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 1034672040  22 WRCPEHGDRVAELFCRRCRRCVCALCPVLGAHRGHPVGLALEAA 65
Cdd:cd19768     1 RCCPEHKDRPLELFCKTCKRCVCALCPILGQHRGHDVRLIDEEA 44

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 1034672040  320 GRHYWEVDVQEAGaGWWVGAAYASlrrRGASAAARLGCNRQSWCLKRYD-LEYWAFHdGQRSRLRPRDDLDRLGVFLDYE 398
Cdd:smart00449   2 GRHYFEVEIGDGG-HWRVGVATKS---VPRGYFALLGEDKGSWGYDGDGgKKYHNST-GPEYGLPLQEPGDVIGCFLDLE 76

                           90       100       110
                   ....*....|....*....|....*....|....
gi 1034672040  399 AGVLAFYDVTGGMSHLHTFRATFQEPLYPALRLW 432
Cdd:smart00449  77 AGTISFYKNGKYLHGLAFFDVKFSGPLYPAFSLG 110

B-box-type 2 zinc finger found in tripartite motif-containing protein 14 (TRIM14) and similar proteins; TRIM14 is a mitochondrial adaptor that facilitates innate immune signaling. It also plays a critical role in tumor development. TRIM14 belongs to an unclassified TRIM (tripartite motif) 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 Bbox2 zinc finger as well as 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 1034672040  22 WRCPEHGDRVAELFCRRCRRCVCALCPVLGAHRGHPVGLALEAA 65
Cdd:cd19768     1 RCCPEHKDRPLELFCKTCKRCVCALCPILGQHRGHDVRLIDEEA 44

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 1034672040 269 PTLDPDTMHARLRLSADRLTVRCGLLGSLGPVPVLRFDALWQVLARDCFATGRHYWEVDVQEAgAGWWVGAAYASLrrRG 348
Cdd:cd12874     1 LTFDPDTAHLNLILSDDLRSVRVGDISQHPPEPPPRFFECWQVLGSQSFSSGRHYWEVDVQDD-SSWYVGVTYKSL--PR 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034672040 349 ASAAARLGCNRQSWCLKRYDLEYWAFHDGQRSRLRPRdDLDRLGVFLDYEAGVLAFYDVTGGMSHLHTFRATFQEPLYPA 428
Cdd:cd12874    78 KGKMSNLGRNNGSWCLEWRENEFSAWHNNPETRLPVT-PPRRLGVFLDCDGGSLSFYGVTDGVQLLYTFKAKFTEPLYPA 156

                         170
                  ....*....|..
gi 1034672040 429 LRLWEGA-ISIP 439
Cdd:cd12874   157 FWLGEGStLSIC 168

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034672040 259 RSLLLKYARTPTLDPDTMHARLRLSADRLTVRCGllGSLGPVPVL--RFDALWQVLARDCFaTGRHYWEVDVqeAGAGWW 336
Cdd:cd16040     1 REEFLKYACQLTLDPNTAHRNLSLSEGNRKVTRV--KEEQPYPDHpeRFDYWPQVLCREGL-SGRCYWEVEW--SGGGVD 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034672040 337 VGAAYASLRRRGASAAARLGCNRQSWCLKRYDLEYWAFHDGQRSRLR-PRDDLDRLGVFLDYEAGVLAFYDVTGGMSHLH 415
Cdd:cd16040    76 IAVAYKGISRKGDGDDSRFGYNDKSWSLECSPSGYSFWHNNKKTEISvPSSSSSRVGVYLDHSAGTLSFYSVSDTMTLLH 155

                         170
                  ....*....|....*....
gi 1034672040 416 TFRATFQEPLYPALRLWEG 434
Cdd:cd16040   156 TVQTTFTEPLYPGFGVGYG 174

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 1034672040 270 TLDPDTMHARLRLSADRLTVRCGLLG-SLGPVPVlRFDALWQVLARDCFATGRHYWEVDVQEaGAGWWVGAAYASLrrrg 348
Cdd:cd13733     3 TLDPDTAHPNLILSEDLKSVRYGDKRqNLPDNPE-RFDTCVCVLGSEGFSSGRHYWEVEVGG-KTDWDLGVARESV---- 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034672040 349 asaaarlgcNRQS----------WCLKRYDL-EYWAFHDgQRSRLRPRDDLDRLGVFLDYEAGVLAFYDVTgGMSHLHTF 417
Cdd:cd13733    77 ---------NRKGkitlspengyWTVGLRNGnEYKALTS-PSTPLSLREKPQKVGVFLDYEEGQVSFYNVD-DGSHIYTF 145

                         170
                  ....*....|....*
gi 1034672040 418 RATFQEPLYPALRLW 432
Cdd:cd13733   146 TDCFTEKLYPYFSPC 160

PRY/SPRY domain in tripartite motif-containing protein 16 (TRIM16); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM16 and TRIM-like proteins. TRIM16 (also known as estrogen-responsive B box protein or EBBP) does not possess a RING domain like the other TRIM proteins, but contains two B-box domains and can heterodimerize with other TRIM proteins such as TRIM24, Promyelocytic leukemia (PML) protein and Midline-1 (MID1 or TRIM18). It is a regulator of keratinocyte differentiation and a tumor suppressor in retinoid-sensitive neuroblastoma. It has been shown that loss of TRIM16 expression plays an important role in the development of cutaneous squamous cell carcinoma (SCC) and is a determinant of retinoid sensitivity. TRIM16 also has E3 ubiquitin ligase activity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034672040 259 RSLLLKYARTPTLDPDTMHARLRLSADRLTVrCGLLGSLGPVPVL--RFDALWQVLARDCFATGRHYWEVDVQeaGAGWW 336
Cdd:cd12890     1 RDDFLKYAYPLTFDPDTAHRYLRLTEDNRKV-TNTTPWEHPYPDHpeRFEHWRQVLSQQSLYLGRYYFEVEIS--GEGTY 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034672040 337 VGAAYASLRRRGASAAARLGCNRQSWCLKRYDLEYWAFHDGQRSRLrPRDDLDRLGVFLDYEAGVLAFYDVTG-GMSHLH 415
Cdd:cd12890    78 VGLTYKSIDRKGSESNSCISGNNFSWCLQWNGKEFSAWHSDVETPL-KKGPFTRLGIYLDYPGGTLSFYGVEDdGMTLLH 156

                         170
                  ....*....|....*.
gi 1034672040 416 TFRATFQEPLYPALRL 431
Cdd:cd12890   157 KFQCKFTEPLYPAFWL 172

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 1034672040 270 TLDPDTMHARLRLSADRLTVRCGL-LGSLGPVPvLRFDALWQVLARDCFATGRHYWEVDVQEAGaGWWVGAAYASLRRRg 348
Cdd:cd12888     3 TLDPDTAHPRLVLSEDRKSVRWGDtRQDLPDNP-ERFDTWPCVLGCEGFTSGRHYWEVEVGDGG-GWAVGVARESVRRK- 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034672040 349 asaaarlGCNRQS-----WCLKRYDLEYWAFHD-GQRSRLR--PRddldRLGVFLDYEAGVLAFYDVtGGMSHLHTFRAT 420
Cdd:cd12888    80 -------GEISFSpeegiWAVGQWGGQYWALTSpETPLPLSevPR----RIRVYLDYEGGQVAFFDA-DNEAPIFTFPPA 147

                         170
                  ....*....|....*..
gi 1034672040 421 F--QEPLYPALRLWEGA 435
Cdd:cd12888   148 SfaGERIFPWFWVGKGS 164

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034672040 270 TLDPDTMHARLRLSADRLTVRCGLLGSLGPVPVLRFDALWQVLARDCFATGRHYWEVDVQEAgAGWWVGAAYASLRRRga 349
Cdd:cd13745     6 TLDPDTAHPNLVLSEDRKSVRHGDTRQDLPDNPERFDTYPCVLGAEGFTGGRHYWEVEVGDK-TEWTLGVCRESVSRK-- 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034672040 350 saaarlGCNRQS-----WCLKRYDLEYWA-------FHdgqrSRLRPRddldRLGVFLDYEAGVLAFYDVTGGmSHLHTF 417
Cdd:cd13745    83 ------GEVTLSpengyWTVWLRDGKYEAltspptpLP----VSVRPS----RVGIFLDYEAGEVSFYNVTDR-SHLFTF 147

                         170
                  ....*....|
gi 1034672040 418 RATFQEPLYP 427
Cdd:cd13745   148 TDTFSGTLRP 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 1034672040 270 TLDPDTMHARLRLSADRLTVRCGLLGSLGPVPVLRFDALWQVLARDCFATGRHYWEVDVqEAGAGWWVGAAYASLrrrga 349
Cdd:cd15821     7 TLDVDTANNYLIISEDLRSVRCGCFRQNRKELAERFDDALCVLGSPRFTSGRHYWEVDV-GTSTEWDLGVCRESV----- 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034672040 350 saaarlgcNRQS----------WCLK-RYDLEYWAFHDGQRS-RLRPRddLDRLGVFLDYEAGVLAFYDVTGGmSHLHTF 417
Cdd:cd15821    81 --------NRQGpielspehgfWTVSlRDGSVFFASTVPLTVlWVNPR--LHRVGIFLDMEMGTISFYDVSDG-SHIFTF 149

                         170
                  ....*....|.
gi 1034672040 418 RATF-QEPLYP 427
Cdd:cd15821   150 TKISaEEPLRP 160

PRY/SPRY domain of TRIM18/MID1, also known as FXY or RNF59; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is at the C-terminus of the overall domain architecture of MID1 (also known as FXY, RNF59, TRIM18) gene represented by a RING finger domain (RING), two B-box motifs (BBOX), coiled-coil C-terminal to Bbox domain (BBC) and fibronectin type 3 domain (FN3). Mutations in the human MID1 gene result in X-linked Opitz G/BBB syndrome (OS), a disorder affecting development of midline structures, causing craniofacial, urogenital, gastrointestinal and cardiovascular abnormalities. A unique MID1 gene mutation located in a variable loop in the SPRY domain alters conformation of the binding pocket and may affect the binding affinity to the PRY/SPRY domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034672040 271 LDPDTMHARLRLSADRLTVRCGLLGSLGPVPVLRFDAL--WQVLARDCFATGRHYWEVDVqeAGAGWW-VGAAYASlrrr 347
Cdd:cd12892     4 LDPKSAHRKLKVSHDNLTVERDETSSKKSHTPERFTSQgsYGVAGNVFIDSGRHYWEVVI--SGSTWYaIGIAYKS---- 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034672040 348 gASAAARLGCNRQSWCLKRYDLEYWAFHDGQRSRLRPRDDLDRLGVFLDYEAGVLAFYDVTGGMsHLHTFRATFQEPLYP 427
Cdd:cd12892    78 -APKHEWIGKNSASWVLCRCNNNWVVRHNSKEIPIEPSPHLRRVGILLDYDNGSLSFYDALNSI-HLYTFDIAFAQPVCP 155

                         170
                  ....*....|.
gi 1034672040 428 ALRLWEGAISI 438
Cdd:cd12892   156 TFTVWNKCLTI 166

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034672040 269 PTLDPDTMHARLRLSADRLTVRCGLLGSLGPVPVLRFDALWQVLARDCFATGRHYWEVDVQeAGAGWWVGAAYASLRRRG 348
Cdd:cd13740     2 LTLDPDSANPRLILSLDLKSVRLGERAQDLPNHPCRFDTNTRVLASCGFSSGRHHWEVEVG-SKDGWAFGVARESVRRKG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034672040 349 ASAAARlgcNRQSWCLKRYDLEYWAFHDGQRSRLrPRDDLDRLGVFLDYEAGVLAFYDVTgGMSHLHTFRATFQEPLYPA 428
Cdd:cd13740    81 LTPFTP---EEGVWALQLNGGQYWAVTSPERTPL-SCGHLSRVRVALDLEVGAVSFYAAE-DMRHIYTFRVNFQERVFPL 155

                         170
                  ....*....|...
gi 1034672040 429 ---------LRLW 432
Cdd:cd13740   156 fsvcstgtyLRIW 168

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 1034672040 259 RSLLLKYARTPTLDPDTMHARLRLSADRLTVRCGLLGSLGPVPVLRFDALWQVLARDCFATGRHYWEVDVQEaGAGWWVG 338
Cdd:cd15815     5 KKMLRRHQVSVTLDPDTAHPELTLSKDQRQVTYGRCQENLDASPKRFTVLPCVLGCEGFTSGRHYFEVDVGE-GTGWDVG 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034672040 339 AAYASLRrrgasaaarlgcnRQSWCLKRYDLEYWAFhdgqrsRLRPRDDLDRL----------------GVFLDYEAGVL 402
Cdd:cd15815    84 VCLENVQ-------------RGFGMKQEPEFGFWTI------RLCEEDGYVALtspptplplrekplvvGVFLDYEAGLV 144

                         170       180       190
                  ....*....|....*....|....*....|..
gi 1034672040 403 AFYDVTGGmSHLHTF-RATFQEPLYPALRLWE 433
Cdd:cd15815   145 SFYNMTTG-SHIFTFpKASFSDTLRPYFQVYQ 175

PRY/SPRY domain in RING finger protein RNF135; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of the RING finger protein RNF135 (also known as Riplet/RNF135), which ubiquitinates RIG-I (retinoic acid-inducible gene-I) to promote interferon-beta induction during the early phase of viral infection. Normally, RIG-I is activated by TRIM25 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. However, RNF135, consisting of an N-terminal RING finger domain, C-terminal SPRY and PRY motifs and showing sequence similarity to TRIM25, acts as an alternative factor that promotes RIG-I activation independent of TRIM25.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034672040 269 PTLDPDTMHARLRLSADRLTVRCGLLGSLGPVPVLRFDALwQVLARDCFATGRHYWEVDVQeAGAGWWVGAAYASLRRRG 348
Cdd:cd12902     1 PTFDLRSLSCSLEVSEDSRKVTVSHGPQAYAWSPDRFSIS-QVLCSQAFSSGQHYWEVDTR-QCSHWAVGVASWEMSRDQ 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034672040 349 AsaaarLGCNRQSWCLK---RYDLEYWafHDGQRSRL---RPRddldRLGVFLDYEAGVLAFYDVTGGMSHLHTFRATFQ 422
Cdd:cd12902    79 M-----LGRTMDSWCIEwkgTGQLSAW--HMNKETVLgsdKPR----VVGIWLDLEEGKLAFYSVANQERLLHECEVSAS 147

                         170       180
                  ....*....|....*....|.
gi 1034672040 423 EPLYPALRL----WEGAISIP 439
Cdd:cd12902   148 SPLHPAFWLyglePGNSLIIK 168

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 1034672040 270 TLDPDTMHARLRLSADRLTVRCGLLGSLGPVPVLRFDALWQVLARDCFATGRHYWEVDVqEAGAGWWVGAAYASLRRRGA 349
Cdd:cd15813    12 TLDPETAHPNLIFSDDLKSVRLGNKWDRLPDNPERFDSCIIVLGSPSFTSGRHYWEVEV-GDKTGWILGVCKASVSRKGS 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034672040 350 SAaarLGCNRQSWCL---KRYdlEYWAfHDGQRSRLRPRDDLDRLGVFLDYEAGVLAFYDVTgGMSHLHTFRATF-QEPL 425
Cdd:cd15813    91 MT---LSPENGYWVVmmtKRN--EYQA-STSPPTRLWLREPPRRVGIFLDYEAGDISFYNVT-AKSHIYTFTSFSsSGPL 163

                  ..
gi 1034672040 426 YP 427
Cdd:cd15813   164 QP 165

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 1034672040 270 TLDPDTMHARLRLSADRLTVR-CGLLGSLGPVPVlRFDALWQVLARDCFATGRHYWEVDVQEAgAGWWVGAAYASLrrrg 348
Cdd:cd12905     7 TFDPETAHPSLILSRDLTAVTeSDEMQPYPRSPK-RFLQCVNVLASQGFQSGRHYWEVWVGSK-TKWDLGVASESV---- 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034672040 349 asaaarlgcNRQS----------WCLK-RYDLEYWAfHDGQRSRLRPRDDLDRLGVFLDYEAGVLAFYDVTgGMSHLHTF 417
Cdd:cd12905    81 ---------DRQArvklcpengyWTLRlRNGDEYWA-GTQPWTRLRVTSRPQRIGVFLDCEERKVSFYNAD-DMSLLYSF 149

                         170
                  ....*....|
gi 1034672040 418 RATFQEPLYP 427
Cdd:cd12905   150 HQGPRGKVFP 159

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 1034672040 270 TLDPDTMHARLRLSADRLTVRCGLLGSLGPVPVLRFDALWQVLARDCFATGRHYWEVDVQEAgAGWWVGAAYASLrrrGA 349
Cdd:cd15811     3 TLDPDTANPELVLSEDRRSVRRGDLRQALPDSPERFDPGPCVLGRERFTSGRHYWEVEVGDR-TSWALGVCKENV---NR 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034672040 350 SAAARLGCNRQSWCLkrydLEYWAFHDGQRSRLRP-RDDLDRLGVFLDYEAGVLAFYDVTGGmSHLHTFRAT-FQEPLYP 427
Cdd:cd15811    79 KEKGELSAGNGFWIL----VFLGNYYSSERRTFAPlRDPPRRVGIFLDYEAGHLSFYSATDG-SLLFIFPETpFSGTLRP 153

PRY/SPRY domain in tripartite motif-containing domain 25 (TRIM25)-like; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of proteins similar to TRIM25 (composed of RING/B-box/coiled-coil core and also known as RBCC proteins). 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034672040 271 LDPDTMHARLRLSADRLTV-RCGLLGSLGPVPVLRFDALWQVLARDCFATGRHYWEVDVQEAgagwWV--GAAYA-SLRR 346
Cdd:cd13737     3 FDPNTASEELFLFKETHSVlNMGILLESFFGPCQGFNHWPQVLCTRSLCEGCHYWEAEVSNS----WVclGVTYSySHPT 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034672040 347 RGASAAARLGCNRQSWCLKRYDLEYWAFHDGQRSRLRPrDDLDRLGVFLDYEAGVLAFYDVTGGMSHLHTFRATFQEPLY 426
Cdd:cd13737    79 GKSCIFYLIGRNPYSWCLEWDSLKFSVWHNNIQTVVHG-SYYKTIGVLLDYAAGSLTFYGVANTMNLIYRFLTTFTEPLY 157

                         170
                  ....*....|....
gi 1034672040 427 PALRLWEGAISIPR 440
Cdd:cd13737   158 PAVMVSSGASVTLK 171

PRY/SPRY domain of tripartite motif-binding protein 1 (TRIM1) or MID2; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM1 (also known as MID2 or midline 2). MID2 and its close homolog, TRIM18 (also known as MID1), both contain a B30.2-like domain at their C-terminus and a single fibronectin type III (FN3) motif between it and their N-terminal RBCC domain. MID2 and MID1 coiled-coil motifs mediate both homo- and heterodimerization, a prerequisite for association of the rapamycin-sensitive PP2A regulatory subunit Alpha 4 with microtubules. Mutations in MID1 have shown to cause Opitz syndrome, a disorder causing congenital anomalies such as cleft lip and palate as well as heart defects.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034672040 271 LDPDTMHARLRLSADRLTVR---CGLLGSLGPVpvlRFDAL--WQVLARDCFATGRHYWEVDVqeaGAGWW--VGAAYAS 343
Cdd:cd13739     3 LDPKMAHKKLKISNDGLQMEkdeSSLKKSHTPE---RFSGTgcYGAAGNIFIDSGCHYWEVVV---GSSTWyaIGIAYKS 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034672040 344 lrrrgASAAARLGCNRQSWCLKRYDLEYWAFHDGQRSRLRPRDDLDRLGVFLDYEAGVLAFYDVTGGMsHLHTFRATFQE 423
Cdd:cd13739    77 -----APKNEWIGKNSSSWVFSRCNNNFVVRHNNKEMLVDVPPQLKRLGVLLDYDNNMLSFYDPANSL-HLHTFEVSFIL 150

                         170
                  ....*....|....*
gi 1034672040 424 PLYPALRLWEGAISI 438
Cdd:cd13739   151 PVCPTFTIWNKSLMI 165

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 1034672040 321 RHYWEVDVQEA-GAGWWVGAAYASlrrRGASAAARLGCNRQSWCLK-RYDLEYWAFHDGQRSRLRPRDDlDRLGVFLDYE 398
Cdd:pfam00622   1 RHYFEVEIFGQdGGGWRVGWATKS---VPRKGERFLGDESGSWGYDgWTGKKYWASTSPLTGLPLFEPG-DVIGCFLDYE 76