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 1751297068 292 DVKLDPATAHPSLLLTADLRSVQDGEPWRDVPNNPERFDTWPCILGLQSFSSGRHYWEVLVGERAEWGLGVCQDALPRKG 371
Cdd:cd15816     1 DVKLDPATAHPSLLLTADLRSVQDGELWRDVPGNPERFDTWPCVLGLQSFSSGRHYWEVAVGEKAEWGLGVCQDSAPRKG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1751297068 372 ETTPSPENGVWALWLLKGNEYMVLASPSVPLLQLESPRCIGIFLDYEAGEISFYNVTNGSYIYTFNQLFSGLLRPYFFIC 451
Cdd:cd15816    81 ETTPSPENGVWAVWLLKGNEYMVLASPSVPLLQLRRPRRVGVFLDYEAGEISFYNVTAGSHIYTFRQLFSGILRPYFFVC 160

                  ....*...
gi 1751297068 452 DATPLILP 459
Cdd:cd15816   161 DTTPLTLP 168

B-box-type 2 zinc finger found in tripartite motif-containing proteins TRIM39, TRIM58 and similar proteins; The family includes TRIM39 and TRIM58, both of which belong to the C-IV subclass of 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 SPRY/B30.2 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. TRIM39, also termed RING finger protein 23 (RNF23), or testis-abundant finger protein, is an E3 ubiquitin-protein ligase that plays a role in controlling DNA damage-induced apoptosis through inhibition of the anaphase promoting complex (APC/C), a multiprotein ubiquitin ligase that controls multiple cell cycle regulators, including cyclins, geminin, and others. TRIM39 also functions as a regulator of several key processes in the proliferative cycle. It directly regulates p53 stability and modulates cell cycle progression and DNA damage responses via stabilization of p21. TRIM39 also negatively regulates the nuclear factor kappaB (NFkappaB)-mediated signaling pathway through stabilization of Cactin, an inhibitor of NFkappaB- and Toll-like receptor (TLR)-mediated transcription, which is induced by inflammatory stimulants such as tumor necrosis factor alpha (TNFalpha). TRIM39 is a MOAP-1-binding protein that can promote apoptosis signaling through stabilization of MOAP-1 via the inhibition of its poly-ubiquitination process. TRIM58, also known as protein BIA2, is an erythroid E3 ubiquitin-protein ligase induced during late erythropoiesis. It binds and ubiquitinates the intermediate chain of the microtubule motor dynein (DYNC1LI1/DYNC1LI2), stimulating the degradation of the dynein holoprotein complex. It may participate in the erythroblast enucleation process through regulation of nuclear polarization.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1751297068  92 GARRCARHGEELNRFCEEDQAALCWVCDAGPEHRTHRTAPLQEA 135
Cdd:cd19780     1 EESLCARHREALSLFCEEDQEAVCLVCEISHDHRAHTLVPLQDA 44

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 1751297068 292 DVKLDPATAHPSLLLTADLRSVQDGEPWRDVPNNPERFDTWPCILGLQSFSSGRHYWEVLVGERAEWGLGVCQDALPRKG 371
Cdd:cd15816     1 DVKLDPATAHPSLLLTADLRSVQDGELWRDVPGNPERFDTWPCVLGLQSFSSGRHYWEVAVGEKAEWGLGVCQDSAPRKG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1751297068 372 ETTPSPENGVWALWLLKGNEYMVLASPSVPLLQLESPRCIGIFLDYEAGEISFYNVTNGSYIYTFNQLFSGLLRPYFFIC 451
Cdd:cd15816    81 ETTPSPENGVWAVWLLKGNEYMVLASPSVPLLQLRRPRRVGVFLDYEAGEISFYNVTAGSHIYTFRQLFSGILRPYFFVC 160

                  ....*...
gi 1751297068 452 DATPLILP 459
Cdd:cd15816   161 DTTPLTLP 168

Domain in SPla and the RYanodine Receptor; Domain of unknown function. Distant homologues are domains in butyrophilin/marenostrin/pyrin homologues.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1751297068  343 SGRHYWEVLVGERAEWGLGVCQDALPRKGETTPSPENGVWALWLLKGNEYMVLASPSVPLLQLESPRCIGIFLDYEAGEI 422
Cdd:smart00449   1 SGRHYFEVEIGDGGHWRVGVATKSVPRGYFALLGEDKGSWGYDGDGGKKYHNSTGPEYGLPLQEPGDVIGCFLDLEAGTI 80

                           90       100
                   ....*....|....*....|....*....
gi 1751297068  423 SFYNVTNGSYIYTFNQL-FSGLLRPYFFI 450
Cdd:smart00449  81 SFYKNGKYLHGLAFFDVkFSGPLYPAFSL 109

B-box-type 2 zinc finger found in tripartite motif-containing proteins TRIM39, TRIM58 and similar proteins; The family includes TRIM39 and TRIM58, both of which belong to the C-IV subclass of 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 SPRY/B30.2 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. TRIM39, also termed RING finger protein 23 (RNF23), or testis-abundant finger protein, is an E3 ubiquitin-protein ligase that plays a role in controlling DNA damage-induced apoptosis through inhibition of the anaphase promoting complex (APC/C), a multiprotein ubiquitin ligase that controls multiple cell cycle regulators, including cyclins, geminin, and others. TRIM39 also functions as a regulator of several key processes in the proliferative cycle. It directly regulates p53 stability and modulates cell cycle progression and DNA damage responses via stabilization of p21. TRIM39 also negatively regulates the nuclear factor kappaB (NFkappaB)-mediated signaling pathway through stabilization of Cactin, an inhibitor of NFkappaB- and Toll-like receptor (TLR)-mediated transcription, which is induced by inflammatory stimulants such as tumor necrosis factor alpha (TNFalpha). TRIM39 is a MOAP-1-binding protein that can promote apoptosis signaling through stabilization of MOAP-1 via the inhibition of its poly-ubiquitination process. TRIM58, also known as protein BIA2, is an erythroid E3 ubiquitin-protein ligase induced during late erythropoiesis. It binds and ubiquitinates the intermediate chain of the microtubule motor dynein (DYNC1LI1/DYNC1LI2), stimulating the degradation of the dynein holoprotein complex. It may participate in the erythroblast enucleation process through regulation of nuclear polarization.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1751297068  92 GARRCARHGEELNRFCEEDQAALCWVCDAGPEHRTHRTAPLQEA 135
Cdd:cd19780     1 EESLCARHREALSLFCEEDQEAVCLVCEISHDHRAHTLVPLQDA 44

B-Box-type zinc finger;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 1751297068   93 ARRCARHGEE-LNRFCEEDQAALCWVCDAgPEHRTHRTAPL 132
Cdd:smart00336   3 APKCDSHGDEpAEFFCEECGALLCRTCDE-AEHRGHTVVLL 42

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1751297068  15 RCPVCLDFLQEPVSVDCGHSFCLRCISEFCEKSDIaqggvyaCPQCRGPFRPAGFRPNRQLAGLVESVRRLG 86
Cdd:COG5432    27 RCRICDCRISIPCETTCGHTFCSLCIRRHLGTQPF-------CPVCREDPCESRLRGSSGSREINESHARNR 91

B-box zinc finger;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1751297068  94 RRCARHGEE-LNRFCEEDQAALCWVCDAGpEHRTHRTAPL 132
Cdd:pfam00643   4 RLCPEHEEEpLTLYCNDCQELLCEECSVG-EHRGHTVVPL 42

phosphodiesterase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1751297068 140 QVKLQMALELVRKELEDAlTQEANVGKKTVI--WKEKVEMQRQRFRLEFEKHRGFLAQ--------EEQL--QLRRLEAE 207
Cdd:PRK12704   30 EAKIKEAEEEAKRILEEA-KKEAEAIKKEALleAKEEIHKLRNEFEKELRERRNELQKlekrllqkEENLdrKLELLEKR 108

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1751297068 208 EratlQRLRESKSRLVQQSKALKELADELQERCQRQalgllegvRGVLSRSKAVTRLEAENIPME 272
Cdd:PRK12704  109 E----EELEKKEKELEQKQQELEKKEEELEELIEEQ--------LQELERISGLTAEEAKEILLE 161

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1751297068 134 EAAGRYQvKLQMALELVRKEL-----EDALTQEANVGKKtviwKEKVEMQRQRFRLEFEKHRgflAQEEQLQLRRLEAEE 208
Cdd:COG1196   210 EKAERYR-ELKEELKELEAELlllklRELEAELEELEAE----LEELEAELEELEAELAELE---AELEELRLELEELEL 281

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1751297068 209 R-----ATLQRLRESKSRLVQQSKALKELADELQERCQRQALGLLEGVRGVLSRSKAVTRLEAE 267
Cdd:COG1196   282 EleeaqAEEYELLAELARLEQDIARLEERRRELEERLEELEEELAELEEELEELEEELEELEEE 345

B-Box C-terminal domain; Coiled coil region C-terminal to (some) B-Box domains

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1751297068  141 VKLQMALELVRKELEDALTQEANVGKKTVIWKEKVEMQRQRFRLEFEKHRGFLAQEEQLQLRRLEAEERATLQRLRESKS 220
Cdd:smart00502   3 EALEELLTKLRKKAAELEDALKQLISIIQEVEENAADVEAQIKAAFDELRNALNKRKKQLLEDLEEQKENKLKVLEQQLE 82

                           90       100
                   ....*....|....*....|.
gi 1751297068  221 RLVQQSKALKELADELQERCQ 241
Cdd:smart00502  83 SLTQKQEKLSHAINFTEEALN 103

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 1751297068 292 DVKLDPATAHPSLLLTADLRSVQDGEPWRDVPNNPERFDTWPCILGLQSFSSGRHYWEVLVGERAEWGLGVCQDALPRKG 371
Cdd:cd15816     1 DVKLDPATAHPSLLLTADLRSVQDGELWRDVPGNPERFDTWPCVLGLQSFSSGRHYWEVAVGEKAEWGLGVCQDSAPRKG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1751297068 372 ETTPSPENGVWALWLLKGNEYMVLASPSVPLLQLESPRCIGIFLDYEAGEISFYNVTNGSYIYTFNQLFSGLLRPYFFIC 451
Cdd:cd15816    81 ETTPSPENGVWAVWLLKGNEYMVLASPSVPLLQLRRPRRVGVFLDYEAGEISFYNVTAGSHIYTFRQLFSGILRPYFFVC 160

                  ....*...
gi 1751297068 452 DATPLILP 459
Cdd:cd15816   161 DTTPLTLP 168

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 1751297068 289 FQVDVKLDPATAHPSLLLTADLRSVQDGEPWRDVPNNPERFDTWPCILGLQSFSSGRHYWEVLVGERAEWGLGVCQDALP 368
Cdd:cd13745     1 FAVDVTLDPDTAHPNLVLSEDRKSVRHGDTRQDLPDNPERFDTYPCVLGAEGFTGGRHYWEVEVGDKTEWTLGVCRESVS 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1751297068 369 RKGETTPSPENGVWALWlLKGNEYMVLASPSVPLLQLESPRCIGIFLDYEAGEISFYNVTNGSYIYTFNQLFSGLLRPYF 448
Cdd:cd13745    81 RKGEVTLSPENGYWTVW-LRDGKYEALTSPPTPLPVSVRPSRVGIFLDYEAGEVSFYNVTDRSHLFTFTDTFSGTLRPYF 159

                         170
                  ....*....|....*.
gi 1751297068 449 FIC------DATPLIL 458
Cdd:cd13745   160 YPGlnaggkNAAPLII 175

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 1751297068 287 RKFQVDVKLDPATAHPSLLLTADLRSVQDGEPWRDVPNNPERFDTWPCILGLQSFSSGRHYWEVLVGERAEWGLGVCQDA 366
Cdd:cd15813     5 QAHAVNVTLDPETAHPNLIFSDDLKSVRLGNKWDRLPDNPERFDSCIIVLGSPSFTSGRHYWEVEVGDKTGWILGVCKAS 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1751297068 367 LPRKGETTPSPENGVWALWLLKGNEYMVLASPSVPLLQLESPRCIGIFLDYEAGEISFYNVTNGSYIYTFNQLFS-GLLR 445
Cdd:cd15813    85 VSRKGSMTLSPENGYWVVMMTKRNEYQASTSPPTRLWLREPPRRVGIFLDYEAGDISFYNVTAKSHIYTFTSFSSsGPLQ 164

                  ...
gi 1751297068 446 PYF 448
Cdd:cd15813   165 PIF 167

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 1751297068 283 RELLRKFQVDVKLDPATAHPSLLLTADLRSVQDGEPWRDVPNNPERFDTWPCILGLQSFSSGRHYWEVLVGERAEWGLGV 362
Cdd:cd15815     5 KKMLRRHQVSVTLDPDTAHPELTLSKDQRQVTYGRCQENLDASPKRFTVLPCVLGCEGFTSGRHYFEVDVGEGTGWDVGV 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1751297068 363 CQDALPRKGETTPSPENGVWALWLLKGNEYMVLASPSVPLLQLESPRCIGIFLDYEAGEISFYNVTNGSYIYTFNQL-FS 441
Cdd:cd15815    85 CLENVQRGFGMKQEPEFGFWTIRLCEEDGYVALTSPPTPLPLREKPLVVGVFLDYEAGLVSFYNMTTGSHIFTFPKAsFS 164

                         170
                  ....*....|....*...
gi 1751297068 442 GLLRPYFFICDATPLILP 459
Cdd:cd15815   165 DTLRPYFQVYQYSPLFLP 182

PRY/SPRY domain in tripartite motif-binding protein 7 (TRIM7)-like, including TRIM7, TRIM10, TRIM15, TRIM26, TRIM39, TRIM41; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of several tripartite motif-containing (TRIM) proteins, including TRIM7 (also referred to as glycogenin-interacting protein, RING finger protein 90 or RNF90), TRIM10, TRIM15, TRIM26, TRIM39 and TRIM41. TRIM7 or GNIP interacts with glycogenin and stimulates its self-glucosylating activity via its SPRY domain. TRIM10 (also known as hematopoietic RING finger 1 (HERF1) or TRIM10/HERF1) plays a key role in definitive erythroid development; downregulation of the Spi-1/PU.1 oncogene induces the expression of TRIM10/HERF1, a key factor required for terminal erythroid cell differentiation and survival. Antiviral activity of TRIM15 is dependent on the ability of its B-box to interact with the MLV Gag precursor protein; downregulation of TRIM15, along with TRIM11, enhances virus release suggesting that these proteins contribute to the endogenous restriction of retroviruses in cells. Tripartite motif-containing 26 (TRIM26) function is as yet unknown; however, since it is localized in the human histocompatibility complex (MHC) class I region, TRIM26 may play a role in immune response although studies show no association between TRIM26 polymorphisms and the risk of aspirin-exacerbated respiratory disease. TRIM39 is a MOAP-1 (Modulator of Apoptosis)-binding protein that stabilizes MOAP-1 through inhibition of its poly-ubiquitination process. TRIM41 (also known as RING finger-interacting protein with C kinase or RINCK) functions as an E3 ligase that catalyzes the ubiquitin-mediated degradation of protein kinase C.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1751297068 292 DVKLDPATAHPSLLLTADLRSVQDGEPWRDVPNNPERFDTWPCILGLQSFSSGRHYWEVLVGERAEWGLGVCQDALPRKG 371
Cdd:cd12888     1 NVTLDPDTAHPRLVLSEDRKSVRWGDTRQDLPDNPERFDTWPCVLGCEGFTSGRHYWEVEVGDGGGWAVGVARESVRRKG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1751297068 372 ETTPSPENGVWALWLLKGnEYMVLASPSVPLLQLESPRCIGIFLDYEAGEISFYNVTNGSYIYTFNQ-LFSG-LLRPYFF 449
Cdd:cd12888    81 EISFSPEEGIWAVGQWGG-QYWALTSPETPLPLSEVPRRIRVYLDYEGGQVAFFDADNEAPIFTFPPaSFAGeRIFPWFW 159

                  ....*....
gi 1751297068 450 ICDATPLIL 458
Cdd:cd12888   160 VGKGSQLKL 168

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 1751297068 288 KFQVDVKLDPATAHPSLLLTADLRSVQDGEPWRDVPNNPERFDTWPCILGLQSFSSGRHYWEVLVGERAEWGLGVCQDAL 367
Cdd:cd15821     1 KFQVDMTLDVDTANNYLIISEDLRSVRCGCFRQNRKELAERFDDALCVLGSPRFTSGRHYWEVDVGTSTEWDLGVCRESV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1751297068 368 PRKGETTPSPENGVWALWLLKGNEYMVLASPSVPLLQLESPRCIGIFLDYEAGEISFYNVTNGSYIYTFNQLF-SGLLRP 446
Cdd:cd15821    81 NRQGPIELSPEHGFWTVSLRDGSVFFASTVPLTVLWVNPRLHRVGIFLDMEMGTISFYDVSDGSHIFTFTKISaEEPLRP 160

                  ....*....
gi 1751297068 447 YFfiCDATP 455
Cdd:cd15821   161 FF--APANP 167

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 1751297068 291 VDVKLDPATAHPSLLLTADLRSVQDGEPWRDVPNNPERFDTWPCILGLQSFSSGRHYWEVLVGERAEWGLGVCQDALPRK 370
Cdd:cd15814     2 VDVTLDPDTAYPSLILSDNLRQVRYSYLQQDLPDNPERFNLFPCVLGSPCFIAGRHYWEVEVGDKAKWTIGVCEDSVCRK 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1751297068 371 GETTPSPENGVWALWLLKGNEYMVLASPsVPLLQLESP-RCIGIFLDYEAGEISFYNVTNGSYIYTFNQ-LFSGLLRPYF 448
Cdd:cd15814    82 GGVTSAPQNGFWAVSLWYGKEYWALTSP-MTALPLRTPlQRVGIFLDYDAGEVSFYNVTERCHTFTFSHaTFCGPVRPYF 160

                         170
                  ....*....|....*
gi 1751297068 449 FIC-----DATPLIL 458
Cdd:cd15814   161 SLSysggkSAAPLII 175

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 1751297068 292 DVKLDPATAHPSLLLTADLRSVQDGEPWRDVPNNPERFDTWPCILGLQSFSSGRHYWEVLVGERAEWGLGVCQDALPRKG 371
Cdd:cd15817     1 DLILDPETAHPNLIVSEDRKAVRYRRMKPNCPYDPRRFTVYPAVLGSEGFDSGRHFWEVEVGGKGEWILGVCKDSLPRNA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1751297068 372 ETTPSPENGVWALWlLKGNEYMVLASPSVPLLQLESPRCIGIFLDYEAGEISFYNVTNGSYIYTFNQLFSGLLRPYFFI- 450
Cdd:cd15817    81 QDPPSPLGGCWQIG-RYMSGYVASGPKTTQLLPVVKPSRIGIFLDYELGEVSFYNMNDRSHLYTFTDTFTGKLIPYFYVg 159

                  ....*.
gi 1751297068 451 CDATPL 456
Cdd:cd15817   160 PDSEPL 165

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 1751297068 293 VKLDPATAHPSLLLTADLRSVQDGEPWRDVPNNPERFDTWPCILGLQSFSSGRHYWEVLVGERAEWGLGVCQDALPRKGE 372
Cdd:cd15818    15 ITLDPKTAHPNLILSEDLTCVWHGDTKQMLPDNPERFDSSVAVLGSEGFTSGKHYWEVEVAKKTKWTLGVVRESINRKGN 94

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1751297068 373 TTPSPENGVWALWLLKGNEYMVLASPSVPLLQLESPRCIGIFLDYEAGEISFYNVTNGSYIYTFNQLFSGLLRPYFFIC 451
Cdd:cd15818    95 CPLSPEDGFWLLRLRNQNELKALDVPSFSLTLTSNLNKVGIYLDYEGGQVSFYNANTMSHIYTFSDTFTEKIYPYFCPC 173

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 1751297068 292 DVKLDPATAHPSLLLTADLRSVQDGEPWRDVPNNPERFDTWPCILGLQSFSSGRHYWEV---LVGErAEWGLGVCQDALP 368
Cdd:cd15812     1 DVVPDPSTAYPYLLLYESRQRRYLSTPPDGTPCSKDRFLAYPCAVGQETFSSGRHYWEVgmnLTGD-ALWALGVCRDNVS 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1751297068 369 RKGETTPSPENGVWALWLLKGNEYMVLASPSVPLLQLESPRCIGIFLDYEAGEISFYNVTNGSYIYTFNQ-LFSGLLRPY 447
Cdd:cd15812    80 RKDRVPKSPENGFWVVQLSKGKKYLSAMSALTPVTLTEPPSHMGIFLDFEAGEVSFYSVNDGSHLHTYSQaAFPGPLQPF 159

                  ....*...
gi 1751297068 448 FfiCDATP 455
Cdd:cd15812   160 F--CLGAP 165

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 1751297068 295 LDPATAHPSLLLTADLRSVQDGEPWRDVPNNPERFDTWPCILGLQSFSSGRHYWEVLVGERAEWGLGVCQDALPRKGETT 374
Cdd:cd12905     8 FDPETAHPSLILSRDLTAVTESDEMQPYPRSPKRFLQCVNVLASQGFQSGRHYWEVWVGSKTKWDLGVASESVDRQARVK 87

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1751297068 375 PSPENGVWALWLLKGNEYMVLASPSVPLLQLESPRCIGIFLDYEAGEISFYNVTNGSYIYTFNQLFSGLLRPYFFIC 451
Cdd:cd12905    88 LCPENGYWTLRLRNGDEYWAGTQPWTRLRVTSRPQRIGVFLDCEERKVSFYNADDMSLLYSFHQGPRGKVFPFFSTC 164

PRY/SPRY domain in tripartite motif-binding protein 7 (TRIM7); 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 7 (TRIM7), also referred to as glycogenin-interacting protein (GNIP) or RING finger protein 90 (RNF90). TRIM7 or GNIP interacts with glycogenin and stimulates its self-glucosylating activity via its SPRY domain. The GNIP gene encodes at least four distinct isoforms of GNIP, of which three (GNIP1, GNIP2, and GNIP3) have the B30.2 domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1751297068 292 DVKLDPATAHPSLLLTADLRSVQDGEPWRDVPNNPERFDTWPCILGLQSFSSGRHYWEVLVGERAEWGLGVCQDALPRKG 371
Cdd:cd13740     1 ELTLDPDSANPRLILSLDLKSVRLGERAQDLPNHPCRFDTNTRVLASCGFSSGRHHWEVEVGSKDGWAFGVARESVRRKG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1751297068 372 ETTPSPENGVWALWlLKGNEYMVLASPSvpllqlESPRCIG------IFLDYEAGEISFYNVTNGSYIYTFNQLFSGLLR 445
Cdd:cd13740    81 LTPFTPEEGVWALQ-LNGGQYWAVTSPE------RTPLSCGhlsrvrVALDLEVGAVSFYAAEDMRHIYTFRVNFQERVF 153

                  ....*.
gi 1751297068 446 PYFFIC 451
Cdd:cd13740   154 PLFSVC 159

PRY/SPRY domain in tripartite motif-binding protein 41 (TRIM41); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of tripartite motif-containing protein 41 (TRIM41). TRIM41 (also known as RING finger-interacting protein with C kinase or RINCK) is localized to speckles in the cytoplasm and nucleus, and functions as an E3 ligase that catalyzes the ubiquitin-mediated degradation of protein kinase C.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1751297068 292 DVKLDPATAHPSLLLTADLRSVQDGEPWRDVPNNPERFDTWPCILGLQSFSSGRHYWEVLVGERAEWGLGVCQDALPRKG 371
Cdd:cd13741     1 DLTLDPDTAHPALLLSPDRRGVRLAERRQEVPEHPKRFSADCCVLGAQGFRSGRHYWEVEVGGRRGWAVGAARESTHHKE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1751297068 372 ETTPSPENGVWA-------------------------LWLL--KGNEYMVLASPSVPLLQ-LESPRCIGIFLDYEAGEIS 423
Cdd:cd13741    81 KVGSGGSSVSSGdasssrhhhrrrrlhlpqqpllqreVWCVgtNGKRYQAQSSTEQTLLSpSEKPRRFGVYLDYEAGRLG 160

                         170       180
                  ....*....|....*....|....*...
gi 1751297068 424 FYNVTNGSYIYTFNQLFSG-LLRPYFFI 450
Cdd:cd13741   161 FYNAETLAHVHTFSAAFLGeRVFPFFRV 188

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 1751297068 289 FQVDVKLDPATAHPSLLLTADLRSVQDGEP----------------WRDVPNNP---ERFDTWPCILGLQSFSSGRHYWE 349
Cdd:cd15809     1 FQVAVNLAEDTAHPKLVFSQEGRYVKNGASasswplfstawsyftgWRNPQKTTqfvERFQHLPCVLGKNVFTSGKHYWE 80