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 13236585 165 PSAPViDLAESLVADNCVTLVWRMPDED-SKIDHYVLEYRRTNfegpprlkeDQPWMVIEG--IRQTEYTLTGLKFDMKY 241
Cdd:cd00063   1 PSPPT-NLRVTDVTSTSVTLSWTPPEDDgGPITGYVVEYREKG---------SGDWKEVEVtpGSETSYTLTGLKPGTEY 70

                        90       100
                ....*....|....*....|....
gi 13236585 242 mNFRVKACNKAVAGEFSEPVTLET 265
Cdd:cd00063  71 -EFRVRAVNGGGESPPSESVTVTT 93

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 13236585 165 PSAPViDLAESLVADNCVTLVWRMPDED-SKIDHYVLEYRRTNfegpprlkeDQPWMVIEG--IRQTEYTLTGLKFDMKY 241
Cdd:cd00063   1 PSPPT-NLRVTDVTSTSVTLSWTPPEDDgGPITGYVVEYREKG---------SGDWKEVEVtpGSETSYTLTGLKPGTEY 70

                        90       100
                ....*....|....*....|....
gi 13236585 242 mNFRVKACNKAVAGEFSEPVTLET 265
Cdd:cd00063  71 -EFRVRAVNGGGESPPSESVTVTT 93

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13236585      4 QREALRKIIKTLAVKNEEIQSFIYSLKQMLLNVEANSAKVQEDLEAEFQSLFSLLEELKEGMLMKIKQDRASRTYELQNQ 83
Cdd:smart00502   1 QREALEELLTKLRKKAAELEDALKQLISIIQEVEENAADVEAQIKAAFDELRNALNKRKKQLLEDLEEQKENKLKVLEQQ 80

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 13236585     84 LAACTRALESSEELLETANQTLQAMDSEDFPQAAKQI 120
Cdd:smart00502  81 LESLTQKQEKLSHAINFTEEALNSGDPTELLLSKKLI 117

SPRY domain; SPRY Domain is named from SPla and the RYanodine Receptor and it is found in many eukaryotic proteins with a wide range of functions. It is a protein-interaction module involved in many important signalling pathways like RNA processing, regulation of histone H3 methylation, innate immunity or embryonic development. It can be divided into 11 subfamilies based on amino acid sequence similarity or the presence of additional protein domains. The greater SPRY family is divided into the SPRY/B30.2 (which contains a PRY extension at the N-terminal) and SPRY-only sub-families which are preceded by a subdomain that is structurally similar to the PRY region. SPRY/B30.2 structures revealed a bent beta-sandwich fold comprised of two beta-sheets. Distant homologs are domains in butyrophilin/ marenostrin/pyrin.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13236585   356 HYWEVRYE-PDSKAFGVGVAYRS--LGRFEQLGKTAASWCLHvNNWLQVSFTAKHANKVKVLDAPvPDCLGVHCDFHQGL 432
Cdd:pfam00622   2 HYFEVEIFgQDGGGWRVGWATKSvpRKGERFLGDESGSWGYD-GWTGKKYWASTSPLTGLPLFEP-GDVIGCFLDYEAGT 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 13236585   433 LSFYNArTKQVLHTFKT-RFTQPLLPAFTVWCG-SFQVTTGLQ 473
Cdd:pfam00622  80 ISFTKN-GKSLGYAFRDvPFAGPLFPAVSLGAGeGLKFNFGLR 121

Fibronectin type III domain;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 13236585   182 VTLVWRMPDE-DSKIDHYVLEYRRTNfegpprlKEDQPWMVIEGIRQTEYTLTGLKFDMKYmNFRVKACNKAVAGEFS 258
Cdd:pfam00041  16 LTVSWTPPPDgNGPITGYEVEYRPKN-------SGEPWNEITVPGTTTSVTLTGLKPGTEY-EVRVQAVNGGGEGPPS 85

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 13236585 270 FRLDASTSHQNLRV--DDLSVEWDamggkvqdikarekdgkgrtaspinspargtpsPKRMPSGRGGRDRFTAESYTVLG 347
Cdd:cd13734   1 FKLDPKTAHRKLRLsnDNLTVEYD---------------------------------PEGSKDQAAVLPRRFTGSPAVLG 47

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13236585 348 DTLIDGGEHYWEVRYEpDSKAFGVGVAYRSLGRFEQLGKTAASWCLHVNNwlqVSFTAKHANKVKVLD-APVPDCLGVHC 426
Cdd:cd13734  48 DVAISSGRHYWEVSVS-RSTSYRVGVAYKSAPRDEDLGKNSTSWCLSRDN---NRYTARHDGKVVDLRvTGHPARIGVLL 123

                       170       180       190       200
                ....*....|....*....|....*....|....*....|..
gi 13236585 427 DFHQGLLSFYNARTKQVLHTFKTRFTQPLLPAFTVWCGSFQV 468
Cdd:cd13734 124 DYDNGTLSFYDAESKQHLYTFHVDFEGPVCPAFAVWNGSLTL 165

PRY/SPRY domain of TRIM18/MID1, also known as FXY or RNF59; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is at the C-terminus of the overall domain architecture of MID1 (also known as FXY, RNF59, TRIM18) gene represented by a RING finger domain (RING), two B-box motifs (BBOX), coiled-coil C-terminal to Bbox domain (BBC) and fibronectin type 3 domain (FN3). Mutations in the human MID1 gene result in X-linked Opitz G/BBB syndrome (OS), a disorder affecting development of midline structures, causing craniofacial, urogenital, gastrointestinal and cardiovascular abnormalities. A unique MID1 gene mutation located in a variable loop in the SPRY domain alters conformation of the binding pocket and may affect the binding affinity to the PRY/SPRY domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13236585 270 FRLDASTSHQNLRV--DDLSVEWDAMGGKvqdikarekdgkgRTASPinspargtpspkrmpsgrggrDRFTAE-SYTVL 346
Cdd:cd12892   2 FKLDPKSAHRKLKVshDNLTVERDETSSK-------------KSHTP---------------------ERFTSQgSYGVA 47

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13236585 347 GDTLIDGGEHYWEVRYEpDSKAFGVGVAYRSLGRFEQLGKTAASW--CLHVNNWLqvsftAKHANK-VKVLDAPVPDCLG 423
Cdd:cd12892  48 GNVFIDSGRHYWEVVIS-GSTWYAIGIAYKSAPKHEWIGKNSASWvlCRCNNNWV-----VRHNSKeIPIEPSPHLRRVG 121

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|..
gi 13236585 424 VHCDFHQGLLSFYNARTKQVLHTFKTRFTQPLLPAFTVWCGSFQVTTGLQVP 475
Cdd:cd12892 122 ILLDYDNGSLSFYDALNSIHLYTFDIAFAQPVCPTFTVWNKCLTILTGLPIP 173

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13236585 270 FRLDASTSHQNLRVDDlsvewdamggkvqDIKAREKDgkgrtaspiNSPARGTPSPKRMpSGRGgrdrftaeSYTVLGDT 349
Cdd:cd13739   1 FKLDPKMAHKKLKISN-------------DGLQMEKD---------ESSLKKSHTPERF-SGTG--------CYGAAGNI 49

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13236585 350 LIDGGEHYWEVRYEpDSKAFGVGVAYRSLGRFEQLGKTAASWCL-HVNNwlqvSFTAKHANKVKVLDAPvPDC--LGVHC 426
Cdd:cd13739  50 FIDSGCHYWEVVVG-SSTWYAIGIAYKSAPKNEWIGKNSSSWVFsRCNN----NFVVRHNNKEMLVDVP-PQLkrLGVLL 123

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*.
gi 13236585 427 DFHQGLLSFYNARTKQVLHTFKTRFTQPLLPAFTVWCGSFQVTTGL 472
Cdd:cd13739 124 DYDNNMLSFYDPANSLHLHTFEVSFILPVCPTFTIWNKSLMILSGL 169

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 13236585 345 VLGDTLIDGGEHYWEVRYEPDSKAFGVGVAYRSLGR-----FEQLGKTAASWCLH---VNNWlqvSFTAKHANKVKVLDA 416
Cdd:cd13738  43 VLSRDSFFSGRHYWEVDLQEAGAGWWVGAAYPSIGRkgdseAARLGWNRQSWCLKrydLEYW---AFHDGQRSRLRPEDD 119

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|
gi 13236585 417 pvPDCLGVHCDFHQGLLSFYNARTKQV-LHTFKTRFTQPLLPAFTVWCGS 465
Cdd:cd13738 120 --PDRLGVFLDYEAGILSFYDVTGGMThLHTFRATFQEPLYPALRLWEGS 167

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 13236585 336 DRFTAESytVLGDTLIDGGEHYWEVRYEpDSKAFGVGVAYRSLGRFEQLGKTAASWCLHVNNWLQVSftAKHANKVKVLD 415
Cdd:cd12902  35 DRFSISQ--VLCSQAFSSGQHYWEVDTR-QCSHWAVGVASWEMSRDQMLGRTMDSWCIEWKGTGQLS--AWHMNKETVLG 109

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 13236585 416 APVPDCLGVHCDFHQGLLSFYN-ARTKQVLHTFKTRFTQPLLPAF 459
Cdd:cd12902 110 SDKPRVVGIWLDLEEGKLAFYSvANQERLLHECEVSASSPLHPAF 154

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 13236585 345 VLGDTLIDGGEHYWEVRYEpDSKAFGVGVAYRSLGRFEQLGKTAASWclhVNNWLQVSFTAKHANKVkvldAPV-----P 419
Cdd:cd12903  46 VLGDTPVTSGRHYWEVTVK-RSQEFRIGVADVDMSRDECIGTNESSW---VFAYAQRKWYAMVANET----VPVplvgkP 117

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 13236585 420 DCLGVHCDFHQGLLSFYNARTKQVLHTFKTRFTQPLLPAFTVWCG 464
Cdd:cd12903 118 DRVGLLLDYEAGKLSLVDVEKNSVVHTMSAEFRGPVVPAFALWDG 162

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 13236585 165 PSAPViDLAESLVADNCVTLVWRMPDED-SKIDHYVLEYRRTNfegpprlkeDQPWMVIEG--IRQTEYTLTGLKFDMKY 241
Cdd:cd00063   1 PSPPT-NLRVTDVTSTSVTLSWTPPEDDgGPITGYVVEYREKG---------SGDWKEVEVtpGSETSYTLTGLKPGTEY 70

                        90       100
                ....*....|....*....|....
gi 13236585 242 mNFRVKACNKAVAGEFSEPVTLET 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 13236585    354 GEHYWEVRYEpDSKAFGVGVAYRS--LGRFEQLGKTAASWCLHVNNWLQVsftakHANKVKVLDAPV---PDCLGVHCDF 428
Cdd:smart00449   2 GRHYFEVEIG-DGGHWRVGVATKSvpRGYFALLGEDKGSWGYDGDGGKKY-----HNSTGPEYGLPLqepGDVIGCFLDL 75

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 13236585    429 HQGLLSFYNARTKQV-LHTFKTRFTQPLLPAFTVWCG 464
Cdd:smart00449  76 EAGTISFYKNGKYLHgLAFFDVKFSGPLYPAFSLGSG 112

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 13236585 354 GEHYWEVRYEPDSKAFGVGVAYR-SLGR---FEQLGKTAASWCLHvnnWLQVSFTAKHANKVKVLDAPVPDCLGVHCDFH 429
Cdd:cd13737  53 GCHYWEAEVSNSWVCLGVTYSYShPTGKsciFYLIGRNPYSWCLE---WDSLKFSVWHNNIQTVVHGSYYKTIGVLLDYA 129

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 13236585 430 QGLLSFYN-ARTKQVLHTFKTRFTQPLLPAFTVWCGS 465
Cdd:cd13737 130 AGSLTFYGvANTMNLIYRFLTTFTEPLYPAVMVSSGA 166

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 13236585 337 RFTAEsYTVLGDTLIDGGEHYWEVRYEpDSKAFGVGVAYRSLGRFE--QLGKTAASWCLHVNNWLQVSFTAKHANKVKVL 414
Cdd:cd13744  50 RFDVE-VSVLGSEGFSGGVHYWEVVVS-EKTQWMIGLAHEAVSRKGsiQIQPGRGFYCIVMHDGNQYSACTEPWTRLNVK 127

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 13236585 415 DAPvpDCLGVHCDFHQGLLSFYNARTKQVLHTFKTRFTQPLLPAFT 460
Cdd:cd13744 128 SKL--EKVGVYLDYDKGLLIFYNADDMSWLYTFREKFPGKLCSYFS 171

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 13236585 354 GEHYWEVryepDSKAFG--VGVAYRSLGRFEQ-----LGKTAASWCLHvnnWLQVSFTAKHANKVKVLDAPVPDCLGVHC 426
Cdd:cd12890  63 GRYYFEV----EISGEGtyVGLTYKSIDRKGSesnscISGNNFSWCLQ---WNGKEFSAWHSDVETPLKKGPFTRLGIYL 135

                        90       100       110
                ....*....|....*....|....*....|....*
gi 13236585 427 DFHQGLLSFY--NARTKQVLHTFKTRFTQPLLPAF 459
Cdd:cd12890 136 DYPGGTLSFYgvEDDGMTLLHKFQCKFTEPLYPAF 170

PRY/SPRY domain of tripartite motif-binding protein 60 and 75 (TRIM60 and TRIM75); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM60 and TRIM75, both composed of RING/B-box/coiled-coil core and also known as RBCC proteins. TRIM60 domain is also known as RING finger protein 33 (RNF33) or 129 (RNF129). Based on its expression profile, RNF33 likely plays an important role in the spermatogenesis process, the development of the pre-implantation embryo, and in testicular functions; Rnf33 is temporally transcribed in the unfertilized egg and the pre-implantation embryo, and is permanently silenced before the blastocyst stage. Mice experiments have shown that RNF33 associates with the cytoplasmic motor proteins, kinesin-2 family members 3A (KIF3A) and 3B (KIF3B), suggesting possible contribution to cargo movement along the microtubule in the expressed sites. TRIM75, also known as Gm794, has a single site of positive selection in its RING domain associated with E3 ubiquitin ligase activity. It has not been detectably expressed experimentally due to their constant turnover by the proteasome, and therefore not been characterized.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13236585 337 RFTAESyTVLGDTLIDGGEHYWEVRYEPDSKaFGVGVAYRSLGRFEQLGKTAASWCLHVNNWLQvSFTAKHANKVKVLDA 416
Cdd:cd15817  37 RFTVYP-AVLGSEGFDSGRHFWEVEVGGKGE-WILGVCKDSLPRNAQDPPSPLGGCWQIGRYMS-GYVASGPKTTQLLPV 113

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 13236585 417 PVPDCLGVHCDFHQGLLSFYNARTKQVLHTFKTRFTQPLLPAFTV 461
Cdd:cd15817 114 VKPSRIGIFLDYELGEVSFYNMNDRSHLYTFTDTFTGKLIPYFYV 158

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 13236585 337 RFTaESYTVLGDTLIDGGEHYWEVRYEpDSKAFGVGVAYRSLGRFEQLGKTAAS--WCL-HVNNWLQVSFTAKHANKVKV 413
Cdd:cd12893  37 RFD-PYPCVLGSEGFTSGKHSWDVEVG-DNTSWMLGVAKESVQRKGKFTLSPESgfWTIgFSEGKYSARTSPEPRTPLRV 114

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|...
gi 13236585 414 ldAPVPDCLGVHCDFHQGLLSFYNARTKQVLHTFKTRFTQPLLPAFTVWCGSF 466
Cdd:cd12893 115 --KQKPQRIRVQLDWDRGKVSFSDPDTNTHIHTFTHTFTERVFPYFYTGCKSE 165

PRY/SPRY domain in tripartite motif-containing proteins, TRIM9 and TRIM67; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM9 proteins. TRIM9 protein is expressed mainly in the cerebral cortex, and functions as an E3 ubiquitin ligase. It has been shown that TRIM9 is localized to the neurons in the normal human brain and its immunoreactivity in affected brain areas in Parkinson's disease and dementia with Lewy bodies is severely decreased, possibly playing an important role in the regulation of neuronal function and participating in pathological process of Lewy body disease through its ligase. TRIM67 negatively regulates Ras activity via degradation of 80K-H, leading to neural differentiation, including neuritogenesis.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13236585 339 TAESY---TVLGDTLIDGGEHYWEV---RYEPDSK-AFgvGVAYRSLGRFEQLGKTAASWCLHVNN---WLQvsFTAKHA 408
Cdd:cd12889  31 TCNSYedrVVLGSVGFSRGVHYWEVtidRYDGHPDpAF--GVARIDVNKDKMLGKDDKGWSMYIDNnrsWFL--HNNEHS 106

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 13236585 409 NKVKVlDAPVPDCLGVHCDFHQGLLSFYNARTKQVLHTFKTRFTQpLLPAFTVWCGSfQVT--TGLQVP 475
Cdd:cd12889 107 NRTEG-GITVGSVVGVLLDLDRHTLSFYVNDEPQGPIAFRNLPGV-FYPAVSLNRNV-QVTlhTGLEPP 172

PRY/SPRY domain in tripartite motif-binding protein 7 (TRIM7)-like, including TRIM7, TRIM10, TRIM15, TRIM26, TRIM39, TRIM41; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of several tripartite motif-containing (TRIM) proteins, including TRIM7 (also referred to as glycogenin-interacting protein, RING finger protein 90 or RNF90), TRIM10, TRIM15, TRIM26, TRIM39 and TRIM41. TRIM7 or GNIP interacts with glycogenin and stimulates its self-glucosylating activity via its SPRY domain. TRIM10 (also known as hematopoietic RING finger 1 (HERF1) or TRIM10/HERF1) plays a key role in definitive erythroid development; downregulation of the Spi-1/PU.1 oncogene induces the expression of TRIM10/HERF1, a key factor required for terminal erythroid cell differentiation and survival. Antiviral activity of TRIM15 is dependent on the ability of its B-box to interact with the MLV Gag precursor protein; downregulation of TRIM15, along with TRIM11, enhances virus release suggesting that these proteins contribute to the endogenous restriction of retroviruses in cells. Tripartite motif-containing 26 (TRIM26) function is as yet unknown; however, since it is localized in the human histocompatibility complex (MHC) class I region, TRIM26 may play a role in immune response although studies show no association between TRIM26 polymorphisms and the risk of aspirin-exacerbated respiratory disease. TRIM39 is a MOAP-1 (Modulator of Apoptosis)-binding protein that stabilizes MOAP-1 through inhibition of its poly-ubiquitination process. TRIM41 (also known as RING finger-interacting protein with C kinase or RINCK) functions as an E3 ligase that catalyzes the ubiquitin-mediated degradation of protein kinase C.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 13236585 319 ARGTPSPKRMPSGRGgrdRFTAEsYTVLGDTLIDGGEHYWEVRYEpDSKAFGVGVAYRSLGRFEQLGKTAAS--WCLHVN 396
Cdd:cd12888  22 VRWGDTRQDLPDNPE---RFDTW-PCVLGCEGFTSGRHYWEVEVG-DGGGWAVGVARESVRRKGEISFSPEEgiWAVGQW 96

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 13236585 397 NWLqvsFTAKHANKVKVLDAPVPDCLGVHCDFHQGLLSFYNARTKQVLHTFKTRF--TQPLLPAFTVWCGS 465
Cdd:cd12888  97 GGQ---YWALTSPETPLPLSEVPRRIRVYLDYEGGQVAFFDADNEAPIFTFPPASfaGERIFPWFWVGKGS 164

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 13236585 337 RFTAESyTVLGDTLIDGGEHYWEVRYE-PDSKAFGVGVAYRSLGRFEQLGKTAAS--WCL---HVNNWlqvsftAKHANK 410
Cdd:cd15826  37 RFDGLP-AVLGSPGFSSGRHRWQVEVQlGDGGGCTVGVAGESVRRKGEMGLSAEDgvWAVilsHQQCW------ASTSPG 109

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|..
gi 13236585 411 VKVLDAPVPDCLGVHCDFHQGLLSFYNARTKQVLHTFKTRFTQPLLPAFTVW 462
Cdd:cd15826 110 TDLPLSEIPRRVGVALDYEAGTVTLTNAETQEPIFTFTASFSGKVFPFFAVW 161

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 13236585 345 VLGDTLIDGGEHYWEVRYEpDSKAFGVGVAYRSLGRfeqLGKTAAS--------WCLHVNNWLQVSftakhANKVKVLDA 416
Cdd:cd15816  44 VLGLQSFSSGRHYWEVAVG-EKAEWGLGVCQDSAPR---KGETTPSpengvwavWLLKGNEYMVLA-----SPSVPLLQL 114

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 13236585 417 PVPDCLGVHCDFHQGLLSFYNARTKQVLHTFKTRFTQPLLPAFTV 461
Cdd:cd15816 115 RRPRRVGVFLDYEAGEISFYNVTAGSHIYTFRQLFSGILRPYFFV 159

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 13236585 345 VLGDTLIDGGEHYWEVRYEpDSKAFGVGVAYRSLGRFEQLGKTAAS--WClhVNNWLQVSFTAKHANKVKVLDAPVPDCL 422
Cdd:cd15828  54 VLGSEGFHSGRQYWEVEVG-DKPEWTLGVCQDCLPRNWSNQPSVQDglWA--IGRYSESNYVALGPKKIQLLPKVRPSKI 130

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 13236585 423 GVHCDFHQGLLSFYNARTKQVLHTFKTRFTQPLLPAF 459
Cdd:cd15828 131 GIFLDYELGEVSFYNMNDRSLLYTFSDSFTGTLWPYF 167