Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671499  52 VADNSVTVAWRMPEEDN-KIDHFILEHRKTNFDGlprvkdercWEIIDN--IKGTEYTLSGLKFDSKYmNFRVRACNKAV 128
Cdd:cd00063    12 VTSTSVTLSWTPPEDDGgPITGYVVEYREKGSGD---------WKEVEVtpGSETSYTLTGLKPGTEY-EFRVRAVNGGG 81

                          90
                  ....*....|..
gi 1034671499 129 AGEYSDPVTLET 140
Cdd:cd00063    82 ESPPSESVTVTT 93

Domain in SPla and the RYanodine Receptor; Domain of unknown function. Distant homologues are domains in butyrophilin/marenostrin/pyrin homologues.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671499  236 SGQHYWEVKAQKDcKSYSVGVAYKT--LGKFDQLGKTNTSWCIH---VNNWlqntfaakHNNKVKALDVTVPEK---IGV 307
Cdd:smart00449   1 SGRHYFEVEIGDG-GHWRVGVATKSvpRGYFALLGEDKGSWGYDgdgGKKY--------HNSTGPEYGLPLQEPgdvIGC 71

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 1034671499  308 FCDFDGGQLSFYDANSKQLLYSFKT-KFTQPVLPGFMVWCGG 348
Cdd:smart00449  72 FLDLEAGTISFYKNGKYLHGLAFFDvKFSGPLYPAFSLGSGN 113

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 1034671499 239 HYWEVKAQKDCK-SYSVGVAYKT--LGKFDQLGKTNTSWCIHVNN---WLQNTFAAKHNNKVKALDVtvpekIGVFCDFD 312
Cdd:pfam00622   2 HYFEVEIFGQDGgGWRVGWATKSvpRKGERFLGDESGSWGYDGWTgkkYWASTSPLTGLPLFEPGDV-----IGCFLDYE 76

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1034671499 313 GGQLSFYDaNSKQLLYSFKT-KFTQPVLPGF 342
Cdd:pfam00622  77 AGTISFTK-NGKSLGYAFRDvPFAGPLFPAV 106

Fibronectin type 3 domain [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671499  54 DNSVTVAWRmPEEDNKIDHFILEhRKTNFDGlprvkderCWEIIDNIKGTEYTLSGLKFDSKYmNFRVRACNKA-VAGEY 132
Cdd:COG3401   246 PGSVTLSWD-PVTESDATGYRVY-RSNSGDG--------PFTKVATVTTTSYTDTGLTNGTTY-YYRVTAVDAAgNESAP 314

                  ....*...
gi 1034671499 133 SDPVTLET 140
Cdd:COG3401   315 SNVVSVTT 322

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671499 145 FNLDNSSSHLNLKVED--TCVEWDPTGGKGQESkikgkenkgsvhvtslkkhtrsgtpspkrtsvgsrppavrgSRDRFT 222
Cdd:cd13734     1 FKLDPKTAHRKLRLSNdnLTVEYDPEGSKDQAA-----------------------------------------VLPRRF 39

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671499 223 GESYTVLGDTAIESGQHYWEVKAQKDCkSYSVGVAYKTLGKFDQLGKTNTSWCIHVNNwlqNTFAAKHNNKVKALDVTV- 301
Cdd:cd13734    40 TGSPAVLGDVAISSGRHYWEVSVSRST-SYRVGVAYKSAPRDEDLGKNSTSWCLSRDN---NRYTARHDGKVVDLRVTGh 115

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 1034671499 302 PEKIGVFCDFDGGQLSFYDANSKQLLYSFKTKFTQPVLPGFMVWCGGLSL 351
Cdd:cd13734   116 PARIGVLLDYDNGTLSFYDAESKQHLYTFHVDFEGPVCPAFAVWNGSLTL 165

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 1034671499 203 KRTSVGSRPPAVRGSRDRFTgeSYTVLGDTAIESGQHYWEVKAQKdCKSYSVGVAYKTL---GKFDQLGKTNTSWCIHVN 279
Cdd:cd12891    19 KTVTCSSENQHYPDSPERFT--HSQVLSTQSFSSGRHYWEVEVSE-SGGWSVGVAYPSIerkGDESRIGRNDKSWCLEWQ 95

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671499 280 NwlqNTFAAKHNNKVKALDVTVPEKIGVFCDFDGGQLSFYD-ANSKQLLYSFKTKFTQPVLPGFMVWCGG 348
Cdd:cd12891    96 D---KSFSAWHNNEETPLPSVSSRRLGVYLDYEAGRLSFYElSDPIRHLHTFTATFTEPLHPAFWVLEGG 162

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 1034671499 199 TPSPKRTSVGSRPPAVRGSRDRFTGESytVLGDTAIESGQHYWEVKAQKdCKSYSVGVAYKTLGKFDQLGKTNTSWCIHV 278
Cdd:cd12902    15 SEDSRKVTVSHGPQAYAWSPDRFSISQ--VLCSQAFSSGQHYWEVDTRQ-CSHWAVGVASWEMSRDQMLGRTMDSWCIEW 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671499 279 NNWLQntFAAKHNNKVKALDVTVPEKIGVFCDFDGGQLSFYD-ANSKQLLYSFKTKFTQPVLPGFmvWCGGLSLSTGMQV 357
Cdd:cd12902    92 KGTGQ--LSAWHMNKETVLGSDKPRVVGIWLDLEEGKLAFYSvANQERLLHECEVSASSPLHPAF--WLYGLEPGNSLII 167

                  .
gi 1034671499 358 P 358
Cdd:cd12902   168 K 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 1034671499 236 SGQHYWEVkaQKDCKSYSVGVAYKTL---GKFDQ--LGKTNTSWCIhvnNWLQNTFAAKHNNKVKALDVTVPE--KIGVF 308
Cdd:cd16040    60 SGRCYWEV--EWSGGGVDIAVAYKGIsrkGDGDDsrFGYNDKSWSL---ECSPSGYSFWHNNKKTEISVPSSSssRVGVY 134

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1034671499 309 CDFDGGQLSFYDANSK-QLLYSFKTKFTQPVLPGFMVWCGG 348
Cdd:cd16040   135 LDHSAGTLSFYSVSDTmTLLHTVQTTFTEPLYPGFGVGYGS 175

PRY/SPRY domain in tripartite motif-containing domain 25 (TRIM25); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM25 proteins (composed of RING/B-box/coiled-coil core and also known as RBCC proteins). TRIM25 (also called Efp) ubiquitinates the N terminus of the viral RNA receptor retinoic acid-inducible gene-I (RIG-I) in response to viral infection, leading to activation of the RIG-I signaling pathway, thus resulting in type I interferon production to limit viral replication. It has been shown that the influenza A virus targets TRIM25 and disables its antiviral function.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671499 206 SVGSRPPAVRGSRDRFTGESyTVLGDTAIESGQHYWEVKAQKD--CksySVGVAYKTL---GKFDQLGKTNTSWCIHvnn 280
Cdd:cd13736    22 SVSDDPQNYREHPQRFTYCS-QVLGLHCFKQGIHYWEVELQKNnfC---GVGICYGSMdrqGPESRLGRNSESWCVE--- 94

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1034671499 281 WLQNTFAAKHNNKVKALDVTVPEKIGVFCDFDGGQLSFYDANSK-QLLYSFKTKFTQPVLPGFMVWCGGLSLS 352
Cdd:cd13736    95 WFNVKISAWHNNVEKTLPSTKATRVGVLLNCDHGFVIFFAVQDKvHLMYKFKVDFTEALYPAFWVFSAGTTLS 167

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 1034671499 228 VLGDTAIESGQHYWEVKAQKDCKSYSVGVAYKTLGK-----FDQLGKTNTSWCIH---VNNWlqntfaAKHNNKVKALDV 299
Cdd:cd13738    43 VLSRDSFFSGRHYWEVDLQEAGAGWWVGAAYPSIGRkgdseAARLGWNRQSWCLKrydLEYW------AFHDGQRSRLRP 116

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1034671499 300 TV-PEKIGVFCDFDGGQLSFYDANSKQL-LYSFKTKFTQPVLPGFMVWCGGLSLS 352
Cdd:cd13738   117 EDdPDRLGVFLDYEAGILSFYDVTGGMThLHTFRATFQEPLYPALRLWEGSISIC 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 1034671499 201 SPKRTSV--GSRPPAVRGSRDRFTgESYTVLGDTAIESGQHYWEVKAqKDCKSYSVGVAYKTLgkfDQLGKTNTS----- 273
Cdd:cd13733    16 SEDLKSVryGDKRQNLPDNPERFD-TCVCVLGSEGFSSGRHYWEVEV-GGKTDWDLGVARESV---NRKGKITLSpengy 90

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034671499 274 WCIhvnnWLQNtfaakhNNKVKALD--------VTVPEKIGVFCDFDGGQLSFYDANSKQLLYSFKTKFTQPVLPGF 342
Cdd:cd13733    91 WTV----GLRN------GNEYKALTspstplslREKPQKVGVFLDYEEGQVSFYNVDDGSHIYTFTDCFTEKLYPYF 157

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671499 210 RPPAVRGSRDRFTGESYTVLGDTAIESGQHYWEVKAQKdcKSYSVGVAYKTL------GKFDQLGKTNTSW--CIHvnnw 281
Cdd:cd12896    36 RSAARGVPASPGSFELWQVQCTQSFQHGHHYWEVEVSS--HSVTLGVTYPGLprhkqgGHKDNIGRNPCSWglQIQ---- 109

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1034671499 282 lQNTFAAKHNNKVKALDVTVPEKIGVFCDFDGGQLSFY-DANSKQLLYSFKTKFTQPVLPGFmvW-CGGLSLS 352
Cdd:cd12896   110 -EDSLQAWHNGRAQKLQGVSYRLLGVDLDLEAGTLTFYgLEPGTQRLHTFHAIFTQPLYPVF--WlLEGRTLT 179

PRY/SPRY domain of tripartite motif-binding protein 60 (TRIM60) also known as RING finger protein 33 (RNF33); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM60, which is also known as RING finger protein 33 (RNF33) or 129 (RNF129). TRIM60 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671499 181 ENKGSVHVTSLKKHTrsgTPSPKRTSVGsrpPAVRGSrdrftgESYTvlgdtaieSGQHYWEVKAQKDCKsYSVGVAYKT 260
Cdd:cd15828    27 EDRKSVLYGEMKQNV---CYNPRRFYLC---PAVLGS------EGFH--------SGRQYWEVEVGDKPE-WTLGVCQDC 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671499 261 L--GKFDQLGKTNTSWCIhvNNWLQNTFAAKHNNKVKALDVTVPEKIGVFCDFDGGQLSFYDANSKQLLYSFKTKFTQPV 338
Cdd:cd15828    86 LprNWSNQPSVQDGLWAI--GRYSESNYVALGPKKIQLLPKVRPSKIGIFLDYELGEVSFYNMNDRSLLYTFSDSFTGTL 163

                  ....
gi 1034671499 339 LPGF 342
Cdd:cd15828   164 WPYF 167

PRY/SPRY domain in tripartite motif-containing domain 25 (TRIM25)-like; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of proteins similar to TRIM25 (composed of RING/B-box/coiled-coil core and also known as RBCC proteins). TRIM25 (also called Efp) ubiquitinates the N terminus of the viral RNA receptor retinoic acid-inducible gene-I (RIG-I) in response to viral infection, leading to activation of the RIG-I signaling pathway, thus resulting in type I interferon production to limit viral replication. It has been shown that the influenza A virus targets TRIM25 and disables its antiviral function.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671499 228 VLGDTAIESGQHYWEVKAQKD--CksysVGVAYK---TLGK---FDQLGKTNTSWCIHvnnWLQNTFAAKHNNKVKALDV 299
Cdd:cd13737    44 VLCTRSLCEGCHYWEAEVSNSwvC----LGVTYSyshPTGKsciFYLIGRNPYSWCLE---WDSLKFSVWHNNIQTVVHG 116

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1034671499 300 TVPEKIGVFCDFDGGQLSFYD-ANSKQLLYSFKTKFTQPVLPGFMVWCG 347
Cdd:cd13737   117 SYYKTIGVLLDYAAGSLTFYGvANTMNLIYRFLTTFTEPLYPAVMVSSG 165

zinc-binding protein A33-like; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM69 and TRIM proteins NF7 and bloodthirsty (bty). TRIM69 is a novel testis E3 ubiquitin ligase that may function to ubiquitinate its particular substrates during spermatogenesis. In humans, TRIM69 localizes in the cytoplasm and nucleus, and requires an intact RING finger domain to function. TRIM protein NF7, which also contains a chromodomain (CHD) at the N-terminus and an RFP (Ret finger protein)-like domain at the C-terminus, is required for its association with transcriptional units of RNA polymerase II which is mediated by a trimeric B box. In Xenopus oocyte, xNF7 has been identified as a nuclear microtubule-associated protein (MAP) whose microtubule-bundling activity, but not E3-ligase activity, contributes to microtubule organization and spindle integrity. Bloodthirsty (bty) is a novel gene identified in zebrafish and has been shown to likely play a role in in regulation of the terminal steps of erythropoiesis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671499 201 SPKRTSV--GSRPPAVRGSRDRFTgESYTVLGDTAIESGQHYWEVKAQKDCKsYSVGVAYKTLGKFD--QLGKTNTSWCI 276
Cdd:cd12905    20 SRDLTAVteSDEMQPYPRSPKRFL-QCVNVLASQGFQSGRHYWEVWVGSKTK-WDLGVASESVDRQArvKLCPENGYWTL 97

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1034671499 277 HVNNwlQNTFAAKHNNKVKALDVTVPEKIGVFCDFDGGQLSFYDANSKQLLYSFKTKFTQPVLPGF 342
Cdd:cd12905    98 RLRN--GDEYWAGTQPWTRLRVTSRPQRIGVFLDCEERKVSFYNADDMSLLYSFHQGPRGKVFPFF 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 1034671499 205 TSV--GSRPPAVRGSRDRFTGeSYTVLGDTAIESGQHYWEVKAqKDCKSYSVGVAYKTL---GKFDqLGKTNTSWCIhvn 279
Cdd:cd12893    20 TSVrySSEKQQLPDNPERFDP-YPCVLGSEGFTSGKHSWDVEV-GDNTSWMLGVAKESVqrkGKFT-LSPESGFWTI--- 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671499 280 nWLqntfaakHNNKVKALD-------VTV---PEKIGVFCDFDGGQLSFYDANSKQLLYSFKTKFTQPVLPGFMVWCGGL 349
Cdd:cd12893    94 -GF-------SEGKYSARTspeprtpLRVkqkPQRIRVQLDWDRGKVSFSDPDTNTHIHTFTHTFTERVFPYFYTGCKSE 165

                  ..
gi 1034671499 350 SL 351
Cdd:cd12893   166 PL 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671499 228 VLGDTAIESGQHYWEVKAqKDCKSYsVGVAYKTLgkfDQLGK--------TNTSWCIHvnnWLQNTFAAKHNNKVKALDV 299
Cdd:cd12890    54 VLSQQSLYLGRYYFEVEI-SGEGTY-VGLTYKSI---DRKGSesnscisgNNFSWCLQ---WNGKEFSAWHSDVETPLKK 125

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1034671499 300 TVPEKIGVFCDFDGGQLSFY--DANSKQLLYSFKTKFTQPVLPGF 342
Cdd:cd12890   126 GPFTRLGIYLDYPGGTLSFYgvEDDGMTLLHKFQCKFTEPLYPAF 170

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671499 211 PPAVRGSRDRFTGEsYTVLGDTAIESGQHYWEVKAQKDCKsYSVGVAYKTLGKFD--QLGKTNTSWCIHVNNwlQNTFAA 288
Cdd:cd13744    41 PQPLQDSPKRFDVE-VSVLGSEGFSGGVHYWEVVVSEKTQ-WMIGLAHEAVSRKGsiQIQPGRGFYCIVMHD--GNQYSA 116

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671499 289 ------KHNNKVKAldvtvpEKIGVFCDFDGGQLSFYDANSKQLLYSFKTKFTQPVLPGF 342
Cdd:cd13744   117 ctepwtRLNVKSKL------EKVGVYLDYDKGLLIFYNADDMSWLYTFREKFPGKLCSYF 170

PRY/SPRY domain of tripartite motif-binding protein 5, 6, 22 and 34 (TRIM5, TRIM6, TRIM22 and TRIM34); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of very close paralogs, TRIM5, TRIM6, TRIM22 and TRIM34. These domains are composed of RING/B-box/coiled-coil core and are also known as RBCC proteins. They form a locus of four closely related TRIM genes within an olfactory receptor-rich region on chromosome 11 of the human genome. Genetic analysis of this locus indicates that these four genes have evolved by gene duplication from a common ancestral gene. All genes in the TRIM6/TRIM34/TRIM5/TRIM22 locus are type I interferon inducible, with TRIM5 and TRIM22 possessing antiviral properties. TRIM5 promotes innate immune signaling by activating the TAK1 kinase complex by cooperating with the heterodimeric E2, UBC13/UEV1A. It also stimulates NFkB and AP-1 signaling, and the transcription of inflammatory cytokines and chemokines, amplifying these activities upon retroviral infection. Interaction of its PRY-SPRY or cyclophilin domains with the retroviral capsid lattice stimulates the formation of a complementary lattice by TRIM5, with greatly increased TRIM5 E3 activity, and host cell signal transduction. TRIM6 is selectively expressed in embryonic stem (ES) cells and interacts with the proto-oncogene product Myc, maintaining the pluripotency of the ES cells. TRIM6, together with E2 Ubiquitin conjugase (UbE2K) and K48-linked poly-Ub chains, is critical for the IkappaB kinase epsilon (IKKepsilon) branch of type I interferon (IFN-I) signaling pathway and subsequent establishment of a protective antiviral response. TRIM22 plays an integral role in the host innate immune response to viruses; it has been shown to inhibit the replication of a number of viruses, including HIV-1, hepatitis B, and influenza A. Altered TRIM22 expression has also been associated with multiple sclerosis, cancer, and autoimmune disease. While the PRY-SPRY domain of TRIM5a provides specificity and the capsid recognition motif to retroviral restriction, TRIM34 binds HIV-1 capsid but does not restrict HIV-1 infection.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671499 201 SPKRTSVGSRPPAVRGSRDRFTGESYTVLGDTAIESGQHYWEV--------------KAQKDCKSYSVGVAYKTLGKFDQ 266
Cdd:cd15810    16 SEDQRQVRIVPPQTSGQALTNNNYDFGVLGSQYFSSGKHYWEVdvskksawilgvcsHKRSDAMTKSNANQINHQNVYSR 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671499 267 LGKTNTSWCIHVNNWLQ-NTF--AAKHNNKVKALDVTV-PEKIGVFCDFDGGQLSFYD-ANSKQLLYSF-KTKFTQPVLP 340
Cdd:cd15810    96 YQPQYGYWVIGLQNESEyNAFedSSSFNPHVLTLSVTVpPHRVGVFLDYEAGTVSFFNvTNHGSLIYKFsKCCFSTTVCP 175

                  ....*
gi 1034671499 341 GFMVW 345
Cdd:cd15810   176 YFNPW 180

PRY/SPRY domain in tripartite motif-binding protein 50 (TRIM50); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM50. 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. It is specifically expressed in gastric parietal cells and may play an essential role in tubulovesicular dynamics. It also interacts with and increases the level of p62, a multifunctional adaptor protein that is implicated in various cellular processes such as the autophagy clearance of polyubiquitinated protein aggregates.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671499 219 DRFTgESYTVLGDTAIESGQHYWEVkaQKDCKS-YSVGVAYKTLGKFDQLGKT--NTSWCIHVNNwlQNTFAAKHNNKVK 295
Cdd:cd13743    48 ERFD-YSNCVLASRGFSSGKHYWEV--VVGSKSkWRLGLIKGTTSRKGKLNKSpeNGVWLIGLKE--GRVYEAFANPRVP 122

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1034671499 296 ALDVTVPEKIGVFCDFDGGQLSFYDANSKQLL---YSFKTKFTQPVLPGF-MVW 345
Cdd:cd13743   123 LPLSTRPQRIGVFLDYEKGELTFYNADSPDELvpiYTFQAEFQGKLYPLLdVCW 176

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 1034671499 201 SPKRTSV--GSRPPAVRGSRDRFTgESYTVLGDTAIESGQHYWEVKAqKDCKSYSVGVAYKTLGKFD--QLGKTNTSWCI 276
Cdd:cd15811    16 SEDRRSVrrGDLRQALPDSPERFD-PGPCVLGRERFTSGRHYWEVEV-GDRTSWALGVCKENVNRKEkgELSAGNGFWIL 93

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034671499 277 hvnnwlqnTFAAKHNNKVKALDVTV---PEKIGVFCDFDGGQLSFYDANSKQLLYSF-KTKFTQPVLPGF 342
Cdd:cd15811    94 --------VFLGNYYSSERRTFAPLrdpPRRVGIFLDYEAGHLSFYSATDGSLLFIFpETPFSGTLRPLF 155

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 1034671499 201 SPKRTSV--GSRPPAVRGSRDRFTGEsYTVLGDTAIESGQHYWEVKAQKDcKSYSVGVAYKTLGKFDQLGKTNTS----- 273
Cdd:cd13741    16 SPDRRGVrlAERRQEVPEHPKRFSAD-CCVLGAQGFRSGRHYWEVEVGGR-RGWAVGAARESTHHKEKVGSGGSSvssgd 93