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 24233550 281 LSRIIKQFQADVTFDRDTAHPQLVISEDRKSVFYKEAWPCVCASPQKFHLWPALLGCKGFDSGRQYWEVKVGDKPRWTLG 360
Cdd:cd15828   1 LDRIIKRFQVDVTLDPETAHPQLTVSEDRKSVLYGEMKQNVCYNPRRFYLCPAVLGSEGFHSGRQYWEVEVGDKPEWTLG 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24233550 361 VCQAHFSGDWSNQSS---GFWAIGRYAENSYVTYGPLRTEFLPVVRPSKVGIFLDYELGELSFYNMNDRSLLYTFRNSFT 437
Cdd:cd15828  81 VCQDCLPRNWSNQPSvqdGLWAIGRYSESNYVALGPKKIQLLPKVRPSKIGIFLDYELGEVSFYNMNDRSLLYTFSDSFT 160

                       170       180
                ....*....|....*....|
gi 24233550 438 STLWPYFYIGTDSESLEILT 457
Cdd:cd15828 161 GTLWPYFYTGTDSEPLKICT 180

B-box-type zinc finger superfamily; The B-box-type zinc finger is a short zinc binding domain of around 40 amino acid residues in length. It has been found in transcription factors, ribonucleoproteins and proto-oncoproteins, such as in TRIM (tripartite motif) proteins that consist of an N-terminal RING finger (originally called an A-box), followed by 1-2 B-box domains and a coiled-coil domain (also called RBCC for Ring, B-box, Coiled-Coil). The B-box-type zinc finger often presents in combination with other motifs, like RING zinc finger, NHL motif, coiled-coil or RFP domain in functionally unrelated proteins, most likely mediating protein-protein interactions. Based on different consensus sequences and the spacing of the 7-8 zinc-binding residues, B-box-type zinc fingers can be divided into two groups, type 1 (Bbox1: C6H2) and type 2 (Bbox2: CHC3H2).

                        10        20        30
                ....*....|....*....|....*....|....*....
gi 24233550  94 TVCPKHDQPLVLFCVRDRDVLCTQCSLSVEHQGHYTCPI 132
Cdd:cd19791   1 TLCEKHNQPLTKFCKKDLEPLCPQCSQSTDHQHHVVVPL 39

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 24233550 281 LSRIIKQFQADVTFDRDTAHPQLVISEDRKSVFYKEAWPCVCASPQKFHLWPALLGCKGFDSGRQYWEVKVGDKPRWTLG 360
Cdd:cd15828   1 LDRIIKRFQVDVTLDPETAHPQLTVSEDRKSVLYGEMKQNVCYNPRRFYLCPAVLGSEGFHSGRQYWEVEVGDKPEWTLG 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24233550 361 VCQAHFSGDWSNQSS---GFWAIGRYAENSYVTYGPLRTEFLPVVRPSKVGIFLDYELGELSFYNMNDRSLLYTFRNSFT 437
Cdd:cd15828  81 VCQDCLPRNWSNQPSvqdGLWAIGRYSESNYVALGPKKIQLLPKVRPSKIGIFLDYELGEVSFYNMNDRSLLYTFSDSFT 160

                       170       180
                ....*....|....*....|
gi 24233550 438 STLWPYFYIGTDSESLEILT 457
Cdd:cd15828 161 GTLWPYFYTGTDSEPLKICT 180

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 24233550    342 SGRQYWEVKVGDKPRWTLGVCQAHFSGDWSNQS---SGFWAIGRYAENSYVTYGPLRTEFLPVVRPSKVGIFLDYELGEL 418
Cdd:smart00449   1 SGRHYFEVEIGDGGHWRVGVATKSVPRGYFALLgedKGSWGYDGDGGKKYHNSTGPEYGLPLQEPGDVIGCFLDLEAGTI 80

                           90       100       110
                   ....*....|....*....|....*....|
gi 24233550    419 SFYNMNDRSLLYTFRN-SFTSTLWPYFYIG 447
Cdd:smart00449  81 SFYKNGKYLHGLAFFDvKFSGPLYPAFSLG 110

B-box-type 2 zinc finger found in tripartite motif-containing proteins, TRIM60, TRIM61, TRIM75 and similar proteins; This family includes a group of tripartite motif-containing proteins, including TRIM60, TRIM61 and TRIM75. TRIM60, also known as RING finger protein 129 (RNF129) or RING finger protein 33 (RNF33), is a cytoplasmic protein expressed in the testis. It may play an important role in the spermatogenesis process, the development of the preimplantation embryo, and in testicular functions. TRIM60 interacts with the cytoplasmic kinesin motor proteins KIF3A and KIF3B suggesting possible contribution to cargo movement along the microtubule in the expressed sites. It is also involved in spermatogenesis in Sertoli cells under the regulation of nuclear factor-kappaB (NF-kappaB). TRIM61 is closely related to TRIM60, but its biological function remains unclear. TRIM75 could be the product of a pseudogene. Its biological function remains unclear. TRIM60 and TRIM75 belong to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a RING finger, Bbox2, and two coiled coil domains, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. In contrast, TRIM61 belongs to the C-V subclass of TRIM family that contains RBCC domains only. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                        10        20        30
                ....*....|....*....|....*....|....*....
gi 24233550  94 TVCPKHDQPLVLFCVRDRDVLCTQCSLSVEHQGHYTCPI 132
Cdd:cd19791   1 TLCEKHNQPLTKFCKKDLEPLCPQCSQSTDHQHHVVVPL 39

RING-finger-containing E3 ubiquitin ligase [Signal transduction mechanisms];

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 24233550   5 ALKILQDKCICYICSDFMEDPVTSRCGHNFCFACLRllwDDLQGNIFCPVCQTPF 59
Cdd:COG5432  18 SLKGLDSMLRCRICDCRISIPCETTCGHTFCSLCIR---RHLGTQPFCPVCREDP 69

DNA repair protein rad18; All proteins in this family for which functions are known are involved in nucleotide excision repair.This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 24233550     4 TALKILQDKCICYICSDFMEDPVTSRCGHNFCFACLRllwDDLQGNIFCPVCQTPFPPKSFSRNYQFRNMTETIRLLQK 82
Cdd:TIGR00599  18 PSLYPLDTSLRCHICKDFFDVPVLTSCSHTFCSLCIR---RCLSNQPKCPLCRAEDQESKLRSNWLVSEIVESFKNLRP 93

B-Box-type zinc finger;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 24233550     94 TVCPKH-DQPLVLFCVRDRDVLCTQCSLSvEHQGHYTCPI 132
Cdd:smart00336   4 PKCDSHgDEPAEFFCEECGALLCRTCDEA-EHRGHTVVLL 42

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 24233550 281 LSRIIKQFQADVTFDRDTAHPQLVISEDRKSVFYKEAWPCVCASPQKFHLWPALLGCKGFDSGRQYWEVKVGDKPRWTLG 360
Cdd:cd15828   1 LDRIIKRFQVDVTLDPETAHPQLTVSEDRKSVLYGEMKQNVCYNPRRFYLCPAVLGSEGFHSGRQYWEVEVGDKPEWTLG 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24233550 361 VCQAHFSGDWSNQSS---GFWAIGRYAENSYVTYGPLRTEFLPVVRPSKVGIFLDYELGELSFYNMNDRSLLYTFRNSFT 437
Cdd:cd15828  81 VCQDCLPRNWSNQPSvqdGLWAIGRYSESNYVALGPKKIQLLPKVRPSKIGIFLDYELGEVSFYNMNDRSLLYTFSDSFT 160

                       170       180
                ....*....|....*....|
gi 24233550 438 STLWPYFYIGTDSESLEILT 457
Cdd:cd15828 161 GTLWPYFYTGTDSEPLKICT 180

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 24233550 291 DVTFDRDTAHPQLVISEDRKSVFYKEAWPCVCASPQKFHLWPALLGCKGFDSGRQYWEVKVGDKPRWTLGVCQAHFSGDW 370
Cdd:cd15817   1 DLILDPETAHPNLIVSEDRKAVRYRRMKPNCPYDPRRFTVYPAVLGSEGFDSGRHFWEVEVGGKGEWILGVCKDSLPRNA 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24233550 371 SNQSS---GFWAIGRYaENSYVTYGPLRTEFLPVVRPSKVGIFLDYELGELSFYNMNDRSLLYTFRNSFTSTLWPYFYIG 447
Cdd:cd15817  81 QDPPSplgGCWQIGRY-MSGYVASGPKTTQLLPVVKPSRIGIFLDYELGEVSFYNMNDRSHLYTFTDTFTGKLIPYFYVG 159

                ....*...
gi 24233550 448 TDSESLEI 455
Cdd:cd15817 160 PDSEPLTI 167

PRY/SPRY domain in tripartite motif-binding protein 39 (TRIM39) and TRIM39-like; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of pyrin, several tripartite motif-containing proteins (TRIMs), including E3 ubiquitin-protein ligase (TRIM21), RET finger protein (RFP)/tripartite motif protein 27 (TRIM27), as well as butyrophilin (Btns) and butyrophilin-like (Btnl) family members, with the exception of Btnl2. Btn and Btnl family members are novel regulators of immune responses, with many of the genes located within the MHC. They are implicated in T-cell inhibition and modulation of epithelial cell-T cell interactions. TRIM21 (also known as RO52, SSA1 or RNF81) is a major autoantigen in autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and Sjorgen's syndrome. TRIM27 (also known as Ret finger protein, RFP or RNF76) negatively regulates CD4 T-cells by ubiquitinating and inhibiting the class II phosphatidylinositol 3 kinase C2beta (PI3K-C2beta), a kinase critical for KCa3.1 channel activation. The PRY/SPRY domain of Pyrin, which is mutated in familial Mediterranean fever patients, interacts with inflammasome components and inhibits proIL-1beta processing.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24233550 288 FQADVTFDRDTAHPQLVISEDRKSVFYKEAWPCVCASPQKFHLWPALLGCKGFDSGRQYWEVKVGDKPRWTLGVCQAHFS 367
Cdd:cd13745   1 FAVDVTLDPDTAHPNLVLSEDRKSVRHGDTRQDLPDNPERFDTYPCVLGAEGFTGGRHYWEVEVGDKTEWTLGVCRESVS 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24233550 368 GDWSNQSS---GFWAI----GRYAENsyvTYGPLRtefLPV-VRPSKVGIFLDYELGELSFYNMNDRSLLYTFRNSFTST 439
Cdd:cd13745  81 RKGEVTLSpenGYWTVwlrdGKYEAL---TSPPTP---LPVsVRPSRVGIFLDYEAGEVSFYNVTDRSHLFTFTDTFSGT 154

                ....*...
gi 24233550 440 LWPYFYIG 447
Cdd:cd13745 155 LRPYFYPG 162

PRY/SPRY domain of tripartite motif-binding protein 38 (TRIM38), also known as Ring finger protein 15 (RNF15); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM38, which is also known as RING finger protein 15 (RNF15) or RORET. TRIM38 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. TRIM38 has been shown to act as a suppressor in TOLL-like receptor (TLR)-mediated interferon (IFN)-beta induction by promoting degradation of TRAF6 and NAP1 through the ubiquitin-proteasome system. Another study has shown that TRIM38 may act as a novel negative regulator for TLR3-mediated IFN-beta signaling by targeting TRIF for degradation. TRIM38 has been identified as a critical negative regulator in TNFalpha- and IL-1beta-triggered activation of NF-kappaB and MAP Kinases (MAPKs); it causes degradation of two essential cellular components, TGFbeta-associated kinase 1 (TAK1)-associating chaperones 2 and 3 (TAB2/3). The degradation is promoted through a lysosomal-dependent pathway, which requires the C-terminal PRY-SPRY of TRIM38. Enterovirus 71 infection induces degradation of TRIM38, suggesting that TRIM38 may play a role in viral infections.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24233550 278 YSGLSRIIKQFQADVTFDRDTAHPQLVISEDRKSVFYKEAWPCVCASPQKFHLWPALLGCKGFDSGRQYWEVKVGDKPRW 357
Cdd:cd15815   1 YFDVKKMLRRHQVSVTLDPDTAHPELTLSKDQRQVTYGRCQENLDASPKRFTVLPCVLGCEGFTSGRHYFEVDVGEGTGW 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24233550 358 TLGVC----QAHFsGDWSNQSSGFWAIGRYAENSYVTYGPLRTEFLPVVRPSKVGIFLDYELGELSFYNMNDRSLLYTF- 432
Cdd:cd15815  81 DVGVClenvQRGF-GMKQEPEFGFWTIRLCEEDGYVALTSPPTPLPLREKPLVVGVFLDYEAGLVSFYNMTTGSHIFTFp 159

                       170
                ....*....|..
gi 24233550 433 RNSFTSTLWPYF 444
Cdd:cd15815 160 KASFSDTLRPYF 171

PRY/SPRY domain in tripartite motif-binding protein 20 (TRIM20), also known as pyrin; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM20, which is also known as pyrin or marenostrin. Unlike TRIM domains that are composed of RING/B-box/coiled-coil core, the N-terminal RING domain in TRIM20 is exchanged by a PYRIN domain (PYD), a prime mediator of protein interactions necessary for apoptosis, inflammation and innate immune signaling pathway, and it also harbors a C-terminal B30.2 domain. Mutations in pyrin (TRIM20) are associated with familial Mediterranean fever (FMF), a recessively hereditary periodic fever syndrome, characterized by episodes of inflammation and fever. These mutations cluster in the C-terminal B30.2 domain and therefore it is assumed that pyrin plays a role in the innate immune system by possibly effecting caspase-1-dependent IL-1beta maturation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24233550 283 RIIKQFQADVTFDRDTAHPQLVISEDRKSVFYKEAWPCVCASPQKFHLWPALLGCKGFDSGRQYWEVKVGDKPRWTLGVC 362
Cdd:cd15813   2 RAAQAHAVNVTLDPETAHPNLIFSDDLKSVRLGNKWDRLPDNPERFDSCIIVLGSPSFTSGRHYWEVEVGDKTGWILGVC 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24233550 363 QAHFSGDWSNQSS---GFWAIGRYAENSYVTYGPLRTEFLPVVRPSKVGIFLDYELGELSFYNMNDRSLLYTFRNSFTS- 438
Cdd:cd15813  82 KASVSRKGSMTLSpenGYWVVMMTKRNEYQASTSPPTRLWLREPPRRVGIFLDYEAGDISFYNVTAKSHIYTFTSFSSSg 161

                       170
                ....*....|.
gi 24233550 439 TLWPYFYIGTD 449
Cdd:cd15813 162 PLQPIFSPGTH 172

PRY/SPRY domain of butyrophilin 3 (BTN3), includes BTN3A1, BTN3A2, BTN3A3 as well as BTN-like 3 (BTNL3); BTN3A also known as CD277; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of butyrophilin family 3A (BTN3A); duplication events have led to three paralogs in primates: BTN3A1, BTN3A2, and BTN3A3. BTNs belong to receptor glycoproteins of immunoglobulin (Ig) superfamily, characterized by the presence of extracellular Ig-like domains (IgV and/or IgC). BTN3 transcripts are ubiquitously present in all immune cells (T cells, B cells, NK cells, monocytes, dendritic cells, and hematopoietic precursors) with different expression levels; BTN3A1 and BTN3A2 are expressed mainly by CD4+ and CD8+ T cells, BTN3A2 is the major form expressed in NK cells, and BTN3A3 is poorly expressed in these immune cells. The PRY/SPRY domain of the BTN3A1 isoform mediates phosphoantigen (pAg)-induced activation by binding directly to the pAg.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24233550 288 FQ-ADVTFDRDTAHPQLVISEDRKSVFYKEAWPCVCASPQKFHLWPALLGCKGFDSGRQYWEVKVGDKPRWTLGVCQAHF 366
Cdd:cd15820   1 FQpADVILDPDTANPILLISEDQRSLQWADEPQNLPDNPKRFDWHYCVLGCKSFTSGRHFWEVEVGDRKEWYVGVCRENV 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24233550 367 S-GDWSNQS--SGFWAIGRYAENSYVTYGPLRTEFLPVVRPSKVGIFLDYELGELSFYNMNDRSLLYTF-RNSFTSTLWP 442
Cdd:cd15820  81 ErKLWVKMApeNGFWTIGLSDGNDYQALTDPRTKLTIANPPQRVGVFLDYETGEVSFYNAMDGSHIYTFpHTSFSGPLYP 160

                       170
                ....*....|....*
gi 24233550 443 YFYI-GTDSESLEIL 456
Cdd:cd15820 161 VFRLlSWDPTALTIC 175

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 24233550 292 VTFDRDTAHPQLVISEDRKSVFYKEAWPCVCASPQKFHLWPALLGCKGFDSGRQYWEVKVGDKPRWTLGVCQahFSGD-- 369
Cdd:cd12893   2 VTLDPNTAHPWLSLSEDLTSVRYSSEKQQLPDNPERFDPYPCVLGSEGFTSGKHSWDVEVGDNTSWMLGVAK--ESVQrk 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24233550 370 ---WSNQSSGFWAIGRYaENSYVTYGPLRTEFLPVV--RPSKVGIFLDYELGELSFYNMNDRSLLYTFRNSFTSTLWPYF 444
Cdd:cd12893  80 gkfTLSPESGFWTIGFS-EGKYSARTSPEPRTPLRVkqKPQRIRVQLDWDRGKVSFSDPDTNTHIHTFTHTFTERVFPYF 158

                       170
                ....*....|..
gi 24233550 445 YIGTDSESLEIL 456
Cdd:cd12893 159 YTGCKSEPLRIL 170

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 24233550 290 ADVTFDRDTAHPQLVISEDRKSVFYKEAWPCVCASPQKFHLWPALLGCKGFDSGRQYWEVKVGDKPRWTLGVcqahfSGD 369
Cdd:cd12905   4 APLTFDPETAHPSLILSRDLTAVTESDEMQPYPRSPKRFLQCVNVLASQGFQSGRHYWEVWVGSKTKWDLGV-----ASE 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24233550 370 WSNQS--------SGFWAIGRYAENSYVTYGPLRTEFLPVVRPSKVGIFLDYELGELSFYNMNDRSLLYTFRNSFTSTLW 441
Cdd:cd12905  79 SVDRQarvklcpeNGYWTLRLRNGDEYWAGTQPWTRLRVTSRPQRIGVFLDCEERKVSFYNADDMSLLYSFHQGPRGKVF 158

                ...
gi 24233550 442 PYF 444
Cdd:cd12905 159 PFF 161

PRY/SPRY domain in tripartite motif-containing protein 27 (TRIM27), also known as RING finger protein 76 (RNF76); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM27, also known as RING finger protein 76 (RNF76) or RET finger protein (RFP). TRIM27 domain is composed of RING/B-box/coiled-coil core and also known as RBCC proteins. It is highly expressed in the spleen, thymus and in cells of the hematopoietic compartment. TRIM27 exhibits either nuclear or cytosolic localization depending on the cell type. TRIM27 negatively regulates nucleotide-binding oligomerization domain containing 2 (NOD2)-mediated signaling by proteasomal degradation of NOD2, suggesting that TRIM27 could be a new target for therapeutic intervention in NOD2-associated diseases such as Crohn's. High expression of TRIM27 is observed in several human cancers, including breast and endometrial cancer, where elevated TRIM27 expression predicts poor prognosis. Also, TRIM27 forms an oncogenic fusion protein with Ret proto-oncogene. It is involved in different stages of spermatogenesis and its significant expression in male germ cells and seminomas, suggests that TRIM27 may be associated with the regulation of testicular germ cell proliferation and histological-type of germ cell tumors. TRIM27 could also be a predictive marker for chemoresistance in ovarian cancer patients. In the neurotoxin model of Parkinson's disease (PD), deficiency of TRIM27 decreases apoptosis and protects dopaminergic neurons, making TRIM27 an effective potential target during the treatment of PD.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24233550 291 DVTFDRDTAHPQLVISEDRKSVFYKEAWPCVCASPQKFHLWPALLGCKGFDSGRQYWEVKVGDKPRWTLGVCQAHF---S 367
Cdd:cd15814   3 DVTLDPDTAYPSLILSDNLRQVRYSYLQQDLPDNPERFNLFPCVLGSPCFIAGRHYWEVEVGDKAKWTIGVCEDSVcrkG 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24233550 368 GDWSNQSSGFWAIGR-YAENSYVTYGPLRTefLPVVRP-SKVGIFLDYELGELSFYNMNDRSLLYTFRN-SFTSTLWPYF 444
Cdd:cd15814  83 GVTSAPQNGFWAVSLwYGKEYWALTSPMTA--LPLRTPlQRVGIFLDYDAGEVSFYNVTERCHTFTFSHaTFCGPVRPYF 160

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 24233550 292 VTFDRDTAHPQLVISEDRKSVFYKEAWPCVCASPQKFHLWPALLGCKGFDSGRQYWEVKV--GDKPRWTLGVCQAHF--S 367
Cdd:cd15826   2 VTLDPQTASGSLVLSEDRKSVRYTRQKQNLPDSPLRFDGLPAVLGSPGFSSGRHRWQVEVqlGDGGGCTVGVAGESVrrK 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24233550 368 GDWS-NQSSGFWAIGRYAENSYVTYGPlRTEFLPVVRPSKVGIFLDYELGELSFYNMNDRSLLYTFRNSFTSTLWPYFYI 446
Cdd:cd15826  82 GEMGlSAEDGVWAVILSHQQCWASTSP-GTDLPLSEIPRRVGVALDYEAGTVTLTNAETQEPIFTFTASFSGKVFPFFAV 160

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24233550 292 VTFDRDTAHPQLVISEDRKSVFYKEAWPCVCASPQKFHLWPALLGCKGFDSGRQYWEVKVGDKPRWTLGVC------QAH 365
Cdd:cd12900   5 ITLDPDTANPWLILSKDRRQVRLGDTHQNVPENEERFDNYPMVLGAQRFNSGKHYWEVDVTGKEAWDLGVCrdsvrrKGQ 84

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24233550 366 FSGDWSNqssGFWAIGRYAENSYVTYGPLRTEFLpVVRPSKVGIFLDYELGELSFYNMNDR-SLLYTFRN-SFTSTLWPY 443
Cdd:cd12900  85 FLLSPEN---GFWTIWLWNKKYEAGTSPQTTLHL-QVPPCQVGIFLDYEAGVVSFYNITDHgSLIYTFSEcAFTGPLRPF 160

                ....
gi 24233550 444 FYIG 447
Cdd:cd12900 161 FNPG 164

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 24233550 290 ADVTFDRDTAHPQLVISEDRKSVFYKEAWP-CVCASPQKFHLWPALLGCKGFDSGRQYWEVKVGDKPRWTLGVCQAHFSG 368
Cdd:cd13744  12 AALTLDPVTAHQRLILSDDCTIVAYGNLHPqPLQDSPKRFDVEVSVLGSEGFSGGVHYWEVVVSEKTQWMIGLAHEAVSR 91

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24233550 369 DWSNQ---SSGFWAIGRYAENSYVTYGPLRTEFLPVVRPSKVGIFLDYELGELSFYNMNDRSLLYTFRNSFTSTLWPYFY 445
Cdd:cd13744  92 KGSIQiqpGRGFYCIVMHDGNQYSACTEPWTRLNVKSKLEKVGVYLDYDKGLLIFYNADDMSWLYTFREKFPGKLCSYFS 171

                ..
gi 24233550 446 IG 447
Cdd:cd13744 172 PG 173

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 24233550 292 VTFDRDTAHPQLVISEDRKSVFY---KEAWPCvcaSPQKFhLWPALLGCKGFDSGRQYWEVKVGDKPRWTLGVCQAHFS- 367
Cdd:cd12891   1 LTLDPNTAHNNLALSGDLKTVTCsseNQHYPD---SPERF-THSQVLSTQSFSSGRHYWEVEVSESGGWSVGVAYPSIEr 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24233550 368 -GD-----WSNQSsgfWAIGRYAENSYVTYGPLRTEfLPVVRPSKVGIFLDYELGELSFYNMNDR-SLLYTFRNSFTSTL 440
Cdd:cd12891  77 kGDesrigRNDKS---WCLEWQDKSFSAWHNNEETP-LPSVSSRRLGVYLDYEAGRLSFYELSDPiRHLHTFTATFTEPL 152

                ....*.
gi 24233550 441 WPYFYI 446
Cdd:cd12891 153 HPAFWV 158

RING finger, HC subclass, found in tripartite motif-containing protein 77 (TRIM77) and similar proteins; TRIM77 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including two consecutive zinc-binding domains, a C3HC4-type RING-HC finger and Bbox2, as well as a SPRY/B30.2 domain positioned C-terminal to the RBCC domain.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 24233550  10 QDKCICYICSDFMEDPVTSRCGHNFCFACLRLLWDDLQGNIFCPVCQTPFPPKS 63
Cdd:cd16543   1 EDQLTCSICLDLLKDPVTIPCGHSFCMNCITLLWDRKQGVPSCPQCRESFPPRP 54

PRY/SPRY domain in tripartite motif-binding protein 72 (TRIM72); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM72. Muscle-specific TRIM72 (also known as Mitsugumin 53 or MG53) 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. It is expressed specifically in skeletal muscle and heart, and tethered to the plasma membrane and cytoplasmic vesicles via its interaction with phosphatidylserine. TRIM72 interacts with dysferlin, a sarcolemmal protein whose deficiency causes Miyoshi myopathy (MM) and limb girdle muscular dystrophy type 2B (LGMD2B); this coordination plays an important role in the repair of sarcolemma damage.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24233550 286 KQFQA------DVTFDRDTAHPQLVISEDRKSVFYKEAWPCVCAS-PQKFHLWPALLGCKGFDSGRQYWEVKVGDKPRWT 358
Cdd:cd13742   2 KMFRAlmpaleNLTFDPDTAHPYLVVSSDGKRVECADQKQAVSSDdPNRFDKANCVVSHQSFSEGEHYWEVIVGDKPRWA 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24233550 359 LGVCQAHFSGDWSNQ---SSGFWAIGRYAENSYVTY------GPLRTEflpvVRPSKVGIFLDYELGELSFYNMNDRS-- 427
Cdd:cd13742  82 LGVISAEAGRKGRLHalpSNGFWLLGCKEGKVYEAHvehkepRALRVE----GRPTRIGVYLSFSDGVLSFYDASDEDnl 157

                       170       180       190
                ....*....|....*....|....*....|....
gi 24233550 428 -LLYTFRNSFTSTLWPYFYI-----GTDSESLEI 455
Cdd:cd13742 158 vQLFAFHERFPGPLYPFFDVcwhdkGKNSQPLKI 191

PRY/SPRY domain of tripartite motif-binding protein 17 (TRIM17), also known as testis RING finger protein (terf); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM17, also known as RING finger protein 16 (RNF16) or testis RING finger protein (terf). TRIM17 domain is composed of RING/B-box/coiled-coil core and also known as RBCC protein, expressed almost exclusively in the testis. It exhibits E3 ligase activity, causing protein degradation of ZW10 interacting protein (ZWINT), a known component of the kinetochore complex required for the mitotic spindle checkpoint, and negatively regulates proliferation of breast cancer cells. TRIM17 undergoes ubiquitination in COS7 fibroblast-like cells but is inhibited and stabilized by TRIM44.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24233550 291 DVTFDRDTAHPQLVISEDRKSVFYK---EAWPCvcaSPQKFHLWPALLGCKGFDSGRQYWEVKV---GDKpRWTLGVCQA 364
Cdd:cd15812   1 DVVPDPSTAYPYLLLYESRQRRYLStppDGTPC---SKDRFLAYPCAVGQETFSSGRHYWEVGMnltGDA-LWALGVCRD 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24233550 365 HFS-GDWSNQS--SGFWAIGRYAENSYVTYGPLRTEFLPVVRPSKVGIFLDYELGELSFYNMNDRSLLYTF-RNSFTSTL 440
Cdd:cd15812  77 NVSrKDRVPKSpeNGFWVVQLSKGKKYLSAMSALTPVTLTEPPSHMGIFLDFEAGEVSFYSVNDGSHLHTYsQAAFPGPL 156

                       170
                ....*....|....*....
gi 24233550 441 WPYFYIGT-DSESLEILTH 458
Cdd:cd15812 157 QPFFCLGApKSGQMVISTV 175