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 568951736   7 VDIRDEVTCPICLELLTEPLSIDCGHSFCQVCIIGNSNNSVFgQGGRSSCPVCRTSYQPGNLRPNRHLAAIVK 79
Cdd:cd16591    1 VNIKEEVTCPICLELLTEPLSLDCGHSFCQACITANHKESVN-QEGESSCPVCRTSYQPENLRPNRHLANIVE 72

DNA double-strand break repair ATPase Rad50;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568951736 146 ESLKKLRREQQEAEKLKALIQEKRESwKSQVEPEKRRIQTEFKQLRSIL----------------------DREEQRELK 203
Cdd:PRK03918 221 EELEKLEKEVKELEELKEEIEELEKE-LESLEGSKRKLEEKIRELEERIeelkkeieeleekvkelkelkeKAEEYIKLS 299

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 568951736 204 KLEVEERKGLSIIEKAEGDLIHQSQSLKDLISDLE 238
Cdd:PRK03918 300 EFYEEYLDELREIEKRLSRLEEEINGIEERIKELE 334

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 568951736   7 VDIRDEVTCPICLELLTEPLSIDCGHSFCQVCIIGNSNNSVFgQGGRSSCPVCRTSYQPGNLRPNRHLAAIVK 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
                 ....*....|....*....|....*....|....*...
gi 568951736  97 CALHGEKLQLFCKEDGKLICWLCERSQEHRGHHTFLME 134
Cdd:cd19761    3 CEHHGEKLLLFCQEDGKVICWLCERSQEHRGHHTFLLE 40

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 568951736   15 CPICLELLTEPLsIDCGHSFCQVCIIGNSNNSvfgqGGRSSCP 57
Cdd:pfam13445   1 CPICLELFTDPV-LPCGHTFCRECLEEMSQKK----GGKFKCP 38

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 568951736    15 CPICLE-LLTEPLSIDCGHSFCQVCIIGNSNNSVFgqggrsSCPVC 59
Cdd:smart00184   1 CPICLEeYLKDPVILPCGHTFCRSCIRKWLESGNN------TCPIC 40

DNA double-strand break repair ATPase Rad50;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568951736 146 ESLKKLRREQQEAEKLKALIQEKRESwKSQVEPEKRRIQTEFKQLRSIL----------------------DREEQRELK 203
Cdd:PRK03918 221 EELEKLEKEVKELEELKEEIEELEKE-LESLEGSKRKLEEKIRELEERIeelkkeieeleekvkelkelkeKAEEYIKLS 299

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 568951736 204 KLEVEERKGLSIIEKAEGDLIHQSQSLKDLISDLE 238
Cdd:PRK03918 300 EFYEEYLDELREIEKRLSRLEEEINGIEERIKELE 334

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568951736   147 SLKKLRREQQEAEKLKALIQEKRE--------SWKSQVEpEKRRIQTEFKQLRSILDrEEQRELKKLE--VEE-RKGLSI 215
Cdd:TIGR02168  201 QLKSLERQAEKAERYKELKAELRElelallvlRLEELRE-ELEELQEELKEAEEELE-ELTAELQELEekLEElRLEVSE 278

                           90       100
                   ....*....|....*....|....*
gi 568951736   216 IEKAEGDLIHQSQSLKDLISDLEHR 240
Cdd:TIGR02168  279 LEEEIEELQKELYALANEISRLEQQ 303

Uncharacterized protein, contains DUF3084 domain [Function unknown];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568951736 133 MEEVAQEYQDMfQESLKKLRREQQEAEKLKALIQEKRESWKSQVEPEKRRIQTEFKQLRSILDREEQRELKKLEVEERKG 212
Cdd:COG4372  117 LEELQKERQDL-EQQRKQLEAQIAELQSEIAEREEELKELEEQLESLQEELAALEQELQALSEAEAEQALDELLKEANRN 195

                         90       100
                 ....*....|....*....|....*...
gi 568951736 213 LSIIEKAEGDLIHQSQSLKDLISDLEHR 240
Cdd:COG4372  196 AEKEEELAEAEKLIESLPRELAEELLEA 223

Outer membrane protein (OmpH-like); This family includes outer membrane proteins such as OmpH among others. Skp (OmpH) has been characterized as a molecular chaperone that interacts with unfolded proteins as they emerge in the periplasm from the Sec translocation machinery.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568951736   133 MEEVAQEYQDMFQESLKKLRREQQE----AEKLKA----LIQEKRESWKSQVEPEKRRIQTEFKQLRSILDREEQRELKK 204
Cdd:smart00935  16 GKAAQKQLEKEFKKRQAELEKLEKElqklKEKLQKdaatLSEAAREKKEKELQKKVQEFQRKQQKLQQDLQKRQQEELQK 95

                           90       100
                   ....*....|....*....|....*..
gi 568951736   205 LEVEERKGLSIIEKAEG-DLIHQSQSL 230
Cdd:smart00935  96 ILDKINKAIKEVAKKKGyDLVLDRNAV 122

PRY/SPRY domain of tripartite motif-binding protein 5, 6, 22 and 34 (TRIM5, TRIM6, TRIM22 and TRIM34); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of very close paralogs, TRIM5, TRIM6, TRIM22 and TRIM34. These domains are composed of RING/B-box/coiled-coil core and are also known as RBCC proteins. They form a locus of four closely related TRIM genes within an olfactory receptor-rich region on chromosome 11 of the human genome. Genetic analysis of this locus indicates that these four genes have evolved by gene duplication from a common ancestral gene. All genes in the TRIM6/TRIM34/TRIM5/TRIM22 locus are type I interferon inducible, with TRIM5 and TRIM22 possessing antiviral properties. TRIM5 promotes innate immune signaling by activating the TAK1 kinase complex by cooperating with the heterodimeric E2, UBC13/UEV1A. It also stimulates NFkB and AP-1 signaling, and the transcription of inflammatory cytokines and chemokines, amplifying these activities upon retroviral infection. Interaction of its PRY-SPRY or cyclophilin domains with the retroviral capsid lattice stimulates the formation of a complementary lattice by TRIM5, with greatly increased TRIM5 E3 activity, and host cell signal transduction. TRIM6 is selectively expressed in embryonic stem (ES) cells and interacts with the proto-oncogene product Myc, maintaining the pluripotency of the ES cells. TRIM6, together with E2 Ubiquitin conjugase (UbE2K) and K48-linked poly-Ub chains, is critical for the IkappaB kinase epsilon (IKKepsilon) branch of type I interferon (IFN-I) signaling pathway and subsequent establishment of a protective antiviral response. TRIM22 plays an integral role in the host innate immune response to viruses; it has been shown to inhibit the replication of a number of viruses, including HIV-1, hepatitis B, and influenza A. Altered TRIM22 expression has also been associated with multiple sclerosis, cancer, and autoimmune disease. While the PRY-SPRY domain of TRIM5a provides specificity and the capsid recognition motif to retroviral restriction, TRIM34 binds HIV-1 capsid but does not restrict HIV-1 infection.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568951736 302 DVTLNPQTANLNLVLSKNRRQVRFVGAQLSEPSSLEEHYDCSVLGSQHFSSGKYYWEVDVSKKTAWILGVCSTPVDP--M 379
Cdd:cd15810    1 DVTLNPVNISLNIVISEDQRQVRIVPPQTSGQALTNNNYDFGVLGSQYFSSGKHYWEVDVSKKSAWILGVCSHKRSDamT 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568951736 380 FSFSQYSSKQGAYSRYQPQCGYWVIGLQCKHEYRAYEDSS----PSLLLSMTVPPRRIGIFLDCEAGTVSFYNVTNHGLP 455
Cdd:cd15810   81 KSNANQINHQNVYSRYQPQYGYWVIGLQNESEYNAFEDSSsfnpHVLTLSVTVPPHRVGVFLDYEAGTVSFFNVTNHGSL 160

                        170       180
                 ....*....|....*....|....*....
gi 568951736 456 IYTFSKYYFPSALCPYFNPCSCIVPMTLR 484
Cdd:cd15810  161 IYKFSKCCFSTTVCPYFNPWNCPVPMTLC 189

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 568951736 299 YWVDVTLNPQTANLNLVLSKNRRQVRFVgaqlsEPSSLEEHYDCS-----VLGSQHFSSGKYYWEVDVSKKTAWILGVCS 373
Cdd:cd15824    1 YWVDVMLNPVNAVSNVVVSADQRQVTVV-----HICMFRNSNPCDfsafdVLGCQYFSSGKYYWEVDVSGKIAWILGVYS 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568951736 374 TPVDP------MFSFSQYSSKQGAYSRYQPQCGYWVIGLQCKHEYRAYEDSSPS----LLLSMTVPPRRIGIFLDCEAGT 443
Cdd:cd15824   76 KRNNLnkrkssGFAFDPNVNHPNVYSRYRPQNGYWVIGLQNESEYNAFEDSSSSdpkvLTLSMAVPPHRVGVFLDYEAGT 155

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|...
gi 568951736 444 VSFYNVTNHGLPIYTFSKYYFPSALCPYFNPCSCIVPMTLRRP 486
Cdd:cd15824  156 VSFFNVTNHGSLIYKFSKCCFSQPVYPYFNPWNCPAPMTLCPP 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 568951736 302 DVTLNPQTANLNLVLSKNRRQVRFVGAQLSEPSSLEEHYDC-SVLGSQHFSSGKYYWEVDVSKKTAWILGVCStpvdpmf 380
Cdd:cd13733    1 DVTLDPDTAHPNLILSEDLKSVRYGDKRQNLPDNPERFDTCvCVLGSEGFSSGRHYWEVEVGGKTDWDLGVAR------- 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568951736 381 sfsqYSSKQGAYSRYQPQCGYWVIGLQCKHEYRAYedSSPSLLLSMTVPPRRIGIFLDCEAGTVSFYNVTNHGLpIYTFS 460
Cdd:cd13733   74 ----ESVNRKGKITLSPENGYWTVGLRNGNEYKAL--TSPSTPLSLREKPQKVGVFLDYEEGQVSFYNVDDGSH-IYTFT 146

                        170
                 ....*....|....*
gi 568951736 461 KyYFPSALCPYFNPC 475
Cdd:cd13733  147 D-CFTEKLYPYFSPC 160

PRY/SPRY domain in tripartite motif-binding protein 20 (TRIM20), also known as pyrin; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM20, which is also known as pyrin or marenostrin. Unlike TRIM domains that are composed of RING/B-box/coiled-coil core, the N-terminal RING domain in TRIM20 is exchanged by a PYRIN domain (PYD), a prime mediator of protein interactions necessary for apoptosis, inflammation and innate immune signaling pathway, and it also harbors a C-terminal B30.2 domain. Mutations in pyrin (TRIM20) are associated with familial Mediterranean fever (FMF), a recessively hereditary periodic fever syndrome, characterized by episodes of inflammation and fever. These mutations cluster in the C-terminal B30.2 domain and therefore it is assumed that pyrin plays a role in the innate immune system by possibly effecting caspase-1-dependent IL-1beta maturation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568951736 293 LTDVQSYWVDVTLNPQTANLNLVLSKNRRQVRFVGAQLSEPSSLEEHYDC-SVLGSQHFSSGKYYWEVDVSKKTAWILGV 371
Cdd:cd15813    1 LRAAQAHAVNVTLDPETAHPNLIFSDDLKSVRLGNKWDRLPDNPERFDSCiIVLGSPSFTSGRHYWEVEVGDKTGWILGV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568951736 372 CSTPVdpmfsfsqysSKQGAYSrYQPQCGYWVIGLQCKHEYRAyeDSSPSLLLSMTVPPRRIGIFLDCEAGTVSFYNVTN 451
Cdd:cd15813   81 CKASV----------SRKGSMT-LSPENGYWVVMMTKRNEYQA--STSPPTRLWLREPPRRVGIFLDYEAGDISFYNVTA 147

                        170       180
                 ....*....|....*....|....
gi 568951736 452 HGLpIYTFSKYYFPSALCPYFNPC 475
Cdd:cd15813  148 KSH-IYTFTSFSSSGPLQPIFSPG 170

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 568951736 301 VDVTLNPQTANLNLVLSKNRRQVRFVGAQLSEPSSLE--EHYDCsVLGSQHFSSGKYYWEVDVSKKTAWILGVCSTPVdp 378
Cdd:cd15819    2 VNVTLDPDTAHPALILSEDGRSVTWGETRQDLPENPErfDSLPC-VLGQEGFTSGRHYWEVEVGDRTSWDLGVCRDNV-- 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568951736 379 mfsfsqysSKQGAYSrYQPQCGYWVIGLQcKHEYRAYedSSPSLLLSMTVPPRRIGIFLDCEAGTVSFYNVTNhGLPIYT 458
Cdd:cd15819   79 --------MRKGRVT-LSPENGFWAIRLY-GNEYWAL--TSPETPLTLKEPPRRVGIFLDYEAGDVSFYNMTD-GSHIYT 145

                        170
                 ....*....|....*....
gi 568951736 459 FSKYYFPSALCPYFNPCSC 477
Cdd:cd15819  146 FPQTAFSGPLRPFFRLWSS 164

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568951736 301 VDVTLNPQTANLNLVLSKNRRQVRfVGAQLSEPSSLEEHYDCS--VLGSQHFSSGKYYWEVDVSKKTAWILGVCSTPVdp 378
Cdd:cd15821    4 VDMTLDVDTANNYLIISEDLRSVR-CGCFRQNRKELAERFDDAlcVLGSPRFTSGRHYWEVDVGTSTEWDLGVCRESV-- 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568951736 379 mfsfsqysSKQGAYSrYQPQCGYWVIGLQCKHEYRAyeDSSPSLLLSMTVPPRRIGIFLDCEAGTVSFYNVTNhGLPIYT 458
Cdd:cd15821   81 --------NRQGPIE-LSPEHGFWTVSLRDGSVFFA--STVPLTVLWVNPRLHRVGIFLDMEMGTISFYDVSD-GSHIFT 148

                        170       180
                 ....*....|....*....|
gi 568951736 459 FSKYYFPSALCPYFNPCSCI 478
Cdd:cd15821  149 FTKISAEEPLRPFFAPANPY 168

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 568951736 303 VTLNPQTANLNLVLSKNRRQVRFVGAQLSEPSsLEEHYDCS--VLGSQHFSSGKYYWEVDVSKKTAWILGVCSTPVDpmf 380
Cdd:cd15818   15 ITLDPKTAHPNLILSEDLTCVWHGDTKQMLPD-NPERFDSSvaVLGSEGFTSGKHYWEVEVAKKTKWTLGVVRESIN--- 90

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568951736 381 sfsqyssKQGAYSrYQPQCGYWVIGLQCKHEYRAYEdsSPSLLLSMTVPPRRIGIFLDCEAGTVSFYNVtNHGLPIYTFS 460
Cdd:cd15818   91 -------RKGNCP-LSPEDGFWLLRLRNQNELKALD--VPSFSLTLTSNLNKVGIYLDYEGGQVSFYNA-NTMSHIYTFS 159

                        170
                 ....*....|....*
gi 568951736 461 KyYFPSALCPYFNPC 475
Cdd:cd15818  160 D-TFTEKIYPYFCPC 173

PRY/SPRY domain of tripartite motif-binding protein 75 (TRIM75); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM75, also known as Gm794. TRIM75 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. TRIM75 has a single site of positive selection in its RING domain associated with E3 ubiquitin ligase activity. It has not been detectably expressed experimentally due to their constant turnover by the proteasome, and therefore not been characterized.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568951736 283 LRKMLKVFReltdvqsywVDVTLNPQTANLNLVLSKNRRQVRFVGAQLSEPSSLEEH-YDCSVLGSQHFSSGKYYWEVDV 361
Cdd:cd15829   10 LQKIIKKFR---------VDVTLDPETAHPNLLVSEDKKCVTFTKKKQRVPDSPKRFtVNPVVLGFPGFHSGRHFWEVEV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568951736 362 SKKTAWILGVCSTPVdpmfsfsqysSKQGAYSRYQPQcGYWVIGLQcKHEYRAyEDSSPSLLLSmTVPPRRIGIFLDCEA 441
Cdd:cd15829   81 GDKPEWAVGVCKDSL----------STKARRPPSGQQ-GCWRIQLQ-GGDYDA-PGAVPPPLLL-EVKPRGIGVFLDYEL 146

                        170       180       190
                 ....*....|....*....|....*....|...
gi 568951736 442 GTVSFYNVTN--HglpIYTFSKyYFPSALCPYF 472
Cdd:cd15829  147 GEISFYNMPEksH---IHTFTD-TFSGPLRPYF 175

zinc-binding protein A33-like; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM69 and TRIM proteins NF7 and bloodthirsty (bty). 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568951736 303 VTLNPQTANLNLVLSKNRRQVRFVGAQLSEPSSLEEHYDC-SVLGSQHFSSGKYYWEVDVSKKTAWILGVCSTPVDpmfs 381
Cdd:cd12905    6 LTFDPETAHPSLILSRDLTAVTESDEMQPYPRSPKRFLQCvNVLASQGFQSGRHYWEVWVGSKTKWDLGVASESVD---- 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568951736 382 fsqysskQGAYSRYQPQCGYWVIGLQCKHEYRAyeDSSPSLLLSMTVPPRRIGIFLDCEAGTVSFYNVTNHGLpIYTFSK 461
Cdd:cd12905   82 -------RQARVKLCPENGYWTLRLRNGDEYWA--GTQPWTRLRVTSRPQRIGVFLDCEERKVSFYNADDMSL-LYSFHQ 151

                        170
                 ....*....|....
gi 568951736 462 YYfPSALCPYFNPC 475
Cdd:cd12905  152 GP-RGKVFPFFSTC 164

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 568951736 303 VTLNPQTANLNLVLSKNRRQVRfVGAQLSEPSSLEEHYDCS--VLGSQHFSSGKYYWEVDVSKKTAWILGVCSTPVDpmf 380
Cdd:cd12874    1 LTFDPDTAHLNLILSDDLRSVR-VGDISQHPPEPPPRFFECwqVLGSQSFSSGRHYWEVDVQDDSSWYVGVTYKSLP--- 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568951736 381 sfsqyssKQGAYSRYQPQCGYWVIGLQcKHEYRAYEDSSPSLLLSmtVPPRRIGIFLDCEAGTVSFYNVTNHGLPIYTFs 460
Cdd:cd12874   77 -------RKGKMSNLGRNNGSWCLEWR-ENEFSAWHNNPETRLPV--TPPRRLGVFLDCDGGSLSFYGVTDGVQLLYTF- 145

                        170
                 ....*....|....*..
gi 568951736 461 KYYFPSALCPYFNPCSC 477
Cdd:cd12874  146 KAKFTEPLYPAFWLGEG 162

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 568951736 302 DVTLNPQTANLNLVLSKNRRQVRFVGAQLSEPSSLEE-HYDCSVLGSQHFSSGKYYWEVDVSKKTAWILGVCSTPVdpmf 380
Cdd:cd12888    1 NVTLDPDTAHPRLVLSEDRKSVRWGDTRQDLPDNPERfDTWPCVLGCEGFTSGRHYWEVEVGDGGGWAVGVARESV---- 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568951736 381 sfsqysSKQGAySRYQPQCGYWVIGlQCKHEYRAyeDSSPSLLLSMTVPPRRIGIFLDCEAGTVSFYNVTNhGLPIYTFS 460
Cdd:cd12888   77 ------RRKGE-ISFSPEEGIWAVG-QWGGQYWA--LTSPETPLPLSEVPRRIRVYLDYEGGQVAFFDADN-EAPIFTFP 145

                        170
                 ....*....|...
gi 568951736 461 KYYFPSA-LCPYF 472
Cdd:cd12888  146 PASFAGErIFPWF 158

PRY/SPRY domain of tripartite motif-binding protein 60 and 75 (TRIM60 and TRIM75); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM60 and TRIM75, both composed of RING/B-box/coiled-coil core and also known as RBCC proteins. TRIM60 domain is also known as RING finger protein 33 (RNF33) or 129 (RNF129). Based on its expression profile, RNF33 likely plays an important role in the spermatogenesis process, the development of the pre-implantation embryo, and in testicular functions; Rnf33 is temporally transcribed in the unfertilized egg and the pre-implantation embryo, and is permanently silenced before the blastocyst stage. Mice experiments have shown that RNF33 associates with the cytoplasmic motor proteins, kinesin-2 family members 3A (KIF3A) and 3B (KIF3B), suggesting possible contribution to cargo movement along the microtubule in the expressed sites. TRIM75, also known as Gm794, has a single site of positive selection in its RING domain associated with E3 ubiquitin ligase activity. It has not been detectably expressed experimentally due to their constant turnover by the proteasome, and therefore not been characterized.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568951736 302 DVTLNPQTANLNLVLSKNRRQVRFVGAQLSEPSSLEEHYDC-SVLGSQHFSSGKYYWEVDVSKKTAWILGVCstpvdpmf 380
Cdd:cd15817    1 DLILDPETAHPNLIVSEDRKAVRYRRMKPNCPYDPRRFTVYpAVLGSEGFDSGRHFWEVEVGGKGEWILGVC-------- 72

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568951736 381 sfsQYSSKQGAYSRYQPQCGYWVIGLQcKHEYRAYEDSSPSLLlsMTVPPRRIGIFLDCEAGTVSFYNVTNHGLpIYTFS 460
Cdd:cd15817   73 ---KDSLPRNAQDPPSPLGGCWQIGRY-MSGYVASGPKTTQLL--PVVKPSRIGIFLDYELGEVSFYNMNDRSH-LYTFT 145

                        170
                 ....*....|..
gi 568951736 461 KyYFPSALCPYF 472
Cdd:cd15817  146 D-TFTGKLIPYF 156

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 568951736 303 VTLNPQTANLNLVLSKNRRQVRFVGAQLSEPSSLEEHYDCSVLGSQHFSSGKYYWEVDVSKKTAWILGVCstpvdpmfsf 382
Cdd:cd12891    1 LTLDPNTAHNNLALSGDLKTVTCSSENQHYPDSPERFTHSQVLSTQSFSSGRHYWEVEVSESGGWSVGVA---------- 70

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568951736 383 sqYSS--KQGAYSR--YQPQ--CGYWviglqCKHEYRAYEDSSPSLLLSmtVPPRRIGIFLDCEAGTVSFYNVTNHGLPI 456
Cdd:cd12891   71 --YPSieRKGDESRigRNDKswCLEW-----QDKSFSAWHNNEETPLPS--VSSRRLGVYLDYEAGRLSFYELSDPIRHL 141