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 1046863774 620 KVSLKCPITFRRIQLPARGHDCKHVQCFDLESYLQLNCERGTWRCPVCNKTALLEGLEVDQYMW 683
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 1046863774 620 KVSLKCPITFRRIQLPARGHDCKHVQCFDLESYLQLNCERGTWRCPVCNKTALLEGLEVDQYMW 683
Cdd:cd16822     1 KVSLKCPITFRRIQLPARGHDCKHVQCFDLESYLQLNCERGTWRCPVCNKTALLEGLEVDQYMW 64

large tegument protein UL36; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046863774   59 GNPMANASNPMNPGGNPMASGMSTSNPGLNSPQFAGQQQQFSTKAGPAQPYIQPNMygRPGYPGSGGFGASYPGGPSAPA 138
Cdd:PHA03247  2610 GPAPPSPLPPDTHAPDPPPPSPSPAANEPDPHPPPTVPPPERPRDDPAPGRVSRPR--RARRLGRAAQASSPPQRPRRRA 2687

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046863774  139 gmgIPPHTRPPADFTQPAAAAAAAAVAAAAATATATATAtvaalqetqnkdinqygpvcssfqmGPTQAYNSQFMNQPGP 218
Cdd:PHA03247  2688 ---ARPTVGSLTSLADPPPPPPTPEPAPHALVSATPLPP-------------------------GPAAARQASPALPAAP 2739

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046863774  219 RGPASMGGSMNPASMAAGMTPSGMSGPPmgmnQPRPPGISPFGthgqrmpqqtyPGPRPQSLPIQSIKRSYPGEPNYGNQ 298
Cdd:PHA03247  2740 APPAVPAGPATPGGPARPARPPTTAGPP----APAPPAAPAAG-----------PPRRLTRPAVASLSESRESLPSPWDP 2804

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046863774  299 QYGPNSQFPTQPGQYPTPNPPRPLTSPNYPGQRMPSQPStgQYPPPTVNMGQYYKP----EQFNGQNNTFSSGSSYSSYS 374
Cdd:PHA03247  2805 ADPPAAVLAPAAALPPAASPAGPLPPPTSAQPTAPPPPP--GPPPPSLPLGGSVAPggdvRRRPPSRSPAAKPAAPARPP 2882

                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1046863774  375 QGSVNRPPRPVPVANYPHSPVPgnPTPPMTPGSSIPPYLSPSQDVKP-PFPPDIKPNMSALPPPP 438
Cdd:PHA03247  2883 VRRLARPAVSRSTESFALPPDQ--PERPPQPQAPPPPQPQPQPPPPPqPQPPPPPPPRPQPPLAP 2945

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 1046863774 262 THGQRMPQQTYPGPRpqSLPIQSIKRSYPGEPNYGNQqyGPNSQFPTQPGQYPTpnpprpltSPNYPGQRMPSQPSTGQY 341
Cdd:TIGR01628 369 AHLQDQFMQLQPRMR--QLPMGSPMGGAMGQPPYYGQ--GPQQQFNGQPLGWPR--------MSMMPTPMGPGGPLRPNG 436

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046863774 342 PPPTVNMGQYYKPEQfngqnntfssgssyssysqgsvNRPPRPvPVANYPHSP-------VPGNPTPPMTPGSSIPPYLS 414
Cdd:TIGR01628 437 LAPMNAVRAPSRNAQ----------------------NAAQKP-PMQPVMYPPnyqslplSQDLPQPQSTASQGGQNKKL 493

                  ...
gi 1046863774 415 PSQ 417
Cdd:TIGR01628 494 AQV 496

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 1046863774 620 KVSLKCPITFRRIQLPARGHDCKHVQCFDLESYLQLNCERGTWRCPVCNKTALLEGLEVDQYMW 683
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 1046863774 622 SLKCPITFRRIQLPARGHDCKHVQCFDLESYLQLNCERGTWRCPVCNK 669
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 1046863774 621 VSLKCPITFRRIQLPARGHDCKHVQCFDLESYLQLNCERGTWRCPVCNK 669
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 1046863774 623 LKCPITFRRIQLPARGHDCKHvqCFDLESYLQLNCER-GTWRCPVCN 668
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 1046863774 617 TAIKVSLKCPITFRRIQLPARGHDCKHVQCFDLESYLQLNCERGTWRCPVCNKTALLE 674
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 1046863774 617 TAIKVSLKCPITFRRIQLPARGHDCKHVQCFDLESYLQLNCERGTWRCPVCNKTALLEGL 676
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 1046863774 621 VSLKCPITFRRIQLPARGHDCKHVQCFDLESYLQLNCERGTWRCPVC 667
Cdd:cd16793     4 MSLQCPISYTRMKYPSKSINCKHLQCFDALWFLHSQLQIPTWQCPVC 50

large tegument protein UL36; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046863774   59 GNPMANASNPMNPGGNPMASGMSTSNPGLNSPQFAGQQQQFSTKAGPAQPYIQPNMygRPGYPGSGGFGASYPGGPSAPA 138
Cdd:PHA03247  2610 GPAPPSPLPPDTHAPDPPPPSPSPAANEPDPHPPPTVPPPERPRDDPAPGRVSRPR--RARRLGRAAQASSPPQRPRRRA 2687

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046863774  139 gmgIPPHTRPPADFTQPAAAAAAAAVAAAAATATATATAtvaalqetqnkdinqygpvcssfqmGPTQAYNSQFMNQPGP 218
Cdd:PHA03247  2688 ---ARPTVGSLTSLADPPPPPPTPEPAPHALVSATPLPP-------------------------GPAAARQASPALPAAP 2739

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046863774  219 RGPASMGGSMNPASMAAGMTPSGMSGPPmgmnQPRPPGISPFGthgqrmpqqtyPGPRPQSLPIQSIKRSYPGEPNYGNQ 298
Cdd:PHA03247  2740 APPAVPAGPATPGGPARPARPPTTAGPP----APAPPAAPAAG-----------PPRRLTRPAVASLSESRESLPSPWDP 2804

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046863774  299 QYGPNSQFPTQPGQYPTPNPPRPLTSPNYPGQRMPSQPStgQYPPPTVNMGQYYKP----EQFNGQNNTFSSGSSYSSYS 374
Cdd:PHA03247  2805 ADPPAAVLAPAAALPPAASPAGPLPPPTSAQPTAPPPPP--GPPPPSLPLGGSVAPggdvRRRPPSRSPAAKPAAPARPP 2882

                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1046863774  375 QGSVNRPPRPVPVANYPHSPVPgnPTPPMTPGSSIPPYLSPSQDVKP-PFPPDIKPNMSALPPPP 438
Cdd:PHA03247  2883 VRRLARPAVSRSTESFALPPDQ--PERPPQPQAPPPPQPQPQPPPPPqPQPPPPPPPRPQPPLAP 2945

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 1046863774   6 NSMSSMKPTLSHSDGSFPYDSVPWQQNTNQPPGSLSVVTTVWGVTNTSQSQVLGNPMANASNPMNPGGNPMASGMSTSNP 85
Cdd:pfam09606  51 RDMSKKAAQQQQPQGGQGNGGMGGGQQGMPDPINALQNLAGQGTRPQMMGPMGPGPGGPMGQQMGGPGTASNLLASLGRP 130

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046863774  86 GL--------NSPQFAGQQQQFSTKAGPAQPYIQPNMYGRPGYPGSGGfGASYPGGPSAPAGMGIPPHTRPPADFTQPAA 157
Cdd:pfam09606 131 QMpmggagfpSQMSRVGRMQPGGQAGGMMQPSSGQPGSGTPNQMGPNG-GPGQGQAGGMNGGQQGPMGGQMPPQMGVPGM 209

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046863774 158 AAAAAAVAAAAATATATATATVAALQETQNKDINQYGPVcssfQMGPTQAYNSQFMNQPGPRGPASMGGSmnpasmaagm 237
Cdd:pfam09606 210 PGPADAGAQMGQQAQANGGMNPQQMGGAPNQVAMQQQQP----QQQGQQSQLGMGINQMQQMPQGVGGGA---------- 275

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046863774 238 tPSGMSGPPMGMNQPRPPGISPFGTHGQRMPQQTYPGPRPQSLPIQSIKRSYPGEPnygNQQYGPNSQFPTQPGQyptpN 317
Cdd:pfam09606 276 -GQGGPGQPMGPPGQQPGAMPNVMSIGDQNNYQQQQTRQQQQQQGGNHPAAHQQQM---NQSVGQGGQVVALGGL----N 347

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046863774 318 PPRPLTSPNYPGQRMPSQpstGQYPPPTVNMGQYYKPEQFNGQNntfssgssyssysqgsvnrPPRPVPVANYPHSPVPG 397
Cdd:pfam09606 348 HLETWNPGNFGGLGANPM---QRGQPGMMSSPSPVPGQQVRQVT-------------------PNQFMRQSPQPSVPSPQ 405

                         410       420       430       440
                  ....*....|....*....|....*....|....*....|....*.
gi 1046863774 398 NPT---PPMTPGSSIPPylspsqdvkPPFPPDIKPNMSALPPPPAN 440
Cdd:pfam09606 406 GPGsqpPQSHPGGMIPS---------PALIPSPSPQMSQQPAQQRT 442

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 1046863774   1 MQPPLNSMSSMKPTLSHsdgsfPYDSVPWQQNTNQPPGSLSVVTTVWGVTNTSQSQV---LGNPMANAsnPMNPGGN--- 74
Cdd:pfam09606 149 MQPGGQAGGMMQPSSGQ-----PGSGTPNQMGPNGGPGQGQAGGMNGGQQGPMGGQMppqMGVPGMPG--PADAGAQmgq 221

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046863774  75 --PMASGMSTSNPGLNSPQFAGQQQQFSTKAGPAQPYIQPNMYGRPGYPGSGGFGASYPGGPsapagmGIPPHTRPPAdf 152
Cdd:pfam09606 222 qaQANGGMNPQQMGGAPNQVAMQQQQPQQQGQQSQLGMGINQMQQMPQGVGGGAGQGGPGQP------MGPPGQQPGA-- 293

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046863774 153 tQPAAAAAAAAVAAAAATATATATATVAALQETQNKDINQygPVCSSFQMGPTQAYNSQFMNQPGPRGPASMGGsmnpas 232
Cdd:pfam09606 294 -MPNVMSIGDQNNYQQQQTRQQQQQQGGNHPAAHQQQMNQ--SVGQGGQVVALGGLNHLETWNPGNFGGLGANP------ 364

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046863774 233 maAGMTPSGMsgppMGMNQPRPPGISPFGTHGQRMPQQtypgprpqslpiQSIKRSYPGEPNYGNQQYGPNSQFPTqPGQ 312
Cdd:pfam09606 365 --MQRGQPGM----MSSPSPVPGQQVRQVTPNQFMRQS------------PQPSVPSPQGPGSQPPQSHPGGMIPS-PAL 425

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*...
gi 1046863774 313 YPTPNPPrplTSPNYPGQRMPSQPSTGQyppPTVNMGQYYKPEQFNGQ 360
Cdd:pfam09606 426 IPSPSPQ---MSQQPAQQRTIGQDSPGG---SLNTPGQSAVNSPLNPQ 467

Zinc-finger of the MIZ type in Nse subunit; Nse1 and Nse2 are novel non-SMC subunits of the fission yeast Smc5-6 DNA repair complex. This family is the zinc-finger domain similar to the MIZ type of zinc-finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 1046863774 620 KVSLKCPITFRRIQLPARGHDCKHVqcFDLESYLQLNCERGTWRCPV 666
Cdd:pfam11789   9 TISLTCPLTLQPFVEPVTSKKCNHV--FEKDAILEMLKRNPTVKCPV 53

104 kDa microneme/rhoptry antigen; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046863774 198 SSFQMGPTQAYNSQFMNQPgPRGPASMGgsMNPASMAAGMTPSGMSGPPMGMNQPR---PPGISPFGTHGQRmpqqtyPG 274
Cdd:PTZ00449  492 SKKKLAPIEEEDSDKHDEP-PEGPEASG--LPPKAPGDKEGEEGEHEDSKESDEPKeggKPGETKEGEVGKK------PG 562

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046863774 275 P----RPQSLPIQSIKRSYPGEPNYGNQQYGPNS----QFPTQPGQYPTPNPPRPLTSPNYPgqRMPSQPSTGQYPPPtv 346
Cdd:PTZ00449  563 PakehKPSKIPTLSKKPEFPKDPKHPKDPEEPKKpkrpRSAQRPTRPKSPKLPELLDIPKSP--KRPESPKSPKRPPP-- 638

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046863774 347 nmgqyykpeqfngqnntfssgssyssysqgsvnrPPRPVPvanyphspvPGNPTPPMTPGSSIPPYlSPsqdvKPPFPPD 426
Cdd:PTZ00449  639 ----------------------------------PQRPSS---------PERPEGPKIIKSPKPPK-SP----KPPFDPK 670

                  ..
gi 1046863774 427 IK 428
Cdd:PTZ00449  671 FK 672

DNA polymerase III subunits gamma and tau; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046863774 382 PRPVPVANYPHSPVP----GNPTP---PMTPGSSIPPYLSPSQDVKPPFPPDIKPNMSALPPPPANHNDELRLTFPVRDG 454
Cdd:PRK14950  362 PVPAPQPAKPTAAAPspvrPTPAPstrPKAAAAANIPPKEPVRETATPPPVPPRPVAPPVPHTPESAPKLTRAAIPVDEK 441

                  ....*
gi 1046863774 455 VVLEP 459
Cdd:PRK14950  442 PKYTP 446

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 1046863774 211 QFMnQPGPRGPASMGGSMNPASMAA----GMTPSGMSGPPMGMNQPRPPGISPFGTHGQRMPQqTYPGPRPQSLPIQSiK 286
Cdd:TIGR01628 374 QFM-QLQPRMRQLPMGSPMGGAMGQppyyGQGPQQQFNGQPLGWPRMSMMPTPMGPGGPLRPN-GLAPMNAVRAPSRN-A 450

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1046863774 287 RSYPGEPNYGNQQYGPNSQFPTQPGQYPTPNP 318
Cdd:TIGR01628 451 QNAAQKPPMQPVMYPPNYQSLPLSQDLPQPQS 482

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 1046863774 230 PASMAAGMTPSGMSGPPMGMNQPRPPGIS---PFGTHGQRMPQQTYPGP------RPQSLPIQSIKRSYPGEPNYGNQQY 300
Cdd:pfam09770 213 QPAPAPAQPPAAPPAQQAQQQQQFPPQIQqqqQPQQQPQQPQQHPGQGHpvtilqRPQSPQPDPAQPSIQPQAQQFHQQP 292

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1046863774 301 GPNSQFPTQ---------PGQYPTPNPPRPLTSPNYPGQRMPSQPSTGQYPP 343
Cdd:pfam09770 293 PPVPVQPTQilqnpnrlsAARVGYPQNPQPGVQPAPAHQAHRQQGSFGRQAP 344

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 1046863774 229 NPASMAAGMTPSgmsgPPMGMNQPRPPGISPFGTHGQRMPQQTYPGPRPQSLPIQSIKRSYPGEPNYGNQQYGPNSQFPT 308
Cdd:pfam03154 244 SPHPPLQPMTQP----PPPSQVSPQPLPQPSLHGQMPPMPHSLQTGPSHMQHPVPPQPFPLTPQSSQSQVPPGPSPAAPG 319

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046863774 309 QPGQYPTPNPPRPLTSPNYPGQRMPSQPSTGQY----PPPTVNMgqyykPEQFNGQNNTFSSGSSYSSYSQGSVNRPPRP 384
Cdd:pfam03154 320 QSQQRIHTPPSQSQLQSQQPPREQPLPPAPLSMphikPPPTTPI-----PQLPNPQSHKHPPHLSGPSPFQMNSNLPPPP 394

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1046863774 385 V--PVANYPHSPVPGNPTPP---MTPGSSIPPylspsqdvkPPFPPDIKPNMSALPPPPANH 441
Cdd:pfam03154 395 AlkPLSSLSTHHPPSAHPPPlqlMPQSQQLPP---------PPAQPPVLTQSQSLPPPAASH 447