SPRY domain; SPRY domains, first identified in the SP1A kinase of Dictyostelium and rabbit Ryanodine receptor (hence the name), are homologous to B30.2. SPRY domains have been identified in at least 11 protein families, covering a wide range of functions, including regulation of cytokine signaling (SOCS), RNA metabolism (DDX1 and hnRNP), immunity to retroviruses (TRIM5alpha), intracellular calcium release (ryanodine receptors or RyR) and regulatory and developmental processes (HERC1 and Ash2L). B30.2 also contains residues in the N-terminus that form a distinct PRY domain structure; i.e. 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 or RBCC core); Stonutoxin (secreted poisonous protein of the stonefish Synanceia horrida). TRIM/RBCC proteins are involved in a variety of processes, including apoptosis, cell cycle regulation, cell growth, senescence, viral response, meiosis, cell differentiation, and vesicular transport. Genes belonging to this family are implicated in several human diseases that vary from cancer to rare genetic syndromes. The PRY-SPRY domain in these TRIM families is suggested to serve as the target binding site. 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. Mutations found in the SPRY-containing proteins have shown to cause Mediterranean fever and Opitz syndrome.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462496425 294 RFRVEISFHFEVTNHNIRLFEDVRSwmFRRGPLNSDRSDYFAAW-------GARVFSFGKHYWELDVDNSCDWALGVCNN 366
Cdd:cd15821     1 KFQVDMTLDVDTANNYLIISEDLRS--VRCGCFRQNRKELAERFddalcvlGSPRFTSGRHYWEVDVGTSTEWDLGVCRE 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462496425 367 SWIRKNSTMVNSEDIFLLLCLKVDNHFnLLTTSPVFPHYIEKPLGRVGVFLDFESGSVSFLNVTKSSLIWSYPAGSLTFP 446
Cdd:cd15821    79 SVNRQGPIELSPEHGFWTVSLRDGSVF-FASTVPLTVLWVNPRLHRVGIFLDMEMGTISFYDVSDGSHIFTFTKISAEEP 157

                  ....*
gi 2462496425 447 VRPFF 451
Cdd:cd15821   158 LRPFF 162

coiled-coil (CC) domain of Drosophila brain tumor (brat) and similar proteins; This family contains the coiled-coil (CC) region of Drosophila brain tumor (Brat), a translational repressor that belongs to the tripartite motif (TRIM) protein superfamily. TRIM proteins play important roles in various cellular processes and are involved in many diseases which consists of two B-box domains and a coiled-coil (CC) domain at the N-terminal region, and an NHL domain at the C-terminus. Brat localizes at the basal cortex during asymmetric division of Drosophila neuroblasts by directly interacting with the scaffolding protein Miranda (Mira), which it does through the CC-NHL domain tandem, indicating that the function of the Brat CC domain is to assemble Brat-NHL in dimeric form which is necessary for Mira binding. Brat CC forms an elongated antiparallel dimer similar to its other TRIM protein counterparts, but the overall length of Brat CC dimer is shorter than the TRIMs.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462496425  141 EAAEEDREKLLKQMRILWKKIQENQRNLYEERrtafllrgdvvlraQMIRNEYRKLHPVLHKEEKQHLERLNKEYQEIFQ 220
Cdd:smart00502  10 TKLRKKAAELEDALKQLISIIQEVEENAADVE--------------AQIKAAFDELRNALNKRKKQLLEDLEEQKENKLK 75

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2462496425  221 QLQRSWVKMDQKSKHLK---EMYQELMEMCHKPEVELLQDLgdIVARSESVL 269
Cdd:smart00502  76 VLEQQLESLTQKQEKLShaiNFTEEALNSGDPTELLLSKKL--IIERLQNLL 125

Ret finger protein-like (RFPL), includes RFP1, 2, 3, 4; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of RFPL protein family, which includes RFPL1, RFPL2, RFPL3 and RFPL4. In humans, RFPL transcripts can be detected at the onset of neurogenesis in differentiating human embryonic stem cells, and in the developing human neocortex. The human RFPL1, 2, 3 genes have a role in neocortex development. RFPL1 is a primate-specific target gene of Pax6, a key transcription factor for pancreas, eye and neocortex development; human RFPL1 decreases cell number through its RFPL-defining motif (RDM) and SPRY domains. The RFPL4 (also known as RFPL4A) gene encodes a putative E3 ubiquitin-protein ligase expressed in adult germ cells and interacts with oocyte proteins of the ubiquitin-proteasome degradation pathway.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462496425 294 RFRVEISFHFEVTNHNIRLFEDVRSwmFRRGPLNSDRSDYFAAW-------GARVFSFGKHYWELDVDNSCDWALGVCNN 366
Cdd:cd15821     1 KFQVDMTLDVDTANNYLIISEDLRS--VRCGCFRQNRKELAERFddalcvlGSPRFTSGRHYWEVDVGTSTEWDLGVCRE 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462496425 367 SWIRKNSTMVNSEDIFLLLCLKVDNHFnLLTTSPVFPHYIEKPLGRVGVFLDFESGSVSFLNVTKSSLIWSYPAGSLTFP 446
Cdd:cd15821    79 SVNRQGPIELSPEHGFWTVSLRDGSVF-FASTVPLTVLWVNPRLHRVGIFLDMEMGTISFYDVSDGSHIFTFTKISAEEP 157

                  ....*
gi 2462496425 447 VRPFF 451
Cdd:cd15821   158 LRPFF 162

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 2462496425  345 GKHYWELDVDNSCDWALGVCNNSWIRKNSTMVNSEDIFLLLCLKVDNHFNLLTTSPVFPHYIEKPLgRVGVFLDFESGSV 424
Cdd:smart00449   2 GRHYFEVEIGDGGHWRVGVATKSVPRGYFALLGEDKGSWGYDGDGGKKYHNSTGPEYGLPLQEPGD-VIGCFLDLEAGTI 80

                           90       100
                   ....*....|....*....|....*...
gi 2462496425  425 SFLNVTKSSLIWSYPAGSLTFPVRPFFY 452
Cdd:smart00449  81 SFYKNGKYLHGLAFFDVKFSGPLYPAFS 108

zinc finger of C3HC4-type, RING; This is a family of primate-specific Ret finger protein-like (RFPL) zinc-fingers of the C3HC4 type. Ret finger protein-like proteins are primate-specific target genes of Pax6, a key transcription factor for pancreas, eye and neocortex development. This domain is likely to be DNA-binding. This zinc-finger domain together with the RDM domain, pfam11002, forms a large zinc-finger structure of the RING/U-Box superfamily. RING-containing proteins are known to exert an E3 ubiquitin protein ligase activity with the zinc-finger structure being mandatory for binding to the E2 ubiquitin-conjugating enzyme.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 2462496425  25 CVICLNYLVDPVTICCGHSFCRPCLCLSWEEAQSPA-NCPAC 65
Cdd:pfam15227   1 CPICLDYLEKPVSIECGHSFCLSCINSLQKEPDGESlLCPQC 42

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 2462496425   25 CVICL-NYLVDPVTICCGHSFCRPCLCLSWEeaQSPANCPAC 65
Cdd:smart00184   1 CPICLeEYLKDPVILPCGHTFCRSCIRKWLE--SGNNTCPIC 40

E3 ubiquitin-protein ligase RMA2; Provisional

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 2462496425  22 ELTCVICLNYLVDPVTICCGHSFCRPCL-------------CLSWEEAQSPANCPACR 66
Cdd:PLN03208   18 DFDCNICLDQVRDPVVTLCGHLFCWPCIhkwtyasnnsrqrVDQYDHKREPPKCPVCK 75

Ezrin/radixin/moesin, alpha-helical domain; The ERM family consists of three closely-related proteins, ezrin, radixin and moesin. Ezrin was first identified as a constituent of microvilli, radixin as a barbed, end-capping actin-modulating protein from isolated junctional fractions, and moesin as a heparin binding protein. A tumour suppressor molecule responsible for neurofibromatosis type 2 (NF2) is highly similar to ERM proteins and has been designated merlin (moesin-ezrin-radixin-like protein). ERM molecules contain 3 domains, an N-terminal globular domain, an extended alpha-helical domain and a charged C-terminal domain (pfam00769). Ezrin, radixin and merlin also contain a polyproline linker region between the helical and C-terminal domains. The N-terminal domain is highly conserved and is also found in merlin, band 4.1 proteins and members of the band 4.1 superfamily, designated the FERM domain. ERM proteins crosslink actin filaments with plasma membranes. They co-localize with CD44 at actin filament plasma membrane interaction sites, associating with CD44 via their N-terminal domains and with actin filaments via their C-terminal domains. This is the alpha-helical domain, which is involved in intramolecular masking of protein-protein interaction sites, regulating the activity of this proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462496425 141 EAAEEDREKLLKQMRILWKKIQENQRNLYEERRTAFLLrgdvvlraqmirNEYRKLHpvlhKEEKQHLERLNKEYQEIFQ 220
Cdd:pfam20492   2 EEAEREKQELEERLKQYEEETKKAQEELEESEETAEEL------------EEERRQA----EEEAERLEQKRQEAEEEKE 65

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 2462496425 221 QLQRSwVKMDQKSKHLKEmyQELMEmcHKPEVELLQD 257
Cdd:pfam20492  66 RLEES-AEMEAEEKEQLE--AELAE--AQEEIARLEE 97

Ret finger protein-like (RFPL), includes RFP1, 2, 3, 4; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of RFPL protein family, which includes RFPL1, RFPL2, RFPL3 and RFPL4. In humans, RFPL transcripts can be detected at the onset of neurogenesis in differentiating human embryonic stem cells, and in the developing human neocortex. The human RFPL1, 2, 3 genes have a role in neocortex development. RFPL1 is a primate-specific target gene of Pax6, a key transcription factor for pancreas, eye and neocortex development; human RFPL1 decreases cell number through its RFPL-defining motif (RDM) and SPRY domains. The RFPL4 (also known as RFPL4A) gene encodes a putative E3 ubiquitin-protein ligase expressed in adult germ cells and interacts with oocyte proteins of the ubiquitin-proteasome degradation pathway.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462496425 294 RFRVEISFHFEVTNHNIRLFEDVRSwmFRRGPLNSDRSDYFAAW-------GARVFSFGKHYWELDVDNSCDWALGVCNN 366
Cdd:cd15821     1 KFQVDMTLDVDTANNYLIISEDLRS--VRCGCFRQNRKELAERFddalcvlGSPRFTSGRHYWEVDVGTSTEWDLGVCRE 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462496425 367 SWIRKNSTMVNSEDIFLLLCLKVDNHFnLLTTSPVFPHYIEKPLGRVGVFLDFESGSVSFLNVTKSSLIWSYPAGSLTFP 446
Cdd:cd15821    79 SVNRQGPIELSPEHGFWTVSLRDGSVF-FASTVPLTVLWVNPRLHRVGIFLDMEMGTISFYDVSDGSHIFTFTKISAEEP 157

                  ....*
gi 2462496425 447 VRPFF 451
Cdd:cd15821   158 LRPFF 162

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 2462496425 314 EDVRSwmFRRG------PLNSDRSDYFAA-WGARVFSFGKHYWELDVDNSCDWALGVCNNSWIRKNSTMVNSEDIFLLLC 386
Cdd:cd13733    17 EDLKS--VRYGdkrqnlPDNPERFDTCVCvLGSEGFSSGRHYWEVEVGGKTDWDLGVARESVNRKGKITLSPENGYWTVG 94

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2462496425 387 LKVDNHFNLLTTSPVFPHYIEKPlGRVGVFLDFESGSVSFLNVTKSSLIWSYPaGSLTFPVRPFFYTG 454
Cdd:cd13733    95 LRNGNEYKALTSPSTPLSLREKP-QKVGVFLDYEEGQVSFYNVDDGSHIYTFT-DCFTEKLYPYFSPC 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 2462496425 325 PLNSDR-SDYFAAWGARVFSFGKHYWELDVDNSCDWALGVCNNSWIRKNSTMVNSEDIFLLLCLKVDNHfnLLTTSPVFP 403
Cdd:cd12900    35 PENEERfDNYPMVLGAQRFNSGKHYWEVDVTGKEAWDLGVCRDSVRRKGQFLLSPENGFWTIWLWNKKY--EAGTSPQTT 112

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2462496425 404 HYIEKPLGRVGVFLDFESGSVSFLNVTK-SSLIWSYPAGSLTFPVRPFFYTG 454
Cdd:cd12900   113 LHLQVPPCQVGIFLDYEAGVVSFYNITDhGSLIYTFSECAFTGPLRPFFNPG 164

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 2462496425 338 GARVFSFGKHYWELDVDNSCDWALGVCNNSWIRKNSTMVNSEDIFLLLCLKVDNHFNLltTSPVFPHYIEKPLGRVGVFL 417
Cdd:cd15819    48 GQEGFTSGRHYWEVEVGDRTSWDLGVCRDNVMRKGRVTLSPENGFWAIRLYGNEYWAL--TSPETPLTLKEPPRRVGIFL 125

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 2462496425 418 DFESGSVSFLNVTKSSLIWSYPAGSLTFPVRPFFY 452
Cdd:cd15819   126 DYEAGDVSFYNMTDGSHIYTFPQTAFSGPLRPFFR 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 2462496425 309 NIRLFEDVRSWmfRRGPLNSDRsdyFAAW----GARVFSFGKHYWELDVDNSCDWALGVCNNSWIRKNSTMVNSEDIFLL 384
Cdd:cd15816    18 DLRSVQDGELW--RDVPGNPER---FDTWpcvlGLQSFSSGRHYWEVAVGEKAEWGLGVCQDSAPRKGETTPSPENGVWA 92

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2462496425 385 LCLKVDNHFNLLTTSPVfPHYIEKPLGRVGVFLDFESGSVSFLNVTKSSLIWSYpAGSLTFPVRPFFY 452
Cdd:cd15816    93 VWLLKGNEYMVLASPSV-PLLQLRRPRRVGVFLDYEAGEISFYNVTAGSHIYTF-RQLFSGILRPYFF 158

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 2462496425  19 FQKELTCVICLNYLVDPVTICCGHSFCRPCLCLSWEEAQSPANCPACREPSPKMDFKTN 77
Cdd:cd16594     2 LQEELTCPICLDYFTDPVTLDCGHSFCRACIARCWEEPETSASCPQCRETCPQRNLRPN 60

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 2462496425 318 SWMFRRGPLNSDRSDYF-AAWGARVFSFGKHYWELDVDNSCDWALGVCNNSWIRKNSTMVNSEDIFLLLCLKVDNHFNLL 396
Cdd:cd15814    27 SYLQQDLPDNPERFNLFpCVLGSPCFIAGRHYWEVEVGDKAKWTIGVCEDSVCRKGGVTSAPQNGFWAVSLWYGKEYWAL 106

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462496425 397 TtSPVFPHYIEKPLGRVGVFLDFESGSVSFLNVTKSSLIWSYPAGSLTFPVRPFF---YTGHR 456
Cdd:cd15814   107 T-SPMTALPLRTPLQRVGIFLDYDAGEVSFYNVTERCHTFTFSHATFCGPVRPYFslsYSGGK 168

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 2462496425  20 QKELTCVICLNYLVDPVTICCGHSFCRPCLCLSWEEAQSPANCPACREPSPKM 72
Cdd:cd16543     1 EDQLTCSICLDLLKDPVTIPCGHSFCMNCITLLWDRKQGVPSCPQCRESFPPR 53

PRY/SPRY domain in tripartite motif-containing protein 34 (TRIM34), also known as RING finger protein 21 (RNF21) or interferon-responsive finger protein (IFP1); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM34, also known as RING finger protein 21 (RNF21) or interferon-responsive finger protein (IFP1). TRIM34 domain is composed of RING/B-box/coiled-coil core and also known as RBCC protein. The TRIM21 cDNA possesses at least three kinds of isoforms, due to alternative splicing, of which only the long and medium forms contain the SPRY domain. It is an interferon-induced protein, predominantly expressed in the testis, kidney, and ovary. The SPRY domain provides the capsid recognition motif that dictates specificity to retroviral restriction. While the PRY-SPRY domain provides specificity and the capsid recognition motif to retroviral restriction, TRIM34 binds HIV-1 capsid but does not restrict HIV-1 infection.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462496425 296 RVEISFHFEVTNHNIRLFEDVRSwmFRRGPLNSDRSDYFAAWGARVFSFGKHYWELDVDNSCDWALGV------CNNSWI 369
Cdd:cd15825     1 WVDFTLNPVNLNLNLVLSEDQRQ--VTSVPIWPFKCYNYGILGSQYFSSGKHYWEVDVSKKTAWILGVycrkrsRTFKYV 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462496425 370 RKNSTMVNS------EDIFLLLCLKVDNHFNLLTTSPVF-PH----YIEKPLGRVGVFLDFESGSVSFLNVTK-SSLIWS 437
Cdd:cd15825    79 RQGKNHPNVysryrpQYGYWVIGLQNKSEYYAFEDSSTSdPKvltlSVATPPHRVGVFLDYEAGTVSFFNVTNhGSLIYK 158

                         170
                  ....*....|....
gi 2462496425 438 YPAGSLTFPVRPFF 451
Cdd:cd15825   159 FSKCCFSQPVYPYF 172

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 2462496425 298 EISFHFEVTNHNIRLFEDVRSwmFRRGPLNS---DRSDYF----AAWGARVFSFGKHYWELDVDNSCDWALGVCNNSWIR 370
Cdd:cd15811     1 DVTLDPDTANPELVLSEDRRS--VRRGDLRQalpDSPERFdpgpCVLGRERFTSGRHYWEVEVGDRTSWALGVCKENVNR 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462496425 371 KNSTMVNSEDIFLLLCLKvdNHFNLLTTSPVFPhyIEKPLGRVGVFLDFESGSVSFLNVTKSSLIWSYPAGSLTFPVRPF 450
Cdd:cd15811    79 KEKGELSAGNGFWILVFL--GNYYSSERRTFAP--LRDPPRRVGIFLDYEAGHLSFYSATDGSLLFIFPETPFSGTLRPL 154

                  .
gi 2462496425 451 F 451
Cdd:cd15811   155 F 155

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 2462496425 316 VRSWMFRrgplNSDRSDY--FAAWGARVFSFGKHYWELDVDNSCDWALGVC---NNSWIRKNSTM-----VNSEDI---- 381
Cdd:cd15824    28 VHICMFR----NSNPCDFsaFDVLGCQYFSSGKYYWEVDVSGKIAWILGVYskrNNLNKRKSSGFafdpnVNHPNVysry 103

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462496425 382 -----FLLLCLKVDNHFN-----------LLTTS-PVFPHyiekplgRVGVFLDFESGSVSFLNVTK-SSLIWSYPAGSL 443
Cdd:cd15824   104 rpqngYWVIGLQNESEYNafedssssdpkVLTLSmAVPPH-------RVGVFLDYEAGTVSFFNVTNhGSLIYKFSKCCF 176

                  ....*...
gi 2462496425 444 TFPVRPFF 451
Cdd:cd15824   177 SQPVYPYF 184

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 2462496425  20 QKELTCVICLNYLVDPVTICCGHSFCRPCLCLSWEEAQSPANCPACREPSPKMDFKTN 77
Cdd:cd16590     4 QEELTCPICLDYFQDPVSIECGHNFCRGCLHRNWAPGGGPFPCPECRHPSAPAALRPN 61

RING finger, HC subclass, found in tripartite motif-containing protein 35 (TRIM35) and similar proteins; TRIM35, also known as hemopoietic lineage switch protein 5 (HLS5), is a putative hepatocellular carcinoma (HCC) suppressor that inhibits phosphorylation of pyruvate kinase isoform M2 (PKM2), which is involved in aerobic glycolysis of cancer cells and further suppresses the Warburg effect and tumorigenicity in HCC. It also negatively regulates Toll-like receptor 7 (TLR7)- and TLR9-mediated type I interferon production by suppressing the stability of interferon regulatory factor 7 (IRF7). Moreover, TRIM35 regulates erythroid differentiation by modulating globin transcription factor 1 (GATA-1) activity. TRIM35 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, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2462496425  19 FQKELTCVICLNYLVDPVTICCGHSFCRPCLCLSWEEAQSPAnCPACREPSPKMDFKTNILLKNLV 84
Cdd:cd16599     1 FKEELLCPICYEPFREAVTLRCGHNFCKGCVSRSWERQPRAP-CPVCKEASSSDDLRTNHTLNNLV 65

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 2462496425 294 RFRVEISFHFEVTNHNIRLFEDVRSWMF----RRGPLNSDRsdyFAA----WGARVFSFGKHYWELDVDNSCDWALGVCN 365
Cdd:cd15829    16 KFRVDVTLDPETAHPNLLVSEDKKCVTFtkkkQRVPDSPKR---FTVnpvvLGFPGFHSGRHFWEVEVGDKPEWAVGVCK 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462496425 366 NSWIRK--NSTMVNSEDIFLLLClkvDNHFNLLTTSPVFPHYIEKPlGRVGVFLDFESGSVSFLNVTKSSLIWSYpAGSL 443
Cdd:cd15829    93 DSLSTKarRPPSGQQGCWRIQLQ---GGDYDAPGAVPPPLLLEVKP-RGIGVFLDYELGEISFYNMPEKSHIHTF-TDTF 167

                         170
                  ....*....|..
gi 2462496425 444 TFPVRPFFYTGH 455
Cdd:cd15829   168 SGPLRPYFYVGP 179

RING finger, HC subclass, found in tripartite motif-containing protein TRIM17 and similar proteins; TRIM17, also known as RING finger protein 16 (RNF16) or testis RING finger protein (Terf), is a crucial E3 ubiquitin ligase that is necessary and sufficient for neuronal apoptosis and contributes to Mcl-1 ubiquitination in cerebellar granule neurons (CGNs). It interacts in a SUMO-dependent manner with nuclear factor of activated T cell NFATc3 transcription factor, and thus inhibits the activity of NFATc3 by preventing its nuclear localization. In contrast, it binds to and inhibits NFATc4 transcription factor in a SUMO-independent manner. Moreover, TRIM17 stimulates degradation of kinetochore protein ZW10 interacting protein (ZWINT), a known component of the kinetochore complex required for the mitotic spindle checkpoint, and negatively regulates cell proliferation. TRIM17 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, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2462496425  20 QKELTCVICLNYLVDPVTICCGHSFCRPCLCLSWEEAQSPAN---------CPACREPSPKMDFKTN 77
Cdd:cd16595     3 QEEATCSICLDYFTDPVMTTCGHNFCRACIQLSWEKARGKKGrrkqkgsfpCPECREMSPQRNLRPN 69

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 2462496425 312 LFEDVRSwmFRRG------PLNSDRSDY-FAAWGARVFSFGKHYWELDVDNSCDWALGVCNNSWIRKNSTMVNSED-IFl 383
Cdd:cd12888    15 LSEDRKS--VRWGdtrqdlPDNPERFDTwPCVLGCEGFTSGRHYWEVEVGDGGGWAVGVARESVRRKGEISFSPEEgIW- 91

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2462496425 384 llCLKVDNHFNLLTTSPVFPHYIEKPLGRVGVFLDFESGSVSFLNVTKSSLIWSYPAGS-LTFPVRPFFYTG 454
Cdd:cd12888    92 --AVGQWGGQYWALTSPETPLPLSEVPRRIRVYLDYEGGQVAFFDADNEAPIFTFPPASfAGERIFPWFWVG 161

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 2462496425 308 HNIRLFED---VRSWMFRRGPLNSDRSDYFAAW----GARVFSFGKHYWELDVDNSCDWALGVC-----NNSWIRKNSTm 375
Cdd:cd13734    10 RKLRLSNDnltVEYDPEGSKDQAAVLPRRFTGSpavlGDVAISSGRHYWEVSVSRSTSYRVGVAyksapRDEDLGKNST- 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462496425 376 vnSEdiflllCLKVDNH-FNLLTTSPVFPHYIEKPLGRVGVFLDFESGSVSFLNVTKSSLIWSYPAgSLTFPVRPFFYTG 454
Cdd:cd13734    89 --SW------CLSRDNNrYTARHDGKVVDLRVTGHPARIGVLLDYDNGTLSFYDAESKQHLYTFHV-DFEGPVCPAFAVW 159

                  .
gi 2462496425 455 H 455
Cdd:cd13734   160 N 160

RING finger, HC subclass, found in RING finger protein 39 (RNF39) and similar proteins; RNF39, also called protein HZFw, may play a role in prolonged long term-potentiation (LTP) maintenance. It is involved in the etiology of Behcet's disease (BD). It may also be involved in HIV-1 replication. RNF39 acts as an E3 ubiquitin ligase that inhibits retinoic acid-inducible gene-I (RIG-I)-like receptor (RLR) pathways by mediating K48-linked ubiquitination and proteasomal degradation of DDX3X (DEAD-box RNA helicase 3, X-linked). RNF39 contains a typical C3HC4-type RING-HC finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 2462496425  20 QKELTCVICLNYLVDPVTICCGHSFCRPCLCLSWEEAQSPAN------CPACREPSP 70
Cdd:cd16592     2 QEETTCPICLGYFKDPVILDCEHSFCRACIARHWGQEAMEGNgaegvfCPQCGEPCP 58

RING finger, HC subclass, found in tripartite motif-containing protein 69 (TRIM69) and similar proteins; TRIM69, also known as RFP-like domain-containing protein trimless or RING finger protein 36 (RNF36), is a testis E3 ubiquitin-protein ligase that plays a specific role in apoptosis and may also play an important role in germ cell homeostasis during spermatogenesis. TRIM69 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, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 2462496425  22 ELTCVICLNYLVDPVTICCGHSFCRPCLCLSWEEAQSPANCPACREPSPKMDFKTN 77
Cdd:cd16611     4 ELHCPLCLDFFRDPVMLSCGHNFCQSCITGFWELQAEDTTCPECRELCQYRNLTPN 59