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 578819647  743 KVSLKCPITFRRIQLPARGHDCKHVQCFDLESYLQLNCERGTWRCPVCNKTALLEGLEVDQYMW 806
Cdd:cd16822     1 KVSLKCPITFRRIQLPARGHDCKHVQCFDLESYLQLNCERGTWRCPVCNKTALLEGLEVDQYMW 64

DNA translocase FtsK; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578819647  386 THGQRMPQQTYPGPRPQSL------PIQNIKRPYPGEPnygnqQYGPNSQFPTQPGQYPAPNPPRPLTSPNYPGQRMPSQ 459
Cdd:PRK10263  706 TQQQRYSGEQPAGANPFSLddfefsPMKALLDDGPHEP-----LFTPIVEPVQQPQQPVAPQQQYQQPQQPVAPQPQYQQ 780

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578819647  460 PSSGQYPPPtvnmgQYYKPEQFNGQNNTFSGSSYSNYSQGNVNRPPRpvPVANYPHSPVPGNPTPPMTPGSSIPPYLSPS 539
Cdd:PRK10263  781 PQQPVAPQP-----QYQQPQQPVAPQPQYQQPQQPVAPQPQYQQPQQ--PVAPQPQYQQPQQPVAPQPQDTLLHPLLMRN 853

                         170       180
                  ....*....|....*....|....
gi 578819647  540 QDVKPPFPPDIK-PNMSALPPPPA 562
Cdd:PRK10263  854 GDSRPLHKPTTPlPSLDLLTPPPS 877

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 578819647  743 KVSLKCPITFRRIQLPARGHDCKHVQCFDLESYLQLNCERGTWRCPVCNKTALLEGLEVDQYMW 806
Cdd:cd16822     1 KVSLKCPITFRRIQLPARGHDCKHVQCFDLESYLQLNCERGTWRCPVCNKTALLEGLEVDQYMW 64

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 578819647   184 NPMANANNPMNPGGNPMASGMTTSNPglNSPQFAGQQQQFSAKAGPAQPYIQQSMYGRPNYPGSGGfGASYPGGPNAPAG 263
Cdd:pfam09606  115 GGPGTASNLLASLGRPQMPMGGAGFP--SQMSRVGRMQPGGQAGGMMQPSSGQPGSGTPNQMGPNG-GPGQGQAGGMNGG 191

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578819647   264 MGIPPHTRPPADFTQPAAAAAAAAVAAAAATATATATATVAALQETQNKDINQYGPVcssfQMGPTQAYNSQFMNQP--- 340
Cdd:pfam09606  192 QQGPMGGQMPPQMGVPGMPGPADAGAQMGQQAQANGGMNPQQMGGAPNQVAMQQQQP----QQQGQQSQLGMGINQMqqm 267

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578819647   341 -----GPRGPASMGGSMNPASMAAGMTPSGMS--GPPM-----GMNQPRPPGISPFGTHGQRMPQQTYPGPRPQSLPIQN 408
Cdd:pfam09606  268 pqgvgGGAGQGGPGQPMGPPGQQPGAMPNVMSigDQNNyqqqqTRQQQQQQGGNHPAAHQQQMNQSVGQGGQVVALGGLN 347

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 578819647   409 IKRPY--------------PGEPNY--GNQQYGPNSQFPTQPGQYPAPNPPRPLTSPNYPGQRMPSQPSSGQYPPP 468
Cdd:pfam09606  348 HLETWnpgnfgglganpmqRGQPGMmsSPSPVPGQQVRQVTPNQFMRQSPQPSVPSPQGPGSQPPQSHPGGMIPSP 423

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 578819647   386 THGQRMPQQTYPGPRPQSLPIQNIkrPYPGEPNYGNQqyGPNSQFPTQPGQYPApnpprpltSPNYPGQRMPSQPSSGQY 465
Cdd:TIGR01628  369 AHLQDQFMQLQPRMRQLPMGSPMG--GAMGQPPYYGQ--GPQQQFNGQPLGWPR--------MSMMPTPMGPGGPLRPNG 436

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 578819647   466 PPPTVNMGQYYKPEQFNGQNNTFSGSSYSNYSQGNVNRPPRPVPVANYPH 515
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 578819647   452 PGQRMPSQPSSGQypPPTVNMGQYykpEQFNGQNNTFSGSSYSNYSQGNvNRPPRPVPVANYPHSPVPGNPTPPMTPGSS 531
Cdd:TIGR01628  385 LPMGSPMGGAMGQ--PPYYGQGPQ---QQFNGQPLGWPRMSMMPTPMGP-GGPLRPNGLAPMNAVRAPSRNAQNAAQKPP 458

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 578819647   532 IPPYLSPSQDVKPPFPPDiKPNmsalPPPPANHNDELRLT 571
Cdd:TIGR01628  459 MQPVMYPPNYQSLPLSQD-LPQ----PQSTASQGGQNKKL 493

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 578819647  743 KVSLKCPITFRRIQLPARGHDCKHVQCFDLESYLQLNCERGTWRCPVCNKTALLEGLEVDQYMW 806
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 578819647  745 SLKCPITFRRIQLPARGHDCKHVQCFDLESYLQLNCERGTWRCPVCNK 792
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 578819647   744 VSLKCPITFRRIQLPARGHDCKHVQCFDLESYLQLNCERGTWRCPVCNK 792
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 578819647  746 LKCPITFRRIQLPARGHDCKHvqCFDLESYLQLNCER-GTWRCPVCN 791
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 578819647  740 TAIKVSLKCPITFRRIQLPARGHDCKHVQCFDLESYLQLNCERGTWRCPVCNKTALLE 797
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 578819647  740 TAIKVSLKCPITFRRIQLPARGHDCKHVQCFDLESYLQLNCERGTWRCPVCNKTALLEGL 799
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 578819647  744 VSLKCPITFRRIQLPARGHDCKHVQCFDLESYLQLNCERGTWRCPVC 790
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 578819647  746 LKCPITFRRIQLPARGHDCKHVqcFDLESYLQ-LNCERGTWRCPV--CNKTALLEGLEVDQYMW 806
Cdd:cd16651     1 LKCPITQQLMVDPVRNKKCGHT--YEKAAILQyLQSRKKKAKCPVagCRNTVSKSDLVPDPELK 62

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578819647  185 PMANANNPMNPGGNPMASGMTTSNPGLNSPQfagQQQQFSAKAGPAQPYIQQSMYGRPNYPgsggfgASYPGGPNAPAgm 264
Cdd:PHA03247 2619 PDTHAPDPPPPSPSPAANEPDPHPPPTVPPP---ERPRDDPAPGRVSRPRRARRLGRAAQA------SSPPQRPRRRA-- 2687

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578819647  265 gIPPHTRPPADFTQPAAAAAAAAVAAAAATATATAtatvaalqetqnkdinqygPVCSSFQMGPTQAYNSQFMNQPGPRG 344
Cdd:PHA03247 2688 -ARPTVGSLTSLADPPPPPPTPEPAPHALVSATPL-------------------PPGPAAARQASPALPAAPAPPAVPAG 2747

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578819647  345 PASMGGSMNPASMAAGMTPSGMSGP--PMGMNQPR--PPGISPFGTHGQRMPQQTYPGPRPQSLPIQNIKRPYPGEPNYG 420
Cdd:PHA03247 2748 PATPGGPARPARPPTTAGPPAPAPPaaPAAGPPRRltRPAVASLSESRESLPSPWDPADPPAAVLAPAAALPPAASPAGP 2827

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578819647  421 NQQygPNSQFPTQPGQYPAPNPPR-PLTSPNYPGQRMPSQPSSGQyPPPTVNMGQYYKPEQFNGQNNTFSGSSYSnysqg 499
Cdd:PHA03247 2828 LPP--PTSAQPTAPPPPPGPPPPSlPLGGSVAPGGDVRRRPPSRS-PAAKPAAPARPPVRRLARPAVSRSTESFA----- 2899

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578819647  500 nvnRPPRPVPVANYPHSPVPGNPTPPMTPGSSIPPYLSPSQDVKPPFPPDIKPnMSALPPPPANHNDELRLTFPVRDGVV 579
Cdd:PHA03247 2900 ---LPPDQPERPPQPQAPPPPQPQPQPPPPPQPQPPPPPPPRPQPPLAPTTDP-AGAGEPSGAVPQPWLGALVPGRVAVP 2975

EBNA-3B; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578819647  342 PRGPASMggSMNPASMAAGMTPSGMSGPPMGMNQPRPpgiSPFGTHGQRMPQQTypgPRPQSLPIQNiKRPYPGEPNYGN 421
Cdd:PHA03378  606 PEPPTTQ--SHIPETSAPRQWPMPLRPIPMRPLRMQP---ITFNVLVFPTPHQP---PQVEITPYKP-TWTQIGHIPYQP 676

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578819647  422 QQYGPNSQFPTQ--PGQY-PAPNPPRPLTSPNY-PGQRMPSQPSSGQYPPPTVNMGQYYKPEQFNGQNNTFSGSSysnys 497
Cdd:PHA03378  677 SPTGANTMLPIQwaPGTMqPPPRAPTPMRPPAApPGRAQRPAAATGRARPPAAAPGRARPPAAAPGRARPPAAAP----- 751

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578819647  498 qgNVNRPPRPVPVANYPHSPVPGNPTPPMTPGSSIPPYLSPSQDVKPPFPPDIKPNMSALPPP-------PANHNDELRL 570
Cdd:PHA03378  752 --GRARPPAAAPGRARPPAAAPGAPTPQPPPQAPPAPQQRPRGAPTPQPPPQAGPTSMQLMPRaapgqqgPTKQILRQLL 829

                  ....*..
gi 578819647  571 TFPVRDG 577
Cdd:PHA03378  830 TGGVKRG 836

104 kDa microneme/rhoptry antigen; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578819647  322 SSFQMGPTQAYNSQFMNQPgPRGPASMGgsMNPASMAAGMTPSGMSGPPMGMNQPR---PPGISPFGTHGQRmpqqtyPG 398
Cdd:PTZ00449  492 SKKKLAPIEEEDSDKHDEP-PEGPEASG--LPPKAPGDKEGEEGEHEDSKESDEPKeggKPGETKEGEVGKK------PG 562

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578819647  399 P----RPQSLPIQNIKRPYPGEPNYGNQQYGPNS----QFPTQPGQYPAPNPPRPLTSPNYPgqRMPSQPSSGQYPPPTV 470
Cdd:PTZ00449  563 PakehKPSKIPTLSKKPEFPKDPKHPKDPEEPKKpkrpRSAQRPTRPKSPKLPELLDIPKSP--KRPESPKSPKRPPPPQ 640

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578819647  471 NMGQYYKPEQFNGQNNTFSGSS-------------YSNYSQG------NVNRPPRPVPVANYPHSPVPGNPTPPMTPGSS 531
Cdd:PTZ00449  641 RPSSPERPEGPKIIKSPKPPKSpkppfdpkfkekfYDDYLDAaakskeTKTTVVLDESFESILKETLPETPGTPFTTPRP 720

                         250       260       270
                  ....*....|....*....|....*....|...
gi 578819647  532 IPPYL--SPSQDVKPPFPPDI-KPNMSALPPPP 561
Cdd:PTZ00449  721 LPPKLprDEEFPFEPIGDPDAeQPDDIEFFTPP 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 578819647   386 THGQRMPQQTYPGPRPQSLPIQNIkrPYPGEPNYGNQqyGPNSQFPTQPGQYPApnpprpltSPNYPGQRMPSQPSSGQY 465
Cdd:TIGR01628  369 AHLQDQFMQLQPRMRQLPMGSPMG--GAMGQPPYYGQ--GPQQQFNGQPLGWPR--------MSMMPTPMGPGGPLRPNG 436

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 578819647   466 PPPTVNMGQYYKPEQFNGQNNTFSGSSYSNYSQGNVNRPPRPVPVANYPH 515
Cdd:TIGR01628  437 LAPMNAVRAPSRNAQNAAQKPPMQPVMYPPNYQSLPLSQDLPQPQSTASQ 486

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 578819647   328 PTQAYNSQFMNQPGPRGPASMGGSMNPASMAAGMTPSGMSGPPMGMNQPRPPGISPFGTHGQRMPQ----QTYPGPRPQS 403
Cdd:pfam03154  213 ATSQPPNQTQSTAAPHTLIQQTPTLHPQRLPSPHPPLQPMTQPPPPSQVSPQPLPQPSLHGQMPPMphslQTGPSHMQHP 292

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578819647   404 LPIQnikrPYPGEPNYGNQQY--GPNSQFPTQPGQYPAPNPPRPLTSPNYPGQRMPSQPSSGQY----PPPTVNMGQYYK 477
Cdd:pfam03154  293 VPPQ----PFPLTPQSSQSQVppGPSPAAPGQSQQRIHTPPSQSQLQSQQPPREQPLPPAPLSMphikPPPTTPIPQLPN 368

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578819647   478 PEQFNGQNNTFSGSSYsnysQGNVNRPPRPV--PVANYPHSPVPGNPTPP---MTPGSSIPPylspsqdvkPPFPPDIKP 552
Cdd:pfam03154  369 PQSHKHPPHLSGPSPF----QMNSNLPPPPAlkPLSSLSTHHPPSAHPPPlqlMPQSQQLPP---------PPAQPPVLT 435

                          250
                   ....*....|..
gi 578819647   553 NMSALPPPPANH 564
Cdd:pfam03154  436 QSQSLPPPAASH 447

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 578819647   111 HQKSRQSDPPGKLPMQPPLSSMSSMKPTLSHSDGSFPYDSVPWQQNTNQP-----PGSLSVVTTVWGVTNTSQSQvlgNP 185
Cdd:pfam09606  125 ASLGRPQMPMGGAGFPSQMSRVGRMQPGGQAGGMMQPSSGQPGSGTPNQMgpnggPGQGQAGGMNGGQQGPMGGQ---MP 201

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578819647   186 MA----NANNPMNPGGN-----PMASGMTTSNPGLNSPQFAGQQQQFSAKAGPAQPYIQQSMYGRPNYPGSGGFGASYPG 256
Cdd:pfam09606  202 PQmgvpGMPGPADAGAQmgqqaQANGGMNPQQMGGAPNQVAMQQQQPQQQGQQSQLGMGINQMQQMPQGVGGGAGQGGPG 281

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578819647   257 GPNAPAGMGipPHTRPPADFTQPAAAAAAAAVAAAAATATATATATVAALQETQNKDINQYGPVCSSFQMGPTQAYNSQF 336
Cdd:pfam09606  282 QPMGPPGQQ--PGAMPNVMSIGDQNNYQQQQTRQQQQQQGGNHPAAHQQQMNQSVGQGGQVVALGGLNHLETWNPGNFGG 359

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578819647   337 MNQPGP-RGPASMGGSMNPASMAAGMTPSGMSGPPMGMNQPRPPGISPFGTHGQRMPQQTYPGPRPQSLPIQNIKRPYPG 415
Cdd:pfam09606  360 LGANPMqRGQPGMMSSPSPVPGQQVRQVTPNQFMRQSPQPSVPSPQGPGSQPPQSHPGGMIPSPALIPSPSPQMSQQPAQ 439

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 578819647   416 EPNYGnqQYGPNSQFPTqPGQYPAPNPPRPLTSPNYpgqrMPSQPSSGQYPPPTVNM 472
Cdd:pfam09606  440 QRTIG--QDSPGGSLNT-PGQSAVNSPLNPQEEQLY----REKYRQLTKYIEPLKRM 489

Topoisomerase II-associated protein PAT1; Members of this family are necessary for accurate chromosome transmission during cell division.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578819647   327 GPTQAYNSQFMnQPGPRGPASMGGSMNPASMAAGMTPSGMSGPPM-----GMNQPRPPGISPFGTHGQRMPQQTYPGPRP 401
Cdd:pfam09770  220 QPPAAPPAQQA-QQQQQFPPQIQQQQQPQQQPQQPQQHPGQGHPVtilqrPQSPQPDPAQPSIQPQAQQFHQQPPPVPVQ 298

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 578819647   402 QSLPIQNIKRPYPGEPNYGNQQYGPNSQFPTQPGQYPAPNPPRPLTSPNYPGQRM 456
Cdd:pfam09770  299 PTQILQNPNRLSAARVGYPQNPQPGVQPAPAHQAHRQQGSFGRQAPIITHPQQLA 353

chromosomal replication initiator protein DnaA;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578819647  392 PQQTYPGPRPQSLPiqniKRPYPGepnygnqqYGPNSQFPTQPGqyPAPNPPRPLTSPNYPGQRMPSQPssGQYPPPTVN 471
Cdd:PRK14086  101 HARRTSEPELPRPG----RRPYEG--------YGGPRADDRPPG--LPRQDQLPTARPAYPAYQQRPEP--GAWPRAADD 164

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 578819647  472 MGQYYKPEQFNGQNNTFSGSSYS--------NYSQGNVNRPPR------PVPVANYPHS-------PVPGNPTPPMTPGS 530
Cdd:PRK14086  165 YGWQQQRLGFPPRAPYASPASYApeqerdrePYDAGRPEYDQRrrdydhPRPDWDRPRRdrtdrpePPPGAGHVHRGGPG 244

                         170       180       190
                  ....*....|....*....|....*....|....
gi 578819647  531 SIPPYLSPSQDVKPPFPPDIKPNMSALPPPPANH 564
Cdd:PRK14086  245 PPERDDAPVVPIRPSAPGPLAAQPAPAPGPGEPT 278

capsid maturational protease; Provisional

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 578819647  392 PQQTYPGPRPQSLPIQNIKRPYPGEPNYGNQQYGPNSQFPTQPGqypapnpPRPLTSPNYPGQRMPSQPSSGQYPPPT 469
Cdd:PHA03369  371 APQTHTGPADRQRPQRPDGIPYSVPARSPMTAYPPVPQFCGDPG-------LVSPYNPQSPGTSYGPEPVGPVPPQPT 441