RING finger (Really Interesting New Gene) domain and U-box domain superfamily; The RING finger is a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc. It is defined by the "cross-brace" motif that chelates zinc atoms by eight amino acid residues, typically Cys or His, arranged in a characteristic spacing. Canonical RING motifs have been categorized into two major subclasses, RING-HC (C3HC4-type) and RING-H2 (C3H2C3-type), according to their Cys/His content. There are also many variants of RING fingers: some have different Cys/His patterns while some lack a single Cys or His residue at typical Zn ligand positions (the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can indeed chelate Zn in a RING finger as well). C4C4-, C3HC3D-, C2H2C4-, and C3HC5-type RING fingers are closely related to RING-HC fingers. In contrast, C4HC3- (RING-CH alias RINGv), C3H3C2-, C3H2C2D-, C3DHC3-, and C4HC2H-type RING fingers are more closely related to RING-H2 fingers. However, not all RING finger-containing proteins display regular RING finger features, and the RING finger family has turned out to be multifarious. The degenerate RING fingers of the Siz/PIAS RING (SP-RING) family proteins and sporulation protein RMD5, are characterized by lacking the second, fifth, and sixth Zn2+ ion-coordinating residues. They bind only one Zn2+ ion. On the other hand, the RING fingers of the human APC11 and RBX1 proteins can bind a third Zn atom since they harbor four additional Zn ligands. U-box is a modified form of the RING finger domain that lacks metal chelating Cys and His residues. It resembles the cross-brace RING structure consisting of three beta-sheets and a single alpha-helix, which would be stabilized by salt bridges instead of chelated metal ions. U-box proteins are widely distributed among eukaryotic organisms and show a higher prevalence in plants than in other organisms. RING finger/U-box-containing proteins are a group of diverse proteins with a variety of cellular functions, including oncogenesis, development, viral replication, signal transduction, the cell cycle and apoptosis. Many of them are ubiquitin-protein ligases (E3s) that serve as scaffolds for binding to ubiquitin-conjugating enzymes (E2s, also referred to as ubiquitin carrier proteins or UBCs) in close proximity to substrate proteins, which enable efficient transfer of ubiquitin from E2 to the substrates.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1953328024  12 ELICHICKDYFTDPFTISCGHSFCAPCICLLWEDAQHPARCPVCRAVSPRIYL 64
Cdd:cd16603     4 ELTCPICMNYFIDPVTIDCGHSFCRPCLYLNWQDIPFLAQCPECRKTTEQRNL 56

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 1953328024  338 SGKHYWEVDVGNSCNWIVGLCKESwINRNDMLLNSEDIF-LLLCIKVNDLCRLFSASPLLLHYIQRPQGwIGVFLDYECG 416
Cdd:smart00449   1 SGRHYFEVEIGDGGHWRVGVATKS-VPRGYFALLGEDKGsWGYDGDGGKKYHNSTGPEYGLPLQEPGDV-IGCFLDLEAG 78

                           90       100       110
                   ....*....|....*....|....*....|....
gi 1953328024  417 TVSFVNVAKSSLICNFLSCSFSFPLRPFICYGPK 450
Cdd:smart00449  79 TISFYKNGKYLHGLAFFDVKFSGPLYPAFSLGSG 112

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 1953328024  87 NSAKQVCRTHQTAKDLFCPIEKNLLCGHCSHSPGHATHRHSPISKATKHYREK 139
Cdd:cd19783     1 SSEEQICGTHRETKKLFCEADKSLLCLLCSSSQEHRAHRHYPIEWAAEEHREK 53

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 1953328024   9 VPSELICHICKDYFTDPFTISCGHSFCAPCI--CLlwedAQHPaRCPVCRAVSPRIYLEKIIFAEEQVHAIKKSISCQLp 86
Cdd:TIGR00599  23 LDTSLRCHICKDFFDVPVLTSCSHTFCSLCIrrCL----SNQP-KCPLCRAEDQESKLRSNWLVSEIVESFKNLRPSLL- 96

                          90
                  ....*....|....*
gi 1953328024  87 nsakQVCRTHQTAKD 101
Cdd:TIGR00599  97 ----EFLRIPKTTPV 107

RING-type zinc-finger; This zinc-finger is a typical RING-type of plant ubiquitin ligases.

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1953328024  15 CHICKDYFTDPfTISCGHSFCAPCICLLWEDAQHPARCP 53
Cdd:pfam13445   1 CPICLELFTDP-VLPCGHTFCRECLEEMSQKKGGKFKCP 38

E3 ubiquitin-protein ligase RMA2; Provisional

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1953328024   2 DSTFVQNVPSELICHICKDYFTDPFTISCGHSFCAPCI-------------CLLWEDAQHPARCPVCRA 57
Cdd:PLN03208    8 DDTTLVDSGGDFDCNICLDQVRDPVVTLCGHLFCWPCIhkwtyasnnsrqrVDQYDHKREPPKCPVCKS 76

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 1953328024 289 ITLDHNISNYRVALFEDLIHLQCSSDHQDMPHSPASLQYTP--LwGAQTFTSGKHYWEVDVGNSCNWIVGLCKESwINRN 366
Cdd:cd13733     2 VTLDPDTAHPNLILSEDLKSVRYGDKRQNLPDNPERFDTCVcvL-GSEGFSSGRHYWEVEVGGKTDWDLGVARES-VNRK 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1953328024 367 DML-LNSEDIFLLLCIKVNDLCRLFSASPLLLHYIQRPQGwIGVFLDYECGTVSFVNVAKSSLICNFlSCSFSFPLRPFI 445
Cdd:cd13733    80 GKItLSPENGYWTVGLRNGNEYKALTSPSTPLSLREKPQK-VGVFLDYEEGQVSFYNVDDGSHIYTF-TDCFTEKLYPYF 157

                  .
gi 1953328024 446 C 446
Cdd:cd13733   158 S 158

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 1953328024 285 FRVYITLDHNISNYRVALFEDLIHLQCSSDHQDMPHSPASLQYTPL-WGAQTFTSGKHYWEVDVGNSCNWIVGLCKESWI 363
Cdd:cd12900     1 HMVHITLDPDTANPWLILSKDRRQVRLGDTHQNVPENEERFDNYPMvLGAQRFNSGKHYWEVDVTGKEAWDLGVCRDSVR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1953328024 364 NRNDMLLNSEDIFLLLCIkVNDLCRLFSASPLLLHyIQRPQGWIGVFLDYECGTVSFVNVAK-SSLICNFLSCSFSFPLR 442
Cdd:cd12900    81 RKGQFLLSPENGFWTIWL-WNKKYEAGTSPQTTLH-LQVPPCQVGIFLDYEAGVVSFYNITDhGSLIYTFSECAFTGPLR 158

                  ....*.
gi 1953328024 443 PFICYG 448
Cdd:cd12900   159 PFFNPG 164

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1953328024 282 LNNFRVYITLDHNISNYRVALFEDLIHLQCSSDHQDMPHSPASLQYTP-LWGAQTFTSGKHYWEVDVGNSCNWIVGLCKE 360
Cdd:cd15815     8 LRRHQVSVTLDPDTAHPELTLSKDQRQVTYGRCQENLDASPKRFTVLPcVLGCEGFTSGRHYFEVDVGEGTGWDVGVCLE 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1953328024 361 SWINRNDMLLNSEDIF--LLLCIKvNDLCRLFSAsPLLLHYIQRPQgWIGVFLDYECGTVSFVNVAKSSLICNFLSCSFS 438
Cdd:cd15815    88 NVQRGFGMKQEPEFGFwtIRLCEE-DGYVALTSP-PTPLPLREKPL-VVGVFLDYEAGLVSFYNMTTGSHIFTFPKASFS 164

                  ....*...
gi 1953328024 439 FPLRPFIC 446
Cdd:cd15815   165 DTLRPYFQ 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 1953328024 289 ITLDHNISNYRVALFEDLIHLQCSSDHQDMPHSPASLQYTP-LWGAQTFTSGKHYWEVDVGNSCNWIVGLCKESwINRND 367
Cdd:cd15811     2 VTLDPDTANPELVLSEDRRSVRRGDLRQALPDSPERFDPGPcVLGRERFTSGRHYWEVEVGDRTSWALGVCKEN-VNRKE 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1953328024 368 M-LLNSEDIFLLLCIkvndLCRLFSASPLLLHYIQRPQGWIGVFLDYECGTVSFVNVAKSSLICNFLSCSFSFPLRPF 444
Cdd:cd15811    81 KgELSAGNGFWILVF----LGNYYSSERRTFAPLRDPPRRVGIFLDYEAGHLSFYSATDGSLLFIFPETPFSGTLRPL 154

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 1953328024 287 VYITLDHNISNYRVALFEDLIHLQCSSDHQDMPHSPASLQYTP-LWGAQTFTSGKHYWEVDVGNSCNWIVGLCKESWINR 365
Cdd:cd15819     2 VNVTLDPDTAHPALILSEDGRSVTWGETRQDLPENPERFDSLPcVLGQEGFTSGRHYWEVEVGDRTSWDLGVCRDNVMRK 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1953328024 366 NDMLLNSEDIFLLLCIKVNDLCRLFSA-SPLLLHyiQRPQGwIGVFLDYECGTVSFVNVAKSSLICNFLSCSFSFPLRPF 444
Cdd:cd15819    82 GRVTLSPENGFWAIRLYGNEYWALTSPeTPLTLK--EPPRR-VGIFLDYEAGDVSFYNMTDGSHIYTFPQTAFSGPLRPF 158

                  ..
gi 1953328024 445 IC 446
Cdd:cd15819   159 FR 160

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 1953328024 277 GMSERLNNFRVYITLDHNISNYRVALFEDLIHLQCSSDHQDMPHSPASLQYT-PLWGAQTFTSGKHYWEVDVGNSCNWIV 355
Cdd:cd15818     3 EMKSILNPGLSLITLDPKTAHPNLILSEDLTCVWHGDTKQMLPDNPERFDSSvAVLGSEGFTSGKHYWEVEVAKKTKWTL 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1953328024 356 GLCKESWINRNDMLLNSEDIFLLLCIKVNDLCRLFSASPLLLHYIQRPQGwIGVFLDYECGTVSFVNVAKSSLICNFlSC 435
Cdd:cd15818    83 GVVRESINRKGNCPLSPEDGFWLLRLRNQNELKALDVPSFSLTLTSNLNK-VGIYLDYEGGQVSFYNANTMSHIYTF-SD 160

                         170
                  ....*....|.
gi 1953328024 436 SFSFPLRPFIC 446
Cdd:cd15818   161 TFTEKIYPYFC 171

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 1953328024 285 FRVYITLDHNISNYRVALFEDLIHLQCSSDHQDMPHSPASLQYTP-LWGAQTFTSGKHYWEVDVGNSCNWIVGLCKESWI 363
Cdd:cd15828     8 FQVDVTLDPETAHPQLTVSEDRKSVLYGEMKQNVCYNPRRFYLCPaVLGSEGFHSGRQYWEVEVGDKPEWTLGVCQDCLP 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1953328024 364 NRNDMLLNSEDIF--LLLCIKVNdlCRLFSASPLLLHYIQRPQGwIGVFLDYECGTVSFVNVAKSSLICNFlSCSFSFPL 441
Cdd:cd15828    88 RNWSNQPSVQDGLwaIGRYSESN--YVALGPKKIQLLPKVRPSK-IGIFLDYELGEVSFYNMNDRSLLYTF-SDSFTGTL 163

                  ....*..
gi 1953328024 442 RPFICYG 448
Cdd:cd15828   164 WPYFYTG 170

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 1953328024 289 ITLDHNISNYRVALFEDLIHLQCSSDHQDMPHSPASLQYTP-LWGAQTFTSGKHYWEVDVGNSCNWIVGLCKESWINRND 367
Cdd:cd12888     2 VTLDPDTAHPRLVLSEDRKSVRWGDTRQDLPDNPERFDTWPcVLGCEGFTSGRHYWEVEVGDGGGWAVGVARESVRRKGE 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1953328024 368 MLLNSED-IF-LLLCikvNDLCRLFSA--SPLLLHYIQRpqgWIGVFLDYECGTVSFVNVAKSSLICNFLSCSFS-FPLR 442
Cdd:cd12888    82 ISFSPEEgIWaVGQW---GGQYWALTSpeTPLPLSEVPR---RIRVYLDYEGGQVAFFDADNEAPIFTFPPASFAgERIF 155

                  ....*..
gi 1953328024 443 PFICYGP 449
Cdd:cd12888   156 PWFWVGK 162

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 1953328024 289 ITLDHNISNYRVALFEDLIHLQCSSDHQDMPHSPasLQYTPLW---GAQTFTSGKHYWEVDVGNSCNWIVGLCKESwINR 365
Cdd:cd12874     1 LTFDPDTAHLNLILSDDLRSVRVGDISQHPPEPP--PRFFECWqvlGSQSFSSGRHYWEVDVQDDSSWYVGVTYKS-LPR 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1953328024 366 --NDMLLNSEDIFllLCIKVNDLcrLFSAS------PLLLHYIQRpqgwIGVFLDYECGTVSFVNVAKS-SLICNFLsCS 436
Cdd:cd12874    78 kgKMSNLGRNNGS--WCLEWREN--EFSAWhnnpetRLPVTPPRR----LGVFLDCDGGSLSFYGVTDGvQLLYTFK-AK 148

                  ....*...
gi 1953328024 437 FSFPLRPF 444
Cdd:cd12874   149 FTEPLYPA 156

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 1953328024  338 SGKHYWEVDVGNSCNWIVGLCKESwINRNDMLLNSEDIF-LLLCIKVNDLCRLFSASPLLLHYIQRPQGwIGVFLDYECG 416
Cdd:smart00449   1 SGRHYFEVEIGDGGHWRVGVATKS-VPRGYFALLGEDKGsWGYDGDGGKKYHNSTGPEYGLPLQEPGDV-IGCFLDLEAG 78

                           90       100       110
                   ....*....|....*....|....*....|....
gi 1953328024  417 TVSFVNVAKSSLICNFLSCSFSFPLRPFICYGPK 450
Cdd:smart00449  79 TISFYKNGKYLHGLAFFDVKFSGPLYPAFSLGSG 112

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 1953328024  12 ELICHICKDYFTDPFTISCGHSFCAPCICLLWEDAQHPARCPVCRAVSPRIYL 64
Cdd:cd16603     4 ELTCPICMNYFIDPVTIDCGHSFCRPCLYLNWQDIPFLAQCPECRKTTEQRNL 56

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 1953328024  87 NSAKQVCRTHQTAKDLFCPIEKNLLCGHCSHSPGHATHRHSPISKATKHYREK 139
Cdd:cd19783     1 SSEEQICGTHRETKKLFCEADKSLLCLLCSSSQEHRAHRHYPIEWAAEEHREK 53

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 1953328024 289 ITLDHNISNYRVALFEDLIHLQCSSDHQDMPHSPASLQYTP-LWGAQTFTSGKHYWEVDV----GNSCnwIVGLCKESWI 363
Cdd:cd15826     2 VTLDPQTASGSLVLSEDRKSVRYTRQKQNLPDSPLRFDGLPaVLGSPGFSSGRHRWQVEVqlgdGGGC--TVGVAGESVR 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1953328024 364 NRNDMLLNSEDIFLLLCIKvNDLCRLFSASPLLLHYIQRPQGwIGVFLDYECGTVSFVNVAKSSLICNFlSCSFSFPLRP 443
Cdd:cd15826    80 RKGEMGLSAEDGVWAVILS-HQQCWASTSPGTDLPLSEIPRR-VGVALDYEAGTVTLTNAETQEPIFTF-TASFSGKVFP 156

                  ..
gi 1953328024 444 FI 445
Cdd:cd15826   157 FF 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 1953328024  12 ELICHICKDYFTDPFTISCGHSFCAPCICLLWEDAQHPARCPVCRAVSPR 61
Cdd:cd16594     5 ELTCPICLDYFTDPVTLDCGHSFCRACIARCWEEPETSASCPQCRETCPQ 54

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 1953328024 330 LWGAQTFTSGKHYWEVDVGNSCNWIVGL-CKESWINRN-------DMLLNSEDIF-------------LLLCIKVNDLCR 388
Cdd:cd15824    46 VLGCQYFSSGKYYWEVDVSGKIAWILGVySKRNNLNKRkssgfafDPNVNHPNVYsryrpqngywvigLQNESEYNAFED 125

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1953328024 389 LFSASP-LLLHYIQRPQGWIGVFLDYECGTVSFVNVAK-SSLICNFLSCSFSFPLRPFI----CYGP 449
Cdd:cd15824   126 SSSSDPkVLTLSMAVPPHRVGVFLDYEAGTVSFFNVTNhGSLIYKFSKCCFSQPVYPYFnpwnCPAP 192

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 1953328024 332 GAQTFTSGKHYWEVDVGNSCN--WIVGLCKESwINRNDMLLNS-EDIFLL--LCIKVNDLCRLFSASPLLLhyiQRPQGW 406
Cdd:cd15812    46 GQETFSSGRHYWEVGMNLTGDalWALGVCRDN-VSRKDRVPKSpENGFWVvqLSKGKKYLSAMSALTPVTL---TEPPSH 121

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1953328024 407 IGVFLDYECGTVSFVNVAKSSLICNFLSCSFSFPLRPFICYG-PK 450
Cdd:cd15812   122 MGIFLDFEAGEVSFYSVNDGSHLHTYSQAAFPGPLQPFFCLGaPK 166

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
                  ....*....|....*....|....*....|....*....|....*....
gi 1953328024  12 ELICHICKDYFTDPFTISCGHSFCAPCICLLWEDAQHPARCPVCRAVSP 60
Cdd:cd16611     4 ELHCPLCLDFFRDPVMLSCGHNFCQSCITGFWELQAEDTTCPECRELCQ 52

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 1953328024 332 GAQTFTSGKHYWEVDVGNSCNWIVGL------CKESWINRNDMLLNSED----------IFLLLCIKVNDLCRLFSASPL 395
Cdd:cd15825    41 GSQYFSSGKHYWEVDVSKKTAWILGVycrkrsRTFKYVRQGKNHPNVYSryrpqygywvIGLQNKSEYYAFEDSSTSDPK 120

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1953328024 396 LLH-YIQRPQGWIGVFLDYECGTVSFVNVAK-SSLICNFLSCSFSFPLRPFI----CYGP 449
Cdd:cd15825   121 VLTlSVATPPHRVGVFLDYEAGTVSFFNVTNhGSLIYKFSKCCFSQPVYPYFnpwnCPAP 180