Pyrin Death Domain found in ASC; Pyrin Death Domain found in ASC (Apoptosis-associated speck-like protein containing a CARD) and similar proteins. ASC is an adaptor molecule that functions in the assembly of the 'inflammasome', a multiprotein platform, which is responsible for caspase-1 activation and regulation of IL-1beta maturation. ASC contains two domains from the Death Domain (DD) superfamily, an N-terminal pyrin-like domain and a C-terminal Caspase activation and recruitment domain (CARD). Through these 2 domains, ASC serves as an adaptor for inflammasome integrity and oligomerizes to form supramolecular assemblies. Included in this family is human PYNOD (also known as NLRP10 or NOD8) which via its Pyrin domain suppresses oligomerization of ASC, and ASC-mediated NF-kappaB activation. Other members of this subfamily are associated with ATPase domains and their function remains unknown. In general, Pyrin is a subfamily of the DD superfamily and functions in several signaling pathways. DDs are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including CARD and Death Effector Domain (DED). They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1016685788   6 SDHLLYSLEELVPYDFEKFKFKLQNTSLEkEHPRIPRGQLQTARPVKVAALLLSHYGEKSAVRLTLQVLRAMNQHLLAEE 85
Cdd:cd08321     1 RDLLLDALEDLGEEELKKFKWKLRDIPLE-GYPRIPRGKLENADRVDLVDLLVSYYGEDYAVEVTVEVLRAINQNDLAEK 79

                  ...
gi 1016685788  86 LHR 88
Cdd:cd08321    80 LQK 82

Trichohyalin-plectin-homology domain; This family is a mixtrue of two different families of eukaryotic proteins. Trichoplein or mitostatin, was first defined as a meiosis-specific nuclear structural protein. It has since been linked with mitochondrial movement. It is associated with the mitochondrial outer membrane, and over-expression leads to reduction in mitochondrial motility whereas lack of it enhances mitochondrial movement. The activity appears to be mediated through binding the mitochondria to the actin intermediate filaments (IFs). The family is in the trichohyalin-plectin-homology domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1016685788 416 EEAALDYKEQIRKQLEHLKELRRFGEEQRSQGDKNTEKYLK--------QTEIQKQRVRYQLEQLCRFLEQQERlfvawL 487
Cdd:pfam13868 112 EEDQAEAEEKLEKQRQLREEIDEFNEEQAEWKELEKEEEREederileyLKEKAEREEEREAEREEIEEEKERE-----I 186

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1016685788 488 EKLGQtigQVRETYDTQVSRDVALLNKLIEELEAKQCQQEWELMQ 532
Cdd:pfam13868 187 ARLRA---QQEKAQDEKAERDELRAKLYQEEQERKERQKEREEAE 228

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 1016685788 655 RHYWEVEVG--DKTGWVLGICKASTSRKGNMALSPENGYWVVMMMKRNEYQASTFPPTRLRMREPPRRVGIFLDYEAGDI 732
Cdd:pfam00622   1 RHYFEVEIFgqDGGGWRVGWATKSVPRKGERFLGDESGSWGYDGWTGKKYWASTSPLTGLPLFEPGDVIGCFLDYEAGTI 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1016685788 733 SFYNVTaKSHIYTFTSFSSSGPLQPVFSPGTHDGGKNMDPLI 774
Cdd:pfam00622  81 SFTKNG-KSLGYAFRDVPFAGPLFPAVSLGAGEGLKFNFGLR 121

Pyrin Death Domain found in ASC; Pyrin Death Domain found in ASC (Apoptosis-associated speck-like protein containing a CARD) and similar proteins. ASC is an adaptor molecule that functions in the assembly of the 'inflammasome', a multiprotein platform, which is responsible for caspase-1 activation and regulation of IL-1beta maturation. ASC contains two domains from the Death Domain (DD) superfamily, an N-terminal pyrin-like domain and a C-terminal Caspase activation and recruitment domain (CARD). Through these 2 domains, ASC serves as an adaptor for inflammasome integrity and oligomerizes to form supramolecular assemblies. Included in this family is human PYNOD (also known as NLRP10 or NOD8) which via its Pyrin domain suppresses oligomerization of ASC, and ASC-mediated NF-kappaB activation. Other members of this subfamily are associated with ATPase domains and their function remains unknown. In general, Pyrin is a subfamily of the DD superfamily and functions in several signaling pathways. DDs are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including CARD and Death Effector Domain (DED). They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1016685788   6 SDHLLYSLEELVPYDFEKFKFKLQNTSLEkEHPRIPRGQLQTARPVKVAALLLSHYGEKSAVRLTLQVLRAMNQHLLAEE 85
Cdd:cd08321     1 RDLLLDALEDLGEEELKKFKWKLRDIPLE-GYPRIPRGKLENADRVDLVDLLVSYYGEDYAVEVTVEVLRAINQNDLAEK 79

                  ...
gi 1016685788  86 LHR 88
Cdd:cd08321    80 LQK 82

B-box-type 2 zinc finger found in tripartite motif-containing protein TRIM20 and similar proteins; TRIM20, also termed Pyrin, or Marenostrin (MEFV), is involved in the regulation of innate immunity and the inflammatory response in response to IFNG/IFN-gamma. TRIM20 belongs to unclassified TRIM family of proteins that do not have RING fingers and thus lack the characteristic tripartite (RING (R), B-box, and coiled coil (CC)) RBCC motif. It contains a pyrin domain, a Bbox2 zinc finger, and a C-terminal SPRY/B30.2 domain. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1016685788 376 PQCERHMKQVQLlFCEDHGEPICLICSLSQEHRGHRVRPI 415
Cdd:cd19771     1 PQCKLHLEQLKL-FCEDHREPICLICQLSQEHQGHRVRPI 39

B-box zinc finger;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1016685788 373 NPLPQCERHMKQVQLLFCEDHGEPICLICSLSqEHRGHRVRPI 415
Cdd:pfam00643   1 SKERLCPEHEEEPLTLYCNDCQELLCEECSVG-EHRGHTVVPL 42

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 1016685788 602 NVFLDAETAHPNLIVSDDLKSARLGNKWNRMPDSPERFDSCIFALGSPSFLSGRHYWEVEVGDKTGWVLGICKASTSRKG 681
Cdd:cd13733     1 DVTLDPDTAHPNLILSEDLKSVRYGDKRQNLPDNPERFDTCVCVLGSEGFSSGRHYWEVEVGGKTDWDLGVARESVNRKG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1016685788 682 NMALSPENGYWVVMMMKRNEYQASTFPPTRLRMREPPRRVGIFLDYEAGDISFYNVTAKSHIYTFTSfSSSGPLQPVFSP 761
Cdd:cd13733    81 KITLSPENGYWTVGLRNGNEYKALTSPSTPLSLREKPQKVGVFLDYEEGQVSFYNVDDGSHIYTFTD-CFTEKLYPYFSP 159

                         170
                  ....*....|....*
gi 1016685788 762 GTHDGGKNMDPLIIC 776
Cdd:cd13733   160 CLNDGGKNSAPLIIC 174

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1016685788 600 AVNVFLDAETAHPNLIVSDDLKSARLGNKWNRMPDSPERFDS--CIfaLGSPSFLSGRHYWEVEVGDKTGWVLGICKAST 677
Cdd:cd15819     1 AVNVTLDPDTAHPALILSEDGRSVTWGETRQDLPENPERFDSlpCV--LGQEGFTSGRHYWEVEVGDRTSWDLGVCRDNV 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1016685788 678 SRKGNMALSPENGYWVVMMMKrNEYQASTFPPTRLRMREPPRRVGIFLDYEAGDISFYNVTAKSHIYTFTSFSSSGPLQP 757
Cdd:cd15819    79 MRKGRVTLSPENGFWAIRLYG-NEYWALTSPETPLTLKEPPRRVGIFLDYEAGDVSFYNMTDGSHIYTFPQTAFSGPLRP 157

                         170
                  ....*....|....*....
gi 1016685788 758 VFSPGTHDGGknmdPLIIC 776
Cdd:cd15819   158 FFRLWSSDSG----PLTIC 172

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1016685788 584 EMETFNVPELidaqahaVNVFLDAETAHPNLIVSDDLKSARLGNKWNRMPDSPERFDSCIFALGSPSFLSGRHYWEVEVG 663
Cdd:cd15818     3 EMKSILNPGL-------SLITLDPKTAHPNLILSEDLTCVWHGDTKQMLPDNPERFDSSVAVLGSEGFTSGKHYWEVEVA 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1016685788 664 DKTGWVLGICKASTSRKGNMALSPENGYWVVMMMKRNEYQASTFPPTRLRMREPPRRVGIFLDYEAGDISFYNVTAKSHI 743
Cdd:cd15818    76 KKTKWTLGVVRESINRKGNCPLSPEDGFWLLRLRNQNELKALDVPSFSLTLTSNLNKVGIYLDYEGGQVSFYNANTMSHI 155

                         170       180       190
                  ....*....|....*....|....*....|...
gi 1016685788 744 YTF-TSFSSSgpLQPVFSPGTHDGGKNMDPLII 775
Cdd:cd15818   156 YTFsDTFTEK--IYPYFCPCLNDSGENKEPLKI 186

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 1016685788 601 VNVFLDAETAHPNLIVSDDLKSARLGNKWNRMPDSPERFDSCIFALGSPSFLSGRHYWEVEVGDKTGWVLGICKASTSRK 680
Cdd:cd15829    19 VDVTLDPETAHPNLLVSEDKKCVTFTKKKQRVPDSPKRFTVNPVVLGFPGFHSGRHFWEVEVGDKPEWAVGVCKDSLSTK 98

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1016685788 681 GNMALSPENGYWVVmMMKRNEYQASTFPPTRLRMREPPRRVGIFLDYEAGDISFYNVTAKSHIYTFTSfSSSGPLQPVFS 760
Cdd:cd15829    99 ARRPPSGQQGCWRI-QLQGGDYDAPGAVPPPLLLEVKPRGIGVFLDYELGEISFYNMPEKSHIHTFTD-TFSGPLRPYFY 176

                         170
                  ....*....|....*.
gi 1016685788 761 PGTHDGgknmdPLIIC 776
Cdd:cd15829   177 VGPDSK-----PLRIC 187

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 1016685788 600 AVNVFLDAETAHPNLIVSDDLKSARLGNKWNRMPDSPERFDSCIFALGSPSFLSGRHYWEVEVGDKTGWVLGICKASTSR 679
Cdd:cd15814     1 SVDVTLDPDTAYPSLILSDNLRQVRYSYLQQDLPDNPERFNLFPCVLGSPCFIAGRHYWEVEVGDKAKWTIGVCEDSVCR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1016685788 680 KGNMALSPENGYWVVMMMKRNEYQASTFPPTRLRMREPPRRVGIFLDYEAGDISFYNVTAKSHIYTFTSFSSSGPLQPVF 759
Cdd:cd15814    81 KGGVTSAPQNGFWAVSLWYGKEYWALTSPMTALPLRTPLQRVGIFLDYDAGEVSFYNVTERCHTFTFSHATFCGPVRPYF 160

                         170
                  ....*....|....*...
gi 1016685788 760 SPgTHDGGKNMDPLIICP 777
Cdd:cd15814   161 SL-SYSGGKSAAPLIICP 177

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 1016685788 605 LDAETAHPNLIVSDDLKSARLGNKWNRMPDSPERFDSCIFALGSPSFLSGRHYWEVEVGDKTGWVLGICKASTSRKGNMA 684
Cdd:cd12874     3 FDPDTAHLNLILSDDLRSVRVGDISQHPPEPPPRFFECWQVLGSQSFSSGRHYWEVDVQDDSSWYVGVTYKSLPRKGKMS 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1016685788 685 -LSPENGYWVVMMMKrNEYQAST-FPPTRLRMRePPRRVGIFLDYEAGDISFYNVT-AKSHIYTFTSfSSSGPLQPVFSP 761
Cdd:cd12874    83 nLGRNNGSWCLEWRE-NEFSAWHnNPETRLPVT-PPRRLGVFLDCDGGSLSFYGVTdGVQLLYTFKA-KFTEPLYPAFWL 159

                  ..
gi 1016685788 762 GT 763
Cdd:cd12874   160 GE 161

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 1016685788 602 NVFLDAETAHPNLIVSDDLKSARLGNKWNRMPDSPERFDSCIFALGSPSFLSGRHYWEVEVGDKTGWVLGICKASTSRKG 681
Cdd:cd12888     1 NVTLDPDTAHPRLVLSEDRKSVRWGDTRQDLPDNPERFDTWPCVLGCEGFTSGRHYWEVEVGDGGGWAVGVARESVRRKG 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1016685788 682 NMALSPENGYWVVMMMKrNEYQASTFPPTRLRMREPPRRVGIFLDYEAGDISFYNVTAKSHIYTFTSFSSSG 753
Cdd:cd12888    81 EISFSPEEGIWAVGQWG-GQYWALTSPETPLPLSEVPRRIRVYLDYEGGQVAFFDADNEAPIFTFPPASFAG 151

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 1016685788 599 HAVNVFLDAETAHPNLIVSDDLKSARLGNKWNRMPDSPERFDS--CIfaLGSPSFLSGRHYWEVEVGDKTGWVLGICKAS 676
Cdd:cd15815    11 HQVSVTLDPDTAHPELTLSKDQRQVTYGRCQENLDASPKRFTVlpCV--LGCEGFTSGRHYFEVDVGEGTGWDVGVCLEN 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1016685788 677 TSRKGNMALSPENGYWVVMMMKRNEYQASTFPPTRLRMREPPRRVGIFLDYEAGDISFYNVTAKSHIYTFTSFSSSGPLQ 756
Cdd:cd15815    89 VQRGFGMKQEPEFGFWTIRLCEEDGYVALTSPPTPLPLREKPLVVGVFLDYEAGLVSFYNMTTGSHIFTFPKASFSDTLR 168

                  ...
gi 1016685788 757 PVF 759
Cdd:cd15815   169 PYF 171

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 1016685788 602 NVFLDAETAHPNLIVSDDLKSARLGNKWNRMPDSPERFDSCIFALGSPSFLSGRHYWEVEVGDKTGWVLGICKASTSRKG 681
Cdd:cd15817     1 DLILDPETAHPNLIVSEDRKAVRYRRMKPNCPYDPRRFTVYPAVLGSEGFDSGRHFWEVEVGGKGEWILGVCKDSLPRNA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1016685788 682 NMALSPENGYWVVmMMKRNEYQASTFPPTRLRMREPPRRVGIFLDYEAGDISFYNVTAKSHIYTFTSfSSSGPLQPVFSP 761
Cdd:cd15817    81 QDPPSPLGGCWQI-GRYMSGYVASGPKTTQLLPVVKPSRIGIFLDYELGEVSFYNMNDRSHLYTFTD-TFTGKLIPYFYV 158

                         170
                  ....*....|....*
gi 1016685788 762 GThdggkNMDPLIIC 776
Cdd:cd15817   159 GP-----DSEPLTIC 168

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 1016685788 605 LDAETAHPNLIVSDDLKSARLGNKWNR-MPDSPERFDSCIFALGSPSFLSGRHYWEVEVGDKTGWVLGICKASTSRKGNM 683
Cdd:cd13744    16 LDPVTAHQRLILSDDCTIVAYGNLHPQpLQDSPKRFDVEVSVLGSEGFSGGVHYWEVVVSEKTQWMIGLAHEAVSRKGSI 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1016685788 684 ALSPENGYWVVMMMKRNEYQASTFPPTRLRMREPPRRVGIFLDYEAGDISFYNVTAKSHIYTFTSfSSSGPLQPVFSPG- 762
Cdd:cd13744    96 QIQPGRGFYCIVMHDGNQYSACTEPWTRLNVKSKLEKVGVYLDYDKGLLIFYNADDMSWLYTFRE-KFPGKLCSYFSPGq 174

                         170
                  ....*....|...
gi 1016685788 763 THDGGKNMDPLII 775
Cdd:cd13744   175 SHANGKNVQPLRI 187

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 1016685788 603 VFLDAETAHPNLIVSDDLKSARLGNKWNRMPDSPERFDSCIFALGSPSFLSGRHYWEVEV--GDKTGWVLGICKASTSRK 680
Cdd:cd15826     2 VTLDPQTASGSLVLSEDRKSVRYTRQKQNLPDSPLRFDGLPAVLGSPGFSSGRHRWQVEVqlGDGGGCTVGVAGESVRRK 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1016685788 681 GNMALSPENGYWVVmMMKRNEYQASTFPPTRLRMREPPRRVGIFLDYEAGDISFYNVTAKSHIYTFTSfSSSGPLQPVFS 760
Cdd:cd15826    82 GEMGLSAEDGVWAV-ILSHQQCWASTSPGTDLPLSEIPRRVGVALDYEAGTVTLTNAETQEPIFTFTA-SFSGKVFPFFA 159

                  ....*.
gi 1016685788 761 ---PGT 763
Cdd:cd15826   160 vwkKGS 165

PRY/SPRY domain in tripartite motif-binding protein 5 (TRIM5), also known as RING finger protein 88 (RNF88); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM5 which is also known as RING finger protein 88 (RNF88) or TRIM5alpha (TRIM5a), an antiretroviral restriction factor and a retrovirus capsid sensor in immune signaling. TRIM5 domain is composed of RING/B-box/coiled-coil core and also known as RBCC protein. It blocks retrovirus infection soon after the virion core enters the cell cytoplasm by recognizing the capsid protein lattice that encases the viral genomic RNA; the SPRY domain provides the capsid recognition motif that dictates specificity to retroviral restriction. TRIM5a, an E3 ubiquitin ligase, promotes innate immune signaling by activating the TAK1 kinase complex by cooperating with the heterodimeric E2, UBC13/UEV1A. It also stimulates NFkB and AP-1 signaling, and the transcription of inflammatory cytokines and chemokines, and amplifies these activities upon retroviral infection. Interaction of its PRY-SPRY or cyclophilin domains with the retroviral capsid lattice stimulates the formation of a complementary lattice by TRIM5, with greatly increased TRIM5 E3 activity, and host cell signal transduction.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1016685788 591 PELIDAQAHAVNVFLDAETAhPNLIVSDDLKSARLGNKWNRMPDSPERFDSCIfaLGSPSFLSGRHYWEVEVGDKTGWVL 670
Cdd:cd15822     2 NELTDVQRYWVHVTLDPSNN-KNIVISEDRRQVRYVRKQQRYNSNGNNEDYGV--LGSPSITSGKHYWEVDVSKKRAWIL 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1016685788 671 GIC-----KASTSRKGNMALS---------PENGYWVVMMMKRNEYQA---STFPPTR---LRMREPPRRVGIFLDYEAG 730
Cdd:cd15822    79 GVCggkypNSTLKDFNKQGKNnqkqcsnyqPKYGYWVIGLQNKSEYNAfedSSSSDPLiltLSLTVPPCRVGVFLDYEAG 158

                         170       180       190
                  ....*....|....*....|....*....|....
gi 1016685788 731 DISFYNVTakSH---IYTFTSFSSSGPLQPVFSP 761
Cdd:cd15822   159 TVSFFNVT--NHgflIYKFSSCSFSQEVFPYFNP 190

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 1016685788 602 NVFLDAETAHPNLIVSDDLKSARLGNKWNRMPDSPERFDSCIFALGSPSFLSGRHYWEVEVGDKTGWVLGICKASTSRKG 681
Cdd:cd12897    13 SLTFDPATAHPLLVVSSGGTVVECGLQKQRRASQPERFDKSTCVVASQGFSEGEHYWEVVVGDKPRWALGVIKGTASRKG 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1016685788 682 NMALSPENGYWVVMMMKRNEYQASTFP--PTRLRMREPPRRVGIFLDYEAGDISFYNVTAKSHIYTFTSFSS--SGPLQP 757
Cdd:cd12897    93 KLHASPSHGVWLIGLKEGKVYEAHGEPkePRPLRVAGRPHRIGVYLSFEDGVLSFFDASDPDDLRTLYTFQErfQGKLYP 172

                         170
                  ....*....|....*...
gi 1016685788 758 VFSPGTHDGGKNMDPLII 775
Cdd:cd12897   173 FFDVCWHDKGKNSQPLVL 190

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 1016685788 602 NVFLDAETAHPNLIVSDDLKSAR-LGNKWNRMPDSPERFDSCIFALGSPSFLSGRHYWEVEVGDKTGWVLGICKASTSRK 680
Cdd:cd13742    13 NLTFDPDTAHPYLVVSSDGKRVEcADQKQAVSSDDPNRFDKANCVVSHQSFSEGEHYWEVIVGDKPRWALGVISAEAGRK 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1016685788 681 GNMALSPENGYWVVMMMKRNEYQAST--FPPTRLRMREPPRRVGIFLDYEAGDISFYNVTAKSHIYTFTSFSS--SGPLQ 756
Cdd:cd13742    93 GRLHALPSNGFWLLGCKEGKVYEAHVehKEPRALRVEGRPTRIGVYLSFSDGVLSFYDASDEDNLVQLFAFHErfPGPLY 172

                         170       180
                  ....*....|....*....|
gi 1016685788 757 PVFSPGTHDGGKNMDPLIIC 776
Cdd:cd13742   173 PFFDVCWHDKGKNSQPLKIF 192