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 154350234   7 TNIQEKTTCPVCQELLTKALSLGCGHRVCQACLITKKNAVINPREKSSCPVCGTRFSLENLQANKHLANVVE 78
Cdd:cd16591    1 VNIKEEVTCPICLELLTEPLSLDCGHSFCQACITANHKESVNQEGESSCPVCRTSYQPENLRPNRHLANIVE 72

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 154350234 133 EEAVRECQENLQKALTRLRKEQEKVETLEADIKEDRLSWKcQVQTERQRIQTGFNQLRRILDKEEQrELKRLREEEQMIL 212
Cdd:COG1196  273 RLELEELELELEEAQAEEYELLAELARLEQDIARLEERRR-ELEERLEELEEELAELEEELEELEE-ELEELEEELEEAE 350

                         90       100       110
                 ....*....|....*....|....*....|...
gi 154350234 213 DSLAGAEAELAQQSQLVEELISDL-ELRREWSD 244
Cdd:COG1196  351 EELEEAEAELAEAEEALLEAEAELaEAEEELEE 383

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 154350234   7 TNIQEKTTCPVCQELLTKALSLGCGHRVCQACLITKKNAVINPREKSSCPVCGTRFSLENLQANKHLANVVE 78
Cdd:cd16591    1 VNIKEEVTCPICLELLTEPLSLDCGHSFCQACITANHKESVNQEGESSCPVCRTSYQPENLRPNRHLANIVE 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 154350234  94 DLCVHHGEKLLLFCKEDKKAICWVCERSQEHRGHHTFLWE 133
Cdd:cd19761    1 DHCEHHGEKLLLFCQEDGKVICWLCERSQEHRGHHTFLLE 40

B-Box-type zinc finger;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 154350234    92 KRDLC-VHHGEKLLLFCKEDKKAICWVCERSqEHRGHHTFL 131
Cdd:smart00336   2 RAPKCdSHGDEPAEFFCEECGALLCRTCDEA-EHRGHTVVL 41

DNA double-strand break repair Rad50 ATPase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 154350234 134 EAVRECQENLQkALTRLRKEQ-----EKVETLEADIKEDRLSwkcQVQTERQRIQTGFNQLrrildkEEqrELKRLREEE 208
Cdd:PRK02224 609 ERLREKREALA-ELNDERRERlaekrERKRELEAEFDEARIE---EAREDKERAEEYLEQV------EE--KLDELREER 676

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 154350234 209 QMILDSLAGAEAELAQQSQLVEELiSDLELRRE-----WSDTELLQDMSGILK 256
Cdd:PRK02224 677 DDLQAEIGAVENELEELEELRERR-EALENRVEalealYDEAEELESMYGDLR 728

B-box zinc finger;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 154350234   91 TKRDLC-VHHGEKLLLFCKEDKKAICWVCERSqEHRGHHT 129
Cdd:pfam00643   1 SKERLCpEHEEEPLTLYCNDCQELLCEECSVG-EHRGHTV 39

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 154350234   15 CPVCQELLTKALsLGCGHRVCQACLITKKnavINPREKSSCP 56
Cdd:pfam13445   1 CPICLELFTDPV-LPCGHTFCRECLEEMS---QKKGGKFKCP 38

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 154350234   140 QENLQKALTRLRKEQEKVE----TLEADIKEDRlswKCQVQTERQRIQTGFNQLRRILDKEEQRELKRLREEEQMILDSL 215
Cdd:smart00935  31 QAELEKLEKELQKLKEKLQkdaaTLSEAAREKK---EKELQKKVQEFQRKQQKLQQDLQKRQQEELQKILDKINKAIKEV 107

                   ....
gi 154350234   216 AGAE 219
Cdd:smart00935 108 AKKK 111

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 154350234 301 NFTFNPENLNLNLILSEDHRQVTSVSIWPFKCC------NNGILGSKCFSSGKHYWEVDVSEKKAWTLGVYTRKRT--LR 372
Cdd:cd15810    1 DVTLNPVNISLNIVISEDQRQVRIVPPQTSGQAltnnnyDFGVLGSQYFSSGKHYWEVDVSKKSAWILGVCSHKRSdaMT 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 154350234 373 FDVRQRKGQPNGYHRYKPQNGYWVIGLQHGSKYSIFEDSSNCDPTVLNPFVATPLHRVGVFLDCEEGTVSFLNVTNHGSL 452
Cdd:cd15810   81 KSNANQINHQNVYSRYQPQYGYWVIGLQNESEYNAFEDSSSFNPHVLTLSVTVPPHRVGVFLDYEAGTVSFFNVTNHGSL 160

                        170       180
                 ....*....|....*....|....*....
gi 154350234 453 IYKFSQCCFSQPAYPYFNPWDCPAPMTLC 481
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 154350234 298 YWDNFTFNPENLNLNLILSEDHRQVTSVSIWPFKCCNN------GILGSKCFSSGKHYWEVDVSEKKAWTLGVYTRKRTL 371
Cdd:cd15824    1 YWVDVMLNPVNAVSNVVVSADQRQVTVVHICMFRNSNPcdfsafDVLGCQYFSSGKYYWEVDVSGKIAWILGVYSKRNNL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 154350234 372 R------FDVRQRKGQPNGYHRYKPQNGYWVIGLQHGSKYSIFEDSSNCDPTVLNPFVATPLHRVGVFLDCEEGTVSFLN 445
Cdd:cd15824   81 NkrkssgFAFDPNVNHPNVYSRYRPQNGYWVIGLQNESEYNAFEDSSSSDPKVLTLSMAVPPHRVGVFLDYEAGTVSFFN 160

                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 154350234 446 VTNHGSLIYKFSQCCFSQPAYPYFNPWDCPAPMTLCP 482
Cdd:cd15824  161 VTNHGSLIYKFSKCCFSQPVYPYFNPWNCPAPMTLCP 197

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 154350234 301 NFTFNPENLNLNLILSEDHRQVTSVSIWP--------FKCCNNgILGSKCFSSGKHYWEVDVSEKKAWTLGVytrkrtlr 372
Cdd:cd13733    1 DVTLDPDTAHPNLILSEDLKSVRYGDKRQnlpdnperFDTCVC-VLGSEGFSSGRHYWEVEVGGKTDWDLGV-------- 71

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 154350234 373 fdVRQ---RKGQpngyHRYKPQNGYWVIGLQHGSKYSIFEDSsncdPTVLNpfVATPLHRVGVFLDCEEGTVSFLNVTNh 449
Cdd:cd13733   72 --AREsvnRKGK----ITLSPENGYWTVGLRNGNEYKALTSP----STPLS--LREKPQKVGVFLDYEEGQVSFYNVDD- 138

                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 154350234 450 GSLIYKFSQcCFSQPAYPYFNPWD-----CPAPMTLC 481
Cdd:cd13733  139 GSHIYTFTD-CFTEKLYPYFSPCLndggkNSAPLIIC 174

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 154350234 302 FTFNPENLNLNLILSEDHRQVTSVSIWP--------FKCCNNgILGSKCFSSGKHYWEVDVSEKKAWTLGVyTRKRTLRF 373
Cdd:cd12874    1 LTFDPDTAHLNLILSDDLRSVRVGDISQhppeppprFFECWQ-VLGSQSFSSGRHYWEVDVQDDSSWYVGV-TYKSLPRK 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 154350234 374 DVRQRKGqpngyhrykPQNGYWVIGLQHGSkysiFEDSSNCDPTVLNPfvaTPLHRVGVFLDCEEGTVSFLNVTNHGSLI 453
Cdd:cd12874   79 GKMSNLG---------RNNGSWCLEWRENE----FSAWHNNPETRLPV---TPPRRLGVFLDCDGGSLSFYGVTDGVQLL 142

                        170       180
                 ....*....|....*....|....*...
gi 154350234 454 YKFsQCCFSQPAYPYFNPWDCpAPMTLC 481
Cdd:cd12874  143 YTF-KAKFTEPLYPAFWLGEG-STLSIC 168

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 154350234 305 NPENLNLNLILSEDHRQVTSVSI--------WPFKCcNNGILGSKCFSSGKHYWEVDVSEKKAWTLGVytrkrtLRFDVr 376
Cdd:cd15820    9 DPDTANPILLISEDQRSLQWADEpqnlpdnpKRFDW-HYCVLGCKSFTSGRHFWEVEVGDRKEWYVGV------CRENV- 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 154350234 377 QRKGQPNgyhrYKPQNGYWVIGLQHGSKYSIFEDSSncdpTVLNpfVATPLHRVGVFLDCEEGTVSFLNVTNhGSLIYKF 456
Cdd:cd15820   81 ERKLWVK----MAPENGFWTIGLSDGNDYQALTDPR----TKLT--IANPPQRVGVFLDYETGEVSFYNAMD-GSHIYTF 149

                        170       180
                 ....*....|....*....|....*...
gi 154350234 457 SQCCFSQPAYPYFN--PWDcPAPMTLCP 482
Cdd:cd15820  150 PHTSFSGPLYPVFRllSWD-PTALTICP 176

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 154350234 303 TFNPENLNLNLILSEDHRQVTSVSI---WP-----FKCCNNgILGSKCFSSGKHYWEVDVSEKKAWTLGVytrkrtLRFD 374
Cdd:cd13745    6 TLDPDTAHPNLVLSEDRKSVRHGDTrqdLPdnperFDTYPC-VLGAEGFTGGRHYWEVEVGDKTEWTLGV------CRES 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 154350234 375 VRqRKGQPngyhRYKPQNGYWVIGLQHGsKYSifedssncdpTVLNPFvaTPLH------RVGVFLDCEEGTVSFLNVTN 448
Cdd:cd13745   79 VS-RKGEV----TLSPENGYWTVWLRDG-KYE----------ALTSPP--TPLPvsvrpsRVGIFLDYEAGEVSFYNVTD 140

                        170       180       190
                 ....*....|....*....|....*....|....*....
gi 154350234 449 HgSLIYKFSqCCFSQPAYPYFNPWDCP-----APMTLCP 482
Cdd:cd13745  141 R-SHLFTFT-DTFSGTLRPYFYPGLNAggknaAPLIICP 177

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 154350234 303 TFNPENLNLNLILSEDHRQVTSVSI----------WPFKCCnngILGSKCFSSGKHYWEVDVSEKKAWTLGVyTRkrtlr 372
Cdd:cd15821    7 TLDVDTANNYLIISEDLRSVRCGCFrqnrkelaerFDDALC---VLGSPRFTSGRHYWEVDVGTSTEWDLGV-CR----- 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 154350234 373 fDVRQRKGQPNgyhrYKPQNGYWVIGLQHGSKYSifedSSNCDPTVLnpFVATPLHRVGVFLDCEEGTVSFLNVTNhGSL 452
Cdd:cd15821   78 -ESVNRQGPIE----LSPEHGFWTVSLRDGSVFF----ASTVPLTVL--WVNPRLHRVGIFLDMEMGTISFYDVSD-GSH 145

                        170       180       190
                 ....*....|....*....|....*....|...
gi 154350234 453 IYKFSQCCFSQPAYPYFNPWDCP----APMTLC 481
Cdd:cd15821  146 IFTFTKISAEEPLRPFFAPANPYgddqGVLSIC 178

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 154350234 303 TFNPENLNLNLILSEDHRQVT-SVSIWPFKC-------CNNgILGSKCFSSGKHYWEVDVSEKKAWTLGVY--TRKRTLR 372
Cdd:cd12905    7 TFDPETAHPSLILSRDLTAVTeSDEMQPYPRspkrflqCVN-VLASQGFQSGRHYWEVWVGSKTKWDLGVAseSVDRQAR 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 154350234 373 FdvrqrkgqpngyhRYKPQNGYWVIGLQHGSKYsifedSSNCDP-TVLNPfvATPLHRVGVFLDCEEGTVSFLNVTNHgS 451
Cdd:cd12905   86 V-------------KLCPENGYWTLRLRNGDEY-----WAGTQPwTRLRV--TSRPQRIGVFLDCEERKVSFYNADDM-S 144

                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 154350234 452 LIYKFSQCCFSQpAYPYFNPwdC-------PAPMTLC 481
Cdd:cd12905  145 LLYSFHQGPRGK-VFPFFST--CfsddgqnAEPMRLL 178

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 154350234 301 NFTFNPENLNLNLILSEDHRQVTSVSIW-----------PFKCcnngILGSKCFSSGKHYWEVDVSEKKAWTLGVYTrkr 369
Cdd:cd15816    1 DVKLDPATAHPSLLLTADLRSVQDGELWrdvpgnperfdTWPC----VLGLQSFSSGRHYWEVAVGEKAEWGLGVCQ--- 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 154350234 370 tlrfDVRQRKGQPNGyhryKPQNGYWVIGLQHGSKYSIFedssnCDPTVlnPFVAT--PlHRVGVFLDCEEGTVSFLNVT 447
Cdd:cd15816   74 ----DSAPRKGETTP----SPENGVWAVWLLKGNEYMVL-----ASPSV--PLLQLrrP-RRVGVFLDYEAGEISFYNVT 137

                        170       180       190
                 ....*....|....*....|....*....|...
gi 154350234 448 nHGSLIYKFSQcCFSQPAYPYFNPWDcPAPMTL 480
Cdd:cd15816  138 -AGSHIYTFRQ-LFSGILRPYFFVCD-TTPLTL 167

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 154350234 301 NFTFNPENLNLNLILSEDHRQV---TSVSIWP-----FKCCNnGILGSKCFSSGKHYWEVDVSEKKAWTLGVytrkrtLR 372
Cdd:cd15818   14 LITLDPKTAHPNLILSEDLTCVwhgDTKQMLPdnperFDSSV-AVLGSEGFTSGKHYWEVEVAKKTKWTLGV------VR 86

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 154350234 373 FDVRQRKGQPngyhrYKPQNGYWVIGLQHGSKYSIFEDSSNCdpTVLNpfvaTPLHRVGVFLDCEEGTVSFLNVtNHGSL 452
Cdd:cd15818   87 ESINRKGNCP-----LSPEDGFWLLRLRNQNELKALDVPSFS--LTLT----SNLNKVGIYLDYEGGQVSFYNA-NTMSH 154

                        170
                 ....*....|....*....
gi 154350234 453 IYKFSqCCFSQPAYPYFNP 471
Cdd:cd15818  155 IYTFS-DTFTEKIYPYFCP 172

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 154350234 303 TFNPENLNLNLILSEDHRQVTSVSIWPFKCCNN-------GILGSKCFSSGKHYWEVDVSEKKAWTLGVYtrKRTLrfdV 375
Cdd:cd15828   13 TLDPETAHPQLTVSEDRKSVLYGEMKQNVCYNPrrfylcpAVLGSEGFHSGRQYWEVEVGDKPEWTLGVC--QDCL---P 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 154350234 376 RQRKGQPNgyhrykPQNGYWVIGLQHGSKYSIFEDSSncdpTVLNPfVATPlHRVGVFLDCEEGTVSFLNVtNHGSLIYK 455
Cdd:cd15828   88 RNWSNQPS------VQDGLWAIGRYSESNYVALGPKK----IQLLP-KVRP-SKIGIFLDYELGEVSFYNM-NDRSLLYT 154

                        170       180
                 ....*....|....*....|....*..
gi 154350234 456 FSQcCFSQPAYPYFNPWDCPAPMTLCP 482
Cdd:cd15828  155 FSD-SFTGTLWPYFYTGTDSEPLKICT 180

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 154350234 303 TFNPENLNLNLILSEDHRQVTSVSIW------PFKCCNNGILGSKCFSSGKHYWEVDVSEKKAWTLGV-YTRKRtlrfdv 375
Cdd:cd12891    2 TLDPNTAHNNLALSGDLKTVTCSSENqhypdsPERFTHSQVLSTQSFSSGRHYWEVEVSESGGWSVGVaYPSIE------ 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 154350234 376 rqRKGqPNGYHRYKPQNgyWviGLQ-HGSKYSIFEDSSncdPTVLNPfvaTPLHRVGVFLDCEEGTVSFLNVTNHGSLIY 454
Cdd:cd12891   76 --RKG-DESRIGRNDKS--W--CLEwQDKSFSAWHNNE---ETPLPS---VSSRRLGVYLDYEAGRLSFYELSDPIRHLH 142

                        170
                 ....*....|....*....
gi 154350234 455 KFSqCCFSQPAYPYFNPWD 473
Cdd:cd12891  143 TFT-ATFTEPLHPAFWVLE 160