Variant RING finger, HC subclass (C4C4-type), found in Ret finger protein-like (RFPL) family; The RFPL family, also known as the RING-B30 family, represents a group of RFPL gene products, RFPL1, RFPL2, RFPL3, and RFPL4A, which are characterized by containing an N-terminal RFPL1, 2, 3-specifying helix (RSH), a C4C4- or a variant C4C4-type RING finger, whose overall folding is similar to that of the typical C3HC4-type RING-HC finger, an RFPL-defining motif (RDM), and C-terminal PRY/SPRY-forming B30.2 domain. RFPL1, also known as RING finger protein 78 (RNF78), is expressed during cell differentiation. RFPL2, also known as RING finger protein 79 (RNF79), shows high sequence similarity with other RFPL gene products. Its biological role remains unclear. RFPL3 interacts directly with CREB binding protein (CBP) in the nucleus of lung cancer cells. RFPL3 and CBP synergistically upregulate TERT activity and promote lung cancer growth. Moreover, RFPL3 acts as a novel E3 ubiquitin ligase modulating the integration activity of human immunodeficiency virus, type 1 (HIV-1) preintegration complex. RFPL4A, also known as RING finger protein 210 (RNF210), is a novel factor that increases the G1 population and decreases sensitivity to chemotherapy in human colorectal cancer cells. This model corresponds to the C4C4-type RING finger. RFPL4A lacks the fourth conserved zinc-binding residue, cysteine, and the eighth zinc-binding residue, cysteine; in RFPL2, it is replaced by serine.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 2029297694  99 SSCPVCSDYLEKPMSLECGCAVCLKCINSLQKEPHGEDLLCCCSSMVS 146
Cdd:cd16621     1 SSCPVCSDYLEKPVSLECGYACCLQCLNSLQKEPHGEGLLCCCCSVVS 48

Domain in SPla and the RYanodine Receptor; Domain of unknown function. Distant homologues are domains in butyrophilin/marenostrin/pyrin homologues.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2029297694  238 CGRHCWEVDVGTSTEWDLGVCRESVHRKGRIQLTTELGFWTVSLRDGGRLSATTVPLTFLFVDRKLQRVGIFLDMGMQNV 317
Cdd:smart00449   1 SGRHYFEVEIGDGGHWRVGVATKSVPRGYFALLGEDKGSWGYDGDGGKKYHNSTGPEYGLPLQEPGDVIGCFLDLEAGTI 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 2029297694  318 SFFDAESGSHVYTFRSVSAEEPLRPFLAPSvppNGDQGVLSICPL 362
Cdd:smart00449  81 SFYKNGKYLHGLAFFDVKFSGPLYPAFSLG---SGNSVRLNFGPL 122

Variant RING finger, HC subclass (C4C4-type), found in Ret finger protein-like (RFPL) family; The RFPL family, also known as the RING-B30 family, represents a group of RFPL gene products, RFPL1, RFPL2, RFPL3, and RFPL4A, which are characterized by containing an N-terminal RFPL1, 2, 3-specifying helix (RSH), a C4C4- or a variant C4C4-type RING finger, whose overall folding is similar to that of the typical C3HC4-type RING-HC finger, an RFPL-defining motif (RDM), and C-terminal PRY/SPRY-forming B30.2 domain. RFPL1, also known as RING finger protein 78 (RNF78), is expressed during cell differentiation. RFPL2, also known as RING finger protein 79 (RNF79), shows high sequence similarity with other RFPL gene products. Its biological role remains unclear. RFPL3 interacts directly with CREB binding protein (CBP) in the nucleus of lung cancer cells. RFPL3 and CBP synergistically upregulate TERT activity and promote lung cancer growth. Moreover, RFPL3 acts as a novel E3 ubiquitin ligase modulating the integration activity of human immunodeficiency virus, type 1 (HIV-1) preintegration complex. RFPL4A, also known as RING finger protein 210 (RNF210), is a novel factor that increases the G1 population and decreases sensitivity to chemotherapy in human colorectal cancer cells. This model corresponds to the C4C4-type RING finger. RFPL4A lacks the fourth conserved zinc-binding residue, cysteine, and the eighth zinc-binding residue, cysteine; in RFPL2, it is replaced by serine.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 2029297694  99 SSCPVCSDYLEKPMSLECGCAVCLKCINSLQKEPHGEDLLCCCSSMVS 146
Cdd:cd16621     1 SSCPVCSDYLEKPVSLECGYACCLQCLNSLQKEPHGEGLLCCCCSVVS 48

zinc finger of C3HC4-type, RING; This is a family of primate-specific Ret finger protein-like (RFPL) zinc-fingers of the C3HC4 type. Ret finger protein-like proteins are primate-specific target genes of Pax6, a key transcription factor for pancreas, eye and neocortex development. This domain is likely to be DNA-binding. This zinc-finger domain together with the RDM domain, pfam11002, forms a large zinc-finger structure of the RING/U-Box superfamily. RING-containing proteins are known to exert an E3 ubiquitin protein ligase activity with the zinc-finger structure being mandatory for binding to the E2 ubiquitin-conjugating enzyme.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 2029297694 101 CPVCSDYLEKPMSLECGCAVCLKCINSLQKEPHGEDLLCCC 141
Cdd:pfam15227   1 CPICLDYLEKPVSIECGHSFCLSCINSLQKEPDGESLLCPQ 41

PRY/SPRY domain in tripartite motif-containing (TRIM) proteins, including TRIM5, TRIM6, TRIM7, TRIM10, TRIM11, TRIM17, TRIM20, TRIM21, TRIM27, TRIM35, TRIM38, TRIM41, TRIM50, TRIM58, TRIM60, TRIM62, TRIM69, TRIM72, NF7 and bloodthirsty; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of several Class IV TRIM proteins, including TRIM7, TRIM35, TRIM41, TRIM50, TRIM62, TRIM69, TRIM72, TRIM protein NF7 and bloodthirsty (bty). TRIM7 interacts with glycogenin and stimulates its self-glucosylating activity via its SPRY domain. TRIM35 may play a role as a tumor suppressor and is implicated in the cell death mechanism. TRIM41 is localized to speckles in the cytoplasm and nucleus, and functions as an E3 ligase that catalyzes the ubiquitin-mediated degradation of protein kinase C. TRIM50, an E3 ubiquitin ligase, is deleted in Williams-Beuren (WBS) syndrome, a multi-system neurodevelopmental disorder caused by the deletion of contiguous genes at chromosome region 7q11.23. TRIM62 is involved in the morphogenesis of the mammary gland; loss of TRIM62 gene expression in breast is associated with increased risk of recurrence in early-onset breast cancer. TRIM69 is a novel testis E3 ubiquitin ligase that may function to ubiquitinate its particular substrates during spermatogenesis. In humans, TRIM69 localizes in the cytoplasm and nucleus, and requires an intact RING finger domain to function. TRIM protein NF7, which also contains a chromodomain (CHD) at the N-terminus and an RFP (Ret finger protein)-like domain at the C-terminus, is required for its association with transcriptional units of RNA polymerase II which is mediated by a trimeric B box. In Xenopus oocyte, xNF7 has been identified as a nuclear microtubule-associated protein (MAP) whose microtubule-bundling activity, but not E3-ligase activity, contributes to microtubule organization and spindle integrity. Bloodthirsty (bty) is a novel gene identified in zebrafish and has been shown to likely play a role in in regulation of the terminal steps of erythropoiesis. TRIM72 has been shown to perform a critical function in membrane repair following acute muscle injury by nucleating the assembly of the repair machinery at injury sites. The PRY-SPRY domain in these TRIM families is suggested to serve as the target binding site.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2029297694 187 DMTLDANTANNFLLISDDLRSVRSGRIRQNRQDLAERFDVSVCILGSPRFTCGRHCWEVDVGTSTEWDLGVCRESVHRKG 266
Cdd:cd13733     1 DVTLDPDTAHPNLILSEDLKSVRYGDKRQNLPDNPERFDTCVCVLGSEGFSSGRHYWEVEVGGKTDWDLGVARESVNRKG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2029297694 267 RIQLTTELGFWTVSLRDGGRLSATTVPLTFLFVDRKLQRVGIFLDMGMQNVSFFDAESGSHVYTFRSVSAeEPLRPFLAP 346
Cdd:cd13733    81 KITLSPENGYWTVGLRNGNEYKALTSPSTPLSLREKPQKVGVFLDYEEGQVSFYNVDDGSHIYTFTDCFT-EKLYPYFSP 159

                         170
                  ....*....|....*
gi 2029297694 347 SVPPNGDQGV-LSIC 360
Cdd:cd13733   160 CLNDGGKNSApLIIC 174

butyrophilin subfamily member A1 and A2 (BTN1A and BTN2A); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of butyrophilin family 1A and 2A (BTN1A and BTN2A). BTNs belong to receptor glycoproteins of immunoglobulin (Ig) superfamily, characterized by the presence of extracellular Ig-like domains (IgV and/or IgC). BTN1A plays a role in the secretion, formation and stabilization of milk fat globules. The B30.2 domain of BTN1A1 binds the enzyme xanthine oxidoreductase (XOR) in order to participate in milk fat globule secretion; this interaction may lead to the production of reactive oxygen species, which have immunomodulatory and antimicrobial functions. Duplication events have led to three paralogs of BTN2A in primates: BTN2A1, BTN2A2, and BTN2A3. In humans, only BTN2A1 has been functionally characterized; it has been detected on epithelial cells and leukocytes, and identified as a novel ligand of dendritic cell-specific ICAM-3 grabbing nonintegrin (DCSIGN), a C-type lectin receptor that acts as an internalization receptor for HIV-1, HCV, and other pathogens. BTN2A2 mRNA has been shown to be expressed in circulating human immune cells.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2029297694 186 VDMTLDANTANNFLLISDDLRSVRSGRIRQNRQDLAERFDVSVCILGSPRFTCGRHCWEVDVGTSTEWDLGVCRESVHRK 265
Cdd:cd15819     2 VNVTLDPDTAHPALILSEDGRSVTWGETRQDLPENPERFDSLPCVLGQEGFTSGRHYWEVEVGDRTSWDLGVCRDNVMRK 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2029297694 266 GRIQLTTELGFWTVSLrDGGRLSATTVPLTFLFVDRKLQRVGIFLDMGMQNVSFFDAESGSHVYTFRSVSAEEPLRPF-- 343
Cdd:cd15819    82 GRVTLSPENGFWAIRL-YGNEYWALTSPETPLTLKEPPRRVGIFLDYEAGDVSFYNMTDGSHIYTFPQTAFSGPLRPFfr 160

                         170
                  ....*....|....*..
gi 2029297694 344 LAPSvppngDQGVLSIC 360
Cdd:cd15819   161 LWSS-----DSGPLTIC 172

PRY/SPRY domain in tripartite motif-binding protein 20 (TRIM20), also known as pyrin; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM20, which is also known as pyrin or marenostrin. Unlike TRIM domains that are composed of RING/B-box/coiled-coil core, the N-terminal RING domain in TRIM20 is exchanged by a PYRIN domain (PYD), a prime mediator of protein interactions necessary for apoptosis, inflammation and innate immune signaling pathway, and it also harbors a C-terminal B30.2 domain. Mutations in pyrin (TRIM20) are associated with familial Mediterranean fever (FMF), a recessively hereditary periodic fever syndrome, characterized by episodes of inflammation and fever. These mutations cluster in the C-terminal B30.2 domain and therefore it is assumed that pyrin plays a role in the innate immune system by possibly effecting caspase-1-dependent IL-1beta maturation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2029297694 180 RMRKFQVDMTLDANTANNFLLISDDLRSVRSGRIRQNRQDLAERFDVSVCILGSPRFTCGRHCWEVDVGTSTEWDLGVCR 259
Cdd:cd15813     3 AAQAHAVNVTLDPETAHPNLIFSDDLKSVRLGNKWDRLPDNPERFDSCIIVLGSPSFTSGRHYWEVEVGDKTGWILGVCK 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2029297694 260 ESVHRKGRIQLTTELGFWTVSLRDGGRLSATTVPLTFLFVDRKLQRVGIFLDMGMQNVSFFDAESGSHVYTFRSVSAEEP 339
Cdd:cd15813    83 ASVSRKGSMTLSPENGYWVVMMTKRNEYQASTSPPTRLWLREPPRRVGIFLDYEAGDISFYNVTAKSHIYTFTSFSSSGP 162

                         170       180
                  ....*....|....*....|..
gi 2029297694 340 LRPFLAPSVPPNG-DQGVLSIC 360
Cdd:cd15813   163 LQPIFSPGTHDGGkNMDPLTIC 184

PRY/SPRY domain in tripartite motif-binding protein 69 (TRIM69), also known as RING finger protein 36 (RNF36); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM69, which is also known as RING finger protein 36 (RNF36) or testis-specific ring finger (Trif). TRIM69 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. It is a novel testis E3 ubiquitin ligase that may function to ubiquitinate its particular substrates during spermatogenesis. In humans, TRIM69 localizes in the cytoplasm and nucleus, and requires an intact RING finger domain to function. The mouse ortholog of this gene is specifically expressed in germ cells at the round spermatid stages during spermatogenesis and, when overexpressed, induces apoptosis. TRIM69 has been shown to be a novel regulator of mitotic spindle assembly in tumor cells; it associates with spindle poles and promotes centrosomal clustering, and is therefore essential for formation of a bipolar spindle.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2029297694 188 MTLDANTANNFLLISDDLRSVRSGRIRQNRQDLAERFDVSVCILGSPRFTCGRHCWEVDVGTSTEWDLGVCRESVHRKGR 267
Cdd:cd15818    15 ITLDPKTAHPNLILSEDLTCVWHGDTKQMLPDNPERFDSSVAVLGSEGFTSGKHYWEVEVAKKTKWTLGVVRESINRKGN 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2029297694 268 IQLTTELGFWTVSLRDGGRLSATTVPLTFLFVDRKLQRVGIFLDMGMQNVSFFDAESGSHVYTFrSVSAEEPLRPFLAPS 347
Cdd:cd15818    95 CPLSPEDGFWLLRLRNQNELKALDVPSFSLTLTSNLNKVGIYLDYEGGQVSFYNANTMSHIYTF-SDTFTEKIYPYFCPC 173

                  ....*...
gi 2029297694 348 VPPNGDQG 355
Cdd:cd15818   174 LNDSGENK 181

PRY/SPRY domain in tripartite motif-binding protein 7 (TRIM7)-like, including TRIM7, TRIM10, TRIM15, TRIM26, TRIM39, TRIM41; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of several tripartite motif-containing (TRIM) proteins, including TRIM7 (also referred to as glycogenin-interacting protein, RING finger protein 90 or RNF90), TRIM10, TRIM15, TRIM26, TRIM39 and TRIM41. TRIM7 or GNIP interacts with glycogenin and stimulates its self-glucosylating activity via its SPRY domain. TRIM10 (also known as hematopoietic RING finger 1 (HERF1) or TRIM10/HERF1) plays a key role in definitive erythroid development; downregulation of the Spi-1/PU.1 oncogene induces the expression of TRIM10/HERF1, a key factor required for terminal erythroid cell differentiation and survival. Antiviral activity of TRIM15 is dependent on the ability of its B-box to interact with the MLV Gag precursor protein; downregulation of TRIM15, along with TRIM11, enhances virus release suggesting that these proteins contribute to the endogenous restriction of retroviruses in cells. Tripartite motif-containing 26 (TRIM26) function is as yet unknown; however, since it is localized in the human histocompatibility complex (MHC) class I region, TRIM26 may play a role in immune response although studies show no association between TRIM26 polymorphisms and the risk of aspirin-exacerbated respiratory disease. TRIM39 is a MOAP-1 (Modulator of Apoptosis)-binding protein that stabilizes MOAP-1 through inhibition of its poly-ubiquitination process. TRIM41 (also known as RING finger-interacting protein with C kinase or RINCK) functions as an E3 ligase that catalyzes the ubiquitin-mediated degradation of protein kinase C.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2029297694 187 DMTLDANTANNFLLISDDLRSVRSGRIRQNRQDLAERFDVSVCILGSPRFTCGRHCWEVDVGTSTEWDLGVCRESVHRKG 266
Cdd:cd12888     1 NVTLDPDTAHPRLVLSEDRKSVRWGDTRQDLPDNPERFDTWPCVLGCEGFTSGRHYWEVEVGDGGGWAVGVARESVRRKG 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2029297694 267 RIQLTTELGFWTVSlRDGGRLSATTVPLTFLFVDRKLQRVGIFLDMGMQNVSFFDAESGSHVYTFRSVS-AEEPLRPFL 344
Cdd:cd12888    81 EISFSPEEGIWAVG-QWGGQYWALTSPETPLPLSEVPRRIRVYLDYEGGQVAFFDADNEAPIFTFPPASfAGERIFPWF 158

PRY/SPRY domain of tripartite motif-binding protein 75 (TRIM75); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM75, also known as Gm794. TRIM75 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. TRIM75 has a single site of positive selection in its RING domain associated with E3 ubiquitin ligase activity. It has not been detectably expressed experimentally due to their constant turnover by the proteasome, and therefore not been characterized.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2029297694 171 LKKILQmnprmrKFQVDMTLDANTANNFLLISDDLRSVRSGRIRQNRQDLAERFDVSVCILGSPRFTCGRHCWEVDVGTS 250
Cdd:cd15829    10 LQKIIK------KFRVDVTLDPETAHPNLLVSEDKKCVTFTKKKQRVPDSPKRFTVNPVVLGFPGFHSGRHFWEVEVGDK 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2029297694 251 TEWDLGVCRESVHRKGRIQLTTELGFWTVSLRDGGRLSATTVPLTFLFvDRKLQRVGIFLDMGMQNVSFFDAESGSHVYT 330
Cdd:cd15829    84 PEWAVGVCKDSLSTKARRPPSGQQGCWRIQLQGGDYDAPGAVPPPLLL-EVKPRGIGVFLDYELGEISFYNMPEKSHIHT 162

                         170
                  ....*....|...
gi 2029297694 331 FRSVSAeEPLRPF 343
Cdd:cd15829   163 FTDTFS-GPLRPY 174

zinc-binding protein A33-like; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM69 and TRIM proteins NF7 and bloodthirsty (bty). TRIM69 is a novel testis E3 ubiquitin ligase that may function to ubiquitinate its particular substrates during spermatogenesis. In humans, TRIM69 localizes in the cytoplasm and nucleus, and requires an intact RING finger domain to function. TRIM protein NF7, which also contains a chromodomain (CHD) at the N-terminus and an RFP (Ret finger protein)-like domain at the C-terminus, is required for its association with transcriptional units of RNA polymerase II which is mediated by a trimeric B box. In Xenopus oocyte, xNF7 has been identified as a nuclear microtubule-associated protein (MAP) whose microtubule-bundling activity, but not E3-ligase activity, contributes to microtubule organization and spindle integrity. Bloodthirsty (bty) is a novel gene identified in zebrafish and has been shown to likely play a role in in regulation of the terminal steps of erythropoiesis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2029297694 188 MTLDANTANNFLLISDDLRSVRSGRIRQNRQDLAERFDVSVCILGSPRFTCGRHCWEVDVGTSTEWDLGVCRESVHRKGR 267
Cdd:cd12905     6 LTFDPETAHPSLILSRDLTAVTESDEMQPYPRSPKRFLQCVNVLASQGFQSGRHYWEVWVGSKTKWDLGVASESVDRQAR 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2029297694 268 IQLTTELGFWTVSLRDGGRLSATTVPLTFLFVDRKLQRVGIFLDMGMQNVSFFDAESGSHVYTFRSVSAEEpLRPFLAPS 347
Cdd:cd12905    86 VKLCPENGYWTLRLRNGDEYWAGTQPWTRLRVTSRPQRIGVFLDCEERKVSFYNADDMSLLYSFHQGPRGK-VFPFFSTC 164

                  ....*.
gi 2029297694 348 VPPNGD 353
Cdd:cd12905   165 FSDDGQ 170

PRY/SPRY domain of tripartite motif-binding protein 11 (TRIM11), also known as RING finger protein 92 (RNF92); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM11, also known as RING finger protein 92 (RNF92) or BIA1. TRIM11 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. It localizes to the nucleus and the cytoplasm; it is overexpressed in high-grade gliomas and promotes proliferation, invasion, migration and glial tumor growth. TRIM11 increases expression of dopamine beta-hydroxylase gene by interacting with the homeodomain transcription factor, PHOX2B, via the B30.2/SPRY domain, thus playing a potential role in the specification of noradrenergic (NA) neuron phenotype. It has also been shown that TRIM11 plays a critical role in the clearance of mutant PHOX2B, which causes congenital central hypoventilation syndrome, via the proteasome. TRIM11 binds a key component of the activator-mediated cofactor complex (ARC105), and destabilizes it, through the ubiquitin-proteasome system; ARC105 mediates chromatin-directed transcription activation and is a key regulatory factor for transforming growth factor beta (TGFbeta) signaling.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2029297694 187 DMTLDANTANNFLLISDDLRSVRSGRIRQNRQDLAERFDVSVCILGSPRFTCGRHCWEVDVGTSTEWDLGVCRESVHRKG 266
Cdd:cd15811     1 DVTLDPDTANPELVLSEDRRSVRRGDLRQALPDSPERFDPGPCVLGRERFTSGRHYWEVEVGDRTSWALGVCKENVNRKE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2029297694 267 RIQLTTELGFWTVSLRDGGRLS--ATTVPLTflfvdRKLQRVGIFLDMGMQNVSFFDAESGSHVYTFRSVSAEEPLRPFL 344
Cdd:cd15811    81 KGELSAGNGFWILVFLGNYYSSerRTFAPLR-----DPPRRVGIFLDYEAGHLSFYSATDGSLLFIFPETPFSGTLRPLF 155

                  ..
gi 2029297694 345 AP 346
Cdd:cd15811   156 SP 157

PRY/SPRY domain of tripartite motif-binding protein 60 and 75 (TRIM60 and TRIM75); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM60 and TRIM75, both composed of RING/B-box/coiled-coil core and also known as RBCC proteins. TRIM60 domain is also known as RING finger protein 33 (RNF33) or 129 (RNF129). Based on its expression profile, RNF33 likely plays an important role in the spermatogenesis process, the development of the pre-implantation embryo, and in testicular functions; Rnf33 is temporally transcribed in the unfertilized egg and the pre-implantation embryo, and is permanently silenced before the blastocyst stage. Mice experiments have shown that RNF33 associates with the cytoplasmic motor proteins, kinesin-2 family members 3A (KIF3A) and 3B (KIF3B), suggesting possible contribution to cargo movement along the microtubule in the expressed sites. TRIM75, also known as Gm794, has a single site of positive selection in its RING domain associated with E3 ubiquitin ligase activity. It has not been detectably expressed experimentally due to their constant turnover by the proteasome, and therefore not been characterized.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2029297694 187 DMTLDANTANNFLLISDDLRSVRSGRIRQNRQDLAERFDVSVCILGSPRFTCGRHCWEVDVGTSTEWDLGVCRESVHRKG 266
Cdd:cd15817     1 DLILDPETAHPNLIVSEDRKAVRYRRMKPNCPYDPRRFTVYPAVLGSEGFDSGRHFWEVEVGGKGEWILGVCKDSLPRNA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2029297694 267 RIQLTTELGFWTVSLRDGGRLSATTVPlTFLFVDRKLQRVGIFLDMGMQNVSFFDAESGSHVYTFrSVSAEEPLRPFLap 346
Cdd:cd15817    81 QDPPSPLGGCWQIGRYMSGYVASGPKT-TQLLPVVKPSRIGIFLDYELGEVSFYNMNDRSHLYTF-TDTFTGKLIPYF-- 156

                         170
                  ....*....|....
gi 2029297694 347 SVPPngDQGVLSIC 360
Cdd:cd15817   157 YVGP--DSEPLTIC 168

PRY/SPRY domain of tripartite motif-binding protein 60 (TRIM60) also known as RING finger protein 33 (RNF33); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM60, which is also known as RING finger protein 33 (RNF33) or 129 (RNF129). TRIM60 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. Based on its expression profile, RNF33 likely plays an important role in the spermatogenesis process, the development of the pre-implantation embryo, and in testicular functions; Rnf33 is temporally transcribed in the unfertilized egg and the pre-implantation embryo, and is permanently silenced before the blastocyst stage. Mice experiments have shown that RNF33 associates with the cytoplasmic motor proteins, kinesin-2 family members 3A (KIF3A) and 3B (KIF3B), suggesting possible contribution to cargo movement along the microtubule in the expressed sites.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2029297694 171 LKKILQmnprmrKFQVDMTLDANTANNFLLISDDLRSVRSGRIRQNRQDLAERFDVSVCILGSPRFTCGRHCWEVDVGTS 250
Cdd:cd15828     1 LDRIIK------RFQVDVTLDPETAHPQLTVSEDRKSVLYGEMKQNVCYNPRRFYLCPAVLGSEGFHSGRQYWEVEVGDK 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2029297694 251 TEWDLGVCRESVHRKGRIQLTTELGFWTVslrdgGRLSATTVpltFLFVDRKLQ--------RVGIFLDMGMQNVSFFDA 322
Cdd:cd15828    75 PEWTLGVCQDCLPRNWSNQPSVQDGLWAI-----GRYSESNY---VALGPKKIQllpkvrpsKIGIFLDYELGEVSFYNM 146

                         170       180
                  ....*....|....*....|.
gi 2029297694 323 ESGSHVYTFRSvSAEEPLRPF 343
Cdd:cd15828   147 NDRSLLYTFSD-SFTGTLWPY 166

PRY/SPRY domain in tripartite motif-binding protein 15 (TRIM15); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of tripartite motif-containing protein 15 (TRIM15), also referred to as RING finger protein 93 (RNF93) or Zinc finger protein B7 or 178 (ZNFB7 or ZNF178). TRIM15 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. The PRY and SPRY/B30.2 domains can function as immune defense components and in pathogen sensing. TRIM15 has been shown to regulate inflammatory and innate immune signaling, in addition to displaying antiviral activities. Down-regulation of TRIM15, as well as TRIM11, enhances virus release, suggesting that these proteins contribute to the endogenous restriction of retroviruses in cells. TRIM15 is also a regulatory component of focal adhesion turnover and cell migration.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2029297694 188 MTLDANTANNFLLISDDLRSVRSGRIRQNRQDLAERFDVSVCILGSPRFTCGRHCWEVDV--GTSTEWDLGVCRESVHRK 265
Cdd:cd15826     2 VTLDPQTASGSLVLSEDRKSVRYTRQKQNLPDSPLRFDGLPAVLGSPGFSSGRHRWQVEVqlGDGGGCTVGVAGESVRRK 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2029297694 266 GRIQLTTELGFWTVSLRDGGrLSATTVPLTFLFVDRKLQRVGIFLDMGMQNVSFFDAESGSHVYTFrSVSAEEPLRPFLA 345
Cdd:cd15826    82 GEMGLSAEDGVWAVILSHQQ-CWASTSPGTDLPLSEIPRRVGVALDYEAGTVTLTNAETQEPIFTF-TASFSGKVFPFFA 159

PRY/SPRY domain in tripartite motif-binding (TRIM) proteins TRIM50 and TRIM72; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of several TRIM proteins, including TRIM72 and TRIM50. TRIM72 (also known as MG53) has been shown to perform a critical function in membrane repair following acute muscle injury by nucleating the assembly of the repair machinery at injury sites. It is expressed specifically in skeletal muscle and heart, and tethered to the plasma membrane and cytoplasmic vesicles via its interaction with phosphatidylserine. TRIM50, an E3 ubiquitin ligase, is deleted in Williams-Beuren (WBS) syndrome, a multi-system neurodevelopmental disorder caused by the deletion of contiguous genes at chromosome region 7q11.23.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2029297694 187 DMTLDANTANNFLLISDDLRSVRSGRIRQNRQDLAERFDVSVCILGSPRFTCGRHCWEVDVGTSTEWDLGVCRESVHRKG 266
Cdd:cd12897    13 SLTFDPATAHPLLVVSSGGTVVECGLQKQRRASQPERFDKSTCVVASQGFSEGEHYWEVVVGDKPRWALGVIKGTASRKG 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2029297694 267 RIQLTTELGFWTVSLRDGGRLSATTVPLTF--LFVDRKLQRVGIFLDMGMQNVSFFDAESGSH---VYTFRSvSAEEPLR 341
Cdd:cd12897    93 KLHASPSHGVWLIGLKEGKVYEAHGEPKEPrpLRVAGRPHRIGVYLSFEDGVLSFFDASDPDDlrtLYTFQE-RFQGKLY 171

                  ...
gi 2029297694 342 PFL 344
Cdd:cd12897   172 PFF 174

PRY/SPRY domain in tripartite motif-binding protein 50 (TRIM50); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM50. TRIM50, an E3 ubiquitin ligase, is deleted in Williams-Beuren (WBS) syndrome, a multi-system neurodevelopmental disorder caused by the deletion of contiguous genes at chromosome region 7q11.23. It is specifically expressed in gastric parietal cells and may play an essential role in tubulovesicular dynamics. It also interacts with and increases the level of p62, a multifunctional adaptor protein that is implicated in various cellular processes such as the autophagy clearance of polyubiquitinated protein aggregates.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2029297694 188 MTLDANTANNFLLISDDLRSVRSGRIRQNRQDLAERFDVSVCILGSPRFTCGRHCWEVDVGTSTEWDLGVCRESVHRKGR 267
Cdd:cd13743    14 LKLDPLTAHPMLELSKGNTVVECGLLAQRLPSNPERFDYSNCVLASRGFSSGKHYWEVVVGSKSKWRLGLIKGTTSRKGK 93

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2029297694 268 IQLTTELGFWTVSLRDGGRLSATTVPLTFLFVDRKLQRVGIFLDMGMQNVSFFDAESGSHVYTFRSVSAE 337
Cdd:cd13743    94 LNKSPENGVWLIGLKEGRVYEAFANPRVPLPLSTRPQRIGVFLDYEKGELTFYNADSPDELVPIYTFQAE 163

PRY/SPRY domain in tripartite motif-binding protein 41 (TRIM41); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of tripartite motif-containing protein 41 (TRIM41). TRIM41 (also known as RING finger-interacting protein with C kinase or RINCK) is localized to speckles in the cytoplasm and nucleus, and functions as an E3 ligase that catalyzes the ubiquitin-mediated degradation of protein kinase C.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2029297694 187 DMTLDANTANNFLLISDDLRSVRSGRIRQNRQDLAERFDVSVCILGSPRFTCGRHCWEVDVGTSTEWDLGVCRESVHRK- 265
Cdd:cd13741     1 DLTLDPDTAHPALLLSPDRRGVRLAERRQEVPEHPKRFSADCCVLGAQGFRSGRHYWEVEVGGRRGWAVGAARESTHHKe 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2029297694 266 ---------------------GRIQLTTELG------FWTVSlRDGGRLSA-TTVPLTFLFVDRKLQRVGIFLDMGMQNV 317
Cdd:cd13741    81 kvgsggssvssgdasssrhhhRRRRLHLPQQpllqreVWCVG-TNGKRYQAqSSTEQTLLSPSEKPRRFGVYLDYEAGRL 159

                         170       180
                  ....*....|....*....|....*..
gi 2029297694 318 SFFDAESGSHVYTFRSVSAEEPLRPFL 344
Cdd:cd13741   160 GFYNAETLAHVHTFSAAFLGERVFPFF 186

PRY/SPRY domain of tripartite motif-binding protein 17 (TRIM17), also known as testis RING finger protein (terf); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM17, also known as RING finger protein 16 (RNF16) or testis RING finger protein (terf). TRIM17 domain is composed of RING/B-box/coiled-coil core and also known as RBCC protein, expressed almost exclusively in the testis. It exhibits E3 ligase activity, causing protein degradation of ZW10 interacting protein (ZWINT), a known component of the kinetochore complex required for the mitotic spindle checkpoint, and negatively regulates proliferation of breast cancer cells. TRIM17 undergoes ubiquitination in COS7 fibroblast-like cells but is inhibited and stabilized by TRIM44.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2029297694 222 ERFDVSVCILGSPRFTCGRHCWEVDVGTSTE--WDLGVCRESVHRKGRIQLTTELGFWTVSLRDGGR-LSA--TTVPLTF 296
Cdd:cd15812    36 DRFLAYPCAVGQETFSSGRHYWEVGMNLTGDalWALGVCRDNVSRKDRVPKSPENGFWVVQLSKGKKyLSAmsALTPVTL 115

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2029297694 297 LFVDrklQRVGIFLDMGMQNVSFFDAESGSHVYTFRSVSAEEPLRPFLAPSVPPNGdQGVLS 358
Cdd:cd15812   116 TEPP---SHMGIFLDFEAGEVSFYSVNDGSHLHTYSQAAFPGPLQPFFCLGAPKSG-QMVIS 173

Variant RING finger, HC subclass (C4C4-type), found in Ret finger protein-like (RFPL) family; The RFPL family, also known as the RING-B30 family, represents a group of RFPL gene products, RFPL1, RFPL2, RFPL3, and RFPL4A, which are characterized by containing an N-terminal RFPL1, 2, 3-specifying helix (RSH), a C4C4- or a variant C4C4-type RING finger, whose overall folding is similar to that of the typical C3HC4-type RING-HC finger, an RFPL-defining motif (RDM), and C-terminal PRY/SPRY-forming B30.2 domain. RFPL1, also known as RING finger protein 78 (RNF78), is expressed during cell differentiation. RFPL2, also known as RING finger protein 79 (RNF79), shows high sequence similarity with other RFPL gene products. Its biological role remains unclear. RFPL3 interacts directly with CREB binding protein (CBP) in the nucleus of lung cancer cells. RFPL3 and CBP synergistically upregulate TERT activity and promote lung cancer growth. Moreover, RFPL3 acts as a novel E3 ubiquitin ligase modulating the integration activity of human immunodeficiency virus, type 1 (HIV-1) preintegration complex. RFPL4A, also known as RING finger protein 210 (RNF210), is a novel factor that increases the G1 population and decreases sensitivity to chemotherapy in human colorectal cancer cells. This model corresponds to the C4C4-type RING finger. RFPL4A lacks the fourth conserved zinc-binding residue, cysteine, and the eighth zinc-binding residue, cysteine; in RFPL2, it is replaced by serine.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 2029297694  99 SSCPVCSDYLEKPMSLECGCAVCLKCINSLQKEPHGEDLLCCCSSMVS 146
Cdd:cd16621     1 SSCPVCSDYLEKPVSLECGYACCLQCLNSLQKEPHGEGLLCCCCSVVS 48