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 1331802279 276 CSFPPQYSALQRIIKKFKVEIILDPETAHPNLIVSEDKKRVRFTKRKQKVPGFPKRFTVKPVVLGFPYFHSGRHFWEIEV 355
Cdd:cd15829     1 CSFPPQYSALQKIIKKFRVDVTLDPETAHPNLLVSEDKKCVTFTKKKQRVPDSPKRFTVNPVVLGFPGFHSGRHFWEVEV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331802279 356 GDKSEWAIGICKDSLPTKARRPSSAQQECWRIELQDDGYHAPGAFPTPLLLEVKARAIGIFLDYEMGEISFYNMAEKSHI 435
Cdd:cd15829    81 GDKPEWAVGVCKDSLSTKARRPPSGQQGCWRIQLQGGDYDAPGAVPPPLLLEVKPRGIGVFLDYELGEISFYNMPEKSHI 160

                         170       180
                  ....*....|....*....|....*..
gi 1331802279 436 CTFSDTFTGPLRPYFYVGPDSQPLRIC 462
Cdd:cd15829   161 HTFTDTFSGPLRPYFYVGPDSKPLRIC 187

B-box-type 2 zinc finger found in tripartite motif-containing proteins, TRIM60, TRIM61, TRIM75 and similar proteins; This family includes a group of tripartite motif-containing proteins, including TRIM60, TRIM61 and TRIM75. TRIM60, also known as RING finger protein 129 (RNF129) or RING finger protein 33 (RNF33), is a cytoplasmic protein expressed in the testis. It may play an important role in the spermatogenesis process, the development of the preimplantation embryo, and in testicular functions. TRIM60 interacts with the cytoplasmic kinesin motor proteins KIF3A and KIF3B suggesting possible contribution to cargo movement along the microtubule in the expressed sites. It is also involved in spermatogenesis in Sertoli cells under the regulation of nuclear factor-kappaB (NF-kappaB). TRIM61 is closely related to TRIM60, but its biological function remains unclear. TRIM75 could be the product of a pseudogene. Its biological function remains unclear. TRIM60 and TRIM75 belong 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 RING finger, Bbox2, and two coiled coil domains, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. In contrast, TRIM61 belongs to the C-V subclass of TRIM family that contains RBCC domains only. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1331802279  95 TLCEKHNQPLSVFCKEDLMVLCPLCTQPPDHQGHHVRPI 133
Cdd:cd19791     1 TLCEKHNQPLTKFCKKDLEPLCPQCSQSTDHQHHVVVPL 39

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 1331802279 276 CSFPPQYSALQRIIKKFKVEIILDPETAHPNLIVSEDKKRVRFTKRKQKVPGFPKRFTVKPVVLGFPYFHSGRHFWEIEV 355
Cdd:cd15829     1 CSFPPQYSALQKIIKKFRVDVTLDPETAHPNLLVSEDKKCVTFTKKKQRVPDSPKRFTVNPVVLGFPGFHSGRHFWEVEV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331802279 356 GDKSEWAIGICKDSLPTKARRPSSAQQECWRIELQDDGYHAPGAFPTPLLLEVKARAIGIFLDYEMGEISFYNMAEKSHI 435
Cdd:cd15829    81 GDKPEWAVGVCKDSLSTKARRPPSGQQGCWRIQLQGGDYDAPGAVPPPLLLEVKPRGIGVFLDYELGEISFYNMPEKSHI 160

                         170       180
                  ....*....|....*....|....*..
gi 1331802279 436 CTFSDTFTGPLRPYFYVGPDSQPLRIC 462
Cdd:cd15829   161 HTFTDTFSGPLRPYFYVGPDSKPLRIC 187

RING finger, HC subclass, found in tripartite motif-containing proteins TRIM60, TRIM61, TRIM75 and similar proteins; TRIM60, also known as RING finger protein 129 (RNF129) or RING finger protein 33 (RNF33), is a cytoplasmic protein expressed in the testis. It may play an important role in the spermatogenesis process, the development of the preimplantation embryo, and in testicular functions. RNF33 interacts with the cytoplasmic kinesin motor proteins KIF3A and KIF3B suggesting possible contribution to cargo movement along the microtubule in the expressed sites. It is also involved in spermatogenesis in Sertoli cells under the regulation of nuclear factor-kappaB (NF-kappaB). TRIM75 mainly localizes within spindles, suggesting it may function in spindle organization and thereby affect meiosis. Both TRIM60 and TRIM75 belong 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 B2-box, and two coiled coil domains, as well as a PRY domain and a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. In contrast, TRIM61 belongs to the C-V subclass of the TRIM family that contains RBCC domains only. Its biological function remains unclear.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1331802279  13 EAKCSICLDYLSDPVTIECGHNFCRSCIQQSWLDLQELFPCPVCRHQC 60
Cdd:cd16607     1 EASCPICLDYLKDPVTINCGHNFCRSCISMSWKDLQDTFPCPVCRFCC 48

B-box-type 2 zinc finger found in tripartite motif-containing proteins, TRIM60, TRIM61, TRIM75 and similar proteins; This family includes a group of tripartite motif-containing proteins, including TRIM60, TRIM61 and TRIM75. TRIM60, also known as RING finger protein 129 (RNF129) or RING finger protein 33 (RNF33), is a cytoplasmic protein expressed in the testis. It may play an important role in the spermatogenesis process, the development of the preimplantation embryo, and in testicular functions. TRIM60 interacts with the cytoplasmic kinesin motor proteins KIF3A and KIF3B suggesting possible contribution to cargo movement along the microtubule in the expressed sites. It is also involved in spermatogenesis in Sertoli cells under the regulation of nuclear factor-kappaB (NF-kappaB). TRIM61 is closely related to TRIM60, but its biological function remains unclear. TRIM75 could be the product of a pseudogene. Its biological function remains unclear. TRIM60 and TRIM75 belong 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 RING finger, Bbox2, and two coiled coil domains, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. In contrast, TRIM61 belongs to the C-V subclass of TRIM family that contains RBCC domains only. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1331802279  95 TLCEKHNQPLSVFCKEDLMVLCPLCTQPPDHQGHHVRPI 133
Cdd:cd19791     1 TLCEKHNQPLTKFCKKDLEPLCPQCSQSTDHQHHVVVPL 39

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331802279   5 AALTGLQAEAKCSICLDYLSDPVTIECGHNFCRSCIQQSwldLQELFPCPVCRHQCQEGHFRSNTQLGRMIEIAKLLQST 84
Cdd:TIGR00599  18 PSLYPLDTSLRCHICKDFFDVPVLTSCSHTFCSLCIRRC---LSNQPKCPLCRAEDQESKLRSNWLVSEIVESFKNLRPS 94

                          90
                  ....*....|....*....
gi 1331802279  85 KSNKRKQEETTLCEKHNQP 103
Cdd:TIGR00599  95 LLEFLRIPKTTPVENPDLA 113

Ring finger; E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of c-Cbl and is likely to be a general function of this domain; Various RING fingers exhibit binding activity towards E2 ubiquitin-conjugating enzymes (Ubc' s)

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1331802279   16 CSICLD-YLSDPVTIECGHNFCRSCIQQSWldLQELFPCPVC 56
Cdd:smart00184   1 CPICLEeYLKDPVILPCGHTFCRSCIRKWL--ESGNNTCPIC 40

B-Box-type zinc finger;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1331802279   92 EETTLCEKH-NQPLSVFCKEDLMVLCPLCTQpPDHQGHHVRPI 133
Cdd:smart00336   1 QRAPKCDSHgDEPAEFFCEECGALLCRTCDE-AEHRGHTVVLL 42

reticulocyte binding/rhoptry protein; This model represents a group of paralogous families in plasmodium species alternately annotated as reticulocyte binding protein, 235-kDa family protein and rhoptry protein. Rhoptry protein is localized on the cell surface and is extremely large (although apparently lacking in repeat structure) and is important for the process of invasion of the RBCs by the parasite. These proteins are found in P. falciparum, P. vivax and P. yoelii.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331802279  152 KKQLADLQKLISTQSKKpleLREM-----------VENQRQELSSEFEHLNQFLDREQQAVLSRLAEEEKDNQQKLSANI 220
Cdd:TIGR01612  695 KAKLDDLKSKIDKEYDK---IQNMetatvelhlsnIENKKNELLDIIVEIKKHIHGEINKDLNKILEDFKNKEKELSNKI 771

                           90       100
                   ....*....|....*....|
gi 1331802279  221 TAFSNYSATL---KSQLSKV 237
Cdd:TIGR01612  772 NDYAKEKDELnkyKSKISEI 791

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 1331802279 276 CSFPPQYSALQRIIKKFKVEIILDPETAHPNLIVSEDKKRVRFTKRKQKVPGFPKRFTVKPVVLGFPYFHSGRHFWEIEV 355
Cdd:cd15829     1 CSFPPQYSALQKIIKKFRVDVTLDPETAHPNLLVSEDKKCVTFTKKKQRVPDSPKRFTVNPVVLGFPGFHSGRHFWEVEV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331802279 356 GDKSEWAIGICKDSLPTKARRPSSAQQECWRIELQDDGYHAPGAFPTPLLLEVKARAIGIFLDYEMGEISFYNMAEKSHI 435
Cdd:cd15829    81 GDKPEWAVGVCKDSLSTKARRPPSGQQGCWRIQLQGGDYDAPGAVPPPLLLEVKPRGIGVFLDYELGEISFYNMPEKSHI 160

                         170       180
                  ....*....|....*....|....*..
gi 1331802279 436 CTFSDTFTGPLRPYFYVGPDSQPLRIC 462
Cdd:cd15829   161 HTFTDTFSGPLRPYFYVGPDSKPLRIC 187

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 1331802279 285 LQRIIKKFKVEIILDPETAHPNLIVSEDKKRVRFTKRKQKVPGFPKRFTVKPVVLGFPYFHSGRHFWEIEVGDKSEWAIG 364
Cdd:cd15828     1 LDRIIKRFQVDVTLDPETAHPQLTVSEDRKSVLYGEMKQNVCYNPRRFYLCPAVLGSEGFHSGRQYWEVEVGDKPEWTLG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331802279 365 ICKDSLPTKARRPSSAQQECWRIEL-QDDGYHAPGAFPTPLLLEVKARAIGIFLDYEMGEISFYNMAEKSHICTFSDTFT 443
Cdd:cd15828    81 VCQDCLPRNWSNQPSVQDGLWAIGRySESNYVALGPKKIQLLPKVRPSKIGIFLDYELGEVSFYNMNDRSLLYTFSDSFT 160

                         170       180
                  ....*....|....*....|
gi 1331802279 444 GPLRPYFYVGPDSQPLRICT 463
Cdd:cd15828   161 GTLWPYFYTGTDSEPLKICT 180

PRY/SPRY domain in tripartite motif-containing (TRIM) proteins, including TRIM5, TRIM6, TRIM7, TRIM10, TRIM11, TRIM17, TRIM20, TRIM21, TRIM27, TRIM35, TRIM38, TRIM41, TRIM50, TRIM58, TRIM60, TRIM62, TRIM69, TRIM72, NF7 and bloodthirsty; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of several Class IV TRIM proteins, including TRIM7, TRIM35, TRIM41, TRIM50, TRIM62, TRIM69, TRIM72, TRIM protein NF7 and bloodthirsty (bty). TRIM7 interacts with glycogenin and stimulates its self-glucosylating activity via its SPRY domain. TRIM35 may play a role as a tumor suppressor and is implicated in the cell death mechanism. TRIM41 is localized to speckles in the cytoplasm and nucleus, and functions as an E3 ligase that catalyzes the ubiquitin-mediated degradation of protein kinase C. TRIM50, an E3 ubiquitin ligase, is deleted in Williams-Beuren (WBS) syndrome, a multi-system neurodevelopmental disorder caused by the deletion of contiguous genes at chromosome region 7q11.23. TRIM62 is involved in the morphogenesis of the mammary gland; loss of TRIM62 gene expression in breast is associated with increased risk of recurrence in early-onset breast cancer. TRIM69 is a novel testis E3 ubiquitin ligase that may function to ubiquitinate its particular substrates during spermatogenesis. In humans, TRIM69 localizes in the cytoplasm and nucleus, and requires an intact RING finger domain to function. TRIM protein NF7, which also contains a chromodomain (CHD) at the N-terminus and an RFP (Ret finger protein)-like domain at the C-terminus, is required for its association with transcriptional units of RNA polymerase II which is mediated by a trimeric B box. In Xenopus oocyte, xNF7 has been identified as a nuclear microtubule-associated protein (MAP) whose microtubule-bundling activity, but not E3-ligase activity, contributes to microtubule organization and spindle integrity. Bloodthirsty (bty) is a novel gene identified in zebrafish and has been shown to likely play a role in in regulation of the terminal steps of erythropoiesis. TRIM72 has been shown to perform a critical function in membrane repair following acute muscle injury by nucleating the assembly of the repair machinery at injury sites. The PRY-SPRY domain in these TRIM families is suggested to serve as the target binding site.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331802279 295 EIILDPETAHPNLIVSEDKKRVRFTKRKQKVPGFPKRFTVKPVVLGFPYFHSGRHFWEIEVGDKSEWAIGICKDSLPTKA 374
Cdd:cd13733     1 DVTLDPDTAHPNLILSEDLKSVRYGDKRQNLPDNPERFDTCVCVLGSEGFSSGRHYWEVEVGGKTDWDLGVARESVNRKG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331802279 375 RRPSSAQQECWRIELQD-DGYHAPGAFPTPLLLEVKARAIGIFLDYEMGEISFYNMAEKSHICTFSDTFTGPLRPYFYV- 452
Cdd:cd13733    81 KITLSPENGYWTVGLRNgNEYKALTSPSTPLSLREKPQKVGVFLDYEEGQVSFYNVDDGSHIYTFTDCFTEKLYPYFSPc 160

                         170
                  ....*....|....
gi 1331802279 453 ----GPDSQPLRIC 462
Cdd:cd13733   161 lndgGKNSAPLIIC 174

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 1331802279 287 RIIKKFKVEIILDPETAHPNLIVSEDKKRVRFTKRKQKVPGFPKRFTVKPVVLGFPYFHSGRHFWEIEVGDKSEWAIGIC 366
Cdd:cd15813     2 RAAQAHAVNVTLDPETAHPNLIFSDDLKSVRLGNKWDRLPDNPERFDSCIIVLGSPSFTSGRHYWEVEVGDKTGWILGVC 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331802279 367 KDSLPTKARRPSSAQQECWRIEL-QDDGYHAPGAFPTPLLLEVKARAIGIFLDYEMGEISFYNMAEKSHICTFSDTF-TG 444
Cdd:cd15813    82 KASVSRKGSMTLSPENGYWVVMMtKRNEYQASTSPPTRLWLREPPRRVGIFLDYEAGDISFYNVTAKSHIYTFTSFSsSG 161

                         170       180
                  ....*....|....*....|...
gi 1331802279 445 PLRPYFYV-----GPDSQPLRIC 462
Cdd:cd15813   162 PLQPIFSPgthdgGKNMDPLTIC 184

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 1331802279 295 EIILDPETAHPNLIVSEDKKRVRFTKRKQKVPGFPKRFTVKPVVLGFPYFHSGRHFWEIEVGDKSEWAIGICKDSLPTKA 374
Cdd:cd15816     1 DVKLDPATAHPSLLLTADLRSVQDGELWRDVPGNPERFDTWPCVLGLQSFSSGRHYWEVAVGEKAEWGLGVCQDSAPRKG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331802279 375 RRPSSAQQECWRI-ELQDDGYHAPGAFPTPLLLEVKARAIGIFLDYEMGEISFYNMAEKSHICTFSDTFTGPLRPYFYVG 453
Cdd:cd15816    81 ETTPSPENGVWAVwLLKGNEYMVLASPSVPLLQLRRPRRVGVFLDYEAGEISFYNVTAGSHIYTFRQLFSGILRPYFFVC 160

                  ....*.
gi 1331802279 454 pDSQPL 459
Cdd:cd15816   161 -DTTPL 165

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 1331802279 295 EIILDPETAHPNLIVSEDKKRVRFTKRKQKVPGFPKRFTVKPVVLGFPYFHSGRHFWEIEVGDKSEWAIGICKDSLPTKA 374
Cdd:cd12888     1 NVTLDPDTAHPRLVLSEDRKSVRWGDTRQDLPDNPERFDTWPCVLGCEGFTSGRHYWEVEVGDGGGWAVGVARESVRRKG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331802279 375 RRPSSAQQECWRIELQDDGYHAPGAFPTPLLLEVKARAIGIFLDYEMGEISFYNMAEKSHICTFSDTF--TGPLRPYFYV 452
Cdd:cd12888    81 EISFSPEEGIWAVGQWGGQYWALTSPETPLPLSEVPRRIRVYLDYEGGQVAFFDADNEAPIFTFPPASfaGERIFPWFWV 160

                         170
                  ....*....|
gi 1331802279 453 GPDSQpLRIC 462
Cdd:cd12888   161 GKGSQ-LKLC 169

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 1331802279 282 YSALQRIIKKFKVEIILDPETAHPNLIVSEDKKRVRFTKRKQKVPGFPKRFTVKPVVLGFPYFHSGRHFWEIEVGDKSEW 361
Cdd:cd15815     1 YFDVKKMLRRHQVSVTLDPDTAHPELTLSKDQRQVTYGRCQENLDASPKRFTVLPCVLGCEGFTSGRHYFEVDVGEGTGW 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331802279 362 AIGICKDSLPTKARRPSSAQQECWRIEL-QDDGYHAPGAFPTPLLLEVKARAIGIFLDYEMGEISFYNMAEKSHICTFSD 440
Cdd:cd15815    81 DVGVCLENVQRGFGMKQEPEFGFWTIRLcEEDGYVALTSPPTPLPLREKPLVVGVFLDYEAGLVSFYNMTTGSHIFTFPK 160

                         170       180
                  ....*....|....*....|
gi 1331802279 441 -TFTGPLRPYFYVGPDSqPL 459
Cdd:cd15815   161 aSFSDTLRPYFQVYQYS-PL 179

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331802279 292 FKVEIILDPETAHPNLIVSEDKKRVRFTKRKQKVPGFPKRFTVKPVVLGFPYFHSGRHFWEIEVGDKSEWAIGICKDSLP 371
Cdd:cd12900     1 HMVHITLDPDTANPWLILSKDRRQVRLGDTHQNVPENEERFDNYPMVLGAQRFNSGKHYWEVDVTGKEAWDLGVCRDSVR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331802279 372 TKARRPSSAQQECWRIELQDDGYHApGAFP-TPLLLEVKARAIGIFLDYEMGEISFYNMAE-KSHICTFSD-TFTGPLRP 448
Cdd:cd12900    81 RKGQFLLSPENGFWTIWLWNKKYEA-GTSPqTTLHLQVPPCQVGIFLDYEAGVVSFYNITDhGSLIYTFSEcAFTGPLRP 159

                         170
                  ....*....|....*....
gi 1331802279 449 YF-----YVGPDSQPLRIC 462
Cdd:cd12900   160 FFnpgfnDSGGNAAPLTLC 178

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331802279 295 EIILDPETAHPNLIVSEDKKRVRFTKRKQKVPGFPKRFTVKPVVLGFPYFHSGRHFWEIEVGDKSEWAIGICKDSLPTKA 374
Cdd:cd15811     1 DVTLDPDTANPELVLSEDRRSVRRGDLRQALPDSPERFDPGPCVLGRERFTSGRHYWEVEVGDRTSWALGVCKENVNRKE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331802279 375 RRPSSAQQECWRIELQDDGYHAPGAFPTPllLEVKARAIGIFLDYEMGEISFYNMAEKSHICTFSDT-FTGPLRPYFY-V 452
Cdd:cd15811    81 KGELSAGNGFWILVFLGNYYSSERRTFAP--LRDPPRRVGIFLDYEAGHLSFYSATDGSLLFIFPETpFSGTLRPLFSpL 158

                         170
                  ....*....|
gi 1331802279 453 GPDSQPLRIC 462
Cdd:cd15811   159 SSSPTPMTIC 168

PRY/SPRY domain, also known as B30.2; This domain contains residues in the N-terminus that form a distinct PRY domain structure such that the 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 core); Stonutoxin (secreted poisonous protein of the stonefish Synanceia horrida). 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. Among the TRIM proteins, also known as the N-terminal RING finger/B-box/coiled coil (RBCC) family, only Classes I and II contain the B30.2 domain that has evolved under positive selection. Class I TRIM proteins include multiple members involved in antiviral immunity at various levels of interferon signaling cascade. Among the 75 human TRIMs, roughly half enhance immune response, which they do at multiple levels in signaling pathways. 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 1331802279 296 IILDPETAHPNLIVSEDKKRVRFTKRKQKVPGFPKRFTVKPVVLGFPYFHSGRHFWEIEVGDKSEWAIGICKDSLPTK-- 373
Cdd:cd12874     1 LTFDPDTAHLNLILSDDLRSVRVGDISQHPPEPPPRFFECWQVLGSQSFSSGRHYWEVDVQDDSSWYVGVTYKSLPRKgk 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331802279 374 ----ARRPSSaqqecWRIELQDDGYHAPGAFPTPLLLEVKARAIGIFLDYEMGEISFYNMAE-KSHICTFSDTFTGPLRP 448
Cdd:cd12874    81 msnlGRNNGS-----WCLEWRENEFSAWHNNPETRLPVTPPRRLGVFLDCDGGSLSFYGVTDgVQLLYTFKAKFTEPLYP 155

                         170
                  ....*....|....
gi 1331802279 449 YFYVGPDSqPLRIC 462
Cdd:cd12874   156 AFWLGEGS-TLSIC 168

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 1331802279 295 EIILDPETAHPNLIVSEDKKRVRFTKRKQKVPGFPKRFTVKPVVLGFPYFHSGRHFWEIEVGDKSEWAIGICKDSLPTK- 373
Cdd:cd13741     1 DLTLDPDTAHPALLLSPDRRGVRLAERRQEVPEHPKRFSADCCVLGAQGFRSGRHYWEVEVGGRRGWAVGAARESTHHKe 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331802279 374 ----------------------ARRPSSAQQ-----ECWRIELQDDGYHAPGAFPTPLLL-EVKARAIGIFLDYEMGEIS 425
Cdd:cd13741    81 kvgsggssvssgdasssrhhhrRRRLHLPQQpllqrEVWCVGTNGKRYQAQSSTEQTLLSpSEKPRRFGVYLDYEAGRLG 160

                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 1331802279 426 FYNMAEKSHICTFSDTFTGP-LRPYFYVGPDSQPLRICT 463
Cdd:cd13741   161 FYNAETLAHVHTFSAAFLGErVFPFFRVLSKGTRIKLCP 199

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 1331802279 296 IILDPETAHPNLIVSEDKKRVRFTKRKQKVPGFPKRFTVKPvVLGFPYFHSGRHFWEIEVGDKSEWAIGICKDSLPTKAR 375
Cdd:cd12891     1 LTLDPNTAHNNLALSGDLKTVTCSSENQHYPDSPERFTHSQ-VLSTQSFSSGRHYWEVEVSESGGWSVGVAYPSIERKGD 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331802279 376 R------PSSaqqecWRIELQDDGY---HAPGAFPTPlllEVKARAIGIFLDYEMGEISFYNMAEK-SHICTFSDTFTGP 445
Cdd:cd12891    80 EsrigrnDKS-----WCLEWQDKSFsawHNNEETPLP---SVSSRRLGVYLDYEAGRLSFYELSDPiRHLHTFTATFTEP 151

                         170
                  ....*....|....*..
gi 1331802279 446 LRPYFYVGPDSQpLRIC 462
Cdd:cd12891   152 LHPAFWVLEGGW-IRIK 167

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 1331802279 295 EIILDPETAHPNLIVSEDKKRVRFTKRKQKVPGFPKRFTVKPVVLGFPYFHSGRHFWEIEV---GDkSEWAIGICKDSLP 371
Cdd:cd15812     1 DVVPDPSTAYPYLLLYESRQRRYLSTPPDGTPCSKDRFLAYPCAVGQETFSSGRHYWEVGMnltGD-ALWALGVCRDNVS 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331802279 372 TKARRPSSAQQECWRIELQDDGYHAPG-AFPTPLLLEVKARAIGIFLDYEMGEISFYNMAEKSHICTFSD-TFTGPLRPY 449
Cdd:cd15812    80 RKDRVPKSPENGFWVVQLSKGKKYLSAmSALTPVTLTEPPSHMGIFLDFEAGEVSFYSVNDGSHLHTYSQaAFPGPLQPF 159

                         170
                  ....*....|....*..
gi 1331802279 450 FYVG-PDSQPLRICTGT 465
Cdd:cd15812   160 FCLGaPKSGQMVISTVT 176

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1331802279 298 LDPETAHPNLIVSEDKKRVRFTKRKQKVPGFPKRFTVKPVVLGFPYFHSGRHFWEIEVGDKSEWAIGICKDSLPTKARRP 377
Cdd:cd13743    16 LDPLTAHPMLELSKGNTVVECGLLAQRLPSNPERFDYSNCVLASRGFSSGKHYWEVVVGSKSKWRLGLIKGTTSRKGKLN 95