RING finger, HC subclass, found in tripartite motif-containing protein 35 (TRIM35) and similar proteins; TRIM35, also known as hemopoietic lineage switch protein 5 (HLS5), is a putative hepatocellular carcinoma (HCC) suppressor that inhibits phosphorylation of pyruvate kinase isoform M2 (PKM2), which is involved in aerobic glycolysis of cancer cells and further suppresses the Warburg effect and tumorigenicity in HCC. It also negatively regulates Toll-like receptor 7 (TLR7)- and TLR9-mediated type I interferon production by suppressing the stability of interferon regulatory factor 7 (IRF7). Moreover, TRIM35 regulates erythroid differentiation by modulating globin transcription factor 1 (GATA-1) activity. TRIM35 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 56404980  15 FKEELLCAVCYDPFRDAVTLRCGHNFCRGCVSRCWEVQVSPTCPVCKDRASPADLRTNHTLNNLVE 80
Cdd:cd16599   1 FKEELLCPICYEPFREAVTLRCGHNFCKGCVSRSWERQPRAPCPVCKEASSSDDLRTNHTLNNLVE 66

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 56404980   188 RQEFDKLREFLRVEEQ--AIL----DAMAEETRQKQLLADEKMKQL---TEETEVLAHEIERLQ--MEMKEDDVSFLMK 255
Cdd:pfam10174 323 KQHIEVLKESLTAKEQraAILqtevDALRLRLEEKESFLNKKTKQLqdlTEEKSTLAGEIRDLKdmLDVKERKINVLQK 401

RING finger, HC subclass, found in tripartite motif-containing protein 35 (TRIM35) and similar proteins; TRIM35, also known as hemopoietic lineage switch protein 5 (HLS5), is a putative hepatocellular carcinoma (HCC) suppressor that inhibits phosphorylation of pyruvate kinase isoform M2 (PKM2), which is involved in aerobic glycolysis of cancer cells and further suppresses the Warburg effect and tumorigenicity in HCC. It also negatively regulates Toll-like receptor 7 (TLR7)- and TLR9-mediated type I interferon production by suppressing the stability of interferon regulatory factor 7 (IRF7). Moreover, TRIM35 regulates erythroid differentiation by modulating globin transcription factor 1 (GATA-1) activity. TRIM35 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 56404980  15 FKEELLCAVCYDPFRDAVTLRCGHNFCRGCVSRCWEVQVSPTCPVCKDRASPADLRTNHTLNNLVE 80
Cdd:cd16599   1 FKEELLCPICYEPFREAVTLRCGHNFCKGCVSRSWERQPRAPCPVCKEASSSDDLRTNHTLNNLVE 66

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 56404980   356 HAWEVALGGLQS--WRVGVVRVRQDSGAEGHShscyhDTRSGFWYVCRTQGVEgdHCVTSDPATSPLVLAIPRRLRVELE 433
Cdd:pfam00622   2 HYFEVEIFGQDGggWRVGWATKSVPRKGERFL-----GDESGSWGYDGWTGKK--YWASTSPLTGLPLFEPGDVIGCFLD 74

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 56404980   434 CEEGELSFYDAErHCHLYTFH-ARF-GEVRPYFYLGGARGAGPPEPLR 479
Cdd:pfam00622  75 YEAGTISFTKNG-KSLGYAFRdVPFaGPLFPAVSLGAGEGLKFNFGLR 121

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 56404980    15 FKEELLCAVCYDPFRDAVTLRCGHNFCRGCVSRCWEVQvsPTCPVCKDRASPADLRTNHTLNNLVE 80
Cdd:TIGR00599  23 LDTSLRCHICKDFFDVPVLTSCSHTFCSLCIRRCLSNQ--PKCPLCRAEDQESKLRSNWLVSEIVE 86

Zinc finger, C3HC4 type (RING finger); The C3HC4 type zinc-finger (RING finger) is a cysteine-rich domain of 40 to 60 residues that coordinates two zinc ions, and has the consensus sequence: C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-C-X2-C-X(4-48)-C-X2-C where X is any amino acid. Many proteins containing a RING finger play a key role in the ubiquitination pathway.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 56404980    21 CAVCYDPFRDAV-TLRCGHNFCRGCVSRCWEVQvSPTCPVC 60
Cdd:pfam00097   1 CPICLEEPKDPVtLLPCGHLFCSKCIRSWLESG-NVTCPLC 40

B-Box-type zinc finger;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 56404980     99 RVCRLHRGQ-LSLFCLEDKELLCCSCQAdPRHQGHRVQPV 137
Cdd:smart00336   4 PKCDSHGDEpAEFFCEECGALLCRTCDE-AEHRGHTVVLL 42

E3 ubiquitin-protein ligase RMA2; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 56404980   21 CAVCYDPFRDAVTLRCGHNFCRGCVSRcWEVQVS---------------PTCPVCKDRASPADL 69
Cdd:PLN03208  21 CNICLDQVRDPVVTLCGHLFCWPCIHK-WTYASNnsrqrvdqydhkrepPKCPVCKSDVSEATL 83

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56404980 152 EHALREKAKAFwamrRSYEAIAKhnqvEAAWLEGRIRQEFDKLREFLRVEEQAILDAMAEETRQKQLLADEKMKQLTEET 231
Cdd:COG4717 384 EEELRAALEQA----EEYQELKE----ELEELEEQLEELLGELEELLEALDEEELEEELEELEEELEELEEELEELREEL 455

                        90
                ....*....|
gi 56404980 232 EVLAHEIERL 241
Cdd:COG4717 456 AELEAELEQL 465

B-box zinc finger;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 56404980    99 RVCRLHRGQ-LSLFCLEDKELLC--CSCQAdprHQGHRVQPV 137
Cdd:pfam00643   4 RLCPEHEEEpLTLYCNDCQELLCeeCSVGE---HRGHTVVPL 42

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 56404980 303 PFSFDPNTAAGWLSVSDDLTSVTNHGYRVQV-ENPERFSSAPCLLGSRVFSQGSHAWEVALGGLQSWRVGVVRVRQDSGA 381
Cdd:cd13733   1 DVTLDPDTAHPNLILSEDLKSVRYGDKRQNLpDNPERFDTCVCVLGSEGFSSGRHYWEVEVGGKTDWDLGVARESVNRKG 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56404980 382 EghshsCYHDTRSGFWYVCRTQGVEgdHCVTSDPATsPLVLAI-PRRLRVELECEEGELSFYDAERHCHLYTFHARF-GE 459
Cdd:cd13733  81 K-----ITLSPENGYWTVGLRNGNE--YKALTSPST-PLSLREkPQKVGVFLDYEEGQVSFYNVDDGSHIYTFTDCFtEK 152

                       170       180
                ....*....|....*....|..
gi 56404980 460 VRPYFYLGGARGAGPPEPLRIC 481
Cdd:cd13733 153 LYPYFSPCLNDGGKNSAPLIIC 174

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 56404980 305 SFDPNTAAGWLSVSDDLTSVTnHGYRVQ--VENPERFSSAPCLLGSRVFSQGSHAWEVALGGLQSWRVGVVR--VRQ--- 377
Cdd:cd12888   3 TLDPDTAHPRLVLSEDRKSVR-WGDTRQdlPDNPERFDTWPCVLGCEGFTSGRHYWEVEVGDGGGWAVGVAResVRRkge 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56404980 378 -DSGAEGhshscyhdtrsGFWYVcrtqGVEGDHCV--TSDPATSPLvLAIPRRLRVELECEEGELSFYDAERHCHLYTFH 454
Cdd:cd12888  82 iSFSPEE-----------GIWAV----GQWGGQYWalTSPETPLPL-SEVPRRIRVYLDYEGGQVAFFDADNEAPIFTFP 145

                       170       180       190
                ....*....|....*....|....*....|
gi 56404980 455 ARF--GE-VRPYFYLGgaRGAgppePLRIC 481
Cdd:cd12888 146 PASfaGErIFPWFWVG--KGS----QLKLC 169

PRY/SPRY domain in tripartite motif-binding protein 39 (TRIM39) and TRIM39-like; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of pyrin, several tripartite motif-containing proteins (TRIMs), including E3 ubiquitin-protein ligase (TRIM21), RET finger protein (RFP)/tripartite motif protein 27 (TRIM27), as well as butyrophilin (Btns) and butyrophilin-like (Btnl) family members, with the exception of Btnl2. Btn and Btnl family members are novel regulators of immune responses, with many of the genes located within the MHC. They are implicated in T-cell inhibition and modulation of epithelial cell-T cell interactions. TRIM21 (also known as RO52, SSA1 or RNF81) is a major autoantigen in autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and Sjorgen's syndrome. TRIM27 (also known as Ret finger protein, RFP or RNF76) negatively regulates CD4 T-cells by ubiquitinating and inhibiting the class II phosphatidylinositol 3 kinase C2beta (PI3K-C2beta), a kinase critical for KCa3.1 channel activation. The PRY/SPRY domain of Pyrin, which is mutated in familial Mediterranean fever patients, interacts with inflammasome components and inhibits proIL-1beta processing.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56404980 306 FDPNTAAGWLSVSDDLTSVTnHGYRVQ--VENPERFSSAPCLLGSRVFSQGSHAWEVALGGLQSWRVGVVR--VRQdsga 381
Cdd:cd13745   7 LDPDTAHPNLVLSEDRKSVR-HGDTRQdlPDNPERFDTYPCVLGAEGFTGGRHYWEVEVGDKTEWTLGVCResVSR---- 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56404980 382 EGHSHScyhDTRSGFWYVCRTqgvEGDHCVTSDPATSPLVLAIPRRLRVELECEEGELSFYDAERHCHLYTFHARF-GEV 460
Cdd:cd13745  82 KGEVTL---SPENGYWTVWLR---DGKYEALTSPPTPLPVSVRPSRVGIFLDYEAGEVSFYNVTDRSHLFTFTDTFsGTL 155

                       170       180
                ....*....|....*....|..
gi 56404980 461 RPYFYLGGARGAGPPEPLRICP 482
Cdd:cd13745 156 RPYFYPGLNAGGKNAAPLIICP 177

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 56404980 307 DPNTAAGWLSVSDDLTSVTN-HGYRVQVENPERFSSAPCLLGSRVFSQGSHAWEVALGGLQSWRVGVVR---VRQDSGAE 382
Cdd:cd15816   5 DPATAHPSLLLTADLRSVQDgELWRDVPGNPERFDTWPCVLGLQSFSSGRHYWEVAVGEKAEWGLGVCQdsaPRKGETTP 84

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56404980 383 GHSHscyhdtrsGFWYVCRTQGveGDHCVTSDPATSPLVLAIPRRLRVELECEEGELSFYDAERHCHLYTFHARF-GEVR 461
Cdd:cd15816  85 SPEN--------GVWAVWLLKG--NEYMVLASPSVPLLQLRRPRRVGVFLDYEAGEISFYNVTAGSHIYTFRQLFsGILR 154

                ....*
gi 56404980 462 PYFYL 466
Cdd:cd15816 155 PYFFV 159

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 56404980 301 SVPFSFDPNTAAGWLSVSDDLTSVtNHGYRVQ--VENPERFSSAPCLLGSRVFSQGSHAWEVALGGLQSWRVGVVrvrQD 378
Cdd:cd15814   1 SVDVTLDPDTAYPSLILSDNLRQV-RYSYLQQdlPDNPERFNLFPCVLGSPCFIAGRHYWEVEVGDKAKWTIGVC---ED 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56404980 379 SGA-EGHSHSCyhdTRSGFWYVCRTQGVEgdHCVTSDPATSpLVLAIP-RRLRVELECEEGELSFYDAERHCHLYTF-HA 455
Cdd:cd15814  77 SVCrKGGVTSA---PQNGFWAVSLWYGKE--YWALTSPMTA-LPLRTPlQRVGIFLDYDAGEVSFYNVTERCHTFTFsHA 150

                       170       180       190
                ....*....|....*....|....*....|.
gi 56404980 456 RF-GEVRPYF---YLGGARGAgppePLRICP 482
Cdd:cd15814 151 TFcGPVRPYFslsYSGGKSAA----PLIICP 177

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 56404980 307 DPNTAAGWLSVSDDLTSVTNHGYRVQV-ENPERFSSAPCLLGSRVFSQGSHAWEVALGGLQSWRVGVVRvrqdsgaEGHS 385
Cdd:cd15820   9 DPDTANPILLISEDQRSLQWADEPQNLpDNPKRFDWHYCVLGCKSFTSGRHFWEVEVGDRKEWYVGVCR-------ENVE 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56404980 386 HSCYHDT--RSGFWYVCRTQGveGDHCVTSDPATSPLVLAIPRRLRVELECEEGELSFYDAERHCHLYTF-HARF-GEVR 461
Cdd:cd15820  82 RKLWVKMapENGFWTIGLSDG--NDYQALTDPRTKLTIANPPQRVGVFLDYETGEVSFYNAMDGSHIYTFpHTSFsGPLY 159

                       170       180
                ....*....|....*....|.
gi 56404980 462 PYFYLGGARgagpPEPLRICP 482
Cdd:cd15820 160 PVFRLLSWD----PTALTICP 176

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 56404980 302 VPFSFDPNTAAGWLSVSDDLTSVTNHGYRVQV-ENPERFSSAPCLLGSRVFSQGSHAWEVALGGLQSWRVGVVRvrqDSG 380
Cdd:cd12900   3 VHITLDPDTANPWLILSKDRRQVRLGDTHQNVpENEERFDNYPMVLGAQRFNSGKHYWEVDVTGKEAWDLGVCR---DSV 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56404980 381 AEGHSHSCyhDTRSGFWYVCRTQGVegdHCVTSDPATSPLVLAIPRRLRVELECEEGELSFYDAERHCHL-YTFH--ARF 457
Cdd:cd12900  80 RRKGQFLL--SPENGFWTIWLWNKK---YEAGTSPQTTLHLQVPPCQVGIFLDYEAGVVSFYNITDHGSLiYTFSecAFT 154

                       170       180
                ....*....|....*....|....*.
gi 56404980 458 GEVRPYFYLGGARGAGPPEPLRICPL 483
Cdd:cd12900 155 GPLRPFFNPGFNDSGGNAAPLTLCPL 180

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 56404980 307 DPNTAAGWLSVSDDLTSVTnhgYRVQVEN----PERFSSAPCLLGSRVFSQGSHAWEVALGGLQSWRVGVVRVRQDSGAE 382
Cdd:cd15817   5 DPETAHPNLIVSEDRKAVR---YRRMKPNcpydPRRFTVYPAVLGSEGFDSGRHFWEVEVGGKGEWILGVCKDSLPRNAQ 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56404980 383 GHShscyhDTRSGFWYVcrtqGVEGDHCVTSDPATSPLVLAI-PRRLRVELECEEGELSFYDAERHCHLYTFHARF-GEV 460
Cdd:cd15817  82 DPP-----SPLGGCWQI----GRYMSGYVASGPKTTQLLPVVkPSRIGIFLDYELGEVSFYNMNDRSHLYTFTDTFtGKL 152

                       170       180
                ....*....|....*....|.
gi 56404980 461 RPYFYLGGARgagppEPLRIC 481
Cdd:cd15817 153 IPYFYVGPDS-----EPLTIC 168

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 56404980 307 DPNTAAGWLSVSDDLTSVTNHGYRVQV-ENPERFSSAPCLLGSRVFSQGSHAWEVALGGLQSWRVGVVR--VRQdsgAEG 383
Cdd:cd15819   7 DPDTAHPALILSEDGRSVTWGETRQDLpENPERFDSLPCVLGQEGFTSGRHYWEVEVGDRTSWDLGVCRdnVMR---KGR 83

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56404980 384 HSHSCYHdtrsGFWYVcrtQGVEGDHCVTSDPATsPLVLAI-PRRLRVELECEEGELSFYDAERHCHLYTF-HARF-GEV 460
Cdd:cd15819  84 VTLSPEN----GFWAI---RLYGNEYWALTSPET-PLTLKEpPRRVGIFLDYEAGDVSFYNMTDGSHIYTFpQTAFsGPL 155

                       170       180
                ....*....|....*....|.
gi 56404980 461 RPYFYLggarGAGPPEPLRIC 481
Cdd:cd15819 156 RPFFRL----WSSDSGPLTIC 172

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 56404980 295 MLASVESVPFSFDPNTAAGWLSVSDDLTSVT--NHGYRVQvENPERFSSAPCLLGSRVFSQGSHAWEVALGGLQSWRVGV 372
Cdd:cd15813   2 RAAQAHAVNVTLDPETAHPNLIFSDDLKSVRlgNKWDRLP-DNPERFDSCIIVLGSPSFTSGRHYWEVEVGDKTGWILGV 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56404980 373 VRVrqDSGAEGhshSCYHDTRSGFWYVCRTQGVEgdHCVTSDPATSPLVLAIPRRLRVELECEEGELSFYDAERHCHLYT 452
Cdd:cd15813  81 CKA--SVSRKG---SMTLSPENGYWVVMMTKRNE--YQASTSPPTRLWLREPPRRVGIFLDYEAGDISFYNVTAKSHIYT 153

                       170       180       190
                ....*....|....*....|....*....|.
gi 56404980 453 FHARF--GEVRPYFYLGGARGAGPPEPLRIC 481
Cdd:cd15813 154 FTSFSssGPLQPIFSPGTHDGGKNMDPLTIC 184

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 56404980 290 RVWKKMLASVESVpfSFDPNTAAGWLSVSDDLTSVtNHGYRVQ--VENPERFSSAPCLLGSRVFSQGSHAWEVALGGLQS 367
Cdd:cd13743   2 RLHRKVLPAPELL--KLDPLTAHPMLELSKGNTVV-ECGLLAQrlPSNPERFDYSNCVLASRGFSSGKHYWEVVVGSKSK 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56404980 368 WRVGVVRvrqdsGAEGHSHSCYHDTRSGFWYVCRTQGVegdhcVTSDPATSPLVLAI---PRRLRVELECEEGELSFYDA 444
Cdd:cd13743  79 WRLGLIK-----GTTSRKGKLNKSPENGVWLIGLKEGR-----VYEAFANPRVPLPLstrPQRIGVFLDYEKGELTFYNA 148

                       170       180
                ....*....|....*....|....
gi 56404980 445 ERHCHL---YTFHARF-GEVRPYF 464
Cdd:cd13743 149 DSPDELvpiYTFQAEFqGKLYPLL 172

PRY/SPRY domain in tripartite motif-binding (TRIM) proteins TRIM50 and TRIM72; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of several TRIM proteins, including TRIM72 and TRIM50. TRIM72 (also known as MG53) has been shown to perform a critical function in membrane repair following acute muscle injury by nucleating the assembly of the repair machinery at injury sites. It is expressed specifically in skeletal muscle and heart, and tethered to the plasma membrane and cytoplasmic vesicles via its interaction with phosphatidylserine. TRIM50, an E3 ubiquitin ligase, is deleted in Williams-Beuren (WBS) syndrome, a multi-system neurodevelopmental disorder caused by the deletion of contiguous genes at chromosome region 7q11.23.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56404980 290 RVWKKMLASVESVpfSFDPNTAAGWLSVSDDLTSVTNHGYRVQV-ENPERFSSAPCLLGSRVFSQGSHAWEVALGGLQSW 368
Cdd:cd12897   2 KMFRALMPALESL--TFDPATAHPLLVVSSGGTVVECGLQKQRRaSQPERFDKSTCVVASQGFSEGEHYWEVVVGDKPRW 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56404980 369 RVGVVRvrqdsgAEGHSHSCYHDTRS-GFWYV-CRTQGVEGDHCVTSDPATSPlVLAIPRRLRVELECEEGELSFYDAER 446
Cdd:cd12897  80 ALGVIK------GTASRKGKLHASPShGVWLIgLKEGKVYEAHGEPKEPRPLR-VAGRPHRIGVYLSFEDGVLSFFDASD 152

                       170       180
                ....*....|....*....|..
gi 56404980 447 HCH---LYTFHARF-GEVRPYF 464
Cdd:cd12897 153 PDDlrtLYTFQERFqGKLYPFF 174