RING finger, HC subclass, found in tripartite motif-containing proteins TRIM5, TRIM6, TRIM22, TRIM34 and similar proteins; TRIM5, TRIM6, TRIM22, and TRIM34, four 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, 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. TRIM5, also known as RING finger protein 88 (RNF88), is a capsid-specific restriction factor that prevents infection from non-host-adapted retroviruses in a species-specific manner by binding to and destabilizing the retroviral capsid lattice before reverse transcription is completed. Its retroviral restriction activity correlates with the ability to activate TAK1-dependent innate immune signaling. TRIM5 also acts as a pattern recognition receptor that activates innate immune signaling in response to the retroviral capsid lattice. Moreover, TRIM5 plays a role in regulating autophagy through activation of autophagy regulator BECN1 by causing its dissociation from its inhibitors BCL2 and TAB2. It also plays a role in autophagy by acting as a selective autophagy receptor which recognizes and targets HIV-1 capsid protein p24 for autophagic destruction. TRIM6, also known as RING finger protein 89 (RNF89), is an E3-ubiquitin ligase that cooperates with the E2-ubiquitin conjugase UbE2K to catalyze the synthesis of unanchored K48-linked polyubiquitin chains, and further stimulates the interferon-I kappa B kinase epsilon (IKKepsilon) kinase-mediated antiviral response. It also regulates the transcriptional activity of Myc during the maintenance of embryonic stem (ES) cell pluripotency, and may act as a novel regulator for Myc-mediated transcription in ES cells. TRIM22, also known as 50 kDa-stimulated trans-acting factor (Staf-50) or RING finger protein 94 (RNF94), is an E3 ubiquitin-protein ligase that 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 acts as a suppressor of basal HIV-1 long terminal repeat (LTR)-driven transcription by preventing the transcription factor specificity protein 1 (Sp1) binding to the HIV-1 promoter. It also controls FoxO4 activity and cell survival by directing Toll-like receptor 3 (TLR3)-stimulated cells toward type I interferon (IFN) type I gene induction or apoptosis. Moreover, TRIM22 can activate the noncanonical nuclear factor-kappaB (NF-kappaB) pathway by activating I kappa B kinase alpha (IKKalpha). It also regulates nucleotide binding oligomerization domain containing 2 (NOD2)-dependent activation of interferon-beta signaling and nuclear factor-kappaB. TRIM34, also known as interferon-responsive finger protein 1 or RING finger protein 21 (RNF21), may function as antiviral protein that contribute to the defense against retroviral infections.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 18087807   7 LNVQEEVTCPICLELLTEPLSLDCGHSLCRACITVSNKEAVTsMGGKSSCPVCGISYSFEHLQANQHLANIVE 79
Cdd:cd16591   1 VNIKEEVTCPICLELLTEPLSLDCGHSFCQACITANHKESVN-QEGESSCPVCRTSYQPENLRPNRHLANIVE 72

RING finger, HC subclass, found in tripartite motif-containing proteins TRIM5, TRIM6, TRIM22, TRIM34 and similar proteins; TRIM5, TRIM6, TRIM22, and TRIM34, four 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, 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. TRIM5, also known as RING finger protein 88 (RNF88), is a capsid-specific restriction factor that prevents infection from non-host-adapted retroviruses in a species-specific manner by binding to and destabilizing the retroviral capsid lattice before reverse transcription is completed. Its retroviral restriction activity correlates with the ability to activate TAK1-dependent innate immune signaling. TRIM5 also acts as a pattern recognition receptor that activates innate immune signaling in response to the retroviral capsid lattice. Moreover, TRIM5 plays a role in regulating autophagy through activation of autophagy regulator BECN1 by causing its dissociation from its inhibitors BCL2 and TAB2. It also plays a role in autophagy by acting as a selective autophagy receptor which recognizes and targets HIV-1 capsid protein p24 for autophagic destruction. TRIM6, also known as RING finger protein 89 (RNF89), is an E3-ubiquitin ligase that cooperates with the E2-ubiquitin conjugase UbE2K to catalyze the synthesis of unanchored K48-linked polyubiquitin chains, and further stimulates the interferon-I kappa B kinase epsilon (IKKepsilon) kinase-mediated antiviral response. It also regulates the transcriptional activity of Myc during the maintenance of embryonic stem (ES) cell pluripotency, and may act as a novel regulator for Myc-mediated transcription in ES cells. TRIM22, also known as 50 kDa-stimulated trans-acting factor (Staf-50) or RING finger protein 94 (RNF94), is an E3 ubiquitin-protein ligase that 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 acts as a suppressor of basal HIV-1 long terminal repeat (LTR)-driven transcription by preventing the transcription factor specificity protein 1 (Sp1) binding to the HIV-1 promoter. It also controls FoxO4 activity and cell survival by directing Toll-like receptor 3 (TLR3)-stimulated cells toward type I interferon (IFN) type I gene induction or apoptosis. Moreover, TRIM22 can activate the noncanonical nuclear factor-kappaB (NF-kappaB) pathway by activating I kappa B kinase alpha (IKKalpha). It also regulates nucleotide binding oligomerization domain containing 2 (NOD2)-dependent activation of interferon-beta signaling and nuclear factor-kappaB. TRIM34, also known as interferon-responsive finger protein 1 or RING finger protein 21 (RNF21), may function as antiviral protein that contribute to the defense against retroviral infections.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 18087807   7 LNVQEEVTCPICLELLTEPLSLDCGHSLCRACITVSNKEAVTsMGGKSSCPVCGISYSFEHLQANQHLANIVE 79
Cdd:cd16591   1 VNIKEEVTCPICLELLTEPLSLDCGHSFCQACITANHKESVN-QEGESSCPVCRTSYQPENLRPNRHLANIVE 72

B-box-type 2 zinc finger found in tripartite motif-containing proteins, TRIM5, TRIM6, TRIM22, TRIM34, TRIM38 and similar proteins; The family includes TRIM5, TRIM6, TRIM22, TRIM34, and TRIM38, all of which belong to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a RING finger, Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif. TRIM5, also termed RING finger protein 88 (RNF88), is a capsid-specific restriction factor that prevents infection from non-host-adapted retroviruses in a species-specific manner by binding to and destabilizing the retroviral capsid lattice before reverse transcription is completed. Its retroviral restriction activity correlates with the ability to activate TAK1-dependent innate immune signaling. TRIM5 also acts as a pattern recognition receptor that activates innate immune signaling in response to the retroviral capsid lattice. Moreover, TRIM5 plays a role in regulating autophagy through activation of autophagy regulator BECN1 by causing its dissociation from its inhibitors BCL2 and TAB2. It also plays a role in autophagy by acting as a selective autophagy receptor which recognizes and targets HIV-1 capsid protein p24 for autophagic destruction. TRIM6, also termed RING finger protein 89 (RNF89), is an E3-ubiquitin ligase that cooperates with the E2-ubiquitin conjugase UbE2K to catalyze the synthesis of unanchored K48-linked polyubiquitin chains, and further stimulates the interferon-I kappa B kinase epsilon (IKKepsilon) kinase-mediated antiviral response. It also regulates the transcriptional activity of Myc during the maintenance of embryonic stem (ES) cell pluripotency, and may act as a novel regulator for Myc-mediated transcription in ES cells. TRIM22, also termed 50 kDa-stimulated trans-acting factor (Staf-50), or RING finger protein 94 (RNF94), is an E3 ubiquitin-protein ligase that 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 acts as a suppressor of basal HIV-1 long terminal repeat (LTR)-driven transcription by preventing transcription factor specificity protein 1 (Sp1) binding to the HIV-1 promoter. It also controls FoxO4 activity and cell survival by directing Toll-like receptor 3 (TLR3)-stimulated cells toward type I interferon (IFN) type I gene induction or apoptosis. Moreover, TRIM22 can activate the noncanonical nuclear factor-kappaB (NF-kappaB) pathway by activating I kappa B kinase alpha (IKKalpha). It also regulates nucleotide binding oligomerization domain containing 2 (NOD2)-dependent activation of interferon-beta signaling and nuclear factor-kappaB. TRIM34, also termed interferon-responsive finger protein 1, or RING finger protein 21 (RNF21), may function as an antiviral protein that contributes to the defense against retroviral infections. TRIM38, also known as RING finger protein 15 (RNF15) or zinc finger protein RoRet, is an E3 ubiquitin-protein ligase that promotes K63- and K48-linked ubiquitination of cellular proteins and also catalyzes self-ubiquitination. It negatively regulates tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta-triggered nuclear factor-kappaB (NF-kappaB) activation by mediating lysosomal-dependent degradation of transforming growth factor beta (TGFbeta)-activated kinase 1 (TAK1)-binding protein (TAB)2/3, two critical components of the TAK1 kinase complex. It also inhibits TLR3/4-mediated activation of NF-kappaB and interferon regulatory factor 3 (IRF3) by mediating ubiquitin-proteasomal degradation of TNF receptor-associated factor 6 (Traf6) and NAK-associated protein 1 (Nap1), respectively. Moreover, TRIM38 negatively regulates TLR3-mediated interferon beta (IFN-beta) signaling by targeting ubiquitin-proteasomal degradation of TIR domain-containing adaptor inducing IFN-beta (TRIF). It functions as a valid target for autoantibodies in primary Sjogren's Syndrome.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|
gi 18087807  95 DLCDHHGEKLLLFCKEDRKVICWLCERSQEHRGHHTVLTE 134
Cdd:cd19761   1 DHCEHHGEKLLLFCQEDGKVICWLCERSQEHRGHHTFLLE 40

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 18087807    15 CPICLELLTEPLSLDCGHSLCRACITVSNKEavtSMGGKSSCPVC 59
Cdd:pfam15227   1 CPICLDYLEKPVSIECGHSFCLSCINSLQKE---PDGESLLCPQC 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 18087807     15 CPICLE-LLTEPLSLDCGHSLCRACITVSNKEavtsmgGKSSCPVC 59
Cdd:smart00184   1 CPICLEeYLKDPVILPCGHTFCRSCIRKWLES------GNNTCPIC 40

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

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 18087807  15 CPICLELLTEPLSLDCGHSLCRACITvsnkeavTSMGGKSSCPVCGISYSFEHLQANQHLANIVE 79
Cdd:COG5432  28 CRICDCRISIPCETTCGHTFCSLCIR-------RHLGTQPFCPVCREDPCESRLRGSSGSREINE 85

PRY/SPRY domain in tripartite motif-binding protein 5 (TRIM5), also known as RING finger protein 88 (RNF88); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM5 which is also known as RING finger protein 88 (RNF88) or TRIM5alpha (TRIM5a), an antiretroviral restriction factor and a retrovirus capsid sensor in immune signaling. TRIM5 domain is composed of RING/B-box/coiled-coil core and also known as RBCC protein. It blocks retrovirus infection soon after the virion core enters the cell cytoplasm by recognizing the capsid protein lattice that encases the viral genomic RNA; the SPRY domain provides the capsid recognition motif that dictates specificity to retroviral restriction. TRIM5a, an E3 ubiquitin ligase, promotes innate immune signaling by activating the TAK1 kinase complex by cooperating with the heterodimeric E2, UBC13/UEV1A. It also stimulates NFkB and AP-1 signaling, and the transcription of inflammatory cytokines and chemokines, and amplifies these activities upon retroviral infection. Interaction of its PRY-SPRY or cyclophilin domains with the retroviral capsid lattice stimulates the formation of a complementary lattice by TRIM5, with greatly increased TRIM5 E3 activity, and host cell signal transduction.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087807 290 FRELTAVRCYWVDVTLNSVNLNLNLVLsEDQRQVISVPIWPF-----QCYNYGVLGSQYFSSGKHYWEVDVSKKTAWILG 364
Cdd:cd15822   1 FNELTDVQRYWVHVTLDPSNNKNIVIS-EDRRQVRYVRKQQRynsngNNEDYGVLGSPSITSGKHYWEVDVSKKRAWILG 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087807 365 VYCRTYSR-HMKYVVRRCANRQNLYTKYRPLFGYWVIGLQNKCKYGVFEESLSSDPEVLTLSMAVPPCRVGVFLDYEAGI 443
Cdd:cd15822  80 VCGGKYPNsTLKDFNKQGKNNQKQCSNYQPKYGYWVIGLQNKSEYNAFEDSSSSDPLILTLSLTVPPCRVGVFLDYEAGT 159

                       170       180       190       200
                ....*....|....*....|....*....|....*....|.
gi 18087807 444 VSFFNVTSHGSLIYKFSKCCFSQPVYPYFNPWNCPAPMTLC 484
Cdd:cd15822 160 VSFFNVTNHGFLIYKFSSCSFSQEVFPYFNPMKCPVPMTLC 200

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 18087807 299 YWVDVTLNSVNLNLNLVLSEDQRQVISVPIWPFQCYN------YGVLGSQYFSSGKHYWEVDVSKKTAWILGVYCRTYSR 372
Cdd:cd15824   1 YWVDVMLNPVNAVSNVVVSADQRQVTVVHICMFRNSNpcdfsaFDVLGCQYFSSGKYYWEVDVSGKIAWILGVYSKRNNL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087807 373 HMK----YVVRRCANRQNLYTKYRPLFGYWVIGLQNKCKYGVFEESLSSDPEVLTLSMAVPPCRVGVFLDYEAGIVSFFN 448
Cdd:cd15824  81 NKRkssgFAFDPNVNHPNVYSRYRPQNGYWVIGLQNESEYNAFEDSSSSDPKVLTLSMAVPPHRVGVFLDYEAGTVSFFN 160

                       170       180       190
                ....*....|....*....|....*....|....*...
gi 18087807 449 VTSHGSLIYKFSKCCFSQPVYPYFNPWNCPAPMTLCPP 486
Cdd:cd15824 161 VTNHGSLIYKFSKCCFSQPVYPYFNPWNCPAPMTLCPP 198

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 18087807 318 EDQRQVISVPIWP--------FQCYnYGVLGSQYFSSGKHYWEVDVSKKTAWILGvycrtysrhmkyVVRRCANRQNlYT 389
Cdd:cd13733  17 EDLKSVRYGDKRQnlpdnperFDTC-VCVLGSEGFSSGRHYWEVEVGGKTDWDLG------------VARESVNRKG-KI 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087807 390 KYRPLFGYWVIGLQNKCKYGVfeeslSSDPEVLtLSMAVPPCRVGVFLDYEAGIVSFFNVTsHGSLIYKFSkCCFSQPVY 469
Cdd:cd13733  83 TLSPENGYWTVGLRNGNEYKA-----LTSPSTP-LSLREKPQKVGVFLDYEEGQVSFYNVD-DGSHIYTFT-DCFTEKLY 154

                       170       180
                ....*....|....*....|
gi 18087807 470 PYFNPW-----NCPAPMTLC 484
Cdd:cd13733 155 PYFSPClndggKNSAPLIIC 174

RING finger, HC subclass, found in tripartite motif-containing proteins TRIM5, TRIM6, TRIM22, TRIM34 and similar proteins; TRIM5, TRIM6, TRIM22, and TRIM34, four 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, 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. TRIM5, also known as RING finger protein 88 (RNF88), is a capsid-specific restriction factor that prevents infection from non-host-adapted retroviruses in a species-specific manner by binding to and destabilizing the retroviral capsid lattice before reverse transcription is completed. Its retroviral restriction activity correlates with the ability to activate TAK1-dependent innate immune signaling. TRIM5 also acts as a pattern recognition receptor that activates innate immune signaling in response to the retroviral capsid lattice. Moreover, TRIM5 plays a role in regulating autophagy through activation of autophagy regulator BECN1 by causing its dissociation from its inhibitors BCL2 and TAB2. It also plays a role in autophagy by acting as a selective autophagy receptor which recognizes and targets HIV-1 capsid protein p24 for autophagic destruction. TRIM6, also known as RING finger protein 89 (RNF89), is an E3-ubiquitin ligase that cooperates with the E2-ubiquitin conjugase UbE2K to catalyze the synthesis of unanchored K48-linked polyubiquitin chains, and further stimulates the interferon-I kappa B kinase epsilon (IKKepsilon) kinase-mediated antiviral response. It also regulates the transcriptional activity of Myc during the maintenance of embryonic stem (ES) cell pluripotency, and may act as a novel regulator for Myc-mediated transcription in ES cells. TRIM22, also known as 50 kDa-stimulated trans-acting factor (Staf-50) or RING finger protein 94 (RNF94), is an E3 ubiquitin-protein ligase that 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 acts as a suppressor of basal HIV-1 long terminal repeat (LTR)-driven transcription by preventing the transcription factor specificity protein 1 (Sp1) binding to the HIV-1 promoter. It also controls FoxO4 activity and cell survival by directing Toll-like receptor 3 (TLR3)-stimulated cells toward type I interferon (IFN) type I gene induction or apoptosis. Moreover, TRIM22 can activate the noncanonical nuclear factor-kappaB (NF-kappaB) pathway by activating I kappa B kinase alpha (IKKalpha). It also regulates nucleotide binding oligomerization domain containing 2 (NOD2)-dependent activation of interferon-beta signaling and nuclear factor-kappaB. TRIM34, also known as interferon-responsive finger protein 1 or RING finger protein 21 (RNF21), may function as antiviral protein that contribute to the defense against retroviral infections.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 18087807   7 LNVQEEVTCPICLELLTEPLSLDCGHSLCRACITVSNKEAVTsMGGKSSCPVCGISYSFEHLQANQHLANIVE 79
Cdd:cd16591   1 VNIKEEVTCPICLELLTEPLSLDCGHSFCQACITANHKESVN-QEGESSCPVCRTSYQPENLRPNRHLANIVE 72

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087807 338 VLGSQYFSSGKHYWEVDVSKKTAWILGVyCRTysrhmkyVVRRCANrqnlyTKYRPLFGYWVIGLQNKcKYgvfeESLSS 417
Cdd:cd13745  47 VLGAEGFTGGRHYWEVEVGDKTEWTLGV-CRE-------SVSRKGE-----VTLSPENGYWTVWLRDG-KY----EALTS 108

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 18087807 418 DPEVLTLSmaVPPCRVGVFLDYEAGIVSFFNVTSHgSLIYKFSkCCFSQPVYPYFNPWNCP-----APMTLCP 485
Cdd:cd13745 109 PPTPLPVS--VRPSRVGIFLDYEAGEVSFYNVTDR-SHLFTFT-DTFSGTLRPYFYPGLNAggknaAPLIICP 177

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087807 318 EDQRQVI------SVPIWP--FQcYNYGVLGSQYFSSGKHYWEVDVSKKTAWILGVyCRtysrhmKYVVRRCanrqnlYT 389
Cdd:cd15820  21 EDQRSLQwadepqNLPDNPkrFD-WHYCVLGCKSFTSGRHFWEVEVGDRKEWYVGV-CR------ENVERKL------WV 86

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087807 390 KYRPLFGYWVIGLQNKCKYGVFeeslsSDPEVlTLSMAVPPCRVGVFLDYEAGIVSFFNVTShGSLIYKFSKCCFSQPVY 469
Cdd:cd15820  87 KMAPENGFWTIGLSDGNDYQAL-----TDPRT-KLTIANPPQRVGVFLDYETGEVSFYNAMD-GSHIYTFPHTSFSGPLY 159

                       170
                ....*....|....*...
gi 18087807 470 PYFN--PWNcPAPMTLCP 485
Cdd:cd15820 160 PVFRllSWD-PTALTICP 176

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 18087807 338 VLGSQYFSSGKHYWEVDVSKKTAWILGvycrtysrhmkyVVRRCANRQNLYTkYRPLFGYWVIGLQNKCKYgvfeESLSS 417
Cdd:cd15818  57 VLGSEGFTSGKHYWEVEVAKKTKWTLG------------VVRESINRKGNCP-LSPEDGFWLLRLRNQNEL----KALDV 119

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 18087807 418 DPEVLTLSMAvpPCRVGVFLDYEAGIVSFFNVT--SHgslIYKFSkCCFSQPVYPYFNP 474
Cdd:cd15818 120 PSFSLTLTSN--LNKVGIYLDYEGGQVSFYNANtmSH---IYTFS-DTFTEKIYPYFCP 172

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 18087807 294 TAVRCYWVDVTLNSVNLNLNLVLSEDQRQV--------ISVPIWPFQ---CynygVLGSQYFSSGKHYWEVDVSKKTAWI 362
Cdd:cd15815   6 KMLRRHQVSVTLDPDTAHPELTLSKDQRQVtygrcqenLDASPKRFTvlpC----VLGCEGFTSGRHYFEVDVGEGTGWD 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087807 363 LGVyCrtysrhMKYVVRrcanrqNLYTKYRPLFGYWVIGLQNKCKYgvfeESLSSDPEVLTLSMAvpPCRVGVFLDYEAG 442
Cdd:cd15815  82 VGV-C------LENVQR------GFGMKQEPEFGFWTIRLCEEDGY----VALTSPPTPLPLREK--PLVVGVFLDYEAG 142

                       170       180       190
                ....*....|....*....|....*....|
gi 18087807 443 IVSFFNVTShGSLIYKFSKCCFSQPVYPYF 472
Cdd:cd15815 143 LVSFYNMTT-GSHIFTFPKASFSDTLRPYF 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 18087807 318 EDQRQVISVPIWPFQCYN----Y---GVLGSQYFSSGKHYWEVDVSKKTAWILGVyCR-TYSRhmkyvvrrcaNRQNlyt 389
Cdd:cd15828  27 EDRKSVLYGEMKQNVCYNprrfYlcpAVLGSEGFHSGRQYWEVEVGDKPEWTLGV-CQdCLPR----------NWSN--- 92

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087807 390 kyRPLF--GYWVIGLQNKCKYGVFeeslssDPEVLTLSMAVPPCRVGVFLDYEAGIVSFFNVtSHGSLIYKFSKcCFSQP 467
Cdd:cd15828  93 --QPSVqdGLWAIGRYSESNYVAL------GPKKIQLLPKVRPSKIGIFLDYELGEVSFYNM-NDRSLLYTFSD-SFTGT 162

                       170
                ....*....|....*...
gi 18087807 468 VYPYFNPWNCPAPMTLCP 485
Cdd:cd15828 163 LWPYFYTGTDSEPLKICT 180

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 18087807 329 WPfqCynygVLGSQYFSSGKHYWEVDVSKKTAWILGVyCRTysrhmkyvvrrCANRQNLYTKyRPLFGYWVIGLQNKCKY 408
Cdd:cd15816  41 WP--C----VLGLQSFSSGRHYWEVAVGEKAEWGLGV-CQD-----------SAPRKGETTP-SPENGVWAVWLLKGNEY 101

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 18087807 409 GVFeeSLSSDPEVLTLSmavpPCRVGVFLDYEAGIVSFFNVTsHGSLIYKFSKcCFSQPVYPYFnpWNC-PAPMTL 483
Cdd:cd15816 102 MVL--ASPSVPLLQLRR----PRRVGVFLDYEAGEISFYNVT-AGSHIYTFRQ-LFSGILRPYF--FVCdTTPLTL 167

PRY/SPRY domain in tripartite motif-containing protein 35 (TRIM35); This PRY/SPRY domain is found at the C-terminus of the overall domain architecture of tripartite motif 35, TRIM35 (also known as hemopoietic lineage switch protein), which includes a RING finger domain (RING) and a B-box motif (BBOX). TRIM35 may play a role as a tumor suppressor and is implicated in the cell death mechanism.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087807 334 YNYGVLGSQYFSSGKHYWEVDVSKKTAWILGVYCRTYSRHMKYVVrrcanrqnlytkyRPLFGYWVIGLQNkckyGVFEE 413
Cdd:cd12893  40 PYPCVLGSEGFTSGKHSWDVEVGDNTSWMLGVAKESVQRKGKFTL-------------SPESGFWTIGFSE----GKYSA 102

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 18087807 414 SLSSDPEVLtLSMAVPPCRVGVFLDYEAGIVSFFNVTSHgSLIYKFSKcCFSQPVYPYFNPWNCPAPMTLCP 485
Cdd:cd12893 103 RTSPEPRTP-LRVKQKPQRIRVQLDWDRGKVSFSDPDTN-THIHTFTH-TFTERVFPYFYTGCKSEPLRILP 171

PRY/SPRY domain in tripartite motif-binding protein 50 (TRIM50); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM50. 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. It is specifically expressed in gastric parietal cells and may play an essential role in tubulovesicular dynamics. It also interacts with and increases the level of p62, a multifunctional adaptor protein that is implicated in various cellular processes such as the autophagy clearance of polyubiquitinated protein aggregates.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087807 333 CYNYGVLGSQYFSSGKHYWEVDVSKKTAWILGvycrtysrhmkyVVRRCANRQNLYTKyRPLFGYWVIGLqnkcKYGVFE 412
Cdd:cd13743  51 DYSNCVLASRGFSSGKHYWEVVVGSKSKWRLG------------LIKGTTSRKGKLNK-SPENGVWLIGL----KEGRVY 113

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 18087807 413 ESLSSdPEVlTLSMAVPPCRVGVFLDYEAGIVSFFNVTSHGSL--IYKFsKCCFSQPVYPYFN 473
Cdd:cd13743 114 EAFAN-PRV-PLPLSTRPQRIGVFLDYEKGELTFYNADSPDELvpIYTF-QAEFQGKLYPLLD 173

PRY/SPRY domain in tripartite motif-containing (TRIM) proteins, including TRIM14-like, TRIM16-like, TRIM25-like, TRIM47-like, TRIM65 and RNF135, and stonustoxin; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of several Class I TRIM proteins, including TRIM14, TRIM16 and TRIM25, TRIM47 as well as RING finger protein RNF135 and stonustoxin, a secreted poisonous protein of the stonefish Synanceja horrida. TRIM16 (also known as estrogen-responsive B box protein or EBBP) has E3 ubiquitin ligase activity. It is a regulator of keratinocyte differentiation and a tumor suppressor in retinoid-sensitive neuroblastoma. TRIM25 (also called Efp) ubiquitinates the N terminus of the viral RNA receptor retinoic acid-inducible gene-I (RIG-I) in response to viral infection, leading to activation of the RIG-I signaling pathway, thus resulting in type I interferon production to limit viral replication. It has been shown that the influenza A virus targets TRIM25 and disables its antiviral function. TRIM47, also known as GOA (Gene overexpressed in astrocytoma protein) or RNF100 (RING finger protein 100), is highly expressed in kidney tubular cells, but low expressed in most tissue. It is overexpressed in astrocytoma tumor cells and plays an important role in the process of dedifferentiation that is associated with astrocytoma tumorigenesis. RNF135 ubiquitinates RIG-I (retinoic acid-inducible gene-I) to promote interferon-beta induction during the early phase of viral infection. Stonustoxin (STNX) is a hypotensive and lethal protein factor that also possesses other biological activities such as species-specific hemolysis (due to its ability to form pores in the cell membrane) and platelet aggregation, edema-induction, and endothelium-dependent vasorelaxation (mediated by the nitric oxide pathway and activation of potassium channels). The PRY-SPRY domain in these TRIM families is suggested to serve as the target binding site.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087807 338 VLGSQYFSSGKHYWEVDVSKKTAWILGVycrTYSRhmkyvVRRCANRQNLytkyrplfGY----WVIGLQNKcKYGVFEE 413
Cdd:cd12891  42 VLSTQSFSSGRHYWEVEVSESGGWSVGV---AYPS-----IERKGDESRI--------GRndksWCLEWQDK-SFSAWHN 104

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 18087807 414 SLSSDpevltLSmAVPPCRVGVFLDYEAGIVSFFNVTSHGSLIYKFsKCCFSQPVYPYFNPW 475
Cdd:cd12891 105 NEETP-----LP-SVSSRRLGVYLDYEAGRLSFYELSDPIRHLHTF-TATFTEPLHPAFWVL 159

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 18087807 334 YNYGVLGSQYFSSGKHYWEVDVSKKTAWILGVYCRTYSRHM-------KYVVRRCANRqnlytkyrplfgYWVIGlqnkc 406
Cdd:cd13734  41 GSPAVLGDVAISSGRHYWEVSVSRSTSYRVGVAYKSAPRDEdlgknstSWCLSRDNNR------------YTARH----- 103

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087807 407 kygvfeeslssDPEVLTLSMAVPPCRVGVFLDYEAGIVSFFNVTShGSLIYKFsKCCFSQPVYPYFNPWN 476
Cdd:cd13734 104 -----------DGKVVDLRVTGHPARIGVLLDYDNGTLSFYDAES-KQHLYTF-HVDFEGPVCPAFAVWN 160

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 18087807 334 YNYGVLGSQYFSSGKHYWEVDVSKKTAWILGVYCRTYSRHMKYvvrrcanrqnlytKYRPLFGYWVIGlqnkCKYGVFEE 413
Cdd:cd12897  52 KSTCVVASQGFSEGEHYWEVVVGDKPRWALGVIKGTASRKGKL-------------HASPSHGVWLIG----LKEGKVYE 114

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 18087807 414 SLSSDPEVLTLSMAVPPCRVGVFLDYEAGIVSFFNVTSHGSL--IYKFSKcCFSQPVYPYFN 473
Cdd:cd12897 115 AHGEPKEPRPLRVAGRPHRIGVYLSFEDGVLSFFDASDPDDLrtLYTFQE-RFQGKLYPFFD 175

PRY/SPRY domain in tripartite motif-binding protein 41 (TRIM41); 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 41 (TRIM41). TRIM41 (also known as RING finger-interacting protein with C kinase or RINCK) 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087807 335 NYGVLGSQYFSSGKHYWEVDVSKKTAWILGVyCRTYSRHMKYVV--------------RRCANRQNLYTKYRPLFG--YW 398
Cdd:cd13741  41 DCCVLGAQGFRSGRHYWEVEVGGRRGWAVGA-ARESTHHKEKVGsggssvssgdasssRHHHRRRRLHLPQQPLLQreVW 119

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18087807 399 VIGLQNKcKYgvfeESLSSDPEVLtLSMAVPPCRVGVFLDYEAGIVSFFNVTSHGSlIYKFSKCCFSQPVYPYFNPWNCP 478
Cdd:cd13741 120 CVGTNGK-RY----QAQSSTEQTL-LSPSEKPRRFGVYLDYEAGRLGFYNAETLAH-VHTFSAAFLGERVFPFFRVLSKG 192

                ....*..
gi 18087807 479 APMTLCP 485
Cdd:cd13741 193 TRIKLCP 199

RING finger, HC subclass, found in tripartite motif-containing protein TRIM21 and similar proteins; TRIM21, also known as 52 kDa Ro protein, 52 kDa ribonucleoprotein autoantigen Ro/SS-A, Ro(SS-A), RING finger protein 81 (RNF81), or Sjoegren syndrome type A antigen (SS-A), is a ubiquitously expressed E3 ubiquitin-protein ligase and a high affinity antibody receptor uniquely expressed in the cytosol of mammalian cells. As a cytosolic Fc receptor, TRIM21 binds the Fc of virus-associated antibodies and targets the complex in the cytosol for proteasomal degradation in a process known as antibody-dependent intracellular neutralization (ADIN), and provides an intracellular immune response to protect host defense against pathogen infection. It shows remarkably broad isotype specificity as it does not only bind IgG, but also IgM and IgA. Moreover, TRIM21 promotes the cytosolic DNA sensor cGAS and the cytosolic RNA sensor RIG-I sensing of viral genomes during infection by antibody-opsonized virus. It stimulates inflammatory signaling and activates innate transcription factors, such as nuclear factor-kappaB (NF-kappaB). TRIM21 also plays an essential role in p62-regulated redox homeostasis, suggesting it may be a viable target for treating pathological conditions resulting from oxidative damage. Furthermore, TRIM21 may have implications for various autoimmune diseases associated with uncontrolled antiviral signaling through the regulation of Nmi-IFI35 complex-mediated inhibition of innate antiviral response. TRIM21 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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 18087807  11 EEVTCPICLELLTEPLSLDCGHSLCRACITVSNKEavtsmgGKSSCPVCGISYSFEHLQANQHLANIVERLKEV 84
Cdd:cd16596   8 EEVTCPICLDPFVEPVSIECGHSFCQECISQVGKG------GGSVCPVCRQRFLLKNLRPNRQLANMVNNLKEI 75