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 209862805   9 FQRALTCPICMNYFLDPVTIDCGHSFCRPCLYLNWQDTAVLAQCSECKKTTRQRNLNTD 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
                 ....*....|....*....|....*....|....*....|...
gi 209862805  87 SSEEQICGMHRETKKMFCEVDKSLLCLPCSNSQEHRNHIHCPI 129
Cdd:cd19783    1 SSEEQICGTHRETKKLFCEADKSLLCLLCSSSQEHRAHRHYPI 43

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 209862805   9 FQRALTCPICMNYFLDPVTIDCGHSFCRPCLYLNWQDTAVLAQCSECKKTTRQRNLNTD 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
                 ....*....|....*....|....*....|....*....|...
gi 209862805  87 SSEEQICGMHRETKKMFCEVDKSLLCLPCSNSQEHRNHIHCPI 129
Cdd:cd19783    1 SSEEQICGTHRETKKLFCEADKSLLCLLCSSSQEHRAHRHYPI 43

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 209862805  340 KYYWEVHMG--DSWNWAFGVCnnYWKEKRQNDKIDG-EEGLFLL-GCvkeDTHCSLFTTSPLVVQYVPRPTSTVGLFLDC 415
Cdd:pfam00622   1 RHYFEVEIFgqDGGGWRVGWA--TKSVPRKGERFLGdESGSWGYdGW---TGKKYWASTSPLTGLPLFEPGDVIGCFLDY 75

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 209862805  416 EGRTVSFVDVDQsSLIYTIPNCSFSPPLRPIFCCSH 451
Cdd:pfam00622  76 EAGTISFTKNGK-SLGYAFRDVPFAGPLFPAVSLGA 110

RING-finger-containing E3 ubiquitin ligase [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 209862805  15 CPICMNYFLDPVTIDCGHSFCRPCLYLNWQDTAVLaQCSECkktTRQRNLNTDICLK 71
Cdd:COG5574  218 CFLCLEEPEVPSCTPCGHLFCLSCLLISWTKKKYE-FCPLC---RAKVYPKKVIILR 270

Ring finger; E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of c-Cbl and is likely to be a general function of this domain; Various RING fingers exhibit binding activity towards E2 ubiquitin-conjugating enzymes (Ubc' s)

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 209862805    15 CPICMNYFL-DPVTIDCGHSFCRPCLyLNWQDTAVlAQCSEC 55
Cdd:smart00184   1 CPICLEEYLkDPVILPCGHTFCRSCI-RKWLESGN-NTCPIC 40

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 209862805   9 FQRALTCPICMNYFLDPVTIDCGHSFCRPCLYLNWQDTAVLAQCSECKKTTRQRNLNTD 67
Cdd:cd16603    1 FQRELTCPICMNYFIDPVTIDCGHSFCRPCLYLNWQDIPFLAQCPECRKTTEQRNLKTN 59

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 209862805 287 VDFTLQPERANSHIFLCGDLRSMNVG--CDPQddPDITGKSE-CFLVWGAQAFTSGKYYWEVHMGDSWNWAFGVCNNYWK 363
Cdd:cd15813    9 VNVTLDPETAHPNLIFSDDLKSVRLGnkWDRL--PDNPERFDsCIIVLGSPSFTSGRHYWEVEVGDKTGWILGVCKASVS 86

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209862805 364 EKRQNDkIDGEEGLFLLGCVKEDTHCSLftTSPLVVQYVPRPTSTVGLFLDCEGRTVSFVDVDQSSLIYTIPNCSFSPPL 443
Cdd:cd15813   87 RKGSMT-LSPENGYWVVMMTKRNEYQAS--TSPPTRLWLREPPRRVGIFLDYEAGDISFYNVTAKSHIYTFTSFSSSGPL 163

                 ....*
gi 209862805 444 RPIFC 448
Cdd:cd15813  164 QPIFS 168

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 209862805 285 FRVDFTLQPERANSHIFLCGDLRSMNVGCDPQDDPDITGKSECF-LVWGAQAFTSGKYYWEVHMGDSWNWAFGVCNNYWK 363
Cdd:cd12900    1 HMVHITLDPDTANPWLILSKDRRQVRLGDTHQNVPENEERFDNYpMVLGAQRFNSGKHYWEVDVTGKEAWDLGVCRDSVR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209862805 364 EKRQNdKIDGEEGLFLLGCVKEDTHCSLFTTSPLVVQYVPRptsTVGLFLDCEGRTVSFVDV-DQSSLIYTIPNCSFSPP 442
Cdd:cd12900   81 RKGQF-LLSPENGFWTIWLWNKKYEAGTSPQTTLHLQVPPC---QVGIFLDYEAGVVSFYNItDHGSLIYTFSECAFTGP 156

                 ....*
gi 209862805 443 LRPIF 447
Cdd:cd12900  157 LRPFF 161

butyrophilin subfamily member A1 and A2 (BTN1A and BTN2A); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of butyrophilin family 1A and 2A (BTN1A and BTN2A). BTNs belong to receptor glycoproteins of immunoglobulin (Ig) superfamily, characterized by the presence of extracellular Ig-like domains (IgV and/or IgC). BTN1A plays a role in the secretion, formation and stabilization of milk fat globules. The B30.2 domain of BTN1A1 binds the enzyme xanthine oxidoreductase (XOR) in order to participate in milk fat globule secretion; this interaction may lead to the production of reactive oxygen species, which have immunomodulatory and antimicrobial functions. Duplication events have led to three paralogs of BTN2A in primates: BTN2A1, BTN2A2, and BTN2A3. In humans, only BTN2A1 has been functionally characterized; it has been detected on epithelial cells and leukocytes, and identified as a novel ligand of dendritic cell-specific ICAM-3 grabbing nonintegrin (DCSIGN), a C-type lectin receptor that acts as an internalization receptor for HIV-1, HCV, and other pathogens. BTN2A2 mRNA has been shown to be expressed in circulating human immune cells.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209862805 287 VDFTLQPERANSHIFLCGDLRSMNVGCDPQDDPDITGKSECFL-VWGAQAFTSGKYYWEVHMGDSWNWAFGVCnnywkek 365
Cdd:cd15819    2 VNVTLDPDTAHPALILSEDGRSVTWGETRQDLPENPERFDSLPcVLGQEGFTSGRHYWEVEVGDRTSWDLGVC------- 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209862805 366 RQNDKIDG------EEGLFLLGcVKEDTHCSLftTSPLVVQYVPRPTSTVGLFLDCEGRTVSFVDVDQSSLIYTIPNCSF 439
Cdd:cd15819   75 RDNVMRKGrvtlspENGFWAIR-LYGNEYWAL--TSPETPLTLKEPPRRVGIFLDYEAGDVSFYNMTDGSHIYTFPQTAF 151

                 ....*....
gi 209862805 440 SPPLRPIFC 448
Cdd:cd15819  152 SGPLRPFFR 160

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 209862805 288 DFTLQPERANSHIFLCGDLRSMNVGCDPQDDPditGKSECFLVW----GAQAFTSGKYYWEVHMGDSWNWAFGVCNNYWK 363
Cdd:cd15816    1 DVKLDPATAHPSLLLTADLRSVQDGELWRDVP---GNPERFDTWpcvlGLQSFSSGRHYWEVAVGEKAEWGLGVCQDSAP 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209862805 364 EKRQNDKiDGEEGLFLLGCVKEDTHCSLFTTS-PLVVQYVPRptsTVGLFLDCEGRTVSFVDVDQSSLIYTIpNCSFSPP 442
Cdd:cd15816   78 RKGETTP-SPENGVWAVWLLKGNEYMVLASPSvPLLQLRRPR---RVGVFLDYEAGEISFYNVTAGSHIYTF-RQLFSGI 152

                 ....*
gi 209862805 443 LRPIF 447
Cdd:cd15816  153 LRPYF 157

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 209862805 288 DFTLQPERANSHIFLCGDLRSMNVGCDPQ---DDPDITGKSECFLvwGAQAFTSGKYYWEVHMGDSWNWAFGVCNNYWKE 364
Cdd:cd15811    1 DVTLDPDTANPELVLSEDRRSVRRGDLRQalpDSPERFDPGPCVL--GRERFTSGRHYWEVEVGDRTSWALGVCKENVNR 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209862805 365 KRQNDKIDGeEGLFLLGCVKEDTHCSLFTTSPLvvqyvPRPTSTVGLFLDCEGRTVSFVDVDQSSLIYTIPNCSFSPPLR 444
Cdd:cd15811   79 KEKGELSAG-NGFWILVFLGNYYSSERRTFAPL-----RDPPRRVGIFLDYEAGHLSFYSATDGSLLFIFPETPFSGTLR 152

                 ...
gi 209862805 445 PIF 447
Cdd:cd15811  153 PLF 155

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
                 ....*....|....*....|....*....|....*....|...
gi 209862805  87 SSEEQICGMHRETKKMFCEVDKSLLCLPCSNSQEHRNHIHCPI 129
Cdd:cd19783    1 SSEEQICGTHRETKKLFCEADKSLLCLLCSSSQEHRAHRHYPI 43

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 209862805 287 VDFTLQPERANSHIFLCGDLRSMNVGCDPQ----DDPDITGksecFLVWGAQAFTSGKYYWEVHMGDSWNWAFGVC---N 359
Cdd:cd15824    3 VDVMLNPVNAVSNVVVSADQRQVTVVHICMfrnsNPCDFSA----FDVLGCQYFSSGKYYWEVDVSGKIAWILGVYskrN 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209862805 360 NYWKEK-----------RQN--DKIDGEEGLFLLGCVKEDTHCSL---FTTSPLVVQ-YVPRPTSTVGLFLDCEGRTVSF 422
Cdd:cd15824   79 NLNKRKssgfafdpnvnHPNvySRYRPQNGYWVIGLQNESEYNAFedsSSSDPKVLTlSMAVPPHRVGVFLDYEAGTVSF 158

                        170       180
                 ....*....|....*....|....*.
gi 209862805 423 VDV-DQSSLIYTIPNCSFSPPLRPIF 447
Cdd:cd15824  159 FNVtNHGSLIYKFSKCCFSQPVYPYF 184

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 209862805 290 TLQPERANSHIFLCGDLRSMNVGCDPQDDPDITGK--SECFlVWGAQAFTSGKYYWEVHMGDSWNWAFGVCnnywKE--K 365
Cdd:cd12888    3 TLDPDTAHPRLVLSEDRKSVRWGDTRQDLPDNPERfdTWPC-VLGCEGFTSGRHYWEVEVGDGGGWAVGVA----REsvR 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209862805 366 RQND-KIDGEEGLFLLGCVKEDTHCSLFTTSPLVVQYVPRptsTVGLFLDCEGRTVSFVDVDQSSLIYTIPNCSFS-PPL 443
Cdd:cd12888   78 RKGEiSFSPEEGIWAVGQWGGQYWALTSPETPLPLSEVPR---RIRVYLDYEGGQVAFFDADNEAPIFTFPPASFAgERI 154

                 ....*
gi 209862805 444 RPIFC 448
Cdd:cd12888  155 FPWFW 159

PRY/SPRY domain, also known as B30.2; This domain 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. B30.2 domains comprise the C-terminus of three protein families: BTNs (receptor glycoproteins of immunoglobulin superfamily); several TRIM proteins (composed of RING/B-box/coiled-coil core); Stonutoxin (secreted poisonous protein of the stonefish Synanceia horrida). While SPRY domains are evolutionarily ancient, B30.2 domains are a more recent adaptation where the SPRY/PRY combination is a possible component of immune defense. Among the TRIM proteins, also known as the N-terminal RING finger/B-box/coiled coil (RBCC) family, only Classes I and II contain the B30.2 domain that has evolved under positive selection. Class I TRIM proteins include multiple members involved in antiviral immunity at various levels of interferon signaling cascade. Among the 75 human TRIMs, roughly half enhance immune response, which they do at multiple levels in signaling pathways. 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 209862805 289 FTLQPERANSHIFLCGDLRSMNVGCDPQDDPDITGKS-ECFLVWGAQAFTSGKYYWEVHMGDSWNWAFGVCnnYWKEKRQ 367
Cdd:cd12874    1 LTFDPDTAHLNLILSDDLRSVRVGDISQHPPEPPPRFfECWQVLGSQSFSSGRHYWEVDVQDDSSWYVGVT--YKSLPRK 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209862805 368 NDKID-GEEGLFLLGCVKEDThcslFTTSPLVVQYV--PRPTSTVGLFLDCEGRTVSFVDV-DQSSLIYTIpNCSFSPPL 443
Cdd:cd12874   79 GKMSNlGRNNGSWCLEWRENE----FSAWHNNPETRlpVTPPRRLGVFLDCDGGSLSFYGVtDGVQLLYTF-KAKFTEPL 153

                 ....
gi 209862805 444 RPIF 447
Cdd:cd12874  154 YPAF 157

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 209862805 285 FRVDFTLQPERANSHIFLCGDLRSMN-VGCDPQDDPDITGKSECFlVWGAQAFTSGKYYWEVHMGDSWNWAFGVCNN--- 360
Cdd:cd15823    1 YWVDVTLNPHTANLNLVLSKNRRQVRfVGAKLSGPSYLEEHYDCS-VLGSQHFSSGKHYWEVDVTKKTAWILGVCSHslg 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209862805 361 -------YWKEKRQNDKIDGEEGLFLLGCVKEDTHCSLFTTSPLVVQYVPRPTSTVGLFLDCEGRTVSFVDVDQSSL-IY 432
Cdd:cd15823   80 ptfsfnqYAQNHNAYSRYQPQSGYWVIGLQHNHEYRAYEDSSTSLLLSMTVPPRRVGVFLDYEAGTVSFYNVTNHGFpIY 159

                        170
                 ....*....|....*
gi 209862805 433 TIPNCSFSPPLRPIF 447
Cdd:cd15823  160 TFSKYYFPTTLCPYF 174

RING finger, HC subclass, found in tripartite motif-containing proteins, TRIM7, TRIM11 and TRIM27, and similar proteins; TRIM7, TRIM11 and TRIM27, closely related tripartite motif-containing proteins, 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 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. TRIM7, also known as glycogenin-interacting protein (GNIP) or RING finger protein 90 (RNF90), is an E3 ubiquitin-protein ligase that mediates c-Jun/AP-1 activation by Ras signalling. Its phosphorylation and activation by MSK1 in response to direct activation by the Ras-Raf-MEK-ERK pathway can stimulate TRIM7 E3 ubiquitin ligase activity in mediating Lys63-linked ubiquitination of the AP-1 coactivator RACO-1, leading to RACO-1 protein stabilization. Moreover, TRIM7 binds and activates glycogenin, the self-glucosylating initiator of glycogen biosynthesis. TRIM11, also known as protein BIA1, or RING finger protein 92 (RNF92), is an E3 ubiquitin-protein ligase involved in the development of the central nervous system. It is overexpressed in high-grade gliomas and promotes proliferation, invasion, migration and glial tumor growth. TRIM11 acts as a potential therapeutic target for congenital central hypoventilation syndrome (CCHS) by mediating the degradation of CCHS-associated polyalanine-expanded Phox2b. TRIM11 modulates the function of neurogenic transcription factor Pax6 through the ubiquitin-proteosome system, and thus plays an essential role for Pax6-dependent neurogenesis. It also binds to and destabilizes a key component of the activator-mediated cofactor complex (ARC105), humanin, a neuroprotective peptide against Alzheimer's disease-relevant insults, and further regulates ARC105 function in transforming growth factor beta (TGFbeta) signaling. Moreover, TRIM11 negatively regulates retinoic acid-inducible gene-I (RIG-I)-mediated interferon-beta (IFNbeta) production and antiviral activity by targeting TANK-binding kinase-1 (TBK1). It may contribute to the endogenous restriction of retroviruses in cells. It enhances N-tropic murine leukemia virus (N-MLV) entry by interfering with Ref1 restriction. It also suppresses the early steps of human immunodeficiency virus HIV-1 transduction, resulting in decreased reverse transcripts. TRIM27, also known as RING finger protein 76 (RNF76), RET finger protein (RFP), or zinc finger protein RFP, is a nuclear E3 ubiquitin-protein ligase that is highly expressed in testis and in various tumor cell lines. Expression of TRIM27 is associated with prognosis of colon and endometrial cancers. TRIM27 was first identified as a fusion partner of the RET receptor tyrosine kinase. It functions as a transcriptional repressor and associates with several proteins involved in transcriptional activity, such as enhancer of polycomb 1 (Epc1), a member of the Polycomb group proteins, and Mi-2beta, a main component of the nucleosome remodeling and deacetylase (NuRD) complex, and the cell cycle regulator retinoblastoma protein (RB1). It also interacts with HDAC1, leading to downregulation of thioredoxin binding protein 2 (TBP-2), which inhibits the function of thioredoxin. Moreover, TRIM27 mediates Pax7-induced ubiquitination of MyoD in skeletal muscle atrophy. In addition, it inhibits muscle differentiation by modulating serum response factor (SRF) and Epc1. TRIM27 promotes a non-canonical polyubiquitination of PTEN, a lipid phosphatase that catalyzes PtdIns(3,4,5)P3 (PIP3) to PtdIns(4,5)P2 (PIP2). It is an IKKepsilon-interacting protein that regulates IkappaB kinase (IKK) function and negatively regulates signaling involved in the antiviral response and inflammation. TRIM27 also forms a protein complex with MBD4 or MBD2 or MBD3, and thus plays an important role in the enhancement of transcriptional repression through MBD proteins in tumorigenesis, spermatogenesis, and embryogenesis. It is a component of an estrogen receptor 1 (ESR1) regulatory complex that is involved in estrogen receptor-mediated transcription in MCF-7 cells.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 209862805   9 FQRALTCPICMNYFLDPVTIDCGHSFCRPCLYLNWQDTAVLAQCSECKKTTRQRNL 64
Cdd:cd16594    2 LQEELTCPICLDYFTDPVTLDCGHSFCRACIARCWEEPETSASCPQCRETCPQRNL 57

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 209862805 332 GAQAFTSGKYYWEVHM---GDSWnWAFGVCNNYWKEKRQNDKIDgEEGLFLLGCVKEDTHCSLFTTSPLVVqyVPRPTST 408
Cdd:cd15812   46 GQETFSSGRHYWEVGMnltGDAL-WALGVCRDNVSRKDRVPKSP-ENGFWVVQLSKGKKYLSAMSALTPVT--LTEPPSH 121

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 209862805 409 VGLFLDCEGRTVSFVDVDQSSLIYTIPNCSFSPPLRPIFC 448
Cdd:cd15812  122 MGIFLDFEAGEVSFYSVNDGSHLHTYSQAAFPGPLQPFFC 161

PRY/SPRY domain in tripartite motif-binding protein 69 (TRIM69), also known as RING finger protein 36 (RNF36); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM69, which is also known as RING finger protein 36 (RNF36) or testis-specific ring finger (Trif). TRIM69 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. It 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. The mouse ortholog of this gene is specifically expressed in germ cells at the round spermatid stages during spermatogenesis and, when overexpressed, induces apoptosis. TRIM69 has been shown to be a novel regulator of mitotic spindle assembly in tumor cells; it associates with spindle poles and promotes centrosomal clustering, and is therefore essential for formation of a bipolar spindle.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209862805 290 TLQPERANSHIFLCGDLRSMNVGCDPQDDPDITGKSECFL-VWGAQAFTSGKYYWEVHMGDSWNWAFGVCnnywKE---K 365
Cdd:cd15818   16 TLDPKTAHPNLILSEDLTCVWHGDTKQMLPDNPERFDSSVaVLGSEGFTSGKHYWEVEVAKKTKWTLGVV----REsinR 91

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209862805 366 RQNDKIDGEEGLFLLGCVKE------DTH-CSLFTTSPLvvqyvprptSTVGLFLDCEGRTVSFVDVDQSSLIYTIpNCS 438
Cdd:cd15818   92 KGNCPLSPEDGFWLLRLRNQnelkalDVPsFSLTLTSNL---------NKVGIYLDYEGGQVSFYNANTMSHIYTF-SDT 161

                        170
                 ....*....|
gi 209862805 439 FSPPLRPIFC 448
Cdd:cd15818  162 FTEKIYPYFC 171

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
                 ....*....|....*....|....*....|....*....|....*..
gi 209862805  10 QRALTCPICMNYFLDPVTIDCGHSFCRPCLYLNWQDTAVLAQCSECK 56
Cdd:cd16590    4 QEELTCPICLDYFQDPVSIECGHNFCRGCLHRNWAPGGGPFPCPECR 50

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 209862805 290 TLQPERANSHIFLCGDLRSMNVGCDPQDDPDITGKSECF-LVWGAQAFTSGKYYW--EVHMGDSWNWAFGVCNNywKEKR 366
Cdd:cd15826    3 TLDPQTASGSLVLSEDRKSVRYTRQKQNLPDSPLRFDGLpAVLGSPGFSSGRHRWqvEVQLGDGGGCTVGVAGE--SVRR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209862805 367 QND-KIDGEEGLFLLGCVKEDTHCSlftTSP---LVVQYVPRptsTVGLFLDCEGRTVSFVDVDQSSLIYTIPnCSFSPP 442
Cdd:cd15826   81 KGEmGLSAEDGVWAVILSHQQCWAS---TSPgtdLPLSEIPR---RVGVALDYEAGTVTLTNAETQEPIFTFT-ASFSGK 153

                 ....*
gi 209862805 443 LRPIF 447
Cdd:cd15826  154 VFPFF 158

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 209862805 288 DFTLQPERANSHIFLCGDLRSMNVGCDPQ---DDPDITGKSECFLvwGAQAFTSGKYYWEVHMGDSWNWAFGVCNNYWKE 364
Cdd:cd12897   13 SLTFDPATAHPLLVVSSGGTVVECGLQKQrraSQPERFDKSTCVV--ASQGFSEGEHYWEVVVGDKPRWALGVIKGTASR 90

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 209862805 365 KRQNDKIDgEEGLFLLGCvKEDTHCSLFT--TSPLVVQYVPRPTStVGLFLDCEGRTVSFVDVDQSS---LIYTIpNCSF 439
Cdd:cd12897   91 KGKLHASP-SHGVWLIGL-KEGKVYEAHGepKEPRPLRVAGRPHR-IGVYLSFEDGVLSFFDASDPDdlrTLYTF-QERF 166

                        170
                 ....*....|...
gi 209862805 440 SPPLRPIF-CCSH 451
Cdd:cd12897  167 QGKLYPFFdVCWH 179