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 530381358 210 AADVVLDPDTAHPELFLSEDRRSVRRGPYRQRVPDNPERFDSQPCVLGWESFASGKHYWEVEVENVMVWTVGVCRHSVER 289
Cdd:cd15819    1 AVNVTLDPDTAHPALILSEDGRSVTWGETRQDLPENPERFDSLPCVLGQEGFTSGRHYWEVEVGDRTSWDLGVCRDNVMR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381358 290 KGEVLLIPQNGFWTLEMFGNQYRALSSPERILPLKESLCRVGVFLDYEAGDVSFYNMRDRSHIYTCPRSAFTVPVRPFFR 369
Cdd:cd15819   81 KGRVTLSPENGFWAIRLYGNEYWALTSPETPLTLKEPPRRVGIFLDYEAGDVSFYNMTDGSHIYTFPQTAFSGPLRPFFR 160

                        170
                 ....*....|..
gi 530381358 370 LGSDDS-PIFIC 380
Cdd:cd15819  161 LWSSDSgPLTIC 172

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 530381358 210 AADVVLDPDTAHPELFLSEDRRSVRRGPYRQRVPDNPERFDSQPCVLGWESFASGKHYWEVEVENVMVWTVGVCRHSVER 289
Cdd:cd15819    1 AVNVTLDPDTAHPALILSEDGRSVTWGETRQDLPENPERFDSLPCVLGQEGFTSGRHYWEVEVGDRTSWDLGVCRDNVMR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381358 290 KGEVLLIPQNGFWTLEMFGNQYRALSSPERILPLKESLCRVGVFLDYEAGDVSFYNMRDRSHIYTCPRSAFTVPVRPFFR 369
Cdd:cd15819   81 KGRVTLSPENGFWAIRLYGNEYWALTSPETPLTLKEPPRRVGIFLDYEAGDVSFYNMTDGSHIYTFPQTAFSGPLRPFFR 160

                        170
                 ....*....|..
gi 530381358 370 LGSDDS-PIFIC 380
Cdd:cd15819  161 LWSSDSgPLTIC 172

SPRY-associated domain; PRY is a 50-60 amino acids domain associated with SPRY domains, adjacent to its N-terminal. PRY and SPRY domains are structurally very similar and consist of a beta sandwich fold. Distant homologs are domains in butyrophilin/marenostrin/pyrin, evolutionarily more ancient than SPRY/B30.2 counterpart.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 530381358  213 VVLDPDTAHPELFLSEDRRSVRRGPYRQRVPDNPERFDSQPCVLGWESF 261
Cdd:pfam13765   1 VTLDPNTAHPSLVLSEDLKSVRYGDERQNVPDNPERFDSWPCVLGSEGF 49

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 530381358 210 AADVVLDPDTAHPELFLSEDRRSVRRGPYRQRVPDNPERFDSQPCVLGWESFASGKHYWEVEVENVMVWTVGVCRHSVER 289
Cdd:cd15819    1 AVNVTLDPDTAHPALILSEDGRSVTWGETRQDLPENPERFDSLPCVLGQEGFTSGRHYWEVEVGDRTSWDLGVCRDNVMR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381358 290 KGEVLLIPQNGFWTLEMFGNQYRALSSPERILPLKESLCRVGVFLDYEAGDVSFYNMRDRSHIYTCPRSAFTVPVRPFFR 369
Cdd:cd15819   81 KGRVTLSPENGFWAIRLYGNEYWALTSPETPLTLKEPPRRVGIFLDYEAGDVSFYNMTDGSHIYTFPQTAFSGPLRPFFR 160

                        170
                 ....*....|..
gi 530381358 370 LGSDDS-PIFIC 380
Cdd:cd15819  161 LWSSDSgPLTIC 172

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 530381358 209 HAADVVLDPDTAHPELFLSEDRRSVRRGPYRQRVPDNPERFDSQPCVLGWESFASGKHYWEVEVENVMVWTVGVCRHSVE 288
Cdd:cd13745    1 FAVDVTLDPDTAHPNLVLSEDRKSVRHGDTRQDLPDNPERFDTYPCVLGAEGFTGGRHYWEVEVGDKTEWTLGVCRESVS 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381358 289 RKGEVLLIPQNGFWTLEMFGNQYRALSSPERILPLKESLCRVGVFLDYEAGDVSFYNMRDRSHIYTCPRSaFTVPVRPFF 368
Cdd:cd13745   81 RKGEVTLSPENGYWTVWLRDGKYEALTSPPTPLPVSVRPSRVGIFLDYEAGEVSFYNVTDRSHLFTFTDT-FSGTLRPYF 159

                        170
                 ....*....|....*...
gi 530381358 369 RLGSDD-----SPIFICP 381
Cdd:cd13745  160 YPGLNAggknaAPLIICP 177

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 530381358 203 WRRTFLHAADVVLDPDTAHPELFLSEDRRSVRRGPYRQRVPDNPERFDSQPCVLGWESFASGKHYWEVEVENVMVWTVGV 282
Cdd:cd15813    1 LRAAQAHAVNVTLDPETAHPNLIFSDDLKSVRLGNKWDRLPDNPERFDSCIIVLGSPSFTSGRHYWEVEVGDKTGWILGV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381358 283 CRHSVERKGEVLLIPQNGFWTLEMF-GNQYRALSSPERILPLKESLCRVGVFLDYEAGDVSFYNMRDRSHIYTCPRSAFT 361
Cdd:cd15813   81 CKASVSRKGSMTLSPENGYWVVMMTkRNEYQASTSPPTRLWLREPPRRVGIFLDYEAGDISFYNVTAKSHIYTFTSFSSS 160

                        170       180
                 ....*....|....*....|....
gi 530381358 362 VPVRPFFRLGSDD-----SPIFIC 380
Cdd:cd15813  161 GPLQPIFSPGTHDggknmDPLTIC 184

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 530381358 212 DVVLDPDTAHPELFLSEDRRSVRRGPYRQRVPDNPERFDSQPCVLGWESFASGKHYWEVEVENVMVWTVGVCRHSVERKG 291
Cdd:cd15821    5 DMTLDVDTANNYLIISEDLRSVRCGCFRQNRKELAERFDDALCVLGSPRFTSGRHYWEVDVGTSTEWDLGVCRESVNRQG 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381358 292 EVLLIPQNGFWTLEM-FGNQYRALSSPERILPLKESLCRVGVFLDYEAGDVSFYNMRDRSHIYTCPRSAFTVPVRPFF-- 368
Cdd:cd15821   85 PIELSPEHGFWTVSLrDGSVFFASTVPLTVLWVNPRLHRVGIFLDMEMGTISFYDVSDGSHIFTFTKISAEEPLRPFFap 164

                        170
                 ....*....|....
gi 530381358 369 --RLGSDDSPIFIC 380
Cdd:cd15821  165 anPYGDDQGVLSIC 178

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381358 209 HAADVVLDPDTAHPELFLSEDRRSVRRGPYRQRVPDNPERFDSQPCVLGWESFASGKHYWEVEVENVMVWTVGVCRHSVE 288
Cdd:cd15815   11 HQVSVTLDPDTAHPELTLSKDQRQVTYGRCQENLDASPKRFTVLPCVLGCEGFTSGRHYFEVDVGEGTGWDVGVCLENVQ 90

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381358 289 RKGEVLLIPQNGFWTLEMF-GNQYRALSSPERILPLKESLCRVGVFLDYEAGDVSFYNMRDRSHIYTCPRSAFTVPVRPF 367
Cdd:cd15815   91 RGFGMKQEPEFGFWTIRLCeEDGYVALTSPPTPLPLREKPLVVGVFLDYEAGLVSFYNMTTGSHIFTFPKASFSDTLRPY 170

                        170
                 ....*....|..
gi 530381358 368 FRLgSDDSPIFI 379
Cdd:cd15815  171 FQV-YQYSPLFL 181

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 530381358 209 HAADVVLDPDTAHPELFLSEDRRSVRRGPYRQRVPDNPERFDSQPCVLGWESFASGKHYWEVEVENVMVWTVGVCRHSVE 288
Cdd:cd12900    1 HMVHITLDPDTANPWLILSKDRRQVRLGDTHQNVPENEERFDNYPMVLGAQRFNSGKHYWEVDVTGKEAWDLGVCRDSVR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381358 289 RKGEVLLIPQNGFWTLEMFGNQYRALSSPERILPLKESLCRVGVFLDYEAGDVSFYNMRDR-SHIYTCPRSAFTVPVRPF 367
Cdd:cd12900   81 RKGQFLLSPENGFWTIWLWNKKYEAGTSPQTTLHLQVPPCQVGIFLDYEAGVVSFYNITDHgSLIYTFSECAFTGPLRPF 160

                        170
                 ....*....|....*....
gi 530381358 368 FRLGSDDS-----PIFICP 381
Cdd:cd12900  161 FNPGFNDSggnaaPLTLCP 179

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 530381358 213 VVLDPDTAHPELFLSEDRRSVRRGPYRQRVPDNPERFDSQPCVLGWESFASGKHYWEVEVENVMVWTVGVCRHSVERKGE 292
Cdd:cd15818   15 ITLDPKTAHPNLILSEDLTCVWHGDTKQMLPDNPERFDSSVAVLGSEGFTSGKHYWEVEVAKKTKWTLGVVRESINRKGN 94

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381358 293 VLLIPQNGFWTLEMF-GNQYRALSSPERILPLKESLCRVGVFLDYEAGDVSFYNMRDRSHIYTCpRSAFTVPVRPFFrlg 371
Cdd:cd15818   95 CPLSPEDGFWLLRLRnQNELKALDVPSFSLTLTSNLNKVGIYLDYEGGQVSFYNANTMSHIYTF-SDTFTEKIYPYF--- 170

                        170
                 ....*....|..
gi 530381358 372 sddspifiCPAL 383
Cdd:cd15818  171 --------CPCL 174

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 530381358 212 DVVLDPDTAHPELFLSEDRRSVRRGPYRQRVPDNPERFDSQPCVLGWESFASGKHYWEVEVENVMVWTVGVCRHSVERKG 291
Cdd:cd15816    1 DVKLDPATAHPSLLLTADLRSVQDGELWRDVPGNPERFDTWPCVLGLQSFSSGRHYWEVAVGEKAEWGLGVCQDSAPRKG 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381358 292 EVLLIPQNGFWTLEMF-GNQYRALSSPERILPLKESLCRVGVFLDYEAGDVSFYNMRDRSHIYTCpRSAFTVPVRPFFrl 370
Cdd:cd15816   81 ETTPSPENGVWAVWLLkGNEYMVLASPSVPLLQLRRPRRVGVFLDYEAGEISFYNVTAGSHIYTF-RQLFSGILRPYF-- 157

                        170
                 ....*....|
gi 530381358 371 gsddspiFIC 380
Cdd:cd15816  158 -------FVC 160

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 530381358 212 DVVLDPDTAHPELFLSEDRRSVRRGPYRQRVPDNPERFDSQPCVLGWESFASGKHYWEVEVENVMVWTVGVCRHSVERKG 291
Cdd:cd15817    1 DLILDPETAHPNLIVSEDRKAVRYRRMKPNCPYDPRRFTVYPAVLGSEGFDSGRHFWEVEVGGKGEWILGVCKDSLPRNA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381358 292 EVLLIPQNGFWTLEMFGNQYRALSSPERILPLKESLCRVGVFLDYEAGDVSFYNMRDRSHIYTCpRSAFTVPVRPFFRLG 371
Cdd:cd15817   81 QDPPSPLGGCWQIGRYMSGYVASGPKTTQLLPVVKPSRIGIFLDYELGEVSFYNMNDRSHLYTF-TDTFTGKLIPYFYVG 159

                 ....*....
gi 530381358 372 SDDSPIFIC 380
Cdd:cd15817  160 PDSEPLTIC 168

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 530381358 211 ADVVLDPDTAHPELFLSEDRRSVRRGPYRQRVPDNPERFDSQPCVLGWESFASGKHYWEVEVENVMVWTVGVCRHSVERK 290
Cdd:cd12905    4 APLTFDPETAHPSLILSRDLTAVTESDEMQPYPRSPKRFLQCVNVLASQGFQSGRHYWEVWVGSKTKWDLGVASESVDRQ 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381358 291 GEVLLIPQNGFWTLEMF-GNQYRALSSPERILPLKESLCRVGVFLDYEAGDVSFYNMRDRSHIYTcprsaFTVPVR---- 365
Cdd:cd12905   84 ARVKLCPENGYWTLRLRnGDEYWAGTQPWTRLRVTSRPQRIGVFLDCEERKVSFYNADDMSLLYS-----FHQGPRgkvf 158

                        170       180
                 ....*....|....*....|
gi 530381358 366 PFFRLGSDDS-----PIFIC 380
Cdd:cd12905  159 PFFSTCFSDDgqnaePMRLL 178

PRY/SPRY domain in tripartite motif-binding protein 15 (TRIM15); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of tripartite motif-containing protein 15 (TRIM15), also referred to as RING finger protein 93 (RNF93) or Zinc finger protein B7 or 178 (ZNFB7 or ZNF178). TRIM15 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. The PRY and SPRY/B30.2 domains can function as immune defense components and in pathogen sensing. TRIM15 has been shown to regulate inflammatory and innate immune signaling, in addition to displaying antiviral activities. Down-regulation of TRIM15, as well as TRIM11, enhances virus release, suggesting that these proteins contribute to the endogenous restriction of retroviruses in cells. TRIM15 is also a regulatory component of focal adhesion turnover and cell migration.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381358 213 VVLDPDTAHPELFLSEDRRSVRRGPYRQRVPDNPERFDSQPCVLGWESFASGKHYWEVEVE--NVMVWTVGVCRHSVERK 290
Cdd:cd15826    2 VTLDPQTASGSLVLSEDRKSVRYTRQKQNLPDSPLRFDGLPAVLGSPGFSSGRHRWQVEVQlgDGGGCTVGVAGESVRRK 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381358 291 GEVLLIPQNGFWTLEMFGNQYRALSSPERILPLKESLCRVGVFLDYEAGDVSFYNMRDRSHIYTCPRSaFTVPVRPFFRL 370
Cdd:cd15826   82 GEMGLSAEDGVWAVILSHQQCWASTSPGTDLPLSEIPRRVGVALDYEAGTVTLTNAETQEPIFTFTAS-FSGKVFPFFAV 160

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 530381358 213 VVLDPDTAHPELFLSEDRRSVRRGPYRQRVPDNPERFDSQPcVLGWESFASGKHYWEVEVENVMVWTVGVCRHSVERKGE 292
Cdd:cd12891    1 LTLDPNTAHNNLALSGDLKTVTCSSENQHYPDSPERFTHSQ-VLSTQSFSSGRHYWEVEVSESGGWSVGVAYPSIERKGD 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381358 293 VLLIPQNGF-WTLEMFGNQYRALSSPERILPLKESLCRVGVFLDYEAGDVSFYNMRDR-SHIYTCpRSAFTVPVRPFFRL 370
Cdd:cd12891   80 ESRIGRNDKsWCLEWQDKSFSAWHNNEETPLPSVSSRRLGVYLDYEAGRLSFYELSDPiRHLHTF-TATFTEPLHPAFWV 158

                        170
                 ....*....|
gi 530381358 371 gSDDSPIFIC 380
Cdd:cd12891  159 -LEGGWIRIK 167

PRY/SPRY domain in tripartite motif-binding protein 50 (TRIM50); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM50. TRIM50, an E3 ubiquitin ligase, is deleted in Williams-Beuren (WBS) syndrome, a multi-system neurodevelopmental disorder caused by the deletion of contiguous genes at chromosome region 7q11.23. It is specifically expressed in gastric parietal cells and may play an essential role in tubulovesicular dynamics. It also interacts with and increases the level of p62, a multifunctional adaptor protein that is implicated in various cellular processes such as the autophagy clearance of polyubiquitinated protein aggregates.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381358 215 LDPDTAHPELFLSEDRRSVRRGPYRQRVPDNPERFDSQPCVLGWESFASGKHYWEVEVENVMVWTVGVCRHSVERKGEVL 294
Cdd:cd13743   16 LDPLTAHPMLELSKGNTVVECGLLAQRLPSNPERFDYSNCVLASRGFSSGKHYWEVVVGSKSKWRLGLIKGTTSRKGKLN 95

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 530381358 295 LIPQNGFWTLEMF-GNQYRALSSPERILPLKESLCRVGVFLDYEAGDVSFYN 345
Cdd:cd13743   96 KSPENGVWLIGLKeGRVYEAFANPRVPLPLSTRPQRIGVFLDYEKGELTFYN 147

PRY/SPRY domain of tripartite motif-binding protein 10 (TRIM10) also known as hematopoietic RING finger 1 (HERF1); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM10, also known as RING finger protein 9 (RNF9) or hematopoietic RING finger 1 (HERF1). TRIM10 domain is composed of RING/B-box/coiled-coil core and also known as RBCC protein. TRIM10/HERF1 is predominantly expressed during definitive erythropoiesis and in embryonic liver, and minimally expressed in adult liver, kidney, and colon. It is critical for erythroid cell differentiation and its down-regulation leads to cell death; inhibition of TRIM10 expression blocks terminal erythroid differentiation, while its over-expression in erythroid cells induces beta-major globin expression and erythroid differentiation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381358 211 ADVVLDPDTAHPELFLSEDRRSVRRGPYRQRVPDNPERFDSQPCVLGWESFASGKHYWEVEVENVM--VWTVGVCRHSVE 288
Cdd:cd15827    2 AHISLDPQTSHPKLLLSEDHQRARFSYKWQNSPDNPQRFDRATCVLAHDGFTGGRHTWVVSVDLAHggSCTVGVVSEDVR 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381358 289 RKGEVLLIPQNGFWTLEMFGNQYRALSS-PERiLPLKESLCRVGVFLDYEAGDVSFYNMRDRSHIYTCPRSaFTVPVRPF 367
Cdd:cd15827   82 RKGELRLRPEEGVWAVRLAWGFVSALGSfPTR-LALEEQPRQVRVSLDYEVGWVTFVNAVTQEPIYTFTAS-FTQKVFPF 159

                 ...
gi 530381358 368 FRL 370
Cdd:cd15827  160 FGL 162

Stonustoxin subunit alpha or SNTX subunit alpha; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of Stonustoxin alpha proteins. Stonustoxin (SNTX) is a multifunctional lethal protein isolated from venom elaborated by the stonefish. It comprises two subunits, termed alpha and beta. SNTX elicits an array of biological responses, particularly a potent hypotension and respiratory difficulties.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381358 204 RRTFL-HAADVVLDPDTAHPELFLSEDRRSVRRGPYRQRVPDNPERFDSQPCVLGWESFaSGKHYWEVEVENVMVwTVGV 282
Cdd:cd16040    1 REEFLkYACQLTLDPNTAHRNLSLSEGNRKVTRVKEEQPYPDHPERFDYWPQVLCREGL-SGRCYWEVEWSGGGV-DIAV 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381358 283 CRHSVERKGEVlliPQNGF------WTLEMFGNQYRALSSPERI---LPlKESLCRVGVFLDYEAGDVSFYNMRD-RSHI 352
Cdd:cd16040   79 AYKGISRKGDG---DDSRFgyndksWSLECSPSGYSFWHNNKKTeisVP-SSSSSRVGVYLDHSAGTLSFYSVSDtMTLL 154

                        170       180
                 ....*....|....*....|...
gi 530381358 353 YTCpRSAFTVPVRPFFRLGSDDS 375
Cdd:cd16040  155 HTV-QTTFTEPLYPGFGVGYGSS 176

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 530381358 212 DVVLDPDTAHPELFLSEDRRSVR---RGPYRQRVPDNPERFDsqpcVLGWESFASGKHYWEVEVENVMVWTVGVCRHSVE 288
Cdd:cd15810    1 DVTLNPVNISLNIVISEDQRQVRivpPQTSGQALTNNNYDFG----VLGSQYFSSGKHYWEVDVSKKSAWILGVCSHKRS 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381358 289 ---RKGEVLLI----------PQNGFWTLEM-FGNQYRAL----SSPERILPLKESLC--RVGVFLDYEAGDVSFYNMRD 348
Cdd:cd15810   77 damTKSNANQInhqnvysryqPQYGYWVIGLqNESEYNAFedssSFNPHVLTLSVTVPphRVGVFLDYEAGTVSFFNVTN 156

                        170       180       190
                 ....*....|....*....|....*....|...
gi 530381358 349 R-SHIYTCPRSAFTVPVRPFFRLGSDDSPIFIC 380
Cdd:cd15810  157 HgSLIYKFSKCCFSTTVCPYFNPWNCPVPMTLC 189

PRY/SPRY domain in tripartite motif-binding protein 4 (TRIM4), also known as RING finger protein 87 (RNF87); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM4 which is also known as RING finger protein 87 (RNF87). TRIM4 domain is composed of RING/B-box/coiled-coil core and also known as RBCC protein. It is a positive regulator of RIG-I-mediated interferon (IFN) induction. It regulates virus-induced IFN induction and cellular antiviral innate immunity by targeting RIG-I for K63-linked poly-ubiquitination. Over-expression of TRIM4 enhances virus-triggered activation of transcription factors IRF3 and NF-kappaB, as well as IFN-beta induction. Expression of TRIM4 differs significantly in Huntington's Disease (HD) neural cells when compared with wild-type controls, possibly impacting down-regulation of the Huntingtin (HTT) gene, which is involved in the regulation of diverse cellular activities that are impaired in Huntington's Disease (HD) cells.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381358 213 VVLDPDTAHPELFLSEDRRSVRRGP-----------------YR--QRVPDNPERFDSQPCVLGWESFASGKHYWEVEVE 273
Cdd:cd15809    5 VNLAEDTAHPKLVFSQEGRYVKNGAsasswplfstawsyftgWRnpQKTTQFVERFQHLPCVLGKNVFTSGKHYWEVENR 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381358 274 NVMVWTVGVCRHSV-ERKGEVLLIPQNGFWTLEMFGNQYRALSSPErILPLKE--SLCRVGVFLDYEAGDVSFYNMRDRS 350
Cdd:cd15809   85 DSLEIAVGVCREDVmGITDGSEMSPHVGIWAICWSSAGYRPLTSSP-VSPTKQepALHRVGVFLDHGAGEVSFYSAVDGV 163