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 281366014  715 SLKCPITKSRIRLPARGHECKHVQCFDLEAYLMINSERGSWRCPECSK 762
Cdd:cd16791     1 SLKCPITFRRITLPARGHDCKHIQCFDLESYLQLNCERGTWRCPVCNK 48

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 281366014  715 SLKCPITKSRIRLPARGHECKHVQCFDLEAYLMINSERGSWRCPECSK 762
Cdd:cd16791     1 SLKCPITFRRITLPARGHDCKHIQCFDLESYLQLNCERGTWRCPVCNK 48

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 281366014   139 YTGMVAASQQHQQQQPHHHQQQQQQQQQQHMGSMD-----------------AMGGYSQMGGGMHPGPNSGMMGNMNGQy 201
Cdd:pfam09606   39 YLGTVARLILHVRDMSKKAAQQQQPQGGQGNGGMGggqqgmpdpinalqnlaGQGTRPQMMGPMGPGPGGPMGQQMGGP- 117

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281366014   202 mnGGSGQGGYNGAQGMGMGYGGGGSMGPQRHHQMTPMNQMQNMSMGPGVGGSGGMGGGMNPlqqqaaqqqmggmnPMAKM 281
Cdd:pfam09606  118 --GTASNLLASLGRPQMPMGGAGFPSQMSRVGRMQPGGQAGGMMQPSSGQPGSGTPNQMGP--------------NGGPG 181

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281366014   282 QGMANGGYPQQAPPSLTQQQQQQQQRRMAPYPHPQMHMAQKRAAAGVGGAGGM---YPGNPMQQQQAQMYGNQQMhPGSG 358
Cdd:pfam09606  182 QGQAGGMNGGQQGPMGGQMPPQMGVPGMPGPADAGAQMGQQAQANGGMNPQQMggaPNQVAMQQQQPQQQGQQSQ-LGMG 260

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281366014   359 GGVPLPMqAGGAGNGYGRSGPmgvgnggygrmsaGNGMGPTggpvmgPMGPGGMTAGGMGPGPGCMSQQRFMPQGSGGGM 438
Cdd:pfam09606  261 INQMQQM-PQGVGGGAGQGGP-------------GQPMGPP------GQQPGAMPNVMSIGDQNNYQQQQTRQQQQQQGG 320

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281366014   439 PGVgyggvggaASHQGQfypgsgQSAGMQQAGGMCPAGPGAVATTGNPYQNQGFQQNYQHSPVPGN-PTPPLTPACSVPY 517
Cdd:pfam09606  321 NHP--------AAHQQQ------MNQSVGQGGQVVALGGLNHLETWNPGNFGGLGANPMQRGQPGMmSSPSPVPGQQVRQ 386

                          410
                   ....*....|
gi 281366014   518 VSPNPDIKPP 527
Cdd:pfam09606  387 VTPNQFMRQS 396

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 281366014  715 SLKCPITKSRIRLPARGHECKHVQCFDLEAYLMINSERGSWRCPECSK 762
Cdd:cd16791     1 SLKCPITFRRITLPARGHDCKHIQCFDLESYLQLNCERGTWRCPVCNK 48

SP-RING finger found in zinc finger MIZ domain-containing protein 2 (Zmiz2) and similar proteins; Zmiz2, also known as PIAS-like protein Zimp7 (zinc finger-containing, Miz1, PIAS-like protein on chromosome 7), 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 interacts with beta-catenin and enhances Wnt/beta-catenin-mediated transcription. It also associates with BRG1 and BAF57, components of the ATP-dependent mammalian SWI/SNF-like BAF chromatin-remodeling complexes, and thus plays a potential role in modulation of AR and/or other nuclear receptor-mediated transcription. For instance, it can increase the effects of BRG1 on AR-mediated transcriptional activity. Moreover, Zmiz2 physically interacts with PIAS proteins, especially PIAS3. Through this interaction, PIAS3 augments Zmiz2-mediated transcription, suggesting PIAS proteins may play a regulatory role in Zmiz-mediated transcription. Furthermore, Zmiz2 is involved in transcriptional regulation of factors essential for patterning in the dorsoventral axis. It is required for the restriction of the zebrafish organizer and mesoderm development. Zmiz2 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 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
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 281366014  713 KISLKCPITKSRIRLPARGHECKHVQCFDLEAYLMINSERGSWRCPECSKSAITD 767
Cdd:cd16823     6 KVSLKCPITFRRIQLPARGHDCRHIQCFDLESYLQLNCERGTWRCPVCNKTALLE 60

SP-RING finger found in the Siz/PIAS RING (SP-RING) family of SUMO E3 ligases; The SP-RING family includes PIAS (protein inhibitor of activated STAT) proteins, Zmiz proteins, and Siz proteins from plants and fungi. PIAS proteins modulate the activity of several transcription factors and act as E3 ubiquitin ligases in the sumoylation pathway. There are 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. PIAS proteins have SUMO E3-ligase activity and interaction of PIAS proteins with transcription factors often results in sumoylation of that protein. Zmiz1 (Zimp10) and its homolog Zmiz2 (Zimp7) were initially identified in humans as androgen receptor (AR) interacting proteins that 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. SIZ1 proteins from plants and fungi are also founding members of this family. SIZ1-mediated conjugation of SUMO1 and SUMO2 to other intracellular proteins is essential in Arabidopsis. Yeast SIZ proteins are SUMO E3 ligases involved in a novel pathway of chromosome maintenance. They enhance SUMO modification to many substrates in vivo, but also exhibit unique substrate specificity. PIAS proteins contain 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. The SP-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 binds a single Zn ion, instead of two ions bound by typical RING fingers.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 281366014  715 SLKCPITKSRIRLPARGHECKHVQCFDLEAYLMINSERGSWRCPECSK 762
Cdd:cd16650     1 SLRCPLSLKRIKTPARGKHCKHLQCFDLDSYLEFNKRKPTWKCPICDK 48

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 281366014  716 LKCPITKSRIRLPARGHECKHvqCFDLEAYL-MINSERGSWRCPECS 761
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 281366014  713 KISLKCPITKSRIRLPARGHECKHVQCFDLEAYLMINSERGSWRCPECSKSA 764
Cdd:cd16821     4 RVSLICPLVKMRLSVPCRAETCAHLQCFDAVFYLQMNEKKPTWTCPVCDKPA 55

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 281366014  715 SLKCPITKSRIRLPARGHECKHVQCFDLEAYLMINSERGSWRCPECSK 762
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 281366014  714 ISLKCPITKSRIRLPARGHECKHVQCFDLEAYLMINSERGSWRCPEC 760
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        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 281366014   712 AKISLKCPITKSRIRLPARGHECKHVqcFDLEAYLMINSERGSWRCP--ECS 761
Cdd:pfam11789    8 ETISLTCPLTLQPFVEPVTSKKCNHV--FEKDAILEMLKRNPTVKCPviGCS 57