Pyrin Death Domain found in ASC; Pyrin Death Domain found in ASC (Apoptosis-associated speck-like protein containing a CARD) and similar proteins. ASC is an adaptor molecule that functions in the assembly of the 'inflammasome', a multiprotein platform, which is responsible for caspase-1 activation and regulation of IL-1beta maturation. ASC contains two domains from the Death Domain (DD) superfamily, an N-terminal pyrin-like domain and a C-terminal Caspase activation and recruitment domain (CARD). Through these 2 domains, ASC serves as an adaptor for inflammasome integrity and oligomerizes to form supramolecular assemblies. Included in this family is human PYNOD (also known as NLRP10 or NOD8) which via its Pyrin domain suppresses oligomerization of ASC, and ASC-mediated NF-kappaB activation. Other members of this subfamily are associated with ATPase domains and their function remains unknown. In general, Pyrin is a subfamily of the DD superfamily and functions in several signaling pathways. DDs are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including CARD and Death Effector Domain (DED). They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1570468134   6 SDHVLESLESLVPSDFEKFKFKLQNISLEkDHSRIPRGQLPNARPVRLADLMITHYGEEYAVRLTLQVLRAINQNFLAEE 85
Cdd:cd08321     1 RDLLLDALEDLGEEELKKFKWKLRDIPLE-GYPRIPRGKLENADRVDLVDLLVSYYGEDYAVEVTVEVLRAINQNDLAEK 79

                  .
gi 1570468134  86 L 86
Cdd:cd08321    80 L 80

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 1570468134  494 QLKMEEAKFRLQQVPLFQEQIQKQLEHLKELRKCGEEQ----RSQGDKKTAKfLKQTETQKQRLRHQLEQLYHLLEqQEK 569
Cdd:TIGR02168  851 SEDIESLAAEIEELEELIEELESELEALLNERASLEEAlallRSELEELSEE-LRELESKRSELRRELEELREKLA-QLE 928

                           90       100
                   ....*....|....*....|...
gi 1570468134  570 LFVASIE-DLNQTIGQVREKYST 591
Cdd:TIGR02168  929 LRLEGLEvRIDNLQERLSEEYSL 951

SPRY domain; SPRY Domain is named from SPla and the RYanodine Receptor and it is found in many eukaryotic proteins with a wide range of functions. It is a protein-interaction module involved in many important signalling pathways like RNA processing, regulation of histone H3 methylation, innate immunity or embryonic development. It can be divided into 11 subfamilies based on amino acid sequence similarity or the presence of additional protein domains. The greater SPRY family is divided into the SPRY/B30.2 (which contains a PRY extension at the N-terminal) and SPRY-only sub-families which are preceded by a subdomain that is structurally similar to the PRY region. SPRY/B30.2 structures revealed a bent beta-sandwich fold comprised of two beta-sheets. Distant homologs are domains in butyrophilin/ marenostrin/pyrin.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1570468134 743 RHYWEVEVGN--KTGWILGICKASASRKGSMTLSPDNGYWVVMMMKRNEYQVSTIPPTRLQIKEPPRRVGIFLDYKAGDI 820
Cdd:pfam00622   1 RHYFEVEIFGqdGGGWRVGWATKSVPRKGERFLGDESGSWGYDGWTGKKYWASTSPLTGLPLFEPGDVIGCFLDYEAGTI 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1570468134 821 SFYNVTyKSLIYTFTSFSSSGPLQPMFSPGTHDGGKNMDPLT 862
Cdd:pfam00622  81 SFTKNG-KSLGYAFRDVPFAGPLFPAVSLGAGEGLKFNFGLR 121

Pyrin Death Domain found in ASC; Pyrin Death Domain found in ASC (Apoptosis-associated speck-like protein containing a CARD) and similar proteins. ASC is an adaptor molecule that functions in the assembly of the 'inflammasome', a multiprotein platform, which is responsible for caspase-1 activation and regulation of IL-1beta maturation. ASC contains two domains from the Death Domain (DD) superfamily, an N-terminal pyrin-like domain and a C-terminal Caspase activation and recruitment domain (CARD). Through these 2 domains, ASC serves as an adaptor for inflammasome integrity and oligomerizes to form supramolecular assemblies. Included in this family is human PYNOD (also known as NLRP10 or NOD8) which via its Pyrin domain suppresses oligomerization of ASC, and ASC-mediated NF-kappaB activation. Other members of this subfamily are associated with ATPase domains and their function remains unknown. In general, Pyrin is a subfamily of the DD superfamily and functions in several signaling pathways. DDs are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including CARD and Death Effector Domain (DED). They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1570468134   6 SDHVLESLESLVPSDFEKFKFKLQNISLEkDHSRIPRGQLPNARPVRLADLMITHYGEEYAVRLTLQVLRAINQNFLAEE 85
Cdd:cd08321     1 RDLLLDALEDLGEEELKKFKWKLRDIPLE-GYPRIPRGKLENADRVDLVDLLVSYYGEDYAVEVTVEVLRAINQNDLAEK 79

                  .
gi 1570468134  86 L 86
Cdd:cd08321    80 L 80

B-box-type 2 zinc finger found in tripartite motif-containing protein TRIM20 and similar proteins; TRIM20, also termed Pyrin, or Marenostrin (MEFV), is involved in the regulation of innate immunity and the inflammatory response in response to IFNG/IFN-gamma. TRIM20 belongs to unclassified TRIM family of proteins that do not have RING fingers and thus lack the characteristic tripartite (RING (R), B-box, and coiled coil (CC)) RBCC motif. It contains a pyrin domain, a Bbox2 zinc finger, and a C-terminal SPRY/B30.2 domain. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1570468134 443 PQCERHMKQVQLlFCEDHKEPICLICRLSQEHQGHWVRPI 482
Cdd:cd19771     1 PQCKLHLEQLKL-FCEDHREPICLICQLSQEHQGHRVRPI 39

B-box zinc finger;

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 1570468134 445 CERHMKQVQLLFCEDHKEPICLICrLSQEHQGHWVRPI 482
Cdd:pfam00643   6 CPEHEEEPLTLYCNDCQELLCEEC-SVGEHRGHTVVPL 42

chromosome partition protein MukB;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1570468134  413 LSLASLTVNNSEDYkhQEGLQIASlspKSLPQCERHMKQvQLLFCEDHKE----PICLICRLSQEhqghwVRPiEEAale 488
Cdd:PRK04863   430 CGLPDLTADNAEDW--LEEFQAKE---QEATEELLSLEQ-KLSVAQAAHSqfeqAYQLVRKIAGE-----VSR-SEA--- 494

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1570468134  489 yksWHQLKMEEAKFRLQQVPLFQEQiqkQLE-HLKELRKCGEEQRSQgdkktAKFLKQTEtqkQRLRHQL---EQLYHLL 564
Cdd:PRK04863   495 ---WDVARELLRRLREQRHLAEQLQ---QLRmRLSELEQRLRQQQRA-----ERLLAEFC---KRLGKNLddeDELEQLQ 560

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1570468134  565 EQQEklfvASIEDLNQTIGQVREKYsTQVSRDIALLDELIGELEAKqyQPEWELMQD 621
Cdd:PRK04863   561 EELE----ARLESLSESVSEARERR-MALRQQLEQLQARIQRLAAR--APAWLAAQD 610

Flagellar FliJ protein;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1570468134 498 EEAKFRLQQVPLFQEQIQKQLEHLKELR-KCGEEQRSQGDKKTAKFLKQTETQKQRLRHQLEQLYHLLEQQEK 569
Cdd:pfam02050   1 DEAARELAEAQRELQQAEEKLEELQQYRaEYQQQLSGAGQGISAAELRNYQAFISQLDEAIAQQQQELAQAEA 73

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 1570468134 690 NVILDAETAHPNLIFSNNLKSVKLGNKWNRLPDNPERFDSCIIALGLPSFLSGRHYWEVEVGNKTGWILGICKASASRKG 769
Cdd:cd13733     1 DVTLDPDTAHPNLILSEDLKSVRYGDKRQNLPDNPERFDTCVCVLGSEGFSSGRHYWEVEVGGKTDWDLGVARESVNRKG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1570468134 770 SMTLSPDNGYWVVMMMKRNEYQVSTIPPTRLQIKEPPRRVGIFLDYKAGDISFYNVTYKSLIYTFTSfSSSGPLQPMFSP 849
Cdd:cd13733    81 KITLSPENGYWTVGLRNGNEYKALTSPSTPLSLREKPQKVGVFLDYEEGQVSFYNVDDGSHIYTFTD-CFTEKLYPYFSP 159

                         170
                  ....*....|....*
gi 1570468134 850 GTHDGGKNMDPLTIC 864
Cdd:cd13733   160 CLNDGGKNSAPLIIC 174

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 1570468134 688 AVNVILDAETAHPNLIFSNNLKSVKLGNKWNRLPDNPERFDSCIIALGLPSFLSGRHYWEVEVGNKTGWILGICKASASR 767
Cdd:cd15819     1 AVNVTLDPDTAHPALILSEDGRSVTWGETRQDLPENPERFDSLPCVLGQEGFTSGRHYWEVEVGDRTSWDLGVCRDNVMR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1570468134 768 KGSMTLSPDNGYWVVMMMKrNEYQVSTIPPTRLQIKEPPRRVGIFLDYKAGDISFYNVTYKSLIYTFTSFSSSGPLQPMF 847
Cdd:cd15819    81 KGRVTLSPENGFWAIRLYG-NEYWALTSPETPLTLKEPPRRVGIFLDYEAGDVSFYNMTDGSHIYTFPQTAFSGPLRPFF 159

                         170
                  ....*....|....*..
gi 1570468134 848 SPGTHDGGknmdPLTIC 864
Cdd:cd15819   160 RLWSSDSG----PLTIC 172

PRY/SPRY domain in tripartite motif-binding protein 21 (TRIM21) also known as 52kD Ribonucleoprotein Autoantigen (Ro52); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM21, which is also known as Sjogren Syndrome Antigen A (SSA), SSA1, 52kD Ribonucleoprotein Autoantigen (Ro52, Ro/SSA, SS-A/Ro) or RING finger protein 81 (RNF81). TRIM21 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. As an E3 ligase, TRIM21 mediates target specificity in ubiquitination; it regulates type 1 interferon and proinflammatory cytokines via ubiquitination of interferon regulatory factors (IRFs). It is up-regulated at the site of autoimmune inflammation, such as cutaneous lupus lesions, indicating a central role in the tissue destructive inflammatory process. It interacts with auto-antigens in patients with Sjogren syndrome and systemic lupus erythematosus, a chronic systemic autoimmune disease characterized by the presence of autoantibodies against the protein component of the human intracellular ribonucleoprotein-RNA complexes and more specifically TRIM21, Ro60/TROVE2 and La/SSB proteins. It binds the Fc part of IgG molecules via its PRY-SPRY domain with unexpectedly high affinity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1570468134 687 HAVNVILDAETAHPNLIFSNNLKSVKLGNKWNRLPDNPERFDSCIIALGLPSFLSGRHYWEVEVGNKTGWILGICKASAS 766
Cdd:cd12900     1 HMVHITLDPDTANPWLILSKDRRQVRLGDTHQNVPENEERFDNYPMVLGAQRFNSGKHYWEVDVTGKEAWDLGVCRDSVR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1570468134 767 RKGSMTLSPDNGYWVVMMMKRnEYQVSTIPPTRLQIKEPPRRVGIFLDYKAGDISFYNVT-YKSLIYTFTSFSSSGPLQP 845
Cdd:cd12900    81 RKGQFLLSPENGFWTIWLWNK-KYEAGTSPQTTLHLQVPPCQVGIFLDYEAGVVSFYNITdHGSLIYTFSECAFTGPLRP 159

                         170       180
                  ....*....|....*....|.
gi 1570468134 846 MFSPGTHDGGKNMDPLTICPV 866
Cdd:cd12900   160 FFNPGFNDSGGNAAPLTLCPL 180

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 1570468134 690 NVILDAETAHPNLIFSNNLKSVKLGNKWNRLPDNPERFDSCIIALGLPSFLSGRHYWEVEVGNKTGWILGICKASASRKG 769
Cdd:cd15818    14 LITLDPKTAHPNLILSEDLTCVWHGDTKQMLPDNPERFDSSVAVLGSEGFTSGKHYWEVEVAKKTKWTLGVVRESINRKG 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1570468134 770 SMTLSPDNGYWVVMMMKRNEYQVSTIPPTRLQIKEPPRRVGIFLDYKAGDISFYNVTYKSLIYTF-TSFSSSgpLQPMFS 848
Cdd:cd15818    94 NCPLSPEDGFWLLRLRNQNELKALDVPSFSLTLTSNLNKVGIYLDYEGGQVSFYNANTMSHIYTFsDTFTEK--IYPYFC 171

                         170
                  ....*....|....*
gi 1570468134 849 PGTHDGGKNMDPLTI 863
Cdd:cd15818   172 PCLNDSGENKEPLKI 186

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 1570468134 690 NVILDAETAHPNLIFSNNLKSVKLGNKWNRLPDNPERFDSCIIALGLPSFLSGRHYWEVEVGNKTGWILGICKASASRKG 769
Cdd:cd15816     1 DVKLDPATAHPSLLLTADLRSVQDGELWRDVPGNPERFDTWPCVLGLQSFSSGRHYWEVAVGEKAEWGLGVCQDSAPRKG 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1570468134 770 SMTLSPDNGYWVVMMMKRNEYQVSTIPPTRLQIKEPPRRVGIFLDYKAGDISFYNVTYKSLIYTFTSfSSSGPLQPMF 847
Cdd:cd15816    81 ETTPSPENGVWAVWLLKGNEYMVLASPSVPLLQLRRPRRVGVFLDYEAGEISFYNVTAGSHIYTFRQ-LFSGILRPYF 157

PRY/SPRY domain in tripartite motif-containing protein 27 (TRIM27), also known as RING finger protein 76 (RNF76); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM27, also known as RING finger protein 76 (RNF76) or RET finger protein (RFP). TRIM27 domain is composed of RING/B-box/coiled-coil core and also known as RBCC proteins. It is highly expressed in the spleen, thymus and in cells of the hematopoietic compartment. TRIM27 exhibits either nuclear or cytosolic localization depending on the cell type. TRIM27 negatively regulates nucleotide-binding oligomerization domain containing 2 (NOD2)-mediated signaling by proteasomal degradation of NOD2, suggesting that TRIM27 could be a new target for therapeutic intervention in NOD2-associated diseases such as Crohn's. High expression of TRIM27 is observed in several human cancers, including breast and endometrial cancer, where elevated TRIM27 expression predicts poor prognosis. Also, TRIM27 forms an oncogenic fusion protein with Ret proto-oncogene. It is involved in different stages of spermatogenesis and its significant expression in male germ cells and seminomas, suggests that TRIM27 may be associated with the regulation of testicular germ cell proliferation and histological-type of germ cell tumors. TRIM27 could also be a predictive marker for chemoresistance in ovarian cancer patients. In the neurotoxin model of Parkinson's disease (PD), deficiency of TRIM27 decreases apoptosis and protects dopaminergic neurons, making TRIM27 an effective potential target during the treatment of PD.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1570468134 688 AVNVILDAETAHPNLIFSNNLKSVKLGNKWNRLPDNPERFDSCIIALGLPSFLSGRHYWEVEVGNKTGWILGICKASASR 767
Cdd:cd15814     1 SVDVTLDPDTAYPSLILSDNLRQVRYSYLQQDLPDNPERFNLFPCVLGSPCFIAGRHYWEVEVGDKAKWTIGVCEDSVCR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1570468134 768 KGSMTLSPDNGYWVVMMMKRNEYQVSTIPPTRLQIKEPPRRVGIFLDYKAGDISFYNVTYKSLIYTFTSFSSSGPLQPMF 847
Cdd:cd15814    81 KGGVTSAPQNGFWAVSLWYGKEYWALTSPMTALPLRTPLQRVGIFLDYDAGEVSFYNVTERCHTFTFSHATFCGPVRPYF 160

                         170
                  ....*....|....*...
gi 1570468134 848 SPgTHDGGKNMDPLTICP 865
Cdd:cd15814   161 SL-SYSGGKSAAPLIICP 177

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 1570468134 691 VILDAETAHPNLIFSNNLKSVKLGNKWNRLPDNPERFDSCIIALGLPSFLSGRHYWEVEVGNKTGWILGICKASASRKGS 770
Cdd:cd12905     6 LTFDPETAHPSLILSRDLTAVTESDEMQPYPRSPKRFLQCVNVLASQGFQSGRHYWEVWVGSKTKWDLGVASESVDRQAR 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1570468134 771 MTLSPDNGYWVVMMMKRNEYQVSTIPPTRLQIKEPPRRVGIFLDYKAGDISFYNVTYKSLIYTFTSfSSSGPLQPMFSPG 850
Cdd:cd12905    86 VKLCPENGYWTLRLRNGDEYWAGTQPWTRLRVTSRPQRIGVFLDCEERKVSFYNADDMSLLYSFHQ-GPRGKVFPFFSTC 164

                         170
                  ....*....|....
gi 1570468134 851 THDGGKNMDPLTIC 864
Cdd:cd12905   165 FSDDGQNAEPMRLL 178

PRY/SPRY domain of tripartite motif-binding protein 11 (TRIM11), also known as RING finger protein 92 (RNF92); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM11, also known as RING finger protein 92 (RNF92) or BIA1. TRIM11 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. It localizes to the nucleus and the cytoplasm; it is overexpressed in high-grade gliomas and promotes proliferation, invasion, migration and glial tumor growth. TRIM11 increases expression of dopamine beta-hydroxylase gene by interacting with the homeodomain transcription factor, PHOX2B, via the B30.2/SPRY domain, thus playing a potential role in the specification of noradrenergic (NA) neuron phenotype. It has also been shown that TRIM11 plays a critical role in the clearance of mutant PHOX2B, which causes congenital central hypoventilation syndrome, via the proteasome. TRIM11 binds a key component of the activator-mediated cofactor complex (ARC105), and destabilizes it, through the ubiquitin-proteasome system; ARC105 mediates chromatin-directed transcription activation and is a key regulatory factor for transforming growth factor beta (TGFbeta) signaling.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1570468134 690 NVILDAETAHPNLIFSNNLKSVKLGNKWNRLPDNPERFDSCIIALGLPSFLSGRHYWEVEVGNKTGWILGICKASASRKG 769
Cdd:cd15811     1 DVTLDPDTANPELVLSEDRRSVRRGDLRQALPDSPERFDPGPCVLGRERFTSGRHYWEVEVGDRTSWALGVCKENVNRKE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1570468134 770 SMTLSPDNGYWV-VMMMKRNEYQVSTIPPTRlqikEPPRRVGIFLDYKAGDISFYNVTYKSLIYTFTSFSSSGPLQPMFS 848
Cdd:cd15811    81 KGELSAGNGFWIlVFLGNYYSSERRTFAPLR----DPPRRVGIFLDYEAGHLSFYSATDGSLLFIFPETPFSGTLRPLFS 156

                         170
                  ....*....|....*.
gi 1570468134 849 PGThdggKNMDPLTIC 864
Cdd:cd15811   157 PLS----SSPTPMTIC 168

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 1570468134 690 NVILDAETAHPNLIFSNNLKSVKLGNKWNRLPDNPERFDSCIIALGLPSFLSGRHYWEVEVGNKTGWILGICKASASRKG 769
Cdd:cd15817     1 DLILDPETAHPNLIVSEDRKAVRYRRMKPNCPYDPRRFTVYPAVLGSEGFDSGRHFWEVEVGGKGEWILGVCKDSLPRNA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1570468134 770 SMTLSPDNGYWVVmMMKRNEYQVSTIPPTRLQIKEPPRRVGIFLDYKAGDISFYNVTYKSLIYTFTSfSSSGPLQPMFSP 849
Cdd:cd15817    81 QDPPSPLGGCWQI-GRYMSGYVASGPKTTQLLPVVKPSRIGIFLDYELGEVSFYNMNDRSHLYTFTD-TFTGKLIPYFYV 158

                         170
                  ....*....|....*
gi 1570468134 850 GThdggkNMDPLTIC 864
Cdd:cd15817   159 GP-----DSEPLTIC 168

PRY/SPRY domain in tripartite motif-binding protein 62 (TRIM62); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM62. It is also called DEAR1 ductal epithelium (associated RING chromosome 1) and 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 and thus, making TRIM62 a predictive biomarker. Non-small cell lung cancer lesions show a step-wise loss of TRIM62 levels during disease progression, indicating that it may play a role in the evolution of lung cancer. Decreased levels of TRIM62 also represent an independent adverse prognostic factor in AML.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1570468134 693 LDAETAHPNLIFSNNLKSVKLGNKWNR-LPDNPERFDSCIIALGLPSFLSGRHYWEVEVGNKTGWILGICKASASRKGSM 771
Cdd:cd13744    16 LDPVTAHQRLILSDDCTIVAYGNLHPQpLQDSPKRFDVEVSVLGSEGFSGGVHYWEVVVSEKTQWMIGLAHEAVSRKGSI 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1570468134 772 TLSPDNGYWVVMMMKRNEYQVSTIPPTRLQIKEPPRRVGIFLDYKAGDISFYNVTYKSLIYTFTSfSSSGPLQPMFSPG- 850
Cdd:cd13744    96 QIQPGRGFYCIVMHDGNQYSACTEPWTRLNVKSKLEKVGVYLDYDKGLLIFYNADDMSWLYTFRE-KFPGKLCSYFSPGq 174

                         170
                  ....*....|...
gi 1570468134 851 THDGGKNMDPLTI 863
Cdd:cd13744   175 SHANGKNVQPLRI 187

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 1570468134 679 PELICAQAHAVNVILDAETAhPNLIFSNNLKSVKLGNKWNRLPDNPERFDSCIiaLGLPSFLSGRHYWEVEVGNKTGWIL 758
Cdd:cd15822     2 NELTDVQRYWVHVTLDPSNN-KNIVISEDRRQVRYVRKQQRYNSNGNNEDYGV--LGSPSITSGKHYWEVDVSKKRAWIL 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1570468134 759 GIC---KASASRKGSMTLS-----------PDNGYWVVMMMKRNEYQV---STIPPTR---LQIKEPPRRVGIFLDYKAG 818
Cdd:cd15822    79 GVCggkYPNSTLKDFNKQGknnqkqcsnyqPKYGYWVIGLQNKSEYNAfedSSSSDPLiltLSLTVPPCRVGVFLDYEAG 158

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 1570468134 819 DISFYNVT-YKSLIYTFTSFSSSGPLQPMFSPGTHDGgknmdPLTIC 864
Cdd:cd15822   159 TVSFFNVTnHGFLIYKFSSCSFSQEVFPYFNPMKCPV-----PMTLC 200

PRY/SPRY domain of tripartite motif-binding protein 17 (TRIM17), also known as testis RING finger protein (terf); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM17, also known as RING finger protein 16 (RNF16) or testis RING finger protein (terf). TRIM17 domain is composed of RING/B-box/coiled-coil core and also known as RBCC protein, expressed almost exclusively in the testis. It exhibits E3 ligase activity, causing protein degradation of ZW10 interacting protein (ZWINT), a known component of the kinetochore complex required for the mitotic spindle checkpoint, and negatively regulates proliferation of breast cancer cells. TRIM17 undergoes ubiquitination in COS7 fibroblast-like cells but is inhibited and stabilized by TRIM44.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1570468134 690 NVILDAETAHPNLIFSNNLKSVKLGNKWNRLPDNPERFDSCIIALGLPSFLSGRHYWEVEVgNKTG---WILGICKASAS 766
Cdd:cd15812     1 DVVPDPSTAYPYLLLYESRQRRYLSTPPDGTPCSKDRFLAYPCAVGQETFSSGRHYWEVGM-NLTGdalWALGVCRDNVS 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1570468134 767 RKGSMTLSPDNGYWVVMMMKRNEYQVSTIPPTRLQIKEPPRRVGIFLDYKAGDISFYNVTYKSLIYTFTSFSSSGPLQPM 846
Cdd:cd15812    80 RKDRVPKSPENGFWVVQLSKGKKYLSAMSALTPVTLTEPPSHMGIFLDFEAGEVSFYSVNDGSHLHTYSQAAFPGPLQPF 159

                         170
                  ....*....|
gi 1570468134 847 FSPGTHDGGK 856
Cdd:cd15812   160 FCLGAPKSGQ 169

PRY/SPRY domain in tripartite motif-binding protein 6 (TRIM6), also known as RING finger protein 89 (RNF89); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM6, also known as RING finger protein 89 (RNF89). TRIM6 domain is composed of RING/B-box/coiled-coil core and also known as RBCC protein. It 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1570468134 689 VNVILDAETAHPNLIFSNNLKSVK-LGNKWNRLPDNPERFDSCIiaLGLPSFLSGRHYWEVEVGNKTGWILGICKASASR 767
Cdd:cd15823     3 VDVTLNPHTANLNLVLSKNRRQVRfVGAKLSGPSYLEEHYDCSV--LGSQHFSSGKHYWEVDVTKKTAWILGVCSHSLGP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1570468134 768 KGSMT-----------LSPDNGYWVVMMMKRNEYQV--STIPPTRLQIKEPPRRVGIFLDYKAGDISFYNVTYKSL-IYT 833
Cdd:cd15823    81 TFSFNqyaqnhnaysrYQPQSGYWVIGLQHNHEYRAyeDSSTSLLLSMTVPPRRVGVFLDYEAGTVSFYNVTNHGFpIYT 160

                         170
                  ....*....|....*.
gi 1570468134 834 FTSFSSSGPLQPMFSP 849
Cdd:cd15823   161 FSKYYFPTTLCPYFNP 176