TRIM C-terminal subgroup One Signature domain; This domain is found in the C-terminal region of the TRIM subgroup C-1 proteins such as E3 ubiquitin-protein ligase Midline-1 protein which is required for the proper development during embryogenesis. Mutations of MID1 are associated with X-linked Opitz G syndrome, characterized by midline anomalies. This domain is also found in MURF1-3 proteins that do not contain the FNIII and B30.2 domains. MUF1-3 proteins are also associated with microtubules. Deletion of the COS domain does not affect MID1 dimerization but disrupts the localization to the microtubules.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 569011765   56 NDHARFLQTAKNITERVSMATASSQVLIPEINLNDTFDTFALDFSREKKLLE 107
Cdd:pfam18568   1 TDHARFLQTAKNVHERVSMATASSQVLIPDINLNDAFENFALDFSREKKLLE 52

coiled-coil (CC) domain of Drosophila brain tumor (brat) and similar proteins; This family contains the coiled-coil (CC) region of Drosophila brain tumor (Brat), a translational repressor that belongs to the tripartite motif (TRIM) protein superfamily. TRIM proteins play important roles in various cellular processes and are involved in many diseases which consists of two B-box domains and a coiled-coil (CC) domain at the N-terminal region, and an NHL domain at the C-terminus. Brat localizes at the basal cortex during asymmetric division of Drosophila neuroblasts by directly interacting with the scaffolding protein Miranda (Mira), which it does through the CC-NHL domain tandem, indicating that the function of the Brat CC domain is to assemble Brat-NHL in dimeric form which is necessary for Mira binding. Brat CC forms an elongated antiparallel dimer similar to its other TRIM protein counterparts, but the overall length of Brat CC dimer is shorter than the TRIMs.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 569011765    24 RLRKLAQQIANCKQCLERSASLISQAEHSLKENDHARFLQTAKNITERVSMATA 77
Cdd:smart00502  73 KLKVLEQQLESLTQKQEKLSHAINFTEEALNSGDPTELLLSKKLIIERLQNLLK 126

TRIM C-terminal subgroup One Signature domain; This domain is found in the C-terminal region of the TRIM subgroup C-1 proteins such as E3 ubiquitin-protein ligase Midline-1 protein which is required for the proper development during embryogenesis. Mutations of MID1 are associated with X-linked Opitz G syndrome, characterized by midline anomalies. This domain is also found in MURF1-3 proteins that do not contain the FNIII and B30.2 domains. MUF1-3 proteins are also associated with microtubules. Deletion of the COS domain does not affect MID1 dimerization but disrupts the localization to the microtubules.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 569011765   56 NDHARFLQTAKNITERVSMATASSQVLIPEINLNDTFDTFALDFSREKKLLE 107
Cdd:pfam18568   1 TDHARFLQTAKNVHERVSMATASSQVLIPDINLNDAFENFALDFSREKKLLE 52

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 569011765  286 RHYWEVV--TSGSTWYAIGLAYRSAP--KHEWIGKNAASWALCRC--HNHWAVRHDGKETPIAPAPhlRRVGVLLDYDNG 359
Cdd:pfam00622   1 RHYFEVEifGQDGGGWRVGWATKSVPrkGERFLGDESGSWGYDGWtgKKYWASTSPLTGLPLFEPG--DVIGCFLDYEAG 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 569011765  360 SIAFYDALSSvHLHTFH-AALAQPVCPTFTV-WNKCLTIVTGLP 401
Cdd:pfam00622  79 TISFTKNGKS-LGYAFRdVPFAGPLFPAVSLgAGEGLKFNFGLR 121

Fibronectin type 3 domain; One of three types of internal repeat within the plasma protein, fibronectin. The tenth fibronectin type III repeat contains a RGD cell recognition sequence in a flexible loop between 2 strands. Type III modules are present in both extracellular and intracellular proteins.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011765   130 DTITVHWTSEDEFSVVSYELQYTIFTGQANvvnvacdgtcllgsaglcnsaDSWMIVP-NIKQNHYTVHGLQSGTKYIFT 208
Cdd:smart00060  15 TSVTLSWEPPPDDGITGYIVGYRVEYREEG---------------------SEWKEVNvTPSSTSYTLTGLKPGTEYEFR 73

                   ....*....
gi 569011765   209 VKAINQAGS 217
Cdd:smart00060  74 VRAVNGAGE 82

Fibronectin type 3 domain [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011765 113 TAPNPPAireELcTASYDT---ITVHWTSEDEFSVVSYELQYTIftgqanvvnvacdgtcllgsaglcNSADSWMIVPNI 189
Cdd:COG3401  231 TPPSAPT---GL-TATADTpgsVTLSWDPVTESDATGYRVYRSN------------------------SGDGPFTKVATV 282

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 569011765 190 KQNHYTVHGLQSGTKYIFTVKAINQAGSRS--SEPGKLKTNSQP 231
Cdd:COG3401  283 TTTSYTDTGLTNGTTYYYRVTAVDAAGNESapSNVVSVTTDLTP 326

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011765 232 FRLDPKSAHRKLKVSHDNLTVERDESSSKKSHAPERFAGQGSYGVAGNVFIDSGRHYWEVVTSGSTWYAIGLAYRSAPKH 311
Cdd:cd13739    1 FKLDPKMAHKKLKISNDGLQMEKDESSLKKSHTPERFSGTGCYGAAGNIFIDSGCHYWEVVVGSSTWYAIGIAYKSAPKN 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011765 312 EWIGKNAASWALCRCHNHWAVRHDGKETPIAPAPHLRRVGVLLDYDNGSIAFYDALSSVHLHTFHAALAQPVCPTFTVWN 391
Cdd:cd13739   81 EWIGKNSSSWVFSRCNNNFVVRHNNKEMLVDVPPQLKRLGVLLDYDNNMLSFYDPANSLHLHTFEVSFILPVCPTFTIWN 160

                        170
                 ....*....|
gi 569011765 392 KCLTIVTGLP 401
Cdd:cd13739  161 KSLMILSGLP 170

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011765 234 LDPKSAHRKLKVSHDNLTVERDESSSKKSHAPERFAgqgSYGVAGNVFIDSGRHYWEVVTSGSTWYAIGLAYRSAPKHE- 312
Cdd:cd12891    3 LDPNTAHNNLALSGDLKTVTCSSENQHYPDSPERFT---HSQVLSTQSFSSGRHYWEVEVSESGGWSVGVAYPSIERKGd 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011765 313 --WIGKNAASWALCRCHNHWAVRHDGKETPIAPAPHlRRVGVLLDYDNGSIAFYDALSSV-HLHTFHAALAQPVCPTFTV 389
Cdd:cd12891   80 esRIGRNDKSWCLEWQDKSFSAWHNNEETPLPSVSS-RRLGVYLDYEAGRLSFYELSDPIrHLHTFTATFTEPLHPAFWV 158

                 ....*...
gi 569011765 390 W-NKCLTI 396
Cdd:cd12891  159 LeGGWIRI 166

Fibronectin type III and SPRY containing 1 (FSD1) domain includes PRY at the N-terminus; This domain is part of the fibronectin type III and SPRY domain containing 1 (FSD1) and FSD1-like (FSD1L) proteins. These are centrosome-associated proteins that are characterized by an N-terminal coiled-coil region downstream of B-box (BBC) domain, a central fibronectin type III (FN3) domain, and C-terminal repeats in PRY/SPRY domain. The FSD1 protein associates with a subset of microtubules and may be involved in the stability and organization of microtubules during cytokinesis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011765 232 FRLDPKSAHRKLKVshDNLTVERDESSSK------------KSHAP----------------------ERFAGQgSYGVA 277
Cdd:cd12901    1 FKLDASSSHQNLKV--EDLSVEWDATGGKvlqkikgrendgRSRTAsprnssarcqspkrmpsarggrDRFTAE-SYTVL 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011765 278 GNVFIDSGRHYWEV-VTSGSTWYAIGLAYRSAPKHEWIGKNAASWALcrcH-NHW-----AVRHDGKETPI-APAPHlrR 349
Cdd:cd12901   78 GDTLIDGGQHYWEVrAQKDSKAFSVGVAYRSLGKFDQLGKTNASWCL---HvNNWlqnsfAAKHNNKAKTLdVPVPD--R 152

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 569011765 350 VGVLLDYDNGSIAFYDALSSVHLHTFHAALAQPVCPTFTVWNKCLTIVTGLPIPD 404
Cdd:cd12901  153 IGVYCDFDEGQLSFYNARTKQLLHTFKMKFTQPVLPAFMVWCGGLSVSTGLQVPS 207

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 569011765 231 PFRLDPKSAHRKLKVSHDNLTVERDESSSKKSHAPERFagQGSYGVAGNVFIDSGRHYWEVVTSGSTWYAIGLAYRSAPK 310
Cdd:cd13733    1 DVTLDPDTAHPNLILSEDLKSVRYGDKRQNLPDNPERF--DTCVCVLGSEGFSSGRHYWEVEVGGKTDWDLGVARESVNR 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011765 311 HEWIGKNAAS--WALCRCHNH--WAvrHDGKETPIAPAPHLRRVGVLLDYDNGSIAFYDALSSVHLHTFHAALAQPVCPT 386
Cdd:cd13733   79 KGKITLSPENgyWTVGLRNGNeyKA--LTSPSTPLSLREKPQKVGVFLDYEEGQVSFYNVDDGSHIYTFTDCFTEKLYPY 156

                 .
gi 569011765 387 F 387
Cdd:cd13733  157 F 157

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011765 234 LDPKSAHRKLKVSHDNLTVERDESSSKKSHAPERFagQGSYGVAGNVFIDSGRHYWEV--VTSGSTWYaIGLAYRS---- 307
Cdd:cd13738    3 LEPDTLHPRLRLSDDRLTVSCGWLGTLGLCPPQRF--DKLWQVLSRDSFFSGRHYWEVdlQEAGAGWW-VGAAYPSigrk 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011765 308 -APKHEWIGKNAASWALCRCHNHWAVRHDGKETPIAPAPHLRRVGVLLDYDNGSIAFYDALSSV-HLHTFHAALAQPVCP 385
Cdd:cd13738   80 gDSEAARLGWNRQSWCLKRYDLEYWAFHDGQRSRLRPEDDPDRLGVFLDYEAGILSFYDVTGGMtHLHTFRATFQEPLYP 159

                        170
                 ....*....|.
gi 569011765 386 TFTVWNKCLTI 396
Cdd:cd13738  160 ALRLWEGSISI 170

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 569011765 234 LDPKSAHRKLKVSHDNLTVERDESSSKKSHAPERFAGqgSYGVAGNVFIDSGRHYWEV-VTSGSTWyAIGLAYRSAPKHE 312
Cdd:cd12888    4 LDPDTAHPRLVLSEDRKSVRWGDTRQDLPDNPERFDT--WPCVLGCEGFTSGRHYWEVeVGDGGGW-AVGVARESVRRKG 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011765 313 WIGKNAAS--WALCRCHN-HWAVRHDGKETPIAPAPhlRRVGVLLDYDNGSIAFYDALSSVHLHTFHAA--LAQPVCPTF 387
Cdd:cd12888   81 EISFSPEEgiWAVGQWGGqYWALTSPETPLPLSEVP--RRIRVYLDYEGGQVAFFDADNEAPIFTFPPAsfAGERIFPWF 158

                 ...
gi 569011765 388 TVW 390
Cdd:cd12888  159 WVG 161

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 569011765 231 PFRLDPKSAHRKLKVShDNLTVERDesSSKKSHA---PERFagQGSYGVAGNVFIDSGRHYWEVVTSGSTWYAIGLAYRS 307
Cdd:cd12893    1 PVTLDPNTAHPWLSLS-EDLTSVRY--SSEKQQLpdnPERF--DPYPCVLGSEGFTSGKHSWDVEVGDNTSWMLGVAKES 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011765 308 APKHEWIGKNAAS--WALCRCHNHWAVRHDGKE-TPIAPAPHLRRVGVLLDYDNGSIAFYDALSSVHLHTFHAALAQPVC 384
Cdd:cd12893   76 VQRKGKFTLSPESgfWTIGFSEGKYSARTSPEPrTPLRVKQKPQRIRVQLDWDRGKVSFSDPDTNTHIHTFTHTFTERVF 155

                 ....*...
gi 569011765 385 PTFTVWNK 392
Cdd:cd12893  156 PYFYTGCK 163

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 569011765 234 LDPKSAHRKLKVSHDNLTVERDESSSKKSHAPERFAGqgSYGVAGNVFIDSGRHYWEVVTSGSTWYAIGLAYRSAPKHEW 313
Cdd:cd13741    4 LDPDTAHPALLLSPDRRGVRLAERRQEVPEHPKRFSA--DCCVLGAQGFRSGRHYWEVEVGGRRGWAVGAARESTHHKEK 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011765 314 IGKNAASW----ALCRCHNH-----------------WAVRHDGK---------ETPIAPAPHLRRVGVLLDYDNGSIAF 363
Cdd:cd13741   82 VGSGGSSVssgdASSSRHHHrrrrlhlpqqpllqrevWCVGTNGKryqaqssteQTLLSPSEKPRRFGVYLDYEAGRLGF 161

                        170       180       190
                 ....*....|....*....|....*....|
gi 569011765 364 YDALSSVHLHTFHAA-LAQPVCPTFTVWNK 392
Cdd:cd13741  162 YNAETLAHVHTFSAAfLGERVFPFFRVLSK 191

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 569011765 231 PFRLDPKSAHRKLKVSHDNLTVERDESSSKKSHAPERFagQGSYGVAGNVFIDSGRHYWEVVTSGSTWYAIGLAyrsapk 310
Cdd:cd12905    5 PLTFDPETAHPSLILSRDLTAVTESDEMQPYPRSPKRF--LQCVNVLASQGFQSGRHYWEVWVGSKTKWDLGVA------ 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011765 311 HEWIGKnAASWALCRCHNHWAVR-HDGKE--------TPIAPAPHLRRVGVLLDYDNGSIAFYDALSSVHLHTFHAALAQ 381
Cdd:cd12905   77 SESVDR-QARVKLCPENGYWTLRlRNGDEywagtqpwTRLRVTSRPQRIGVFLDCEERKVSFYNADDMSLLYSFHQGPRG 155

                 ....*..
gi 569011765 382 PVCPTFT 388
Cdd:cd12905  156 KVFPFFS 162

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 569011765 234 LDPKSAHRKLKVSHDNLTVERDESSSKKSHAPERFAGQGSygVAGNVFIDSGRHYWEVvtsgstwyAIGlayrsapkhew 313
Cdd:cd15819    6 LDPDTAHPALILSEDGRSVTWGETRQDLPENPERFDSLPC--VLGQEGFTSGRHYWEV--------EVG----------- 64

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011765 314 igkNAASWALCRCHNH---------------WAVRHDGKE--------TPIAPAPHLRRVGVLLDYDNGSIAFYDALSSV 370
Cdd:cd15819   65 ---DRTSWDLGVCRDNvmrkgrvtlspengfWAIRLYGNEywaltspeTPLTLKEPPRRVGIFLDYEAGDVSFYNMTDGS 141

                        170       180       190
                 ....*....|....*....|....*....|.
gi 569011765 371 HLHTF-HAALAQPVCPTFTVWN---KCLTIV 397
Cdd:cd15819  142 HIYTFpQTAFSGPLRPFFRLWSsdsGPLTIC 172

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 569011765 234 LDPKSAHRKLKVSHDNLTVERDESSSKKSHAPERFAGQGsyGVAGNVFIDSGRHYW--EVVTSGSTWYAIGLAYRSAPKH 311
Cdd:cd15826    4 LDPQTASGSLVLSEDRKSVRYTRQKQNLPDSPLRFDGLP--AVLGSPGFSSGRHRWqvEVQLGDGGGCTVGVAGESVRRK 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011765 312 EWIGKNAAS--WALCRCHNH-WAVRHDGKETPIAPAPhlRRVGVLLDYDNGSIAFYDALSSVHLHTFHAALAQPVCPTFT 388
Cdd:cd15826   82 GEMGLSAEDgvWAVILSHQQcWASTSPGTDLPLSEIP--RRVGVALDYEAGTVTLTNAETQEPIFTFTASFSGKVFPFFA 159

                        170
                 ....*....|
gi 569011765 389 VWNK--CLTI 396
Cdd:cd15826  160 VWKKgsRLTL 169

Ret finger protein-like (RFPL), includes RFP1, 2, 3, 4; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of RFPL protein family, which includes RFPL1, RFPL2, RFPL3 and RFPL4. In humans, RFPL transcripts can be detected at the onset of neurogenesis in differentiating human embryonic stem cells, and in the developing human neocortex. The human RFPL1, 2, 3 genes have a role in neocortex development. RFPL1 is a primate-specific target gene of Pax6, a key transcription factor for pancreas, eye and neocortex development; human RFPL1 decreases cell number through its RFPL-defining motif (RDM) and SPRY domains. The RFPL4 (also known as RFPL4A) gene encodes a putative E3 ubiquitin-protein ligase expressed in adult germ cells and interacts with oocyte proteins of the ubiquitin-proteasome degradation pathway.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011765 234 LDPKSAHRKLKVSHDNLTVERDESSSKKSHAPERFagQGSYGVAGNVFIDSGRHYWEVVTSGSTWYAIGLAYRSAPKHEW 313
Cdd:cd15821    8 LDVDTANNYLIISEDLRSVRCGCFRQNRKELAERF--DDALCVLGSPRFTSGRHYWEVDVGTSTEWDLGVCRESVNRQGP 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011765 314 IgknaaswALCRCHNHWAVRHDGKE---------TPIAPAPHLRRVGVLLDYDNGSIAFYDALSSVHLHTFHAALAQ-PV 383
Cdd:cd15821   86 I-------ELSPEHGFWTVSLRDGSvffastvplTVLWVNPRLHRVGIFLDMEMGTISFYDVSDGSHIFTFTKISAEePL 158

                 ....
gi 569011765 384 CPTF 387
Cdd:cd15821  159 RPFF 162

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011765 232 FRLDPKSAHRKLKVSHDNLTV----ERDESSSKKSHAPErfagqgsygVAGNVFIDSGRHYWEVVTSGSTWYAIGLAYRS 307
Cdd:cd12898    4 FLLLRETAHPALHISSDRGTViyfhERRRKMSSLTECPS---------VLGEELPSCGQYYWETTVTRCPAYRLGICSSS 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011765 308 APKHEWIGKNAASWAL--------CRCHnhwaVRHDGKETPIAPAPHLRRVGVLLDYDNGSIAFYDALSSVHLHTFHAAL 379
Cdd:cd12898   75 ASQAGALGEGSTSWCLhcvptsepCRYT----LLHSGIVSDVFVTERPARVGTLLDYNNGRLIFINAESGQLLGIFRHRF 150

                 ....*...
gi 569011765 380 AQPVCPTF 387
Cdd:cd12898  151 AQPCHPAF 158

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 569011765 234 LDPKSAHRKLKVSHDNLTVERDESSSKKSHAPERFAgqgSYG-VAGNVFIDSGRHYWEVVTSGSTWYAIGLAYRSAPKHE 312
Cdd:cd13745    7 LDPDTAHPNLVLSEDRKSVRHGDTRQDLPDNPERFD---TYPcVLGAEGFTGGRHYWEVEVGDKTEWTLGVCRESVSRKG 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011765 313 WIgknaaswALCRCHNHWAVRHDGKE--------TPIAPAPHLRRVGVLLDYDNGSIAFYDALSSVHLHTFHAALAQPVC 384
Cdd:cd13745   84 EV-------TLSPENGYWTVWLRDGKyealtsppTPLPVSVRPSRVGIFLDYEAGEVSFYNVTDRSHLFTFTDTFSGTLR 156

                 ...
gi 569011765 385 PTF 387
Cdd:cd13745  157 PYF 159

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011765 234 LDPKSAHRKLKVSHDNLTVERDESSSKKSHAPERFAGQGSygVAGNVFIDSGRHYWEVVTSGSTWYAIGLAYRSAPKHEW 313
Cdd:cd15817    4 LDPETAHPNLIVSEDRKAVRYRRMKPNCPYDPRRFTVYPA--VLGSEGFDSGRHFWEVEVGGKGEWILGVCKDSLPRNAQ 81

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 569011765 314 I--GKNAASWALCRCHNHWAVrHDGKETPIAPAPHLRRVGVLLDYDNGSIAFYDALSSVHLHTFHAALAQPVCPTFTV 389
Cdd:cd15817   82 DppSPLGGCWQIGRYMSGYVA-SGPKTTQLLPVVKPSRIGIFLDYELGEVSFYNMNDRSHLYTFTDTFTGKLIPYFYV 158

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 569011765 231 PFRLDPKSAHRKLKVSHDNLTVERDESSSKKSHAPERFagQGSYGVAGNVFIDSGRHYWEVVTSGSTWYAIGLAYRSAPK 310
Cdd:cd15818   14 LITLDPKTAHPNLILSEDLTCVWHGDTKQMLPDNPERF--DSSVAVLGSEGFTSGKHYWEVEVAKKTKWTLGVVRESINR 91

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569011765 311 HewigknaASWALCRCHNHWAVR----HDGKETPIAP-----APHLRRVGVLLDYDNGSIAFYDALSSVHLHTFHAALAQ 381
Cdd:cd15818   92 K-------GNCPLSPEDGFWLLRlrnqNELKALDVPSfsltlTSNLNKVGIYLDYEGGQVSFYNANTMSHIYTFSDTFTE 164

                 ....*.
gi 569011765 382 PVCPTF 387
Cdd:cd15818  165 KIYPYF 170