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 119572531 134 RKMFRALMPALEELTFDPSSAHPSLVVSSSGRRVECSEQKAPPAGEDPRQFDKAVAVVAHQQLSEGEHYWEVDVGDKPRW 213
Cdd:cd13742    1 RKMFRALMPALENLTFDPDTAHPYLVVSSDGKRVECADQKQAVSSDDPNRFDKANCVVSHQSFSEGEHYWEVIVGDKPRW 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119572531 214 ALGVIAAEAPRRGRLHAVPSQGLWLLGLREGKILEAHVEAKEPRALRSPErRPTRIGLYLSFGDGVLSFYDASDADALVP 293
Cdd:cd13742   81 ALGVISAEAGRKGRLHALPSNGFWLLGCKEGKVYEAHVEHKEPRALRVEG-RPTRIGVYLSFSDGVLSFYDASDEDNLVQ 159

                        170       180       190
                 ....*....|....*....|....*....|...
gi 119572531 294 LFAFHERLPRPVYPFFDVCWHDKGKNAQPLLLV 326
Cdd:cd13742  160 LFAFHERFPGPLYPFFDVCWHDKGKNSQPLKIF 192

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 119572531 134 RKMFRALMPALEELTFDPSSAHPSLVVSSSGRRVECSEQKAPPAGEDPRQFDKAVAVVAHQQLSEGEHYWEVDVGDKPRW 213
Cdd:cd13742    1 RKMFRALMPALENLTFDPDTAHPYLVVSSDGKRVECADQKQAVSSDDPNRFDKANCVVSHQSFSEGEHYWEVIVGDKPRW 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119572531 214 ALGVIAAEAPRRGRLHAVPSQGLWLLGLREGKILEAHVEAKEPRALRSPErRPTRIGLYLSFGDGVLSFYDASDADALVP 293
Cdd:cd13742   81 ALGVISAEAGRKGRLHALPSNGFWLLGCKEGKVYEAHVEHKEPRALRVEG-RPTRIGVYLSFSDGVLSFYDASDEDNLVQ 159

                        170       180       190
                 ....*....|....*....|....*....|...
gi 119572531 294 LFAFHERLPRPVYPFFDVCWHDKGKNAQPLLLV 326
Cdd:cd13742  160 LFAFHERFPGPLYPFFDVCWHDKGKNSQPLKIF 192

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 119572531  201 HYWEVDVG--DKPRWALGVIAAEAPRRGRLHAVPSQGLWLLGLREGKILEAhveAKEPRALRSPERRPTRIGLYLSFGDG 278
Cdd:pfam00622   2 HYFEVEIFgqDGGGWRVGWATKSVPRKGERFLGDESGSWGYDGWTGKKYWA---STSPLTGLPLFEPGDVIGCFLDYEAG 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 119572531  279 VLSFYDASdadalVPL-FAFH-ERLPRPVYPFFDVCWHDKGKN 319
Cdd:pfam00622  79 TISFTKNG-----KSLgYAFRdVPFAGPLFPAVSLGAGEGLKF 116

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 119572531 134 RKMFRALMPALEELTFDPSSAHPSLVVSSSGRRVECSEQKAPPAGEDPRQFDKAVAVVAHQQLSEGEHYWEVDVGDKPRW 213
Cdd:cd13742    1 RKMFRALMPALENLTFDPDTAHPYLVVSSDGKRVECADQKQAVSSDDPNRFDKANCVVSHQSFSEGEHYWEVIVGDKPRW 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119572531 214 ALGVIAAEAPRRGRLHAVPSQGLWLLGLREGKILEAHVEAKEPRALRSPErRPTRIGLYLSFGDGVLSFYDASDADALVP 293
Cdd:cd13742   81 ALGVISAEAGRKGRLHALPSNGFWLLGCKEGKVYEAHVEHKEPRALRVEG-RPTRIGVYLSFSDGVLSFYDASDEDNLVQ 159

                        170       180       190
                 ....*....|....*....|....*....|...
gi 119572531 294 LFAFHERLPRPVYPFFDVCWHDKGKNAQPLLLV 326
Cdd:cd13742  160 LFAFHERFPGPLYPFFDVCWHDKGKNSQPLKIF 192

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 119572531 146 ELTFDPSSAHPSLVVSSSGRRVECSEQKAPPAgEDPRQFDKAVAVVAHQQLSEGEHYWEVDVGDKPRWALGVIAAEAPRR 225
Cdd:cd13733    1 DVTLDPDTAHPNLILSEDLKSVRYGDKRQNLP-DNPERFDTCVCVLGSEGFSSGRHYWEVEVGGKTDWDLGVARESVNRK 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119572531 226 GRLHAVPSQGLWLLGLREGKILEAHveAKEPRALRSPErRPTRIGLYLSFGDGVLSFYDASDAdalVPLFAFHERLPRPV 305
Cdd:cd13733   80 GKITLSPENGYWTVGLRNGNEYKAL--TSPSTPLSLRE-KPQKVGVFLDYEEGQVSFYNVDDG---SHIYTFTDCFTEKL 153

                        170
                 ....*....|....*...
gi 119572531 306 YPFFDVCWHDKGKNAQPL 323
Cdd:cd13733  154 YPYFSPCLNDGGKNSAPL 171

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 119572531 142 PALEELTFDPSSAHPSLVVSSSGRRV-ECSEQKapPAGEDPRQFDKAVAVVAHQQLSEGEHYWEVDVGDKPRWALGVIAA 220
Cdd:cd12905    1 PGPAPLTFDPETAHPSLILSRDLTAVtESDEMQ--PYPRSPKRFLQCVNVLASQGFQSGRHYWEVWVGSKTKWDLGVASE 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119572531 221 EAPRRGRLHAVPSQGLWLLGLREGKILEAhveAKEPRALRSPERRPTRIGLYLSFGDGVLSFYDASDadaLVPLFAFHER 300
Cdd:cd12905   79 SVDRQARVKLCPENGYWTLRLRNGDEYWA---GTQPWTRLRVTSRPQRIGVFLDCEERKVSFYNADD---MSLLYSFHQG 152

                        170       180
                 ....*....|....*....|....*
gi 119572531 301 LPRPVYPFFDVCWHDKGKNAQPLLL 325
Cdd:cd12905  153 PRGKVFPFFSTCFSDDGQNAEPMRL 177

PRY/SPRY domain in tripartite motif-binding protein 39 (TRIM39) and TRIM39-like; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of pyrin, several tripartite motif-containing proteins (TRIMs), including E3 ubiquitin-protein ligase (TRIM21), RET finger protein (RFP)/tripartite motif protein 27 (TRIM27), as well as butyrophilin (Btns) and butyrophilin-like (Btnl) family members, with the exception of Btnl2. Btn and Btnl family members are novel regulators of immune responses, with many of the genes located within the MHC. They are implicated in T-cell inhibition and modulation of epithelial cell-T cell interactions. TRIM21 (also known as RO52, SSA1 or RNF81) is a major autoantigen in autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and Sjorgen's syndrome. TRIM27 (also known as Ret finger protein, RFP or RNF76) negatively regulates CD4 T-cells by ubiquitinating and inhibiting the class II phosphatidylinositol 3 kinase C2beta (PI3K-C2beta), a kinase critical for KCa3.1 channel activation. The PRY/SPRY domain of Pyrin, which is mutated in familial Mediterranean fever patients, interacts with inflammasome components and inhibits proIL-1beta processing.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119572531 146 ELTFDPSSAHPSLVVSSSGRRVECSE--QKAPpagEDPRQFDKAVAVVAHQQLSEGEHYWEVDVGDKPRWALGVIAAEAP 223
Cdd:cd13745    4 DVTLDPDTAHPNLVLSEDRKSVRHGDtrQDLP---DNPERFDTYPCVLGAEGFTGGRHYWEVEVGDKTEWTLGVCRESVS 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119572531 224 RRGRLHAVPSQGLWLLGLREGKiLEAhveAKEPRALRSPERRPTRIGLYLSFGDGVLSFYDASDADAlvpLFAFHERLPR 303
Cdd:cd13745   81 RKGEVTLSPENGYWTVWLRDGK-YEA---LTSPPTPLPVSVRPSRVGIFLDYEAGEVSFYNVTDRSH---LFTFTDTFSG 153

                        170       180
                 ....*....|....*....|..
gi 119572531 304 PVYPFFDVCWHDKGKNAQPLLL 325
Cdd:cd13745  154 TLRPYFYPGLNAGGKNAAPLII 175

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 119572531 134 RKMFRALMPALEELTFDPSSAHPSLVVSSSGRRVECSEQKAPPAGEDPRQFDKAVAVVAHQQLSEGEHYWEVDVGDKPRW 213
Cdd:cd13744    1 KSLFQDIHPVPAALTLDPVTAHQRLILSDDCTIVAYGNLHPQPLQDSPKRFDVEVSVLGSEGFSGGVHYWEVVVSEKTQW 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119572531 214 ALGVIAAEAPRRGRLHAVPSQGLWLLGLREGKILEAhveAKEPRALRSPERRPTRIGLYLSFGDGVLSFYDASDadaLVP 293
Cdd:cd13744   81 MIGLAHEAVSRKGSIQIQPGRGFYCIVMHDGNQYSA---CTEPWTRLNVKSKLEKVGVYLDYDKGLLIFYNADD---MSW 154

                        170       180       190
                 ....*....|....*....|....*....|.
gi 119572531 294 LFAFHERLPRPVYPFFDVCW-HDKGKNAQPL 323
Cdd:cd13744  155 LYTFREKFPGKLCSYFSPGQsHANGKNVQPL 185

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 119572531 147 LTFDPSSAHPSLVVSSSGRRVECSEQKAPPaGEDPRQFDKAVAVVAHQQLSEGEHYWEVDVGDKPRWALGVIAAEAPRRG 226
Cdd:cd12874    1 LTFDPDTAHLNLILSDDLRSVRVGDISQHP-PEPPPRFFECWQVLGSQSFSSGRHYWEVDVQDDSSWYVGVTYKSLPRKG 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119572531 227 -RLHAVPSQGLWLLGLREGKILEAHVEAKEPraLRSpeRRPTRIGLYLSFGDGVLSFYDASDADALvpLFAFHERLPRPV 305
Cdd:cd12874   80 kMSNLGRNNGSWCLEWRENEFSAWHNNPETR--LPV--TPPRRLGVFLDCDGGSLSFYGVTDGVQL--LYTFKAKFTEPL 153

                        170
                 ....*....|..
gi 119572531 306 YPFFdvcWHDKG 317
Cdd:cd12874  154 YPAF---WLGEG 162

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 119572531 148 TFDPSSAHPSLVVSSSGRRVECSEqKAPPAGEDPRQFDKAVAVVAHQQLSEGEHYWEVDVGDKPRWALGVIAAEAPRRGR 227
Cdd:cd15813   12 TLDPETAHPNLIFSDDLKSVRLGN-KWDRLPDNPERFDSCIIVLGSPSFTSGRHYWEVEVGDKTGWILGVCKASVSRKGS 90

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119572531 228 LHAVPSQGLWLLGLREGKILEAHVEAKEPRALRSPerrPTRIGLYLSFGDGVLSFYDASDADAlvpLFAF-HERLPRPVY 306
Cdd:cd15813   91 MTLSPENGYWVVMMTKRNEYQASTSPPTRLWLREP---PRRVGIFLDYEAGDISFYNVTAKSH---IYTFtSFSSSGPLQ 164

                        170
                 ....*....|....*..
gi 119572531 307 PFFDVCWHDKGKNAQPL 323
Cdd:cd15813  165 PIFSPGTHDGGKNMDPL 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 119572531 146 ELTFDPSSAHPSLVVSSSGRRVECSE-QKAPPAGedPRQFDKAVAVVAHQQLSEGEHYWEVDVGDKPRWALGVIAAEAPR 224
Cdd:cd12888    1 NVTLDPDTAHPRLVLSEDRKSVRWGDtRQDLPDN--PERFDTWPCVLGCEGFTSGRHYWEVEVGDGGGWAVGVARESVRR 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119572531 225 RGRLHAVPSQGLWLLGLREGKIleahveakepRALRSPERR------PTRIGLYLSFGDGVLSFYDASDADalvPLFAF- 297
Cdd:cd12888   79 KGEISFSPEEGIWAVGQWGGQY----------WALTSPETPlplsevPRRIRVYLDYEGGQVAFFDADNEA---PIFTFp 145

                        170       180
                 ....*....|....*....|.
gi 119572531 298 -----HERlprpVYPFFDVCW 313
Cdd:cd12888  146 pasfaGER----IFPWFWVGK 162

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 119572531 145 EELTFDPSSAHPSLVVSSSGRRVECSE--QKAPPAgedPRQFDKAVAVVAHQQLSEGEHYWEVDVGDKPRWALGVIAAEA 222
Cdd:cd15829   19 VDVTLDPETAHPNLLVSEDKKCVTFTKkkQRVPDS---PKRFTVNPVVLGFPGFHSGRHFWEVEVGDKPEWAVGVCKDSL 95

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119572531 223 PRRGRLHAVPSQGLWLLGLREGkileahvEAKEPRALRSP---ERRPTRIGLYLSFGDGVLSFYDASDADAlvpLFAFHE 299
Cdd:cd15829   96 STKARRPPSGQQGCWRIQLQGG-------DYDAPGAVPPPlllEVKPRGIGVFLDYELGEISFYNMPEKSH---IHTFTD 165

                        170       180
                 ....*....|....*....|....
gi 119572531 300 RLPRPVYPFFDVcwhdkGKNAQPL 323
Cdd:cd15829  166 TFSGPLRPYFYV-----GPDSKPL 184

PRY/SPRY domain in tripartite motif-containing protein 27 (TRIM27), also known as RING finger protein 76 (RNF76); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM27, also known as RING finger protein 76 (RNF76) or RET finger protein (RFP). TRIM27 domain is composed of RING/B-box/coiled-coil core and also known as RBCC proteins. It is highly expressed in the spleen, thymus and in cells of the hematopoietic compartment. TRIM27 exhibits either nuclear or cytosolic localization depending on the cell type. TRIM27 negatively regulates nucleotide-binding oligomerization domain containing 2 (NOD2)-mediated signaling by proteasomal degradation of NOD2, suggesting that TRIM27 could be a new target for therapeutic intervention in NOD2-associated diseases such as Crohn's. High expression of TRIM27 is observed in several human cancers, including breast and endometrial cancer, where elevated TRIM27 expression predicts poor prognosis. Also, TRIM27 forms an oncogenic fusion protein with Ret proto-oncogene. It is involved in different stages of spermatogenesis and its significant expression in male germ cells and seminomas, suggests that TRIM27 may be associated with the regulation of testicular germ cell proliferation and histological-type of germ cell tumors. TRIM27 could also be a predictive marker for chemoresistance in ovarian cancer patients. In the neurotoxin model of Parkinson's disease (PD), deficiency of TRIM27 decreases apoptosis and protects dopaminergic neurons, making TRIM27 an effective potential target during the treatment of PD.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119572531 146 ELTFDPSSAHPSLVVSSSGRRVECS--EQKAPpagEDPRQFDKAVAVVAHQQLSEGEHYWEVDVGDKPRWALGVIAAEAP 223
Cdd:cd15814    3 DVTLDPDTAYPSLILSDNLRQVRYSylQQDLP---DNPERFNLFPCVLGSPCFIAGRHYWEVEVGDKAKWTIGVCEDSVC 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119572531 224 RRGRLHAVPSQGLWLLGLREGKILEAHVEAKEPRALRSPERrptRIGLYLSFGDGVLSFYDASDAdalVPLFAF-HERLP 302
Cdd:cd15814   80 RKGGVTSAPQNGFWAVSLWYGKEYWALTSPMTALPLRTPLQ---RVGIFLDYDAGEVSFYNVTER---CHTFTFsHATFC 153

                        170       180
                 ....*....|....*....|...
gi 119572531 303 RPVYPFFDVCWhDKGKNAQPLLL 325
Cdd:cd15814  154 GPVRPYFSLSY-SGGKSAAPLII 175

PRY/SPRY domain in tripartite motif-containing proteins 1, 9, 18, 36, 46, 67,76 (TRIM1, TRIM9, TRIM18, TRIM36, TRIM46, TRIM67, TRIM76); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of several Class I TRIM proteins, including TRIM1, TRIM9, TRIM18, TRIM36, TRIM46, TRIM67 and TRIM76. TRIM1 (also known as MID2) and its close homolog, TRIM18 (also known as MID1), both contain a B30.2-like domain at their C-terminus and a single fibronectin type III (FN3) motif between it and their N-terminal RBCC domain. Their coiled-coil motifs mediate both homo- and heterodimerization, a prerequisite for association of the rapamycin-sensitive PP2A regulatory subunit Alpha 4 with microtubules. Mutations in TRIM18 have shown to cause Opitz syndrome, a disorder causing congenital anomalies such as cleft lip and palate as well as heart defects. TRIM9 is expressed mainly in the cerebral cortex, and functions as an E3 ubiquitin ligase. Its immunoreactivity is severely decreased in affected brain areas in Parkinson's disease and dementia with Lewy bodies, possibly playing an important role in the regulation of neuronal function and participating in pathological process of Lewy body disease through its ligase. TRIM36 interacts with centromere protein-H, one of the kinetochore proteins and possibly associates with chromosome segregation; an excess of TRIM36 may cause chromosomal instability. TRIM46 has not yet been characterized. TRIM67 negatively regulates Ras activity via degradation of 80K-H, leading to neural differentiation, including neuritogenesis. TRIM76 (also known as cardiomyopathy-associated protein 5 or CMYA5) is a muscle-specific member of the TRIM superfamily, but lacks the RING domain. It is possibly involved in protein kinase A signaling as well as vesicular trafficking. It has also been implicated in Duchenne muscular dystrophy and cardiac disease. 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 119572531 148 TFDPSSAHPSLVVSSSGRRVECSEQKAPP-AGEDPRQFDKAVAVVAHQQLSEGEHYWEVDVGDKPRWALGVIAAEAPRRG 226
Cdd:cd13734    2 KLDPKTAHRKLRLSNDNLTVEYDPEGSKDqAAVLPRRFTGSPAVLGDVAISSGRHYWEVSVSRSTSYRVGVAYKSAPRDE 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119572531 227 RLHAvpSQGLWLLgLREGKILEAHVEAKEPRaLRSPeRRPTRIGLYLSFGDGVLSFYdasDADALVPLFAFHERLPRPVY 306
Cdd:cd13734   82 DLGK--NSTSWCL-SRDNNRYTARHDGKVVD-LRVT-GHPARIGVLLDYDNGTLSFY---DAESKQHLYTFHVDFEGPVC 153

                 ....*...
gi 119572531 307 PFFDVcWH 314
Cdd:cd13734  154 PAFAV-WN 160

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 119572531 146 ELTFDPSSAHPSLVVSSSGRRVECSEQK-APPagEDPRQFDKAVAVVAHQQLSEGEHYWEVDVGDKPRWALGVIAAEAPR 224
Cdd:cd15811    1 DVTLDPDTANPELVLSEDRRSVRRGDLRqALP--DSPERFDPGPCVLGRERFTSGRHYWEVEVGDRTSWALGVCKENVNR 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119572531 225 RGRLHAVPSQGLWLLglregkILEAHVEAKEPRALRSPERRPTRIGLYLSFGDGVLSFYDASDADAL--VPLFAFHERLp 302
Cdd:cd15811   79 KEKGELSAGNGFWIL------VFLGNYYSSERRTFAPLRDPPRRVGIFLDYEAGHLSFYSATDGSLLfiFPETPFSGTL- 151

                 ....
gi 119572531 303 RPVY 306
Cdd:cd15811  152 RPLF 155

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 119572531 146 ELTFDPSSAHPSLVVSSSGRRVECSEQKAPPAgEDPRQFDKAVAVVAHQQLSEGEHYWEVDVGDKPRWALGVIAAEA--- 222
Cdd:cd13741    1 DLTLDPDTAHPALLLSPDRRGVRLAERRQEVP-EHPKRFSADCCVLGAQGFRSGRHYWEVEVGGRRGWAVGAARESThhk 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119572531 223 ---------------------PRRGRLHaVPSQGL-----WLLGlREGKILEAhVEAKEPRALrSPERRPTRIGLYLSFG 276
Cdd:cd13741   80 ekvgsggssvssgdasssrhhHRRRRLH-LPQQPLlqrevWCVG-TNGKRYQA-QSSTEQTLL-SPSEKPRRFGVYLDYE 155

                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 119572531 277 DGVLSFYDAsDADALVPLF--AFH-ERlprpVYPFFDV 311
Cdd:cd13741  156 AGRLGFYNA-ETLAHVHTFsaAFLgER----VFPFFRV 188

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 119572531 128 FKFQVWRKMFRAlmpaleELTFDPSSAHPSLVVSSSGRRV--ECSEQKAPPAgedPRQFDKAVAVVAHQQLSEGEHYWEV 205
Cdd:cd15815    2 FDVKKMLRRHQV------SVTLDPDTAHPELTLSKDQRQVtyGRCQENLDAS---PKRFTVLPCVLGCEGFTSGRHYFEV 72

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119572531 206 DVGDKPRWALGVIAAEAPRRGRLHAVPSQGLWLLGLREGKILEAHVEAKEPRALRSperRPTRIGLYLSFGDGVLSFYD- 284
Cdd:cd15815   73 DVGEGTGWDVGVCLENVQRGFGMKQEPEFGFWTIRLCEEDGYVALTSPPTPLPLRE---KPLVVGVFLDYEAGLVSFYNm 149

                        170       180
                 ....*....|....*....|....*....
gi 119572531 285 -----------ASDADALVPLFAFHERLP 302
Cdd:cd15815  150 ttgshiftfpkASFSDTLRPYFQVYQYSP 178

PRY/SPRY domain in tripartite motif-containing domain 65 (TRIM65); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM65 proteins (composed of RING/B-box/coiled-coil core and also known as RBCC proteins). The SPRY/PRY combination is a possible component of immune defense. This protein family has not been characterized.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119572531 147 LTFDPSSAHPSLVVSSSGRRVECSEQKAPPAGEDPRQFDkAVAVVAHQQLSEGEHYWEVDVGDkPRWALGVIAAEAPRR- 225
Cdd:cd12896   12 LTFDPRTANKYLELSRQNRRAKHGRSAARGVPASPGSFE-LWQVQCTQSFQHGHHYWEVEVSS-HSVTLGVTYPGLPRHk 89

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119572531 226 --------GRlhavpSQGLWLLGLREGKILEAHveakEPRALRSPERRPTRIGLYLSFGDGVLSFYdaSDADALVPLFAF 297
Cdd:cd12896   90 qgghkdniGR-----NPCSWGLQIQEDSLQAWH----NGRAQKLQGVSYRLLGVDLDLEAGTLTFY--GLEPGTQRLHTF 158

                        170
                 ....*....|....*.
gi 119572531 298 HERLPRPVYPffdVCW 313
Cdd:cd12896  159 HAIFTQPLYP---VFW 171

PRY/SPRY domain in tripartite motif-binding protein 6 (TRIM6), also known as RING finger protein 89 (RNF89); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM6, also known as RING finger protein 89 (RNF89). TRIM6 domain is composed of RING/B-box/coiled-coil core and also known as RBCC protein. It is selectively expressed in embryonic stem (ES) cells and interacts with the proto-oncogene product Myc, maintaining the pluripotency of the ES cells. TRIM6, together with E2 Ubiquitin conjugase (UbE2K) and K48-linked poly-Ub chains, is critical for the IkappaB kinase epsilon (IKKepsilon) branch of type I interferon (IFN-I) signaling pathway and subsequent establishment of a protective antiviral response.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119572531 146 ELTFDPSSAHPSLVVSSSGRRVECSEQKAPPAGEDPRQFDkaVAVVAHQQLSEGEHYWEVDVGDKPRWALGVIA-AEAPR 224
Cdd:cd15823    4 DVTLNPHTANLNLVLSKNRRQVRFVGAKLSGPSYLEEHYD--CSVLGSQHFSSGKHYWEVDVTKKTAWILGVCShSLGPT 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119572531 225 RGRLHAV----------PSQGLWLLGLREGKILEAHvEAKEPRALRSPERRPTRIGLYLSFGDGVLSFYDASDADalVPL 294
Cdd:cd15823   82 FSFNQYAqnhnaysryqPQSGYWVIGLQHNHEYRAY-EDSSTSLLLSMTVPPRRVGVFLDYEAGTVSFYNVTNHG--FPI 158

                        170
                 ....*....|....*....
gi 119572531 295 FAFHE-RLPRPVYPFFDVC 312
Cdd:cd15823  159 YTFSKyYFPTTLCPYFNPC 177