by mediating constitutive NF-kappaB signaling via the cytokine autocrine loop. NSD3 is amplified in human breast cancer cell lines. Moreover, translocation resulting in NUP98 fusion to NSD3 leads to development of acute myeloid leukemia. NSD proteins contain a catalytic suppressor of variegation, enhancer of zeste and trithorax (SET) domain, two proline-tryptophan-tryptophan-proline (PWWP) domains, five plant homeodomain (PHD) fingers, and an NSD-specific Cys-His rich domain (Cys5HisCysHis). This model corresponds to the fourth PHD finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 557440837  184 FCEVCGRSDRedrLLLCDGCDAGYHMECLDppLQEVPVDEWFCPEC 229
Cdd:cd15567     1 WCFICSEGGS---LICCESCPASFHPECLG--LEPPPEGKFYCEDC 41

PHD finger 4 found in nuclear SET domain-containing protein 3 (NSD3); NSD3, also termed histone-lysine N-methyltransferase NSD3, or protein whistle, or WHSC1-like 1 isoform 9 with methyltransferase activity to lysine, or Wolf-Hirschhorn syndrome candidate 1-like protein 1 (WHSC1-like protein 1, or WHSC1L1), is a lysine methyltransferase encoded by gene NSD3, which is amplified in human breast cancer cell lines. Moreover, translocation resulting in NUP98 fusion to NSD3 leads to the development of acute myeloid leukemia. NSD3 contains a catalytic suppressor of variegation, enhancer of zeste and trithorax (SET) domain, two proline-tryptophan-tryptophan-prolin motif (PWWP) domains, five plant-homeodomain (PHD) zinc fingers, and an NSD-specific Cys-His rich domain (Cys5HisCysHis). The SET domain is responsible for histone methyltransferase activity. The PWWP and PHD fingers are involved in protein-protein interactions. This model corresponds to the fourth PHD finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 557440837  184 FCEVCGRSDRedrLLLCDGCDAGYHMECLDPplqEVPVDEWFCPEC 229
Cdd:cd15658     1 FCFVCARGGR---LLCCESCPASFHPECLSI---EMPEGCWNCNEC 40

RING finger, HC subclass, found in RING finger protein 8 (RNF8) and similar proteins; RNF8 is a telomere-associated E3 ubiquitin-protein ligase that plays an important role in DNA double-strand break (DSB) repair via histone ubiquitination. It is localized in the nucleus and interacts with class III E2s (UBE2E2, UbcH6, and UBE2E3), but not with other E2s (UbcH5, UbcH7, UbcH10, hCdc34, and hBendless). It recruits UBC13 for lysine 63-based self polyubiquitylation. Its deficiency causes neuronal pathology and cognitive decline, and its loss results in neuron degeneration. RNF8, together with RNF168, catalyzes a series of ubiquitylation events on substrates such as H2A and H2AX, with the H2AK13/15 ubiquitylation being particularly important for recruitment of repair factors p53-binding protein 1 (53BP1) or the RAP80-BRCA1 complex to sites of DSBs. RNF8 mediates the ubiquitination of gammaH2AX, and recruits 53BP1 and BRCA1 to DNA damage sites which promotes DNA damage response (DDR) and inhibits chromosomal instability. Moreover, RNF8 interacts with retinoid X receptor alpha (RXR alpha) and enhances its transcription-stimulating activity. It also regulates the rate of exit from mitosis and cytokinesis. RNF8 contains an N-terminal forkhead-associated (FHA) domain and a C-terminal C3HC4-type RING-HC finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 557440837  107 CPICLNAFRdQAVGTpeNCAHYFCLDCIVEWSKNANSCPVDRTLFK 152
Cdd:cd16535     4 CSICSELFI-EAVTL--NCSHSFCSYCITEWMKRKKECPICRKPIT 46

RING-type zinc-finger; This zinc-finger is a typical RING-type of plant ubiquitin ligases.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 557440837   107 CPICLNAFRDQAVgtpeNCAHYFCLDCIVEWSKNAN---SCP 145
Cdd:pfam13445    1 CPICLELFTDPVL----PCGHTFCRECLEEMSQKKGgkfKCP 38