RING finger, HC subclass, found in tripartite motif-containing protein 47 (TRIM47) and similar proteins; TRIM47, also known as gene overexpressed in astrocytoma protein (GOA) or RING finger protein 100 (RNF100), belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, a B-box, and two coiled coil domains, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. It plays an important role in the process of dedifferentiation that is associated with astrocytoma tumorigenesis. This subfamily also includes RING finger protein 135 (RNF135). RNF135, also known as RIG-I E3 ubiquitin ligase (REUL) or Riplet, is a widely expressed E3 ubiquitin-protein ligase that consists of an N-terminal C3HC4-type RING-HC finger and C-terminal B30.2/SPRY and PRY motifs, but lacks the B-box and coiled-coil domains that are also typically present in TRIM proteins. RNF135 serves as a specific retinoic acid-inducible gene-I (RIG-I)-interacting protein that ubiquitinates RIG-I and specifically stimulates RIG-I-mediated innate antiviral activity to produce antiviral type-I interferon (IFN) during the early phase of viral infection. It also has been identified as a bio-marker and therapy target of glioblastoma. It associates with the ERK signal transduction pathway and plays a role in glioblastoma cell proliferation, migration and cell cycle.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 269849639  19 LGCIICQGLLDWPATLPCGHSFCRHCLEALWGARDARRWACPTCRQGAA 67
Cdd:cd16604    1 LSCPICLDLLKDPVTLPCGHSFCMGCLGALWGAGRGGRASCPLCRQTFP 49

RING finger, HC subclass, found in tripartite motif-containing protein 47 (TRIM47) and similar proteins; TRIM47, also known as gene overexpressed in astrocytoma protein (GOA) or RING finger protein 100 (RNF100), belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, a B-box, and two coiled coil domains, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. It plays an important role in the process of dedifferentiation that is associated with astrocytoma tumorigenesis. This subfamily also includes RING finger protein 135 (RNF135). RNF135, also known as RIG-I E3 ubiquitin ligase (REUL) or Riplet, is a widely expressed E3 ubiquitin-protein ligase that consists of an N-terminal C3HC4-type RING-HC finger and C-terminal B30.2/SPRY and PRY motifs, but lacks the B-box and coiled-coil domains that are also typically present in TRIM proteins. RNF135 serves as a specific retinoic acid-inducible gene-I (RIG-I)-interacting protein that ubiquitinates RIG-I and specifically stimulates RIG-I-mediated innate antiviral activity to produce antiviral type-I interferon (IFN) during the early phase of viral infection. It also has been identified as a bio-marker and therapy target of glioblastoma. It associates with the ERK signal transduction pathway and plays a role in glioblastoma cell proliferation, migration and cell cycle.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 269849639  19 LGCIICQGLLDWPATLPCGHSFCRHCLEALWGARDARRWACPTCRQGAA 67
Cdd:cd16604    1 LSCPICLDLLKDPVTLPCGHSFCMGCLGALWGAGRGGRASCPLCRQTFP 49

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 269849639  312 KHYWEV--DTRNCSHWAVGVASWEMSR--DQVLGRTMDSCCVEwkGTSQLSAWH-MVKETVLGSDRPG-VVGIWLNLEEG 385
Cdd:pfam00622   1 RHYFEVeiFGQDGGGWRVGWATKSVPRkgERFLGDESGSWGYD--GWTGKKYWAsTSPLTGLPLFEPGdVIGCFLDYEAG 78

                          90       100       110
                  ....*....|....*....|....*....|...
gi 269849639  386 KLAFYsvDNQEKLLYECTI-SASSPLYPAFWLY 417
Cdd:pfam00622  79 TISFT--KNGKSLGYAFRDvPFAGPLFPAVSLG 109

DNA repair protein rad18; All proteins in this family for which functions are known are involved in nucleotide excision repair.This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 269849639   16 EDDLGCIICQGLLDWPATLPCGHSFCRHCLealwgaRDARRW--ACPTCRqGAAQQPHLRKNTLLQDLADKYRRA 88
Cdd:TIGR00599  24 DTSLRCHICKDFFDVPVLTSCSHTFCSLCI------RRCLSNqpKCPLCR-AEDQESKLRSNWLVSEIVESFKNL 91

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 269849639  19 LGCIICQGLLDWPATLPCGHSFCRHCLEALWGARDarrwACPTCRQgAAQQPHLRKNTLLQDLADKYRRaAREIQAGSDP 98
Cdd:COG5432   26 LRCRICDCRISIPCETTCGHTFCSLCIRRHLGTQP----FCPVCRE-DPCESRLRGSSGSREINESHAR-NRDLLRKVLE 99

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 269849639  99 AHCPCPgssslssaaarprrRPE-LQRVAVEKSITEvaQELTELVEHLVDIVRSLQNQRPLSESGpdnelsilgkafssg 177
Cdd:COG5432  100 SLCRLP--------------RPIkEERPCRWETVIA--QDSASGDEEWEDDLASNSSPASIAKKT--------------- 148

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 269849639 178 vdlSMASPKLVTSDTAAGKIRDILHDLEEIQEKLQESVTwkeapeaqmqgeLLEAPSSSSCPLPDQSHPALRRASRF 254
Cdd:COG5432  149 ---SRDSKKRKREDLVHCPACSNLVPHNQINQHLDSCLN------------SPSSPSSSSSPYKNKDNSKSNSLLSF 210

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 269849639 261 PTFNLKSLSCSLEVSKDSRTVTVSHRPQPYRWSCERFSTSQVLCSQALSSGKHYWEVDTRNCSHWAVGVASWEMSR---D 337
Cdd:cd12891    1 LTLDPNTAHNNLALSGDLKTVTCSSENQHYPDSPERFTHSQVLSTQSFSSGRHYWEVEVSESGGWSVGVAYPSIERkgdE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 269849639 338 QVLGRTMDSCCVEWKGtSQLSAWHMVKETVLGSDRPGVVGIWLNLEEGKLAFYSVDNQEKLLYECTISASSPLYPAFWLY 417
Cdd:cd12891   81 SRIGRNDKSWCLEWQD-KSFSAWHNNEETPLPSVSSRRLGVYLDYEAGRLSFYELSDPIRHLHTFTATFTEPLHPAFWVL 159

                        170
                 ....*....|.
gi 269849639 418 GlhpGNYLIIK 428
Cdd:cd12891  160 E---GGWIRIK 167

PRY/SPRY domain in tripartite motif-containing domain 25 (TRIM25); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM25 proteins (composed of RING/B-box/coiled-coil core and also known as RBCC proteins). 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 269849639 262 TFNLKSLSCSLEVSKDSRTVTVSHRPQPYRWSCERFS-TSQVLCSQALSSGKHYWEVDTRNCSHWAVGVASWEMSR---D 337
Cdd:cd13736    2 IFDYNTAHNKVSLSENYTKASVSDDPQNYREHPQRFTyCSQVLGLHCFKQGIHYWEVELQKNNFCGVGICYGSMDRqgpE 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 269849639 338 QVLGRTMDSCCVEWKgTSQLSAWHMVKETVLGSDRPGVVGIWLNLEEGKLAFYSVDNQEKLLYECTISASSPLYPAFWLY 417
Cdd:cd13736   82 SRLGRNSESWCVEWF-NVKISAWHNNVEKTLPSTKATRVGVLLNCDHGFVIFFAVQDKVHLMYKFKVDFTEALYPAFWVF 160

PRY/SPRY domain in tripartite motif-containing proteins 1, 9, 18, 36, 46, 67,76 (TRIM1, TRIM9, TRIM18, TRIM36, TRIM46, TRIM67, TRIM76); 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 TRIM1, TRIM9, TRIM18, TRIM36, TRIM46, TRIM67 and TRIM76. TRIM1 (also known as MID2) and its close homolog, TRIM18 (also known as MID1), both contain a B30.2-like domain at their C-terminus and a single fibronectin type III (FN3) motif between it and their N-terminal RBCC domain. Their coiled-coil motifs mediate both homo- and heterodimerization, a prerequisite for association of the rapamycin-sensitive PP2A regulatory subunit Alpha 4 with microtubules. Mutations in TRIM18 have shown to cause Opitz syndrome, a disorder causing congenital anomalies such as cleft lip and palate as well as heart defects. TRIM9 is expressed mainly in the cerebral cortex, and functions as an E3 ubiquitin ligase. Its immunoreactivity is severely decreased in affected brain areas in Parkinson's disease and dementia with Lewy bodies, possibly playing an important role in the regulation of neuronal function and participating in pathological process of Lewy body disease through its ligase. TRIM36 interacts with centromere protein-H, one of the kinetochore proteins and possibly associates with chromosome segregation; an excess of TRIM36 may cause chromosomal instability. TRIM46 has not yet been characterized. TRIM67 negatively regulates Ras activity via degradation of 80K-H, leading to neural differentiation, including neuritogenesis. TRIM76 (also known as cardiomyopathy-associated protein 5 or CMYA5) is a muscle-specific member of the TRIM superfamily, but lacks the RING domain. It is possibly involved in protein kinase A signaling as well as vesicular trafficking. It has also been implicated in Duchenne muscular dystrophy and cardiac disease. 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 269849639 263 FNL--KSLSCSLEVSKDSRTVTV-SHRPQPYRWSCERFST--SQVLCSQALSSGKHYWEVDTRNCSHWAVGVASWEMSRD 337
Cdd:cd13734    1 FKLdpKTAHRKLRLSNDNLTVEYdPEGSKDQAAVLPRRFTgsPAVLGDVAISSGRHYWEVSVSRSTSYRVGVAYKSAPRD 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 269849639 338 QVLGRTMDSCCVEWKGTSqLSAWHMVKETVLGSDR-PGVVGIWLNLEEGKLAFYSVDNQeKLLYECTISASSPLYPAF 414
Cdd:cd13734   81 EDLGKNSTSWCLSRDNNR-YTARHDGKVVDLRVTGhPARIGVLLDYDNGTLSFYDAESK-QHLYTFHVDFEGPVCPAF 156

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 269849639 272 LEVSKDSRTVTVSHRPQPYRWSCERFST-SQVLCSQALSsGKHYWEVDtRNCSHWAVGVASWEMSR-----DQVLGRTMD 345
Cdd:cd16040   22 LSLSEGNRKVTRVKEEQPYPDHPERFDYwPQVLCREGLS-GRCYWEVE-WSGGGVDIAVAYKGISRkgdgdDSRFGYNDK 99

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 269849639 346 SCCVEWKGTSqLSAWHMVKETVL-----GSDRpgvVGIWLNLEEGKLAFYSVDNQEKLLYecTISA--SSPLYPAFWLY 417
Cdd:cd16040  100 SWSLECSPSG-YSFWHNNKKTEIsvpssSSSR---VGVYLDHSAGTLSFYSVSDTMTLLH--TVQTtfTEPLYPGFGVG 172

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 269849639 262 TFNLKSLSCSLEVSKDSRTVTVSHRPQPYRWSCERFSTS-QVLCSQALSSGKHYWEVDTRNCSHWAVGVASwemsrDQVL 340
Cdd:cd12905    7 TFDPETAHPSLILSRDLTAVTESDEMQPYPRSPKRFLQCvNVLASQGFQSGRHYWEVWVGSKTKWDLGVAS-----ESVD 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 269849639 341 GRTMDSCCVE--------------WKGTsqlSAWhmVKETVlgSDRPGVVGIWLNLEEGKLAFYSVDNQeKLLYECTISA 406
Cdd:cd12905   82 RQARVKLCPEngywtlrlrngdeyWAGT---QPW--TRLRV--TSRPQRIGVFLDCEERKVSFYNADDM-SLLYSFHQGP 153

                 ....*...
gi 269849639 407 SSPLYPAF 414
Cdd:cd12905  154 RGKVFPFF 161

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 269849639   310 SGKHYWEVDTRNCSHWAVGVASWEMSRDQV--LGRTMDSCCVEWKGTSQLSAWHmVKETVLGSDRPG-VVGIWLNLEEGK 386
Cdd:smart00449   1 SGRHYFEVEIGDGGHWRVGVATKSVPRGYFalLGEDKGSWGYDGDGGKKYHNST-GPEYGLPLQEPGdVIGCFLDLEAGT 79

                           90       100       110
                   ....*....|....*....|....*....|..
gi 269849639   387 LAFYSVDNQEKLLYECTISASSPLYPAFWLYG 418
Cdd:smart00449  80 ISFYKNGKYLHGLAFFDVKFSGPLYPAFSLGS 111

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 269849639 238 CPLPDQsHPALRR-ASRFAQWAI------HPtfnlkslscSLEVSKDSRTVTVSHRPQPYRWSCERFSTSQ-VLCSQALS 309
Cdd:cd15829    1 CSFPPQ-YSALQKiIKKFRVDVTldpetaHP---------NLLVSEDKKCVTFTKKKQRVPDSPKRFTVNPvVLGFPGFH 70

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 269849639 310 SGKHYWEVDTRNCSHWAVGVASWEMSRDQVLGRTMDSCC--VEWKGTSqLSAWHMVKETVLGSDRPGVVGIWLNLEEGKL 387
Cdd:cd15829   71 SGRHFWEVEVGDKPEWAVGVCKDSLSTKARRPPSGQQGCwrIQLQGGD-YDAPGAVPPPLLLEVKPRGIGVFLDYELGEI 149

                        170       180
                 ....*....|....*....|....*....
gi 269849639 388 AFYSVdNQEKLLYECTISASSPLYPAFWL 416
Cdd:cd15829  150 SFYNM-PEKSHIHTFTDTFSGPLRPYFYV 177

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 269849639 269 SCSLEVSKDSRTVTVSHRPQPYRWSCERFSTSQ-VLCSQALSSGKHYWEVDTRNCSHWAVGVASWEMSRDqvlGRTmdSC 347
Cdd:cd12888   10 HPRLVLSEDRKSVRWGDTRQDLPDNPERFDTWPcVLGCEGFTSGRHYWEVEVGDGGGWAVGVARESVRRK---GEI--SF 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 269849639 348 CVE--------WKGtsQLSAWHMVKETVLGSDRPGVVGIWLNLEEGKLAFYSVDNQEKLlyeCTISASSP----LYPAFW 415
Cdd:cd12888   85 SPEegiwavgqWGG--QYWALTSPETPLPLSEVPRRIRVYLDYEGGQVAFFDADNEAPI---FTFPPASFagerIFPWFW 159

                 .
gi 269849639 416 L 416
Cdd:cd12888  160 V 160

Fibronectin type III and SPRY containing 1 (FSD1) domain includes PRY at the N-terminus; This domain is part of the fibronectin type III and SPRY domain containing 1 (FSD1) and FSD1-like (FSD1L) proteins. These are centrosome-associated proteins that are characterized by an N-terminal coiled-coil region downstream of B-box (BBC) domain, a central fibronectin type III (FN3) domain, and C-terminal repeats in PRY/SPRY domain. The FSD1 protein associates with a subset of microtubules and may be involved in the stability and organization of microtubules during cytokinesis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 269849639 286 RPQPYRWSCERFSTSQ--VLCSQALSSGKHYWEVD-TRNCSHWAVGVASWEMSRDQVLGRTMDSCCV---EWKGTSqLSA 359
Cdd:cd12901   58 RMPSARGGRDRFTAESytVLGDTLIDGGQHYWEVRaQKDSKAFSVGVAYRSLGKFDQLGKTNASWCLhvnNWLQNS-FAA 136

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 269849639 360 WHMVKETVLGSDRPGVVGIWLNLEEGKLAFYSVDNQEkLLYECTISASSPLYPAF--WLYGLH 420
Cdd:cd12901  137 KHNNKAKTLDVPVPDRIGVYCDFDEGQLSFYNARTKQ-LLHTFKMKFTQPVLPAFmvWCGGLS 198

PRY/SPRY domain in tripartite motif-binding (TRIM) proteins TRIM50 and TRIM72; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of several TRIM proteins, including TRIM72 and TRIM50. TRIM72 (also known as MG53) 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. It is expressed specifically in skeletal muscle and heart, and tethered to the plasma membrane and cytoplasmic vesicles via its interaction with phosphatidylserine. 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 269849639 262 TFNLKSLSCSLEVSKDSRTVTVSHRPQPYRWSCERFSTSQ-VLCSQALSSGKHYWEVDTRNCSHWAVGVASWEMSRDQVL 340
Cdd:cd12897   15 TFDPATAHPLLVVSSGGTVVECGLQKQRRASQPERFDKSTcVVASQGFSEGEHYWEVVVGDKPRWALGVIKGTASRKGKL 94

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 269849639 341 GRTMDS--CCVEWKGTSQLSAWHMVKET-VLGS-DRPGVVGIWLNLEEGKLAFYSVDNQE--KLLYECTISASSPLYPAF 414
Cdd:cd12897   95 HASPSHgvWLIGLKEGKVYEAHGEPKEPrPLRVaGRPHRIGVYLSFEDGVLSFFDASDPDdlRTLYTFQERFQGKLYPFF 174

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 269849639 272 LEVSKDSRTVTVSHRPQPYRWSCERFSTS-QVLCSQALSSGKHYWEVDTRNCSHWAVGVAswemsRDQVLGRTMDSCCVE 350
Cdd:cd15817   13 LIVSEDRKAVRYRRMKPNCPYDPRRFTVYpAVLGSEGFDSGRHFWEVEVGGKGEWILGVC-----KDSLPRNAQDPPSPL 87

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 269849639 351 ---WK---GTSQLSAWHMVKETVLGSDRPGVVGIWLNLEEGKLAFYSVdNQEKLLYECTISASSPLYPAFWL 416
Cdd:cd15817   88 ggcWQigrYMSGYVASGPKTTQLLPVVKPSRIGIFLDYELGEVSFYNM-NDRSHLYTFTDTFTGKLIPYFYV 158

PRY/SPRY domain of tripartite motif-binding protein 60 (TRIM60) also known as RING finger protein 33 (RNF33); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM60, which is also known as RING finger protein 33 (RNF33) or 129 (RNF129). TRIM60 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. Based on its expression profile, RNF33 likely plays an important role in the spermatogenesis process, the development of the pre-implantation embryo, and in testicular functions; Rnf33 is temporally transcribed in the unfertilized egg and the pre-implantation embryo, and is permanently silenced before the blastocyst stage. Mice experiments have shown that RNF33 associates with the cytoplasmic motor proteins, kinesin-2 family members 3A (KIF3A) and 3B (KIF3B), suggesting possible contribution to cargo movement along the microtubule in the expressed sites.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 269849639 262 TFNLKSLSCSLEVSKDSRTVTVSHRPQPYRWSCERFS-TSQVLCSQALSSGKHYWEVDTRNCSHWAVGVASWEMSRD--- 337
Cdd:cd15828   13 TLDPETAHPQLTVSEDRKSVLYGEMKQNVCYNPRRFYlCPAVLGSEGFHSGRQYWEVEVGDKPEWTLGVCQDCLPRNwsn 92

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 269849639 338 QVL--------GRTMDSCCVewkgtsqlsAWHMVKETVLGSDRPGVVGIWLNLEEGKLAFYSVDNQEkLLYECTISASSP 409
Cdd:cd15828   93 QPSvqdglwaiGRYSESNYV---------ALGPKKIQLLPKVRPSKIGIFLDYELGEVSFYNMNDRS-LLYTFSDSFTGT 162

                 ....*
gi 269849639 410 LYPAF 414
Cdd:cd15828  163 LWPYF 167

SPRY domain; SPRY domains, first identified in the SP1A kinase of Dictyostelium and rabbit Ryanodine receptor (hence the name), are homologous to B30.2. SPRY domains have been identified in at least 11 protein families, covering a wide range of functions, including regulation of cytokine signaling (SOCS), RNA metabolism (DDX1 and hnRNP), immunity to retroviruses (TRIM5alpha), intracellular calcium release (ryanodine receptors or RyR) and regulatory and developmental processes (HERC1 and Ash2L). B30.2 also contains residues in the N-terminus that form a distinct PRY domain structure; i.e. B30.2 domain consists of PRY and SPRY subdomains. B30.2 domains comprise the C-terminus of three protein families: BTNs (receptor glycoproteins of immunoglobulin superfamily); several TRIM proteins (composed of RING/B-box/coiled-coil or RBCC core); Stonutoxin (secreted poisonous protein of the stonefish Synanceia horrida). TRIM/RBCC proteins are involved in a variety of processes, including apoptosis, cell cycle regulation, cell growth, senescence, viral response, meiosis, cell differentiation, and vesicular transport. Genes belonging to this family are implicated in several human diseases that vary from cancer to rare genetic syndromes. The PRY-SPRY domain in these TRIM families is suggested to serve as the target binding site. While SPRY domains are evolutionarily ancient, B30.2 domains are a more recent adaptation where the SPRY/PRY combination is a possible component of immune defense. Mutations found in the SPRY-containing proteins have shown to cause Mediterranean fever and Opitz syndrome.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 269849639 311 GKHYWEV--DTRNCSHWAVGVASWEMSRDQ--VLGRTMDSCCVEwkgTSQLSAWHMVKETVLGSD--RPGVVGIWLNLEE 384
Cdd:cd11709    1 GKWYWEVrvDSGNGGLIQVGWATKSFSLDGegGVGDDEESWGYD---GSRLRKGHGGSSGPGGRPwkSGDVVGCLLDLDE 77

                         90       100       110
                 ....*....|....*....|....*....|....
gi 269849639 385 GKLAFYSVDNQEKLLYECTISASSPLYPAFWLYG 418
Cdd:cd11709   78 GTLSFSLNGKDLGVAFTNLFLKGGGLYPAVSLGS 111

PRY/SPRY domain in tripartite motif-containing protein 34 (TRIM34), also known as RING finger protein 21 (RNF21) or interferon-responsive finger protein (IFP1); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM34, also known as RING finger protein 21 (RNF21) or interferon-responsive finger protein (IFP1). TRIM34 domain is composed of RING/B-box/coiled-coil core and also known as RBCC protein. The TRIM21 cDNA possesses at least three kinds of isoforms, due to alternative splicing, of which only the long and medium forms contain the SPRY domain. It is an interferon-induced protein, predominantly expressed in the testis, kidney, and ovary. The SPRY domain provides the capsid recognition motif that dictates specificity to retroviral restriction. While the PRY-SPRY domain 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 269849639 262 TFNLKSLSCSLEVSKDSRTVT-VSHRPqpyrWSCERFStsqVLCSQALSSGKHYWEVDTRNCSHWAVGVASWEMSRDQVL 340
Cdd:cd15825    5 TLNPVNLNLNLVLSEDQRQVTsVPIWP----FKCYNYG---ILGSQYFSSGKHYWEVDVSKKTAWILGVYCRKRSRTFKY 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 269849639 341 GR---TMDSCCVEWK--------GTSQLSAWHMVKETvLGSDrPGV-----------VGIWLNLEEGKLAFYSVDNQEKL 398
Cdd:cd15825   78 VRqgkNHPNVYSRYRpqygywviGLQNKSEYYAFEDS-STSD-PKVltlsvatpphrVGVFLDYEAGTVSFFNVTNHGSL 155

                        170
                 ....*....|....*..
gi 269849639 399 LYE-CTISASSPLYPAF 414
Cdd:cd15825  156 IYKfSKCCFSQPVYPYF 172

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 269849639 261 PTFNLKSLSCSLEVSKDSRTVTVSHrPQPYRWSCER-FSTSQVLCSQALSSGKHYWEVDTRNCSHWAVGVASWEM----- 334
Cdd:cd15810    2 VTLNPVNISLNIVISEDQRQVRIVP-PQTSGQALTNnNYDFGVLGSQYFSSGKHYWEVDVSKKSAWILGVCSHKRsdamt 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 269849639 335 -------------SRDQ------VLGRTMDSCCVEWKGTSQlSAWHMV--KETVLgsdrPGVVGIWLNLEEGKLAFYSVD 393
Cdd:cd15810   81 ksnanqinhqnvySRYQpqygywVIGLQNESEYNAFEDSSS-FNPHVLtlSVTVP----PHRVGVFLDYEAGTVSFFNVT 155

                        170       180
                 ....*....|....*....|....
gi 269849639 394 NQEKLLY---ECtiSASSPLYPAF 414
Cdd:cd15810  156 NHGSLIYkfsKC--CFSTTVCPYF 177

RING finger, HC subclass, found in tripartite motif-containing protein 77 (TRIM77) and similar proteins; TRIM77 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including two consecutive zinc-binding domains, a C3HC4-type RING-HC finger and Bbox2, as well as a SPRY/B30.2 domain positioned C-terminal to the RBCC domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 269849639  16 EDDLGCIICQGLLDWPATLPCGHSFCRHCLEALWGaRDARRWACPTCRQGAAQQP 70
Cdd:cd16543    1 EDQLTCSICLDLLKDPVTIPCGHSFCMNCITLLWD-RKQGVPSCPQCRESFPPRP 54

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 269849639  312 KHYWEV--DTRNCSHWAVGVASWEMSR--DQVLGRTMDSCCVEwkGTSQLSAWH-MVKETVLGSDRPG-VVGIWLNLEEG 385
Cdd:pfam00622   1 RHYFEVeiFGQDGGGWRVGWATKSVPRkgERFLGDESGSWGYD--GWTGKKYWAsTSPLTGLPLFEPGdVIGCFLDYEAG 78

                          90       100       110
                  ....*....|....*....|....*....|...
gi 269849639  386 KLAFYsvDNQEKLLYECTI-SASSPLYPAFWLY 417
Cdd:pfam00622  79 TISFT--KNGKSLGYAFRDvPFAGPLFPAVSLG 109

SPRY domain in Ro-Ret family; This domain, named BSPRY, has been identified in the Ro-Ret family, since the protein is composed of a B-box, an alpha-helical coiled coil and a SPRY domain. The gene for BSPRY resides on human chromosome 9 and is specifically expressed in testis. The function of BSPRY is not known, but several related proteins of the RING-Box-coiled-coil (RBCC) family have been implicated in cell transformation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 269849639 262 TFNLKSLSCSLEVSKDSRTVTVSHRP--QPYRWSCERF-STSQVLCSQALSSGKHYWEVDTRNCSHWAVGVASWEMSR-- 336
Cdd:cd12904    2 RFDERTVSPLLSLSEDRRTLTFSPKKarQSPPDDPERFdHWPNALASLSFSSGTHAWVVDVGKSCAYKVGVCYGSLERkg 81