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 563407067 165 PKAPEIDPVEclvaDNSVTVAWRMPEEDN-KIDHFILEHRKTNFDGlprvkdercWEIIDN--IKGTEYTLSGLKFDSKY 241
Cdd:cd00063    4 PTNLRVTDVT----STSVTLSWTPPEDDGgPITGYVVEYREKGSGD---------WKEVEVtpGSETSYTLTGLKPGTEY 70

                         90       100
                 ....*....|....*....|....
gi 563407067 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 563407067   360 SGQHYWEVKAQKDcKSYSVGVAYKT--LGKFDQLGKTNTSWCIH---VNNWlqntfaakHNNKVKALDVTVPEK---IGV 431
Cdd:smart00449   1 SGRHYFEVEIGDG-GHWRVGVATKSvpRGYFALLGEDKGSWGYDgdgGKKY--------HNSTGPEYGLPLQEPgdvIGC 71

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 563407067   432 FCDFDGGQLSFYDANSKQLLYSFKT-KFTQPVLPGFMVWCGG 472
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 563407067     4 QKEALQRIISTLANKNDEIQNFIDTLHHTLKGVQENSSNILSELDEEFDSLYSILDEVKESMINCIKQEQARKSQELQSQ 83
Cdd:smart00502   1 QREALEELLTKLRKKAAELEDALKQLISIIQEVEENAADVEAQIKAAFDELRNALNKRKKQLLEDLEEQKENKLKVLEQQ 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 563407067    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 563407067   177 VADNSVTVAWRMPEEDNkIDHFILEHRKTNfdglpRVKDERCWEIIDNIKGTEYTLSGLKFDSKYmNFRVRACNKA 252
Cdd:smart00060  12 VTSTSVTLSWEPPPDDG-ITGYIVGYRVEY-----REEGSEWKEVNVTPSSTSYTLTGLKPGTEY-EFRVRAVNGA 80

Fibronectin type III domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 563407067  177 VADNSVTVAWRMPEEDN-KIDHFILEHRKTNfdgLPRVKDERcweiidNIKGTE--YTLSGLKFDSKYmNFRVRACNKAV 253
Cdd:pfam00041  11 VTSTSLTVSWTPPPDGNgPITGYEVEYRPKN---SGEPWNEI------TVPGTTtsVTLTGLKPGTEY-EVRVQAVNGGG 80

                  ....*
gi 563407067  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 563407067    2 DSQKEALQRIISTLANKNDEIQNFIDTLHHTLKGvQENSSNILSeldEEFDSLYSILDEvKESMINcikqEQARKSQELQ 81
Cdd:pfam10174 302 ESELLALQTKLETLTNQNSDCKQHIEVLKESLTA-KEQRAAILQ---TEVDALRLRLEE-KESFLN----KKTKQLQDLT 372

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 563407067   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 563407067 270 FNLDNSSSHLNLKVED--TCVEWDPTGGKGQESkikgkenkgsvhvtslkkhtsgtpspkrtsvgsrppavrgSRDRFTG 347
Cdd:cd13734    1 FKLDPKTAHRKLRLSNdnLTVEYDPEGSKDQAA----------------------------------------VLPRRFT 40

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 563407067 348 ESYTVLGDTAIESGQHYWEVKAQKDCkSYSVGVAYKTLGKFDQLGKTNTSWCIHVNNwlqNTFAAKHNNKVKALDVTV-P 426
Cdd:cd13734   41 GSPAVLGDVAISSGRHYWEVSVSRST-SYRVGVAYKSAPRDEDLGKNSTSWCLSRDN---NRYTARHDGKVVDLRVTGhP 116

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 563407067 427 EKIGVFCDFDGGQLSFYDANSKQLLYSFKTKFTQPVLPGFMVWCGGLSL 475
Cdd:cd13734  117 ARIGVLLDYDNGTLSFYDAESKQHLYTFHVDFEGPVCPAFAVWNGSLTL 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 563407067 327 KRTSVGSRPPAVRGSRDRFTgeSYTVLGDTAIESGQHYWEVKAQKdCKSYSVGVAYKTL---GKFDQLGKTNTSWCIHVN 403
Cdd:cd12891   19 KTVTCSSENQHYPDSPERFT--HSQVLSTQSFSSGRHYWEVEVSE-SGGWSVGVAYPSIerkGDESRIGRNDKSWCLEWQ 95

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 563407067 404 NwlqNTFAAKHNNKVKALDVTVPEKIGVFCDFDGGQLSFYD-ANSKQLLYSFKTKFTQPVLPGFMVWCGG 472
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 563407067 323 TPSPKRTSVGSRPPAVRGSRDRFTGESytVLGDTAIESGQHYWEVKAQKdCKSYSVGVAYKTLGKFDQLGKTNTSWCIHV 402
Cdd:cd12902   15 SEDSRKVTVSHGPQAYAWSPDRFSISQ--VLCSQAFSSGQHYWEVDTRQ-CSHWAVGVASWEMSRDQMLGRTMDSWCIEW 91

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 563407067 403 NNWLQntFAAKHNNKVKALDVTVPEKIGVFCDFDGGQLSFYD-ANSKQLLYSFKTKFTQPVLPGFmvWCGGLSLSTGMQV 481
Cdd:cd12902   92 KGTGQ--LSAWHMNKETVLGSDKPRVVGIWLDLEEGKLAFYSvANQERLLHECEVSASSPLHPAF--WLYGLEPGNSLII 167

                 .
gi 563407067 482 P 482
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 563407067 360 SGQHYWEVkaQKDCKSYSVGVAYKTL---GKFDQ--LGKTNTSWCIhvnNWLQNTFAAKHNNKVKalDVTVPE----KIG 430
Cdd:cd16040   60 SGRCYWEV--EWSGGGVDIAVAYKGIsrkGDGDDsrFGYNDKSWSL---ECSPSGYSFWHNNKKT--EISVPSssssRVG 132

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 563407067 431 VFCDFDGGQLSFYDANSK-QLLYSFKTKFTQPVLPGFMVWCGG 472
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 563407067 330 SVGSRPPAVRGSRDRFTGESyTVLGDTAIESGQHYWEVKAQKD--CksySVGVAYKTL---GKFDQLGKTNTSWCIHvnn 404
Cdd:cd13736   22 SVSDDPQNYREHPQRFTYCS-QVLGLHCFKQGIHYWEVELQKNnfC---GVGICYGSMdrqGPESRLGRNSESWCVE--- 94

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 563407067 405 WLQNTFAAKHNNKVKALDVTVPEKIGVFCDFDGGQLSFYDANSK-QLLYSFKTKFTQPVLPGFMVWCGGLSLS 476
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 563407067 331 VGSRPPAVRGSRDRFTgESYTVLGDTAIESGQHYWEVKAQKDcKSYSVGVAYKTLGKFDQLGKTNTSWcihVNNWLQNT- 409
Cdd:cd12903   26 LGVDPTKVPQNPERFR-DWAVVLGDTPVTSGRHYWEVTVKRS-QEFRIGVADVDMSRDECIGTNESSW---VFAYAQRKw 100

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 563407067 410 FAAKHNNKVKALDVTVPEKIGVFCDFDGGQLSFYDANSKQLLYSFKTKFTQPVLPGFMVWCGGL 473
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 563407067 325 SPKRTSV--GSRPPAVRGSRDRFTgESYTVLGDTAIESGQHYWEVKAqKDCKSYSVGVAYKTLgkfDQLGKTNTS----- 397
Cdd:cd13733   16 SEDLKSVryGDKRQNLPDNPERFD-TCVCVLGSEGFSSGRHYWEVEV-GGKTDWDLGVARESV---NRKGKITLSpengy 90

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 563407067 398 WCIhvnnWLQNtfaakhNNKVKALD--------VTVPEKIGVFCDFDGGQLSFYDANSKQLLYSFKTKFTQPVLPGF 466
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 563407067 334 RPPAVRGSRDRFTGESYTVLGDTAIESGQHYWEVKAQKdcKSYSVGVAYKTL------GKFDQLGKTNTSW--CIHvnnw 405
Cdd:cd12896   36 RSAARGVPASPGSFELWQVQCTQSFQHGHHYWEVEVSS--HSVTLGVTYPGLprhkqgGHKDNIGRNPCSWglQIQ---- 109

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 563407067 406 lQNTFAAKHNNKVKALDVTVPEKIGVFCDFDGGQLSFY-DANSKQLLYSFKTKFTQPVLPGFmvW-CGGLSLS 476
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 563407067 306 ENKGSVHVTSLKKHTSgtPSPKRTSVGsrpPAVRGSrdrftgESYTvlgdtaieSGQHYWEVKAQKDCKsYSVGVAYKTL 385
Cdd:cd15828   27 EDRKSVLYGEMKQNVC--YNPRRFYLC---PAVLGS------EGFH--------SGRQYWEVEVGDKPE-WTLGVCQDCL 86

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 563407067 386 --GKFDQLGKTNTSWCIhvNNWLQNTFAAKHNNKVKALDVTVPEKIGVFCDFDGGQLSFYDANSKQLLYSFKTKFTQPVL 463
Cdd:cd15828   87 prNWSNQPSVQDGLWAI--GRYSESNYVALGPKKIQLLPKVRPSKIGIFLDYELGEVSFYNMNDRSLLYTFSDSFTGTLW 164

                 ...
gi 563407067 464 PGF 466
Cdd:cd15828  165 PYF 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 563407067 352 VLGDTAIESGQHYWEVKAQKD--CksysVGVAYK---TLGK---FDQLGKTNTSWCIHvnnWLQNTFAAKHNNKVKALDV 423
Cdd:cd13737   44 VLCTRSLCEGCHYWEAEVSNSwvC----LGVTYSyshPTGKsciFYLIGRNPYSWCLE---WDSLKFSVWHNNIQTVVHG 116

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 563407067 424 TVPEKIGVFCDFDGGQLSFYD-ANSKQLLYSFKTKFTQPVLPGFMVWCG 471
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 563407067 319 HTSGTPSPKRTSV--GSRPPAVRGSRDRFTgESYTVLGDTAIESGQHYWEVKAQKDCKsYSVGVAYKTLGKFD--QLGKT 394
Cdd:cd12905   14 HPSLILSRDLTAVteSDEMQPYPRSPKRFL-QCVNVLASQGFQSGRHYWEVWVGSKTK-WDLGVASESVDRQArvKLCPE 91

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 563407067 395 NTSWCIHVNNwlQNTFAAKHNNKVKALDVTVPEKIGVFCDFDGGQLSFYDANSKQLLYSFKTKFTQPVLPGF 466
Cdd:cd12905   92 NGYWTLRLRN--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 563407067 306 ENKGSVHVTSLKKHTSGTPSpkrtsvgsrppavrgsrdRFTGESyTVLGDTAIESGQHYWEVKAQK-DCKSYSVGVAYKT 384
Cdd:cd15826   17 EDRKSVRYTRQKQNLPDSPL------------------RFDGLP-AVLGSPGFSSGRHRWQVEVQLgDGGGCTVGVAGES 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 563407067 385 LGKFDQLGKTNTS--WCIHVNNwlQNTFAAKHNNKVKALDVTvPEKIGVFCDFDGGQLSFYDANSKQLLYSFKTKFTQPV 462
Cdd:cd15826   78 VRRKGEMGLSAEDgvWAVILSH--QQCWASTSPGTDLPLSEI-PRRVGVALDYEAGTVTLTNAETQEPIFTFTASFSGKV 154

                        170
                 ....*....|...
gi 563407067 463 LPGFMVWCGGLSL 475
Cdd:cd15826  155 FPFFAVWKKGSRL 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 563407067 352 VLGDTAIESGQHYWEVKAqKDCKSYsVGVAYKTLgkfDQLGK--------TNTSWCIHvnnWLQNTFAAKHNNKVKALDV 423
Cdd:cd12890   54 VLSQQSLYLGRYYFEVEI-SGEGTY-VGLTYKSI---DRKGSesnscisgNNFSWCLQ---WNGKEFSAWHSDVETPLKK 125

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 563407067 424 TVPEKIGVFCDFDGGQLSFY--DANSKQLLYSFKTKFTQPVLPGF 466
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 563407067 345 FTGESYTVLGDTAIESGQHYWEVKAQKD--------CKSYSVGVAYKTLGKFDQLGKT-----NTSWCIHVNNWLQ-NTF 410
Cdd:cd15825   32 FKCYNYGILGSQYFSSGKHYWEVDVSKKtawilgvyCRKRSRTFKYVRQGKNHPNVYSryrpqYGYWVIGLQNKSEyYAF 111

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 563407067 411 --AAKHNNKVKALDVTVP-EKIGVFCDFDGGQLSFYD-ANSKQLLYSF-KTKFTQPVLPGFMVW 469
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 563407067 325 SPKRTSVGSRPPAVRGSRDRFTGESYTVLGDTAIESGQHYWEV--------------KAQKDCKSYSVGVAYKTLGKFDQ 390
Cdd:cd15810   16 SEDQRQVRIVPPQTSGQALTNNNYDFGVLGSQYFSSGKHYWEVdvskksawilgvcsHKRSDAMTKSNANQINHQNVYSR 95

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 563407067 391 LGKTNTSWCIHVNNWLQ-NTF--AAKHNNKVKALDVTV-PEKIGVFCDFDGGQLSFYD-ANSKQLLYSF-KTKFTQPVLP 464
Cdd:cd15810   96 YQPQYGYWVIGLQNESEyNAFedSSSFNPHVLTLSVTVpPHRVGVFLDYEAGTVSFFNvTNHGSLIYKFsKCCFSTTVCP 175

                 ....*
gi 563407067 465 GFMVW 469
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 563407067 332 GSRPPAVRGSRDRFtgESY-TVLGDTAIESGQHYWEVkAQKDCKSYSVGVAYKTLGKfdqLGKTNTS-----WCIhvnnW 405
Cdd:cd15816   25 GELWRDVPGNPERF--DTWpCVLGLQSFSSGRHYWEV-AVGEKAEWGLGVCQDSAPR---KGETTPSpengvWAV----W 94

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 563407067 406 L--QNTFAAKHNNKVKALDVTVPEKIGVFCDFDGGQLSFYDANSKQLLYSFKTKFTQPVLPGFMV 468
Cdd:cd15816   95 LlkGNEYMVLASPSVPLLQLRRPRRVGVFLDYEAGEISFYNVTAGSHIYTFRQLFSGILRPYFFV 159