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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22122567 335 VTLDKSSADPDLTFSQDLKKVTLyivAGKASNRQAKPRPFYPFHCVRGSPGLSSGRQVWEAEIRGPSGGACIVGVVTELA 414
Cdd:cd15826   2 VTLDPQTASGSLVLSEDRKSVRY---TRQKQNLPDSPLRFDGLPAVLGSPGFSSGRHRWQVEVQLGDGGGCTVGVAGESV 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22122567 415 RGAQSQTVSAQSYIWALRISPSGCQPFTNCKAQEYLQVCLKKVGVYVNHDCGEVVFYDAITSKHIYTFQTSFDGKVFPLF 494
Cdd:cd15826  79 RRKGEMGLSAEDGVWAVILSHQQCWASTSPGTDLPLSEIPRRVGVALDYEAGTVTLTNAETQEPIFTFTASFSGKVFPFF 158

                       170
                ....*....|.
gi 22122567 495 GLQVACSHITL 505
Cdd:cd15826 159 AVWKKGSRLTL 169

B-box-type zinc finger superfamily; The B-box-type zinc finger is a short zinc binding domain of around 40 amino acid residues in length. It has been found in transcription factors, ribonucleoproteins and proto-oncoproteins, such as in TRIM (tripartite motif) proteins that consist of an N-terminal RING finger (originally called an A-box), followed by 1-2 B-box domains and a coiled-coil domain (also called RBCC for Ring, B-box, Coiled-Coil). The B-box-type zinc finger often presents in combination with other motifs, like RING zinc finger, NHL motif, coiled-coil or RFP domain in functionally unrelated proteins, most likely mediating protein-protein interactions. Based on different consensus sequences and the spacing of the 7-8 zinc-binding residues, B-box-type zinc fingers can be divided into two groups, type 1 (Bbox1: C6H2) and type 2 (Bbox2: CHC3H2).

                        10        20        30
                ....*....|....*....|....*....|....*..
gi 22122567  94 CQRHKEKLHYFCEQDGAFLCVVCRDSKDHKSHNVTLI 130
Cdd:cd19765   3 CEEHGEKIHFFCEDDGKFLCVVCRESREHRTHTVSLL 39

RIM-binding protein of the cytomatrix active zone; This is a family of proteins that form part of the CAZ (cytomatrix at the active zone) complex which is involved in determining the site of synaptic vesicle fusion. The C-terminus is a PDZ-binding motif that binds directly to RIM (a small G protein Rab-3A effector). The family also contains four coiled-coil domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22122567   183 EFKLLRQRLDEEESFLLSRLDWL----EQQGA-----KQLRQYVTVTEKQLNSLRKLTKSLKirlqsssmELLKDIKDAL 253
Cdd:pfam10174 346 EVDALRLRLEEKESFLNKKTKQLqdltEEKSTlageiRDLKDMLDVKERKINVLQKKIENLQ--------EQLRDKDKQL 417

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22122567   254 SRGKE-FQFLNPNPVPED-----LEkkcsEAKARHESIIKTLTELKDDMNAEgKRDKSAFMNSLNKEEKESWSLLQ---- 323
Cdd:pfam10174 418 AGLKErVKSLQTDSSNTDtalttLE----EALSEKERIIERLKEQREREDRE-RLEELESLKKENKDLKEKVSALQpelt 492

                  ....*...
gi 22122567   324 -KNNSVLP 330
Cdd:pfam10174 493 eKESSLID 500

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 22122567 335 VTLDKSSADPDLTFSQDLKKVTLyivAGKASNRQAKPRPFYPFHCVRGSPGLSSGRQVWEAEIRGPSGGACIVGVVTELA 414
Cdd:cd15826   2 VTLDPQTASGSLVLSEDRKSVRY---TRQKQNLPDSPLRFDGLPAVLGSPGFSSGRHRWQVEVQLGDGGGCTVGVAGESV 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22122567 415 RGAQSQTVSAQSYIWALRISPSGCQPFTNCKAQEYLQVCLKKVGVYVNHDCGEVVFYDAITSKHIYTFQTSFDGKVFPLF 494
Cdd:cd15826  79 RRKGEMGLSAEDGVWAVILSHQQCWASTSPGTDLPLSEIPRRVGVALDYEAGTVTLTNAETQEPIFTFTASFSGKVFPFF 158

                       170
                ....*....|.
gi 22122567 495 GLQVACSHITL 505
Cdd:cd15826 159 AVWKKGSRLTL 169

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 22122567  94 CQRHKEKLHYFCEQDGAFLCVVCRDSKDHKSHNVTLI 130
Cdd:cd19765   3 CEEHGEKIHFFCEDDGKFLCVVCRESREHRTHTVSLL 39

zinc finger of C3HC4-type, RING; This is a family of primate-specific Ret finger protein-like (RFPL) zinc-fingers of the C3HC4 type. Ret finger protein-like proteins are primate-specific target genes of Pax6, a key transcription factor for pancreas, eye and neocortex development. This domain is likely to be DNA-binding. This zinc-finger domain together with the RDM domain, pfam11002, forms a large zinc-finger structure of the RING/U-Box superfamily. RING-containing proteins are known to exert an E3 ubiquitin protein ligase activity with the zinc-finger structure being mandatory for binding to the E2 ubiquitin-conjugating enzyme.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 22122567    16 CPICMEILQDPVTIDCGHNFCLQCISQVGKTSEKIQ--CPLC 55
Cdd:pfam15227   1 CPICLDYLEKPVSIECGHSFCLSCINSLQKEPDGESllCPQC 42

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 22122567     16 CPICME-ILQDPVTIDCGHNFCLQCISQVGKtSEKIQCPLC 55
Cdd:smart00184   1 CPICLEeYLKDPVILPCGHTFCRSCIRKWLE-SGNNTCPIC 40

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 22122567     3 GQPLAC--QLQEEVTCPICMEILQDPVTIDCGHNFCLQCISQVgkTSEKIQCPLCKLSVNKNTFRPNKLLASLAEKIQSM 80
Cdd:TIGR00599  14 TTPIPSlyPLDTSLRCHICKDFFDVPVLTSCSHTFCSLCIRRC--LSNQPKCPLCRAEDQESKLRSNWLVSEIVESFKNL 91

                  ....*....
gi 22122567    81 DPADIQAEK 89
Cdd:TIGR00599  92 RPSLLEFLR 100

RING-finger-containing E3 ubiquitin ligase [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 22122567  16 CPICMEILQDPVTIDCGHNFCLQCISQVGKTSEKIQCPLCK 56
Cdd:COG5574 218 CFLCLEEPEVPSCTPCGHLFCLSCLLISWTKKKYEFCPLCR 258

Uncharacterized conserved protein, contains RING Zn-finger [General function prediction only];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22122567  16 CPICMEILQDPV-TIDCGHNFCLQCISQVGKTSEKiQCPLCKlsvnkntfRPNKLLASLAEkiqsmdpaDIQAEKEDSRC 94
Cdd:COG5222 277 CPLCHCLLRNPMkTPCCGHTFCDECIGTALLDSDF-KCPNCS--------RKDVLLDGLTP--------DIDKKLEVEKA 339

                ....*...
gi 22122567  95 QRHKEKLH 102
Cdd:COG5222 340 LKKQRKKV 347

DNA double-strand break repair ATPase Rad50;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22122567  173 VDLEKL-KIHEEFKLLRQRLDEEESFLLSRLDWLEQqgAKQLRQYVTVTEKQLNSLRKLTKSLKIRLQSSSMELLKDIKD 251
Cdd:PRK03918 515 YNLEELeKKAEEYEKLKEKLIKLKGEIKSLKKELEK--LEELKKKLAELEKKLDELEEELAELLKELEELGFESVEELEE 592

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22122567  252 ALSRGKEF--QFLNPNPVPEDLE-----------------KKCSEAKARHESIIKTLTELKDDMNAEGKRDKSAFMNSLN 312
Cdd:PRK03918 593 RLKELEPFynEYLELKDAEKELEreekelkkleeeldkafEELAETEKRLEELRKELEELEKKYSEEEYEELREEYLELS 672

                 ..
gi 22122567  313 KE 314
Cdd:PRK03918 673 RE 674

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 22122567 335 VTLDKSSADPDLTFSQDLKKVTLyivAGKASNRQAKPRPFYPFHCVRGSPGLSSGRQVWEAEIRGPSGGACIVGVVTELA 414
Cdd:cd15826   2 VTLDPQTASGSLVLSEDRKSVRY---TRQKQNLPDSPLRFDGLPAVLGSPGFSSGRHRWQVEVQLGDGGGCTVGVAGESV 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22122567 415 RGAQSQTVSAQSYIWALRISPSGCQPFTNCKAQEYLQVCLKKVGVYVNHDCGEVVFYDAITSKHIYTFQTSFDGKVFPLF 494
Cdd:cd15826  79 RRKGEMGLSAEDGVWAVILSHQQCWASTSPGTDLPLSEIPRRVGVALDYEAGTVTLTNAETQEPIFTFTASFSGKVFPFF 158

                       170
                ....*....|.
gi 22122567 495 GLQVACSHITL 505
Cdd:cd15826 159 AVWKKGSRLTL 169

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 22122567 334 PVTLDKSSADPDLTFSQDLKKVTLyivAGKASNRQAKPRPFYPFHCVRGSPGLSSGRQVWEAEIRGPSggACIVGVVTEL 413
Cdd:cd13733   1 DVTLDPDTAHPNLILSEDLKSVRY---GDKRQNLPDNPERFDTCVCVLGSEGFSSGRHYWEVEVGGKT--DWDLGVARES 75

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22122567 414 ARGAQSQTVSAQSYIWALRISpSGCQ------PFTNCKaqeyLQVCLKKVGVYVNHDCGEVVFYDAITSKHIYTFQTSFD 487
Cdd:cd13733  76 VNRKGKITLSPENGYWTVGLR-NGNEykaltsPSTPLS----LREKPQKVGVFLDYEEGQVSFYNVDDGSHIYTFTDCFT 150

                ....*..
gi 22122567 488 GKVFPLF 494
Cdd:cd13733 151 EKLYPYF 157

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 22122567 332 SVPVTLDKSSADPDLTFSQDLKKVTLyivagkASNRQ---AKPRPFYPFHCVRGSPGLSSGRQVWEAEIRGpsGGACIVG 408
Cdd:cd15819   1 AVNVTLDPDTAHPALILSEDGRSVTW------GETRQdlpENPERFDSLPCVLGQEGFTSGRHYWEVEVGD--RTSWDLG 72

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22122567 409 VVTELARGAQSQTVSAQSYIWALRISPSGCQPFTNCKAQEYLQVCLKKVGVYVNHDCGEVVFYDAITSKHIYTF-QTSFD 487
Cdd:cd15819  73 VCRDNVMRKGRVTLSPENGFWAIRLYGNEYWALTSPETPLTLKEPPRRVGIFLDYEAGDVSFYNMTDGSHIYTFpQTAFS 152

                ....*....
gi 22122567 488 GKVFPLFGL 496
Cdd:cd15819 153 GPLRPFFRL 161

RING finger, HC subclass, found in tripartite motif-containing protein 31 (TRIM31) and similar proteins; 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. TRIM31 belongs to the C-V subclass of the TRIM (tripartite motif) family of proteins that are defined by an N-terminal RBCC (RING, Bbox, and coiled coil) domain, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as an uncharacterized region positioned C-terminal to the RBCC domain.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 22122567  13 EVTCPICMEILQDPVTIDCGHNFCLQCISQVGKTS-EKIQCPLC 55
Cdd:cd16582   1 EVICPICLDILQKPVTIDCGHNFCLQCITQIGETScGFFKCPLC 44

PRY/SPRY domain of butyrophilin 3 (BTN3), includes BTN3A1, BTN3A2, BTN3A3 as well as BTN-like 3 (BTNL3); BTN3A also known as CD277; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of butyrophilin family 3A (BTN3A); duplication events have led to three paralogs in primates: BTN3A1, BTN3A2, and BTN3A3. BTNs belong to receptor glycoproteins of immunoglobulin (Ig) superfamily, characterized by the presence of extracellular Ig-like domains (IgV and/or IgC). BTN3 transcripts are ubiquitously present in all immune cells (T cells, B cells, NK cells, monocytes, dendritic cells, and hematopoietic precursors) with different expression levels; BTN3A1 and BTN3A2 are expressed mainly by CD4+ and CD8+ T cells, BTN3A2 is the major form expressed in NK cells, and BTN3A3 is poorly expressed in these immune cells. The PRY/SPRY domain of the BTN3A1 isoform mediates phosphoantigen (pAg)-induced activation by binding directly to the pAg.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22122567 335 VTLDKSSADPDLTFSQDLKKVTLyivAGKASNRQAKPRPFYPFHCVRGSPGLSSGRQVWEAEIrGPSGGACiVGVVTELA 414
Cdd:cd15820   6 VILDPDTANPILLISEDQRSLQW---ADEPQNLPDNPKRFDWHYCVLGCKSFTSGRHFWEVEV-GDRKEWY-VGVCRENV 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22122567 415 RGAQSQTVSAQSYIWALRISP-SGCQPFTNCKAQEYLQVCLKKVGVYVNHDCGEVVFYDAITSKHIYTF-QTSFDGKVFP 492
Cdd:cd15820  81 ERKLWVKMAPENGFWTIGLSDgNDYQALTDPRTKLTIANPPQRVGVFLDYETGEVSFYNAMDGSHIYTFpHTSFSGPLYP 160

                ....*
gi 22122567 493 LFGLQ 497
Cdd:cd15820 161 VFRLL 165

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 22122567 333 VPVTLDKSSADPDLTFSQDLKKVTLyivAGKASNRQAKPRPFYPFHCVRGSPGLSSGRQVWEAEIRgpSGGACIVGVVTE 412
Cdd:cd15815  13 VSVTLDPDTAHPELTLSKDQRQVTY---GRCQENLDASPKRFTVLPCVLGCEGFTSGRHYFEVDVG--EGTGWDVGVCLE 87

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22122567 413 -LARGAqSQTVSAQSYIWALRISPSG-----CQPFTNCKAQEYLQVclkkVGVYVNHDCGEVVFYDAITSKHIYTF-QTS 485
Cdd:cd15815  88 nVQRGF-GMKQEPEFGFWTIRLCEEDgyvalTSPPTPLPLREKPLV----VGVFLDYEAGLVSFYNMTTGSHIFTFpKAS 162

                ....*....
gi 22122567 486 FDGKVFPLF 494
Cdd:cd15815 163 FSDTLRPYF 171

RING finger, HC subclass, found in tripartite motif-containing proteins, TRIM7, TRIM11 and TRIM27, and similar proteins; TRIM7, TRIM11 and TRIM27, closely related tripartite motif-containing proteins, 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 C3HC4-type RING-HC finger, Bbox2, and a coiled coil region, as well as a SPRY/B30.2 domain positioned C-terminal to the RBCC domain. TRIM7, also known as glycogenin-interacting protein (GNIP) or RING finger protein 90 (RNF90), is an E3 ubiquitin-protein ligase that mediates c-Jun/AP-1 activation by Ras signalling. Its phosphorylation and activation by MSK1 in response to direct activation by the Ras-Raf-MEK-ERK pathway can stimulate TRIM7 E3 ubiquitin ligase activity in mediating Lys63-linked ubiquitination of the AP-1 coactivator RACO-1, leading to RACO-1 protein stabilization. Moreover, TRIM7 binds and activates glycogenin, the self-glucosylating initiator of glycogen biosynthesis. TRIM11, also known as protein BIA1, or RING finger protein 92 (RNF92), is an E3 ubiquitin-protein ligase involved in the development of the central nervous system. It is overexpressed in high-grade gliomas and promotes proliferation, invasion, migration and glial tumor growth. TRIM11 acts as a potential therapeutic target for congenital central hypoventilation syndrome (CCHS) by mediating the degradation of CCHS-associated polyalanine-expanded Phox2b. TRIM11 modulates the function of neurogenic transcription factor Pax6 through the ubiquitin-proteosome system, and thus plays an essential role for Pax6-dependent neurogenesis. It also binds to and destabilizes a key component of the activator-mediated cofactor complex (ARC105), humanin, a neuroprotective peptide against Alzheimer's disease-relevant insults, and further regulates ARC105 function in transforming growth factor beta (TGFbeta) signaling. Moreover, TRIM11 negatively regulates retinoic acid-inducible gene-I (RIG-I)-mediated interferon-beta (IFNbeta) production and antiviral activity by targeting TANK-binding kinase-1 (TBK1). It may contribute to the endogenous restriction of retroviruses in cells. It enhances N-tropic murine leukemia virus (N-MLV) entry by interfering with Ref1 restriction. It also suppresses the early steps of human immunodeficiency virus HIV-1 transduction, resulting in decreased reverse transcripts. TRIM27, also known as RING finger protein 76 (RNF76), RET finger protein (RFP), or zinc finger protein RFP, is a nuclear E3 ubiquitin-protein ligase that is highly expressed in testis and in various tumor cell lines. Expression of TRIM27 is associated with prognosis of colon and endometrial cancers. TRIM27 was first identified as a fusion partner of the RET receptor tyrosine kinase. It functions as a transcriptional repressor and associates with several proteins involved in transcriptional activity, such as enhancer of polycomb 1 (Epc1), a member of the Polycomb group proteins, and Mi-2beta, a main component of the nucleosome remodeling and deacetylase (NuRD) complex, and the cell cycle regulator retinoblastoma protein (RB1). It also interacts with HDAC1, leading to downregulation of thioredoxin binding protein 2 (TBP-2), which inhibits the function of thioredoxin. Moreover, TRIM27 mediates Pax7-induced ubiquitination of MyoD in skeletal muscle atrophy. In addition, it inhibits muscle differentiation by modulating serum response factor (SRF) and Epc1. TRIM27 promotes a non-canonical polyubiquitination of PTEN, a lipid phosphatase that catalyzes PtdIns(3,4,5)P3 (PIP3) to PtdIns(4,5)P2 (PIP2). It is an IKKepsilon-interacting protein that regulates IkappaB kinase (IKK) function and negatively regulates signaling involved in the antiviral response and inflammation. TRIM27 also forms a protein complex with MBD4 or MBD2 or MBD3, and thus plays an important role in the enhancement of transcriptional repression through MBD proteins in tumorigenesis, spermatogenesis, and embryogenesis. It is a component of an estrogen receptor 1 (ESR1) regulatory complex that is involved in estrogen receptor-mediated transcription in MCF-7 cells.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 22122567  10 LQEEVTCPICMEILQDPVTIDCGHNFCLQCISQV-GKTSEKIQCPLCKLSVNKNTFRPN 67
Cdd:cd16594   2 LQEELTCPICLDYFTDPVTLDCGHSFCRACIARCwEEPETSASCPQCRETCPQRNLRPN 60

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 22122567 332 SVPVTLDKSSADPDLTFSQDLKKVTLyivaGKASNRQAK-PRPFYPFHCVRGSPGLSSGRQVWEAEIRGPSGgaCIVGVV 410
Cdd:cd15813   8 AVNVTLDPETAHPNLIFSDDLKSVRL----GNKWDRLPDnPERFDSCIIVLGSPSFTSGRHYWEVEVGDKTG--WILGVC 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22122567 411 TELARGAQSQTVSAQSYIWALRISpsgcqpftncKAQEY-----LQVCL------KKVGVYVNHDCGEVVFYDAITSKHI 479
Cdd:cd15813  82 KASVSRKGSMTLSPENGYWVVMMT----------KRNEYqastsPPTRLwlreppRRVGIFLDYEAGDISFYNVTAKSHI 151

                       170
                ....*....|....*.
gi 22122567 480 YTFQTSF-DGKVFPLF 494
Cdd:cd15813 152 YTFTSFSsSGPLQPIF 167

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 22122567 335 VTLDKSSADPDLTFSQDLKKVTLyivagkASNRQA---KPRPFYPFHCVRGSPGLSSGRQVWEAEIRGPSGGAciVGVVT 411
Cdd:cd13741   2 LTLDPDTAHPALLLSPDRRGVRL------AERRQEvpeHPKRFSADCCVLGAQGFRSGRHYWEVEVGGRRGWA--VGAAR 73

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22122567 412 ELAR----------GAQSQTVSAQSYIWALRISPSGCQPF---------TNCKAQEYL----QVCL------KKVGVYVN 462
Cdd:cd13741  74 ESTHhkekvgsggsSVSSGDASSSRHHHRRRRLHLPQQPLlqrevwcvgTNGKRYQAQssteQTLLspsekpRRFGVYLD 153

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*.
gi 22122567 463 HDCGEVVFYDAITSKHIYTFQTSFDG-KVFPLFGLQVACSHITLSP 507
Cdd:cd13741 154 YEAGRLGFYNAETLAHVHTFSAAFLGeRVFPFFRVLSKGTRIKLCP 199

RING finger, HC subclass, found in breast cancer type 1 susceptibility protein (BRCA1) and similar proteins; BRCA1, also known as RING finger protein 53 (RNF53), is a RING finger protein encoded by the tumor suppressor gene BRCA1 that regulates all DNA double-strand break (DSB) repair pathways. BRCA1 is frequently mutated in patients with hereditary breast and ovarian cancer (HBOC). Its mutation is also associated with an increased risk of pancreatic, stomach, laryngeal, fallopian tube, and prostate cancer. It plays an important role in the DNA damage response signaling and has been implicated in various cellular processes such as cell cycle regulation, transcriptional regulation, chromatin remodeling, DNA DSBs, and apoptosis. BRCA1 contains an N-terminal C3HC4-type RING-HC finger, and two BRCT (BRCA1 C-terminus domain) repeats at the C-terminus.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22122567  10 LQEEVTCPICMEILQDPVTIDCGHNFCLQCISQV-GKTSEKIQCPLCKLSVNKNTFRPNKLLASLAEKIQSMdpadIQAE 88
Cdd:cd16498  13 MQKNLECPICLELLKEPVSTKCDHQFCRFCILKLlQKKKKPAPCPLCKKSVTKRSLQESTRFKQLVEAVKKL----IDAF 88

                ....
gi 22122567  89 KEDS 92
Cdd:cd16498  89 ELDT 92

RING finger, HC subclass, found in tripartite motif-containing proteins TRIM5, TRIM6, TRIM22, TRIM34 and similar proteins; TRIM5, TRIM6, TRIM22, and TRIM34, four closely related tripartite motif-containing proteins, 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 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. TRIM5, also known as RING finger protein 88 (RNF88), is a capsid-specific restriction factor that prevents infection from non-host-adapted retroviruses in a species-specific manner by binding to and destabilizing the retroviral capsid lattice before reverse transcription is completed. Its retroviral restriction activity correlates with the ability to activate TAK1-dependent innate immune signaling. TRIM5 also acts as a pattern recognition receptor that activates innate immune signaling in response to the retroviral capsid lattice. Moreover, TRIM5 plays a role in regulating autophagy through activation of autophagy regulator BECN1 by causing its dissociation from its inhibitors BCL2 and TAB2. It also plays a role in autophagy by acting as a selective autophagy receptor which recognizes and targets HIV-1 capsid protein p24 for autophagic destruction. TRIM6, also known as RING finger protein 89 (RNF89), is an E3-ubiquitin ligase that cooperates with the E2-ubiquitin conjugase UbE2K to catalyze the synthesis of unanchored K48-linked polyubiquitin chains, and further stimulates the interferon-I kappa B kinase epsilon (IKKepsilon) kinase-mediated antiviral response. It also regulates the transcriptional activity of Myc during the maintenance of embryonic stem (ES) cell pluripotency, and may act as a novel regulator for Myc-mediated transcription in ES cells. TRIM22, also known as 50 kDa-stimulated trans-acting factor (Staf-50) or RING finger protein 94 (RNF94), is an E3 ubiquitin-protein ligase that plays an integral role in the host innate immune response to viruses. It has been shown to inhibit the replication of a number of viruses, including HIV-1, hepatitis B, and influenza A. TRIM22 acts as a suppressor of basal HIV-1 long terminal repeat (LTR)-driven transcription by preventing the transcription factor specificity protein 1 (Sp1) binding to the HIV-1 promoter. It also controls FoxO4 activity and cell survival by directing Toll-like receptor 3 (TLR3)-stimulated cells toward type I interferon (IFN) type I gene induction or apoptosis. Moreover, TRIM22 can activate the noncanonical nuclear factor-kappaB (NF-kappaB) pathway by activating I kappa B kinase alpha (IKKalpha). It also regulates nucleotide binding oligomerization domain containing 2 (NOD2)-dependent activation of interferon-beta signaling and nuclear factor-kappaB. TRIM34, also known as interferon-responsive finger protein 1 or RING finger protein 21 (RNF21), may function as antiviral protein that contribute to the defense against retroviral infections.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22122567  10 LQEEVTCPICMEILQDPVTIDCGHNFCLQCISQVGKTS----EKIQCPLCKLSVNKNTFRPNKLLASLAE 75
Cdd:cd16591   3 IKEEVTCPICLELLTEPLSLDCGHSFCQACITANHKESvnqeGESSCPVCRTSYQPENLRPNRHLANIVE 72

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 22122567  94 CQRHKEKLHYFCEQDGAFLCVVCRDSKDHKSHNVTLI 130
Cdd:cd19765   3 CEEHGEKIHFFCEDDGKFLCVVCRESREHRTHTVSLL 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 22122567 333 VPVTLDKSSADPDLTFSQDLKKVTLyiVAGKASNRQaKPRPFYPFHCVRGSPGLSSGRQVWEAEIRGPSGGAciVGVVTE 412
Cdd:cd15829  19 VDVTLDPETAHPNLLVSEDKKCVTF--TKKKQRVPD-SPKRFTVNPVVLGFPGFHSGRHFWEVEVGDKPEWA--VGVCKD 93

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22122567 413 -LARGAqSQTVSAQSYIWALRISPSGCQPFTNCKAQEYLQVCLKKVGVYVNHDCGEVVFYDAITSKHIYTFQTSFDGKVF 491
Cdd:cd15829  94 sLSTKA-RRPPSGQQGCWRIQLQGGDYDAPGAVPPPLLLEVKPRGIGVFLDYELGEISFYNMPEKSHIHTFTDTFSGPLR 172

                ...
gi 22122567 492 PLF 494
Cdd:cd15829 173 PYF 175

RING finger, HC subclass, found in tripartite motif-containing protein TRIM21 and similar proteins; TRIM21, also known as 52 kDa Ro protein, 52 kDa ribonucleoprotein autoantigen Ro/SS-A, Ro(SS-A), RING finger protein 81 (RNF81), or Sjoegren syndrome type A antigen (SS-A), is a ubiquitously expressed E3 ubiquitin-protein ligase and a high affinity antibody receptor uniquely expressed in the cytosol of mammalian cells. As a cytosolic Fc receptor, TRIM21 binds the Fc of virus-associated antibodies and targets the complex in the cytosol for proteasomal degradation in a process known as antibody-dependent intracellular neutralization (ADIN), and provides an intracellular immune response to protect host defense against pathogen infection. It shows remarkably broad isotype specificity as it does not only bind IgG, but also IgM and IgA. Moreover, TRIM21 promotes the cytosolic DNA sensor cGAS and the cytosolic RNA sensor RIG-I sensing of viral genomes during infection by antibody-opsonized virus. It stimulates inflammatory signaling and activates innate transcription factors, such as nuclear factor-kappaB (NF-kappaB). TRIM21 also plays an essential role in p62-regulated redox homeostasis, suggesting it may be a viable target for treating pathological conditions resulting from oxidative damage. Furthermore, TRIM21 may have implications for various autoimmune diseases associated with uncontrolled antiviral signaling through the regulation of Nmi-IFI35 complex-mediated inhibition of innate antiviral response. TRIM21 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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22122567   9 QLQEEVTCPICMEILQDPVTIDCGHNFCLQCISQVGKTSEKIqCPLCKLSVNKNTFRPNKLLASLAEKIQ 78
Cdd:cd16596   5 MMWEEVTCPICLDPFVEPVSIECGHSFCQECISQVGKGGGSV-CPVCRQRFLLKNLRPNRQLANMVNNLK 73

RING finger, HC subclass, found in tripartite motif-containing protein 69 (TRIM69) and similar proteins; TRIM69, also known as RFP-like domain-containing protein trimless or RING finger protein 36 (RNF36), is a testis E3 ubiquitin-protein ligase that plays a specific role in apoptosis and may also play an important role in germ cell homeostasis during spermatogenesis. TRIM69 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.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 22122567  10 LQEEVTCPICMEILQDPVTIDCGHNFCLQCISQV-GKTSEKIQCPLCKLSVNKNTFRPN 67
Cdd:cd16611   1 LTEELHCPLCLDFFRDPVMLSCGHNFCQSCITGFwELQAEDTTCPECRELCQYRNLTPN 59

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.