PRY/SPRY domain in tripartite motif-binding protein 7 (TRIM7); 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 7 (TRIM7), also referred to as glycogenin-interacting protein (GNIP) or RING finger protein 90 (RNF90). TRIM7 or GNIP interacts with glycogenin and stimulates its self-glucosylating activity via its SPRY domain. The GNIP gene encodes at least four distinct isoforms of GNIP, of which three (GNIP1, GNIP2, and GNIP3) have the B30.2 domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 44680124 135 ELTLDPDTANPRLILSLDLKGVRLGERAQDLPNHPCRFDTNTRVLASCGFSSGRHHWEVEVGSKDGWAFGVARESVRRKG 214
Cdd:cd13740   1 ELTLDPDSANPRLILSLDLKSVRLGERAQDLPNHPCRFDTNTRVLASCGFSSGRHHWEVEVGSKDGWAFGVARESVRRKG 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 44680124 215 LTPFTPEEGVWALQLNGGQYWAVTSPERSPLSCGHLSRVRVALDLEVGAVSFYAVEDMRHLYTFRVNFQERVFPLFSVCS 294
Cdd:cd13740  81 LTPFTPEEGVWALQLNGGQYWAVTSPERTPLSCGHLSRVRVALDLEVGAVSFYAAEDMRHIYTFRVNFQERVFPLFSVCS 160

                ....*....
gi 44680124 295 TGTYLRIWP 303
Cdd:cd13740 161 TGTYLRIWP 169

PRY/SPRY domain in tripartite motif-binding protein 7 (TRIM7); 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 7 (TRIM7), also referred to as glycogenin-interacting protein (GNIP) or RING finger protein 90 (RNF90). TRIM7 or GNIP interacts with glycogenin and stimulates its self-glucosylating activity via its SPRY domain. The GNIP gene encodes at least four distinct isoforms of GNIP, of which three (GNIP1, GNIP2, and GNIP3) have the B30.2 domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 44680124 135 ELTLDPDTANPRLILSLDLKGVRLGERAQDLPNHPCRFDTNTRVLASCGFSSGRHHWEVEVGSKDGWAFGVARESVRRKG 214
Cdd:cd13740   1 ELTLDPDSANPRLILSLDLKSVRLGERAQDLPNHPCRFDTNTRVLASCGFSSGRHHWEVEVGSKDGWAFGVARESVRRKG 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 44680124 215 LTPFTPEEGVWALQLNGGQYWAVTSPERSPLSCGHLSRVRVALDLEVGAVSFYAVEDMRHLYTFRVNFQERVFPLFSVCS 294
Cdd:cd13740  81 LTPFTPEEGVWALQLNGGQYWAVTSPERTPLSCGHLSRVRVALDLEVGAVSFYAAEDMRHIYTFRVNFQERVFPLFSVCS 160

                ....*....
gi 44680124 295 TGTYLRIWP 303
Cdd:cd13740 161 TGTYLRIWP 169

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 44680124   188 RHHWEVEVGSKDG--WAFGVARESVRRKGLTPFTPEEGVWALQLNGGQ-YWAVTSPERSPLSCGHLSRVRVALDLEVGAV 264
Cdd:pfam00622   1 RHYFEVEIFGQDGggWRVGWATKSVPRKGERFLGDESGSWGYDGWTGKkYWASTSPLTGLPLFEPGDVIGCFLDYEAGTI 80

                          90       100
                  ....*....|....*....|....*....
gi 44680124   265 SFYAVEdMRHLYTFR-VNFQERVFPLFSV 292
Cdd:pfam00622  81 SFTKNG-KSLGYAFRdVPFAGPLFPAVSL 108

PRY/SPRY domain in tripartite motif-binding protein 7 (TRIM7); 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 7 (TRIM7), also referred to as glycogenin-interacting protein (GNIP) or RING finger protein 90 (RNF90). TRIM7 or GNIP interacts with glycogenin and stimulates its self-glucosylating activity via its SPRY domain. The GNIP gene encodes at least four distinct isoforms of GNIP, of which three (GNIP1, GNIP2, and GNIP3) have the B30.2 domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 44680124 135 ELTLDPDTANPRLILSLDLKGVRLGERAQDLPNHPCRFDTNTRVLASCGFSSGRHHWEVEVGSKDGWAFGVARESVRRKG 214
Cdd:cd13740   1 ELTLDPDSANPRLILSLDLKSVRLGERAQDLPNHPCRFDTNTRVLASCGFSSGRHHWEVEVGSKDGWAFGVARESVRRKG 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 44680124 215 LTPFTPEEGVWALQLNGGQYWAVTSPERSPLSCGHLSRVRVALDLEVGAVSFYAVEDMRHLYTFRVNFQERVFPLFSVCS 294
Cdd:cd13740  81 LTPFTPEEGVWALQLNGGQYWAVTSPERTPLSCGHLSRVRVALDLEVGAVSFYAAEDMRHIYTFRVNFQERVFPLFSVCS 160

                ....*....
gi 44680124 295 TGTYLRIWP 303
Cdd:cd13740 161 TGTYLRIWP 169

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 44680124 137 TLDPDTANPRLILSLDLKGVRLGERAQDLPNHPCRFDTNTRVLASCGFSSGRHHWEVEVGSKDGWAFGVARESVRRKGLT 216
Cdd:cd13733   3 TLDPDTAHPNLILSEDLKSVRYGDKRQNLPDNPERFDTCVCVLGSEGFSSGRHYWEVEVGGKTDWDLGVARESVNRKGKI 82

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 44680124 217 PFTPEEGVWALQL-NGGQYWAVTSPeRSPLSCGH-LSRVRVALDLEVGAVSFYAVEDMRHLYTFRVNFQERVFPLFSVC 293
Cdd:cd13733  83 TLSPENGYWTVGLrNGNEYKALTSP-STPLSLREkPQKVGVFLDYEEGQVSFYNVDDGSHIYTFTDCFTEKLYPYFSPC 160

PRY/SPRY domain in tripartite motif-containing protein 35 (TRIM35); This PRY/SPRY domain is found at the C-terminus of the overall domain architecture of tripartite motif 35, TRIM35 (also known as hemopoietic lineage switch protein), which includes a RING finger domain (RING) and a B-box motif (BBOX). TRIM35 may play a role as a tumor suppressor and is implicated in the cell death mechanism.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 44680124 137 TLDPDTANPRLILSLDLKGVRLGERAQDLPNHPCRFDTNTRVLASCGFSSGRHHWEVEVGSKDGWAFGVARESVRRKGLT 216
Cdd:cd12893   3 TLDPNTAHPWLSLSEDLTSVRYSSEKQQLPDNPERFDPYPCVLGSEGFTSGKHSWDVEVGDNTSWMLGVAKESVQRKGKF 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 44680124 217 PFTPEEGVWALQLNGGQYWAVTSPE-RSPLSCG-HLSRVRVALDLEVGAVSFYAVEDMRHLYTFRVNFQERVFPLFSVCS 294
Cdd:cd12893  83 TLSPESGFWTIGFSEGKYSARTSPEpRTPLRVKqKPQRIRVQLDWDRGKVSFSDPDTNTHIHTFTHTFTERVFPYFYTGC 162

                ....*....
gi 44680124 295 TGTYLRIWP 303
Cdd:cd12893 163 KSEPLRILP 171

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 44680124 137 TLDPDTANPRLILSLDLKGVRLGERAQDLPNHPCRFDTNTRVLASCGFSSGRHHWEVEVGSKDGWAFGVARESVRRKGLT 216
Cdd:cd13741   3 TLDPDTAHPALLLSPDRRGVRLAERRQEVPEHPKRFSADCCVLGAQGFRSGRHYWEVEVGGRRGWAVGAARESTHHKEKV 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 44680124 217 --------------------------PFTP--EEGVWALQLNGGQYWAVTSPERSPLSCGHL-SRVRVALDLEVGAVSFY 267
Cdd:cd13741  83 gsggssvssgdasssrhhhrrrrlhlPQQPllQREVWCVGTNGKRYQAQSSTEQTLLSPSEKpRRFGVYLDYEAGRLGFY 162

                       170       180       190
                ....*....|....*....|....*....|....*..
gi 44680124 268 AVEDMRHLYTFRVNF-QERVFPLFSVCSTGTYLRIWP 303
Cdd:cd13741 163 NAETLAHVHTFSAAFlGERVFPFFRVLSKGTRIKLCP 199

Ret finger protein-like (RFPL), includes RFP1, 2, 3, 4; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of RFPL protein family, which includes RFPL1, RFPL2, RFPL3 and RFPL4. In humans, RFPL transcripts can be detected at the onset of neurogenesis in differentiating human embryonic stem cells, and in the developing human neocortex. The human RFPL1, 2, 3 genes have a role in neocortex development. RFPL1 is a primate-specific target gene of Pax6, a key transcription factor for pancreas, eye and neocortex development; human RFPL1 decreases cell number through its RFPL-defining motif (RDM) and SPRY domains. The RFPL4 (also known as RFPL4A) gene encodes a putative E3 ubiquitin-protein ligase expressed in adult germ cells and interacts with oocyte proteins of the ubiquitin-proteasome degradation pathway.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 44680124 137 TLDPDTANPRLILSLDLKGVRLGERAQDLPNHPCRFDTNTRVLASCGFSSGRHHWEVEVGSKDGWAFGVARESVRRKGLT 216
Cdd:cd15821   7 TLDVDTANNYLIISEDLRSVRCGCFRQNRKELAERFDDALCVLGSPRFTSGRHYWEVDVGTSTEWDLGVCRESVNRQGPI 86

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 44680124 217 PFTPEEGVWALQL-NGGQYWAVTSPeRSPLSCG-HLSRVRVALDLEVGAVSFYAVEDMRHLYTF-RVNFQERVFPLFS 291
Cdd:cd15821  87 ELSPEHGFWTVSLrDGSVFFASTVP-LTVLWVNpRLHRVGIFLDMEMGTISFYDVSDGSHIFTFtKISAEEPLRPFFA 163

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 44680124 137 TLDPDTANPRLILSLDLKGVRLGERAQDLPNHPCRFDTNTRVLASCGFSSGRHHWEVEV--GSKDGWAFGVARESVRRKG 214
Cdd:cd15826   3 TLDPQTASGSLVLSEDRKSVRYTRQKQNLPDSPLRFDGLPAVLGSPGFSSGRHRWQVEVqlGDGGGCTVGVAGESVRRKG 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 44680124 215 LTPFTPEEGVWALQLNGGQYWAVTSPERSPLSCGHLSRVRVALDLEVGAVSFYAVEDMRHLYTFRVNFQERVFPLFSVCS 294
Cdd:cd15826  83 EMGLSAEDGVWAVILSHQQCWASTSPGTDLPLSEIPRRVGVALDYEAGTVTLTNAETQEPIFTFTASFSGKVFPFFAVWK 162

                ....*
gi 44680124 295 TGTYL 299
Cdd:cd15826 163 KGSRL 167

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 44680124 137 TLDPDTANPRLILSLDLKGVRLGERAQDLPNHPCRFDTNTRVLASCGFSSGRHHWEVEVGSKDGWAFGVARESVRRKGLT 216
Cdd:cd12874   2 TFDPDTAHLNLILSDDLRSVRVGDISQHPPEPPPRFFECWQVLGSQSFSSGRHYWEVDVQDDSSWYVGVTYKSLPRKGKM 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 44680124 217 P-FTPEEGVWALQLNGGQYWAVTSPERSPLSCGHLSRVRVALDLEVGAVSFYAVED-MRHLYTFRVNFQERVFPLFSVCS 294
Cdd:cd12874  82 SnLGRNNGSWCLEWRENEFSAWHNNPETRLPVTPPRRLGVFLDCDGGSLSFYGVTDgVQLLYTFKAKFTEPLYPAFWLGE 161

                ....*..
gi 44680124 295 tGTYLRI 301
Cdd:cd12874 162 -GSTLSI 167

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 44680124 113 LKGMLKKFKEDLrgelekeekvelTLDPDTANPRLILSLDLKGVRLGERAQDLPNHPCRFDTNTRVLASCGFSSGRHHWE 192
Cdd:cd15829  10 LQKIIKKFRVDV------------TLDPETAHPNLLVSEDKKCVTFTKKKQRVPDSPKRFTVNPVVLGFPGFHSGRHFWE 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 44680124 193 VEVGSKDGWAFGVARESVRRKGLTPFTPEEGVWALQLNGGQYwAVTSPERSPLscghLSRVR-----VALDLEVGAVSFY 267
Cdd:cd15829  78 VEVGDKPEWAVGVCKDSLSTKARRPPSGQQGCWRIQLQGGDY-DAPGAVPPPL----LLEVKprgigVFLDYELGEISFY 152

                       170       180       190
                ....*....|....*....|....*....|....
gi 44680124 268 AVEDMRHLYTFRVNFQERVFPLFSVCSTGTYLRI 301
Cdd:cd15829 153 NMPEKSHIHTFTDTFSGPLRPYFYVGPDSKPLRI 186

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 44680124 138 LDPDTANPRLILSLDLKGVRLGERAQDLPNHPCRFDTNTRVLASCGFSSGRHHWEVEVGSKDGWAFGVARESVRRKGLTP 217
Cdd:cd15820   8 LDPDTANPILLISEDQRSLQWADEPQNLPDNPKRFDWHYCVLGCKSFTSGRHFWEVEVGDRKEWYVGVCRENVERKLWVK 87

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 44680124 218 FTPEEGVWALQL-NGGQYWAVTSPeRSPLSCGH-LSRVRVALDLEVGAVSFYAVEDMRHLYTF-RVNFQERVFPLFSVCS 294
Cdd:cd15820  88 MAPENGFWTIGLsDGNDYQALTDP-RTKLTIANpPQRVGVFLDYETGEVSFYNAMDGSHIYTFpHTSFSGPLYPVFRLLS 166

                       170
                ....*....|
gi 44680124 295 T-GTYLRIWP 303
Cdd:cd15820 167 WdPTALTICP 176

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 44680124 137 TLDPDTANPRLILSLDLKGVRLGERAQDLPNHPCRFDTNTRVLASCGFSSGRHHWEVEVGSKDGWAFGVARESVRRKGLT 216
Cdd:cd15817   3 ILDPETAHPNLIVSEDRKAVRYRRMKPNCPYDPRRFTVYPAVLGSEGFDSGRHFWEVEVGGKGEWILGVCKDSLPRNAQD 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 44680124 217 PFTPEEGVWALQLNGGQYWAVTSPERSPLSCGHLSRVRVALDLEVGAVSFYAVEDMRHLYTFRVNFQERVFPLFSVCSTG 296
Cdd:cd15817  83 PPSPLGGCWQIGRYMSGYVASGPKTTQLLPVVKPSRIGIFLDYELGEVSFYNMNDRSHLYTFTDTFTGKLIPYFYVGPDS 162

                ....*
gi 44680124 297 TYLRI 301
Cdd:cd15817 163 EPLTI 167

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 44680124 137 TLDPDTANPRLILSLDLKGVRLGERAQDLPNHPCRFDTNTRVLASCGFSSGRHHWEVEVGSKDGWAFGVARESVRRKGLT 216
Cdd:cd15814   5 TLDPDTAYPSLILSDNLRQVRYSYLQQDLPDNPERFNLFPCVLGSPCFIAGRHYWEVEVGDKAKWTIGVCEDSVCRKGGV 84

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 44680124 217 PFTPEEGVWALQL-NGGQYWAVTSPERS-PLSCGhLSRVRVALDLEVGAVSFYAVEDMRHLYTF-RVNFQERVFPLFSVC 293
Cdd:cd15814  85 TSAPQNGFWAVSLwYGKEYWALTSPMTAlPLRTP-LQRVGIFLDYDAGEVSFYNVTERCHTFTFsHATFCGPVRPYFSLS 163

                ...
gi 44680124 294 STG 296
Cdd:cd15814 164 YSG 166

PRY/SPRY domain of tripartite motif-binding protein 10 (TRIM10) also known as hematopoietic RING finger 1 (HERF1); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM10, also known as RING finger protein 9 (RNF9) or hematopoietic RING finger 1 (HERF1). TRIM10 domain is composed of RING/B-box/coiled-coil core and also known as RBCC protein. TRIM10/HERF1 is predominantly expressed during definitive erythropoiesis and in embryonic liver, and minimally expressed in adult liver, kidney, and colon. It is critical for erythroid cell differentiation and its down-regulation leads to cell death; inhibition of TRIM10 expression blocks terminal erythroid differentiation, while its over-expression in erythroid cells induces beta-major globin expression and erythroid differentiation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 44680124 137 TLDPDTANPRLILSLDLKGVRLGERAQDLPNHPCRFDTNTRVLASCGFSSGRHHWEVEVGSKDGWA--FGVARESVRRKG 214
Cdd:cd15827   5 SLDPQTSHPKLLLSEDHQRARFSYKWQNSPDNPQRFDRATCVLAHDGFTGGRHTWVVSVDLAHGGSctVGVVSEDVRRKG 84

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 44680124 215 LTPFTPEEGVWALQLNGGQYWAVTS-PERSPLScGHLSRVRVALDLEVGAVSFYAVEDMRHLYTFRVNFQERVFPLFSVC 293
Cdd:cd15827  85 ELRLRPEEGVWAVRLAWGFVSALGSfPTRLALE-EQPRQVRVSLDYEVGWVTFVNAVTQEPIYTFTASFTQKVFPFFGLW 163

                ....
gi 44680124 294 STGT 297
Cdd:cd15827 164 GRGS 167

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 44680124 137 TLDPDTANPRLILSLDLKGVRLGERAQDLPNHPCRFDTNTRVLASCGFSSGRHHWEVEVGSKDGWAFGVARESVRRKGLT 216
Cdd:cd12900   6 TLDPDTANPWLILSKDRRQVRLGDTHQNVPENEERFDNYPMVLGAQRFNSGKHYWEVDVTGKEAWDLGVCRDSVRRKGQF 85

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 44680124 217 PFTPEEGVWALQLNGGQYWAVTSPErSPLscgHLS----RVRVALDLEVGAVSFYAVEDMRHL-YTF-RVNFQERVFPLF 290
Cdd:cd12900  86 LLSPENGFWTIWLWNKKYEAGTSPQ-TTL---HLQvppcQVGIFLDYEAGVVSFYNITDHGSLiYTFsECAFTGPLRPFF 161

                ..
gi 44680124 291 SV 292
Cdd:cd12900 162 NP 163

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 44680124 137 TLDPDTANPRLILSLDLKGVRLGE-RAQDLPNHPCRFDTNTRVLASCGFSSGRHHWEVEVGSKDGWAFGVARESVRRKGL 215
Cdd:cd13744  15 TLDPVTAHQRLILSDDCTIVAYGNlHPQPLQDSPKRFDVEVSVLGSEGFSGGVHYWEVVVSEKTQWMIGLAHEAVSRKGS 94

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 44680124 216 TPFTPEEGVWALQL-NGGQYWAVTSPERSPLSCGHLSRVRVALDLEVGAVSFYAVEDMRHLYTFRVNFQERVFPLFS 291
Cdd:cd13744  95 IQIQPGRGFYCIVMhDGNQYSACTEPWTRLNVKSKLEKVGVYLDYDKGLLIFYNADDMSWLYTFREKFPGKLCSYFS 171

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 44680124 137 TLDPDTANPRLILSLDLKGVR---LGERAQDLPNHPCRFDTNTrVLASCGFSSGRHHWEVEVGSKDGWAFGVARESVRRK 213
Cdd:cd13734   2 KLDPKTAHRKLRLSNDNLTVEydpEGSKDQAAVLPRRFTGSPA-VLGDVAISSGRHYWEVSVSRSTSYRVGVAYKSAPRD 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 44680124 214 ---GLTPFTpeegvWALQLNGGQYWAVTSPERSPLSC-GHLSRVRVALDLEVGAVSFYAVEDMRHLYTFRVNFQERVFPL 289
Cdd:cd13734  81 edlGKNSTS-----WCLSRDNNRYTARHDGKVVDLRVtGHPARIGVLLDYDNGTLSFYDAESKQHLYTFHVDFEGPVCPA 155

                ...
gi 44680124 290 FSV 292
Cdd:cd13734 156 FAV 158

Stonustoxin subunit alpha or SNTX subunit alpha; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of Stonustoxin alpha proteins. Stonustoxin (SNTX) is a multifunctional lethal protein isolated from venom elaborated by the stonefish. It comprises two subunits, termed alpha and beta. SNTX elicits an array of biological responses, particularly a potent hypotension and respiratory difficulties.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 44680124 137 TLDPDTANPRLILSLDLKGVRLGERAQDLPNHPCRFDTNTRVLasCGFS-SGRHHWEVEVgSKDGWAFGVARESVRRKGL 215
Cdd:cd16040  12 TLDPNTAHRNLSLSEGNRKVTRVKEEQPYPDHPERFDYWPQVL--CREGlSGRCYWEVEW-SGGGVDIAVAYKGISRKGD 88

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 44680124 216 TpftpEEGV-------WALQLNGGQY--------WAVTSPERSPlscghlSRVRVALDLEVGAVSFYAVED-MRHLYTFR 279
Cdd:cd16040  89 G----DDSRfgyndksWSLECSPSGYsfwhnnkkTEISVPSSSS------SRVGVYLDHSAGTLSFYSVSDtMTLLHTVQ 158

                       170
                ....*....|....*...
gi 44680124 280 VNFQERVFPLFSVCSTGT 297
Cdd:cd16040 159 TTFTEPLYPGFGVGYGSS 176

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 44680124   188 RHHWEVEVGSKDG--WAFGVARESVRRKGLTPFTPEEGVWALQLNGGQ-YWAVTSPERSPLSCGHLSRVRVALDLEVGAV 264
Cdd:pfam00622   1 RHYFEVEIFGQDGggWRVGWATKSVPRKGERFLGDESGSWGYDGWTGKkYWASTSPLTGLPLFEPGDVIGCFLDYEAGTI 80

                          90       100
                  ....*....|....*....|....*....
gi 44680124   265 SFYAVEdMRHLYTFR-VNFQERVFPLFSV 292
Cdd:pfam00622  81 SFTKNG-KSLGYAFRdVPFAGPLFPAVSL 108

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 44680124 139 DPDTANPRLILSLDLKGVRLGERAQDLPNHPCRFDTNTRVLASCGFSSGRHHWEVEV-GSKDG-WAFGVARESVRRKGLT 216
Cdd:cd15812   5 DPSTAYPYLLLYESRQRRYLSTPPDGTPCSKDRFLAYPCAVGQETFSSGRHYWEVGMnLTGDAlWALGVCRDNVSRKDRV 84

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 44680124 217 PFTPEEGVWALQLNGGQYWAVTSPERSPLSCGHL-SRVRVALDLEVGAVSFYAVEDMRHLYTF-RVNFQERVFPLF 290
Cdd:cd15812  85 PKSPENGFWVVQLSKGKKYLSAMSALTPVTLTEPpSHMGIFLDFEAGEVSFYSVNDGSHLHTYsQAAFPGPLQPFF 160