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 1061213982 165 PKAPEIDPVEclvaDNSVTVAWRMPEEDN-KIDHFILEHRKTNFDGlprvkdercWEIIDN--IKGTEYTLSGLKFDSKY 241
Cdd:cd00063     4 PTNLRVTDVT----STSVTLSWTPPEDDGgPITGYVVEYREKGSGD---------WKEVEVtpGSETSYTLTGLKPGTEY 70

                          90       100
                  ....*....|....*....|....
gi 1061213982 242 mNFRVRACNKAVAGEYSDPVTLET 265
Cdd:cd00063    71 -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 1061213982  361 SGQHYWEVKAQKDcKSYSVGVAYKT--LGKFDQLGKTNTSWCIH---VNNWlqntfaakHNNKVKALDVTVPEK---IGV 432
Cdd:smart00449   1 SGRHYFEVEIGDG-GHWRVGVATKSvpRGYFALLGEDKGSWGYDgdgGKKY--------HNSTGPEYGLPLQEPgdvIGC 71

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 1061213982  433 FCDFDGGQLSFYDANSKQLLYSFKT-KFTQPVLPGFMVWCGG 473
Cdd:smart00449  72 FLDLEAGTISFYKNGKYLHGLAFFDvKFSGPLYPAFSLGSGN 113

B-Box C-terminal domain; Coiled coil region C-terminal to (some) B-Box domains

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061213982    4 QKEALQRIISTLANKNDEIQNFIDTLHHTLKGVQENSSNILSELDEEFDSLYSILDEVKESMINCIKQEQARKSQELQSQ 83
Cdd:smart00502   1 QREALEELLTKLRKKAAELEDALKQLISIIQEVEENAADVEAQIKAAFDELRNALNKRKKQLLEDLEEQKENKLKVLEQQ 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 1061213982   84 ISQCNNALENSEELLEFATRSLDIKEPEEFSKAARQIKDRVTMASAF 130
Cdd:smart00502  81 LESLTQKQEKLSHAINFTEEALNSGDPTELLLSKKLIIERLQNLLKQ 127

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1061213982  177 VADNSVTVAWRMPEEDNkIDHFILEHRKTNfdglpRVKDERCWEIIDNIKGTEYTLSGLKFDSKYmNFRVRACNKA 252
Cdd:smart00060  12 VTSTSVTLSWEPPPDDG-ITGYIVGYRVEY-----REEGSEWKEVNVTPSSTSYTLTGLKPGTEY-EFRVRAVNGA 80

Fibronectin type III domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061213982 177 VADNSVTVAWRMPEEDN-KIDHFILEHRKTNfdgLPRVKDERcweiidNIKGTE--YTLSGLKFDSKYmNFRVRACNKAV 253
Cdd:pfam00041  11 VTSTSLTVSWTPPPDGNgPITGYEVEYRPKN---SGEPWNEI------TVPGTTtsVTLTGLKPGTEY-EVRVQAVNGGG 80

                  ....*
gi 1061213982 254 AGEYS 258
Cdd:pfam00041  81 EGPPS 85

RIM-binding protein of the cytomatrix active zone; This is a family of proteins that form part of the CAZ (cytomatrix at the active zone) complex which is involved in determining the site of synaptic vesicle fusion. The C-terminus is a PDZ-binding motif that binds directly to RIM (a small G protein Rab-3A effector). The family also contains four coiled-coil domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061213982   2 DSQKEALQRIISTLANKNDEIQNFIDTLHHTLKGvQENSSNILSeldEEFDSLYSILDEvKESMINcikqEQARKSQELQ 81
Cdd:pfam10174 302 ESELLALQTKLETLTNQNSDCKQHIEVLKESLTA-KEQRAAILQ---TEVDALRLRLEE-KESFLN----KKTKQLQDLT 372

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1061213982  82 SQISQCNNALENSEELLEFATRSLDI--KEPEEFSKaarQIKDR 123
Cdd:pfam10174 373 EEKSTLAGEIRDLKDMLDVKERKINVlqKKIENLQE---QLRDK 413

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 1061213982 270 FNLDNSSSHLNLKVED--TCVEWDPTGGKGQESkikgkenkgsvhvtslkkhtrsgtpspkrtsvgsrppavrgSRDRFT 347
Cdd:cd13734     1 FKLDPKTAHRKLRLSNdnLTVEYDPEGSKDQAA-----------------------------------------VLPRRF 39

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061213982 348 GESYTVLGDTAIESGQHYWEVKAQKDCkSYSVGVAYKTLGKFDQLGKTNTSWCIHVNNwlqNTFAAKHNNKVKALDVTV- 426
Cdd:cd13734    40 TGSPAVLGDVAISSGRHYWEVSVSRST-SYRVGVAYKSAPRDEDLGKNSTSWCLSRDN---NRYTARHDGKVVDLRVTGh 115

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 1061213982 427 PEKIGVFCDFDGGQLSFYDANSKQLLYSFKTKFTQPVLPGFMVWCGGLSL 476
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 1061213982 328 KRTSVGSRPPAVRGSRDRFTgeSYTVLGDTAIESGQHYWEVKAQKdCKSYSVGVAYKTL---GKFDQLGKTNTSWCIHVN 404
Cdd:cd12891    19 KTVTCSSENQHYPDSPERFT--HSQVLSTQSFSSGRHYWEVEVSE-SGGWSVGVAYPSIerkGDESRIGRNDKSWCLEWQ 95

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061213982 405 NwlqNTFAAKHNNKVKALDVTVPEKIGVFCDFDGGQLSFYD-ANSKQLLYSFKTKFTQPVLPGFMVWCGG 473
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 1061213982 324 TPSPKRTSVGSRPPAVRGSRDRFTGESytVLGDTAIESGQHYWEVKAQKdCKSYSVGVAYKTLGKFDQLGKTNTSWCIHV 403
Cdd:cd12902    15 SEDSRKVTVSHGPQAYAWSPDRFSISQ--VLCSQAFSSGQHYWEVDTRQ-CSHWAVGVASWEMSRDQMLGRTMDSWCIEW 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061213982 404 NNWLQntFAAKHNNKVKALDVTVPEKIGVFCDFDGGQLSFYD-ANSKQLLYSFKTKFTQPVLPGFmvWCGGLSLSTGMQV 482
Cdd:cd12902    92 KGTGQ--LSAWHMNKETVLGSDKPRVVGIWLDLEEGKLAFYSvANQERLLHECEVSASSPLHPAF--WLYGLEPGNSLII 167

                  .
gi 1061213982 483 P 483
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 1061213982 361 SGQHYWEVkaQKDCKSYSVGVAYKTL---GKFDQ--LGKTNTSWCIhvnNWLQNTFAAKHNNKVKalDVTVPE----KIG 431
Cdd:cd16040    60 SGRCYWEV--EWSGGGVDIAVAYKGIsrkGDGDDsrFGYNDKSWSL---ECSPSGYSFWHNNKKT--EISVPSssssRVG 132

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1061213982 432 VFCDFDGGQLSFYDANSK-QLLYSFKTKFTQPVLPGFMVWCGG 473
Cdd:cd16040   133 VYLDHSAGTLSFYSVSDTmTLLHTVQTTFTEPLYPGFGVGYGS 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 1061213982 331 SVGSRPPAVRGSRDRFTGESyTVLGDTAIESGQHYWEVKAQKD--CksySVGVAYKTL---GKFDQLGKTNTSWCIHvnn 405
Cdd:cd13736    22 SVSDDPQNYREHPQRFTYCS-QVLGLHCFKQGIHYWEVELQKNnfC---GVGICYGSMdrqGPESRLGRNSESWCVE--- 94

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1061213982 406 WLQNTFAAKHNNKVKALDVTVPEKIGVFCDFDGGQLSFYDANSK-QLLYSFKTKFTQPVLPGFMVWCGGLSLS 477
Cdd:cd13736    95 WFNVKISAWHNNVEKTLPSTKATRVGVLLNCDHGFVIFFAVQDKvHLMYKFKVDFTEALYPAFWVFSAGTTLS 167

PRY/SPRY domain containing protein 4 (SPRYD4); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain and is encoded by the SPRYD4 gene. SPRYD4 (SPRY containing domain 4) is ubiquitously expressed in many human tissues, most strongly in kidney, bladder, brain, thymus and stomach. Subcellular localization demonstrates that SPRYD4 protein is localized in the nucleus when overexpressed in COS-7 green monkey cell. It has remained uncharacterized thus far.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061213982 332 VGSRPPAVRGSRDRFTgESYTVLGDTAIESGQHYWEVKAQKDcKSYSVGVAYKTLGKFDQLGKTNTSWcihVNNWLQNT- 410
Cdd:cd12903    26 LGVDPTKVPQNPERFR-DWAVVLGDTPVTSGRHYWEVTVKRS-QEFRIGVADVDMSRDECIGTNESSW---VFAYAQRKw 100

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1061213982 411 FAAKHNNKVKALDVTVPEKIGVFCDFDGGQLSFYDANSKQLLYSFKTKFTQPVLPGFMVWCGGL 474
Cdd:cd12903   101 YAMVANETVPVPLVGKPDRVGLLLDYEAGKLSLVDVEKNSVVHTMSAEFRGPVVPAFALWDGEL 164

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 1061213982 326 SPKRTSV--GSRPPAVRGSRDRFTgESYTVLGDTAIESGQHYWEVKAqKDCKSYSVGVAYKTLgkfDQLGKTNTS----- 398
Cdd:cd13733    16 SEDLKSVryGDKRQNLPDNPERFD-TCVCVLGSEGFSSGRHYWEVEV-GGKTDWDLGVARESV---NRKGKITLSpengy 90

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1061213982 399 WCIhvnnWLQNtfaakhNNKVKALD--------VTVPEKIGVFCDFDGGQLSFYDANSKQLLYSFKTKFTQPVLPGF 467
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 1061213982 335 RPPAVRGSRDRFTGESYTVLGDTAIESGQHYWEVKAQKdcKSYSVGVAYKTL------GKFDQLGKTNTSW--CIHvnnw 406
Cdd:cd12896    36 RSAARGVPASPGSFELWQVQCTQSFQHGHHYWEVEVSS--HSVTLGVTYPGLprhkqgGHKDNIGRNPCSWglQIQ---- 109

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1061213982 407 lQNTFAAKHNNKVKALDVTVPEKIGVFCDFDGGQLSFY-DANSKQLLYSFKTKFTQPVLPGFmvW-CGGLSLS 477
Cdd:cd12896   110 -EDSLQAWHNGRAQKLQGVSYRLLGVDLDLEAGTLTFYgLEPGTQRLHTFHAIFTQPLYPVF--WlLEGRTLT 179

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 1061213982  361 SGQHYWEVKAQKDcKSYSVGVAYKT--LGKFDQLGKTNTSWCIH---VNNWlqntfaakHNNKVKALDVTVPEK---IGV 432
Cdd:smart00449   1 SGRHYFEVEIGDG-GHWRVGVATKSvpRGYFALLGEDKGSWGYDgdgGKKY--------HNSTGPEYGLPLQEPgdvIGC 71

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 1061213982  433 FCDFDGGQLSFYDANSKQLLYSFKT-KFTQPVLPGFMVWCGG 473
Cdd:smart00449  72 FLDLEAGTISFYKNGKYLHGLAFFDvKFSGPLYPAFSLGSGN 113

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 1061213982 353 VLGDTAIESGQHYWEVKAQKD--CksysVGVAYK---TLGK---FDQLGKTNTSWCIHvnnWLQNTFAAKHNNKVKALDV 424
Cdd:cd13737    44 VLCTRSLCEGCHYWEAEVSNSwvC----LGVTYSyshPTGKsciFYLIGRNPYSWCLE---WDSLKFSVWHNNIQTVVHG 116

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1061213982 425 TVPEKIGVFCDFDGGQLSFYD-ANSKQLLYSFKTKFTQPVLPGFMVWCG 472
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 1061213982 326 SPKRTSV--GSRPPAVRGSRDRFTgESYTVLGDTAIESGQHYWEVKAQKDCKsYSVGVAYKTLGKFD--QLGKTNTSWCI 401
Cdd:cd12905    20 SRDLTAVteSDEMQPYPRSPKRFL-QCVNVLASQGFQSGRHYWEVWVGSKTK-WDLGVASESVDRQArvKLCPENGYWTL 97

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1061213982 402 HVNNwlQNTFAAKHNNKVKALDVTVPEKIGVFCDFDGGQLSFYDANSKQLLYSFKTKFTQPVLPGF 467
Cdd:cd12905    98 RLRN--GDEYWAGTQPWTRLRVTSRPQRIGVFLDCEERKVSFYNADDMSLLYSFHQGPRGKVFPFF 161

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061213982 345 RFTGESyTVLGDTAIESGQHYWEVKAQK-DCKSYSVGVAYKTLGKFDQLGKTNTS--WCIHVNNwlQNTFAAKHNNKVKA 421
Cdd:cd15826    37 RFDGLP-AVLGSPGFSSGRHRWQVEVQLgDGGGCTVGVAGESVRRKGEMGLSAEDgvWAVILSH--QQCWASTSPGTDLP 113

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1061213982 422 LDVTvPEKIGVFCDFDGGQLSFYDANSKQLLYSFKTKFTQPVLPGFMVWCGGLSL 476
Cdd:cd15826   114 LSEI-PRRVGVALDYEAGTVTLTNAETQEPIFTFTASFSGKVFPFFAVWKKGSRL 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 1061213982 353 VLGDTAIESGQHYWEVKAqKDCKSYsVGVAYKTLgkfDQLGK--------TNTSWCIHvnnWLQNTFAAKHNNKVKALDV 424
Cdd:cd12890    54 VLSQQSLYLGRYYFEVEI-SGEGTY-VGLTYKSI---DRKGSesnscisgNNFSWCLQ---WNGKEFSAWHSDVETPLKK 125

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1061213982 425 TVPEKIGVFCDFDGGQLSFY--DANSKQLLYSFKTKFTQPVLPGF 467
Cdd:cd12890   126 GPFTRLGIYLDYPGGTLSFYgvEDDGMTLLHKFQCKFTEPLYPAF 170

PRY/SPRY domain in tripartite motif-containing protein 34 (TRIM34), also known as RING finger protein 21 (RNF21) or interferon-responsive finger protein (IFP1); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM34, also known as RING finger protein 21 (RNF21) or interferon-responsive finger protein (IFP1). TRIM34 domain is composed of RING/B-box/coiled-coil core and also known as RBCC protein. The TRIM21 cDNA possesses at least three kinds of isoforms, due to alternative splicing, of which only the long and medium forms contain the SPRY domain. It is an interferon-induced protein, predominantly expressed in the testis, kidney, and ovary. The SPRY domain provides the capsid recognition motif that dictates specificity to retroviral restriction. While the PRY-SPRY domain 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 1061213982 346 FTGESYTVLGDTAIESGQHYWEVKAQKD--------CKSYSVGVAYKTLGKFDQLGKT-----NTSWCIHVNNWLQ-NTF 411
Cdd:cd15825    32 FKCYNYGILGSQYFSSGKHYWEVDVSKKtawilgvyCRKRSRTFKYVRQGKNHPNVYSryrpqYGYWVIGLQNKSEyYAF 111

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1061213982 412 --AAKHNNKVKALDVTVP-EKIGVFCDFDGGQLSFYD-ANSKQLLYSF-KTKFTQPVLPGFMVW 470
Cdd:cd15825   112 edSSTSDPKVLTLSVATPpHRVGVFLDYEAGTVSFFNvTNHGSLIYKFsKCCFSQPVYPYFNPW 175

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 1061213982 326 SPKRTSVGSRPPAVRGSRDRFTGESYTVLGDTAIESGQHYWEV--------------KAQKDCKSYSVGVAYKTLGKFDQ 391
Cdd:cd15810    16 SEDQRQVRIVPPQTSGQALTNNNYDFGVLGSQYFSSGKHYWEVdvskksawilgvcsHKRSDAMTKSNANQINHQNVYSR 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061213982 392 LGKTNTSWCIHVNNWLQ-NTF--AAKHNNKVKALDVTV-PEKIGVFCDFDGGQLSFYD-ANSKQLLYSF-KTKFTQPVLP 465
Cdd:cd15810    96 YQPQYGYWVIGLQNESEyNAFedSSSFNPHVLTLSVTVpPHRVGVFLDYEAGTVSFFNvTNHGSLIYKFsKCCFSTTVCP 175

                  ....*
gi 1061213982 466 GFMVW 470
Cdd:cd15810   176 YFNPW 180

PRY/SPRY domain in tripartite motif-binding protein 58 (TRIM58), also known as BIA2; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM58, also known as BIA2. TRIM58 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins.It is implicated by genome-wide association studies (GWAS) to regulate erythrocyte traits, including cell size and number. Trim58 facilitates erythroblast enucleation by inducing proteolytic degradation of the microtubule motor dynein.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1061213982 333 GSRPPAVRGSRDRFtgESY-TVLGDTAIESGQHYWEVkAQKDCKSYSVGVAYKTLGKfdqLGKTNTS-----WCIhvnnW 406
Cdd:cd15816    25 GELWRDVPGNPERF--DTWpCVLGLQSFSSGRHYWEV-AVGEKAEWGLGVCQDSAPR---KGETTPSpengvWAV----W 94

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1061213982 407 L--QNTFAAKHNNKVKALDVTVPEKIGVFCDFDGGQLSFYDANSKQLLYSFKTKFTQPVLPGFMV 469
Cdd:cd15816    95 LlkGNEYMVLASPSVPLLQLRRPRRVGVFLDYEAGEISFYNVTAGSHIYTFRQLFSGILRPYFFV 159