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 755544214 282 YFDVKTILRRHQVSVILDPSTAHLDLALTKGGRLVTYKRCPRDLQArsSAKRFYGLPCVLGCEGFTSGRYYFEVSVENAT 361
Cdd:cd15815    1 YFDVKKMLRRHQVSVTLDPDTAHPELTLSKDQRQVTYGRCQENLDA--SPKRFTVLPCVLGCEGFTSGRHYFEVDVGEGT 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755544214 362 SWDLGVCVENVHRGFNMKKEPESGFWTIKMSEEDGLEALTSTPTpPLHLIEKPQILGVFLDYEAGAVSFYSVTTGSHIFT 441
Cdd:cd15815   79 GWDVGVCLENVQRGFGMKQEPEFGFWTIRLCEEDGYVALTSPPT-PLPLREKPLVVGVFLDYEAGLVSFYNMTTGSHIFT 157

                        170       180
                 ....*....|....*....|....*
gi 755544214 442 FPKASFQDTLRPFFQVYQYSPLFLP 466
Cdd:cd15815  158 FPKASFSDTLRPYFQVYQYSPLFLP 182

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
                 ....*....|....*....|....*....|....*
gi 755544214  93 MVCEEHEEKFNRFCEDDGQLLCWRCYWEDRHKGHT 127
Cdd:cd19761    1 DHCEHHGEKLLLFCQEDGKVICWLCERSQEHRGHH 35

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 755544214 282 YFDVKTILRRHQVSVILDPSTAHLDLALTKGGRLVTYKRCPRDLQArsSAKRFYGLPCVLGCEGFTSGRYYFEVSVENAT 361
Cdd:cd15815    1 YFDVKKMLRRHQVSVTLDPDTAHPELTLSKDQRQVTYGRCQENLDA--SPKRFTVLPCVLGCEGFTSGRHYFEVDVGEGT 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755544214 362 SWDLGVCVENVHRGFNMKKEPESGFWTIKMSEEDGLEALTSTPTpPLHLIEKPQILGVFLDYEAGAVSFYSVTTGSHIFT 441
Cdd:cd15815   79 GWDVGVCLENVQRGFGMKQEPEFGFWTIRLCEEDGYVALTSPPT-PLPLREKPLVVGVFLDYEAGLVSFYNMTTGSHIFT 157

                        170       180
                 ....*....|....*....|....*
gi 755544214 442 FPKASFQDTLRPFFQVYQYSPLFLP 466
Cdd:cd15815  158 FPKASFSDTLRPYFQVYQYSPLFLP 182

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 755544214   348 SGRYYFEVSVENATSWDLGVCVENVHRGFNMKKEPESGFWTIKMSEEDGLEALTSTPTPpLHLIEKPQILGVFLDYEAGA 427
Cdd:smart00449   1 SGRHYFEVEIGDGGHWRVGVATKSVPRGYFALLGEDKGSWGYDGDGGKKYHNSTGPEYG-LPLQEPGDVIGCFLDLEAGT 79

                           90       100       110
                   ....*....|....*....|....*....|...
gi 755544214   428 VSFYSVTTGSHIFTFPKASFQDTLRPFFQVYQY 460
Cdd:smart00449  80 ISFYKNGKYLHGLAFFDVKFSGPLYPAFSLGSG 112

B-box-type 2 zinc finger found in tripartite motif-containing proteins, TRIM5, TRIM6, TRIM22, TRIM34, TRIM38 and similar proteins; The family includes TRIM5, TRIM6, TRIM22, TRIM34, and TRIM38, all of which belong to the C-IV subclass of the 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, Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif. TRIM5, also termed RING finger protein 88 (RNF88), is a capsid-specific restriction factor that prevents infection from non-host-adapted retroviruses in a species-specific manner by binding to and destabilizing the retroviral capsid lattice before reverse transcription is completed. Its retroviral restriction activity correlates with the ability to activate TAK1-dependent innate immune signaling. TRIM5 also acts as a pattern recognition receptor that activates innate immune signaling in response to the retroviral capsid lattice. Moreover, TRIM5 plays a role in regulating autophagy through activation of autophagy regulator BECN1 by causing its dissociation from its inhibitors BCL2 and TAB2. It also plays a role in autophagy by acting as a selective autophagy receptor which recognizes and targets HIV-1 capsid protein p24 for autophagic destruction. TRIM6, also termed RING finger protein 89 (RNF89), is an E3-ubiquitin ligase that cooperates with the E2-ubiquitin conjugase UbE2K to catalyze the synthesis of unanchored K48-linked polyubiquitin chains, and further stimulates the interferon-I kappa B kinase epsilon (IKKepsilon) kinase-mediated antiviral response. It also regulates the transcriptional activity of Myc during the maintenance of embryonic stem (ES) cell pluripotency, and may act as a novel regulator for Myc-mediated transcription in ES cells. TRIM22, also termed 50 kDa-stimulated trans-acting factor (Staf-50), or RING finger protein 94 (RNF94), is an E3 ubiquitin-protein ligase that plays an integral role in the host innate immune response to viruses. It has been shown to inhibit the replication of a number of viruses, including HIV-1, hepatitis B, and influenza A. TRIM22 acts as a suppressor of basal HIV-1 long terminal repeat (LTR)-driven transcription by preventing transcription factor specificity protein 1 (Sp1) binding to the HIV-1 promoter. It also controls FoxO4 activity and cell survival by directing Toll-like receptor 3 (TLR3)-stimulated cells toward type I interferon (IFN) type I gene induction or apoptosis. Moreover, TRIM22 can activate the noncanonical nuclear factor-kappaB (NF-kappaB) pathway by activating I kappa B kinase alpha (IKKalpha). It also regulates nucleotide binding oligomerization domain containing 2 (NOD2)-dependent activation of interferon-beta signaling and nuclear factor-kappaB. TRIM34, also termed interferon-responsive finger protein 1, or RING finger protein 21 (RNF21), may function as an antiviral protein that contributes to the defense against retroviral infections. TRIM38, also known as RING finger protein 15 (RNF15) or zinc finger protein RoRet, is an E3 ubiquitin-protein ligase that promotes K63- and K48-linked ubiquitination of cellular proteins and also catalyzes self-ubiquitination. It negatively regulates tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta-triggered nuclear factor-kappaB (NF-kappaB) activation by mediating lysosomal-dependent degradation of transforming growth factor beta (TGFbeta)-activated kinase 1 (TAK1)-binding protein (TAB)2/3, two critical components of the TAK1 kinase complex. It also inhibits TLR3/4-mediated activation of NF-kappaB and interferon regulatory factor 3 (IRF3) by mediating ubiquitin-proteasomal degradation of TNF receptor-associated factor 6 (Traf6) and NAK-associated protein 1 (Nap1), respectively. Moreover, TRIM38 negatively regulates TLR3-mediated interferon beta (IFN-beta) signaling by targeting ubiquitin-proteasomal degradation of TIR domain-containing adaptor inducing IFN-beta (TRIF). It functions as a valid target for autoantibodies in primary Sjogren's Syndrome.

                         10        20        30
                 ....*....|....*....|....*....|....*
gi 755544214  93 MVCEEHEEKFNRFCEDDGQLLCWRCYWEDRHKGHT 127
Cdd:cd19761    1 DHCEHHGEKLLLFCQEDGKVICWLCERSQEHRGHH 35

zinc finger of C3HC4-type, RING; This is a family of primate-specific Ret finger protein-like (RFPL) zinc-fingers of the C3HC4 type. Ret finger protein-like proteins are primate-specific target genes of Pax6, a key transcription factor for pancreas, eye and neocortex development. This domain is likely to be DNA-binding. This zinc-finger domain together with the RDM domain, pfam11002, forms a large zinc-finger structure of the RING/U-Box superfamily. RING-containing proteins are known to exert an E3 ubiquitin protein ligase activity with the zinc-finger structure being mandatory for binding to the E2 ubiquitin-conjugating enzyme.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 755544214   16 CSICKAMMSHPVSINCGHSYCKSCIQSYYCnvspKTGWKMLGCPLC 61
Cdd:pfam15227   1 CPICLDYLEKPVSIECGHSFCLSCINSLQK----EPDGESLLCPQC 42

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 755544214    16 CSICK-AMMSHPVSINCGHSYCKSCIQSYYCNVSPKtgwkmlgCPLC 61
Cdd:smart00184   1 CPICLeEYLKDPVILPCGHTFCRSCIRKWLESGNNT-------CPIC 40

chromosome segregation protein SMC, common bacterial 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. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755544214   138 YKEKLQNTMTKLRELQENHEvQIHFITHQINAWKDAVEdrRQTIKSN-FKNLQSFLQEEEKFYLWRLENEEKEMLVQLEG 216
Cdd:TIGR02168  170 YKERRKETERKLERTRENLD-RLEDILNELERQLKSLE--RQAEKAErYKELKAELRELELALLVLRLEELREELEELQE 246

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 755544214   217 SEANLQQTFERAQCQIQELEAKC-------------QGSAQKLLQDVKNTLSRCEAMKR 262
Cdd:TIGR02168  247 ELKEAEEELEELTAELQELEEKLeelrlevseleeeIEELQKELYALANEISRLEQQKQ 305

B-Box C-terminal domain; Coiled coil region C-terminal to (some) B-Box domains

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755544214   139 KEKLQNTMTKLRELQENHEVQIHFITHQINAWKDAVEDRRQTIKSNFKNLQSFLQEEEKFYLWRLENEEKEMLVQLEGSE 218
Cdd:smart00502   2 REALEELLTKLRKKAAELEDALKQLISIIQEVEENAADVEAQIKAAFDELRNALNKRKKQLLEDLEEQKENKLKVLEQQL 81

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 755544214   219 ANLQQTFERAQCQIQELE-AKCQGSAQKLLQDVKNTLSRCEAMKR 262
Cdd:smart00502  82 ESLTQKQEKLSHAINFTEeALNSGDPTELLLSKKLIIERLQNLLK 126

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 755544214 282 YFDVKTILRRHQVSVILDPSTAHLDLALTKGGRLVTYKRCPRDLQArsSAKRFYGLPCVLGCEGFTSGRYYFEVSVENAT 361
Cdd:cd15815    1 YFDVKKMLRRHQVSVTLDPDTAHPELTLSKDQRQVTYGRCQENLDA--SPKRFTVLPCVLGCEGFTSGRHYFEVDVGEGT 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755544214 362 SWDLGVCVENVHRGFNMKKEPESGFWTIKMSEEDGLEALTSTPTpPLHLIEKPQILGVFLDYEAGAVSFYSVTTGSHIFT 441
Cdd:cd15815   79 GWDVGVCLENVQRGFGMKQEPEFGFWTIRLCEEDGYVALTSPPT-PLPLREKPLVVGVFLDYEAGLVSFYNMTTGSHIFT 157

                        170       180
                 ....*....|....*....|....*
gi 755544214 442 FPKASFQDTLRPFFQVYQYSPLFLP 466
Cdd:cd15815  158 FPKASFSDTLRPYFQVYQYSPLFLP 182

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 755544214 296 VILDPSTAHLDLALTKGGRLVTYKRCPRDLQArsSAKRFYGLPCVLGCEGFTSGRYYFEVSVENATSWDLGVCVENVHRG 375
Cdd:cd13733    2 VTLDPDTAHPNLILSEDLKSVRYGDKRQNLPD--NPERFDTCVCVLGSEGFSSGRHYWEVEVGGKTDWDLGVARESVNRK 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755544214 376 FNMKKEPESGFWTIKMSEEDGLEALTSTPTpPLHLIEKPQILGVFLDYEAGAVSFYSVTTGSHIFTFPkASFQDTLRPFF 455
Cdd:cd13733   80 GKITLSPENGYWTVGLRNGNEYKALTSPST-PLSLREKPQKVGVFLDYEEGQVSFYNVDDGSHIYTFT-DCFTEKLYPYF 157

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 755544214 291 RHQVSVILDPSTAHLDLALTKGGRLVtykRCPRDLQAR-SSAKRFYGLPCVLGCEGFTSGRYYFEVSVENATSWDLGVCV 369
Cdd:cd15821    1 KFQVDMTLDVDTANNYLIISEDLRSV---RCGCFRQNRkELAERFDDALCVLGSPRFTSGRHYWEVDVGTSTEWDLGVCR 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755544214 370 ENVHRGFNMKKEPESGFWTIKMSEEDGLEALTSTPTpPLHLIEKPQILGVFLDYEAGAVSFYSVTTGSHIFTFPKASFQD 449
Cdd:cd15821   78 ESVNRQGPIELSPEHGFWTVSLRDGSVFFASTVPLT-VLWVNPRLHRVGIFLDMEMGTISFYDVSDGSHIFTFTKISAEE 156

                 ....*.
gi 755544214 450 TLRPFF 455
Cdd:cd15821  157 PLRPFF 162

PRY/SPRY domain in tripartite motif-binding protein 20 (TRIM20), also known as pyrin; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM20, which is also known as pyrin or marenostrin. Unlike TRIM domains that are composed of RING/B-box/coiled-coil core, the N-terminal RING domain in TRIM20 is exchanged by a PYRIN domain (PYD), a prime mediator of protein interactions necessary for apoptosis, inflammation and innate immune signaling pathway, and it also harbors a C-terminal B30.2 domain. Mutations in pyrin (TRIM20) are associated with familial Mediterranean fever (FMF), a recessively hereditary periodic fever syndrome, characterized by episodes of inflammation and fever. These mutations cluster in the C-terminal B30.2 domain and therefore it is assumed that pyrin plays a role in the innate immune system by possibly effecting caspase-1-dependent IL-1beta maturation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755544214 290 RRHQVSVILDPSTAHLDLALTKGGRLV----TYKRCPRDLQarssakRFYGLPCVLGCEGFTSGRYYFEVSVENATSWDL 365
Cdd:cd15813    5 QAHAVNVTLDPETAHPNLIFSDDLKSVrlgnKWDRLPDNPE------RFDSCIIVLGSPSFTSGRHYWEVEVGDKTGWIL 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755544214 366 GVCVENVHRGFNMKKEPESGFWTIKMSEEDGLEALTSTPTpPLHLIEKPQILGVFLDYEAGAVSFYSVTTGSHIFTFPKA 445
Cdd:cd15813   79 GVCKASVSRKGSMTLSPENGYWVVMMTKRNEYQASTSPPT-RLWLREPPRRVGIFLDYEAGDISFYNVTAKSHIYTFTSF 157

                        170
                 ....*....|
gi 755544214 446 SFQDTLRPFF 455
Cdd:cd15813  158 SSSGPLQPIF 167

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 755544214 296 VILDPSTAHLDLALTKGGRLVTYKRCPRDLQarSSAKRFYGLPCVLGCEGFTSGRYYFEVSVENATSWDLGVCVENVHRG 375
Cdd:cd15816    2 VKLDPATAHPSLLLTADLRSVQDGELWRDVP--GNPERFDTWPCVLGLQSFSSGRHYWEVAVGEKAEWGLGVCQDSAPRK 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755544214 376 FNMKKEPESGFWTIKMSEEDGLEALTStPTPPLHLIEKPQILGVFLDYEAGAVSFYSVTTGSHIFTFPKaSFQDTLRPFF 455
Cdd:cd15816   80 GETTPSPENGVWAVWLLKGNEYMVLAS-PSVPLLQLRRPRRVGVFLDYEAGEISFYNVTAGSHIYTFRQ-LFSGILRPYF 157

                        170
                 ....*....|.
gi 755544214 456 QVYQYSPLFLP 466
Cdd:cd15816  158 FVCDTTPLTLP 168

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 755544214 296 VILDPSTAHLDLALTKGgrLVTYKRCPRDLQARSSAKRFYGLPCVLGCEGFTSGRYYFEVSVENATSWDLGVCVENVHRG 375
Cdd:cd12893    2 VTLDPNTAHPWLSLSED--LTSVRYSSEKQQLPDNPERFDPYPCVLGSEGFTSGKHSWDVEVGDNTSWMLGVAKESVQRK 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755544214 376 FNMKKEPESGFWTIKMSEEDGLEALTSTPTPPLHLIEKPQILGVFLDYEAGAVSFYSVTTGSHIFTFpKASFQDTLRPFF 455
Cdd:cd12893   80 GKFTLSPESGFWTIGFSEGKYSARTSPEPRTPLRVKQKPQRIRVQLDWDRGKVSFSDPDTNTHIHTF-THTFTERVFPYF 158

                 ...
gi 755544214 456 QVY 458
Cdd:cd12893  159 YTG 161

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 755544214 292 HQVSVILDPSTAHLDLALTKGGRLVTYKRCPRDLQarSSAKRFYGLPCVLGCEGFTSGRYYFEVSVENATSWDLGVCVEN 371
Cdd:cd12900    1 HMVHITLDPDTANPWLILSKDRRQVRLGDTHQNVP--ENEERFDNYPMVLGAQRFNSGKHYWEVDVTGKEAWDLGVCRDS 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755544214 372 VHRGFNMKKEPESGFWTIKMSeEDGLEALTStPTPPLHLIEKPQILGVFLDYEAGAVSFYSVTT-GSHIFTFPKASFQDT 450
Cdd:cd12900   79 VRRKGQFLLSPENGFWTIWLW-NKKYEAGTS-PQTTLHLQVPPCQVGIFLDYEAGVVSFYNITDhGSLIYTFSECAFTGP 156

                 ....*..
gi 755544214 451 LRPFFQV 457
Cdd:cd12900  157 LRPFFNP 163

PRY/SPRY domain of tripartite motif-binding protein 17 (TRIM17), also known as testis RING finger protein (terf); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM17, also known as RING finger protein 16 (RNF16) or testis RING finger protein (terf). TRIM17 domain is composed of RING/B-box/coiled-coil core and also known as RBCC protein, expressed almost exclusively in the testis. It exhibits E3 ligase activity, causing protein degradation of ZW10 interacting protein (ZWINT), a known component of the kinetochore complex required for the mitotic spindle checkpoint, and negatively regulates proliferation of breast cancer cells. TRIM17 undergoes ubiquitination in COS7 fibroblast-like cells but is inhibited and stabilized by TRIM44.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755544214 296 VILDPSTAHLDLALTKGgRLVTYKRCPRDlQARSSAKRFYGLPCVLGCEGFTSGRYYFEVSVeNATS---WDLGVCVENV 372
Cdd:cd15812    2 VVPDPSTAYPYLLLYES-RQRRYLSTPPD-GTPCSKDRFLAYPCAVGQETFSSGRHYWEVGM-NLTGdalWALGVCRDNV 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755544214 373 HRGFNMKKEPESGFWTIKMSEedGLEALTSTPT-PPLHLIEKPQILGVFLDYEAGAVSFYSVTTGSHIFTFPKASFQDTL 451
Cdd:cd15812   79 SRKDRVPKSPENGFWVVQLSK--GKKYLSAMSAlTPVTLTEPPSHMGIFLDFEAGEVSFYSVNDGSHLHTYSQAAFPGPL 156

                 ....
gi 755544214 452 RPFF 455
Cdd:cd15812  157 QPFF 160

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 755544214 296 VILDPSTAHLDLALTKGGRLVTYkrCPRDLQARSSAKRFYGLPCVLGCEGFTSGRYYFEVSVENATSWDLGVCVENVHR- 374
Cdd:cd12874    1 LTFDPDTAHLNLILSDDLRSVRV--GDISQHPPEPPPRFFECWQVLGSQSFSSGRHYWEVDVQDDSSWYVGVTYKSLPRk 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755544214 375 GFNMKKEPESGFWTIKMsEEDGLEALTSTPTPPLHlIEKPQILGVFLDYEAGAVSFYSVT-TGSHIFTFpKASFQDTLRP 453
Cdd:cd12874   79 GKMSNLGRNNGSWCLEW-RENEFSAWHNNPETRLP-VTPPRRLGVFLDCDGGSLSFYGVTdGVQLLYTF-KAKFTEPLYP 155

                        170
                 ....*....|...
gi 755544214 454 FFQVYQYSPLFLP 466
Cdd:cd12874  156 AFWLGEGSTLSIC 168

zinc-binding protein A33-like; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM69 and TRIM proteins NF7 and bloodthirsty (bty). TRIM69 is a novel testis E3 ubiquitin ligase that may function to ubiquitinate its particular substrates during spermatogenesis. In humans, TRIM69 localizes in the cytoplasm and nucleus, and requires an intact RING finger domain to function. TRIM protein NF7, which also contains a chromodomain (CHD) at the N-terminus and an RFP (Ret finger protein)-like domain at the C-terminus, is required for its association with transcriptional units of RNA polymerase II which is mediated by a trimeric B box. In Xenopus oocyte, xNF7 has been identified as a nuclear microtubule-associated protein (MAP) whose microtubule-bundling activity, but not E3-ligase activity, contributes to microtubule organization and spindle integrity. Bloodthirsty (bty) is a novel gene identified in zebrafish and has been shown to likely play a role in in regulation of the terminal steps of erythropoiesis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755544214 295 SVILDPSTAHLDLALTKGGRLVTYKRCPRDLQarSSAKRFygLPCV--LGCEGFTSGRYYFEVSVENATSWDLGVCVENV 372
Cdd:cd12905    5 PLTFDPETAHPSLILSRDLTAVTESDEMQPYP--RSPKRF--LQCVnvLASQGFQSGRHYWEVWVGSKTKWDLGVASESV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755544214 373 HRGFNMKKEPESGFWTIKMSEEDGLEALTsTPTPPLHLIEKPQILGVFLDYEAGAVSFYSVTTGSHIFTFPKASfQDTLR 452
Cdd:cd12905   81 DRQARVKLCPENGYWTLRLRNGDEYWAGT-QPWTRLRVTSRPQRIGVFLDCEERKVSFYNADDMSLLYSFHQGP-RGKVF 158

                 ...
gi 755544214 453 PFF 455
Cdd:cd12905  159 PFF 161

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 755544214 295 SVILDPSTAHLDLALTKGGRLVTYKRCPRDLQarSSAKRFYGLPCVLGCEGFTSGRYYFEVSVE--NATSWDLGVCVENV 372
Cdd:cd15826    1 SVTLDPQTASGSLVLSEDRKSVRYTRQKQNLP--DSPLRFDGLPAVLGSPGFSSGRHRWQVEVQlgDGGGCTVGVAGESV 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755544214 373 HRGFNMKKEPESGFWTIKMSEEdGLEALTStPTPPLHLIEKPQILGVFLDYEAGAVSFYSVTTGSHIFTFPkASFQDTLR 452
Cdd:cd15826   79 RRKGEMGLSAEDGVWAVILSHQ-QCWASTS-PGTDLPLSEIPRRVGVALDYEAGTVTLTNAETQEPIFTFT-ASFSGKVF 155

                 ....*.
gi 755544214 453 PFFQVY 458
Cdd:cd15826  156 PFFAVW 161

PRY/SPRY domain in tripartite motif-binding protein 50 (TRIM50); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM50. TRIM50, an E3 ubiquitin ligase, is deleted in Williams-Beuren (WBS) syndrome, a multi-system neurodevelopmental disorder caused by the deletion of contiguous genes at chromosome region 7q11.23. It is specifically expressed in gastric parietal cells and may play an essential role in tubulovesicular dynamics. It also interacts with and increases the level of p62, a multifunctional adaptor protein that is implicated in various cellular processes such as the autophagy clearance of polyubiquitinated protein aggregates.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755544214 298 LDPSTAHLDLALTKGGRLVT----YKRCPrdlqarSSAKRFYGLPCVLGCEGFTSGRYYFEVSVENATSWDLGVCVENVH 373
Cdd:cd13743   16 LDPLTAHPMLELSKGNTVVEcgllAQRLP------SNPERFDYSNCVLASRGFSSGKHYWEVVVGSKSKWRLGLIKGTTS 89

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755544214 374 RGFNMKKEPESGFWTIKMSEEDGLEALTsTPTPPLHLIEKPQILGVFLDYEAGAVSFYSVTTGSH---IFTFpKASFQDT 450
Cdd:cd13743   90 RKGKLNKSPENGVWLIGLKEGRVYEAFA-NPRVPLPLSTRPQRIGVFLDYEKGELTFYNADSPDElvpIYTF-QAEFQGK 167

                        170       180
                 ....*....|....*....|..
gi 755544214 451 LRPFFQVYQYS------PLFLP 466
Cdd:cd13743  168 LYPLLDVCWHErganklPIILP 189

PRY/SPRY domain of tripartite motif-binding protein 5, 6, 22 and 34 (TRIM5, TRIM6, TRIM22 and TRIM34); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of very close paralogs, TRIM5, TRIM6, TRIM22 and TRIM34. These domains are composed of RING/B-box/coiled-coil core and are also known as RBCC proteins. They form a locus of four closely related TRIM genes within an olfactory receptor-rich region on chromosome 11 of the human genome. Genetic analysis of this locus indicates that these four genes have evolved by gene duplication from a common ancestral gene. All genes in the TRIM6/TRIM34/TRIM5/TRIM22 locus are type I interferon inducible, with TRIM5 and TRIM22 possessing antiviral properties. TRIM5 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, amplifying 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. TRIM6 is selectively expressed in embryonic stem (ES) cells and interacts with the proto-oncogene product Myc, maintaining the pluripotency of the ES cells. TRIM6, together with E2 Ubiquitin conjugase (UbE2K) and K48-linked poly-Ub chains, is critical for the IkappaB kinase epsilon (IKKepsilon) branch of type I interferon (IFN-I) signaling pathway and subsequent establishment of a protective antiviral response. TRIM22 plays an integral role in the host innate immune response to viruses; it has been shown to inhibit the replication of a number of viruses, including HIV-1, hepatitis B, and influenza A. Altered TRIM22 expression has also been associated with multiple sclerosis, cancer, and autoimmune disease. While the PRY-SPRY domain of TRIM5a provides specificity and the capsid recognition motif to retroviral restriction, TRIM34 binds HIV-1 capsid but does not restrict HIV-1 infection.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755544214 296 VILDPSTAHLDLALTKGGRLVTY-KRCPRdlqaRSSAKRFYGLPCVLGCEGFTSGRYYFEVSVENATSWDLGVC---VEN 371
Cdd:cd15810    2 VTLNPVNISLNIVISEDQRQVRIvPPQTS----GQALTNNNYDFGVLGSQYFSSGKHYWEVDVSKKSAWILGVCshkRSD 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755544214 372 VHRGFNMKKE----------PESGFWTIKMSEEDGLEAL--TSTPTP---PLHLIEKPQILGVFLDYEAGAVSFYSVTT- 435
Cdd:cd15810   78 AMTKSNANQInhqnvysryqPQYGYWVIGLQNESEYNAFedSSSFNPhvlTLSVTVPPHRVGVFLDYEAGTVSFFNVTNh 157

                        170       180
                 ....*....|....*....|
gi 755544214 436 GSHIFTFPKASFQDTLRPFF 455
Cdd:cd15810  158 GSLIYKFSKCCFSTTVCPYF 177

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 755544214 295 SVILDPSTAHLDLALTKGGRLVtykRCPRDLQARSS-AKRFYGLPCVLGCEGFTSGRYYFEVSVENATSWDLGVCVENVH 373
Cdd:cd12897   13 SLTFDPATAHPLLVVSSGGTVV---ECGLQKQRRASqPERFDKSTCVVASQGFSEGEHYWEVVVGDKPRWALGVIKGTAS 89

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755544214 374 RGFNMKKEPESGFWTIKMSEEDGLEALTSTPTP-PLHLIEKPQILGVFLDYEAGAVSFYSVTTGSH---IFTFpKASFQD 449
Cdd:cd12897   90 RKGKLHASPSHGVWLIGLKEGKVYEAHGEPKEPrPLRVAGRPHRIGVYLSFEDGVLSFFDASDPDDlrtLYTF-QERFQG 168