RING finger, HC subclass, found in tripartite motif-containing proteins TRIM43, TRIM48, TRIM49, TRIM51, TRIM64 and similar proteins; The family includes a group of closely related uncharacterized tripartite motif-containing proteins, TRIM43, TRIM43B, TRIM48/RNF101, TRIM49/RNF18, TRIM49B, TRIM49C/TRIM49L2, TRIM49D/TRIM49L, TRIM51/SPRYD5, TRIM64, TRIM64B, and TRIM64C, whose biological function remain unclear. TRIM49, also known as testis-specific RING-finger protein, has moderate similarity with SS-A/Ro52 antigen, suggesting it may be one of the target proteins of autoantibodies in the sera of patients with these autoimmune disorders. All family members 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 as well as a SPRY/B30.2 domain positioned C-terminal to the RBCC domain. In RBCC region, they all have a C3HC4-type RING-HC finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1751221780   9 FQRELTCPICMNYFIDPITIDCGHSFCRPCFYLNWQDITVLVQCSKCKKTTRQRNLRTN 67
Cdd:cd16603     1 FQRELTCPICMNYFIDPVTIDCGHSFCRPCLYLNWQDIPFLAQCPECRKTTEQRNLKTN 59

B-box-type 2 zinc finger found in tripartite motif-containing proteins TRIM43, TRIM48, TRIM49, TRIM51, TRIM64, TRIM77 and similar proteins; The family includes a group of closely related uncharacterized tripartite motif-containing proteins, TRIM43, TRIM43B, TRIM48/RNF101, TRIM49/RNF18, TRIM49B, TRIM49C/TRIM49L2, TRIM49D/TRIM49L, TRIM51/SPRYD5, TRIM64, TRIM64B, TRIM64C, and TRIM77, whose biological functions remain unclear. TRIM49, also known as testis-specific RING-finger protein, has moderate similarity with SS-A/Ro52 antigen, suggesting it may be one of target proteins of autoantibodies in the sera of patients with these autoimmune disorders. All family members (except for TRIM51) belong to the C-IV subclass of 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 a coiled coil region, as well as a SPRY/B30.2 domain positioned C-terminal to the RBCC domain. TRIM51 belongs to unclassified TRIM (tripartite motif) family of proteins that do not have RING fingers. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1751221780  87 SSEEQICGTHREIKKVFCEVDKSLLCLLCSNSQEHRDHKHCPIEWAAEEHREK 139
Cdd:cd19783     1 SSEEQICGTHRETKKLFCEADKSLLCLLCSSSQEHRAHRHYPIEWAAEEHREK 53

RING finger, HC subclass, found in tripartite motif-containing proteins TRIM43, TRIM48, TRIM49, TRIM51, TRIM64 and similar proteins; The family includes a group of closely related uncharacterized tripartite motif-containing proteins, TRIM43, TRIM43B, TRIM48/RNF101, TRIM49/RNF18, TRIM49B, TRIM49C/TRIM49L2, TRIM49D/TRIM49L, TRIM51/SPRYD5, TRIM64, TRIM64B, and TRIM64C, whose biological function remain unclear. TRIM49, also known as testis-specific RING-finger protein, has moderate similarity with SS-A/Ro52 antigen, suggesting it may be one of the target proteins of autoantibodies in the sera of patients with these autoimmune disorders. All family members 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 as well as a SPRY/B30.2 domain positioned C-terminal to the RBCC domain. In RBCC region, they all have a C3HC4-type RING-HC finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1751221780   9 FQRELTCPICMNYFIDPITIDCGHSFCRPCFYLNWQDITVLVQCSKCKKTTRQRNLRTN 67
Cdd:cd16603     1 FQRELTCPICMNYFIDPVTIDCGHSFCRPCLYLNWQDIPFLAQCPECRKTTEQRNLKTN 59

B-box-type 2 zinc finger found in tripartite motif-containing proteins TRIM43, TRIM48, TRIM49, TRIM51, TRIM64, TRIM77 and similar proteins; The family includes a group of closely related uncharacterized tripartite motif-containing proteins, TRIM43, TRIM43B, TRIM48/RNF101, TRIM49/RNF18, TRIM49B, TRIM49C/TRIM49L2, TRIM49D/TRIM49L, TRIM51/SPRYD5, TRIM64, TRIM64B, TRIM64C, and TRIM77, whose biological functions remain unclear. TRIM49, also known as testis-specific RING-finger protein, has moderate similarity with SS-A/Ro52 antigen, suggesting it may be one of target proteins of autoantibodies in the sera of patients with these autoimmune disorders. All family members (except for TRIM51) belong to the C-IV subclass of 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 a coiled coil region, as well as a SPRY/B30.2 domain positioned C-terminal to the RBCC domain. TRIM51 belongs to unclassified TRIM (tripartite motif) family of proteins that do not have RING fingers. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1751221780  87 SSEEQICGTHREIKKVFCEVDKSLLCLLCSNSQEHRDHKHCPIEWAAEEHREK 139
Cdd:cd19783     1 SSEEQICGTHRETKKLFCEADKSLLCLLCSSSQEHRAHRHYPIEWAAEEHREK 53

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 1751221780 340 KYYWEVHVG--DSWNWAFGVCnnYWKEKRQNDKIDG-EEGLFLL-GCvkeDAHCSLFTTSPLVVQYVPRPTSRVGLFLDC 415
Cdd:pfam00622   1 RHYFEVEIFgqDGGGWRVGWA--TKSVPRKGERFLGdESGSWGYdGW---TGKKYWASTSPLTGLPLFEPGDVIGCFLDY 75

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1751221780 416 EGRTMTFVDVDQNaLIYTIPNCSFSPPLRPIFCCSH 451
Cdd:pfam00622  76 EAGTISFTKNGKS-LGYAFRDVPFAGPLFPAVSLGA 110

Uncharacterized conserved protein, contains RING and CCCH-type Zn-fingers [General function prediction only];

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1751221780  15 CPICMNYFIDPITIDCGHSFCRPCFYLNWQDITVLVQCSK 54
Cdd:COG5152   199 CGICKKDYESPVVTECGHSFCSLCAIRKYQKGDECGVCGK 238

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1751221780   6 LQVFQRELTCPICMNYFIDPITIDCGHSFCRPCF--YLNWQDitvlvQCSKCKKTTRQRNLRTNIRLKKMA---SIARKa 80
Cdd:TIGR00599  20 LYPLDTSLRCHICKDFFDVPVLTSCSHTFCSLCIrrCLSNQP-----KCPLCRAEDQESKLRSNWLVSEIVesfKNLRP- 93

                  ....*.
gi 1751221780  81 SLRQFL 86
Cdd:TIGR00599  94 SLLEFL 99

B-box zinc finger;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1751221780  88 SEEQICGTH-REIKKVFCEVDKSLLCLLCSnSQEHRDHKHCPI 129
Cdd:pfam00643   1 SKERLCPEHeEEPLTLYCNDCQELLCEECS-VGEHRGHTVVPL 42

RING finger, HC subclass, found in tripartite motif-containing proteins TRIM43, TRIM48, TRIM49, TRIM51, TRIM64 and similar proteins; The family includes a group of closely related uncharacterized tripartite motif-containing proteins, TRIM43, TRIM43B, TRIM48/RNF101, TRIM49/RNF18, TRIM49B, TRIM49C/TRIM49L2, TRIM49D/TRIM49L, TRIM51/SPRYD5, TRIM64, TRIM64B, and TRIM64C, whose biological function remain unclear. TRIM49, also known as testis-specific RING-finger protein, has moderate similarity with SS-A/Ro52 antigen, suggesting it may be one of the target proteins of autoantibodies in the sera of patients with these autoimmune disorders. All family members 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 as well as a SPRY/B30.2 domain positioned C-terminal to the RBCC domain. In RBCC region, they all have a C3HC4-type RING-HC finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1751221780   9 FQRELTCPICMNYFIDPITIDCGHSFCRPCFYLNWQDITVLVQCSKCKKTTRQRNLRTN 67
Cdd:cd16603     1 FQRELTCPICMNYFIDPVTIDCGHSFCRPCLYLNWQDIPFLAQCPECRKTTEQRNLKTN 59

B-box-type 2 zinc finger found in tripartite motif-containing proteins TRIM43, TRIM48, TRIM49, TRIM51, TRIM64, TRIM77 and similar proteins; The family includes a group of closely related uncharacterized tripartite motif-containing proteins, TRIM43, TRIM43B, TRIM48/RNF101, TRIM49/RNF18, TRIM49B, TRIM49C/TRIM49L2, TRIM49D/TRIM49L, TRIM51/SPRYD5, TRIM64, TRIM64B, TRIM64C, and TRIM77, whose biological functions remain unclear. TRIM49, also known as testis-specific RING-finger protein, has moderate similarity with SS-A/Ro52 antigen, suggesting it may be one of target proteins of autoantibodies in the sera of patients with these autoimmune disorders. All family members (except for TRIM51) belong to the C-IV subclass of 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 a coiled coil region, as well as a SPRY/B30.2 domain positioned C-terminal to the RBCC domain. TRIM51 belongs to unclassified TRIM (tripartite motif) family of proteins that do not have RING fingers. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1751221780  87 SSEEQICGTHREIKKVFCEVDKSLLCLLCSNSQEHRDHKHCPIEWAAEEHREK 139
Cdd:cd19783     1 SSEEQICGTHRETKKLFCEADKSLLCLLCSSSQEHRAHRHYPIEWAAEEHREK 53

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 1751221780 288 DFTLQPERANSHIFLYGDLRSINVGCDPQDDPH----FtakSECFLVWGAQTFTSGKYYWEVHVGDSWNWAFGVCnnywK 363
Cdd:cd13733     1 DVTLDPDTAHPNLILSEDLKSVRYGDKRQNLPDnperF---DTCVCVLGSEGFSSGRHYWEVEVGGKTDWDLGVA----R 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1751221780 364 E--KRQ-NDKIDGEEGLFLLGCVKEDAHCSLFTTS-PLVVQYVPRptsRVGLFLDCEGRTMTFVDVDQNALIYTIPNCsF 439
Cdd:cd13733    74 EsvNRKgKITLSPENGYWTVGLRNGNEYKALTSPStPLSLREKPQ---KVGVFLDYEEGQVSFYNVDDGSHIYTFTDC-F 149

                  ....*....
gi 1751221780 440 SPPLRPIFC 448
Cdd:cd13733   150 TEKLYPYFS 158

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 1751221780 285 FRVDFTLQPERANSHIFLYGDLRSINVGCDPQDDPH----FTAkseCFLVWGAQTFTSGKYYWEVHVGDSWNWAFGVC-- 358
Cdd:cd13745     1 FAVDVTLDPDTAHPNLVLSEDRKSVRHGDTRQDLPDnperFDT---YPCVLGAEGFTGGRHYWEVEVGDKTEWTLGVCre 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1751221780 359 -------------NNYWKEKRQNDKIdgeeglfllgcvkeDAHCSLFTTSPLVVqyvpRPtSRVGLFLDCEGRTMTFVDV 425
Cdd:cd13745    78 svsrkgevtlspeNGYWTVWLRDGKY--------------EALTSPPTPLPVSV----RP-SRVGIFLDYEAGEVSFYNV 138

                         170       180
                  ....*....|....*....|...
gi 1751221780 426 DQNALIYTIPNcSFSPPLRPIFC 448
Cdd:cd13745   139 TDRSHLFTFTD-TFSGTLRPYFY 160

PRY/SPRY domain of tripartite motif-binding protein 11 (TRIM11), also known as RING finger protein 92 (RNF92); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM11, also known as RING finger protein 92 (RNF92) or BIA1. TRIM11 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. It localizes to the nucleus and the cytoplasm; it is overexpressed in high-grade gliomas and promotes proliferation, invasion, migration and glial tumor growth. TRIM11 increases expression of dopamine beta-hydroxylase gene by interacting with the homeodomain transcription factor, PHOX2B, via the B30.2/SPRY domain, thus playing a potential role in the specification of noradrenergic (NA) neuron phenotype. It has also been shown that TRIM11 plays a critical role in the clearance of mutant PHOX2B, which causes congenital central hypoventilation syndrome, via the proteasome. TRIM11 binds a key component of the activator-mediated cofactor complex (ARC105), and destabilizes it, through the ubiquitin-proteasome system; ARC105 mediates chromatin-directed transcription activation and is a key regulatory factor for transforming growth factor beta (TGFbeta) signaling.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1751221780 288 DFTLQPERANSHIFLYGDLRSINVGCDPQ---DDPHFTAKSECFLvwGAQTFTSGKYYWEVHVGDSWNWAFGVCNNYWKE 364
Cdd:cd15811     1 DVTLDPDTANPELVLSEDRRSVRRGDLRQalpDSPERFDPGPCVL--GRERFTSGRHYWEVEVGDRTSWALGVCKENVNR 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1751221780 365 KRQNDKIDGeEGLFLLGCVKEDAHCSLFTTSPLvvqyvPRPTSRVGLFLDCEGRTMTFVDVDQNALIYTIPNCSFSPPLR 444
Cdd:cd15811    79 KEKGELSAG-NGFWILVFLGNYYSSERRTFAPL-----RDPPRRVGIFLDYEAGHLSFYSATDGSLLFIFPETPFSGTLR 152

                  ...
gi 1751221780 445 PIF 447
Cdd:cd15811   153 PLF 155

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 1751221780 288 DFTLQPERANSHIFLYGDLRSINVGCDPQDDPHFTAKSECFLVWGAQTFTSGKYYWEVHVGDSWNWAFGVCN-------- 359
Cdd:cd15810     1 DVTLNPVNISLNIVISEDQRQVRIVPPQTSGQALTNNNYDFGVLGSQYFSSGKHYWEVDVSKKSAWILGVCShkrsdamt 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1751221780 360 --NYWKEKRQND--KIDGEEGLFLLGcVKEDAHCSLFTTS-----PLVVQYVPRPTSRVGLFLDCEGRTMTFVDV-DQNA 429
Cdd:cd15810    81 ksNANQINHQNVysRYQPQYGYWVIG-LQNESEYNAFEDSssfnpHVLTLSVTVPPHRVGVFLDYEAGTVSFFNVtNHGS 159

                         170
                  ....*....|....*...
gi 1751221780 430 LIYTIPNCSFSPPLRPIF 447
Cdd:cd15810   160 LIYKFSKCCFSTTVCPYF 177

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 1751221780 279 LDRL-SGFRVDFTLQPERANSHIFLYGDLRSINVGCDPQDDPHFTAK-SECFLVWGAQTFTSGKYYWEVHVGDSWNWAFG 356
Cdd:cd15828     1 LDRIiKRFQVDVTLDPETAHPQLTVSEDRKSVLYGEMKQNVCYNPRRfYLCPAVLGSEGFHSGRQYWEVEVGDKPEWTLG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1751221780 357 VCNNYWKEKRQNdKIDGEEGLFllgCVKEDAHCSLFTTSPLVVQYVPRPT-SRVGLFLDCEGRTMTFVDVDQNALIYTIP 435
Cdd:cd15828    81 VCQDCLPRNWSN-QPSVQDGLW---AIGRYSESNYVALGPKKIQLLPKVRpSKIGIFLDYELGEVSFYNMNDRSLLYTFS 156

                         170
                  ....*....|...
gi 1751221780 436 NCsFSPPLRPIFC 448
Cdd:cd15828   157 DS-FTGTLWPYFY 168

PRY/SPRY domain in tripartite motif-containing protein 22 (TRIM22), also known as RING finger protein 94 (RNF94) or Stimulated trans-acting factor of 50 kDa (STAF50); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM22, also known as RING finger protein 94 (RNF94) or STAF50 (Stimulated trans-acting factor of 50 kDa). TRIM6 domain is composed of RING/B-box/coiled-coil core and also known as RBCC protein. TRIM22 is an interferon-induced protein, predominantly expressed in peripheral blood leukocytes, in lymphoid tissue such as spleen and thymus, and in the ovary.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. TRIM22 inhibits influenza A virus (IAV) infection by targeting the viral nucleoprotein for degradation; it represents a novel restriction factor up-regulated upon IAV infection that curtails its replicative capacity in epithelial cells. Altered TRIM22 expression has also been associated with multiple sclerosis, cancer, and autoimmune disease. A large number of high-risk non-synonymous (ns)SNPs have been identified in the highly polymorphic TRIM22 gene, most of which are located in the SPRY domain and could possibly alter critical regions of the SPRY structural and functional residues, including several sites that undergo post-translational modification. TRIM22 is a direct p53 target gene and inhibits the clonogenic growth of leukemic cells. Its expression in Wilms tumors is negatively associated with disease relapse. It is greatly under-expressed in breast cancer cells as compared to non-malignant cell lines; p53 dysfunction may be one of the mechanisms for its down-regulation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1751221780 287 VDFTLQPERANSHIFLYGDLRSINVGCDPQ----DDPHFTAksecFLVWGAQTFTSGKYYWEVHVGDSWNWAFGVC---N 359
Cdd:cd15824     3 VDVMLNPVNAVSNVVVSADQRQVTVVHICMfrnsNPCDFSA----FDVLGCQYFSSGKYYWEVDVSGKIAWILGVYskrN 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1751221780 360 NYWKEK-----------RQN--DKIDGEEGLFLLGCVKE---DAHCSLFTTSPLVVQ-YVPRPTSRVGLFLDCEGRTMTF 422
Cdd:cd15824    79 NLNKRKssgfafdpnvnHPNvySRYRPQNGYWVIGLQNEseyNAFEDSSSSDPKVLTlSMAVPPHRVGVFLDYEAGTVSF 158

                         170       180
                  ....*....|....*....|....*.
gi 1751221780 423 VDV-DQNALIYTIPNCSFSPPLRPIF 447
Cdd:cd15824   159 FNVtNHGSLIYKFSKCCFSQPVYPYF 184

PRY/SPRY domain of tripartite motif-binding protein 75 (TRIM75); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM75, also known as Gm794. TRIM75 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. TRIM75 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 1751221780 285 FRVDFTLQPERANSHIFLYGDLRSINVGCDPQDDPH----FTAKSecfLVWGAQTFTSGKYYWEVHVGDSWNWAFGVC-- 358
Cdd:cd15829    17 FRVDVTLDPETAHPNLLVSEDKKCVTFTKKKQRVPDspkrFTVNP---VVLGFPGFHSGRHFWEVEVGDKPEWAVGVCkd 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1751221780 359 -------------NNYWKEKRQNDkidgeeglfllGCVKEDAhcslfTTSPLVVQYVPRptsRVGLFLDCEGRTMTFVDV 425
Cdd:cd15829    94 slstkarrppsgqQGCWRIQLQGG-----------DYDAPGA-----VPPPLLLEVKPR---GIGVFLDYELGEISFYNM 154

                         170       180
                  ....*....|....*....|...
gi 1751221780 426 DQNALIYTIPNcSFSPPLRPIFC 448
Cdd:cd15829   155 PEKSHIHTFTD-TFSGPLRPYFY 176

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 1751221780 289 FTLQPERANSHIFLYGDLRSINVGCDPQ---DDPH-FTaksECFLVWGAQTFTSGKYYWEVHVGDSWNWAFGVCnnywKE 364
Cdd:cd12893     2 VTLDPNTAHPWLSLSEDLTSVRYSSEKQqlpDNPErFD---PYPCVLGSEGFTSGKHSWDVEVGDNTSWMLGVA----KE 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1751221780 365 KRQ-NDKIDG--EEGL----FLLGCVKedAHCSLFTTSPLVVQYVPRptsRVGLFLDCEGRTMTFVDVDQNALIYTIPNc 437
Cdd:cd12893    75 SVQrKGKFTLspESGFwtigFSEGKYS--ARTSPEPRTPLRVKQKPQ---RIRVQLDWDRGKVSFSDPDTNTHIHTFTH- 148

                         170
                  ....*....|..
gi 1751221780 438 SFSPPLRPIFCC 449
Cdd:cd12893   149 TFTERVFPYFYT 160

PRY/SPRY domain in tripartite motif-binding protein 6 (TRIM6), also known as RING finger protein 89 (RNF89); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM6, also known as RING finger protein 89 (RNF89). TRIM6 domain is composed of RING/B-box/coiled-coil core and also known as RBCC protein. It 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1751221780 285 FRVDFTLQPERANSHIFLYGDLRSIN-VGCDPQDDPHFTAKSECFlVWGAQTFTSGKYYWEVHVGDSWNWAFGVCNN--- 360
Cdd:cd15823     1 YWVDVTLNPHTANLNLVLSKNRRQVRfVGAKLSGPSYLEEHYDCS-VLGSQHFSSGKHYWEVDVTKKTAWILGVCSHslg 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1751221780 361 -------YWKEKRQNDKIDGEEGLFLLGCVKEDAHCSLFTTSPLVVQYVPRPTSRVGLFLDCEGRTMTFVDVDQNAL-IY 432
Cdd:cd15823    80 ptfsfnqYAQNHNAYSRYQPQSGYWVIGLQHNHEYRAYEDSSTSLLLSMTVPPRRVGVFLDYEAGTVSFYNVTNHGFpIY 159

                         170
                  ....*....|....*
gi 1751221780 433 TIPNCSFSPPLRPIF 447
Cdd:cd15823   160 TFSKYYFPTTLCPYF 174

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 1751221780 287 VDFTLQPERANSHIFLYGDLRSINVGCDPQDDPHFTAKSECF-LVWGAQTFTSGKYYWEVHVGDSWNWAFGVCNNYWKEK 365
Cdd:cd15814     2 VDVTLDPDTAYPSLILSDNLRQVRYSYLQQDLPDNPERFNLFpCVLGSPCFIAGRHYWEVEVGDKAKWTIGVCEDSVCRK 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1751221780 366 RQNDKIDgEEGLFLLGCVKEDAHCSLftTSPLVVQYVPRPTSRVGLFLDCEGRTMTFVDVDQNALIYTIPNCSFSPPLRP 445
Cdd:cd15814    82 GGVTSAP-QNGFWAVSLWYGKEYWAL--TSPMTALPLRTPLQRVGIFLDYDAGEVSFYNVTERCHTFTFSHATFCGPVRP 158

                  ....*.
gi 1751221780 446 IFCCSH 451
Cdd:cd15814   159 YFSLSY 164

RING finger, HC subclass, found in tripartite motif-containing protein TRIM4 and similar proteins; TRIM4 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 three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox2, and a coiled coil region, as well as a SPRY/B30.2 domain positioned C-terminal to the RBCC domain. TRIM4, also known as RING finger protein 87 (RNF87), is a cytoplasmic E3 ubiquitin-protein ligase that has recently evolved and is present only in higher mammals. It transiently interacts with mitochondria, induces mitochondrial aggregation and sensitizes the cells to hydrogen peroxide (H2O2) induced death. Its interaction with peroxiredoxin 1 (PRX1) is critical for the regulation of H2O2 induced cell death. Moreover, TRIM4 functions as a positive regulator of RIG-I-mediated type I interferon induction. It regulates the K63-linked ubiquitination of RIG-1 and assembly of antiviral signaling complex at the mitochondria.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1751221780  10 QRELTCPICMNYFIDPITIDCGHSFCRPCFYLNWQDITVLVQCSKCKKTTRQRNLRTN 67
Cdd:cd16590     4 QEELTCPICLDYFQDPVSIECGHNFCRGCLHRNWAPGGGPFPCPECRHPSAPAALRPN 61

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 1751221780 288 DFTLQPERANSHIFLYGDLRSI-----NVGCdPQDDPHFTAkseCFLVWGAQTFTSGKYYWEVHVGDSWNWAFGVCNNYW 362
Cdd:cd15817     1 DLILDPETAHPNLIVSEDRKAVryrrmKPNC-PYDPRRFTV---YPAVLGSEGFDSGRHFWEVEVGGKGEWILGVCKDSL 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1751221780 363 KEKRQnDKIDGEEGLFLLGCVKEDAHCSLFTTSPLVVQYVPRptsRVGLFLDCEGRTMTFVDVDQNALIYTIPNCsFSPP 442
Cdd:cd15817    77 PRNAQ-DPPSPLGGCWQIGRYMSGYVASGPKTTQLLPVVKPS---RIGIFLDYELGEVSFYNMNDRSHLYTFTDT-FTGK 151

                  ....*
gi 1751221780 443 LRPIF 447
Cdd:cd15817   152 LIPYF 156

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 1751221780 325 SECFLVWGAQTFTSGKYYWEVHVGDSWNWAFGVCnnyWKEKRQNDKIDGEEGLFllgCVKEDAHCSLF----TTSPLVVQ 400
Cdd:cd13734    40 TGSPAVLGDVAISSGRHYWEVSVSRSTSYRVGVA---YKSAPRDEDLGKNSTSW---CLSRDNNRYTArhdgKVVDLRVT 113

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1751221780 401 YVPRptsRVGLFLDCEGRTMTFVDVDQNALIYTIpNCSFSPPLRPIFC 448
Cdd:cd13734   114 GHPA---RIGVLLDYDNGTLSFYDAESKQHLYTF-HVDFEGPVCPAFA 157

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 1751221780 293 PERANSHIFLYGDLRSINVGCDPQDDPHftaKSECFLVW----GAQTFTSGKYYWEVHV---GDSWnWAFGVCNNYWKEK 365
Cdd:cd15812     6 PSTAYPYLLLYESRQRRYLSTPPDGTPC---SKDRFLAYpcavGQETFSSGRHYWEVGMnltGDAL-WALGVCRDNVSRK 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1751221780 366 RQNDKIDgEEGLFLLGCVKEDAHCSLFTTSPLVVqyVPRPTSRVGLFLDCEGRTMTFVDVDQNALIYTIPNCSFSPPLRP 445
Cdd:cd15812    82 DRVPKSP-ENGFWVVQLSKGKKYLSAMSALTPVT--LTEPPSHMGIFLDFEAGEVSFYSVNDGSHLHTYSQAAFPGPLQP 158

                  ...
gi 1751221780 446 IFC 448
Cdd:cd15812   159 FFC 161

PRY/SPRY domain in tripartite motif-binding (TRIM) proteins TRIM50 and TRIM72; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of several TRIM proteins, including TRIM72 and TRIM50. TRIM72 (also known as 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. 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1751221780 288 DFTLQPERANSHIFLYGDLRSINVGCDPQ---DDPHFTAKSECFLvwGAQTFTSGKYYWEVHVGDSWNWAFGVCNNYWKE 364
Cdd:cd12897    13 SLTFDPATAHPLLVVSSGGTVVECGLQKQrraSQPERFDKSTCVV--ASQGFSEGEHYWEVVVGDKPRWALGVIKGTASR 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1751221780 365 KRQNDKIDgEEGLFLLGCvKE----DAHCSlfTTSPLVVQYVPRPTsRVGLFLDCEGRTMTFVDVDQN---ALIYTIpNC 437
Cdd:cd12897    91 KGKLHASP-SHGVWLIGL-KEgkvyEAHGE--PKEPRPLRVAGRPH-RIGVYLSFEDGVLSFFDASDPddlRTLYTF-QE 164

                         170
                  ....*....|....*
gi 1751221780 438 SFSPPLRPIF-CCSH 451
Cdd:cd12897   165 RFQGKLYPFFdVCWH 179