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 54607100 595 KVSLKCPITFRRIQLPARGHDCRHIQCFDLESYLQLNCERGTWRCPVCNKTALLEGLEVDQYM 657
Cdd:cd16822   1 KVSLKCPITFRRIQLPARGHDCKHVQCFDLESYLQLNCERGTWRCPVCNKTALLEGLEVDQYM 63

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 54607100 595 KVSLKCPITFRRIQLPARGHDCRHIQCFDLESYLQLNCERGTWRCPVCNKTALLEGLEVDQYM 657
Cdd:cd16822   1 KVSLKCPITFRRIQLPARGHDCKHVQCFDLESYLQLNCERGTWRCPVCNKTALLEGLEVDQYM 63

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 54607100   721 AALGPGAAPFAPLQPPSAPTPSDYPSQGSNFMGPGTFPESFPSatPTTPNLAEFTQGPPPISYQSDIPSSLLTPdKSTPC 800
Cdd:pfam03154 180 AASPPSPPPPGTTQAATAGPTPSAPSVPPQGSPATSQPPNQTQ--STAAPHTLIQQTPTLHPQRLPSPHPPLQP-MTQPP 256

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 54607100   801 LPGQMAPAGHLDPA-HNPGPPGLHTPNLGPTpgtqlHHPNPSPAsrQPLGQPNTGPISELAFNPASGMMGPPSMTGAGEA 879
Cdd:pfam03154 257 PPSQVSPQPLPQPSlHGQMPPMPHSLQTGPS-----HMQHPVPP--QPFPLTPQSSQSQVPPGPSPAAPGQSQQRIHTPP 329

                  ....*
gi 54607100   880 SEPAL 884
Cdd:pfam03154 330 SQSQL 334

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 54607100 595 KVSLKCPITFRRIQLPARGHDCRHIQCFDLESYLQLNCERGTWRCPVCNKTALLEGLEVDQYM 657
Cdd:cd16822   1 KVSLKCPITFRRIQLPARGHDCKHVQCFDLESYLQLNCERGTWRCPVCNKTALLEGLEVDQYM 63

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 54607100 597 SLKCPITFRRIQLPARGHDCRHIQCFDLESYLQLNCERGTWRCPVCNK 644
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 54607100   596 VSLKCPITFRRIQLPARGHDCRHIQCFDLESYLQLNCERGTWRCPVCNK 644
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 54607100 598 LKCPITFRRIQLPARGHDCRHiqCFDLESYLQLNCER-GTWRCPVCN 643
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 54607100 592 TAIKVSLKCPITFRRIQLPARGHDCRHIQCFDLESYLQLNCERGTWRCPVCNKTALLE 649
Cdd:cd16821   1 TGVRVSLICPLVKMRLSVPCRAETCAHLQCFDAVFYLQMNEKKPTWTCPVCDKPAPYD 58

SP-RING finger found in protein inhibitor of activated signal transducer and activator of transcription (PIAS) proteins; 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. It consists of four members: PIAS1, PIAS2 (also known as PIASx), PIAS3, and PIAS4 (also known as PIASy). PIAS proteins were initially identified as inhibitors of activated STAT only, but are now known to interact with and modulate several other proteins, including androgen receptor (AR), tumor suppressor p53, and the transforming growth factor-beta (TGF-beta) signaling protein SMAD. They interact with STATs in a cytokine-dependent manner. PIAS1, PIAS2, and PIAS3 interact with STAT1, STAT3, and STAT4, respectively. In addition, PIAS4 is associated with STAT1. PIAS proteins have SUMO E3-ligase activity and interaction of PIAS proteins with transcription factors often results in sumoylation of that protein. PIAS proteins contain an N-terminal SAP (scaffold attachment factor A/B (SAF-A/B), acinus and PIAS) box with the LXXLL signature, which is required for the trans-repression of STAT1 activity by PIAS2, a PINT motif, which is essential for nuclear retention of PIAS3L (the long form of PIAS3), a specific RING finger known as Siz/PIAS (protein inhibitor of activated signal transducer and activator of transcription) RING (SP-RING) finger, which is essential for SUMO ligase activity, and the acidic C-terminal domain, which is involved in binding of PIAS3 to the nuclear coactivator TIF2. 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 54607100 597 SLKCPITFRRIQLPARGHDCRHIQCFDLESYLQLNCERGTWRCPVCNK 644
Cdd:cd16790   1 SLMCPLGKMRLTIPCRALTCSHLQCFDAALYLQMNEKKPTWICPVCDK 48

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 54607100 596 VSLKCPITFRRIQLPARGHDCRHIQCFDLESYLQLNCERGTWRCPVC 642
Cdd:cd16793   4 MSLQCPISYTRMKYPSKSINCKHLQCFDALWFLHSQLQIPTWQCPVC 50

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 54607100   595 KVSLKCPITFRRIQLPARGHDCRHIqcFDLESYLQLNCERGTWRCPV 641
Cdd:pfam11789   9 TISLTCPLTLQPFVEPVTSKKCNHV--FEKDAILEMLKRNPTVKCPV 53

transcriptional regulator ICP4; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 54607100   714 PSVMEMIAALGPGAAPFAPLQPPSAPTPSDYPSQGSNFMGPGTFP--ESFPSATPTTPNLAEFTQGPPPisyqSDIPSSL 791
Cdd:PHA03307    5 PDLYDLIEAAAEGGEFFPRPPATPGDAADDLLSGSQGQLVSDSAElaAVTVVAGAAACDRFEPPTGPPP----GPGTEAP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 54607100   792 LTPDKSTPCLPGQMAPAGHLDPAHNPGPPGlHTPNLGPTPGTQLHHPNPSPASRQPLGQPNTGPISELAFNPASGMMGPP 871
Cdd:PHA03307   81 ANESRSTPTWSLSTLAPASPAREGSPTPPG-PSSPDPPPPTPPPASPPPSPAPDLSEMLRPVGSPGPPPAASPPAAGASP 159

                         170
                  ....*....|....*.
gi 54607100   872 SMTGAGEASEPALDLL 887
Cdd:PHA03307  160 AAVASDAASSRQAALP 175

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 54607100   723 LGPGAAPFAPLQ--PPS--APTPS-----------DYPSQGSNFMGPGTFPESFPSATPTTPnlaeftqgPPPISYQSDI 787
Cdd:PHA03247 2555 LPPAAPPAAPDRsvPPPrpAPRPSepavtsrarrpDAPPQSARPRAPVDDRGDPRGPAPPSP--------LPPDTHAPDP 2626

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 54607100   788 PSSLLTPDKSTPCLPGQMAPAGHLDPAHNPGPPGLHTPNLGPTPGTQLHHPNPSPASRQPLGQPNTGPISELAFNPASG- 866
Cdd:PHA03247 2627 PPPSPSPAANEPDPHPPPTVPPPERPRDDPAPGRVSRPRRARRLGRAAQASSPPQRPRRRAARPTVGSLTSLADPPPPPp 2706

                         170       180       190
                  ....*....|....*....|....*....|...
gi 54607100   867 -----------MMGPPSMTGAGEASEPALDLLP 888
Cdd:PHA03247 2707 tpepaphalvsATPLPPGPAAARQASPALPAAP 2739

104 kDa microneme/rhoptry antigen; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 54607100  676 PTCSWKPVPVKPDLHIK--EEPDGPvlKRCRT----VSPAHVLMPSVMEMIAALGPGAAPFAPLQPPSAPTPSDyPSQGS 749
Cdd:PTZ00449 573 PTLSKKPEFPKDPKHPKdpEEPKKP--KRPRSaqrpTRPKSPKLPELLDIPKSPKRPESPKSPKRPPPPQRPSS-PERPE 649

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 54607100  750 NFMGPGTFPESFPSATPTTPNLAE-FTQGPPPISYQSDIPSSLLTPDKSTPCLPGQMAPAGHLDPAHNPGPpglhTPNLG 828
Cdd:PTZ00449 650 GPKIIKSPKPPKSPKPPFDPKFKEkFYDDYLDAAAKSKETKTTVVLDESFESILKETLPETPGTPFTTPRP----LPPKL 725

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 54607100  829 PTPGTQLHHPNPSPASRQPL-GQPNTGPISELAFNPASGMMGPPSMTGAGEASEPalDLLPELTNPDELLSYlgpPDLPT 907
Cdd:PTZ00449 726 PRDEEFPFEPIGDPDAEQPDdIEFFTPPEEERTFFHETPADTPLPDILAEEFKEE--DIHAETGEPDEAMKR---PDSPS 800

                 ....
gi 54607100  908 NSSD 911
Cdd:PTZ00449 801 EHED 804

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 54607100   707 SPAHVLMPSVMEMIAALGPGAAPFAPLQPPSAPTPSDYPSQGSNFMGPGTFPESFPSATPTTPNLAEFTQGPPPISYQSD 786
Cdd:PHA03247 2707 TPEPAPHALVSATPLPPGPAAARQASPALPAAPAPPAVPAGPATPGGPARPARPPTTAGPPAPAPPAAPAAGPPRRLTRP 2786

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 54607100   787 IPSSLltpDKSTPCLPGQMAPAGHldPAHNPGPPGLHTPNLGPTPgtqlhhPNPSPASRQPLGQPNTGPISELAFNPASG 866
Cdd:PHA03247 2787 AVASL---SESRESLPSPWDPADP--PAAVLAPAAALPPAASPAG------PLPPPTSAQPTAPPPPPGPPPPSLPLGGS 2855

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 54607100   867 MM--------GPPSMTGAGEA--SEPALDLLPELTNPDELLSYLGPPDLP 906
Cdd:PHA03247 2856 VApggdvrrrPPSRSPAAKPAapARPPVRRLARPAVSRSTESFALPPDQP 2905

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 54607100   733 LQPPSAPTPSDYPSQGSNFMGPGTFPESFP---SATPTTPNLAEFTQGPPPISYQSDIPSSL----LTPDKSTPcLPGQM 805
Cdd:pfam03154 289 MQHPVPPQPFPLTPQSSQSQVPPGPSPAAPgqsQQRIHTPPSQSQLQSQQPPREQPLPPAPLsmphIKPPPTTP-IPQLP 367

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 54607100   806 APAGHLDPAHNPGPPGLHTP-NLGPTPGTQ------LHHP---NPSPASRQPLGQPNTGP------ISELAFNPASGMMG 869
Cdd:pfam03154 368 NPQSHKHPPHLSGPSPFQMNsNLPPPPALKplsslsTHHPpsaHPPPLQLMPQSQQLPPPpaqppvLTQSQSLPPPAASH 447

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
gi 54607100   870 PPSMTGAGEASEPALDLLPEL-TNPDELLSYLGPPDLPTNS 909
Cdd:pfam03154 448 PPTSGLHQVPSQSPFPQHPFVpGGPPPITPPSGPPTSTSSA 488