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 1003088814 329 TSLRVSLLCPLGKMRLTIPCRALTCSHLQCFDATLYIQMNEKKPTWVCPVCDKKAPYEHL 388
Cdd:cd16818     1 TSLRVSLLCPLGKMRLTIPCRALTCSHLQCFDATLYIQMNEKKPTWVCPVCDKKAPYEHL 60

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 1003088814 329 TSLRVSLLCPLGKMRLTIPCRALTCSHLQCFDATLYIQMNEKKPTWVCPVCDKKAPYEHL 388
Cdd:cd16818     1 TSLRVSLLCPLGKMRLTIPCRALTCSHLQCFDATLYIQMNEKKPTWVCPVCDKKAPYEHL 60

Putative DNA-binding (bihelical) motif predicted to be involved in chromosomal organisation;

                           10        20        30
                   ....*....|....*....|....*....|....*
gi 1003088814   13 VMSLRVSELQVLLGYAGRNKHGRKHELLTKALHLL 47
Cdd:smart00513   1 LAKLKVSELKDELKKRGLSTSGTKAELVDRLLEAL 35

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 1003088814 329 TSLRVSLLCPLGKMRLTIPCRALTCSHLQCFDATLYIQMNEKKPTWVCPVCDKKAPYEHL 388
Cdd:cd16818     1 TSLRVSLLCPLGKMRLTIPCRALTCSHLQCFDATLYIQMNEKKPTWVCPVCDKKAPYEHL 60

SP-RING finger found in protein inhibitor of activated STAT protein 2 (PIAS2) and similar proteins; PIAS2, also known as androgen receptor-interacting protein 3 (ARIP3), DAB2-interacting protein (DIP), Msx-interacting zinc finger protein (Miz1), PIAS-NY protein, protein inhibitor of activated STAT x, protein inhibitor of activated STAT2, is an E3 SUMO-protein ligase highly expressed in the testis. It functions as a transcriptional activator of BCL2 and is essential for blocking c-MYC-induced apoptosis. It also acts as a negative regulator of cell proliferation, induces expression of the cell-cycle inhibitors p15(Ink4b) and p21(Cip1), and activates transcription of the p21(Cip1) gene in response to UV irradiation. Moreover, PIAS2 associates with topoisomerase II binding protein 1 (TopBP1), an essential activator of the Atr kinase. It thus affects the activity of the Atr checkpoint. Receptor of activated C kinase 1 (RACK1), glucocorticoid receptor (GR)-interacting protein 1 (GRIP1), friend leukemia integration-I (FLI-1), and ubiquitously expressed transcript (UXT) are binding partners of PIAS2. The interaction between UXT and PIAS2 may be important for the transcriptional activation of androgen receptor (AR). PIAS2 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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1003088814 329 TSLRVSLLCPLGKMRLTIPCRALTCSHLQCFDATLYIQMNEKKPTWVCPVCDKKAPYEHL 388
Cdd:cd16819     1 TSLRVSLMCPLGKMRLTIPCRAVTCSHLQCFDAALYLQMNEKKPTWICPVCDKKAAYESL 60

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 1003088814 329 TSLRVSLLCPLGKMRLTIPCRALTCSHLQCFDATLYIQMNEKKPTWVCPVCDKKAPYE 386
Cdd:cd16821     1 TGVRVSLICPLVKMRLSVPCRAETCAHLQCFDAVFYLQMNEKKPTWTCPVCDKPAPYD 58

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 1003088814 333 VSLLCPLGKMRLTIPCRALTCSHLQCFDATLYIQMNEKKPTWVCPVCDK 381
Cdd:pfam02891   1 VSLKCPISYLRISIPVRGRFCKHLQCFDLLSYLESNERTPTWNCPVCDK 49

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 1003088814 329 TSLRVSLLCPLGKMRLTIPCRALTCSHLQCFDATLYIQMNEKKPTWVCPVCDKKAPYE 386
Cdd:cd16823     3 TAIKVSLKCPITFRRIQLPARGHDCRHIQCFDLESYLQLNCERGTWRCPVCNKTALLE 60

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 1003088814 334 SLLCPLGKMRLTIPCRALTCSHLQCFDATLYIQMNEKKPTWVCPVCDK 381
Cdd:cd16791     1 SLKCPITFRRITLPARGHDCKHIQCFDLESYLQLNCERGTWRCPVCNK 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        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1003088814 330 SLRVSLLCPLGKMRLTIPCRALTCSHLQCFDATLYIQMNEKKPTWVCPVC 379
Cdd:cd16793     1 STIMSLQCPISYTRMKYPSKSINCKHLQCFDALWFLHSQLQIPTWQCPVC 50

Uncharacterized conserved protein, contains RING Zn-finger [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1003088814 315 KEKLTADPDSEIATTSLRVSLLCPLGKMRLTIPCRALTCSHLQCFDAtlyIQMNEKKPTWVCPVCDKKapyeHLIIDGLF 394
Cdd:COG5222   255 TKAVAEIPDQVYKMQPPNISLKCPLCHCLLRNPMKTPCCGHTFCDEC---IGTALLDSDFKCPNCSRK----DVLLDGLT 327

                  ....*
gi 1003088814 395 MEILK 399
Cdd:COG5222   328 PDIDK 332