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 767958435   2 PEEDN-KIDHFILEHRKTNFDGlprvkdercWEIIDN--IKGTEYTLSGLKFDSKYmNFRVRACNKAVAGEYSDPVTLET 78
Cdd:cd00063   24 PEDDGgPITGYVVEYREKGSGD---------WKEVEVtpGSETSYTLTGLKPGTEY-EFRVRAVNGGGESPPSESVTVTT 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 767958435   174 SGQHYWEVKAQKDcKSYSVGVAYKT--LGKFDQLGKTNTSWCIH---VNNWlqntfaakHNNKVKALDVTVPEK---IGV 245
Cdd:smart00449   1 SGRHYFEVEIGDG-GHWRVGVATKSvpRGYFALLGEDKGSWGYDgdgGKKY--------HNSTGPEYGLPLQEPgdvIGC 71

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 767958435   246 FCDFDGGQLSFYDANSKQLLYSFKT-KFTQPVLPGFMVWCGG 286
Cdd:smart00449  72 FLDLEAGTISFYKNGKYLHGLAFFDvKFSGPLYPAFSLGSGN 113

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 767958435   2 PEEDN-KIDHFILEHRKTNFDGlprvkdercWEIIDN--IKGTEYTLSGLKFDSKYmNFRVRACNKAVAGEYSDPVTLET 78
Cdd:cd00063   24 PEDDGgPITGYVVEYREKGSGD---------WKEVEVtpGSETSYTLTGLKPGTEY-EFRVRAVNGGGESPPSESVTVTT 93

Fibronectin type 3 domain [General function prediction only];

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 767958435  32 WEIIDNIKGTEYTLSGLKFDSKYmNFRVRACNKA-VAGEYSDPVTLET 78
Cdd:COG3401  276 FTKVATVTTTSYTDTGLTNGTTY-YYRVTAVDAAgNESAPSNVVSVTT 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 767958435  83 FNLDNSSSHLNLKVED--TCVEWDPTGGKGQESkikgkenkgsvhvtslkkhtrsgtpspkrtsvgsrppavrgSRDRFT 160
Cdd:cd13734    1 FKLDPKTAHRKLRLSNdnLTVEYDPEGSKDQAA-----------------------------------------VLPRRF 39

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767958435 161 GESYTVLGDTAIESGQHYWEVKAQKDCkSYSVGVAYKTLGKFDQLGKTNTSWCIHVNNwlqNTFAAKHNNKVKALDVTV- 239
Cdd:cd13734   40 TGSPAVLGDVAISSGRHYWEVSVSRST-SYRVGVAYKSAPRDEDLGKNSTSWCLSRDN---NRYTARHDGKVVDLRVTGh 115

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|
gi 767958435 240 PEKIGVFCDFDGGQLSFYDANSKQLLYSFKTKFTQPVLPGFMVWCGGLSL 289
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 767958435 141 KRTSVGSRPPAVRGSRDRFTgeSYTVLGDTAIESGQHYWEVKAQKdCKSYSVGVAYKTL---GKFDQLGKTNTSWCIHVN 217
Cdd:cd12891   19 KTVTCSSENQHYPDSPERFT--HSQVLSTQSFSSGRHYWEVEVSE-SGGWSVGVAYPSIerkGDESRIGRNDKSWCLEWQ 95

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767958435 218 NwlqNTFAAKHNNKVKALDVTVPEKIGVFCDFDGGQLSFYD-ANSKQLLYSFKTKFTQPVLPGFMVWCGG 286
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 767958435 137 TPSPKRTSVGSRPPAVRGSRDRFTGESytVLGDTAIESGQHYWEVKAQKdCKSYSVGVAYKTLGKFDQLGKTNTSWCIHV 216
Cdd:cd12902   15 SEDSRKVTVSHGPQAYAWSPDRFSISQ--VLCSQAFSSGQHYWEVDTRQ-CSHWAVGVASWEMSRDQMLGRTMDSWCIEW 91

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767958435 217 NNWLQntFAAKHNNKVKALDVTVPEKIGVFCDFDGGQLSFYD-ANSKQLLYSFKTKFTQPVLPGFmvWCGGLSLSTGMQV 295
Cdd:cd12902   92 KGTGQ--LSAWHMNKETVLGSDKPRVVGIWLDLEEGKLAFYSvANQERLLHECEVSASSPLHPAF--WLYGLEPGNSLII 167

                 .
gi 767958435 296 P 296
Cdd:cd12902  168 K 168

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 767958435 150 PAVRGSRDRFTGESY--------------TVLGDTAIESGQHYWEVKAQkDCKSYSVGVAYKTLGKFDQLGKTNTSWCIH 215
Cdd:cd12898   13 PALHISSDRGTVIYFherrrkmssltecpSVLGEELPSCGQYYWETTVT-RCPAYRLGICSSSASQAGALGEGSTSWCLH 91

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767958435 216 -VNNWLQNTFAAKHNNKVKALDVT-VPEKIGVFCDFDGGQLSFYDANSKQLLYSFKTKFTQPVLPGF 280
Cdd:cd12898   92 cVPTSEPCRYTLLHSGIVSDVFVTeRPARVGTLLDYNNGRLIFINAESGQLLGIFRHRFAQPCHPAF 158

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 767958435 144 SVGSRPPAVRGSRDRFTGESyTVLGDTAIESGQHYWEVKAQKD--CksySVGVAYKTL---GKFDQLGKTNTSWCIHvnn 218
Cdd:cd13736   22 SVSDDPQNYREHPQRFTYCS-QVLGLHCFKQGIHYWEVELQKNnfC---GVGICYGSMdrqGPESRLGRNSESWCVE--- 94

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 767958435 219 WLQNTFAAKHNNKVKALDVTVPEKIGVFCDFDGGQLSFYDANSK-QLLYSFKTKFTQPVLPGFMVWCGGLSLS 290
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 767958435 166 VLGDTAIESGQHYWEVKAQKDCKSYSVGVAYKTLGK-----FDQLGKTNTSWCIH---VNNWlqntfaAKHNNKVKALDV 237
Cdd:cd13738   43 VLSRDSFFSGRHYWEVDLQEAGAGWWVGAAYPSIGRkgdseAARLGWNRQSWCLKrydLEYW------AFHDGQRSRLRP 116

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 767958435 238 TV-PEKIGVFCDFDGGQLSFYDANSKQL-LYSFKTKFTQPVLPGFMVWCGGLSLS 290
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 767958435 139 SPKRTSV--GSRPPAVRGSRDRFTgESYTVLGDTAIESGQHYWEVKAqKDCKSYSVGVAYKTLgkfDQLGKTNTS----- 211
Cdd:cd13733   16 SEDLKSVryGDKRQNLPDNPERFD-TCVCVLGSEGFSSGRHYWEVEV-GGKTDWDLGVARESV---NRKGKITLSpengy 90

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767958435 212 WCIhvnnWLQNtfaakhNNKVKALD--------VTVPEKIGVFCDFDGGQLSFYDANSKQLLYSFKTKFTQPVLPGF 280
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 767958435 148 RPPAVRGSRDRFTGESYTVLGDTAIESGQHYWEVKAQKdcKSYSVGVAYKTL------GKFDQLGKTNTSW--CIHvnnw 219
Cdd:cd12896   36 RSAARGVPASPGSFELWQVQCTQSFQHGHHYWEVEVSS--HSVTLGVTYPGLprhkqgGHKDNIGRNPCSWglQIQ---- 109

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 767958435 220 lQNTFAAKHNNKVKALDVTVPEKIGVFCDFDGGQLSFY-DANSKQLLYSFKTKFTQPVLPGFmvW-CGGLSLS 290
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 767958435 119 ENKGSVHVTSLKKHTrsgTPSPKRTSVGsrpPAVRGSrdrftgESYTvlgdtaieSGQHYWEVKAQKDCKsYSVGVAYKT 198
Cdd:cd15828   27 EDRKSVLYGEMKQNV---CYNPRRFYLC---PAVLGS------EGFH--------SGRQYWEVEVGDKPE-WTLGVCQDC 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767958435 199 L--GKFDQLGKTNTSWCIhvNNWLQNTFAAKHNNKVKALDVTVPEKIGVFCDFDGGQLSFYDANSKQLLYSFKTKFTQPV 276
Cdd:cd15828   86 LprNWSNQPSVQDGLWAI--GRYSESNYVALGPKKIQLLPKVRPSKIGIFLDYELGEVSFYNMNDRSLLYTFSDSFTGTL 163

                 ....
gi 767958435 277 LPGF 280
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 767958435 166 VLGDTAIESGQHYWEVKAQKD--CksysVGVAYK---TLGK---FDQLGKTNTSWCIHvnnWLQNTFAAKHNNKVKALDV 237
Cdd:cd13737   44 VLCTRSLCEGCHYWEAEVSNSwvC----LGVTYSyshPTGKsciFYLIGRNPYSWCLE---WDSLKFSVWHNNIQTVVHG 116

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 767958435 238 TVPEKIGVFCDFDGGQLSFYD-ANSKQLLYSFKTKFTQPVLPGFMVWCG 285
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 767958435 139 SPKRTSV--GSRPPAVRGSRDRFTgESYTVLGDTAIESGQHYWEVKAQKDCKsYSVGVAYKTLGKFD--QLGKTNTSWCI 214
Cdd:cd12905   20 SRDLTAVteSDEMQPYPRSPKRFL-QCVNVLASQGFQSGRHYWEVWVGSKTK-WDLGVASESVDRQArvKLCPENGYWTL 97

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767958435 215 HVNNwlQNTFAAKHNNKVKALDVTVPEKIGVFCDFDGGQLSFYDANSKQLLYSFKTKFTQPVLPGF 280
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 767958435 143 TSV--GSRPPAVRGSRDRFTGeSYTVLGDTAIESGQHYWEVKAqKDCKSYSVGVAYKTL---GKFDqLGKTNTSWCIhvn 217
Cdd:cd12893   20 TSVrySSEKQQLPDNPERFDP-YPCVLGSEGFTSGKHSWDVEV-GDNTSWMLGVAKESVqrkGKFT-LSPESGFWTI--- 93

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767958435 218 nWLqntfaakHNNKVKALD-------VTV---PEKIGVFCDFDGGQLSFYDANSKQLLYSFKTKFTQPVLPGFMVWCGGL 287
Cdd:cd12893   94 -GF-------SEGKYSARTspeprtpLRVkqkPQRIRVQLDWDRGKVSFSDPDTNTHIHTFTHTFTERVFPYFYTGCKSE 165

                 ..
gi 767958435 288 SL 289
Cdd:cd12893  166 PL 167

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767958435 158 RFTGEsYTVLGDTAIESGQHYWEVKAqKDCKSYSVGVAYKTLGKFDQLGKT--NTSWCIHVNNwlQNTFAAKHNNKVKAL 235
Cdd:cd15820   41 RFDWH-YCVLGCKSFTSGRHFWEVEV-GDRKEWYVGVCRENVERKLWVKMApeNGFWTIGLSD--GNDYQALTDPRTKLT 116

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 767958435 236 DVTVPEKIGVFCDFDGGQLSFYDANSKQLLYSF-KTKFTQPVLPGF 280
Cdd:cd15820  117 IANPPQRVGVFLDYETGEVSFYNAMDGSHIYTFpHTSFSGPLYPVF 162

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 767958435 149 PPAVRGSRDRFTGEsYTVLGDTAIESGQHYWEVKAQKDCKsYSVGVAYKTLGKFD--QLGKTNTSWCIHVNNwlQNTFAA 226
Cdd:cd13744   41 PQPLQDSPKRFDVE-VSVLGSEGFSGGVHYWEVVVSEKTQ-WMIGLAHEAVSRKGsiQIQPGRGFYCIVMHD--GNQYSA 116

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 767958435 227 ------KHNNKVKAldvtvpEKIGVFCDFDGGQLSFYDANSKQLLYSFKTKFTQPVLPGF 280
Cdd:cd13744  117 ctepwtRLNVKSKL------EKVGVYLDYDKGLLIFYNADDMSWLYTFREKFPGKLCSYF 170

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 767958435 157 DRFTgESYTVLGDTAIESGQHYWEVkaQKDCKS-YSVGVAYKTLGKFDQLGKT--NTSWCIHVNNwlQNTFAAKHNNKVK 233
Cdd:cd13743   48 ERFD-YSNCVLASRGFSSGKHYWEV--VVGSKSkWRLGLIKGTTSRKGKLNKSpeNGVWLIGLKE--GRVYEAFANPRVP 122

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 767958435 234 ALDVTVPEKIGVFCDFDGGQLSFYDANSKQLL---YSFKTKFTQPVLPGF-MVW 283
Cdd:cd13743  123 LPLSTRPQRIGVFLDYEKGELTFYNADSPDELvpiYTFQAEFQGKLYPLLdVCW 176

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 767958435 139 SPKRTSVGSRPPAVRGSRDRFTGESYTVLGDTAIESGQHYWEV--------------KAQKDCKSYSVGVAYKTLGKFDQ 204
Cdd:cd15810   16 SEDQRQVRIVPPQTSGQALTNNNYDFGVLGSQYFSSGKHYWEVdvskksawilgvcsHKRSDAMTKSNANQINHQNVYSR 95

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767958435 205 LGKTNTSWCIHVNNWLQ-NTF--AAKHNNKVKALDVTV-PEKIGVFCDFDGGQLSFYD-ANSKQLLYSF-KTKFTQPVLP 278
Cdd:cd15810   96 YQPQYGYWVIGLQNESEyNAFedSSSFNPHVLTLSVTVpPHRVGVFLDYEAGTVSFFNvTNHGSLIYKFsKCCFSTTVCP 175

                 ....*
gi 767958435 279 GFMVW 283
Cdd:cd15810  176 YFNPW 180

PRY/SPRY domain in tripartite motif-binding protein 5 (TRIM5), also known as RING finger protein 88 (RNF88); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM5 which is also known as RING finger protein 88 (RNF88) or TRIM5alpha (TRIM5a), an antiretroviral restriction factor and a retrovirus capsid sensor in immune signaling. TRIM5 domain is composed of RING/B-box/coiled-coil core and also known as RBCC protein. It blocks retrovirus infection soon after the virion core enters the cell cytoplasm by recognizing the capsid protein lattice that encases the viral genomic RNA; the SPRY domain provides the capsid recognition motif that dictates specificity to retroviral restriction. TRIM5a, an E3 ubiquitin ligase, 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, and amplifies 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767958435 162 ESYTVLGDTAIESGQHYWEVK-AQKD-------CKSYSvGVAYKTLGKFDQLGKTNTS--------WCIhvnnWLQNTF- 224
Cdd:cd15822   49 EDYGVLGSPSITSGKHYWEVDvSKKRawilgvcGGKYP-NSTLKDFNKQGKNNQKQCSnyqpkygyWVI----GLQNKSe 123

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 767958435 225 ------AAKHNNKVKALDVTVPEK-IGVFCDFDGGQLSFYDA-NSKQLLYSFKT-KFTQPVLPGF 280
Cdd:cd15822  124 ynafedSSSSDPLILTLSLTVPPCrVGVFLDYEAGTVSFFNVtNHGFLIYKFSScSFSQEVFPYF 188

PRY/SPRY domain in tripartite motif-binding protein 21 (TRIM21) also known as 52kD Ribonucleoprotein Autoantigen (Ro52); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM21, which is also known as Sjogren Syndrome Antigen A (SSA), SSA1, 52kD Ribonucleoprotein Autoantigen (Ro52, Ro/SSA, SS-A/Ro) or RING finger protein 81 (RNF81). TRIM21 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. As an E3 ligase, TRIM21 mediates target specificity in ubiquitination; it regulates type 1 interferon and proinflammatory cytokines via ubiquitination of interferon regulatory factors (IRFs). It is up-regulated at the site of autoimmune inflammation, such as cutaneous lupus lesions, indicating a central role in the tissue destructive inflammatory process. It interacts with auto-antigens in patients with Sjogren syndrome and systemic lupus erythematosus, a chronic systemic autoimmune disease characterized by the presence of autoantibodies against the protein component of the human intracellular ribonucleoprotein-RNA complexes and more specifically TRIM21, Ro60/TROVE2 and La/SSB proteins. It binds the Fc part of IgG molecules via its PRY-SPRY domain with unexpectedly high affinity.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767958435 124 VHVTsLKKHTRSG----TPSPKRTSVGSRPPAVRGSRDRFtgESY-TVLGDTAIESGQHYWEVKAQKDcKSYSVGV---A 195
Cdd:cd12900    3 VHIT-LDPDTANPwlilSKDRRQVRLGDTHQNVPENEERF--DNYpMVLGAQRFNSGKHYWEVDVTGK-EAWDLGVcrdS 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767958435 196 YKTLGKFdQLGKTNTSWCIhvnnWLQNTFAAKHNNKVKALDVTVPE-KIGVFCDFDGGQLSFYD-ANSKQLLYSF-KTKF 272
Cdd:cd12900   79 VRRKGQF-LLSPENGFWTI----WLWNKKYEAGTSPQTTLHLQVPPcQVGIFLDYEAGVVSFYNiTDHGSLIYTFsECAF 153

                 ....*...
gi 767958435 273 TQPVLPGF 280
Cdd:cd12900  154 TGPLRPFF 161