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 564387747  738 KVSLKCPITFRRIQLPARGHDCKHVQCFDLESYLQLNCERGTWRCPVCNKTALLEGLEVDQYMW 801
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 564387747  738 KVSLKCPITFRRIQLPARGHDCKHVQCFDLESYLQLNCERGTWRCPVCNKTALLEGLEVDQYMW 801
Cdd:cd16822     1 KVSLKCPITFRRIQLPARGHDCKHVQCFDLESYLQLNCERGTWRCPVCNKTALLEGLEVDQYMW 64

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564387747  183 GNPMANASNPMNPGGNPMASGMSTSNPGLNSPQFAGQQQQFSTKAGPAQPYIQPNMygRPGYPGSGGFGASYPGGPSAPA 262
Cdd:PHA03247 2610 GPAPPSPLPPDTHAPDPPPPSPSPAANEPDPHPPPTVPPPERPRDDPAPGRVSRPR--RARRLGRAAQASSPPQRPRRRA 2687

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564387747  263 gmgIPPHTRPPADFTQPAAAAAAAAVAAAAATATATAtatvaalqetqnkdinqygPMGPTQAYNSQFMNQPGPRGPASM 342
Cdd:PHA03247 2688 ---ARPTVGSLTSLADPPPPPPTPEPAPHALVSATPL-------------------PPGPAAARQASPALPAAPAPPAVP 2745

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564387747  343 GGSMNPASMAAGMTPSGMSGPPmgmnQPRPPGISPFGthgqrmpqqtyPGPRPQSLPIQSIKRSYPGEPNYGNQQYGPNS 422
Cdd:PHA03247 2746 AGPATPGGPARPARPPTTAGPP----APAPPAAPAAG-----------PPRRLTRPAVASLSESRESLPSPWDPADPPAA 2810

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564387747  423 QFPTQPGQYPTPNPPRPLTSPNYPGQRMPSQPStgQYPPPTVNMGQYYKP----EQFNGQNNTFSSGSSYSSYSQGSVNR 498
Cdd:PHA03247 2811 VLAPAAALPPAASPAGPLPPPTSAQPTAPPPPP--GPPPPSLPLGGSVAPggdvRRRPPSRSPAAKPAAPARPPVRRLAR 2888

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 564387747  499 PPRPVPVANYPHSPVPgnPTPPMTPGSSIPPYLSPSQDVKP-PFPPDIKPNMSALPPPP 556
Cdd:PHA03247 2889 PAVSRSTESFALPPDQ--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 564387747   315 NQYGPMGPTQAYNSQFmnqPGPRGPASMGGsMNPASMAAG---MTPSG-MSGPPMGMN-QPRPPGISPfgthgqrMPQQT 389
Cdd:TIGR01628  376 MQLQPRMRQLPMGSPM---GGAMGQPPYYG-QGPQQQFNGqplGWPRMsMMPTPMGPGgPLRPNGLAP-------MNAVR 444

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 564387747   390 YPGPRPQSLPiqsikrsypGEPNYGNQQYGPNSQFPTQPGQYPTPNP 436
Cdd:TIGR01628  445 APSRNAQNAA---------QKPPMQPVMYPPNYQSLPLSQDLPQPQS 482

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 564387747  738 KVSLKCPITFRRIQLPARGHDCKHVQCFDLESYLQLNCERGTWRCPVCNKTALLEGLEVDQYMW 801
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 564387747  740 SLKCPITFRRIQLPARGHDCKHVQCFDLESYLQLNCERGTWRCPVCNK 787
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 564387747   739 VSLKCPITFRRIQLPARGHDCKHVQCFDLESYLQLNCERGTWRCPVCNK 787
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 564387747  741 LKCPITFRRIQLPARGHDCKHvqCFDLESYLQLNCER-GTWRCPVCN 786
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 564387747  735 TAIKVSLKCPITFRRIQLPARGHDCKHVQCFDLESYLQLNCERGTWRCPVCNKTALLE 792
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 564387747  735 TAIKVSLKCPITFRRIQLPARGHDCKHVQCFDLESYLQLNCERGTWRCPVCNKTALLEGL 794
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 564387747  739 VSLKCPITFRRIQLPARGHDCKHVQCFDLESYLQLNCERGTWRCPVC 785
Cdd:cd16793     4 MSLQCPISYTRMKYPSKSINCKHLQCFDALWFLHSQLQIPTWQCPVC 50

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564387747  185 PMANASNPmnPGGNPMASGMSTSNPGLNSPQFAGQQQQFSTKAGPAQPYIQPNMYGRPGYPGSGGFGASYPGGPSAPAGM 264
Cdd:PHA03247 2631 PSPAANEP--DPHPPPTVPPPERPRDDPAPGRVSRPRRARRLGRAAQASSPPQRPRRRAARPTVGSLTSLADPPPPPPTP 2708

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564387747  265 GIPPHTRPPADFTQPAAAAAAAAVAAAAATATATATATVAALQETQNKDINQYGPMGPTQAYNSQFMNQPGPRGPASMGG 344
Cdd:PHA03247 2709 EPAPHALVSATPLPPGPAAARQASPALPAAPAPPAVPAGPATPGGPARPARPPTTAGPPAPAPPAAPAAGPPRRLTRPAV 2788

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564387747  345 SMNPASMAAGMTPSGMSGPPMGMNQP--------RPPGISPFGTHGQRMPQQTYPGPRPQSLPIQSikRSYPGEPnygNQ 416
Cdd:PHA03247 2789 ASLSESRESLPSPWDPADPPAAVLAPaaalppaaSPAGPLPPPTSAQPTAPPPPPGPPPPSLPLGG--SVAPGGD---VR 2863

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564387747  417 QYGPNSQFPTQPGQYPTPnPPRPLTSPNYPGQRMP-SQPSTGQYPPPTVNMGQYYKPEqfngqnntfssgssyssysqgs 495
Cdd:PHA03247 2864 RRPPSRSPAAKPAAPARP-PVRRLARPAVSRSTESfALPPDQPERPPQPQAPPPPQPQ---------------------- 2920

                         330       340       350       360       370       380
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 564387747  496 vnrPPRPVPVANYPHSPVPGNPTPPMTPGSSIPPYLSPSQDVKPPFPPDIKPNMSALP----PPPA 557
Cdd:PHA03247 2921 ---PQPPPPPQPQPPPPPPPRPQPPLAPTTDPAGAGEPSGAVPQPWLGALVPGRVAVPrfrvPQPA 2983

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 564387747  741 LKCPITFRRIQLPARGHDCKHVqcFDLESYLQ-LNCERGTWRCPV--CNKTALLEGLEVDQYMW 801
Cdd:cd16651     1 LKCPITQQLMVDPVRNKKCGHT--YEKAAILQyLQSRKKKAKCPVagCRNTVSKSDLVPDPELK 62

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564387747  119 PPGKLPMQPPlnsMSSMKPTLSHSDGSFPYDSVPWQQNTNQPPG---SLSVVTTVWGVTNTSQSQVLG----------NP 185
Cdd:PHA03247 2618 PPDTHAPDPP---PPSPSPAANEPDPHPPPTVPPPERPRDDPAPgrvSRPRRARRLGRAAQASSPPQRprrraarptvGS 2694

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564387747  186 MANASNPMNPGGNPMASGMSTSnPGLNSP--QFAGQQQQFSTKAGPAQPYIqPNMYGRPGYPGSGGFGASyPGGPSAPAG 263
Cdd:PHA03247 2695 LTSLADPPPPPPTPEPAPHALV-SATPLPpgPAAARQASPALPAAPAPPAV-PAGPATPGGPARPARPPT-TAGPPAPAP 2771

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564387747  264 MGIPPHTRPPADFTQPAAAAAAAAVAAAAATATATATATVAALQETQNKDINQYGPMGPTQAynSQFMNQPGPRGPA--- 340
Cdd:PHA03247 2772 PAAPAAGPPRRLTRPAVASLSESRESLPSPWDPADPPAAVLAPAAALPPAASPAGPLPPPTS--AQPTAPPPPPGPPpps 2849

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564387747  341 -SMGGSMNPASMAAGMTPSGmSGPPMGMNQPRPPGispfgthgQRMPQ-QTYPGPRPQSLPiqsikrsyPGEPnygnqQY 418
Cdd:PHA03247 2850 lPLGGSVAPGGDVRRRPPSR-SPAAKPAAPARPPV--------RRLARpAVSRSTESFALP--------PDQP-----ER 2907

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564387747  419 GPNSQFPTQPGQYPT-PNPPRPLTSPNYPGQ-RMPSQPSTGQYPPPTVNmgqyykPEQFNGQNNTFSSGSSYSSYSQGSV 496
Cdd:PHA03247 2908 PPQPQAPPPPQPQPQpPPPPQPQPPPPPPPRpQPPLAPTTDPAGAGEPS------GAVPQPWLGALVPGRVAVPRFRVPQ 2981

                         410       420       430       440       450
                  ....*....|....*....|....*....|....*....|....*....|..
gi 564387747  497 NRPPRPVPVAnyPHSPVPGNPTPPMTPGSS--------IPPYLSPSQDVKPP 540
Cdd:PHA03247 2982 PAPSREAPAS--STPPLTGHSLSRVSSWASslalheetDPPPVSLKQTLWPP 3031

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 564387747   738 KVSLKCPITFRRIQLPARGHDCKHVqcFDLESYLQLNCERGTWRCPV 784
Cdd:pfam11789    9 TISLTCPLTLQPFVEPVTSKKCNHV--FEKDAILEMLKRNPTVKCPV 53

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564387747  333 QPGPRGPASMGGSMN-----PASMAAGMTPSGMSGPPMGMNQPRPPgisPFGTHGQRMP-------QQTYPGPRPQSLPI 400
Cdd:PHA03247 2572 RPAPRPSEPAVTSRArrpdaPPQSARPRAPVDDRGDPRGPAPPSPL---PPDTHAPDPPppspspaANEPDPHPPPTVPP 2648

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564387747  401 QSIKRSYPGEPNYGNQQYGPNSQFPTQ---PGQYPTPNPPRPLTSPNYPGQRMPSQPSTGQYPPPTVNMGQYYKPEQFNG 477
Cdd:PHA03247 2649 PERPRDDPAPGRVSRPRRARRLGRAAQassPPQRPRRRAARPTVGSLTSLADPPPPPPTPEPAPHALVSATPLPPGPAAA 2728

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564387747  478 QNNTFSSGSSYSSYSQGS-------VNRPPRPvPVANYPHSPVPGNPTPPMTPGSSIPPYLSPSQDVKP--PFPPDIKPN 548
Cdd:PHA03247 2729 RQASPALPAAPAPPAVPAgpatpggPARPARP-PTTAGPPAPAPPAAPAAGPPRRLTRPAVASLSESREslPSPWDPADP 2807

                  ....*....
gi 564387747  549 MSALPPPPA 557
Cdd:PHA03247 2808 PAAVLAPAA 2816

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 564387747   315 NQYGPMGPTQAYNSQFmnqPGPRGPASMGGsMNPASMAAG---MTPSG-MSGPPMGMN-QPRPPGISPfgthgqrMPQQT 389
Cdd:TIGR01628  376 MQLQPRMRQLPMGSPM---GGAMGQPPYYG-QGPQQQFNGqplGWPRMsMMPTPMGPGgPLRPNGLAP-------MNAVR 444

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 564387747   390 YPGPRPQSLPiqsikrsypGEPNYGNQQYGPNSQFPTQPGQYPTPNP 436
Cdd:TIGR01628  445 APSRNAQNAA---------QKPPMQPVMYPPNYQSLPLSQDLPQPQS 482

DNA polymerase III subunits gamma and tau; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564387747  500 PRPVPVANYPHSPVP----GNPTP---PMTPGSSIPPYLSPSQDVKPPFPPDIKPNMSALPPPPANHNDELRLTFPVRDG 572
Cdd:PRK14950  362 PVPAPQPAKPTAAAPspvrPTPAPstrPKAAAAANIPPKEPVRETATPPPVPPRPVAPPVPHTPESAPKLTRAAIPVDEK 441

                  ....*
gi 564387747  573 VVLEP 577
Cdd:PRK14950  442 PKYTP 446

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 564387747   347 NPASMAAGMTPSgmsgPPMGMNQPRPPGISPFGTHGQRMPQQTYPGPRPQSLPIQSIKRSYPGEPNYGNQQYGPNSQFPT 426
Cdd:pfam03154  244 SPHPPLQPMTQP----PPPSQVSPQPLPQPSLHGQMPPMPHSLQTGPSHMQHPVPPQPFPLTPQSSQSQVPPGPSPAAPG 319

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564387747   427 QPGQYPTPNPPRPLTSPNYPGQRMPSQPSTGQY----PPPTVNMGQYYKPeqfngQNNTFSSGSSYSSYSQGSVNRPPRP 502
Cdd:pfam03154  320 QSQQRIHTPPSQSQLQSQQPPREQPLPPAPLSMphikPPPTTPIPQLPNP-----QSHKHPPHLSGPSPFQMNSNLPPPP 394

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 564387747   503 V--PVANYPHSPVPGNPTPP---MTPGSSIPPylspsqdvkPPFPPDIKPNMSALPPPPANH 559
Cdd:pfam03154  395 AlkPLSSLSTHHPPSAHPPPlqlMPQSQQLPP---------PPAQPPVLTQSQSLPPPAASH 447

capsid maturational protease; Provisional

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 564387747  386 PQQTYPGPRPQSLPIQSIKRSYPGEPNYGNQQYGPNSQFPTQPGqyptpnpPRPLTSPNYPGQRMPSQPSTGQYPPPT 463
Cdd:PHA03369  371 APQTHTGPADRQRPQRPDGIPYSVPARSPMTAYPPVPQFCGDPG-------LVSPYNPQSPGTSYGPEPVGPVPPQPT 441