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 1721869592 362 DVTLDPDTAHPRLILSEDGKQVHDGGVRKRLPDNPKRFTQYIFVLTRQSFSSGRFYFEVQVKDKTDWWLGVARESIDRTG 441
Cdd:cd13733     1 DVTLDPDTAHPNLILSEDLKSVRYGDKRQNLPDNPERFDTCVCVLGSEGFSSGRHYWEVEVGGKTDWDLGVARESVNRKG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1721869592 442 GTEWTPETGYWTL-LYTKDGLVFRDDPPVRLPLRAELRKVGVFVDYDEGLVSFYDVEARVHLCSATGCtFSEPLYPVLYP 520
Cdd:cd13733    81 KITLSPENGYWTVgLRNGNEYKALTSPSTPLSLREKPQKVGVFLDYEEGQVSFYNVDDGSHIYTFTDC-FTEKLYPYFSP 159

                         170
                  ....*....|....*
gi 1721869592 521 GLHYGGNNSAPLIIS 535
Cdd:cd13733   160 CLNDGGKNSAPLIIC 174

B-box-type zinc finger superfamily; The B-box-type zinc finger is a short zinc binding domain of around 40 amino acid residues in length. It has been found in transcription factors, ribonucleoproteins and proto-oncoproteins, such as in TRIM (tripartite motif) proteins that consist of an N-terminal RING finger (originally called an A-box), followed by 1-2 B-box domains and a coiled-coil domain (also called RBCC for Ring, B-box, Coiled-Coil). The B-box-type zinc finger often presents in combination with other motifs, like RING zinc finger, NHL motif, coiled-coil or RFP domain in functionally unrelated proteins, most likely mediating protein-protein interactions. Based on different consensus sequences and the spacing of the 7-8 zinc-binding residues, B-box-type zinc fingers can be divided into two groups, type 1 (Bbox1: C6H2) and type 2 (Bbox2: CHC3H2).

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1721869592  96 CDVCTGTQLKAVKSCLVCLTSYCQTHLEPHHRVAGLKKHRLVEPMDRL 143
Cdd:cd19842     2 CDLCLGRELAAAKTCLTCLASFCPEHLEPHLSSPAFRSHRLCPPERDL 49

phosphodiesterase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1721869592 191 TAQLGMIEAEVKHLIQERQKN--------IQEIKDTVKCSKADADREIADGVQVLTALMRCIEKWQDDLNQMvKEKLKST 262
Cdd:PRK12704   30 EAKIKEAEEEAKRILEEAKKEaeaikkeaLLEAKEEIHKLRNEFEKELRERRNELQKLEKRLLQKEENLDRK-LELLEKR 108

                          90       100
                  ....*....|....*....|....*...
gi 1721869592 263 EKQAEDLIKGLEQEIEDLTNRSSEVKQI 290
Cdd:PRK12704  109 EEELEKKEKELEQKQQELEKKEEELEEL 136

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 1721869592 362 DVTLDPDTAHPRLILSEDGKQVHDGGVRKRLPDNPKRFTQYIFVLTRQSFSSGRFYFEVQVKDKTDWWLGVARESIDRTG 441
Cdd:cd13733     1 DVTLDPDTAHPNLILSEDLKSVRYGDKRQNLPDNPERFDTCVCVLGSEGFSSGRHYWEVEVGGKTDWDLGVARESVNRKG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1721869592 442 GTEWTPETGYWTL-LYTKDGLVFRDDPPVRLPLRAELRKVGVFVDYDEGLVSFYDVEARVHLCSATGCtFSEPLYPVLYP 520
Cdd:cd13733    81 KITLSPENGYWTVgLRNGNEYKALTSPSTPLSLREKPQKVGVFLDYEEGQVSFYNVDDGSHIYTFTDC-FTEKLYPYFSP 159

                         170
                  ....*....|....*
gi 1721869592 521 GLHYGGNNSAPLIIS 535
Cdd:cd13733   160 CLNDGGKNSAPLIIC 174

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1721869592  413 SGRFYFEVQVKDKTDWWLGVARESIDRTGGTEWTPETGYWTLLYTKDGLVF-RDDPPVRLPLRAELRKVGVFVDYDEGLV 491
Cdd:smart00449   1 SGRHYFEVEIGDGGHWRVGVATKSVPRGYFALLGEDKGSWGYDGDGGKKYHnSTGPEYGLPLQEPGDVIGCFLDLEAGTI 80

                           90       100       110
                   ....*....|....*....|....*....|
gi 1721869592  492 SFYDVEARVHLCSATGCTFSEPLYPVLYPG 521
Cdd:smart00449  81 SFYKNGKYLHGLAFFDVKFSGPLYPAFSLG 110

B-box-type 1 zinc finger found in tripartite motif-containing proteins, TRIM25, TRIM47 and similar proteins; The family includes tripartite motif-containing proteins, TRIM25 and TRIM47, both of which belong to the C-IV subclass of TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a RING finger, Bbox1 and Bbox2, and a coiled coil region, as well as a SPRY/B30.2 domain positioned C-terminal to the RBCC domain. The type 1 B-box (Bbox1) zinc finger is characterized by a C6H2 zinc-binding consensus motif. TRIM25, also termed estrogen-responsive finger protein (EFP), or ubiquitin/ISG15-conjugating enzyme TRIM25, or zinc finger protein 147 (ZNF147), or E3 ubiquitin/ISG15 ligase TRIM25, is induced by estrogen and is particularly abundant in placenta and uterus. It has been implicated in cell proliferation, protein modification, and the retinoic acid inducible gene I (RIG-I)-mediated antiviral signaling pathway. It functions as an E3-ubiquitin ligase able to transfer ubiquitin and ISG15 to target proteins. TRIM47, also known as gene overexpressed in astrocytoma protein (GOA) or RING finger protein 100 (RNF100), plays an important role in the process of dedifferentiation that is associated with astrocytoma tumorigenesis.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1721869592  96 CDVCTGTQLKAVKSCLVCLTSYCQTHLEPHHRVAGLKKHRLVEPMDRL 143
Cdd:cd19842     2 CDLCLGRELAAAKTCLTCLASFCPEHLEPHLSSPAFRSHRLCPPERDL 49

RING-type zinc-finger; This zinc-finger is a typical RING-type of plant ubiquitin ligases.

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1721869592  15 CSICLDVFSSPVsTPCGHNFCRTCITKF-WDEQVKYKCP 52
Cdd:pfam13445   1 CPICLELFTDPV-LPCGHTFCRECLEEMsQKKGGKFKCP 38

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 1721869592   15 CSICLDVFSS-PVSTPCGHNFCRTCITKfWDEQVKYKCPVC 54
Cdd:smart00184   1 CPICLEEYLKdPVILPCGHTFCRSCIRK-WLESGNNTCPIC 40

B-box zinc finger;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1721869592 144 EDRMCKKHDR-LLELFCKTEQVCVCQFCTETDHKSHPVIPL 183
Cdd:pfam00643   2 KERLCPEHEEePLTLYCNDCQELLCEECSVGEHRGHTVVPL 42

E3 ubiquitin-protein ligase RMA2; Provisional

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1721869592  12 NFSCSICLDVFSSPVSTPCGHNFCRTCITKF-------------WDEQVK-YKCPVC 54
Cdd:PLN03208   18 DFDCNICLDQVRDPVVTLCGHLFCWPCIHKWtyasnnsrqrvdqYDHKREpPKCPVC 74

Uncharacterized protein, contains DUF3084 domain [Function unknown];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1721869592 141 DRLEDRMCKKHDRLLELFCKTEQVcvcqfctetdhkshpVIPLKEEYEVKTAQLGMIEAEVKHLIQERQKNIQEiKDTVK 220
Cdd:COG4372     2 DRLGEKVGKARLSLFGLRPKTGIL---------------IAALSEQLRKALFELDKLQEELEQLREELEQAREE-LEQLE 65

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1721869592 221 CSKADADREIADGVQVLTALMRCIEKWQDDLNQMvKEKLKSTEKQAEDL---IKGLEQEIEDLTNRSSEVKQ 289
Cdd:COG4372    66 EELEQARSELEQLEEELEELNEQLQAAQAELAQA-QEELESLQEEAEELqeeLEELQKERQDLEQQRKQLEA 136

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1721869592  184 KEEYEVKT---------AQLGMIEAEVKHLIQERQKNIQEIKDTVKcskadadrEIADGVQVLTALMRCIEKWQDDLNQM 254
Cdd:TIGR02169  220 KREYEGYEllkekealeRQKEAIERQLASLEEELEKLTEEISELEK--------RLEEIEQLLEELNKKIKDLGEEEQLR 291

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1721869592  255 VKEKLKSTE---KQAEDLIKGLEQEIEDLTNRSSEVK-QISHTKDHLhflqafRSLKdppptRDwttvevrppsyVGTLR 330
Cdd:TIGR02169  292 VKEKIGELEaeiASLERSIAEKERELEDAEERLAKLEaEIDKLLAEI------EELE-----RE-----------IEEER 349

                          170       180       190
                   ....*....|....*....|....*....|....*.
gi 1721869592  331 RSLDQLEEtlnmEMKKQRDDAELKRVQQYEVDVTLD 366
Cdd:TIGR02169  350 KRRDKLTE----EYAELKEELEDLRAELEEVDKEFA 381

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 1721869592 362 DVTLDPDTAHPRLILSEDGKQVHDGGVRKRLPDNPKRFTQYIFVLTRQSFSSGRFYFEVQVKDKTDWWLGVARESIDRTG 441
Cdd:cd13733     1 DVTLDPDTAHPNLILSEDLKSVRYGDKRQNLPDNPERFDTCVCVLGSEGFSSGRHYWEVEVGGKTDWDLGVARESVNRKG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1721869592 442 GTEWTPETGYWTL-LYTKDGLVFRDDPPVRLPLRAELRKVGVFVDYDEGLVSFYDVEARVHLCSATGCtFSEPLYPVLYP 520
Cdd:cd13733    81 KITLSPENGYWTVgLRNGNEYKALTSPSTPLSLREKPQKVGVFLDYEEGQVSFYNVDDGSHIYTFTDC-FTEKLYPYFSP 159

                         170
                  ....*....|....*
gi 1721869592 521 GLHYGGNNSAPLIIS 535
Cdd:cd13733   160 CLNDGGKNSAPLIIC 174

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 1721869592 353 LKRVQQYEVDVTLDPDTAHPRLILSEDGKQVHDGGVRKRLPDNPKRFTQYIFVLTRQSFSSGRFYFEVQVKDKTDWWLGV 432
Cdd:cd15813     1 LRAAQAHAVNVTLDPETAHPNLIFSDDLKSVRLGNKWDRLPDNPERFDSCIIVLGSPSFTSGRHYWEVEVGDKTGWILGV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1721869592 433 ARESIDRTGGTEWTPETGYWTLLYTK----DGLVFrddPPVRLPLRAELRKVGVFVDYDEGLVSFYDVEARVHLCSATGC 508
Cdd:cd15813    81 CKASVSRKGSMTLSPENGYWVVMMTKrneyQASTS---PPTRLWLREPPRRVGIFLDYEAGDISFYNVTAKSHIYTFTSF 157

                         170       180
                  ....*....|....*....|....*.
gi 1721869592 509 TFSEPLYPVLYPGLHYGGNNSAPLII 534
Cdd:cd15813   158 SSSGPLQPIFSPGTHDGGKNMDPLTI 183

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 1721869592 361 VDVTLDPDTAHPRLILSEDGKQVHDGGVRKRLPDNPKRFTQYIFVLTRQSFSSGRFYFEVQVKDKTDWWLGVARESIDRT 440
Cdd:cd15819     2 VNVTLDPDTAHPALILSEDGRSVTWGETRQDLPENPERFDSLPCVLGQEGFTSGRHYWEVEVGDRTSWDLGVCRDNVMRK 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1721869592 441 GGTEWTPETGYWTLLYTKDGLVFRDDPPVRLPLRAELRKVGVFVDYDEGLVSFYDVEARVHLCSATGCTFSEPLYPVlyp 520
Cdd:cd15819    82 GRVTLSPENGFWAIRLYGNEYWALTSPETPLTLKEPPRRVGIFLDYEAGDVSFYNMTDGSHIYTFPQTAFSGPLRPF--- 158

                         170
                  ....*....|....
gi 1721869592 521 gLHYGGNNSAPLII 534
Cdd:cd15819   159 -FRLWSSDSGPLTI 171

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 1721869592 354 KRVQQYEVDVTLDPDTAHPRLILSEDGKQVHDGGVRKRLPDNPKRFTQYIFVLTRQSFSSGRFYFEVQVKDKTDWWLGVA 433
Cdd:cd15815     6 KMLRRHQVSVTLDPDTAHPELTLSKDQRQVTYGRCQENLDASPKRFTVLPCVLGCEGFTSGRHYFEVDVGEGTGWDVGVC 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1721869592 434 RESIDRTGGTEWTPETGYWTL-LYTKDGLVFRDDPPVRLPLRAELRKVGVFVDYDEGLVSFYDVEARVHLCSATGCTFSE 512
Cdd:cd15815    86 LENVQRGFGMKQEPEFGFWTIrLCEEDGYVALTSPPTPLPLREKPLVVGVFLDYEAGLVSFYNMTTGSHIFTFPKASFSD 165

                  ....
gi 1721869592 513 PLYP 516
Cdd:cd15815   166 TLRP 169

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 1721869592 359 YEVDVTLDPDTAHPRLILSEDGKQVHDGGVRKRLPDNPKRFTQYIFVLTRQSFSSGRFYFEVQVKDKTDWWLGVARESID 438
Cdd:cd15821     2 FQVDMTLDVDTANNYLIISEDLRSVRCGCFRQNRKELAERFDDALCVLGSPRFTSGRHYWEVDVGTSTEWDLGVCRESVN 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1721869592 439 RTGGTEWTPETGYWTL-LYTKDGLVFRDDPPVRLPLRAELRKVGVFVDYDEGLVSFYDVEARVHLCSATGCTFSEPLYPV 517
Cdd:cd15821    82 RQGPIELSPEHGFWTVsLRDGSVFFASTVPLTVLWVNPRLHRVGIFLDMEMGTISFYDVSDGSHIFTFTKISAEEPLRPF 161

                         170
                  ....*....|..
gi 1721869592 518 LYPGLHYGGNNS 529
Cdd:cd15821   162 FAPANPYGDDQG 173

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 1721869592 363 VTLDPDTAHPRLILSEDGKQVHDGGVRKRLPDNPKRFTQYIFVLTRQSFSSGRFYFEVQVKDKTDWWLGVARESIDRTGG 442
Cdd:cd12905     6 LTFDPETAHPSLILSRDLTAVTESDEMQPYPRSPKRFLQCVNVLASQGFQSGRHYWEVWVGSKTKWDLGVASESVDRQAR 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1721869592 443 TEWTPETGYWTL-LYTKDGLVFRDDPPVRLPLRAELRKVGVFVDYDEGLVSFYDVEARVHLCSatgctFSEP----LYPV 517
Cdd:cd12905    86 VKLCPENGYWTLrLRNGDEYWAGTQPWTRLRVTSRPQRIGVFLDCEERKVSFYNADDMSLLYS-----FHQGprgkVFPF 160

                         170
                  ....*....|....*..
gi 1721869592 518 LYPGLHYGGNNSAPLII 534
Cdd:cd12905   161 FSTCFSDDGQNAEPMRL 177

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 1721869592 361 VDVTLDPDTAHPRLILSEDGKQVHDGGVRKRLPDNPKRFTQYIFVLTRQSFSSGRFYFEVQVKDKTDWWLGVARESIDRT 440
Cdd:cd15814     2 VDVTLDPDTAYPSLILSDNLRQVRYSYLQQDLPDNPERFNLFPCVLGSPCFIAGRHYWEVEVGDKAKWTIGVCEDSVCRK 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1721869592 441 GGTEWTPETGYW--TLLYTKDGLVFrDDPPVRLPLRAELRKVGVFVDYDEGLVSFYDVEARVHLCSATGCTFSEPLYPvl 518
Cdd:cd15814    82 GGVTSAPQNGFWavSLWYGKEYWAL-TSPMTALPLRTPLQRVGIFLDYDAGEVSFYNVTERCHTFTFSHATFCGPVRP-- 158

                         170
                  ....*....|....*....
gi 1721869592 519 YPGLHY-GGNNSAPLIISP 536
Cdd:cd15814   159 YFSLSYsGGKSAAPLIICP 177

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 1721869592 362 DVTLDPDTAHPRLILSEDGKQVHDGGVRKRLPDNPKRFTQYIFVLTRQSFSSGRFYFEVQVKDKTDWWLGVARESIDRTG 441
Cdd:cd15816     1 DVKLDPATAHPSLLLTADLRSVQDGELWRDVPGNPERFDTWPCVLGLQSFSSGRHYWEVAVGEKAEWGLGVCQDSAPRKG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1721869592 442 GTEWTPETGYWTL-LYTKDGLVFRDDPPVRLPLRAELRKVGVFVDYDEGLVSFYDVEARVHLcsatgCTFSEPLYPVLYP 520
Cdd:cd15816    81 ETTPSPENGVWAVwLLKGNEYMVLASPSVPLLQLRRPRRVGVFLDYEAGEISFYNVTAGSHI-----YTFRQLFSGILRP 155

                         170
                  ....*....|....
gi 1721869592 521 glHYGGNNSAPLII 534
Cdd:cd15816   156 --YFFVCDTTPLTL 167

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 1721869592 362 DVTLDPDTAHPRLILSEDGKQVHDGGVRKRLPDNPKRFTQYIFVLTRQSFSSGRFYFEVQVKDKTDWWLGVARESIDRTG 441
Cdd:cd15817     1 DLILDPETAHPNLIVSEDRKAVRYRRMKPNCPYDPRRFTVYPAVLGSEGFDSGRHFWEVEVGGKGEWILGVCKDSLPRNA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1721869592 442 GTEWTPETGYWTLLYTKDGLVFRDDPPVRLPLRAELRKVGVFVDYDEGLVSFYDVEARVHLCSATGCtFSEPLYPVLYPG 521
Cdd:cd15817    81 QDPPSPLGGCWQIGRYMSGYVASGPKTTQLLPVVKPSRIGIFLDYELGEVSFYNMNDRSHLYTFTDT-FTGKLIPYFYVG 159

                         170
                  ....*....|....
gi 1721869592 522 LhyggnNSAPLIIS 535
Cdd:cd15817   160 P-----DSEPLTIC 168

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 1721869592 362 DVTLDPDTAHPRLILSEDGKQVHDGGVRKRLPDNPKRFTQYIFVLTRQSFSSGRFYFEVQVKDKTDWWLGVARESIDRTG 441
Cdd:cd15811     1 DVTLDPDTANPELVLSEDRRSVRRGDLRQALPDSPERFDPGPCVLGRERFTSGRHYWEVEVGDRTSWALGVCKENVNRKE 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1721869592 442 GTEWTPETGYWTLLYTkdGLVFRDDPPVRLPLRAELRKVGVFVDYDEGLVSFYDVEARVHLCSATGCTFSEPLYPVLYP 520
Cdd:cd15811    81 KGELSAGNGFWILVFL--GNYYSSERRTFAPLRDPPRRVGIFLDYEAGHLSFYSATDGSLLFIFPETPFSGTLRPLFSP 157

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1721869592 362 DVTLDPDTAHPRLILSEDGKQVHDGGVRKRLPDNPKRFTQYIFVLTRQSFSSGRFYFEVQVKDKTDWWLGVARESIDRTG 441
Cdd:cd12897    13 SLTFDPATAHPLLVVSSGGTVVECGLQKQRRASQPERFDKSTCVVASQGFSEGEHYWEVVVGDKPRWALGVIKGTASRKG 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1721869592 442 GTEWTPETGYWtLLYTKDGLVFR--DDPPVRLPLRAELR--KVGVFVDYDEGLVSFYDV--EARVHLCSATGCTFSEPLY 515
Cdd:cd12897    93 KLHASPSHGVW-LIGLKEGKVYEahGEPKEPRPLRVAGRphRIGVYLSFEDGVLSFFDAsdPDDLRTLYTFQERFQGKLY 171

                         170
                  ....*....|....*....
gi 1721869592 516 PVLYPGLHYGGNNSAPLII 534
Cdd:cd12897   172 PFFDVCWHDKGKNSQPLVL 190

PRY/SPRY domain in tripartite motif-containing (TRIM) proteins, including TRIM14-like, TRIM16-like, TRIM25-like, TRIM47-like, TRIM65 and RNF135, and stonustoxin; 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 TRIM14, TRIM16 and TRIM25, TRIM47 as well as RING finger protein RNF135 and stonustoxin, a secreted poisonous protein of the stonefish Synanceja horrida. TRIM16 (also known as estrogen-responsive B box protein or EBBP) has E3 ubiquitin ligase activity. It is a regulator of keratinocyte differentiation and a tumor suppressor in retinoid-sensitive neuroblastoma. TRIM25 (also called Efp) ubiquitinates the N terminus of the viral RNA receptor retinoic acid-inducible gene-I (RIG-I) in response to viral infection, leading to activation of the RIG-I signaling pathway, thus resulting in type I interferon production to limit viral replication. It has been shown that the influenza A virus targets TRIM25 and disables its antiviral function. TRIM47, also known as GOA (Gene overexpressed in astrocytoma protein) or RNF100 (RING finger protein 100), is highly expressed in kidney tubular cells, but low expressed in most tissue. It is overexpressed in astrocytoma tumor cells and plays an important role in the process of dedifferentiation that is associated with astrocytoma tumorigenesis. RNF135 ubiquitinates RIG-I (retinoic acid-inducible gene-I) to promote interferon-beta induction during the early phase of viral infection. Stonustoxin (STNX) is a hypotensive and lethal protein factor that also possesses other biological activities such as species-specific hemolysis (due to its ability to form pores in the cell membrane) and platelet aggregation, edema-induction, and endothelium-dependent vasorelaxation (mediated by the nitric oxide pathway and activation of potassium channels). 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 1721869592 363 VTLDPDTAHPRLILSEDGKQVHDGGVRKRLPDNPKRFTQYIfVLTRQSFSSGRFYFEVQVKDKTDWWLGVARESIDRTGG 442
Cdd:cd12891     1 LTLDPNTAHNNLALSGDLKTVTCSSENQHYPDSPERFTHSQ-VLSTQSFSSGRHYWEVEVSESGGWSVGVAYPSIERKGD 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1721869592 443 TEWtpeTGY----WTLLYTKDGL-VFRDDPPVRLPlRAELRKVGVFVDYDEGLVSFYDVEARVHLCSATGCTFSEPLYPV 517
Cdd:cd12891    80 ESR---IGRndksWCLEWQDKSFsAWHNNEETPLP-SVSSRRLGVYLDYEAGRLSFYELSDPIRHLHTFTATFTEPLHPA 155