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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 291245069 1362 EMWVHEDCSVWADGVYMAGPNMYGLHDAVRVAKQMTCCSCQQKGASLGCMTKGCEEKYHYLCAVHEGCQLQEENFSMLCP 1441
Cdd:cd15668    22 EVWVHEDCAVWAPGVYLVGGKLYGLEEAVWVAKQSVCSSCQQTGATIGCLHKGCKAKYHYPCAVESGCQLDEENFSLLCP 101

                  ..
gi 291245069 1442 KH 1443
Cdd:cd15668   102 KH 103

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 291245069  363 SPLGQPGSHPSPVPSPATSIRSPVSIHSPNSV----------PSRSPAPSPITVRSPLCGMVQSPAALPSPGS----SNG 428
Cdd:PHA03247 2825 AGPLPPPTSAQPTAPPPPPGPPPPSLPLGGSVapggdvrrrpPSRSPAAKPAAPARPPVRRLARPAVSRSTESfalpPDQ 2904

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 291245069  429 SVKSPLSVPQKSPNNWQQPVSPVGNQTSYKSVPHHQIPNGPYVNPNGQQiSPTQHDSLQNKGALPRLEEMVaflgePKSK 508
Cdd:PHA03247 2905 PERPPQPQAPPPPQPQPQPPPPPQPQPPPPPPPRPQPPLAPTTDPAGAG-EPSGAVPQPWLGALVPGRVAV-----PRFR 2978

                         170
                  ....*....|....*..
gi 291245069  509 GPAAQNSKEDDGNSPKP 525
Cdd:PHA03247 2979 VPQPAPSREAPASSTPP 2995

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 291245069 1362 EMWVHEDCSVWADGVYMAGPNMYGLHDAVRVAKQMTCCSCQQKGASLGCMTKGCEEKYHYLCAVHEGCQLQEENFSMLCP 1441
Cdd:cd15668    22 EVWVHEDCAVWAPGVYLVGGKLYGLEEAVWVAKQSVCSSCQQTGATIGCLHKGCKAKYHYPCAVESGCQLDEENFSLLCP 101

                  ..
gi 291245069 1442 KH 1443
Cdd:cd15668   102 KH 103

SAM domain of EPH family of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH (erythropoietin-producing hepatocyte) family of receptor tyrosine kinases is a C-terminal signal transduction module located in the cytoplasmic region of these receptors. SAM appears to mediate cell-cell initiated signal transduction via binding proteins to a conserved tyrosine that is phosphorylated. In some cases the SAM domain mediates homodimerization/oligomerization and plays a role in the clustering process necessary for signaling. EPH kinases are the largest family of receptor tyrosine kinases. They are classified into two groups based on their abilities to bind ephrin-A and ephrin-B ligands. The EPH receptors are involved in regulation of cell movement, shape, and attachment during embryonic development; they control cell-cell interactions in the vascular, nervous, epithelial, and immune systems, and in many tumors. They are potential molecular markers for cancer diagnostics and potential targets for cancer therapy.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 291245069    5 VERWLETFMCKQYAETFEKCGYKTLSSVCQLDRHTLRSMGV-LEEHCDNIIENVSVL 60
Cdd:cd09488     5 VGEWLESIKMGRYKENFTAAGYTSLDAVAQMTAEDLTRLGVtLVGHQKKILNSIQAL 61

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 291245069  363 SPLGQPGSHPSPVPSPATSIRSPVSIHSPNSV----------PSRSPAPSPITVRSPLCGMVQSPAALPSPGS----SNG 428
Cdd:PHA03247 2825 AGPLPPPTSAQPTAPPPPPGPPPPSLPLGGSVapggdvrrrpPSRSPAAKPAAPARPPVRRLARPAVSRSTESfalpPDQ 2904

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 291245069  429 SVKSPLSVPQKSPNNWQQPVSPVGNQTSYKSVPHHQIPNGPYVNPNGQQiSPTQHDSLQNKGALPRLEEMVaflgePKSK 508
Cdd:PHA03247 2905 PERPPQPQAPPPPQPQPQPPPPPQPQPPPPPPPRPQPPLAPTTDPAGAG-EPSGAVPQPWLGALVPGRVAV-----PRFR 2978

                         170
                  ....*....|....*..
gi 291245069  509 GPAAQNSKEDDGNSPKP 525
Cdd:PHA03247 2979 VPQPAPSREAPASSTPP 2995

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 291245069 1362 EMWVHEDCSVWADGVYMAGPNMYGLHDAVRVAKQMTCCSCQQKGASLGCMTKGCEEKYHYLCAVHEGCQLQEENFSMLCP 1441
Cdd:cd15668    22 EVWVHEDCAVWAPGVYLVGGKLYGLEEAVWVAKQSVCSSCQQTGATIGCLHKGCKAKYHYPCAVESGCQLDEENFSLLCP 101

                  ..
gi 291245069 1442 KH 1443
Cdd:cd15668   102 KH 103

Extended PHD finger (ePHD) found in retinoic acid-induced protein 1 (RAI1); The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model corresponds to the C-terminal ePHD/ADD (ATRX-DNMT3-DNMT3L) domain of RAI1. RAI1, a homolog of stromelysin-1 PDGF (platelet-derived growth factor)-responsive element-binding protein (SPBP, also termed TCF-20), is a chromatin-binding protein implicated in the regulation of gene expression. It is strongly enriched on chromatin in interphase HeLa cells, and displays low nuclear mobility, and has been implicated in Smith-Magenis syndrome, Potocki-Lupski syndrome, and non-syndromic autism. RAI1 contains a region with homology to the novel nucleosome-binding region SPBP and an ePHD/ADD domain with ability to bind nucleosomes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 291245069 1362 EMWVHEDCSVWADGVYMAGPNMYGLHDAVRVAKQMTCCSCQQKGASLGCMTKGCEEKYHYLCAVHEGCQLQEENFSMLCP 1441
Cdd:cd15700    23 EHWVHEACAVWTTGVYLVAGKLFGLQEAVQKAADAKCSSCQGAGATVGCCHKGCTQSYHYICAVEAGCLFEEENFSLRCP 102

                  ..
gi 291245069 1442 KH 1443
Cdd:cd15700   103 KH 104

Extended plant homeodomain (PHD) finger, characterized by Cys2HisCys5HisCys2His; PHD finger is also termed LAP (leukemia-associated protein) motif or TTC (trithorax consensus) domain. The extended PHD finger is characterized as Cys2HisCys5HisCys2His, which has been found in a variety of eukaryotic proteins involved in the control of gene transcription and chromatin dynamics. PHD fingers can recognize the unmodified and modified histone H3 tail, and some have been found to interact with non-histone proteins. They also function as epigenome readers controlling gene expression through molecular recruitment of multi-protein complexes of chromatin regulators and transcription factors.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 291245069 1347 PSPAGSSKC---CKSDSDEMWVHEDCSVWADGVYMAGPNMY---GLHDAVRVAKQMTCCSCQQK-GASLGCMTKGCEEKY 1419
Cdd:cd15571     5 PRSGGALKGggaLKTTSDGLWVHVVCALWSPEVYFDDGTLLeveGVSKIPKRRKKLKCSICGKRgGACIQCSYPGCPRSF 84

                          90       100
                  ....*....|....*....|....*...
gi 291245069 1420 HYLCAVHEGC----QLQEENFSMLCPKH 1443
Cdd:cd15571    85 HVSCAIRAGClfefEDGPGNFVVYCPKH 112

Extended PHD finger 1 found in histone-lysine N-methyltransferase 2C (KMT2C) and 2D (KMT2D); The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model corresponds to the first ePHD finger of KMTC2C and KMTC2D. KMT2C, also termed myeloid/lymphoid or mixed-lineage leukemia protein 3 (MLL3), or homologous to ALR protein, is a histone H3 lysine 4 (H3K4) lysine methyltransferase that functions as a circadian factor contributing to genome-scale circadian transcription. It is a component of a large complex that acts as a coactivator of multiple transcription factors, including the bile acid (BA)-activated nuclear receptor, farnesoid X receptor (FXR), a critical player in BA homeostasis. The MLL3 complex is essential for p53 transactivation of small heterodimer partner (SHP). KMT2C is also a part of activating signal cointegrator-2 (ASC-2)-containing complex (ASCOM) that contains the transcriptional coactivator nuclear receptor coactivator 6 (NCOA6), KMT2C and its paralog MLL4. The ASCOM complex is critical for nuclear receptor (NR) activation of bile acid transporter genes and is down regulated in cholestasis. KMT2D, also termed ALL1-related protein (ALR), is encoded by the gene that was named MLL4, a fourth human homolog of Drosophila trithorax, located on chromosome 12. It enzymatically generates trimethylated histone H3 Lysine 4 (H3K4me3). It plays an essential role in differentiating the human pluripotent embryonal carcinoma cell line NTERA-2 clone D1 (NT2/D1) stem cells by activating differentiation-specific genes, such as HOXA1-3 and NESTIN. KMT2D is also a part of ASCOM. Both KMT2C and KMT2D contain the catalytic domain SET, five plant PHD fingers, two ePHD fingers, a RING finger, an HMG (high-mobilitygroup)-binding motif, and two FY-rich regions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 291245069 1355 CCKSDSDEMWVHEDCSVWADGVYMA-GPNMYGLHDAVRVAKQMTCCSCQQKGASLGCMTKGCEEKYHYLCAVHEGCQLQE 1433
Cdd:cd15665     1 CALCNLGEVYAHHCCAAWSEGVCQTeDGALENVDKAVAKALSQKCSFCLRYGASISCRMPSCSKSFHFPCAAAAGCFQDI 80

                          90
                  ....*....|
gi 291245069 1434 ENFSMLCPKH 1443
Cdd:cd15665    81 KTLTLFCPEH 90

Extended PHD finger found in histone-lysine N-methyltransferase 2B (KMT2B); The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This subfamily includes the ePHD finger of KMT2B. KMT2B is also called trithorax homolog 2 or WW domain-binding protein 7 (WBP-7). KMT2B is encoded by the gene that was first named myeloid/lymphoid or mixed-lineage leukemia 2 (MLL2), a second human homolog of Drosophila trithorax, located on chromosome 19. It belongs to the MLL subfamily of H3K4-specific histone lysine methyltransferases (KMT2) and is vital for normal mammalian embryonic development. KMT2B functions as the catalytic subunit in the MLL2 complex, which contains WDR5, RbBP5, ASH2L and DPY30 as integral core subunits required for the efficient methylation activity of the complex. The MLL2 complex is highly active and specific for histone 3 lysine 4 (H3K4) methylation, which stimulates chromatin transcription in a SAM- and H3K4-dependent manner. Moreover, KMT2B plays a critical role in memory formation by mediating hippocampal H3K4 di- and trimethylation. It is also required for RNA polymerase II association and protection from DNA methylation at the MagohB CpG island promoter. KMT2B contains a CxxC (x for any residue) zinc finger domain, three PHD fingers, this ePHD finger, two FY (phenylalanine tyrosine)-rich domains, and a SET (Suppressor of variegation, Enhancer of zeste, Trithorax) domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 291245069 1364 WVHEDCSVWADGVYMAGP-NMYGLHDAVRVAKQMTCCSCQQKGASLGCMTKGCEEKYHYLCAVHEGCQLQEENfSMLCPK 1442
Cdd:cd15694    26 WTHVNCAIWSAEVFEENDgSLKNVHAAVARGRQMRCEHCQKIGATVGCCLSACLSNFHFMCARASRCCFQDDK-KVFCQK 104

                  .
gi 291245069 1443 H 1443
Cdd:cd15694   105 H 105

Extended PHD finger 2 found in histone-lysine N-methyltransferase 2C (KMT2C); The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model corresponds to the second ePHD finger of 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 PHD fingers, two ePHD fingers, 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 291245069 1362 EMWVHEDCSVWADGVY--MAGPnMYGLHDAVRVAKQMTCCSCQQKGASLGCMTKGCEEKYHYLCAVHEGCQLQEENfSML 1439
Cdd:cd15697    24 DLWVHLNCALWSTEVYetQAGA-LINVELALRRGLQMKCVFCHKTGATSGCHRLRCTNVYHFTCAIKAQCMFFKDK-TML 101

                  ....
gi 291245069 1440 CPKH 1443
Cdd:cd15697   102 CPMH 105

Extended PHD finger 1 found in histone-lysine N-methyltransferase 2D (KMT2D); The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model corresponds to the first ePHD finger of 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 at 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 as HOXA1-3 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 PHD fingers, two ePHD fingers, a RING finger, an HMG (high-mobility group)-binding motif, and two FY-rich regions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 291245069 1355 CCKSDSDEMWVHEDCSVWADGVY-MAGPNMYGLHDAVRVAKQMTCCSCQQKGASLGCMTKGCEEKYHYLCAVHEGCQLQE 1433
Cdd:cd15695     1 CALCNCGECWVHHWCAAWSAGVKqHEGDGLIGVDKAVFSGISQKCEHCKRLGATIQCHAEGCPRFYHFPCAAASGSFQSM 80

                          90
                  ....*....|
gi 291245069 1434 ENFSMLCPKH 1443
Cdd:cd15695    81 KTLLLLCPEH 90

Extended PHD finger 2 found in histone-lysine N-methyltransferase 2D (KMT2D); The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model corresponds to the second ePHD finger of 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 as HOXA1-3 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 PHD fingers, two ePHD fingers, a RING finger, an HMG (high-mobility group)-binding motif, and two FY-rich regions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 291245069 1362 EMWVHEDCSVWADGVY-MAGPNMYGLHDAVRVAKQMTCCSCQQKGASLGCMTKGCEEKYHYLCAVHEGCQLQEENfSMLC 1440
Cdd:cd15698    24 DLWVHLNCALWSTEVYeTQGGALMNVEVALHRGLLTKCSLCQKTGATNSCNRLRCPNVYHFACAIRAKCMFFKDK-TMLC 102

                  ....
gi 291245069 1441 PKHK 1444
Cdd:cd15698   103 PMHK 106

Extended PHD finger found in PHD finger protein 11 (PHF11); The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of PHF11. PHF11, also termed BRCA1 C-terminus-associated protein, or renal carcinoma antigen NY-REN-34, is a transcriptional co-activator of the Th1 effector cytokine genes, interleukin-2 (IL2) and interferon-gamma (IFNG), co-operating with nuclear factor kappa B (NF-kappaB). It is involved in T-cell activation and viability. Polymorphisms within PHF11 are associated with total IgE, allergic asthma and eczema.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 291245069 1358 SDSDEMWVHEDCSVWADGVYMAGP----------NMYGLHDAVRVAKQMTCCSCQQKGASLGCMTKGCEEKYHYLCAVHE 1427
Cdd:cd15712    16 AQEQNIAAHQNCLLYSSGFVESEEynplnldrrfDVESVLNEIKRGKRLKCNFCRKKGATVGCEERACRRSYHYFCALCD 95

                          90       100
                  ....*....|....*....|
gi 291245069 1428 GCQLQEEN----FSMLCPKH 1443
Cdd:cd15712    96 DAAIETDEvrgiYRVFCQKH 115

SAM domain of EPH family of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH (erythropoietin-producing hepatocyte) family of receptor tyrosine kinases is a C-terminal signal transduction module located in the cytoplasmic region of these receptors. SAM appears to mediate cell-cell initiated signal transduction via binding proteins to a conserved tyrosine that is phosphorylated. In some cases the SAM domain mediates homodimerization/oligomerization and plays a role in the clustering process necessary for signaling. EPH kinases are the largest family of receptor tyrosine kinases. They are classified into two groups based on their abilities to bind ephrin-A and ephrin-B ligands. The EPH receptors are involved in regulation of cell movement, shape, and attachment during embryonic development; they control cell-cell interactions in the vascular, nervous, epithelial, and immune systems, and in many tumors. They are potential molecular markers for cancer diagnostics and potential targets for cancer therapy.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 291245069    5 VERWLETFMCKQYAETFEKCGYKTLSSVCQLDRHTLRSMGV-LEEHCDNIIENVSVL 60
Cdd:cd09488     5 VGEWLESIKMGRYKENFTAAGYTSLDAVAQMTAEDLTRLGVtLVGHQKKILNSIQAL 61

Extended PHD finger found in protein Jade-3 and similar proteins; The extended plant homeodomain (ePHD) zinc finger is characterized as Cys2HisCys5HisCys2His. This model includes the ePHD finger of Jade-3. Jade-3, also termed PHD finger protein 16 (PHF16), is a plant homeodomain (PHD) zinc finger protein that is close related to Jade-1, which functions as an essential regulator of multiple cell signaling pathways. Like Jade-1, Jade-3 is required for ING4 and ING5 to associate with histone acetyl transferase (HAT) HBO1 and Eaf6 to form a HBO1 complex that has a histone H4-specific acetyltransferase activity, a reduced activity toward histone H3, and is responsible for the bulk of histone H4 acetylation in vivo. Jade-3 contains a canonical PHD domain followed by this non-canonical ePHD domain, both of which are zinc-binding motifs.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 291245069 1347 PSPAGSSKCCKSDSDemWVHEDCSVWADGVYMAGPNMygLHDAVRVAK------QMTCCSCQQK-GASLGCMTKGCEEKY 1419
Cdd:cd15706     5 PKTGGAMKATRTGTK--WAHVSCALWIPEVSIACPER--MEPITKVSHippsrwALVCSLCKLKtGACIQCSVKSCITAF 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 291245069 1420 HYLCAVHEGCQLQ-------EENFSMLCPKH 1443
Cdd:cd15706    81 HVTCAFEHSLEMKtildegdEVKFKSYCLKH 111

Sterile alpha motif; Widespread domain in signalling and nuclear proteins. In EPH-related tyrosine kinases, appears to mediate cell-cell initiated signal transduction via the binding of SH2-containing proteins to a conserved tyrosine that is phosphorylated. In many cases mediates homodimerisation.

                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|
gi 291245069      5 VERWLETFMCKQYAETFEKCGYKTLSSVCQLDRHTLRSMGV-LEEHCDNIIENVSVLRQT 63
Cdd:smart00454    9 VADWLESIGLEQYADNFRKNGIDGALLLLLTSEEDLKELGItKLGHRKKILKAIQKLKEQ 68

SAM domain of EPH-A2 family of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A2 subfamily of receptor tyrosine kinases is a C-terminal protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A2 receptors and appears to mediate cell-cell initiated signal transduction. For example, SAM domain of EPH-A2 receptors interacts with SAM domain of Ship2 proteins (SH2 containing phosphoinositide 5-phosphotase-2) forming heterodimers; such recruitment of Ship2 by EPH-A2 attenuates the positive signal for receptor endocytosis. Eph-A2 is found overexpressed in many types of human cancer, including breast, prostate, lung and colon cancer. High level of expression could induce cancer progression by a variety of mechanisms and could be used as a novel tag for cancer immunotherapy. EPH-A2 receptors are attractive targets for drag design.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 291245069    5 VERWLETFMCKQYAETFEKCGYKTLSSVCQLDRHTLRSMGV 45
Cdd:cd09543     8 VAEWLESIKMQQYTEHFMAAGYNSIDKVLQMTQEDIKHIGV 48

SAM domain of EPH-A5 subfamily of tyrosine kinase receptors; SAM (sterile alpha motif) domain of EPH-A5 subfamily of receptor tyrosine kinases is a C-terminal potential protein-protein interaction domain. This domain is located in the cytoplasmic region of EPH-A5 receptors and appears to mediate cell-cell initiated signal transduction. Eph-A5 gene is almost exclusively expressed in the nervous system. Murine EPH-A5 receptors participate in axon guidance during embryogenesis and play a role in the adult synaptic plasticity, particularly in neuron-target interactions in multiple neural circuits. Additionally EPH-A5 receptors and its ligand ephrin A5 regulate dopaminergic axon outgrowth and influence the formation of the midbrain dopaminergic pathways. EphA5 gene expression was found decreased in a few different breast cancer cell lines, thus it might be a potential molecular marker for breast cancer carcinogenesis and progression.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 291245069    5 VERWLETFMCKQYAETFEKCGYKTLSSVCQLDRHTLRSMGV-LEEHCDNIIENVSVLR 61
Cdd:cd09546     6 VGEWLEAIKMGRYTEIFMENGYSSMDAVAQVTLEDLRRLGVtLVGHQKKIMNSIQEMR 63

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 291245069  363 SPLGQPGSHPSPVPSPATSIRSPVSIHSPNSV----------PSRSPAPSPITVRSPLCGMVQSPAALPSPGS----SNG 428
Cdd:PHA03247 2825 AGPLPPPTSAQPTAPPPPPGPPPPSLPLGGSVapggdvrrrpPSRSPAAKPAAPARPPVRRLARPAVSRSTESfalpPDQ 2904

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 291245069  429 SVKSPLSVPQKSPNNWQQPVSPVGNQTSYKSVPHHQIPNGPYVNPNGQQiSPTQHDSLQNKGALPRLEEMVaflgePKSK 508
Cdd:PHA03247 2905 PERPPQPQAPPPPQPQPQPPPPPQPQPPPPPPPRPQPPLAPTTDPAGAG-EPSGAVPQPWLGALVPGRVAV-----PRFR 2978

                         170
                  ....*....|....*..
gi 291245069  509 GPAAQNSKEDDGNSPKP 525
Cdd:PHA03247 2979 VPQPAPSREAPASSTPP 2995

SAM domain (Sterile alpha motif);

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 291245069     5 VERWLETFMCKQYAETFEKCGYKTLSSVCQLDRHTLRSMGVL 46
Cdd:pfam07647    9 VADWLRSIGLEQYTDNFRDQGITGAELLLRLTLEDLKRLGIT 50