RING finger, HC subclass, found in tripartite motif-containing protein TRIM50, TRIM73, TRIM74 and similar proteins; TRIM50 is a stomach-specific E3 ubiquitin-protein ligase, encoded by the Williams-Beuren syndrome (WBS) TRIM50 gene, which regulates vesicular trafficking for acid secretion in gastric parietal cells. It colocalizes, interacts with, and increases the level of p62/SQSTM1, a multifunctional adaptor protein implicated in various cellular processes including the autophagy clearance of polyubiquitinated protein aggregates. It also promotes the formation and clearance of aggresome-associated polyubiquitinated proteins through the interaction with histone deacetylase 6 (HDAC6), a tubulin specific deacetylase that regulates microtubule-dependent aggresome formation. TRIM50 can be acetylated by PCAF and p300. TRIM50 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, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. This subfamily also includes two paralogs of TRIM50, tripartite motif-containing protein 73 (TRIM73), also known as tripartite motif-containing protein 50B (TRIM50B), and tripartite motif-containing protein 74 (TRIM74), also known as tripartite motif-containing protein 50C (TRIM50C), both of which are WBS-related genes encoding proteins that may also act as E3 ligases. In contrast with TRIM50, TRIM73 and TRIM74 belong to the C-V subclass of TRIM family of proteins that are defined by N-terminal RBCC domains only.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 568938081  14 LQCPICLEVFKEPLMLQCGHSYCKDCLDNLSQHLDSELCCPVCRQ 58
Cdd:cd16605    1 LLCPICLEVFKEPLMLQCGHSYCKSCLVSLSGELDGQLLCPVCRQ 45

Hemerythrin domain [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568938081 140 ISELKEEHRNVEEHIGKLVNNRTRIINESDVFSWVIR------REFQELHHLVDEEKA--RCLEGLEGHTRGLVASLDMQ 211
Cdd:COG3945    4 TEILRAEHRNIRRLLAVLEKLLDRLEEGEEVDFELLRdildyiREFADRCHHPKEEDIlfPRLEERGGEAAGPIAVLLAE 83

                         90       100       110
                 ....*....|....*....|....*....|..
gi 568938081 212 LEQAQGTQERLAQAEQVLEQFGNESHHEFIRF 243
Cdd:COG3945   84 HEQGRQLTRELEEALEAYLAGDVVARDELAAA 115

RING finger, HC subclass, found in tripartite motif-containing protein TRIM50, TRIM73, TRIM74 and similar proteins; TRIM50 is a stomach-specific E3 ubiquitin-protein ligase, encoded by the Williams-Beuren syndrome (WBS) TRIM50 gene, which regulates vesicular trafficking for acid secretion in gastric parietal cells. It colocalizes, interacts with, and increases the level of p62/SQSTM1, a multifunctional adaptor protein implicated in various cellular processes including the autophagy clearance of polyubiquitinated protein aggregates. It also promotes the formation and clearance of aggresome-associated polyubiquitinated proteins through the interaction with histone deacetylase 6 (HDAC6), a tubulin specific deacetylase that regulates microtubule-dependent aggresome formation. TRIM50 can be acetylated by PCAF and p300. TRIM50 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, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. This subfamily also includes two paralogs of TRIM50, tripartite motif-containing protein 73 (TRIM73), also known as tripartite motif-containing protein 50B (TRIM50B), and tripartite motif-containing protein 74 (TRIM74), also known as tripartite motif-containing protein 50C (TRIM50C), both of which are WBS-related genes encoding proteins that may also act as E3 ligases. In contrast with TRIM50, TRIM73 and TRIM74 belong to the C-V subclass of TRIM family of proteins that are defined by N-terminal RBCC domains only.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 568938081  14 LQCPICLEVFKEPLMLQCGHSYCKDCLDNLSQHLDSELCCPVCRQ 58
Cdd:cd16605    1 LLCPICLEVFKEPLMLQCGHSYCKSCLVSLSGELDGQLLCPVCRQ 45

B-box-type 2 zinc finger found in tripartite motif-containing protein TRIM50, TRIM73, TRIM74 and similar proteins; TRIM50 is a stomach-specific E3 ubiquitin-protein ligase, encoded by the Williams-Beuren syndrome (WBS) TRIM50 gene, which regulates vesicular trafficking for acid secretion in gastric parietal cells. It colocalizes, interacts with, and increases the level of p62/SQSTM1, a multifunctional adaptor protein implicated in various cellular processes including the autophagy clearance of polyubiquitinated protein aggregates. It also promotes the formation and clearance of aggresome-associated polyubiquitinated proteins through the interaction with the histone deacetylase 6 (HDAC6), a tubulin specific deacetylase that regulates microtubule-dependent aggresome formation. TRIM50 can be acetylated by PCAF and p300. TRIM50 belongs 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 B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif. The family also includes two paralogs of TRIM50, tripartite motif-containing protein 73 (TRIM73), also known as tripartite motif-containing protein 50B (TRIM50B), and tripartite motif-containing protein 74 (TRIM74), also known as tripartite motif-containing protein 50C (TRIM50C), both of which are WBS-related genes encoding proteins and may also act as E3 ligases. In contrast with TRIM50, TRIM73 and TRIM74 belong to the C-V subclass of TRIM family of proteins that are defined by the N-terminal RBCC domains only.

                         10        20        30
                 ....*....|....*....|....*....|....*...
gi 568938081  88 VCVHHRNPLSLFCEKDQEFICGLCGLLGSHQHHRVTPV 125
Cdd:cd19787    2 SCPHHHNPLSLFCEKDQEVICGLCGLIGSHRQHKITPV 39

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

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 568938081   16 CPICLEVFKEPlMLQCGHSYCKDCLDNLSQHLDSELCCP 54
Cdd:pfam13445   1 CPICLELFTDP-VLPCGHTFCRECLEEMSQKKGGKFKCP 38

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568938081   9 ELQDQLQCPICLEVFKEPLMLQCGHSYCKDCldnLSQHLDSELCCPVCRQSvDCSSSPPNVSLARVI 75
Cdd:COG5432   21 GLDSMLRCRICDCRISIPCETTCGHTFCSLC---IRRHLGTQPFCPVCRED-PCESRLRGSSGSREI 83

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
                  ....*....|....*....|....*....|....*....|....*....|
gi 568938081   10 LQDQLQCPICLEVFKEPLMLQCGHSYCKDCldnLSQHLDSELCCPVCRQS 59
Cdd:TIGR00599  23 LDTSLRCHICKDFFDVPVLTSCSHTFCSLC---IRRCLSNQPKCPLCRAE 69

Hemerythrin domain [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568938081 140 ISELKEEHRNVEEHIGKLVNNRTRIINESDVFSWVIR------REFQELHHLVDEEKA--RCLEGLEGHTRGLVASLDMQ 211
Cdd:COG3945    4 TEILRAEHRNIRRLLAVLEKLLDRLEEGEEVDFELLRdildyiREFADRCHHPKEEDIlfPRLEERGGEAAGPIAVLLAE 83

                         90       100       110
                 ....*....|....*....|....*....|..
gi 568938081 212 LEQAQGTQERLAQAEQVLEQFGNESHHEFIRF 243
Cdd:COG3945   84 HEQGRQLTRELEEALEAYLAGDVVARDELAAA 115

coiled-coil (CC) domain of Drosophila brain tumor (brat) and similar proteins; This family contains the coiled-coil (CC) region of Drosophila brain tumor (Brat), a translational repressor that belongs to the tripartite motif (TRIM) protein superfamily. TRIM proteins play important roles in various cellular processes and are involved in many diseases which consists of two B-box domains and a coiled-coil (CC) domain at the N-terminal region, and an NHL domain at the C-terminus. Brat localizes at the basal cortex during asymmetric division of Drosophila neuroblasts by directly interacting with the scaffolding protein Miranda (Mira), which it does through the CC-NHL domain tandem, indicating that the function of the Brat CC domain is to assemble Brat-NHL in dimeric form which is necessary for Mira binding. Brat CC forms an elongated antiparallel dimer similar to its other TRIM protein counterparts, but the overall length of Brat CC dimer is shorter than the TRIMs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568938081 131 RMKEELAGRISELKEEHRNVEEHIGKLVNNRTRIINEsdvfswvIRREFQELHHLVDEEKARCLEGLEG-HTRGLVaSLD 209
Cdd:cd20482    7 QLLEEARAKIPELRDALKNVEHALSRLQMQYHKAQNE-------INETFQFYRSMLEERKDELLKELESiYNAKQL-SLN 78

                         90       100       110
                 ....*....|....*....|....*....|.
gi 568938081 210 MQLEQAQGTQERLAQA----EQVLeQFGNES 236
Cdd:cd20482   79 EQQQKLQETIEKIQQGceftERLL-KHGSET 108

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 568938081 282 KRLFRKVLPAPASLKLDPATAHPLLELSKGNTVVHCGLLAQRRASQPERFDYSTCVLASKGFSWGRHYWEVVVGSKSDWR 361
Cdd:cd12897    1 RKMFRALMPALESLTFDPATAHPLLVVSSGGTVVECGLQKQRRASQPERFDKSTCVVASQGFSEGEHYWEVVVGDKPRWA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568938081 362 LGVIKGTASRKGKLNKSPEHGVWLIGLKEGRVYEAFGCPR--LPLPVAGHPHRIGVYLHYEQGELTFFDADRPDDLRTLY 439
Cdd:cd12897   81 LGVIKGTASRKGKLHASPSHGVWLIGLKEGKVYEAHGEPKepRPLRVAGRPHRIGVYLSFEDGVLSFFDASDPDDLRTLY 160

                        170       180       190
                 ....*....|....*....|....*....|.
gi 568938081 440 TFQADFQGKLYPILDTCWHERGSNSLPMVLP 470
Cdd:cd12897  161 TFQERFQGKLYPFFDVCWHDKGKNSQPLVLP 191

PRY/SPRY domain in tripartite motif-binding protein 72 (TRIM72); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM72. Muscle-specific TRIM72 (also known as Mitsugumin 53 or 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. TRIM72 interacts with dysferlin, a sarcolemmal protein whose deficiency causes Miyoshi myopathy (MM) and limb girdle muscular dystrophy type 2B (LGMD2B); this coordination plays an important role in the repair of sarcolemma damage.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568938081 282 KRLFRKVLPAPASLKLDPATAHPLLELSKGNTVVHCGLLAQRRAS-QPERFDYSTCVLASKGFSWGRHYWEVVVGSKSDW 360
Cdd:cd13742    1 RKMFRALMPALENLTFDPDTAHPYLVVSSDGKRVECADQKQAVSSdDPNRFDKANCVVSHQSFSEGEHYWEVIVGDKPRW 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568938081 361 RLGVIKGTASRKGKLNKSPEHGVWLIGLKEGRVYEAFGCPRLP--LPVAGHPHRIGVYLHYEQGELTFFDADRPDDLRTL 438
Cdd:cd13742   81 ALGVISAEAGRKGRLHALPSNGFWLLGCKEGKVYEAHVEHKEPraLRVEGRPTRIGVYLSFSDGVLSFYDASDEDNLVQL 160

                        170       180       190
                 ....*....|....*....|....*....|.
gi 568938081 439 YTFQADFQGKLYPILDTCWHERGSNSLPMVL 469
Cdd:cd13742  161 FAFHERFPGPLYPFFDVCWHDKGKNSQPLKI 191

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 568938081 281 WKRLFRKVLPAPASLKLDPATAHPLLELSKGNTVVHCGLLAQRRASQPERFDYSTCVLASKGFSWGRHYWEVVVGSKSDW 360
Cdd:cd15818    1 WKEMKSILNPGLSLITLDPKTAHPNLILSEDLTCVWHGDTKQMLPDNPERFDSSVAVLGSEGFTSGKHYWEVEVAKKTKW 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568938081 361 RLGVIKGTASRKGKLNKSPEHGVWLIGLKEGRVYEAFGCPRLPLPVAGHPHRIGVYLHYEQGELTFFDAdrpDDLRTLYT 440
Cdd:cd15818   81 TLGVVRESINRKGNCPLSPEDGFWLLRLRNQNELKALDVPSFSLTLTSNLNKVGIYLDYEGGQVSFYNA---NTMSHIYT 157

                        170       180
                 ....*....|....*....|....*..
gi 568938081 441 FQADFQGKLYPILDTCWHERGSNSLPM 467
Cdd:cd15818  158 FSDTFTEKIYPYFCPCLNDSGENKEPL 184

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 568938081 297 LDPATAHPLLELSKGNTVVHCGLLAQRRASQPERFDYSTCVLASKGFSWGRHYWEVVVGSKSDWRLGVIKGTASRKGKLN 376
Cdd:cd12888    4 LDPDTAHPRLVLSEDRKSVRWGDTRQDLPDNPERFDTWPCVLGCEGFTSGRHYWEVEVGDGGGWAVGVARESVRRKGEIS 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568938081 377 KSPEHGVWLIGLKEGRvYEAFGCPRLPLPVAGHPHRIGVYLHYEQGELTFFDAdrpDDLRTLYTFQ-ADFQG-KLYPILd 454
Cdd:cd12888   84 FSPEEGIWAVGQWGGQ-YWALTSPETPLPLSEVPRRIRVYLDYEGGQVAFFDA---DNEAPIFTFPpASFAGeRIFPWF- 158

                 ....*...
gi 568938081 455 tcWHERGS 462
Cdd:cd12888  159 --WVGKGS 164

PRY/SPRY domain in tripartite motif-containing protein 35 (TRIM35); This PRY/SPRY domain is found at the C-terminus of the overall domain architecture of tripartite motif 35, TRIM35 (also known as hemopoietic lineage switch protein), which includes a RING finger domain (RING) and a B-box motif (BBOX). TRIM35 may play a role as a tumor suppressor and is implicated in the cell death mechanism.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568938081 297 LDPATAHPLLELSKGNTVVHCGLLAQRRASQPERFDYSTCVLASKGFSWGRHYWEVVVGSKSDWRLGVIKGTASRKGKLN 376
Cdd:cd12893    4 LDPNTAHPWLSLSEDLTSVRYSSEKQQLPDNPERFDPYPCVLGSEGFTSGKHSWDVEVGDNTSWMLGVAKESVQRKGKFT 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568938081 377 KSPEHGVWLIGLKEGrVYEAFGC--PRLPLPVAGHPHRIGVYLHYEQGELTFFDadrPDDLRTLYTFQADFQGKLYPILD 454
Cdd:cd12893   84 LSPESGFWTIGFSEG-KYSARTSpePRTPLRVKQKPQRIRVQLDWDRGKVSFSD---PDTNTHIHTFTHTFTERVFPYFY 159

                        170
                 ....*....|....*..
gi 568938081 455 TcwherGSNSLPM-VLP 470
Cdd:cd12893  160 T-----GCKSEPLrILP 171

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 568938081 293 ASLKLDPATAHPLLELSKGNTVVHCGLLAQRRASQPERFDYSTCVLASKGFSWGRHYWEVVVGSKSDWRLGVIKGTASRK 372
Cdd:cd15819    2 VNVTLDPDTAHPALILSEDGRSVTWGETRQDLPENPERFDSLPCVLGQEGFTSGRHYWEVEVGDRTSWDLGVCRDNVMRK 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568938081 373 GKLNKSPEHGVWLIGLKEGRvYEAFGCPRLPLPVAGHPHRIGVYLHYEQGELTFFD-ADRPDdlrtLYTF-QADFQGKLY 450
Cdd:cd15819   82 GRVTLSPENGFWAIRLYGNE-YWALTSPETPLTLKEPPRRVGIFLDYEAGDVSFYNmTDGSH----IYTFpQTAFSGPLR 156

                        170
                 ....*....|..
gi 568938081 451 PILDTCWHERGS 462
Cdd:cd15819  157 PFFRLWSSDSGP 168

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 568938081 293 ASLKLDPATAHPLLELSKGNTVVHCGLLAQRRASQPERFDYSTCVLASKGFSWGRHYWEVVVGSKSDWRLGVIKGTASRK 372
Cdd:cd15813    9 VNVTLDPETAHPNLIFSDDLKSVRLGNKWDRLPDNPERFDSCIIVLGSPSFTSGRHYWEVEVGDKTGWILGVCKASVSRK 88

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568938081 373 GKLNKSPEHGVWLIGLKEGRVYEAFGCPRLPLPVAGHPHRIGVYLHYEQGELTFFDADRPDDlrtLYTFQADF-QGKLYP 451
Cdd:cd15813   89 GSMTLSPENGYWVVMMTKRNEYQASTSPPTRLWLREPPRRVGIFLDYEAGDISFYNVTAKSH---IYTFTSFSsSGPLQP 165

                        170
                 ....*....|....*...
gi 568938081 452 ILDTCWHERGSNSLPMVL 469
Cdd:cd15813  166 IFSPGTHDGGKNMDPLTI 183

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 568938081 295 LKLDPATAHPLLELSKGNTVVHCGLLAQRRASQPERFDYSTCVLASKGFSWGRHYWEVVVGSKSDWRLGVIKGTASRKGK 374
Cdd:cd13740    2 LTLDPDSANPRLILSLDLKSVRLGERAQDLPNHPCRFDTNTRVLASCGFSSGRHHWEVEVGSKDGWAFGVARESVRRKGL 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568938081 375 LNKSPEHGVWLIGLKEGRVYEAFGCPRLPLPVaGHPHRIGVYLHYEQGELTFFDAdrpDDLRTLYTFQADFQGKLYPILD 454
Cdd:cd13740   82 TPFTPEEGVWALQLNGGQYWAVTSPERTPLSC-GHLSRVRVALDLEVGAVSFYAA---EDMRHIYTFRVNFQERVFPLFS 157

                 ..
gi 568938081 455 TC 456
Cdd:cd13740  158 VC 159

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 568938081 297 LDPATAHPLLELSKGNTVVHCGLLAQRRASQPERFDYSTCVLASKGFSWGRHYWEVVVGSKSDWRLGVIKGTASRKGKLN 376
Cdd:cd15828   14 LDPETAHPQLTVSEDRKSVLYGEMKQNVCYNPRRFYLCPAVLGSEGFHSGRQYWEVEVGDKPEWTLGVCQDCLPRNWSNQ 93

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568938081 377 KSPEHGVWLIGLKEGRVYEAFGCPRLP-LPVAgHPHRIGVYLHYEQGELTFFDAdrpDDLRTLYTFQADFQGKLYPILDT 455
Cdd:cd15828   94 PSVQDGLWAIGRYSESNYVALGPKKIQlLPKV-RPSKIGIFLDYELGEVSFYNM---NDRSLLYTFSDSFTGTLWPYFYT 169

                        170
                 ....*....|..
gi 568938081 456 cwherGSNSLPM 467
Cdd:cd15828  170 -----GTDSEPL 176

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 568938081 296 KLDPATAHPLLELSKGNTVVHC--GLLAQRRASQPERFDYSTCVLASKGFSWGRHYWEVVVGSKSDWRLGVIKGTASRK- 372
Cdd:cd13734    2 KLDPKTAHRKLRLSNDNLTVEYdpEGSKDQAAVLPRRFTGSPAVLGDVAISSGRHYWEVSVSRSTSYRVGVAYKSAPRDe 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568938081 373 --GKLNKSpehgvWLIGLKEGRvYEAFGCPRL-PLPVAGHPHRIGVYLHYEQGELTFFDAdrpDDLRTLYTFQADFQGKL 449
Cdd:cd13734   82 dlGKNSTS-----WCLSRDNNR-YTARHDGKVvDLRVTGHPARIGVLLDYDNGTLSFYDA---ESKQHLYTFHVDFEGPV 152

                 ..
gi 568938081 450 YP 451
Cdd:cd13734  153 CP 154

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 568938081 294 SLKLDPATAHPLLELSKGNTVVHCGLLAQRRASQPERFDYSTCVLASKGFSWGRHYWEVVV--GSKSDWRLGVIKGTASR 371
Cdd:cd15826    1 SVTLDPQTASGSLVLSEDRKSVRYTRQKQNLPDSPLRFDGLPAVLGSPGFSSGRHRWQVEVqlGDGGGCTVGVAGESVRR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568938081 372 KGKLNKSPEHGVWLIGLKEGRVYeAFGCPRLPLPVAGHPHRIGVYLHYEQGELTFFDADRPDdlrTLYTFQADFQGKLYP 451
Cdd:cd15826   81 KGEMGLSAEDGVWAVILSHQQCW-ASTSPGTDLPLSEIPRRVGVALDYEAGTVTLTNAETQE---PIFTFTASFSGKVFP 156

                 ....*.
gi 568938081 452 ILDTCW 457
Cdd:cd15826  157 FFAVWK 162

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 568938081 293 ASLKLDPATAHPLLELSKGNTVVHCGLLAQRRASQPERFDYSTCVLASKGFSWGRHYWEVVVGSKSDWRLGVIKGTASRK 372
Cdd:cd15815   13 VSVTLDPDTAHPELTLSKDQRQVTYGRCQENLDASPKRFTVLPCVLGCEGFTSGRHYFEVDVGEGTGWDVGVCLENVQRG 92

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568938081 373 GKLNKSPEHGVWLIGLKEGRVYEAFGCPRLPLPVAGHPHRIGVYLHYEQGELTFFDADRPDDlrtLYTF-QADFQGKLYP 451
Cdd:cd15815   93 FGMKQEPEFGFWTIRLCEEDGYVALTSPPTPLPLREKPLVVGVFLDYEAGLVSFYNMTTGSH---IFTFpKASFSDTLRP 169

                        170
                 ....*....|....*....
gi 568938081 452 ILDTCWHErgsnslPMVLP 470
Cdd:cd15815  170 YFQVYQYS------PLFLP 182

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 568938081 295 LKLDPATAHPLLELSKGNTVVHCGLLAQRRASQPERFDYSTCVLASKGFSWGRHYWEVVVGSKSDWRLGVIKGTASRKGK 374
Cdd:cd15817    2 LILDPETAHPNLIVSEDRKAVRYRRMKPNCPYDPRRFTVYPAVLGSEGFDSGRHFWEVEVGGKGEWILGVCKDSLPRNAQ 81

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568938081 375 LNKSPEHGVWLIGLKEGRvYEAFGCPRLPLPVAGHPHRIGVYLHYEQGELTFFD-ADRpddlRTLYTFQADFQGKLYP 451
Cdd:cd15817   82 DPPSPLGGCWQIGRYMSG-YVASGPKTTQLLPVVKPSRIGIFLDYELGEVSFYNmNDR----SHLYTFTDTFTGKLIP 154