B-box-type 2 zinc finger found in tripartite motif-containing proteins, TRIM10, TRIM15, TRIM26, TRIM31 and similar proteins; This family includes TRIM10, TRIM15, TRIM26 and TRIM31. TRIM10, also known as B30-RING finger protein (RFB30), RING finger protein 9 (RNF9), or hematopoietic RING finger 1 (HERF1), is a novel hematopoiesis-specific RING finger protein required for terminal differentiation of erythroid cells. TRIM15, also termed RING finger protein 93 (RNF93), or zinc finger protein 178 (ZNF178), or zinc finger protein B7 (ZNFB7), is a focal adhesion protein that regulates focal adhesion disassembly. It localizes to focal contacts in a myosin-II-independent manner by an interaction between its coiled-coil domain and the LD2 motif of paxillin. TRIM15 can also associate with coronin 1B, cortactin, filamin binding LIM protein1, and vasodilator-stimulated phosphoprotein, which are involved in actin cytoskeleton dynamics. As an additional component of the integrin adhesome, it regulates focal adhesion turnover and cell migration. TRIM26, also known as acid finger protein (AFP), RING finger protein 95 (RNF95), or zinc finger protein 173 (ZNF173), is an E3 ubiquitin-protein ligase that negatively regulates interferon-beta production and antiviral response through polyubiquitination and degradation of nuclear transcription factor IRF3. It functions as an important regulator for RNA virus-triggered innate immune response by bridging TBK1 to NEMO (NF-kappaB essential modulator, also known as IKKgamma) and mediating TBK1 activation. It also acts as a novel tumor suppressor of hepatocellular carcinoma by regulating cancer cell proliferation, colony forming ability, migration, and invasion. TRIM31 is an E3 ubiquitin-protein ligase that primarily localizes to the cytoplasm, but is also associated with the mitochondria. It can negatively regulate cell proliferation and may be a potential biomarker of gastric cancer as it is overexpressed from the early stage of gastric carcinogenesis. TRIM31 is downregulated in non-small cell lung cancer and serves as a potential tumor suppressor. It interacts with p52 (Shc) and inhibits Src-induced anchorage-independent growth. TRIM10, TRIM15 and TRIM26 belong to the C-IV subclass of TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a RING finger, Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. TRIM31 belongs to the C-V subclass of TRIM family of proteins. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                         10        20        30
                 ....*....|....*....|....*....|....*....
gi 149193331  81 TYCEEHGEKIYFFCENDAEFLCVFCREGPTHQAHTVGFL 119
Cdd:cd19765    1 TLCEEHGEKIHFFCEDDGKFLCVVCRESREHRTHTVSLL 39

RecF/RecN/SMC N terminal domain; This domain is found at the N terminus of SMC proteins. The SMC (structural maintenance of chromosomes) superfamily proteins have ATP-binding domains at the N- and C-termini, and two extended coiled-coil domains separated by a hinge in the middle. The eukaryotic SMC proteins form two kind of heterodimers: the SMC1/SMC3 and the SMC2/SMC4 types. These heterodimers constitute an essential part of higher order complexes, which are involved in chromatin and DNA dynamics. This family also includes the RecF and RecN proteins that are involved in DNA metabolism and recombination.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149193331   121 EAIQPYRDRLRSRLEALSTERDEIEDVKCQEDQKLQVL---LTQIESKKHQVETAFERLQQELEQQRclllarlreleqq 197
Cdd:TIGR02169  726 EQLEQEEEKLKERLEELEEDLSSLEQEIENVKSELKELearIEELEEDLHKLEEALNDLEARLSHSR------------- 792

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 149193331   198 iWKERDEYITKVSEEVTRLGAQVKELEEKCQ--QPASELLQDVRVN 241
Cdd:TIGR02169  793 -IPEIQAELSKLEEEVSRIEARLREIEQKLNrlTLEKEYLEKEIQE 837

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 149193331   346 SGRHRWQVDLqlGDGGGCTVGVAGEGVRRKGEMGLSAEDGVWAVIISHQQ-CWASTSPGTDLPLSEIPRGVRVALDYEAG 424
Cdd:smart00449   1 SGRHYFEVEI--GDGGHWRVGVATKSVPRGYFALLGEDKGSWGYDGDGGKkYHNSTGPEYGLPLQEPGDVIGCFLDLEAG 78

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 149193331   425 QVTLHNAQTQEPIFTF-TASFSGKVFPFFAVWKKGSC 460
Cdd:smart00449  79 TISFYKNGKYLHGLAFfDVKFSGPLYPAFSLGSGNSV 115

B-box-type 2 zinc finger found in tripartite motif-containing proteins, TRIM10, TRIM15, TRIM26, TRIM31 and similar proteins; This family includes TRIM10, TRIM15, TRIM26 and TRIM31. TRIM10, also known as B30-RING finger protein (RFB30), RING finger protein 9 (RNF9), or hematopoietic RING finger 1 (HERF1), is a novel hematopoiesis-specific RING finger protein required for terminal differentiation of erythroid cells. TRIM15, also termed RING finger protein 93 (RNF93), or zinc finger protein 178 (ZNF178), or zinc finger protein B7 (ZNFB7), is a focal adhesion protein that regulates focal adhesion disassembly. It localizes to focal contacts in a myosin-II-independent manner by an interaction between its coiled-coil domain and the LD2 motif of paxillin. TRIM15 can also associate with coronin 1B, cortactin, filamin binding LIM protein1, and vasodilator-stimulated phosphoprotein, which are involved in actin cytoskeleton dynamics. As an additional component of the integrin adhesome, it regulates focal adhesion turnover and cell migration. TRIM26, also known as acid finger protein (AFP), RING finger protein 95 (RNF95), or zinc finger protein 173 (ZNF173), is an E3 ubiquitin-protein ligase that negatively regulates interferon-beta production and antiviral response through polyubiquitination and degradation of nuclear transcription factor IRF3. It functions as an important regulator for RNA virus-triggered innate immune response by bridging TBK1 to NEMO (NF-kappaB essential modulator, also known as IKKgamma) and mediating TBK1 activation. It also acts as a novel tumor suppressor of hepatocellular carcinoma by regulating cancer cell proliferation, colony forming ability, migration, and invasion. TRIM31 is an E3 ubiquitin-protein ligase that primarily localizes to the cytoplasm, but is also associated with the mitochondria. It can negatively regulate cell proliferation and may be a potential biomarker of gastric cancer as it is overexpressed from the early stage of gastric carcinogenesis. TRIM31 is downregulated in non-small cell lung cancer and serves as a potential tumor suppressor. It interacts with p52 (Shc) and inhibits Src-induced anchorage-independent growth. TRIM10, TRIM15 and TRIM26 belong to the C-IV subclass of TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a RING finger, Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. TRIM31 belongs to the C-V subclass of TRIM family of proteins. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                         10        20        30
                 ....*....|....*....|....*....|....*....
gi 149193331  81 TYCEEHGEKIYFFCENDAEFLCVFCREGPTHQAHTVGFL 119
Cdd:cd19765    1 TLCEEHGEKIHFFCEDDGKFLCVVCRESREHRTHTVSLL 39

B-Box-type zinc finger;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 149193331    80 ETYCEEHG-EKIYFFCENDAEFLCVFCREgPTHQAHTVGFL 119
Cdd:smart00336   3 APKCDSHGdEPAEFFCEECGALLCRTCDE-AEHRGHTVVLL 42

B-box zinc finger;

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 149193331   80 ETYCEEHG-EKIYFFCENDAEFLCVFCREGpTHQAHTV 116
Cdd:pfam00643   3 ERLCPEHEeEPLTLYCNDCQELLCEECSVG-EHRGHTV 39

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149193331   121 EAIQPYRDRLRSRLEALSTERDEIEDVKCQEDQKLQVL---LTQIESKKHQVETAFERLQQELEQQRclllarlreleqq 197
Cdd:TIGR02169  726 EQLEQEEEKLKERLEELEEDLSSLEQEIENVKSELKELearIEELEEDLHKLEEALNDLEARLSHSR------------- 792

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 149193331   198 iWKERDEYITKVSEEVTRLGAQVKELEEKCQ--QPASELLQDVRVN 241
Cdd:TIGR02169  793 -IPEIQAELSKLEEEVSRIEARLREIEQKLNrlTLEKEYLEKEIQE 837

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 149193331    5 PSLKVVHELPACTLCAGPLEDAVTIPCGHTFCRLCL-PALSQMGaqssgkilLCPLCQEEEQ 65
Cdd:TIGR00599  18 PSLYPLDTSLRCHICKDFFDVPVLTSCSHTFCSLCIrRCLSNQP--------KCPLCRAEDQ 71

Mitochondrial inner membrane protein; Mitofilin controls mitochondrial cristae morphology. Mitofilin is enriched in the narrow space between the inner boundary and the outer membranes, where it forms a homotypic interaction and assembles into a large multimeric protein complex. The first 78 amino acids contain a typical amino-terminal-cleavable mitochondrial presequence rich in positive-charged and hydroxylated residues and a membrane anchor domain. In addition, it has three centrally located coiled coil domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149193331  133 RLEALSterDEIEDVKCQEDQKLQVlltQIESKKHQVETAFERLQQELEQQRclllarlrelEQQIWKERDEYITKVSEE 212
Cdd:pfam09731 295 EIDQLS---KKLAELKKREEKHIER---ALEKQKEELDKLAEELSARLEEVR----------AADEAQLRLEFEREREEI 358

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149193331  213 VTRLGAQVKELEEKCQQPASELLQDVRVNQsRCEMKtfvspeaispdlvkkiRDFHRKILTLPEMMR-MFSENLAhhlEI 291
Cdd:pfam09731 359 RESYEEKLRTELERQAEAHEEHLKDVLVEQ-EIELQ----------------REFLQDIKEKVEEERaGRLLKLN---EL 418

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 149193331  292 DSGVITLDPQTASRSLVLSEDRK---------SVRYTRQKKSlPDSPLR 331
Cdd:pfam09731 419 LANLKGLEKATSSHSEVEDENRKaqqlwlaveALRSTLEDGS-ADSRPR 466

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 149193331 296 ITLDPQTASRSLVLSEDRKSVRYTRQKKSLPDSPLRFDGLPAVLGFPGFSSGRHRWQVDLqlGDGGGCTVGVAGEGVRRK 375
Cdd:cd12888    2 VTLDPDTAHPRLVLSEDRKSVRWGDTRQDLPDNPERFDTWPCVLGCEGFTSGRHYWEVEV--GDGGGWAVGVARESVRRK 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149193331 376 GEMGLSAEDGVWAVIISHQQCWASTSPGTDLPLSEIPRGVRVALDYEAGQVTLHNAQTQEPIFTFT-ASFSG-KVFPFFA 453
Cdd:cd12888   80 GEISFSPEEGIWAVGQWGGQYWALTSPETPLPLSEVPRRIRVYLDYEGGQVAFFDADNEAPIFTFPpASFAGeRIFPWFW 159

                        170
                 ....*....|
gi 149193331 454 VWkKGSCLTL 463
Cdd:cd12888  160 VG-KGSQLKL 168

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149193331 296 ITLDPQTASRSLVLSEDRKSVRYTRQKKSLPDSPLRFDGLPAVLGFPGFSSGRHRWQVDLQLGDGGGCTVGVAGEGVRRK 375
Cdd:cd15827    4 ISLDPQTSHPKLLLSEDHQRARFSYKWQNSPDNPQRFDRATCVLAHDGFTGGRHTWVVSVDLAHGGSCTVGVVSEDVRRK 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149193331 376 GEMGLSAEDGVWAVIISHQQCWASTSPGTDLPLSEIPRGVRVALDYEAGQVTLHNAQTQEPIFTFTASFSGKVFPFFAVW 455
Cdd:cd15827   84 GELRLRPEEGVWAVRLAWGFVSALGSFPTRLALEEQPRQVRVSLDYEVGWVTFVNAVTQEPIYTFTASFTQKVFPFFGLW 163

                 ....*...
gi 149193331 456 KKGSCLTL 463
Cdd:cd15827  164 GRGSSFSL 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 149193331 296 ITLDPQTASRSLVLSEDRKSVRYTRQKKSLPDSPLRFDGLPAVLGFPGFSSGRHRWQVDLqlGDGGGCTVGVAGEGVRRK 375
Cdd:cd15819    4 VTLDPDTAHPALILSEDGRSVTWGETRQDLPENPERFDSLPCVLGQEGFTSGRHYWEVEV--GDRTSWDLGVCRDNVMRK 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149193331 376 GEMGLSAEDGVWAVIISHQQCWASTSPGTDLPLSEIPRGVRVALDYEAGQVTLHNAQTQEPIFTFT-ASFSGKVFPFFAV 454
Cdd:cd15819   82 GRVTLSPENGFWAIRLYGNEYWALTSPETPLTLKEPPRRVGIFLDYEAGDVSFYNMTDGSHIYTFPqTAFSGPLRPFFRL 161

                 ....*....
gi 149193331 455 WKKGS-CLT 462
Cdd:cd15819  162 WSSDSgPLT 170

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 149193331 296 ITLDPQTASRSLVLSEDRKSVRYTRQKKSLPDSPLRFDGLPAVLGFPGFSSGRHRWQVdlQLGDGGGCTVGVAGEGVRRK 375
Cdd:cd15829   21 VTLDPETAHPNLLVSEDKKCVTFTKKKQRVPDSPKRFTVNPVVLGFPGFHSGRHFWEV--EVGDKPEWAVGVCKDSLSTK 98

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 149193331 376 GEMGLSAEDGVWAVIISHQQCWASTSPGTDLPLSEIPRGVRVALDYEAGQVTLHNAQTQEPIFTFTASFSGKVFPFFAV 454
Cdd:cd15829   99 ARRPPSGQQGCWRIQLQGGDYDAPGAVPPPLLLEVKPRGIGVFLDYELGEISFYNMPEKSHIHTFTDTFSGPLRPYFYV 177

PRY/SPRY domain in tripartite motif-binding protein 20 (TRIM20), also known as pyrin; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM20, which is also known as pyrin or marenostrin. Unlike TRIM domains that are composed of RING/B-box/coiled-coil core, the N-terminal RING domain in TRIM20 is exchanged by a PYRIN domain (PYD), a prime mediator of protein interactions necessary for apoptosis, inflammation and innate immune signaling pathway, and it also harbors a C-terminal B30.2 domain. Mutations in pyrin (TRIM20) are associated with familial Mediterranean fever (FMF), a recessively hereditary periodic fever syndrome, characterized by episodes of inflammation and fever. These mutations cluster in the C-terminal B30.2 domain and therefore it is assumed that pyrin plays a role in the innate immune system by possibly effecting caspase-1-dependent IL-1beta maturation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149193331 296 ITLDPQTASRSLVLSEDRKSVRYTRQKKSLPDSPLRFDGLPAVLGFPGFSSGRHRWQVDlqLGDGGGCTVGVAGEGVRRK 375
Cdd:cd15813   11 VTLDPETAHPNLIFSDDLKSVRLGNKWDRLPDNPERFDSCIIVLGSPSFTSGRHYWEVE--VGDKTGWILGVCKASVSRK 88

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 149193331 376 GEMGLSAEDGVWAVIISHQQCW-ASTSPGTDLPLSEIPRGVRVALDYEAGQVTLHNAQTQEPIFTFTASFS-GKVFPFF 452
Cdd:cd15813   89 GSMTLSPENGYWVVMMTKRNEYqASTSPPTRLWLREPPRRVGIFLDYEAGDISFYNVTAKSHIYTFTSFSSsGPLQPIF 167

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 149193331 296 ITLDPQTASRSLVLSEDRKSVRYTRQKKSLPDSPLRFDGLPAVLGFPGFSSGRHRWQVDLQlgDGGGCTVGVAGEGVRRK 375
Cdd:cd15818   15 ITLDPKTAHPNLILSEDLTCVWHGDTKQMLPDNPERFDSSVAVLGSEGFTSGKHYWEVEVA--KKTKWTLGVVRESINRK 92

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 149193331 376 GEMGLSAEDGVWAVIISHQ-QCWASTSPGTDLPLSEIPRGVRVALDYEAGQVTLHNAQTQEPIFTFTASFSGKVFPFF 452
Cdd:cd15818   93 GNCPLSPEDGFWLLRLRNQnELKALDVPSFSLTLTSNLNKVGIYLDYEGGQVSFYNANTMSHIYTFSDTFTEKIYPYF 170

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 149193331 296 ITLDPQTASRSLVLSEDRKSVRYTRQKKSLPDSPLRFDGLPAVLGFPGFSSGRHRWQVdlQLGDGGGCTVGVAGEGVRRK 375
Cdd:cd15817    2 LILDPETAHPNLIVSEDRKAVRYRRMKPNCPYDPRRFTVYPAVLGSEGFDSGRHFWEV--EVGGKGEWILGVCKDSLPRN 79

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 149193331 376 GEMGLSAEDGVWAVIISHQQCWASTSPGTDLPLSEIPRGVRVALDYEAGQVTLHNAQTQEPIFTFTASFSGKVFPFFAV 454
Cdd:cd15817   80 AQDPPSPLGGCWQIGRYMSGYVASGPKTTQLLPVVKPSRIGIFLDYELGEVSFYNMNDRSHLYTFTDTFTGKLIPYFYV 158

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 149193331 296 ITLDPQTASRSLVLSEDRKSVRYTRQKKSLPDSPLRFDGLPAVLGFPGFSSGRHRWQVDLQlgDGGGCTVGVAGEGVRRK 375
Cdd:cd12874    1 LTFDPDTAHLNLILSDDLRSVRVGDISQHPPEPPPRFFECWQVLGSQSFSSGRHYWEVDVQ--DDSSWYVGVTYKSLPRK 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149193331 376 GEMG-LSAEDGVWAVIISHQQCWASTS-PGTDLPLSEiPRGVRVALDYEAGQVTLHNAQTQE-PIFTFTASFSGKVFPFF 452
Cdd:cd12874   79 GKMSnLGRNNGSWCLEWRENEFSAWHNnPETRLPVTP-PRRLGVFLDCDGGSLSFYGVTDGVqLLYTFKAKFTEPLYPAF 157

                        170
                 ....*....|..
gi 149193331 453 AVWkKGSCLTLK 464
Cdd:cd12874  158 WLG-EGSTLSIC 168

PRY/SPRY domain in tripartite motif-containing protein 27 (TRIM27), also known as RING finger protein 76 (RNF76); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM27, also known as RING finger protein 76 (RNF76) or RET finger protein (RFP). TRIM27 domain is composed of RING/B-box/coiled-coil core and also known as RBCC proteins. It is highly expressed in the spleen, thymus and in cells of the hematopoietic compartment. TRIM27 exhibits either nuclear or cytosolic localization depending on the cell type. TRIM27 negatively regulates nucleotide-binding oligomerization domain containing 2 (NOD2)-mediated signaling by proteasomal degradation of NOD2, suggesting that TRIM27 could be a new target for therapeutic intervention in NOD2-associated diseases such as Crohn's. High expression of TRIM27 is observed in several human cancers, including breast and endometrial cancer, where elevated TRIM27 expression predicts poor prognosis. Also, TRIM27 forms an oncogenic fusion protein with Ret proto-oncogene. It is involved in different stages of spermatogenesis and its significant expression in male germ cells and seminomas, suggests that TRIM27 may be associated with the regulation of testicular germ cell proliferation and histological-type of germ cell tumors. TRIM27 could also be a predictive marker for chemoresistance in ovarian cancer patients. In the neurotoxin model of Parkinson's disease (PD), deficiency of TRIM27 decreases apoptosis and protects dopaminergic neurons, making TRIM27 an effective potential target during the treatment of PD.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149193331 296 ITLDPQTASRSLVLSEDRKSVRYTRQKKSLPDSPLRFDGLPAVLGFPGFSSGRHRWQVdlQLGDGGGCTVGVAGEGVRRK 375
Cdd:cd15814    4 VTLDPDTAYPSLILSDNLRQVRYSYLQQDLPDNPERFNLFPCVLGSPCFIAGRHYWEV--EVGDKAKWTIGVCEDSVCRK 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149193331 376 GEMGLSAEDGVWAVIISH-QQCWASTSPGTDLPLSEIPRGVRVALDYEAGQVTLHNAQTQEPIFTFT-ASFSGKVFPFFA 453
Cdd:cd15814   82 GGVTSAPQNGFWAVSLWYgKEYWALTSPMTALPLRTPLQRVGIFLDYDAGEVSFYNVTERCHTFTFShATFCGPVRPYFS 161

                 ....*
gi 149193331 454 VWKKG 458
Cdd:cd15814  162 LSYSG 166

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 149193331 295 VITLDPQTASRSLVLSEDRKSVRYTRQKKSLPDSPLRFDGLPAVLGFPGFSSGRHRWQVDLqlgdgGGCT---VGVAGEG 371
Cdd:cd12905    5 PLTFDPETAHPSLILSRDLTAVTESDEMQPYPRSPKRFLQCVNVLASQGFQSGRHYWEVWV-----GSKTkwdLGVASES 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149193331 372 VRRKGEMGLSAEDGVWAVIISH-QQCWASTSPGTDLPLSEIPRGVRVALDYEAGQVTLHNAQTQEPIFTFTASFSGKVFP 450
Cdd:cd12905   80 VDRQARVKLCPENGYWTLRLRNgDEYWAGTQPWTRLRVTSRPQRIGVFLDCEERKVSFYNADDMSLLYSFHQGPRGKVFP 159

                 ...
gi 149193331 451 FFA 453
Cdd:cd12905  160 FFS 162

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 149193331 296 ITLDPQTASRSLVLSEDRKSVRYTRQKKSLPDSPLRFDGLPAVLGFPGFSSGRHRWQVDLQLGDggGCTVGVAGEGVRRK 375
Cdd:cd12900    5 ITLDPDTANPWLILSKDRRQVRLGDTHQNVPENEERFDNYPMVLGAQRFNSGKHYWEVDVTGKE--AWDLGVCRDSVRRK 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149193331 376 GEMGLSAEDGVWAVIISHQQCWASTSPGTDLPLSEIPRGVRVALDYEAGQVTLHNAQTQEP-IFTFT-ASFSGKVFPFFA 453
Cdd:cd12900   83 GQFLLSPENGFWTIWLWNKKYEAGTSPQTTLHLQVPPCQVGIFLDYEAGVVSFYNITDHGSlIYTFSeCAFTGPLRPFFN 162

                 .
gi 149193331 454 V 454
Cdd:cd12900  163 P 163

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 149193331 296 ITLDPQTASRSLVLSEDRKSVRYTRQKKSLPDSPLRFDGLPAVLGFPGFSSGRHRWQVDlqLGDGGGCTVGVAGEGVRRK 375
Cdd:cd15828   12 VTLDPETAHPQLTVSEDRKSVLYGEMKQNVCYNPRRFYLCPAVLGSEGFHSGRQYWEVE--VGDKPEWTLGVCQDCLPRN 89

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 149193331 376 GEMGLSAEDGVWAV-IISHQQCWASTSPGTDLPLSEIPRGVRVALDYEAGQVTLHNAQTQEPIFTFTASFSGKVFPFF 452
Cdd:cd15828   90 WSNQPSVQDGLWAIgRYSESNYVALGPKKIQLLPKVRPSKIGIFLDYELGEVSFYNMNDRSLLYTFSDSFTGTLWPYF 167

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 149193331 296 ITLDPQTASRSLVLSEDRKSVRY--TRQKKSLPDSPLRFDGLPAVLGFPGFSSGRHRWQVDLQlgDGGGCTVGVAGEGVR 373
Cdd:cd13734    1 FKLDPKTAHRKLRLSNDNLTVEYdpEGSKDQAAVLPRRFTGSPAVLGDVAISSGRHYWEVSVS--RSTSYRVGVAYKSAP 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 149193331 374 RKGEMGLSaeDGVWAVIISHQQCWASTSpGTDLPLSEIPRGVR--VALDYEAGQVTLHNAQTQEPIFTFTASFSGKVFPF 451
Cdd:cd13734   79 RDEDLGKN--STSWCLSRDNNRYTARHD-GKVVDLRVTGHPARigVLLDYDNGTLSFYDAESKQHLYTFHVDFEGPVCPA 155

                        170
                 ....*....|..
gi 149193331 452 FAVWKKgsCLTL 463
Cdd:cd13734  156 FAVWNG--SLTL 165

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 149193331  348 RHRWQVDLQLGDGGGCTVGVAGEGVRRKGEMGLSAEDGVWAVIISHQQC-WASTSPGTDLPLSEIPRGVRVALDYEAGQV 426
Cdd:pfam00622   1 RHYFEVEIFGQDGGGWRVGWATKSVPRKGERFLGDESGSWGYDGWTGKKyWASTSPLTGLPLFEPGDVIGCFLDYEAGTI 80

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 149193331  427 TLHNAqTQEPIFTFT-ASFSGKVFPFFAV-WKKGSCLTL 463
Cdd:pfam00622  81 SFTKN-GKSLGYAFRdVPFAGPLFPAVSLgAGEGLKFNF 118