RING finger (Really Interesting New Gene) domain and U-box domain superfamily; 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 different Cys/His patterns while some lack a single Cys or His residue at typical Zn ligand positions (the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can indeed chelate Zn in a RING finger as well). C4C4-, C3HC3D-, C2H2C4-, and C3HC5-type RING fingers are closely related to RING-HC fingers. In contrast, C4HC3- (RING-CH alias RINGv), C3H3C2-, C3H2C2D-, C3DHC3-, and C4HC2H-type RING fingers are more closely related to RING-H2 fingers. However, not all RING finger-containing proteins display regular RING finger features, and the RING finger family has turned out to be multifarious. The degenerate RING fingers of the Siz/PIAS RING (SP-RING) family proteins and sporulation protein RMD5, are characterized by lacking the second, fifth, and sixth Zn2+ ion-coordinating residues. They bind only one Zn2+ ion. On the other hand, the RING fingers of the human APC11 and RBX1 proteins can bind a third Zn atom since they harbor four additional Zn ligands. U-box is a modified form of the RING finger domain that lacks metal chelating Cys and His residues. It resembles the cross-brace RING structure consisting of three beta-sheets and a single alpha-helix, which would be stabilized by salt bridges instead of chelated metal ions. U-box proteins are widely distributed among eukaryotic organisms and show a higher prevalence in plants than in other organisms. RING finger/U-box-containing proteins are 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 enable efficient transfer of ubiquitin from E2 to the substrates.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 31543543  737 KVSLKCPITFRRIQLPARGHDCKHVQCFDLESYLQLNCERGTWRCPVCNKTALLEGLEVDQYMW 800
Cdd:cd16822    1 KVSLKCPITFRRIQLPARGHDCKHVQCFDLESYLQLNCERGTWRCPVCNKTALLEGLEVDQYMW 64

SP-RING finger found in zinc finger MIZ domain-containing protein 1 (Zmiz1) and similar proteins; Zmiz1, also known as PIAS-like protein Zimp10 (zinc finger-containing, Miz1, PIAS-like protein on chromosome 10) or retinoic acid-induced protein 17, is a novel PIAS-like protein that was initially identified as an androgen receptor (AR) interacting protein and functions as a transcriptional co-activator. It co-localizes with AR and small ubiquitin-like modifier SUMO-1, forms a protein complex at replication foci in the nucleus, and augments AR-mediated transcription. It also functions as a transcriptional co-activator of the p53 tumor suppressor that plays a critical role in cell cycle progression, DNA repair, and apoptosis. Moreover, Zmiz1 dysfunction may be associated with multiple autoimmune diseases and it has been implicated in the development, function, and survival of melanocytes. Zmiz1 also interacts with Smad3/4 proteins and augments Smad-mediated transcription, suggesting it is important in the regulation of the transforming growth factor beta (TGF-beta)/Smad signaling pathway and may have an inhibitory effect on the immune system. Zmiz1 is overexpressed in a significant percentage of human cutaneous squamous cell carcinoma (SCC), breast, ovarian, and colon cancers, suggesting it may play a broader role in epithelial cancers. It functionally interacts with NOTCH1 to promote C-MYC transcription and activity, and thus is involved in a variety of C-MYC-driven cancers. Zmiz1 contains a PAT domain, a highly conserved Siz/PIAS (protein inhibitor of activated signal transducer and activator of transcription) RING (SP-RING) finger, also known as msx-interacting zinc finger (Miz domain), and a putative nuclear localization sequence (NLS), as well as a strong intrinsic transactivation domain within the C-terminus. The SP-RING finger is a variant of RING finger, which lacks the second, fifth, and sixth zinc-binding residues of the consensus C3H2C3-/C3HC4-type RING fingers. It binds a single Zn ion, instead of two ions bound by typical RING fingers.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 31543543  737 KVSLKCPITFRRIQLPARGHDCKHVQCFDLESYLQLNCERGTWRCPVCNKTALLEGLEVDQYMW 800
Cdd:cd16822    1 KVSLKCPITFRRIQLPARGHDCKHVQCFDLESYLQLNCERGTWRCPVCNKTALLEGLEVDQYMW 64

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543543   185 PMANANNPmnPGGNPMASGMTTSNPGLNSPQFAGQQQQFSAKAGPAQPYIQQSMYGRPNYPGSGGFGASYPGGPNAPAGM 264
Cdd:PHA03247 2631 PSPAANEP--DPHPPPTVPPPERPRDDPAPGRVSRPRRARRLGRAAQASSPPQRPRRRAARPTVGSLTSLADPPPPPPTP 2708

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543543   265 GIPPHTRPPADFTQPAAAAAAAAVAAAAATATATATATVAALQETQNKDINQYGPMGPTQAYNSQF-MNQPGPRGPASMG 343
Cdd:PHA03247 2709 EPAPHALVSATPLPPGPAAARQASPALPAAPAPPAVPAGPATPGGPARPARPPTTAGPPAPAPPAApAAGPPRRLTRPAV 2788

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543543   344 GSMNPASMAAGmTPSGMSGPPMGMNQP--------RPPGISPFGTHGQRMPQQTYPGPRPQSLPIQNikRPYPGEPnygN 415
Cdd:PHA03247 2789 ASLSESRESLP-SPWDPADPPAAVLAPaaalppaaSPAGPLPPPTSAQPTAPPPPPGPPPPSLPLGG--SVAPGGD---V 2862

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543543   416 QQYGPNSQFPTQPGQYPAPnPPRPLTSPNYPGQRMP-SQPSSGQYPPPTVNMGQYYKPEqfngqnntfsgssysnysqgn 494
Cdd:PHA03247 2863 RRRPPSRSPAAKPAAPARP-PVRRLARPAVSRSTESfALPPDQPERPPQPQAPPPPQPQ--------------------- 2920

                         330       340       350       360       370       380
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 31543543   495 vnrPPRPVPVANYPHSPVPGNPTPPMTPGSSIPPYLSPSQDVKPPFPPDIKPNMSALP----PPPA 556
Cdd:PHA03247 2921 ---PQPPPPPQPQPPPPPPPRPQPPLAPTTDPAGAGEPSGAVPQPWLGALVPGRVAVPrfrvPQPA 2983

polyadenylate binding protein, human types 1, 2, 3, 4 family; These eukaryotic proteins recognize the poly-A of mRNA and consists of four tandem RNA recognition domains at the N-terminus (rrm: pfam00076) followed by a PABP-specific domain (pfam00658) at the C-terminus. The protein is involved in the transport of mRNA's from the nucleus to the cytoplasm. There are four paralogs in Homo sapiens which are expressed in testis, platelets, broadly expressed and of unknown tissue range.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543543    380 THGQRMPQQTYPGPRPQSLPIQNIkrPYPGEPNYGNQqyGPNSQFPTQPGQYPApnpprpltSPNYPGQRMPSQPSSGQY 459
Cdd:TIGR01628  369 AHLQDQFMQLQPRMRQLPMGSPMG--GAMGQPPYYGQ--GPQQQFNGQPLGWPR--------MSMMPTPMGPGGPLRPNG 436

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 31543543    460 PPPTVNMGQYYKPEQFNGQNNTFSGSSYSNYSQGNVNRPPRPVPVANYPH 509
Cdd:TIGR01628  437 LAPMNAVRAPSRNAQNAAQKPPMQPVMYPPNYQSLPLSQDLPQPQSTASQ 486

SP-RING finger found in zinc finger MIZ domain-containing protein 1 (Zmiz1) and similar proteins; Zmiz1, also known as PIAS-like protein Zimp10 (zinc finger-containing, Miz1, PIAS-like protein on chromosome 10) or retinoic acid-induced protein 17, is a novel PIAS-like protein that was initially identified as an androgen receptor (AR) interacting protein and functions as a transcriptional co-activator. It co-localizes with AR and small ubiquitin-like modifier SUMO-1, forms a protein complex at replication foci in the nucleus, and augments AR-mediated transcription. It also functions as a transcriptional co-activator of the p53 tumor suppressor that plays a critical role in cell cycle progression, DNA repair, and apoptosis. Moreover, Zmiz1 dysfunction may be associated with multiple autoimmune diseases and it has been implicated in the development, function, and survival of melanocytes. Zmiz1 also interacts with Smad3/4 proteins and augments Smad-mediated transcription, suggesting it is important in the regulation of the transforming growth factor beta (TGF-beta)/Smad signaling pathway and may have an inhibitory effect on the immune system. Zmiz1 is overexpressed in a significant percentage of human cutaneous squamous cell carcinoma (SCC), breast, ovarian, and colon cancers, suggesting it may play a broader role in epithelial cancers. It functionally interacts with NOTCH1 to promote C-MYC transcription and activity, and thus is involved in a variety of C-MYC-driven cancers. Zmiz1 contains a PAT domain, a highly conserved Siz/PIAS (protein inhibitor of activated signal transducer and activator of transcription) RING (SP-RING) finger, also known as msx-interacting zinc finger (Miz domain), and a putative nuclear localization sequence (NLS), as well as a strong intrinsic transactivation domain within the C-terminus. The SP-RING finger is a variant of RING finger, which lacks the second, fifth, and sixth zinc-binding residues of the consensus C3H2C3-/C3HC4-type RING fingers. It binds a single Zn ion, instead of two ions bound by typical RING fingers.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 31543543  737 KVSLKCPITFRRIQLPARGHDCKHVQCFDLESYLQLNCERGTWRCPVCNKTALLEGLEVDQYMW 800
Cdd:cd16822    1 KVSLKCPITFRRIQLPARGHDCKHVQCFDLESYLQLNCERGTWRCPVCNKTALLEGLEVDQYMW 64

SP-RING finger found in zinc finger MIZ domain-containing protein Zmiz1, Zmiz2, and similar proteins; This subfamily includes Zmiz1 (Zimp10) and its homolog Zmiz2 (Zimp7), both initially identified in humans as androgen receptor (AR) interacting proteins which function as transcriptional co-activators. They interact with BRG1, the catalytic subunit of the SWI-SNF remodeling complex. They also associate with other hormone nuclear receptors and transcription factors, such as p53 and Smad3/Smad4, and regulate transcription of specific target genes by altering their chromatin structure. This subfamily also includes tonalli (Tna), an ortholog identified in Drosophila. It genetically interacts with the ATP-dependent SWI/SNF and Mediator complexes, suggesting a potential role for the Zmiz proteins in chromatin remodeling. Zmiz proteins contain a highly conserved Siz/PIAS (protein inhibitor of activated signal transducer and activator of transcription) RING (SP-RING) finger, also known as msx-interacting zinc finger (Miz domain), and a strong transactivation domain within the C-terminus. The SP-RING/Miz domain is highly conserved in members of the PIAS family and confers SUMO-conjugating activity. It is a variant of the RING finger, and lacks the second, fifth, and sixth zinc-binding residues of the consensus C3H2C3-/C3HC4-type RING fingers. It binds a single Zn ion, instead of two ions bound by typical RING fingers. The strong intrinsic transactivation domain facilitates Zmiz proteins to augment the transcriptional activity of nuclear hormone receptors and other transcriptional factors. They may act as transcriptional co-regulators.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 31543543  739 SLKCPITFRRIQLPARGHDCKHVQCFDLESYLQLNCERGTWRCPVCNK 786
Cdd:cd16791    1 SLKCPITFRRITLPARGHDCKHIQCFDLESYLQLNCERGTWRCPVCNK 48

MIZ/SP-RING zinc finger; This domain has SUMO (small ubiquitin-like modifier) ligase activity and is involved in DNA repair and chromosome organization.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 31543543    738 VSLKCPITFRRIQLPARGHDCKHVQCFDLESYLQLNCERGTWRCPVCNK 786
Cdd:pfam02891    1 VSLKCPISYLRISIPVRGRFCKHLQCFDLLSYLESNERTPTWNCPVCDK 49

SP-RING finger and SPL-RING finger, variants of RING fingers; This family corresponds to a group of proteins with variants of RING fingers that are characterized by lacking the second, fifth, and sixth Zn2+ ion-coordinating residues compared with the classic C3H2C3-/C3HC4-type RING fingers. They include SP-RING finger found in the Siz/PIAS RING (SP-RING) family of SUMO E3 ligases and SPL-RING finger found in E3 SUMO-protein ligase NSE2. The SP-RING family includes PIAS (protein inhibitor of activated STAT) proteins, Zmiz proteins, and Siz proteins from plants and fungi. The PIAS (protein inhibitor of activated STAT) protein family modulates the activity of several transcription factors and acts as an E3 ubiquitin ligase in the sumoylation pathway. NSE2, also known as MMS21 homolog (MMS21) or non-structural maintenance of chromosomes element 2 homolog (Non-SMC element 2 homolog, NSMCE2), is an autosumoylating small ubiquitin-like modifier (SUMO) ligase required for the response to DNA damage. It regulates sumoylation and nuclear-to-cytoplasmic translocation of skeletal and heart muscle-specific variant of the alpha subunit of nascent polypeptide associated complex (skNAC)-Smyd1 in myogenesis. It is also required for resisting extrinsically induced genotoxic stress.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 31543543  740 LKCPITFRRIQLPARGHDCKHvqCFDLESYLQLNCER-GTWRCPVCN 785
Cdd:cd16452    1 LKCPITQKRMKDPVRGKHCGH--CFDLEAILQYLKRRkKKWKCPVCS 45

SP-RING finger found in protein inhibitor of activated STAT protein 4 (PIAS4) and similar proteins; PIAS4, also known as PIASy or protein inhibitor of activated STAT protein gamma (PIAS-gamma), is an E3 SUMO-protein ligase that interacts with the androgen receptor (AR) and is involved in ubiquitin signaling pathways. It is associated with macro/microcephaly in the novel interstitial 19p13.3 microdeletion/microduplication syndrome. It also regulates the hypoxia signalling pathway by interacting with the tumor suppressor von Hippel-Lindau (VHL), which leads to VHL sumoylation, oligomerization, and impaired function during growth of pancreatic cancer cells. Moreover, PIAS4 acts as a direct binding partner for vitamin D receptor (VDR) and facilitates its modification with SUMO2. The process of SUMOylation modulates VDR-mediated signaling. As components of the DNA-damage response (DDR), PIAS4 together with PIAS1 promote responses to DNA double-strand breaks (DSBs). They are required for effective ubiquitin-adduct formation mediated by RNF8, RNF168, and BRCA1 at sites of DNA damage. PIAS4 contains an N-terminal SAP (scaffold attachment factor A/B (SAF-A/B), acinus and PIAS) box with the LXXLL signature, a PINT motif, a specific RING finger known as Siz/PIAS (protein inhibitor of activated signal transducer and activator of transcription) RING (SP-RING) finger, and an acidic C-terminal domain. The SP-RING finger is a variant of RING finger, which lacks the second, fifth, and sixth zinc-binding residues of the consensus C3H2C3-/C3HC4-type RING fingers. It binds a single Zn ion, instead of two ions bound by typical RING fingers.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 31543543  734 TAIKVSLKCPITFRRIQLPARGHDCKHVQCFDLESYLQLNCERGTWRCPVCNKTALLE 791
Cdd:cd16821    1 TGVRVSLICPLVKMRLSVPCRAETCAHLQCFDAVFYLQMNEKKPTWTCPVCDKPAPYD 58

SP-RING finger found in protein inhibitor of activated STAT protein 1 (PIAS1) and similar proteins; PIAS1, also known as DEAD/H box-binding protein 1, Gu-binding protein (GBP), or RNA helicase II-binding protein, was initially identified as an inhibitor of STAT1 that blocks the DNA-binding activity of STAT1 and specifically inhibits STAT1-mediated gene transcription in response to cytokine stimulation. It selectively inhibits interferon-inducible gene expression and plays an important role in the IFN-gamma- or IFN-beta-mediated innate immune response through negative regulation of STAT1. It also regulates the activity of other transcription factors to regulate immune response, such as NF-kappaB and Smad4. Moreover, PIAS1 functions as an E3 small ubiquitin-like modifier (SUMO)-protein ligase specifying target proteins for SUMO conjugation by Ubc9. The sumoylation activity of PIAS1 can suppress cytokine transforming growth factor beta (TGFbeta)-induced epithelial mesenchymal transition (EMT) in non-transformed epithelial cells to promote activation of the matrix metalloproteinase 2 (MMP2). It thus regulates TGFbeta-induced cancer cell invasion and metastasis. PIAS1 may also be involved in spatial learning and memory formation through its SUMOylation of cAMP-responsive element binding protein (CREB). In addition, PIAS1 is the E3 ligase responsible for SUMOylation of High mobility group nucleosomal binding domain 2 (HMGN2), which is a small and unique non-histone protein that has many functions in a variety of cellular processes, including regulation of chromatin structure, transcription, and DNA repair, as well as antimicrobial activity, cell homing, and regulating cytokine release. Furthermore, PIAS1 is a genuine chromatin-bound androgen receptor (AR) co-regulator that functions in a target gene selective fashion to regulate prostate cancer cell growth. It also mediates the SUMOylation of c-Myc, which is the most frequently overexpressed oncogene in tumors, including breast cancer, colon cancer, and lung cancer. Necdin, a pleiotropic protein that promotes differentiation and survival of mammalian neurons, can suppress PIAS1 both by inhibiting SUMO E3 ligase activity and by promoting ubiquitin-dependent degradation. PIAS1 contains an N-terminal SAP (scaffold attachment factor A/B (SAF-A/B), acinus and PIAS) box with the LXXLL signature, a PINT motif, a specific RING finger known as Siz/PIAS (protein inhibitor of activated signal transducer and activator of transcription) RING (SP-RING) finger, and the acidic C-terminal domain. The SP-RING finger mediates the interaction of PIAS1 with the SUMO E2 conjugating enzyme Ubc9. It binds a single Zn ion, instead of two ions bound by typical RING fingers.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543543  734 TAIKVSLKCPITFRRIQLPARGHDCKHVQCFDLESYLQLNCERGTWRCPVCNKTALLEGL 793
Cdd:cd16818    1 TSLRVSLLCPLGKMRLTIPCRALTCSHLQCFDATLYIQMNEKKPTWVCPVCDKKAPYEHL 60

SP-RING finger found in Saccharomyces cerevisiae E3 SUMO-protein ligase SIZ1, SIZ2, and similar proteins; Saccharomyces cerevisiae SIZ proteins, also known as SAP and Miz-finger domain-containing proteins, are Siz/PIAS RING (SP-RING) family SUMO E3 ligases, and may be involved in a novel pathway of chromosome maintenance. They enhance SUMO modification with many substrates in vivo, but also exhibit unique substrate specificity. SIZ1, also known as ubiquitin-like protein ligase 1 (Ull1), modifies both cytoplasmic and nuclear proteins. It functions as an E3 factor specific for septin components. SIZ1-dependent substrates include Cdc3 and Cdc11 (septin subunits), Prp45 (a splicing factor), and the proliferating cell nuclear antigen (PCNA). SIZ2, also known as NFI1, interacts with Smt3, SUMO/Smt3 conjugating enzyme Ubc9, and a septin component Cdc3. Members of this subfamily contain an N-terminal SAP (scaffold attachment factor A/B (SAF-A/B), acinus and PIAS) box with the LXXLL signature, a PINT motif, a specific RING finger known as Siz/PIAS (protein inhibitor of activated signal transducer and activator of transcription) RING (SP-RING) finger, and an acidic C-terminal domain. The SP-RING finger is a variant of RING finger, which lacks the second, fifth, and sixth zinc-binding residues of the consensus C3H2C3-/C3HC4-type RING fingers. It binds a single Zn ion, instead of two ions bound by typical RING fingers.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 31543543  738 VSLKCPITFRRIQLPARGHDCKHVQCFDLESYLQLNCERGTWRCPVC 784
Cdd:cd16793    4 MSLQCPISYTRMKYPSKSINCKHLQCFDALWFLHSQLQIPTWQCPVC 50

SPL-RING finger found in E3 SUMO-protein ligase NSE2 and similar proteins; NSE2, also known as MMS21 homolog (MMS21) or non-structural maintenance of chromosomes element 2 homolog (Non-SMC element 2 homolog, NSMCE2), is an autosumoylating small ubiquitin-like modifier (SUMO) ligase required for the response to DNA damage. It regulates sumoylation and nuclear-to-cytoplasmic translocation of skeletal and heart muscle-specific variant of the alpha subunit of nascent polypeptide associated complex (skNAC)-Smyd1 in myogenesis. It is also required for resisting extrinsically induced genotoxic stress. Moreover, NSE2 together with its partner proteins SMC6 and SMC5 form a tight subcomplex of the structural maintenance of chromosomes SMC5-6 complex, which includes another two subcomplexes, NSE1-NSE3-NSE4 and NSE5-NSE6. SMC6 and NSE3 are sumoylated in an NSE2-dependent manner, but SMC5 and NSE1 are not. NSE2-dependent E3 SUMO ligase activity is required for efficient DNA repair, but not for SMC5-6 complex stability. NSE2 contains a RING variant known as a Siz/PIAS (protein inhibitor of activated signal transducer and activator of transcription)-like RING (SPL-RING) finger that is likely shared by the SP-RING type SUMO E3 ligases, such as PIAS family proteins. The SPL-RING finger is a variant of the RING finger, which lacks the second, fifth, and sixth zinc-binding residues of the consensus C3H2C3-/C3HC4-type RING fingers. It harbors only one Zn binding site and is required for the sumoylating activity.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 31543543  740 LKCPITFRRIQLPARGHDCKHVqcFDLESYLQ-LNCERGTWRCPV--CNKTALLEGLEVDQYMW 800
Cdd:cd16651    1 LKCPITQQLMVDPVRNKKCGHT--YEKAAILQyLQSRKKKAKCPVagCRNTVSKSDLVPDPELK 62

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543543   185 PMANANNPMNPGGNPMASGMTTSNPGLNSPQfagQQQQFSAKAGPAQPYIQQSMYGRPNYPGSGGFGASYPGGPNAPAGM 264
Cdd:PHA03247 2619 PDTHAPDPPPPSPSPAANEPDPHPPPTVPPP---ERPRDDPAPGRVSRPRRARRLGRAAQASSPPQRPRRRAARPTVGSL 2695

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543543   265 GIPPHTRPPADFTQPAAAAAAAAVAAaaatatatatatvaalqetqnkdinqygPMGPTQAYNSQFMNQPGPRGPASMGG 344
Cdd:PHA03247 2696 TSLADPPPPPPTPEPAPHALVSATPL----------------------------PPGPAAARQASPALPAAPAPPAVPAG 2747

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543543   345 SMNPASMAAGMTPSGMSGPPmgmnQPRPPGISPFGthgqrmPQQTYPGPRPQSLPIQNIKRPYPGEPnygnqQYGPNSQF 424
Cdd:PHA03247 2748 PATPGGPARPARPPTTAGPP----APAPPAAPAAG------PPRRLTRPAVASLSESRESLPSPWDP-----ADPPAAVL 2812

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543543   425 PTQPGQYPAPNPPRPLTSPNYPGQRMPSQPSSgqYPPPTVNMGQYYKPeqfngqNNTFSGSSYSNYSQGNVNRPPRPvPV 504
Cdd:PHA03247 2813 APAAALPPAASPAGPLPPPTSAQPTAPPPPPG--PPPPSLPLGGSVAP------GGDVRRRPPSRSPAAKPAAPARP-PV 2883

                         330       340       350       360       370       380
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 31543543   505 ANYPHSPV----------PGNPTPPMTPGSSIPPYLSPSQDVKP-PFPPDIKPNMSALPPPP 555
Cdd:PHA03247 2884 RRLARPAVsrstesfalpPDQPERPPQPQAPPPPQPQPQPPPPPqPQPPPPPPPRPQPPLAP 2945

EBNA-3B; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543543   306 LQETQNKDINQYGPMGPTQAYNSQFMNQPG--PRGPASMggSMNPASMAAGMTPSGMSGPPMGMNQPRPpgiSPFGTHGQ 383
Cdd:PHA03378  574 IQPLTSPTTSQLASSAPSYAQTPWPVPHPSqtPEPPTTQ--SHIPETSAPRQWPMPLRPIPMRPLRMQP---ITFNVLVF 648

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543543   384 RMPQQTypgPRPQSLPIQNiKRPYPGEPNYGNQQYGPNSQFPTQ--PGQY-PAPNPPRPLTSPNY-PGQRMPSQPSSGQY 459
Cdd:PHA03378  649 PTPHQP---PQVEITPYKP-TWTQIGHIPYQPSPTGANTMLPIQwaPGTMqPPPRAPTPMRPPAApPGRAQRPAAATGRA 724

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543543   460 PPPTVNMGQYYKPEQFNGQNNTFSGSSysnysqgNVNRPPRPVPVANYPHSPVPGNPTPPMTPGSSIPPYLSPSQDVKPP 539
Cdd:PHA03378  725 RPPAAAPGRARPPAAAPGRARPPAAAP-------GRARPPAAAPGRARPPAAAPGAPTPQPPPQAPPAPQQRPRGAPTPQ 797

                         250       260       270
                  ....*....|....*....|....*....|....*....
gi 31543543   540 FPPDIKPNMSALPPP-------PANHNDELRLTFPVRDG 571
Cdd:PHA03378  798 PPPQAGPTSMQLMPRaapgqqgPTKQILRQLLTGGVKRG 836

104 kDa microneme/rhoptry antigen; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543543   336 PRGPASMGgsMNPASMAAGMTPSGMSGPPMGMNQPR---PPGISPFGTHGQRmpqqtyPGP----RPQSLPIQNIKRPYP 408
Cdd:PTZ00449  511 PEGPEASG--LPPKAPGDKEGEEGEHEDSKESDEPKeggKPGETKEGEVGKK------PGPakehKPSKIPTLSKKPEFP 582

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543543   409 GEPNYGNQQYGPNS----QFPTQPGQYPAPNPPRPLTSPNYPgqRMPSQPSSGQYPPPTVNMGQYYKPEQFNGQNNTFSG 484
Cdd:PTZ00449  583 KDPKHPKDPEEPKKpkrpRSAQRPTRPKSPKLPELLDIPKSP--KRPESPKSPKRPPPPQRPSSPERPEGPKIIKSPKPP 660

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543543   485 SS-------------YSNYSQG------NVNRPPRPVPVANYPHSPVPGNPTPPMTPGSSIPPYL--SPSQDVKPPFPPD 543
Cdd:PTZ00449  661 KSpkppfdpkfkekfYDDYLDAaakskeTKTTVVLDESFESILKETLPETPGTPFTTPRPLPPKLprDEEFPFEPIGDPD 740

                         250
                  ....*....|...
gi 31543543   544 I-KPNMSALPPPP 555
Cdd:PTZ00449  741 AeQPDDIEFFTPP 753

polyadenylate binding protein, human types 1, 2, 3, 4 family; These eukaryotic proteins recognize the poly-A of mRNA and consists of four tandem RNA recognition domains at the N-terminus (rrm: pfam00076) followed by a PABP-specific domain (pfam00658) at the C-terminus. The protein is involved in the transport of mRNA's from the nucleus to the cytoplasm. There are four paralogs in Homo sapiens which are expressed in testis, platelets, broadly expressed and of unknown tissue range.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543543    380 THGQRMPQQTYPGPRPQSLPIQNIkrPYPGEPNYGNQqyGPNSQFPTQPGQYPApnpprpltSPNYPGQRMPSQPSSGQY 459
Cdd:TIGR01628  369 AHLQDQFMQLQPRMRQLPMGSPMG--GAMGQPPYYGQ--GPQQQFNGQPLGWPR--------MSMMPTPMGPGGPLRPNG 436

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 31543543    460 PPPTVNMGQYYKPEQFNGQNNTFSGSSYSNYSQGNVNRPPRPVPVANYPH 509
Cdd:TIGR01628  437 LAPMNAVRAPSRNAQNAAQKPPMQPVMYPPNYQSLPLSQDLPQPQSTASQ 486

polyadenylate binding protein, human types 1, 2, 3, 4 family; These eukaryotic proteins recognize the poly-A of mRNA and consists of four tandem RNA recognition domains at the N-terminus (rrm: pfam00076) followed by a PABP-specific domain (pfam00658) at the C-terminus. The protein is involved in the transport of mRNA's from the nucleus to the cytoplasm. There are four paralogs in Homo sapiens which are expressed in testis, platelets, broadly expressed and of unknown tissue range.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543543    329 QFMnQPGPRGPASMGGSMNPASMAA----GMTPSGMSGPPMGMNQPRPPGISPFGTHGQRMPQqTYPGPRPQSLPIQNiK 404
Cdd:TIGR01628  374 QFM-QLQPRMRQLPMGSPMGGAMGQppyyGQGPQQQFNGQPLGWPRMSMMPTPMGPGGPLRPN-GLAPMNAVRAPSRN-A 450

                           90       100       110
                   ....*....|....*....|....*....|..
gi 31543543    405 RPYPGEPNYGNQQYGPNSQFPTQPGQYPAPNP 436
Cdd:TIGR01628  451 QNAAQKPPMQPVMYPPNYQSLPLSQDLPQPQS 482

Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543543    319 PMGPTQAYNSQFMNQPGPRGPASMGGSMNPASMAAGMTPSGMSGPPMGMNQPRPPGISPFGTHGQRMPQ----QTYPGPR 394
Cdd:pfam03154  210 GSPATSQPPNQTQSTAAPHTLIQQTPTLHPQRLPSPHPPLQPMTQPPPPSQVSPQPLPQPSLHGQMPPMphslQTGPSHM 289

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543543    395 PQSLPIQnikrPYPGEPNYGNQQY--GPNSQFPTQPGQYPAPNPPRPLTSPNYPGQRMPSQPSSGQY----PPPTVNMGQ 468
Cdd:pfam03154  290 QHPVPPQ----PFPLTPQSSQSQVppGPSPAAPGQSQQRIHTPPSQSQLQSQQPPREQPLPPAPLSMphikPPPTTPIPQ 365

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543543    469 YYKPEQFNGQNNTFSGSSYsnysQGNVNRPPRPV--PVANYPHSPVPGNPTPP---MTPGSSIPPylspsqdvkPPFPPD 543
Cdd:pfam03154  366 LPNPQSHKHPPHLSGPSPF----QMNSNLPPPPAlkPLSSLSTHHPPSAHPPPlqlMPQSQQLPP---------PPAQPP 432

                          250
                   ....*....|....*
gi 31543543    544 IKPNMSALPPPPANH 558
Cdd:pfam03154  433 VLTQSQSLPPPAASH 447

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543543   362 GPPmgmnQPRPPGISPfgthgqRMPQQTYPGPRPQSLPIQ-----NIKRP-YPGEPNYGNQQYGPNSQFPTQPGQYPAP- 434
Cdd:PHA03247 2550 DPP----PPLPPAAPP------AAPDRSVPPPRPAPRPSEpavtsRARRPdAPPQSARPRAPVDDRGDPRGPAPPSPLPp 2619

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543543   435 --NPPRPLTSPNYPGQRMPSQPSSGQYPPPTVNM-----GQYYKPEQFNGQNNTFSGSSysnYSQGNVNRPPRPV--PVA 505
Cdd:PHA03247 2620 dtHAPDPPPPSPSPAANEPDPHPPPTVPPPERPRddpapGRVSRPRRARRLGRAAQASS---PPQRPRRRAARPTvgSLT 2696

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 31543543   506 NY----PHSPVPGNPTPPMTPGSSIPPYLSPSQDVKPPFPPDIKPnmsalPPPPA 556
Cdd:PHA03247 2697 SLadppPPPPTPEPAPHALVSATPLPPGPAAARQASPALPAAPAP-----PAVPA 2746

ARC105 or Med15 subunit of Mediator complex non-fungal; The approx. 70 residue Med15 domain of the ARC-Mediator co-activator is a three-helix bundle with marked similarity to the KIX domain. The sterol regulatory element binding protein (SREBP) family of transcription activators use the ARC105 subunit to activate target genes in the regulation of cholesterol and fatty acid homeostasis. In addition, Med15 is a critical transducer of gene activation signals that control early metazoan development.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543543    321 GPTQAYNSQFMNQ----PGPRGPASMGGSMNPASM-----AAGMTPSGMSGPPMGMNQPRPPGISPFGTHGQRMPQQTYP 391
Cdd:pfam09606   89 LAGQGTRPQMMGPmgpgPGGPMGQQMGGPGTASNLlaslgRPQMPMGGAGFPSQMSRVGRMQPGGQAGGMMQPSSGQPGS 168

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543543    392 GPRPQSLPIQNIKRPYPGEPNYGnQQYGPNSQfptQPGQYPAPNPPRPLTSPNYPGQRMPS----QPSSGQYPPPTVNMG 467
Cdd:pfam09606  169 GTPNQMGPNGGPGQGQAGGMNGG-QQGPMGGQ---MPPQMGVPGMPGPADAGAQMGQQAQAnggmNPQQMGGAPNQVAMQ 244

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 31543543    468 QYYKPEQFNGQNNTFSGSSYSNYSQGNVNRPPRPVPVANY-PHSPVPGNPTPPMTPG 523
Cdd:pfam09606  245 QQQPQQQGQQSQLGMGINQMQQMPQGVGGGAGQGGPGQPMgPPGQQPGAMPNVMSIG 301

polyadenylate binding protein, human types 1, 2, 3, 4 family; These eukaryotic proteins recognize the poly-A of mRNA and consists of four tandem RNA recognition domains at the N-terminus (rrm: pfam00076) followed by a PABP-specific domain (pfam00658) at the C-terminus. The protein is involved in the transport of mRNA's from the nucleus to the cytoplasm. There are four paralogs in Homo sapiens which are expressed in testis, platelets, broadly expressed and of unknown tissue range.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543543    365 MGMNQPrpPGISPF-GTHGQRM-----PQQTYPGpRPQSLPIQNiKRPYPGEPNYGNQ-----QYGPNSQFPTQPGQYPA 433
Cdd:TIGR01628  380 PRMRQL--PMGSPMgGAMGQPPyygqgPQQQFNG-QPLGWPRMS-MMPTPMGPGGPLRpnglaPMNAVRAPSRNAQNAAQ 455

                           90       100       110
                   ....*....|....*....|....*....|.
gi 31543543    434 PNPPRPLTSPnyPGQRMPSQPSSGQYPPPTV 464
Cdd:TIGR01628  456 KPPMQPVMYP--PNYQSLPLSQDLPQPQSTA 484

EBNA-3C; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543543   183 GNPMANANNPMNPGGNPMASGMTTSNPGLNSPQFAGQQQQFSAKAGP--AQPYIQQSMYGRPNYPGSGGFGA-------S 253
Cdd:PHA03377  561 GPPKASPPVMAPPSTGPRVMATPSTGPRDMAPPSTGPRQQAKCKDGPpaSGPHEKQPPSSAPRDMAPSVVRMflrerllE 640

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543543   254 YPGGPNAP------AGMGIPPHTRPPADFTQPAAAAAAAAVAAAAATATATATATVaalqETQNKDINQYGPMGPTQAYN 327
Cdd:PHA03377  641 QSTGPKPKsfwemrAGRDGSGIQQEPSSRRQPATQSTPPRPSWLPSVFVLPSVDAG----RAQPSEESHLSSMSPTQPIS 716

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543543   328 SQfmNQPGPRGPAsmggsmnpasmaagmTPSGMSGPPMgmNQPRPPGISPFGTHGQ-RMPQQTYPG---PRPQSLPIQNI 403
Cdd:PHA03377  717 HE--EQPRYEDPD---------------DPLDLSLHPD--QAPPPSHQAPYSGHEEpQAQQAPYPGywePRPPQAPYLGY 777

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543543   404 KRPypgepnygNQQYGPNSQFPTQPGQYPA-PNPPRPLTS----PNYPGQRMPSQP--SSGQYPPPTvnmgqyykpeqfn 476
Cdd:PHA03377  778 QEP--------QAQGVQVSSYPGYAGPWGLrAQHPRYRHSwaywSQYPGHGHPQGPwaPRPPHLPPQ------------- 836

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 31543543   477 gqnntFSGSSYSNYSQGNVNRPPRPVPVANYPH-SPVPGNPTPPMTPGSSIPPYLSPsqdvkPPFPPdIKPNMSALPPPP 555
Cdd:PHA03377  837 -----WDGSAGHGQDQVSQFPHLQSETGPPRLQlSQVPQLPYSQTLVSSSAPSWSSP-----QPRAP-IRPIPTRFPPPP 905

                  ....*..
gi 31543543   556 ANHNDEL 562
Cdd:PHA03377  906 MPLQDSM 912

capsid maturational protease; Provisional

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 31543543   386 PQQTYPGPRPQSLPIQNIKRPYPGEPNYGNQQYGPNSQFPTQPGqypapnpPRPLTSPNYPGQRMPSQPSSGQYPPPT 463
Cdd:PHA03369  371 APQTHTGPADRQRPQRPDGIPYSVPARSPMTAYPPVPQFCGDPG-------LVSPYNPQSPGTSYGPEPVGPVPPQPT 441