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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6FLN_A      274 VILDYNTAHNKVALSECYTVASVAEMPQNYRPHPQRFTYCSQVLGLHCYKKGIHYWEVELQKNNFCGVGICYGSMNRQGP 353
Cdd:cd13736   1 VIFDYNTAHNKVSLSENYTKASVSDDPQNYREHPQRFTYCSQVLGLHCFKQGIHYWEVELQKNNFCGVGICYGSMDRQGP 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6FLN_A      354 ESRLGRNSASWCVEWFNTKISAWHNNVEKTLPSTKATRVGVLLNCDHGFVIFFAVADKVHLMYKFRVDFTEALYPAFWVF 433
Cdd:cd13736  81 ESRLGRNSESWCVEWFNVKISAWHNNVEKTLPSTKATRVGVLLNCDHGFVIFFAVQDKVHLMYKFKVDFTEALYPAFWVF 160

                ....*....
6FLN_A      434 SAGATLSIC 442
Cdd:cd13736 161 SAGTTLSLC 169

helix-rich Mycoplasma protein; Members of this family occur strictly within a subset of Mycoplasma species. Members average 750 amino acids in length, including signal peptide. Sequences are predicted (Jpred 3) to be almost entirely alpha-helical. These sequences show strong periodicity (consistent with long alpha helical structures) and low complexity rich in D,E,N,Q, and K. Genes encoding these proteins are often found in tandem. The function is unknown.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6FLN_A         36 DDVRNRQQDVR---MTANRKVEQLQQEYTEMKaLLDASETTSTRKIKEEEKR----------VNSKFDTIYQILLKKKSE 102
Cdd:TIGR04523  47 NELKNKEKELKnldKNLNKDEEKINNSNNKIK-ILEQQIKDLNDKLKKNKDKinklnsdlskINSEIKNDKEQKNKLEVE 125

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
6FLN_A        103 IQTLKEEIEQSLTKRDEF--EFLEKASKLRGISTKpvyipevelNHKLIKGIHqstiDLKNELKQ 165
Cdd:TIGR04523 126 LNKLEKQKKENKKNIDKFltEIKKKEKELEKLNNK---------YNDLKKQKE----ELENELNL 177

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6FLN_A      274 VILDYNTAHNKVALSECYTVASVAEMPQNYRPHPQRFTYCSQVLGLHCYKKGIHYWEVELQKNNFCGVGICYGSMNRQGP 353
Cdd:cd13736   1 VIFDYNTAHNKVSLSENYTKASVSDDPQNYREHPQRFTYCSQVLGLHCFKQGIHYWEVELQKNNFCGVGICYGSMDRQGP 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6FLN_A      354 ESRLGRNSASWCVEWFNTKISAWHNNVEKTLPSTKATRVGVLLNCDHGFVIFFAVADKVHLMYKFRVDFTEALYPAFWVF 433
Cdd:cd13736  81 ESRLGRNSESWCVEWFNVKISAWHNNVEKTLPSTKATRVGVLLNCDHGFVIFFAVQDKVHLMYKFKVDFTEALYPAFWVF 160

                ....*....
6FLN_A      434 SAGATLSIC 442
Cdd:cd13736 161 SAGTTLSLC 169

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6FLN_A        326 IHYWEVEL--QKNNFCGVGICYGSMNRQGpESRLGRNSASWCVEWFNTKISaWHNNVEKT--LPSTKATRVGVLLNCDHG 401
Cdd:pfam00622   1 RHYFEVEIfgQDGGGWRVGWATKSVPRKG-ERFLGDESGSWGYDGWTGKKY-WASTSPLTglPLFEPGDVIGCFLDYEAG 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
6FLN_A        402 fVIFFAVADKvHLMYKFR-VDFTEALYPAFWvFSAGATLSIC 442
Cdd:pfam00622  79 -TISFTKNGK-SLGYAFRdVPFAGPLFPAVS-LGAGEGLKFN 117

Transforming acidic coiled-coil-containing protein (TACC), C-terminal; This entry represents a C-terminal domain found in the the proteins TACC 1, 2 and 3 (TACC1-3). TACC1 is found concentrated in the centrosomes of eukaryotes which may play a conserved role in organizing centrosomal microtubules. The human TACC proteins have been linked to cancer and TACC2 has been identified as a possible tumour suppressor (AZU-1). TACC 3 from Xenopus laevis, also known as maskin, associates XMAP215 and promotes efficient microtubule elongation during mitosis. Maskin is also found to bind CPEB and elF-4E. Interestingly, the functional homolog (Alp7) in Schizosaccharomyces pombe (not included in this entry) has been shown to be required for organization of bipolar spindles.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
6FLN_A         51 RKVEQLQQEYTEMKALLDASETTSTRKIKEEEKRVNskfdtiyqillKKKSEIQTLKEEIEQSLTKRDEFE 121
Cdd:pfam05010  29 AKYEELRRENLEMRKIVAEFEKTIAQMIEEKQKQKE-----------LEHAEIQKVLEEKDQALADLNSVE 88

ATP-dependent Clp protease, ATP-binding subunit ClpA [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6FLN_A       51 RKVEQLQQEYTEMKALLDASETTSTRKIKEEEKRVNSKFDTIYQILLKKK---SEIQTLKEEIEQSLTKRDEFEFLEKAS 127
Cdd:COG0542 418 RRLEQLEIEKEALKKEQDEASFERLAELRDELAELEEELEALKARWEAEKeliEEIQELKEELEQRYGKIPELEKELAEL 497

                        90
                ....*....|....*
6FLN_A      128 KLRGISTKPVYIPEV 142
Cdd:COG0542 498 EEELAELAPLLREEV 512

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6FLN_A      274 VILDYNTAHNKVALSECYTVASVAEMPQNYRPHPQRFTYCSQVLGLHCYKKGIHYWEVELQKNNFCGVGICYGSMNRQGP 353
Cdd:cd13736   1 VIFDYNTAHNKVSLSENYTKASVSDDPQNYREHPQRFTYCSQVLGLHCFKQGIHYWEVELQKNNFCGVGICYGSMDRQGP 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6FLN_A      354 ESRLGRNSASWCVEWFNTKISAWHNNVEKTLPSTKATRVGVLLNCDHGFVIFFAVADKVHLMYKFRVDFTEALYPAFWVF 433
Cdd:cd13736  81 ESRLGRNSESWCVEWFNVKISAWHNNVEKTLPSTKATRVGVLLNCDHGFVIFFAVQDKVHLMYKFKVDFTEALYPAFWVF 160

                ....*....
6FLN_A      434 SAGATLSIC 442
Cdd:cd13736 161 SAGTTLSLC 169

PRY/SPRY domain in tripartite motif-containing (TRIM) proteins, including TRIM14-like, TRIM16-like, TRIM25-like, TRIM47-like, TRIM65 and RNF135, and stonustoxin; 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 TRIM14, TRIM16 and TRIM25, TRIM47 as well as RING finger protein RNF135 and stonustoxin, a secreted poisonous protein of the stonefish Synanceja horrida. TRIM16 (also known as estrogen-responsive B box protein or EBBP) has E3 ubiquitin ligase activity. It is a regulator of keratinocyte differentiation and a tumor suppressor in retinoid-sensitive neuroblastoma. 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. TRIM47, also known as GOA (Gene overexpressed in astrocytoma protein) or RNF100 (RING finger protein 100), is highly expressed in kidney tubular cells, but low 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. RNF135 ubiquitinates RIG-I (retinoic acid-inducible gene-I) to promote interferon-beta induction during the early phase of viral infection. Stonustoxin (STNX) is a hypotensive and lethal protein factor that also possesses other biological activities such as species-specific hemolysis (due to its ability to form pores in the cell membrane) and platelet aggregation, edema-induction, and endothelium-dependent vasorelaxation (mediated by the nitric oxide pathway and activation of potassium channels). 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6FLN_A      274 VILDYNTAHNKVALSECYTVASVAEMPQNYRPHPQRFTYCsQVLGLHCYKKGIHYWEVELQKNNFCGVGICYGSMNRQGP 353
Cdd:cd12891   1 LTLDPNTAHNNLALSGDLKTVTCSSENQHYPDSPERFTHS-QVLSTQSFSSGRHYWEVEVSESGGWSVGVAYPSIERKGD 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6FLN_A      354 ESRLGRNSASWCVEWFNTKISAWHNNVEKTLPSTKATRVGVLLNCDHGFVIFFAVADKVHLMYKFRVDFTEALYPAFWVF 433
Cdd:cd12891  80 ESRIGRNDKSWCLEWQDKSFSAWHNNEETPLPSVSSRRLGVYLDYEAGRLSFYELSDPIRHLHTFTATFTEPLHPAFWVL 159

                ....*....
6FLN_A      434 SaGATLSIC 442
Cdd:cd12891 160 E-GGWIRIK 167

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6FLN_A      264 RPELLEYYIKVILDYNTAHNKVALSE-CYTVASVAEMPQNYRPHPQRFTYCSQVLGLHCYKKGIHYWEVELqKNNFCGVG 342
Cdd:cd12890   1 RDDFLKYAYPLTFDPDTAHRYLRLTEdNRKVTNTTPWEHPYPDHPERFEHWRQVLSQQSLYLGRYYFEVEI-SGEGTYVG 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6FLN_A      343 ICYGSMNRQGPE--SRLGRNSASWCVEWFNTKISAWHNNVEKTLPSTKATRVGVLLNCDHGFVIFFAV-ADKVHLMYKFR 419
Cdd:cd12890  80 LTYKSIDRKGSEsnSCISGNNFSWCLQWNGKEFSAWHSDVETPLKKGPFTRLGIYLDYPGGTLSFYGVeDDGMTLLHKFQ 159

                       170
                ....*....|...
6FLN_A      420 VDFTEALYPAFWV 432
Cdd:cd12890 160 CKFTEPLYPAFWL 172

PRY/SPRY domain in tripartite motif-containing domain 65 (TRIM65); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM65 proteins (composed of RING/B-box/coiled-coil core and also known as RBCC proteins). The SPRY/PRY combination is a possible component of immune defense. This protein family has not been characterized.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6FLN_A      264 RPELLEYYIKVILDYNTAHNKVALSECYTVASVAEMPQNYRP-HPQRF-TYcsQVLGLHCYKKGIHYWEVELQKNnFCGV 341
Cdd:cd12896   2 RAELWKDYRNLTFDPRTANKYLELSRQNRRAKHGRSAARGVPaSPGSFeLW--QVQCTQSFQHGHHYWEVEVSSH-SVTL 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6FLN_A      342 GICYGSM--NRQGPES-RLGRNSASWCVEWFNTKISAWHNNVEKTLPSTKATRVGVLLNCDHGFVIFFAVADKVHLMYKF 418
Cdd:cd12896  79 GVTYPGLprHKQGGHKdNIGRNPCSWGLQIQEDSLQAWHNGRAQKLQGVSYRLLGVDLDLEAGTLTFYGLEPGTQRLHTF 158

                       170       180
                ....*....|....*....|....*
6FLN_A      419 RVDFTEALYPAFWVFSaGATLSICS 443
Cdd:cd12896 159 HAIFTQPLYPVFWLLE-GRTLTLCH 182

PRY/SPRY domain of tripartite motif-binding protein 14 (TRIM14); This is a TRIM14 domain family 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. TRIM14 domains have yet to be characterized. These B30.2 domains are a more recent adaptation where the SPRY/PRY combination is a possible component of immune defense. It belongs to Class IV TRIM protein family which has members involved in antiviral immunity at various levels of interferon signaling cascade.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6FLN_A      275 ILDYNTAHNKVALSECYTVASVAEMPQNYRPHPQRFTYCSQVLGLHCYKKGIHYWEVELQkNNFCG--VGICYGSMNRQG 352
Cdd:cd13738   2 TLEPDTLHPRLRLSDDRLTVSCGWLGTLGLCPPQRFDKLWQVLSRDSFFSGRHYWEVDLQ-EAGAGwwVGAAYPSIGRKG 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6FLN_A      353 PE--SRLGRNSASWCVEWFNTKISAWHNNvEKT--LPSTKATRVGVLLNCDHGFVIFFAVADKVHLMYKFRVDFTEALYP 428
Cdd:cd13738  81 DSeaARLGWNRQSWCLKRYDLEYWAFHDG-QRSrlRPEDDPDRLGVFLDYEAGILSFYDVTGGMTHLHTFRATFQEPLYP 159

                       170
                ....*....|....*.
6FLN_A      429 AF--WvfsaGATLSIC 442
Cdd:cd13738 160 ALrlW----EGSISIC 171

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6FLN_A         324 KGIHYWEVELQKNNFCGVGICYGSMNRqGPESRLGRNSASWCVEWfNTKISAWHNNVEKTLPS--TKATRVGVLLNCDHG 401
Cdd:smart00449   1 SGRHYFEVEIGDGGHWRVGVATKSVPR-GYFALLGEDKGSWGYDG-DGGKKYHNSTGPEYGLPlqEPGDVIGCFLDLEAG 78

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
6FLN_A         402 FVIFFAVADKVHLMYKFRVDFTEALYPAFWVFSAG-ATLSICSP 444
Cdd:smart00449  79 TISFYKNGKYLHGLAFFDVKFSGPLYPAFSLGSGNsVRLNFGPL 122

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6FLN_A      273 KVILDYNTAHNKVALSE-CYTVaSVAEMPQNYRPHPQRFTYCSQVLGLHCYKKGIHYWEVELQKNNFCGVGICYGSMNRQ 351
Cdd:cd12888   1 NVTLDPDTAHPRLVLSEdRKSV-RWGDTRQDLPDNPERFDTWPCVLGCEGFTSGRHYWEVEVGDGGGWAVGVARESVRRK 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6FLN_A      352 GpESRLGRNSASWCVEWFNTKISAWHNNVEKTLPSTKATRVGVLLNCDHGFVIFFAVADKVHLmYKFRVDF--TEALYPA 429
Cdd:cd12888  80 G-EISFSPEEGIWAVGQWGGQYWALTSPETPLPLSEVPRRIRVYLDYEGGQVAFFDADNEAPI-FTFPPASfaGERIFPW 157

                       170
                ....*....|...
6FLN_A      430 FWVFSaGATLSIC 442
Cdd:cd12888 158 FWVGK-GSQLKLC 169

PRY/SPRY domain of tripartite motif-binding protein 60 and 75 (TRIM60 and TRIM75); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM60 and TRIM75, both composed of RING/B-box/coiled-coil core and also known as RBCC proteins. TRIM60 domain is also known as RING finger protein 33 (RNF33) or 129 (RNF129). Based on its expression profile, RNF33 likely plays an important role in the spermatogenesis process, the development of the pre-implantation embryo, and in testicular functions; Rnf33 is temporally transcribed in the unfertilized egg and the pre-implantation embryo, and is permanently silenced before the blastocyst stage. Mice experiments have shown that RNF33 associates with the cytoplasmic motor proteins, kinesin-2 family members 3A (KIF3A) and 3B (KIF3B), suggesting possible contribution to cargo movement along the microtubule in the expressed sites. TRIM75, also known as Gm794, has a single site of positive selection in its RING domain associated with E3 ubiquitin ligase activity. It has not been detectably expressed experimentally due to their constant turnover by the proteasome, and therefore not been characterized.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6FLN_A      274 VILDYNTAHNKVALSECYTVASVAEMPQNYRPHPQRFTYCSQVLGLHCYKKGIHYWEVELQKNNFCGVGICYGSM--NRQ 351
Cdd:cd15817   2 LILDPETAHPNLIVSEDRKAVRYRRMKPNCPYDPRRFTVYPAVLGSEGFDSGRHFWEVEVGGKGEWILGVCKDSLprNAQ 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6FLN_A      352 GPESRLGrnsASWCVEWFNTKISAWHNNVEKTLPSTKATRVGVLLNCDHGFVIFFAVADKVHLmYKFRVDFTEALYPAFW 431
Cdd:cd15817  82 DPPSPLG---GCWQIGRYMSGYVASGPKTTQLLPVVKPSRIGIFLDYELGEVSFYNMNDRSHL-YTFTDTFTGKLIPYFY 157

                       170
                ....*....|.
6FLN_A      432 VFSAGATLSIC 442
Cdd:cd15817 158 VGPDSEPLTIC 168

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6FLN_A      301 QNYRPHPQRFTYCSQVLGLHCYKKGIHYWEVELQKNNFCGVGICYGSMNRQGP--ESRLGRNSASWCVEWFNTKISAWHN 378
Cdd:cd12904  30 QSPPDDPERFDHWPNALASLSFSSGTHAWVVDVGKSCAYKVGVCYGSLERKGSgnEARLGYNAFSWVFSRYDGEFSFSHN 109

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....
6FLN_A      379 NVEKTLPSTKA-TRVGVLLNCDHGFVIFFAvADKVHLMYKFRVDFTEALYPAFWVfsAGATLSI 441
Cdd:cd12904 110 GQHVPLELLKCpARVGVLLDWPSQELLFYD-PDSCTVLHSHREAFAAPLLPVFAV--ADQSISI 170

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6FLN_A      274 VILDYNTAHNKVALSECYTVASVAEMPQNYRPHPQRFTYCSQVLGLHCYKKGIHYWEVELQKNNFCGVGICYGSMNRQGp 353
Cdd:cd13745   5 VTLDPDTAHPNLVLSEDRKSVRHGDTRQDLPDNPERFDTYPCVLGAEGFTGGRHYWEVEVGDKTEWTLGVCRESVSRKG- 83

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6FLN_A      354 ESRLGRNSASWCVEWFNTKISAWHNNVEKTLPSTKATRVGVLLNCDHGFVIFFAVADKVHLmYKFRVDFTEALYPAFWV- 432
Cdd:cd13745  84 EVTLSPENGYWTVWLRDGKYEALTSPPTPLPVSVRPSRVGIFLDYEAGEVSFYNVTDRSHL-FTFTDTFSGTLRPYFYPg 162

                       170
                ....*....|....*
6FLN_A      433 FSAGAT----LSICS 443
Cdd:cd13745 163 LNAGGKnaapLIICP 177

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6FLN_A      274 VILDYNTAHNKVALSECYTVASVAEMPQNYRPHPQRFTYCSQVLGLHCYKKGIHYWEVELQKNNFCGVGICYGSMNRQG- 352
Cdd:cd15819   4 VTLDPDTAHPALILSEDGRSVTWGETRQDLPENPERFDSLPCVLGQEGFTSGRHYWEVEVGDRTSWDLGVCRDNVMRKGr 83

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6FLN_A      353 ----PESRLgrnsasWCVEWFNTKISAWhnnvekTLPSTKAT------RVGVLLNCDHGFVIFFAVADKVHLmYKF-RVD 421
Cdd:cd15819  84 vtlsPENGF------WAIRLYGNEYWAL------TSPETPLTlkepprRVGIFLDYEAGDVSFYNMTDGSHI-YTFpQTA 150

                       170       180
                ....*....|....*....|..
6FLN_A      422 FTEALYPAFWVFSAG-ATLSIC 442
Cdd:cd15819 151 FSGPLRPFFRLWSSDsGPLTIC 172

PRY/SPRY domain of butyrophilin 3 (BTN3), includes BTN3A1, BTN3A2, BTN3A3 as well as BTN-like 3 (BTNL3); BTN3A also known as CD277; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of butyrophilin family 3A (BTN3A); duplication events have led to three paralogs in primates: BTN3A1, BTN3A2, and BTN3A3. BTNs belong to receptor glycoproteins of immunoglobulin (Ig) superfamily, characterized by the presence of extracellular Ig-like domains (IgV and/or IgC). BTN3 transcripts are ubiquitously present in all immune cells (T cells, B cells, NK cells, monocytes, dendritic cells, and hematopoietic precursors) with different expression levels; BTN3A1 and BTN3A2 are expressed mainly by CD4+ and CD8+ T cells, BTN3A2 is the major form expressed in NK cells, and BTN3A3 is poorly expressed in these immune cells. The PRY/SPRY domain of the BTN3A1 isoform mediates phosphoantigen (pAg)-induced activation by binding directly to the pAg.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6FLN_A      274 VILDYNTAHNKVALSECYTVASVAEMPQNYRPHPQRFTYCSQVLGLHCYKKGIHYWEVELQKNNFCGVGICYGSMNRQGP 353
Cdd:cd15820   6 VILDPDTANPILLISEDQRSLQWADEPQNLPDNPKRFDWHYCVLGCKSFTSGRHFWEVEVGDRKEWYVGVCRENVERKLW 85

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6FLN_A      354 ESRLGRNsASWCVEwfntkISAWHNNVEKTLPSTKAT------RVGVLLNCDHGFVIFFAVADKVHLMYKFRVDFTEALY 427
Cdd:cd15820  86 VKMAPEN-GFWTIG-----LSDGNDYQALTDPRTKLTianppqRVGVFLDYETGEVSFYNAMDGSHIYTFPHTSFSGPLY 159

                       170
                ....*....|....*.
6FLN_A      428 PAFWVFSAGAT-LSIC 442
Cdd:cd15820 160 PVFRLLSWDPTaLTIC 175

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6FLN_A      274 VILDYNTAHNKVALSECYTVASVAEMPQNYRPHPQRFTYCSQVLGLHCYKKGIHYWEVELQKNNFCGVGICYGSMNRQG- 352
Cdd:cd12905   6 LTFDPETAHPSLILSRDLTAVTESDEMQPYPRSPKRFLQCVNVLASQGFQSGRHYWEVWVGSKTKWDLGVASESVDRQAr 85

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6FLN_A      353 ----PES-----RLgRNSASWcveWFNTkiSAWhnnvEKTLPSTKATRVGVLLNCDHGFVIFFAvADKVHLMYKFRVDFT 423
Cdd:cd12905  86 vklcPENgywtlRL-RNGDEY---WAGT--QPW----TRLRVTSRPQRIGVFLDCEERKVSFYN-ADDMSLLYSFHQGPR 154

                ....*..
6FLN_A      424 EALYPAF 430
Cdd:cd12905 155 GKVFPFF 161

PRY/SPRY domain in tripartite motif-binding protein 15 (TRIM15); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of tripartite motif-containing protein 15 (TRIM15), also referred to as RING finger protein 93 (RNF93) or Zinc finger protein B7 or 178 (ZNFB7 or ZNF178). TRIM15 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. The PRY and SPRY/B30.2 domains can function as immune defense components and in pathogen sensing. TRIM15 has been shown to regulate inflammatory and innate immune signaling, in addition to displaying antiviral activities. Down-regulation of TRIM15, as well as TRIM11, enhances virus release, suggesting that these proteins contribute to the endogenous restriction of retroviruses in cells. TRIM15 is also a regulatory component of focal adhesion turnover and cell migration.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6FLN_A      274 VILDYNTAHNKVALSECYTVASVAEMPQNYRPHPQRFTYCSQVLGLHCYKKGIHYWEVELQKNNF--CGVGICYGSMNRQ 351
Cdd:cd15826   2 VTLDPQTASGSLVLSEDRKSVRYTRQKQNLPDSPLRFDGLPAVLGSPGFSSGRHRWQVEVQLGDGggCTVGVAGESVRRK 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6FLN_A      352 GpESRLGRNSASWCVEWFNTKIsaWHNNVEKT--LPSTKATRVGVLLNCDHGFVIFFAvADKVHLMYKFRVDFTEALYPA 429
Cdd:cd15826  82 G-EMGLSAEDGVWAVILSHQQC--WASTSPGTdlPLSEIPRRVGVALDYEAGTVTLTN-AETQEPIFTFTASFSGKVFPF 157

                       170
                ....*....|..
6FLN_A      430 FWVFSAGATLSI 441
Cdd:cd15826 158 FAVWKKGSRLTL 169

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6FLN_A      276 LDYNTAHNKVALSECYTVASVAEMPQNYRPHPQRFTYCSQ--VLGLHCYKKGIHYWEVELQKNNFCGVGICYGSMNRQgp 353
Cdd:cd12892   4 LDPKSAHRKLKVSHDNLTVERDETSSKKSHTPERFTSQGSygVAGNVFIDSGRHYWEVVISGSTWYAIGIAYKSAPKH-- 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6FLN_A      354 eSRLGRNSASWCVEWFNTKISAWHNNVEKTL-PSTKATRVGVLLNCDHGFVIFFAVADKVHLmYKFRVDFTEALYPAFWV 432
Cdd:cd12892  82 -EWIGKNSASWVLCRCNNNWVVRHNSKEIPIePSPHLRRVGILLDYDNGSLSFYDALNSIHL-YTFDIAFAQPVCPTFTV 159

                ....*..
6FLN_A      433 FSAGATL 439
Cdd:cd12892 160 WNKCLTI 166

PRY/SPRY domain in tripartite motif-binding protein 62 (TRIM62); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM62. It is also called DEAR1 ductal epithelium (associated RING chromosome 1) and is involved in the morphogenesis of the mammary gland; loss of TRIM62 gene expression in breast is associated with increased risk of recurrence in early-onset breast cancer and thus, making TRIM62 a predictive biomarker. Non-small cell lung cancer lesions show a step-wise loss of TRIM62 levels during disease progression, indicating that it may play a role in the evolution of lung cancer. Decreased levels of TRIM62 also represent an independent adverse prognostic factor in AML.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6FLN_A      276 LDYNTAHNKVALSE-CYTVASVAEMPQNYRPHPQRFTYCSQVLGLHCYKKGIHYWEVELQKNNFCGVGICYGSMNRQGP- 353
Cdd:cd13744  16 LDPVTAHQRLILSDdCTIVAYGNLHPQPLQDSPKRFDVEVSVLGSEGFSGGVHYWEVVVSEKTQWMIGLAHEAVSRKGSi 95

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6FLN_A      354 ESRLGR----------NSASWCVE-WfnTKIsawhnNVEktlpsTKATRVGVLLNCDHGFVIFFAvADKVHLMYKFRVDF 422
Cdd:cd13744  96 QIQPGRgfycivmhdgNQYSACTEpW--TRL-----NVK-----SKLEKVGVYLDYDKGLLIFYN-ADDMSWLYTFREKF 162

                ....*...
6FLN_A      423 TEALYPAF 430
Cdd:cd13744 163 PGKLCSYF 170

PRY/SPRY domain in tripartite motif-containing protein 76 (TRIM76), also called cardiomyopathy-associated protein 5; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM76, a Class I TRIM protein. TRIM76 (also known as cardiomyopathy-associated protein 5 or CMYA5 or myospryn or SPRYD2) is a muscle-specific member of the TRIM superfamily, but lacks the RING domain. It has been suggested that TRIM76 is involved in two distinct processes, protein kinase A signaling and vesicular trafficking. It has also been implicated in Duchenne muscular dystrophy and cardiac disease; gene polymorphism of TRIM76 is associated with left ventricular wall thickness in patients with hypertension while its interactions with M-band titin and calpain 3 link it to tibial and limb-girdle muscular dystrophies.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
6FLN_A      280 TAHNKVALSECYTvaSVAEMPQNYRPHPQrFTYCSQVLGLHCYKKGIHYWEVELQKNNFCGVGICYGSMNRQGPesrLGR 359
Cdd:cd12898  10 TAHPALHISSDRG--TVIYFHERRRKMSS-LTECPSVLGEELPSCGQYYWETTVTRCPAYRLGICSSSASQAGA---LGE 83