B-box-type 1 zinc finger found in tripartite motif-containing protein 16 (TRIM16) and similar proteins; 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 by affecting cell proliferation and migration or tumorigenicity in carcinogenesis. TRIM16 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. The type 1 B-box (Bbox1) zinc finger is characterized by a C6H2 zinc-binding consensus motif.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 48255913  75 VLCDFCLDDTrrVKAVKSCLTCMVNYCEEHLQPHQVNIKLQSHLLTEP 122
Cdd:cd19839   1 VLCDFCLEAK--VKAVKSCLTCMVSYCEGHLRPHLENSKLQAHQLCDP 46

Cation efflux system protein CusB domain 1; The cation efflux system protein CusB from E. coli can be divided into four different domains, the first three domains of the protein are mostly beta-strands and the fourth forms an all alpha-helical domain. This entry represents the first beta-domain (domain 1) of CusB and it is formed by the N and C-terminal ends of the polypeptide (residues 89-102 and 324-385). CusB is part of the copper-transporting efflux system CusCFBA. This domain can also be found in other membrane-fusion proteins, such as HlyD, MdtN, MdtE and AaeA. HlyD is a component of the prototypical alpha-haemolysin (HlyA) bacterial type I secretion system, along with the other components HlyB and TolC. HlyD is anchored in the cytoplasmic membrane by a single transmembrane domain and has a large periplasmic domain within the carboxy-terminal 100 amino acids, HlyB and HlyD form a stable complex that binds the recombinant protein bearing a C-terminal HlyA signal sequence and ATP in the cytoplasm. HlyD, HlyB and TolC combine to form the three-component ABC transporter complex that forms a trans-membrane channel or pore through which HlyA can be transferred directly to the extracellular medium. Cutinase has been shown to be transported effectively through this pore.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 48255913   164 SLDAARRDKEAELQCTQLDLER-KLKLNENAISRLQAnqksvlvsVSEVKAVAEMQfGELLAAV-RKAQANVMLFLEEKE 241
Cdd:pfam00529 107 AAQAAVKAAQAQLAQAQIDLARrRVLAPIGGISRESL--------VTAGALVAQAQ-ANLLATVaQLDQIYVQITQSAAE 177

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 48255913   242 QAAL--SQANGIKAHLEYRSAEMEKSKQELERM---AAISNTVQFLE 283
Cdd:pfam00529 178 NQAEvrSELSGAQLQIAEAEAELKLAKLDLERTeirAPVDGTVAFLS 224

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 48255913   428 RYYFEVEIF---GAGTYVGLTCKGIDRKGEERNSCisgNNFSWSLQ-WNGKEFTAWYSDMETPLKAGPFRRLGVYIDFPG 503
Cdd:pfam00622   1 RHYFEVEIFgqdGGGWRVGWATKSVPRKGERFLGD---ESGSWGYDgWTGKKYWASTSPLTGLPLFEPGDVIGCFLDYEA 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 48255913   504 GILSFYGVEydtMTLVHKFA-CKFSEPVYAAFWLSKKENAIRIVDLG 549
Cdd:pfam00622  78 GTISFTKNG---KSLGYAFRdVPFAGPLFPAVSLGAGEGLKFNFGLR 121

B-box-type 1 zinc finger found in tripartite motif-containing protein 16 (TRIM16) and similar proteins; 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 by affecting cell proliferation and migration or tumorigenicity in carcinogenesis. TRIM16 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. The type 1 B-box (Bbox1) zinc finger is characterized by a C6H2 zinc-binding consensus motif.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 48255913  75 VLCDFCLDDTrrVKAVKSCLTCMVNYCEEHLQPHQVNIKLQSHLLTEP 122
Cdd:cd19839   1 VLCDFCLEAK--VKAVKSCLTCMVSYCEGHLRPHLENSKLQAHQLCDP 46

Cation efflux system protein CusB domain 1; The cation efflux system protein CusB from E. coli can be divided into four different domains, the first three domains of the protein are mostly beta-strands and the fourth forms an all alpha-helical domain. This entry represents the first beta-domain (domain 1) of CusB and it is formed by the N and C-terminal ends of the polypeptide (residues 89-102 and 324-385). CusB is part of the copper-transporting efflux system CusCFBA. This domain can also be found in other membrane-fusion proteins, such as HlyD, MdtN, MdtE and AaeA. HlyD is a component of the prototypical alpha-haemolysin (HlyA) bacterial type I secretion system, along with the other components HlyB and TolC. HlyD is anchored in the cytoplasmic membrane by a single transmembrane domain and has a large periplasmic domain within the carboxy-terminal 100 amino acids, HlyB and HlyD form a stable complex that binds the recombinant protein bearing a C-terminal HlyA signal sequence and ATP in the cytoplasm. HlyD, HlyB and TolC combine to form the three-component ABC transporter complex that forms a trans-membrane channel or pore through which HlyA can be transferred directly to the extracellular medium. Cutinase has been shown to be transported effectively through this pore.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 48255913   164 SLDAARRDKEAELQCTQLDLER-KLKLNENAISRLQAnqksvlvsVSEVKAVAEMQfGELLAAV-RKAQANVMLFLEEKE 241
Cdd:pfam00529 107 AAQAAVKAAQAQLAQAQIDLARrRVLAPIGGISRESL--------VTAGALVAQAQ-ANLLATVaQLDQIYVQITQSAAE 177

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 48255913   242 QAAL--SQANGIKAHLEYRSAEMEKSKQELERM---AAISNTVQFLE 283
Cdd:pfam00529 178 NQAEvrSELSGAQLQIAEAEAELKLAKLDLERTeirAPVDGTVAFLS 224

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 48255913 375 ITFDPDTAHKYLRLQEENRKVTNTTPWEHPYPdLPSRFLHWRQVLSQQSLYLHRYYFEVEIFG-AGTYVGLTCKGIDRKG 453
Cdd:cd12874   1 LTFDPDTAHLNLILSDDLRSVRVGDISQHPPE-PPPRFFECWQVLGSQSFSSGRHYWEVDVQDdSSWYVGVTYKSLPRKG 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 48255913 454 EerNSCISGNNFSWSLQWNGKEFTAWYSDMETPLKAGPFRRLGVYIDFPGGILSFYGVEyDTMTLVHKFACKFSEPVYAA 533
Cdd:cd12874  80 K--MSNLGRNNGSWCLEWRENEFSAWHNNPETRLPVTPPRRLGVFLDCDGGSLSFYGVT-DGVQLLYTFKAKFTEPLYPA 156

                       170
                ....*....|...
gi 48255913 534 FWLSkKENAIRIV 546
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 48255913 365 REQFLQYAYDITFDPDTAHKYLRLQEENRKVTNtTPWEHPYPDLPSRFLHWRQVLSQQSLyLHRYYFEVEIFGAGTYVGL 444
Cdd:cd16040   1 REEFLKYACQLTLDPNTAHRNLSLSEGNRKVTR-VKEEQPYPDHPERFDYWPQVLCREGL-SGRCYWEVEWSGGGVDIAV 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 48255913 445 TCKGIDRKGEERNSCISGNNFSWSLQWNGKEFTAWYSDMETPLKA--GPFRRLGVYIDFPGGILSFYGVeYDTMTLVHKF 522
Cdd:cd16040  79 AYKGISRKGDGDDSRFGYNDKSWSLECSPSGYSFWHNNKKTEISVpsSSSSRVGVYLDHSAGTLSFYSV-SDTMTLLHTV 157

                       170
                ....*....|....
gi 48255913 523 ACKFSEPVYAAFWL 536
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 48255913 374 DITFDPDTAHKYLRLQEENRKVTNTTPWEHPyPDLPSRFLHWRQVLSQQSLYLHRYYFEVEIfGAGT--YVGLTCKGIDR 451
Cdd:cd13733   1 DVTLDPDTAHPNLILSEDLKSVRYGDKRQNL-PDNPERFDTCVCVLGSEGFSSGRHYWEVEV-GGKTdwDLGVARESVNR 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 48255913 452 KGEERNSciSGNNFsWSLQ-WNGKEFTAWySDMETPLK-AGPFRRLGVYIDFPGGILSFYGVeyDTMTLVHKFACKFSEP 529
Cdd:cd13733  79 KGKITLS--PENGY-WTVGlRNGNEYKAL-TSPSTPLSlREKPQKVGVFLDYEEGQVSFYNV--DDGSHIYTFTDCFTEK 152

                       170
                ....*....|..
gi 48255913 530 VYAAFWLSKKEN 541
Cdd:cd13733 153 LYPYFSPCLNDG 164

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 48255913   428 RYYFEVEIF---GAGTYVGLTCKGIDRKGEERNSCisgNNFSWSLQ-WNGKEFTAWYSDMETPLKAGPFRRLGVYIDFPG 503
Cdd:pfam00622   1 RHYFEVEIFgqdGGGWRVGWATKSVPRKGERFLGD---ESGSWGYDgWTGKKYWASTSPLTGLPLFEPGDVIGCFLDYEA 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 48255913   504 GILSFYGVEydtMTLVHKFA-CKFSEPVYAAFWLSKKENAIRIVDLG 549
Cdd:pfam00622  78 GTISFTKNG---KSLGYAFRdVPFAGPLFPAVSLGAGEGLKFNFGLR 121

PRY/SPRY domain in tripartite motif-containing protein 47 (TRIM47), also known as RING finger protein 100 (RNF100) or Gene overexpressed in astrocytoma protein (GOA); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM47, also known as GOA (Gene overexpressed in astrocytoma protein) or RNF100 (RING finger protein 100). TRIM47 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. It is highly expressed in kidney tubular cells, but lowly expressed in most tissue. It is overexpressed in astrocytoma tumor cells and plays an important role in the process of dedifferentiation that is associated with astrocytoma tumorigenesis; astrocytoma, also known as cerebral astrocytoma, is a malignant glioma that arises from astrocytes. Genome wide studies on white matter lesions have identified a novel locus on chromosome 17q25 harboring several genes such as TRIM47 and TRIM65 which pinpoints to possible novel mechanisms leading to these lesions.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 48255913 368 FLQYAYDITFDPDTAHKYLRLQeeNRKVTNTTPWEHPYPDLPSRFLHWRQVLSQQSLYLHRYYFEVEIFGAGTYVGLTCK 447
Cdd:cd15808   3 FLKFAFIVDLDSDTADKFLQLF--GTKGVKRVLCPISYPESPTRFTHCEQVLGEGALDRGTYYWEVEIIEGWVSVGVMAE 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 48255913 448 GIDRKGEERNSCISGNNFSWSLQWNGKEFTAWYSDMETPLKAGPFRRLGVYIDFPGGILSFYGVEYDTMTLVHKFacKFS 527
Cdd:cd15808  81 DFSPREPYDRGRLGRNAHSCCLQWNGRNFSVWFHGLEAPLPHPFSPTVGVCLEYADRALAFYAVRDGKVSLLRRL--KAS 158

                ..
gi 48255913 528 EP 529
Cdd:cd15808 159 RP 160

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 48255913 376 TFDPDTAHKYLRLQEENRKVTnTTPWEHPYPDLPSRFlHWRQVLSQQSLYLHRYYFEVEI-FGAGTYVGLTCKGIDRK-- 452
Cdd:cd12902   2 TFDLRSLSCSLEVSEDSRKVT-VSHGPQAYAWSPDRF-SISQVLCSQAFSSGQHYWEVDTrQCSHWAVGVASWEMSRDqm 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 48255913 453 -GEERNScisgnnfsWSLQWNGK-EFTAWYSDMETPLKAGPFRRLGVYIDFPGGILSFYGVEyDTMTLVHKFACKFSEPV 530
Cdd:cd12902  80 lGRTMDS--------WCIEWKGTgQLSAWHMNKETVLGSDKPRVVGIWLDLEEGKLAFYSVA-NQERLLHECEVSASSPL 150

                ....*.
gi 48255913 531 YAAFWL 536
Cdd:cd12902 151 HPAFWL 156

B-box-type 1 zinc finger found in tripartite motif-containing protein 16 (TRIM16) and similar proteins; 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 by affecting cell proliferation and migration or tumorigenicity in carcinogenesis. TRIM16 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. The type 1 B-box (Bbox1) zinc finger is characterized by a C6H2 zinc-binding consensus motif.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 48255913  75 VLCDFCLDDTrrVKAVKSCLTCMVNYCEEHLQPHQVNIKLQSHLLTEP 122
Cdd:cd19839   1 VLCDFCLEAK--VKAVKSCLTCMVSYCEGHLRPHLENSKLQAHQLCDP 46

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 48255913 374 DITFDPDTAHKYLRLQEENRKVTNTTPWEHPyPDLPSRFLHWRQVLSQQSLYLHRYYFEVEIFGAGTY-VGLTCKGIDRK 452
Cdd:cd12888   1 NVTLDPDTAHPRLVLSEDRKSVRWGDTRQDL-PDNPERFDTWPCVLGCEGFTSGRHYWEVEVGDGGGWaVGVARESVRRK 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 48255913 453 GEernscISgnnFS-----WSLQWNGKEFTAWYS-DMETPLKAGPfRRLGVYIDFPGGILSFYGVeyDTMTLVHKF--AC 524
Cdd:cd12888  80 GE-----IS---FSpeegiWAVGQWGGQYWALTSpETPLPLSEVP-RRIRVYLDYEGGQVAFFDA--DNEAPIFTFppAS 148

                       170
                ....*....|..
gi 48255913 525 KFSEPVYAAFWL 536
Cdd:cd12888 149 FAGERIFPWFWV 160

associated with SPRY domains;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 48255913    372 AYDITFDPDTAHKYLRLQEENRKVTNTTPWeHPYPDLPSRFLHWRQVLSQQSL 424
Cdd:smart00589   1 AVDVTLDPDTAHPYLLLSEDRRSVRYGDLK-QSLPDNPERFDSYPCVLGSQGF 52

B-box-type 1 zinc finger found in tripartite motif-containing proteins, TRIM8, TRIM16, TRIM25, TRIM29, TRIM44, TRIM47 and similar proteins; This family includes a group of tripartite motif-containing proteins, including TRIM8, TRIM16, TRIM25, TRIM29, TRIM44 and TRIM47. TRIM8, also known as glioblastoma-expressed RING finger protein (GERP) or RING finger protein 27 (RNF27), is a probable E3 ubiquitin-protein ligase that may promote proteasomal degradation of suppressor of cytokine signaling 1 (SOCS1) and further regulate interferon-gamma signaling. It functions as a new p53 modulator that stabilizes p53, impairing its association with MDM2 and inducing the reduction of cell proliferation. TRIM16, also termed estrogen-responsive B box protein (EBBP), may play a role in the regulation of keratinocyte differentiation. It may also act as a tumor suppressor by affecting cell proliferation and migration or tumorigenicity in carcinogenesis. TRIM25, also termed estrogen-responsive finger protein (EFP), or ubiquitin/ISG15-conjugating enzyme TRIM25, or zinc finger protein 147 (ZNF147), or E3 ubiquitin/ISG15 ligase TRIM25, is induced by estrogen and is particularly abundant in placenta and uterus. It has been implicated in cell proliferation, protein modification, and the retinoic acid inducible gene I (RIG-I)-mediated antiviral signaling pathway. It functions as an E3-ubiquitin ligase able to transfer ubiquitin and ISG15 to target proteins. 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. TRIM44, also termed protein DIPB, functions as a critical regulator in tumor metastasis and progression. 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. The TRIM (tripartite motif) family of proteins are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a RING finger, Bbox1 and Bbox2, and a coiled coil domain. The type 1 B-box (Bbox1) zinc finger is characterized by a C6H2 zinc-binding consensus motif.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 48255913  76 LCDFClDDTRRVKAVKSCLTCMVNYCEEHLQPHQVNIKLQSHLLTEP 122
Cdd:cd19802   1 LCDFC-DPGKALKAVKSCLTCEASLCEIHLRPHLESPALKSHQLVEP 46

PRY/SPRY domain in tripartite motif-binding protein 41 (TRIM41); 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 41 (TRIM41). TRIM41 (also known as RING finger-interacting protein with C kinase or RINCK) 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 48255913 374 DITFDPDTAHKYLRLQEENRKVtNTTPWEHPYPDLPSRFLHWRQVLSQQSLYLHRYYFEVEIFG-AGTYVGLTCKGIDRK 452
Cdd:cd13741   1 DLTLDPDTAHPALLLSPDRRGV-RLAERRQEVPEHPKRFSADCCVLGAQGFRSGRHYWEVEVGGrRGWAVGAARESTHHK 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 48255913 453 ---GEERNSCISGNNFS----------------------WSLQWNGKEFTAWYSDMETPLKAG--PfRRLGVYIDFPGGI 505
Cdd:cd13741  80 ekvGSGGSSVSSGDASSsrhhhrrrrlhlpqqpllqrevWCVGTNGKRYQAQSSTEQTLLSPSekP-RRFGVYLDYEAGR 158

                       170       180       190       200
                ....*....|....*....|....*....|....*....|.
gi 48255913 506 LSFYGVEydTMTLVHKFACKF-SEPVYAAFWLSKKENAIRI 545
Cdd:cd13741 159 LGFYNAE--TLAHVHTFSAAFlGERVFPFFRVLSKGTRIKL 197

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 48255913 375 ITFDPDTAHKYLRLQEENRKVTNTTpWEHPYPDLPSRFLHWRQVLSQQSLYLHRYYFEVEIFGAGTY-VGLTCKGIDRKG 453
Cdd:cd12905   6 LTFDPETAHPSLILSRDLTAVTESD-EMQPYPRSPKRFLQCVNVLASQGFQSGRHYWEVWVGSKTKWdLGVASESVDRQA 84

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 48255913 454 EERnscISGNNFSWSLQ-WNGKEFTA----WysdmeTPLKAG-PFRRLGVYIDFPGGILSFYGVeyDTMTLVHKF 522
Cdd:cd12905  85 RVK---LCPENGYWTLRlRNGDEYWAgtqpW-----TRLRVTsRPQRIGVFLDCEERKVSFYNA--DDMSLLYSF 149

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 48255913 374 DITFDPDTAHKYLRLQEENRKVTNTTpWEHPYPDLPSRFLHWRQVLSQQSLYLHRYYFEVEIFGAGTYVGLTCK-GIDRK 452
Cdd:cd15811   1 DVTLDPDTANPELVLSEDRRSVRRGD-LRQALPDSPERFDPGPCVLGRERFTSGRHYWEVEVGDRTSWALGVCKeNVNRK 79

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 48255913 453 geERNSCISGNNFsWSLQWngkeFTAWYSDME---TPLKAGPfRRLGVYIDFPGGILSFYGV 511
Cdd:cd15811  80 --EKGELSAGNGF-WILVF----LGNYYSSERrtfAPLRDPP-RRVGIFLDYEAGHLSFYSA 133

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 48255913 371 YAYDITFDPDTAHKYLRLQEENRKVTNTTPwEHPYPDLPSRFLHWRQVLSQQSLYLHRYYFEVEIfGAGTYVGL-TCK-G 448
Cdd:cd13745   1 FAVDVTLDPDTAHPNLVLSEDRKSVRHGDT-RQDLPDNPERFDTYPCVLGAEGFTGGRHYWEVEV-GDKTEWTLgVCReS 78

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 48255913 449 IDRKGEERNSciSGNNFsWSL-QWNGKeFTAWYSDMeTPL--KAGPfRRLGVYIDFPGGILSFYGV 511
Cdd:cd13745  79 VSRKGEVTLS--PENGY-WTVwLRDGK-YEALTSPP-TPLpvSVRP-SRVGIFLDYEAGEVSFYNV 138

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 48255913 375 ITFDPDTAHKYLRLQEENRKVTNTTPWEHpYPDLPSRFLHWRQVLSQQSLYLHRYYFEVEIF---GAGTYVGLTCKGIDR 451
Cdd:cd15826   2 VTLDPQTASGSLVLSEDRKSVRYTRQKQN-LPDSPLRFDGLPAVLGSPGFSSGRHRWQVEVQlgdGGGCTVGVAGESVRR 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 48255913 452 KGEERNSCISGnnfSWSLQWNGKEFTAWYS-DMETPLKAGPfRRLGVYIDFPGGILSFYGVEydTMTLVHKFACKFSEPV 530
Cdd:cd15826  81 KGEMGLSAEDG---VWAVILSHQQCWASTSpGTDLPLSEIP-RRVGVALDYEAGTVTLTNAE--TQEPIFTFTASFSGKV 154

                ....*....
gi 48255913 531 YAAFWLSKK 539
Cdd:cd15826 155 FPFFAVWKK 163

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 48255913  76 LCDFCLDdtRRVKAVKSCLTCMVNYCEEHLQPHQVNIKLQSHLLTEPVKD 125
Cdd:cd19842   1 LCDLCLG--RELAAAKTCLTCLASFCPEHLEPHLSSPAFRSHRLCPPERD 48

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 48255913 371 YAYDITFDPDTAHKYLRLQEENRKV-TNTTPweHPYPDLPSRFLHWRQVLSQQSLYLHRYYFEVEIFGAGTY-VGLTCKG 448
Cdd:cd12900   1 HMVHITLDPDTANPWLILSKDRRQVrLGDTH--QNVPENEERFDNYPMVLGAQRFNSGKHYWEVDVTGKEAWdLGVCRDS 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 48255913 449 IDRKGEernSCISGNNFSWSLQ-WNGKEFTAWYSdmETPLKAG-PFRRLGVYIDFPGGILSFYGVEyDTMTLVHKFA-CK 525
Cdd:cd12900  79 VRRKGQ---FLLSPENGFWTIWlWNKKYEAGTSP--QTTLHLQvPPCQVGIFLDYEAGVVSFYNIT-DHGSLIYTFSeCA 152