B-box-type 2 zinc finger found in tripartite motif-containing proteins, TRIM16, TRIM29, TRIM47 and similar proteins; This family includes a group of tripartite motif-containing proteins, such as TRIM16, TRIM29 and TRIM47. TRIM16, also termed estrogen-responsive B box protein (EBBP), is a regulator that may play a role in the regulation of keratinocyte differentiation. It may also act as a tumor suppressor through affecting cell proliferation and migration or tumorigenicity in carcinogenesis. TRIM29, also termed ataxia telangiectasia group D-associated protein (ATDC), plays a crucial role in the regulation of macrophage activation in response to viral or bacterial infections within the respiratory tract. TRIM47, also known as gene overexpressed in astrocytoma protein (GOA) or RING finger protein 100 (RNF100), plays an important role in the process of dedifferentiation that is associated with astrocytoma tumorigenesis. TRIM16 and TRIM29 belong 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. TRIM47 belongs to the C-IV subclass of TRIM family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a RING finger, Bbox1 and Bbox2, and two coiled coil domains, 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.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 568976577  33 RTCPAHHSPLVSFCHTHQQCICQECGEGEHRGDSTVSLDAARRNKE 78
Cdd:cd19769    1 RVCPIHKKPLELFCRTDQMCICELCAKEEHRGHDVVTVEEEREKKE 46

Synaptonemal complex protein 1 (SCP-1); Synaptonemal complex protein 1 (SCP-1) is the major component of the transverse filaments of the synaptonemal complex. Synaptonemal complexes are structures that are formed between homologous chromosomes during meiotic prophase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976577   87 DLEQKLKLNENAIARLQaNHKSVLVSvsEVKVVAEEKFGELLAAVRKAQADVMVFL---EEKEQAALN-QVNSIKTHLEH 162
Cdd:pfam05483 392 ELEEMTKFKNNKEVELE-ELKKILAE--DEKLLDEKKQFEKIAEELKGKEQELIFLlqaREKEIHDLEiQLTAIKTSEEH 468

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976577  163 RSLEMEKSKQELERLaaisntvlfleeycKLKKTEDTASpsiyiglKDKLSGIRKVITDSTLNLIQLLESYKEKLQEFSR 242
Cdd:pfam05483 469 YLKEVEDLKTELEKE--------------KLKNIELTAH-------CDKLLLENKELTQEASDMTLELKKHQEDIINCKK 527

                         170       180       190
                  ....*....|....*....|....*....|...
gi 568976577  243 EEEYDIRtQVSAIVQRKYRTSKPEPRTRDEFLQ 275
Cdd:pfam05483 528 QEERMLK-QIENLEEKEMNLRDELESVREEFIQ 559

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 568976577   332 HRYYFEVEL-SGGGTYVGLTCKGIDRKGEernSCISGNSFSWSIHWN-GKEFTAWHSDTETPLKVSPFRRLGIYVNFPGG 409
Cdd:smart00449   2 GRHYFEVEIgDGGHWRVGVATKSVPRGYF---ALLGEDKGSWGYDGDgGKKYHNSTGPEYGLPLQEPGDVIGCFLDLEAG 78

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 568976577   410 ILSFYGVEyDAMTLIHKFDCKFSEPVYAAFWLSKKENA 447
Cdd:smart00449  79 TISFYKNG-KYLHGLAFFDVKFSGPLYPAFSLGSGNSV 115

B-box-type 2 zinc finger found in tripartite motif-containing proteins, TRIM16, TRIM29, TRIM47 and similar proteins; This family includes a group of tripartite motif-containing proteins, such as TRIM16, TRIM29 and TRIM47. TRIM16, also termed estrogen-responsive B box protein (EBBP), is a regulator that may play a role in the regulation of keratinocyte differentiation. It may also act as a tumor suppressor through affecting cell proliferation and migration or tumorigenicity in carcinogenesis. TRIM29, also termed ataxia telangiectasia group D-associated protein (ATDC), plays a crucial role in the regulation of macrophage activation in response to viral or bacterial infections within the respiratory tract. TRIM47, also known as gene overexpressed in astrocytoma protein (GOA) or RING finger protein 100 (RNF100), plays an important role in the process of dedifferentiation that is associated with astrocytoma tumorigenesis. TRIM16 and TRIM29 belong 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. TRIM47 belongs to the C-IV subclass of TRIM family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a RING finger, Bbox1 and Bbox2, and two coiled coil domains, 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.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 568976577  33 RTCPAHHSPLVSFCHTHQQCICQECGEGEHRGDSTVSLDAARRNKE 78
Cdd:cd19769    1 RVCPIHKKPLELFCRTDQMCICELCAKEEHRGHDVVTVEEEREKKE 46

B-box zinc finger;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 568976577   30 QDLRTCPAHHS-PLVSFCHTHQQCICQECGEGEHRGDSTVSL 70
Cdd:pfam00643   1 SKERLCPEHEEePLTLYCNDCQELLCEECSVGEHRGHTVVPL 42

Synaptonemal complex protein 1 (SCP-1); Synaptonemal complex protein 1 (SCP-1) is the major component of the transverse filaments of the synaptonemal complex. Synaptonemal complexes are structures that are formed between homologous chromosomes during meiotic prophase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976577   87 DLEQKLKLNENAIARLQaNHKSVLVSvsEVKVVAEEKFGELLAAVRKAQADVMVFL---EEKEQAALN-QVNSIKTHLEH 162
Cdd:pfam05483 392 ELEEMTKFKNNKEVELE-ELKKILAE--DEKLLDEKKQFEKIAEELKGKEQELIFLlqaREKEIHDLEiQLTAIKTSEEH 468

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976577  163 RSLEMEKSKQELERLaaisntvlfleeycKLKKTEDTASpsiyiglKDKLSGIRKVITDSTLNLIQLLESYKEKLQEFSR 242
Cdd:pfam05483 469 YLKEVEDLKTELEKE--------------KLKNIELTAH-------CDKLLLENKELTQEASDMTLELKKHQEDIINCKK 527

                         170       180       190
                  ....*....|....*....|....*....|...
gi 568976577  243 EEEYDIRtQVSAIVQRKYRTSKPEPRTRDEFLQ 275
Cdd:pfam05483 528 QEERMLK-QIENLEEKEMNLRDELESVREEFIQ 559

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 568976577 280 ITFDPDTAHRYLRLQEDNRKVTNTTPWEHPYPdLPSRFLHWRQVLSQQSLYLHRYYFEVELSG-GGTYVGLTCKGIDRKG 358
Cdd:cd12874    1 LTFDPDTAHLNLILSDDLRSVRVGDISQHPPE-PPPRFFECWQVLGSQSFSSGRHYWEVDVQDdSSWYVGVTYKSLPRKG 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976577 359 EerNSCISGNSFSWSIHWNGKEFTAWHSDTETPLKVSPFRRLGIYVNFPGGILSFYGVEyDAMTLIHKFDCKFSEPVYAA 438
Cdd:cd12874   80 K--MSNLGRNNGSWCLEWRENEFSAWHNNPETRLPVTPPRRLGVFLDCDGGSLSFYGVT-DGVQLLYTFKAKFTEPLYPA 156

                        170
                 ....*....|...
gi 568976577 439 FWLSkKENAIRIV 451
Cdd:cd12874  157 FWLG-EGSTLSIC 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 568976577 270 RDEFLQYACDITFDPDTAHRYLRLQEDNRKVTNTtPWEHPYPDLPSRFLHWRQVLSQQSLyLHRYYFEVELSGGGTYVGL 349
Cdd:cd16040    1 REEFLKYACQLTLDPNTAHRNLSLSEGNRKVTRV-KEEQPYPDHPERFDYWPQVLCREGL-SGRCYWEVEWSGGGVDIAV 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976577 350 TCKGIDRKGEERNSCISGNSFSWSIHWNGKEFTAWH--SDTETPLKVSPFRRLGIYVNFPGGILSFYGVeYDAMTLIHKF 427
Cdd:cd16040   79 AYKGISRKGDGDDSRFGYNDKSWSLECSPSGYSFWHnnKKTEISVPSSSSSRVGVYLDHSAGTLSFYSV-SDTMTLLHTV 157

                        170
                 ....*....|....
gi 568976577 428 DCKFSEPVYAAFWL 441
Cdd:cd16040  158 QTTFTEPLYPGFGV 171

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 568976577 279 DITFDPDTAHRYLRLQEDNRKVTNTTPWEHPyPDLPSRFLHWRQVLSQQSLYLHRYYFEVELsGGGT--YVGLTCKGIDR 356
Cdd:cd13733    1 DVTLDPDTAHPNLILSEDLKSVRYGDKRQNL-PDNPERFDTCVCVLGSEGFSSGRHYWEVEV-GGKTdwDLGVARESVNR 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976577 357 KGEERNSciSGNSFsWSI-HWNGKEFTAWHSdTETPLKVS-PFRRLGIYVNFPGGILSFYGVeyDAMTLIHKFDCKFSEP 434
Cdd:cd13733   79 KGKITLS--PENGY-WTVgLRNGNEYKALTS-PSTPLSLReKPQKVGVFLDYEEGQVSFYNV--DDGSHIYTFTDCFTEK 152

                        170
                 ....*....|..
gi 568976577 435 VYAAFWLSKKEN 446
Cdd:cd13733  153 LYPYFSPCLNDG 164

PRY/SPRY domain in tripartite motif-containing domain 25 (TRIM25); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM25 proteins (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 568976577 280 ITFDPDTAHRYLRLQEDNRKVTNTTPWEHpYPDLPSRFLHWRQVLSQQSLYLHRYYFEVELSGGG-TYVGLTCKGIDRKG 358
Cdd:cd13736    1 VIFDYNTAHNKVSLSENYTKASVSDDPQN-YREHPQRFTYCSQVLGLHCFKQGIHYWEVELQKNNfCGVGICYGSMDRQG 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976577 359 EErnSCISGNSFSWSIHWNGKEFTAWHSDTETPLKVSPFRRLGIYVNFPGGILSFYGVEyDAMTLIHKFDCKFSEPVYAA 438
Cdd:cd13736   80 PE--SRLGRNSESWCVEWFNVKISAWHNNVEKTLPSTKATRVGVLLNCDHGFVIFFAVQ-DKVHLMYKFKVDFTEALYPA 156

                 ...
gi 568976577 439 FWL 441
Cdd:cd13736  157 FWV 159

PRY/SPRY domain in tripartite motif-containing proteins 1, 9, 18, 36, 46, 67,76 (TRIM1, TRIM9, TRIM18, TRIM36, TRIM46, TRIM67, TRIM76); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of several Class I TRIM proteins, including TRIM1, TRIM9, TRIM18, TRIM36, TRIM46, TRIM67 and TRIM76. TRIM1 (also known as MID2) and its close homolog, TRIM18 (also known as MID1), both contain a B30.2-like domain at their C-terminus and a single fibronectin type III (FN3) motif between it and their N-terminal RBCC domain. Their coiled-coil motifs mediate both homo- and heterodimerization, a prerequisite for association of the rapamycin-sensitive PP2A regulatory subunit Alpha 4 with microtubules. Mutations in TRIM18 have shown to cause Opitz syndrome, a disorder causing congenital anomalies such as cleft lip and palate as well as heart defects. TRIM9 is expressed mainly in the cerebral cortex, and functions as an E3 ubiquitin ligase. Its immunoreactivity is severely decreased in affected brain areas in Parkinson's disease and dementia with Lewy bodies, possibly playing an important role in the regulation of neuronal function and participating in pathological process of Lewy body disease through its ligase. TRIM36 interacts with centromere protein-H, one of the kinetochore proteins and possibly associates with chromosome segregation; an excess of TRIM36 may cause chromosomal instability. TRIM46 has not yet been characterized. TRIM67 negatively regulates Ras activity via degradation of 80K-H, leading to neural differentiation, including neuritogenesis. TRIM76 (also known as cardiomyopathy-associated protein 5 or CMYA5) is a muscle-specific member of the TRIM superfamily, but lacks the RING domain. It is possibly involved in protein kinase A signaling as well as vesicular trafficking. It has also been implicated in Duchenne muscular dystrophy and cardiac disease. The PRY-SPRY domain in these TRIM families is suggested to serve as the target binding site.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976577 280 ITFDPDTAHRYLRLQEDNRKVT-NTTPWEHPYPDLPSRFLHWRQVLSQQSLYLHRYYFEVELSGGGTY-VGLTckgidRK 357
Cdd:cd13734    1 FKLDPKTAHRKLRLSNDNLTVEyDPEGSKDQAAVLPRRFTGSPAVLGDVAISSGRHYWEVSVSRSTSYrVGVA-----YK 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976577 358 GEERNSCISGNSFSWSIHWNGKEFTAWHSDTETPLKVSPF-RRLGIYVNFPGGILSFYGVEydAMTLIHKFDCKFSEPVY 436
Cdd:cd13734   76 SAPRDEDLGKNSTSWCLSRDNNRYTARHDGKVVDLRVTGHpARIGVLLDYDNGTLSFYDAE--SKQHLYTFHVDFEGPVC 153

                 ...
gi 568976577 437 AAF 439
Cdd:cd13734  154 PAF 156

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 568976577 277 ACDITFDPDTAHRYLRLQEDNRKVTnttpWEHPYPDLPS---RFLHWRQVLSQQSLYLHRYYFEVELSG-GGTYVGLTCK 352
Cdd:cd15819    1 AVNVTLDPDTAHPALILSEDGRSVT----WGETRQDLPEnpeRFDSLPCVLGQEGFTSGRHYWEVEVGDrTSWDLGVCRD 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976577 353 GIDRKGeeRNSCISGNSFsWSIHWNGKEFTAWHS-DTETPLKVSPfRRLGIYVNFPGGILSFYgveydAMT---LIHKFD 428
Cdd:cd15819   77 NVMRKG--RVTLSPENGF-WAIRLYGNEYWALTSpETPLTLKEPP-RRVGIFLDYEAGDVSFY-----NMTdgsHIYTFP 147

                        170
                 ....*....|....
gi 568976577 429 -CKFSEPVYAAFWL 441
Cdd:cd15819  148 qTAFSGPLRPFFRL 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 568976577 279 DITFDPDTAHRYLRLQEDNRKVTNTTPWEHPyPDLPSRFLHWRQVLSQQSLYLHRYYFEVELSGGGTY-VGLTCKGIDRK 357
Cdd:cd12888    1 NVTLDPDTAHPRLVLSEDRKSVRWGDTRQDL-PDNPERFDTWPCVLGCEGFTSGRHYWEVEVGDGGGWaVGVARESVRRK 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976577 358 GEernscisgNSFS-----WSIHWNGKEFTAWHS-DTETPLKVSPfRRLGIYVNFPGGILSFYGVeyDAMTLIHKFDCKF 431
Cdd:cd12888   80 GE--------ISFSpeegiWAVGQWGGQYWALTSpETPLPLSEVP-RRIRVYLDYEGGQVAFFDA--DNEAPIFTFPPAS 148

                        170
                 ....*....|..
gi 568976577 432 --SEPVYAAFWL 441
Cdd:cd12888  149 faGERIFPWFWV 160

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 568976577  333 RYYFEVEL---SGGGTYVGLTCKGIDRKGEERNSCisgNSFSWSIH-WNGKEFTAWHSDTETPLKVSPFRRLGIYVNFPG 408
Cdd:pfam00622   1 RHYFEVEIfgqDGGGWRVGWATKSVPRKGERFLGD---ESGSWGYDgWTGKKYWASTSPLTGLPLFEPGDVIGCFLDYEA 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 568976577  409 GILSFYGVEydaMTLIHKF-DCKFSEPVYAAFWLSKKENAIRIVDLG 454
Cdd:pfam00622  78 GTISFTKNG---KSLGYAFrDVPFAGPLFPAVSLGAGEGLKFNFGLR 121

SPRY domain in Ro-Ret family; This domain, named BSPRY, has been identified in the Ro-Ret family, since the protein is composed of a B-box, an alpha-helical coiled coil and a SPRY domain. The gene for BSPRY resides on human chromosome 9 and is specifically expressed in testis. The function of BSPRY is not known, but several related proteins of the RING-Box-coiled-coil (RBCC) family have been implicated in cell transformation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976577 280 ITFDPDTAHRYLRLQEDNRKVT-NTTPWEHPYPDLPSRFLHWRQVLSQQSLY--LHRYYFEVELSGGgtY-VGLTCKGID 355
Cdd:cd12904    1 LRFDERTVSPLLSLSEDRRTLTfSPKKARQSPPDDPERFDHWPNALASLSFSsgTHAWVVDVGKSCA--YkVGVCYGSLE 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976577 356 RKGEERNSCISGNSFSWSIHWNGKEFTAWHSDTETPLKV--SPfRRLGIYVNFPGGILSFYgvEYDAMTLIHKFDCKFSE 433
Cdd:cd12904   79 RKGSGNEARLGYNAFSWVFSRYDGEFSFSHNGQHVPLELlkCP-ARVGVLLDWPSQELLFY--DPDSCTVLHSHREAFAA 155

                 ....*.
gi 568976577 434 PVYAAF 439
Cdd:cd12904  156 PLLPVF 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 568976577 276 YACDITFDPDTAHRYLRLQEDNRKV-TNTTPweHPYPDLPSRFLHWRQVLSQQSLYLHRYYFEVELSGGGTY-VGLTCKG 353
Cdd:cd12900    1 HMVHITLDPDTANPWLILSKDRRQVrLGDTH--QNVPENEERFDNYPMVLGAQRFNSGKHYWEVDVTGKEAWdLGVCRDS 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976577 354 IDRKGEERNSciSGNSFsWSIH-WNGKEFTAWHSDTETPLKVSPfRRLGIYVNFPGGILSFYGVEyDAMTLIHKF-DCKF 431
Cdd:cd12900   79 VRRKGQFLLS--PENGF-WTIWlWNKKYEAGTSPQTTLHLQVPP-CQVGIFLDYEAGVVSFYNIT-DHGSLIYTFsECAF 153

                 ....*...
gi 568976577 432 SEPVYAAF 439
Cdd:cd12900  154 TGPLRPFF 161

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 568976577 276 YACDITFDPDTAHRYLRLQEDNRKVTNTTPwEHPYPDLPSRFLHWRQVLSQQSLYLHRYYFEVELsGGGTYVGL-TCK-G 353
Cdd:cd13745    1 FAVDVTLDPDTAHPNLVLSEDRKSVRHGDT-RQDLPDNPERFDTYPCVLGAEGFTGGRHYWEVEV-GDKTEWTLgVCReS 78

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 568976577 354 IDRKGEERNSciSGNSFsWSI-HWNGKeFTAWHSDTeTPLKVS--PfRRLGIYVNFPGGILSFYGV 416
Cdd:cd13745   79 VSRKGEVTLS--PENGY-WTVwLRDGK-YEALTSPP-TPLPVSvrP-SRVGIFLDYEAGEVSFYNV 138

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 568976577 280 ITFDPDTAHRYLRLQEDNRKVTNTTpWEHPYPDLPSRFLHWRQVLSQQSLYLHRYYFEVELSGGGTY-VGLTCKGIDRKG 358
Cdd:cd12905    6 LTFDPETAHPSLILSRDLTAVTESD-EMQPYPRSPKRFLQCVNVLASQGFQSGRHYWEVWVGSKTKWdLGVASESVDRQA 84

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568976577 359 EERNSCISGnsfSWSIH-WNGKEFTA----WhsdTETPLKVSPfRRLGIYVNFPGGILSFYGVeyDAMTLIHKF 427
Cdd:cd12905   85 RVKLCPENG---YWTLRlRNGDEYWAgtqpW---TRLRVTSRP-QRIGVFLDCEERKVSFYNA--DDMSLLYSF 149

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 568976577 280 ITFDPDTAHRYLRLQEDNRKVTNTTPwEHPYPDLPSRFLHWRQVLSQQSLYLHRYYFEVELSGGGTY-VGLTCKGIDRKG 358
Cdd:cd15818   15 ITLDPKTAHPNLILSEDLTCVWHGDT-KQMLPDNPERFDSSVAVLGSEGFTSGKHYWEVEVAKKTKWtLGVVRESINRKG 93

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976577 359 eerNSCISGNSFSWSIHW-NGKEFTAWHSDTETPLKVSPFRRLGIYVNFPGGILSFYgvEYDAMTLIHKFDCKFSEPVYA 437
Cdd:cd15818   94 ---NCPLSPEDGFWLLRLrNQNELKALDVPSFSLTLTSNLNKVGIYLDYEGGQVSFY--NANTMSHIYTFSDTFTEKIYP 168

                 ..
gi 568976577 438 AF 439
Cdd:cd15818  169 YF 170

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 568976577 280 ITFDPDTAHRYLRLQEDNRKVTNTTPWEhPYPDLPSRFLHWRQVLSQQSLYLHRYYFEVELsGGGTY--VGLTCKGIDRK 357
Cdd:cd12893    2 VTLDPNTAHPWLSLSEDLTSVRYSSEKQ-QLPDNPERFDPYPCVLGSEGFTSGKHSWDVEV-GDNTSwmLGVAKESVQRK 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976577 358 GEERNSCISGnsfSWSI-HWNGKEFTAWHSDTETPLKVS-PFRRLGIYVNFPGGILSFygveYDA--MTLIHKFDCKFSE 433
Cdd:cd12893   80 GKFTLSPESG---FWTIgFSEGKYSARTSPEPRTPLRVKqKPQRIRVQLDWDRGKVSF----SDPdtNTHIHTFTHTFTE 152

                        170
                 ....*....|....*...
gi 568976577 434 PVYAAFWLSKKENAIRIV 451
Cdd:cd12893  153 RVFPYFYTGCKSEPLRIL 170

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 568976577 276 YACDITFDPDTAHRYLRLQEDNRKVTNTTPWEhPYPDLPSRFLHWRQVLSQQSLYLHRYYFEVELSGGGTYVGLTCK-GI 354
Cdd:cd15813    7 HAVNVTLDPETAHPNLIFSDDLKSVRLGNKWD-RLPDNPERFDSCIIVLGSPSFTSGRHYWEVEVGDKTGWILGVCKaSV 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568976577 355 DRKGEERNSCISGnsfswsiHW-----NGKEFTAWHSdTETPLKV-SPFRRLGIYVNFPGGILSFYGVEydAMTLIHKF- 427
Cdd:cd15813   86 SRKGSMTLSPENG-------YWvvmmtKRNEYQASTS-PPTRLWLrEPPRRVGIFLDYEAGDISFYNVT--AKSHIYTFt 155

                        170
                 ....*....|..
gi 568976577 428 DCKFSEPVYAAF 439
Cdd:cd15813  156 SFSSSGPLQPIF 167