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 149408130  38 SSCPVCSDYLEKPMSLECGCAVCFKCINSLQKEPHGEDLLCCCCSMVS 85
Cdd:cd16621    1 SSCPVCSDYLEKPVSLECGYACCLQCLNSLQKEPHGEGLLCCCCSVVS 48

SPRY domain; SPRY Domain is named from SPla and the RYanodine Receptor and it is found in many eukaryotic proteins with a wide range of functions. It is a protein-interaction module involved in many important signalling pathways like RNA processing, regulation of histone H3 methylation, innate immunity or embryonic development. It can be divided into 11 subfamilies based on amino acid sequence similarity or the presence of additional protein domains. The greater SPRY family is divided into the SPRY/B30.2 (which contains a PRY extension at the N-terminal) and SPRY-only sub-families which are preceded by a subdomain that is structurally similar to the PRY region. SPRY/B30.2 structures revealed a bent beta-sandwich fold comprised of two beta-sheets. Distant homologs are domains in butyrophilin/ marenostrin/pyrin.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149408130  179 RHYWEVDVG--TSTEWDLGVCRESVHRKGRIHLTTERGFWTVSLRDGSRLSASTVPLTFLFVDRKLQRVGIFLDMGMQNV 256
Cdd:pfam00622   1 RHYFEVEIFgqDGGGWRVGWATKSVPRKGERFLGDESGSWGYDGWTGKKYWASTSPLTGLPLFEPGDVIGCFLDYEAGTI 80

                          90       100       110
                  ....*....|....*....|....*....|..
gi 149408130  257 SFFDAeGGSHVYTFRSVSAEEPLHLFFAPPSP 288
Cdd:pfam00622  81 SFTKN-GKSLGYAFRDVPFAGPLFPAVSLGAG 111

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 149408130  38 SSCPVCSDYLEKPMSLECGCAVCFKCINSLQKEPHGEDLLCCCCSMVS 85
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 149408130   40 CPVCSDYLEKPMSLECGCAVCFKCINSLQKEPHGEDLLCCCC 81
Cdd:pfam15227   1 CPICLDYLEKPVSIECGHSFCLSCINSLQKEPDGESLLCPQC 42

Ring finger; E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of c-Cbl and is likely to be a general function of this domain; Various RING fingers exhibit binding activity towards E2 ubiquitin-conjugating enzymes (Ubc' s)

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 149408130    40 CPVC-SDYLEKPMSLECGCAVCFKCINSLQKEPHGEdllCCCC 81
Cdd:smart00184   1 CPIClEEYLKDPVILPCGHTFCRSCIRKWLESGNNT---CPIC 40

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 149408130 126 DMTLDADTANNFLLISDDLRSVRSGCITQNRQDLAERFDVSICILGSPRFTCGRHYWEVDVGTSTEWDLGVCRESVHRKG 205
Cdd:cd13733    1 DVTLDPDTAHPNLILSEDLKSVRYGDKRQNLPDNPERFDTCVCVLGSEGFSSGRHYWEVEVGGKTDWDLGVARESVNRKG 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149408130 206 RIHLTTERGFWTVSLRDGSRLSASTVPLTFLFVDRKLQRVGIFLDMGMQNVSFFDAEGGSHVYTFRSVSAeEPLHLFFAP 285
Cdd:cd13733   81 KITLSPENGYWTVGLRNGNEYKALTSPSTPLSLREKPQKVGVFLDYEEGQVSFYNVDDGSHIYTFTDCFT-EKLYPYFSP 159

                        170
                 ....*....|....*
gi 149408130 286 PSPPNGDKSV-LSIC 299
Cdd:cd13733  160 CLNDGGKNSApLIIC 174

PRY/SPRY domain of butyrophilin 3 (BTN3), includes BTN3A1, BTN3A2, BTN3A3 as well as BTN-like 3 (BTNL3); BTN3A also known as CD277; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of butyrophilin family 3A (BTN3A); duplication events have led to three paralogs in primates: BTN3A1, BTN3A2, and BTN3A3. BTNs belong to receptor glycoproteins of immunoglobulin (Ig) superfamily, characterized by the presence of extracellular Ig-like domains (IgV and/or IgC). BTN3 transcripts are ubiquitously present in all immune cells (T cells, B cells, NK cells, monocytes, dendritic cells, and hematopoietic precursors) with different expression levels; BTN3A1 and BTN3A2 are expressed mainly by CD4+ and CD8+ T cells, BTN3A2 is the major form expressed in NK cells, and BTN3A3 is poorly expressed in these immune cells. The PRY/SPRY domain of the BTN3A1 isoform mediates phosphoantigen (pAg)-induced activation by binding directly to the pAg.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149408130 123 FQ-VDMTLDADTANNFLLISDDLRSVRSGCITQNRQDLAERFDVSICILGSPRFTCGRHYWEVDVGTSTEWDLGVCRESV 201
Cdd:cd15820    1 FQpADVILDPDTANPILLISEDQRSLQWADEPQNLPDNPKRFDWHYCVLGCKSFTSGRHFWEVEVGDRKEWYVGVCRENV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149408130 202 HRKGRIHLTTERGFWTVSLRDGSRLSASTVPLTFLFVDRKLQRVGIFLDMGMQNVSFFDAEGGSHVYTFRSVSAEEPLHL 281
Cdd:cd15820   81 ERKLWVKMAPENGFWTIGLSDGNDYQALTDPRTKLTIANPPQRVGVFLDYETGEVSFYNAMDGSHIYTFPHTSFSGPLYP 160

                        170
                 ....*....|....*....
gi 149408130 282 FFAPPSppnGDKSVLSICP 300
Cdd:cd15820  161 VFRLLS---WDPTALTICP 176

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 149408130 125 VDMTLDADTANNFLLISDDLRSVRSGCITQNRQDLAERFDVSICILGSPRFTCGRHYWEVDVGTSTEWDLGVCRESVHRK 204
Cdd:cd15819    2 VNVTLDPDTAHPALILSEDGRSVTWGETRQDLPENPERFDSLPCVLGQEGFTSGRHYWEVEVGDRTSWDLGVCRDNVMRK 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149408130 205 GRIHLTTERGFWTVSLrDGSRLSASTVPLTFLFVDRKLQRVGIFLDMGMQNVSFFDAEGGSHVYTFRSVSAEEPLHLFFA 284
Cdd:cd15819   82 GRVTLSPENGFWAIRL-YGNEYWALTSPETPLTLKEPPRRVGIFLDYEAGDVSFYNMTDGSHIYTFPQTAFSGPLRPFFR 160

                        170
                 ....*....|....*
gi 149408130 285 PPSppnGDKSVLSIC 299
Cdd:cd15819  161 LWS---SDSGPLTIC 172

PRY/SPRY domain of tripartite motif-binding protein 38 (TRIM38), also known as Ring finger protein 15 (RNF15); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM38, which is also known as RING finger protein 15 (RNF15) or RORET. TRIM38 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. TRIM38 has been shown to act as a suppressor in TOLL-like receptor (TLR)-mediated interferon (IFN)-beta induction by promoting degradation of TRAF6 and NAP1 through the ubiquitin-proteasome system. Another study has shown that TRIM38 may act as a novel negative regulator for TLR3-mediated IFN-beta signaling by targeting TRIF for degradation. TRIM38 has been identified as a critical negative regulator in TNFalpha- and IL-1beta-triggered activation of NF-kappaB and MAP Kinases (MAPKs); it causes degradation of two essential cellular components, TGFbeta-associated kinase 1 (TAK1)-associating chaperones 2 and 3 (TAB2/3). The degradation is promoted through a lysosomal-dependent pathway, which requires the C-terminal PRY-SPRY of TRIM38. Enterovirus 71 infection induces degradation of TRIM38, suggesting that TRIM38 may play a role in viral infections.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149408130 120 MRKFQVDMTLDADTANNFLLISDDLRSVRSGCITQNRQDLAERFDVSICILGSPRFTCGRHYWEVDVGTSTEWDLGVCRE 199
Cdd:cd15815    8 LRRHQVSVTLDPDTAHPELTLSKDQRQVTYGRCQENLDASPKRFTVLPCVLGCEGFTSGRHYFEVDVGEGTGWDVGVCLE 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149408130 200 SVHRKGRIHLTTERGFWTVSLRDGSRLSASTVPLTFLFVDRKLQRVGIFLDMGMQNVSFFDAEGGSHVYTFRSVSAEEPL 279
Cdd:cd15815   88 NVQRGFGMKQEPEFGFWTIRLCEEDGYVALTSPPTPLPLREKPLVVGVFLDYEAGLVSFYNMTTGSHIFTFPKASFSDTL 167

                 ....
gi 149408130 280 HLFF 283
Cdd:cd15815  168 RPYF 171

PRY/SPRY domain, also known as B30.2; This domain contains residues in the N-terminus that form a distinct PRY domain structure such that the B30.2 domain consists of PRY and SPRY subdomains. B30.2 domains comprise the C-terminus of three protein families: BTNs (receptor glycoproteins of immunoglobulin superfamily); several TRIM proteins (composed of RING/B-box/coiled-coil core); Stonutoxin (secreted poisonous protein of the stonefish Synanceia horrida). While SPRY domains are evolutionarily ancient, B30.2 domains are a more recent adaptation where the SPRY/PRY combination is a possible component of immune defense. Among the TRIM proteins, also known as the N-terminal RING finger/B-box/coiled coil (RBCC) family, only Classes I and II contain the B30.2 domain that has evolved under positive selection. Class I TRIM proteins include multiple members involved in antiviral immunity at various levels of interferon signaling cascade. Among the 75 human TRIMs, roughly half enhance immune response, which they do at multiple levels in signaling pathways. 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 149408130 127 MTLDADTANNFLLISDDLRSVRSGCITQNRQDLAERFDVSICILGSPRFTCGRHYWEVDVGTSTEWDLGVCRESVHRKG- 205
Cdd:cd12874    1 LTFDPDTAHLNLILSDDLRSVRVGDISQHPPEPPPRFFECWQVLGSQSFSSGRHYWEVDVQDDSSWYVGVTYKSLPRKGk 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149408130 206 RIHLTTERGFWTVSLRDGSrLSASTV-PLTFLFVdRKLQRVGIFLDMGMQNVSFFDAEGG-SHVYTFRSVSAeEPLHLFF 283
Cdd:cd12874   81 MSNLGRNNGSWCLEWRENE-FSAWHNnPETRLPV-TPPRRLGVFLDCDGGSLSFYGVTDGvQLLYTFKAKFT-EPLYPAF 157

                        170
                 ....*....|....*.
gi 149408130 284 APpsppnGDKSVLSIC 299
Cdd:cd12874  158 WL-----GEGSTLSIC 168

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 149408130 127 MTLDADTANNFLLISDDLRSVRSGCITQNRQDLAERFDVSICILGSPRFTCGRHYWEVDVGTSTEWDLGVCRESVHRKGR 206
Cdd:cd12905    6 LTFDPETAHPSLILSRDLTAVTESDEMQPYPRSPKRFLQCVNVLASQGFQSGRHYWEVWVGSKTKWDLGVASESVDRQAR 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149408130 207 IHLTTERGFWTVSLRDGSRLSASTVPLTFLFVDRKLQRVGIFLDMGMQNVSFFDAEGGSHVYTFRSVSAEEpLHLFFAPP 286
Cdd:cd12905   86 VKLCPENGYWTLRLRNGDEYWAGTQPWTRLRVTSRPQRIGVFLDCEERKVSFYNADDMSLLYSFHQGPRGK-VFPFFSTC 164

                 ....*...
gi 149408130 287 SPPNGDKS 294
Cdd:cd12905  165 FSDDGQNA 172

PRY/SPRY domain in tripartite motif-binding protein 21 (TRIM21) also known as 52kD Ribonucleoprotein Autoantigen (Ro52); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM21, which is also known as Sjogren Syndrome Antigen A (SSA), SSA1, 52kD Ribonucleoprotein Autoantigen (Ro52, Ro/SSA, SS-A/Ro) or RING finger protein 81 (RNF81). TRIM21 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. As an E3 ligase, TRIM21 mediates target specificity in ubiquitination; it regulates type 1 interferon and proinflammatory cytokines via ubiquitination of interferon regulatory factors (IRFs). It is up-regulated at the site of autoimmune inflammation, such as cutaneous lupus lesions, indicating a central role in the tissue destructive inflammatory process. It interacts with auto-antigens in patients with Sjogren syndrome and systemic lupus erythematosus, a chronic systemic autoimmune disease characterized by the presence of autoantibodies against the protein component of the human intracellular ribonucleoprotein-RNA complexes and more specifically TRIM21, Ro60/TROVE2 and La/SSB proteins. It binds the Fc part of IgG molecules via its PRY-SPRY domain with unexpectedly high affinity.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149408130 123 FQVDMTLDADTANNFLLISDDLRSVRSGCITQNRQDLAERFDVSICILGSPRFTCGRHYWEVDVGTSTEWDLGVCRESVH 202
Cdd:cd12900    1 HMVHITLDPDTANPWLILSKDRRQVRLGDTHQNVPENEERFDNYPMVLGAQRFNSGKHYWEVDVTGKEAWDLGVCRDSVR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149408130 203 RKGRIHLTTERGFWTVSLRDGSrLSASTVPLTFLFVDRKLQRVGIFLDMGMQNVSFFD-AEGGSHVYTFRSVSAEEPLHL 281
Cdd:cd12900   81 RKGQFLLSPENGFWTIWLWNKK-YEAGTSPQTTLHLQVPPCQVGIFLDYEAGVVSFYNiTDHGSLIYTFSECAFTGPLRP 159

                        170       180
                 ....*....|....*....|.
gi 149408130 282 FFAPPSPPNGDKSV-LSICPV 301
Cdd:cd12900  160 FFNPGFNDSGGNAApLTLCPL 180

PRY/SPRY domain in tripartite motif-binding protein 58 (TRIM58), also known as BIA2; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM58, also known as BIA2. TRIM58 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins.It is implicated by genome-wide association studies (GWAS) to regulate erythrocyte traits, including cell size and number. Trim58 facilitates erythroblast enucleation by inducing proteolytic degradation of the microtubule motor dynein.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149408130 126 DMTLDADTANNFLLISDDLRSVRSGCITQNRQDLAERFDVSICILGSPRFTCGRHYWEVDVGTSTEWDLGVCRESVHRKG 205
Cdd:cd15816    1 DVKLDPATAHPSLLLTADLRSVQDGELWRDVPGNPERFDTWPCVLGLQSFSSGRHYWEVAVGEKAEWGLGVCQDSAPRKG 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 149408130 206 RIHLTTERGFWTVSLRDGSR---LSASTVPltfLFVDRKLQRVGIFLDMGMQNVSFFDAEGGSHVYTFRSV 273
Cdd:cd15816   81 ETTPSPENGVWAVWLLKGNEymvLASPSVP---LLQLRRPRRVGVFLDYEAGEISFYNVTAGSHIYTFRQL 148

PRY/SPRY domain in tripartite motif-binding protein 62 (TRIM62); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM62. It is also called DEAR1 ductal epithelium (associated RING chromosome 1) and 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 and thus, making TRIM62 a predictive biomarker. Non-small cell lung cancer lesions show a step-wise loss of TRIM62 levels during disease progression, indicating that it may play a role in the evolution of lung cancer. Decreased levels of TRIM62 also represent an independent adverse prognostic factor in AML.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149408130 127 MTLDADTANNFLLISDDLRSVRSGCI-TQNRQDLAERFDVSICILGSPRFTCGRHYWEVDVGTSTEWDLGVCRESVHRKG 205
Cdd:cd13744   14 LTLDPVTAHQRLILSDDCTIVAYGNLhPQPLQDSPKRFDVEVSVLGSEGFSGGVHYWEVVVSEKTQWMIGLAHEAVSRKG 93

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 149408130 206 RIHLTTERGFWTVSLRDGSRLSASTVPLTFLFVDRKLQRVGIFLDMGMQNVSFFDAEGGSHVYTFR 271
Cdd:cd13744   94 SIQIQPGRGFYCIVMHDGNQYSACTEPWTRLNVKSKLEKVGVYLDYDKGLLIFYNADDMSWLYTFR 159

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 149408130 110 LKKILQmnprmrKFQVDMTLDADTANNFLLISDDLRSVRSGCITQNRQDLAERFDVSICILGSPRFTCGRHYWEVDVGTS 189
Cdd:cd15828    1 LDRIIK------RFQVDVTLDPETAHPQLTVSEDRKSVLYGEMKQNVCYNPRRFYLCPAVLGSEGFHSGRQYWEVEVGDK 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149408130 190 TEWDLGVCRESVHRKGRIHLTTERGFWTVSLRDGSRLSASTVPLTFLFVDRKLQRVGIFLDMGMQNVSFFDAEGGSHVYT 269
Cdd:cd15828   75 PEWTLGVCQDCLPRNWSNQPSVQDGLWAIGRYSESNYVALGPKKIQLLPKVRPSKIGIFLDYELGEVSFYNMNDRSLLYT 154

                 ..
gi 149408130 270 FR 271
Cdd:cd15828  155 FS 156

SPRY domain; SPRY Domain is named from SPla and the RYanodine Receptor and it is found in many eukaryotic proteins with a wide range of functions. It is a protein-interaction module involved in many important signalling pathways like RNA processing, regulation of histone H3 methylation, innate immunity or embryonic development. It can be divided into 11 subfamilies based on amino acid sequence similarity or the presence of additional protein domains. The greater SPRY family is divided into the SPRY/B30.2 (which contains a PRY extension at the N-terminal) and SPRY-only sub-families which are preceded by a subdomain that is structurally similar to the PRY region. SPRY/B30.2 structures revealed a bent beta-sandwich fold comprised of two beta-sheets. Distant homologs are domains in butyrophilin/ marenostrin/pyrin.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149408130  179 RHYWEVDVG--TSTEWDLGVCRESVHRKGRIHLTTERGFWTVSLRDGSRLSASTVPLTFLFVDRKLQRVGIFLDMGMQNV 256
Cdd:pfam00622   1 RHYFEVEIFgqDGGGWRVGWATKSVPRKGERFLGDESGSWGYDGWTGKKYWASTSPLTGLPLFEPGDVIGCFLDYEAGTI 80

                          90       100       110
                  ....*....|....*....|....*....|..
gi 149408130  257 SFFDAeGGSHVYTFRSVSAEEPLHLFFAPPSP 288
Cdd:pfam00622  81 SFTKN-GKSLGYAFRDVPFAGPLFPAVSLGAG 111

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 149408130 126 DMTLDADTANNFLLISDDLRSVRSGCITQNRQDLAERFDVSICILGSPRFTCGRHYWEVDVGTSTEWDLGVCRESVHRKG 205
Cdd:cd15817    1 DLILDPETAHPNLIVSEDRKAVRYRRMKPNCPYDPRRFTVYPAVLGSEGFDSGRHFWEVEVGGKGEWILGVCKDSLPRNA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149408130 206 RIHLTTERGFWTVSLRDgSRLSASTVPLTFLFVDRKLQRVGIFLDMGMQNVSFFDAEGGSHVYTFRSVSAEEPLHLFFAP 285
Cdd:cd15817   81 QDPPSPLGGCWQIGRYM-SGYVASGPKTTQLLPVVKPSRIGIFLDYELGEVSFYNMNDRSHLYTFTDTFTGKLIPYFYVG 159

                 ..
gi 149408130 286 PS 287
Cdd:cd15817  160 PD 161

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 149408130 127 MTLDADTANNFLLISDDLRSVRSGCITQNRQDLAERFDVSICILGSPRFTCGRHYWEVDVGTSTEWDLGVCRESVHRKGR 206
Cdd:cd13743   14 LKLDPLTAHPMLELSKGNTVVECGLLAQRLPSNPERFDYSNCVLASRGFSSGKHYWEVVVGSKSKWRLGLIKGTTSRKGK 93

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149408130 207 IHLTTERGFWTVSLRDGSRLSASTVPLTFLFVDRKLQRVGIFLDMGMQNVSFFDAEGGSHVYTFRSVSAE 276
Cdd:cd13743   94 LNKSPENGVWLIGLKEGRVYEAFANPRVPLPLSTRPQRIGVFLDYEKGELTFYNADSPDELVPIYTFQAE 163

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 149408130 126 DMTLDADTANNFLLISDDLRSVRSGCITQNRQDLAERFDVSICILGSPRFTCGRHYWEVDVGTSTE--WDLGVCRESVHR 203
Cdd:cd15812    1 DVVPDPSTAYPYLLLYESRQRRYLSTPPDGTPCSKDRFLAYPCAVGQETFSSGRHYWEVGMNLTGDalWALGVCRDNVSR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149408130 204 KGRIHLTTERGFWTVSLRDGSR----LSASTvPLTFLFVDrklQRVGIFLDMGMQNVSFFDAEGGSHVYTFRSVSAEEPL 279
Cdd:cd15812   81 KDRVPKSPENGFWVVQLSKGKKylsaMSALT-PVTLTEPP---SHMGIFLDFEAGEVSFYSVNDGSHLHTYSQAAFPGPL 156

                        170
                 ....*....|....*...
gi 149408130 280 HLFFAPPSPPNGdKSVLS 297
Cdd:cd15812  157 QPFFCLGAPKSG-QMVIS 173

PRY/SPRY domain in tripartite motif-binding protein 72 (TRIM72); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM72. Muscle-specific TRIM72 (also known as Mitsugumin 53 or 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. TRIM72 interacts with dysferlin, a sarcolemmal protein whose deficiency causes Miyoshi myopathy (MM) and limb girdle muscular dystrophy type 2B (LGMD2B); this coordination plays an important role in the repair of sarcolemma damage.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149408130 126 DMTLDADTANNFLLISDDLRSVRsgCITQNRQ---DLAERFDVSICILGSPRFTCGRHYWEVDVGTSTEWDLGVCRESVH 202
Cdd:cd13742   13 NLTFDPDTAHPYLVVSSDGKRVE--CADQKQAvssDDPNRFDKANCVVSHQSFSEGEHYWEVIVGDKPRWALGVISAEAG 90

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149408130 203 RKGRIHLTTERGFWTVSLRDGSRLSAST---VPLTfLFVDRKLQRVGIFLDMGMQNVSFFDAEGGSHV---YTFRSvSAE 276
Cdd:cd13742   91 RKGRLHALPSNGFWLLGCKEGKVYEAHVehkEPRA-LRVEGRPTRIGVYLSFSDGVLSFYDASDEDNLvqlFAFHE-RFP 168

                 ....*....
gi 149408130 277 EPLHLFFAP 285
Cdd:cd13742  169 GPLYPFFDV 177

PRY/SPRY domain in tripartite motif-containing protein 34 (TRIM34), also known as RING finger protein 21 (RNF21) or interferon-responsive finger protein (IFP1); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM34, also known as RING finger protein 21 (RNF21) or interferon-responsive finger protein (IFP1). TRIM34 domain is composed of RING/B-box/coiled-coil core and also known as RBCC protein. The TRIM21 cDNA possesses at least three kinds of isoforms, due to alternative splicing, of which only the long and medium forms contain the SPRY domain. It is an interferon-induced protein, predominantly expressed in the testis, kidney, and ovary. The SPRY domain provides the capsid recognition motif that dictates specificity to retroviral restriction. While the PRY-SPRY domain provides specificity and the capsid recognition motif to retroviral restriction, TRIM34 binds HIV-1 capsid but does not restrict HIV-1 infection.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149408130 125 VDMTLDADTANNFLLISDDLRSVRSGCITQNRQDlaerfdvSICILGSPRFTCGRHYWEVDVGTSTEWDLGV-CRESVH- 202
Cdd:cd15825    2 VDFTLNPVNLNLNLVLSEDQRQVTSVPIWPFKCY-------NYGILGSQYFSSGKHYWEVDVSKKTAWILGVyCRKRSRt 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149408130 203 ----RKGRIHLTT------ERGFWTVSLRDGSRLSASTVPLTF------LFVDRKLQRVGIFLDMGMQNVSFFDAEG-GS 265
Cdd:cd15825   75 fkyvRQGKNHPNVysryrpQYGYWVIGLQNKSEYYAFEDSSTSdpkvltLSVATPPHRVGVFLDYEAGTVSFFNVTNhGS 154

                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 149408130 266 HVYTFRSVSAEEPLHLFFAP---PSPpngdksvLSICP 300
Cdd:cd15825  155 LIYKFSKCCFSQPVYPYFNPwncPAP-------MTLCP 185