PRY/SPRY domain of tripartite motif-binding protein 17 (TRIM17), also known as testis RING finger protein (terf); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM17, also known as RING finger protein 16 (RNF16) or testis RING finger protein (terf). TRIM17 domain is composed of RING/B-box/coiled-coil core and also known as RBCC protein, expressed almost exclusively in the testis. It exhibits E3 ligase activity, causing protein degradation of ZW10 interacting protein (ZWINT), a known component of the kinetochore complex required for the mitotic spindle checkpoint, and negatively regulates proliferation of breast cancer cells. TRIM17 undergoes ubiquitination in COS7 fibroblast-like cells but is inhibited and stabilized by TRIM44.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444726835 278 DVVPDPTSAYPYLLLYESRQRRYLSSPPEGSiLCSKDRFMAYPCAVGQKTFSSGRHYWEVGMNLTGDALWALGVCRDNVS 357
Cdd:cd15812    1 DVVPDPSTAYPYLLLYESRQRRYLSTPPDGT-PCSKDRFLAYPCAVGQETFSSGRHYWEVGMNLTGDALWALGVCRDNVS 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444726835 358 RKDRVPKSPENGFWVVQLSKGKKYSSTMSAPIPVTLTEPPSHMGIFLDFEAGEVSFYSVNDGSHLHTYSQGAFPGPLQPF 437
Cdd:cd15812   80 RKDRVPKSPENGFWVVQLSKGKKYLSAMSALTPVTLTEPPSHMGIFLDFEAGEVSFYSVNDGSHLHTYSQAAFPGPLQPF 159

                        170
                 ....*....|....*..
gi 444726835 438 FCLGAPKSGQMVISTVT 454
Cdd:cd15812  160 FCLGAPKSGQMVISTVT 176

B-box-type 2 zinc finger found in tripartite motif-containing proteins TRIM7, TRIM27 and similar proteins; The family includes TRIM7 and TRIM27, both of which belong to the C-IV subclass of TRIM (tripartite motif) family of proteins that are defined by an N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a RING finger, Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif. 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. TRIM27, also termed RING finger protein 76 (RNF76), or 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. It also inhibits muscle differentiation by modulating serum response factor (SRF) and Epc1. Furthermore, TRIM27 promotes 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. In addition, TRIM27 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 also a component of an estrogen receptor 1 (ESR1) regulatory complex, and is involved in estrogen receptor-mediated transcription in MCF-7 cells. Meanwhile, TRIM27 interacts with the hinge region of chromosome 3 protein (SMC3), a component of the multimeric cohesin complex that holds sister chromatids together and prevents their premature separation during mitosis.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 444726835  98 LCQVHQEPLKLFCEEDQIPICVVCRESREHRTHTVLPMEEAVK 140
Cdd:cd19762    2 VCEKHQEPLKLFCKEDKRPICVVCDRSREHRHHTVLPVEEAAQ 44

PRY/SPRY domain of tripartite motif-binding protein 17 (TRIM17), also known as testis RING finger protein (terf); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM17, also known as RING finger protein 16 (RNF16) or testis RING finger protein (terf). TRIM17 domain is composed of RING/B-box/coiled-coil core and also known as RBCC protein, expressed almost exclusively in the testis. It exhibits E3 ligase activity, causing protein degradation of ZW10 interacting protein (ZWINT), a known component of the kinetochore complex required for the mitotic spindle checkpoint, and negatively regulates proliferation of breast cancer cells. TRIM17 undergoes ubiquitination in COS7 fibroblast-like cells but is inhibited and stabilized by TRIM44.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444726835 278 DVVPDPTSAYPYLLLYESRQRRYLSSPPEGSiLCSKDRFMAYPCAVGQKTFSSGRHYWEVGMNLTGDALWALGVCRDNVS 357
Cdd:cd15812    1 DVVPDPSTAYPYLLLYESRQRRYLSTPPDGT-PCSKDRFLAYPCAVGQETFSSGRHYWEVGMNLTGDALWALGVCRDNVS 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444726835 358 RKDRVPKSPENGFWVVQLSKGKKYSSTMSAPIPVTLTEPPSHMGIFLDFEAGEVSFYSVNDGSHLHTYSQGAFPGPLQPF 437
Cdd:cd15812   80 RKDRVPKSPENGFWVVQLSKGKKYLSAMSALTPVTLTEPPSHMGIFLDFEAGEVSFYSVNDGSHLHTYSQAAFPGPLQPF 159

                        170
                 ....*....|....*..
gi 444726835 438 FCLGAPKSGQMVISTVT 454
Cdd:cd15812  160 FCLGAPKSGQMVISTVT 176

RING finger, HC subclass, found in tripartite motif-containing protein TRIM17 and similar proteins; TRIM17, also known as RING finger protein 16 (RNF16) or testis RING finger protein (Terf), is a crucial E3 ubiquitin ligase that is necessary and sufficient for neuronal apoptosis and contributes to Mcl-1 ubiquitination in cerebellar granule neurons (CGNs). It interacts in a SUMO-dependent manner with nuclear factor of activated T cell NFATc3 transcription factor, and thus inhibits the activity of NFATc3 by preventing its nuclear localization. In contrast, it binds to and inhibits NFATc4 transcription factor in a SUMO-independent manner. Moreover, TRIM17 stimulates degradation of kinetochore protein ZW10 interacting protein (ZWINT), a known component of the kinetochore complex required for the mitotic spindle checkpoint, and negatively regulates cell proliferation. TRIM17 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 444726835   9 KLQEEATCSICLDYFIDPVMTTCGHNFCRECIQLSWEKAKGKKGRRKRKSSFSCPECREMSPQRNLRPNR 78
Cdd:cd16595    1 RLQEEATCSICLDYFTDPVMTTCGHNFCRACIQLSWEKARGKKGRRKQKGSFPCPECREMSPQRNLRPNR 70

B-box-type 2 zinc finger found in tripartite motif-containing proteins TRIM7, TRIM27 and similar proteins; The family includes TRIM7 and TRIM27, both of which belong to the C-IV subclass of TRIM (tripartite motif) family of proteins that are defined by an N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a RING finger, Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif. 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. TRIM27, also termed RING finger protein 76 (RNF76), or 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. It also inhibits muscle differentiation by modulating serum response factor (SRF) and Epc1. Furthermore, TRIM27 promotes 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. In addition, TRIM27 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 also a component of an estrogen receptor 1 (ESR1) regulatory complex, and is involved in estrogen receptor-mediated transcription in MCF-7 cells. Meanwhile, TRIM27 interacts with the hinge region of chromosome 3 protein (SMC3), a component of the multimeric cohesin complex that holds sister chromatids together and prevents their premature separation during mitosis.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 444726835  98 LCQVHQEPLKLFCEEDQIPICVVCRESREHRTHTVLPMEEAVK 140
Cdd:cd19762    2 VCEKHQEPLKLFCKEDKRPICVVCDRSREHRHHTVLPVEEAAQ 44

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 444726835   16 CSICLDYFIDPVmTTCGHNFCRECIQLSWEkakgkkgrrKRKSSFSCP 63
Cdd:pfam13445   1 CPICLELFTDPV-LPCGHTFCRECLEEMSQ---------KKGGKFKCP 38

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        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 444726835    16 CSICLDYFI-DPVMTTCGHNFCRECIQLSWEkakgkkgrrkrKSSFSCPEC 65
Cdd:smart00184   1 CPICLEEYLkDPVILPCGHTFCRSCIRKWLE-----------SGNNTCPIC 40

MAEBL; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444726835   64 ECREMSPQRNLRPNRLLTKVAEMARQHpgLQKRDLCQVHQEPLKLFCEEDQIPICVVCRESREHRTHTVLPMEEavKEYK 143
Cdd:PTZ00121 1585 EAKKAEEARIEEVMKLYEEEKKMKAEE--AKKAEEAKIKAEELKKAEEEKKKVEQLKKKEAEEKKKAEELKKAE--EENK 1660

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444726835  144 LKLEEDMKYLREEMMKTENL-QAKEEQTLAEWQDKVKERRERIMAEFEKMGlflmEEERRLLQALKKEEdkimaglQESK 222
Cdd:PTZ00121 1661 IKAAEEAKKAEEDKKKAEEAkKAEEDEKKAAEALKKEAEEAKKAEELKKKE----AEEKKKAEELKKAE-------EENK 1729

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 444726835  223 TSLEQQSHSLEmlllqmEDRHEREPLRMLQDMKNPLGRTVCRVPGQIEVLKGFQEDVV 280
Cdd:PTZ00121 1730 IKAEEAKKEAE------EDKKKAEEAKKDEEEKKKIAHLKKEEEKKAEEIRKEKEAVI 1781

RNase Y N-terminal region;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444726835  163 LQAKEE--QTLAEWQDKVKERRerimAEFEKMglflmeeERRLLQalkKEE--DKIMAGLQESKTSLEQQSHSLEMLLLQ 238
Cdd:pfam12072  56 LEAKEEihKLRAEAERELKERR----NELQRQ-------ERRLLQ---KEEtlDRKDESLEKKEESLEKKEKELEAQQQQ 121

                  ....*.
gi 444726835  239 MEDRHE 244
Cdd:pfam12072 122 LEEKEE 127

E3 ubiquitin-protein ligase RMA2; Provisional

                         10        20
                 ....*....|....*....|....*.
gi 444726835  16 CSICLDYFIDPVMTTCGHNFCRECIQ 41
Cdd:PLN03208  21 CNICLDQVRDPVVTLCGHLFCWPCIH 46

PRY/SPRY domain of tripartite motif-binding protein 17 (TRIM17), also known as testis RING finger protein (terf); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM17, also known as RING finger protein 16 (RNF16) or testis RING finger protein (terf). TRIM17 domain is composed of RING/B-box/coiled-coil core and also known as RBCC protein, expressed almost exclusively in the testis. It exhibits E3 ligase activity, causing protein degradation of ZW10 interacting protein (ZWINT), a known component of the kinetochore complex required for the mitotic spindle checkpoint, and negatively regulates proliferation of breast cancer cells. TRIM17 undergoes ubiquitination in COS7 fibroblast-like cells but is inhibited and stabilized by TRIM44.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444726835 278 DVVPDPTSAYPYLLLYESRQRRYLSSPPEGSiLCSKDRFMAYPCAVGQKTFSSGRHYWEVGMNLTGDALWALGVCRDNVS 357
Cdd:cd15812    1 DVVPDPSTAYPYLLLYESRQRRYLSTPPDGT-PCSKDRFLAYPCAVGQETFSSGRHYWEVGMNLTGDALWALGVCRDNVS 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444726835 358 RKDRVPKSPENGFWVVQLSKGKKYSSTMSAPIPVTLTEPPSHMGIFLDFEAGEVSFYSVNDGSHLHTYSQGAFPGPLQPF 437
Cdd:cd15812   80 RKDRVPKSPENGFWVVQLSKGKKYLSAMSALTPVTLTEPPSHMGIFLDFEAGEVSFYSVNDGSHLHTYSQAAFPGPLQPF 159

                        170
                 ....*....|....*..
gi 444726835 438 FCLGAPKSGQMVISTVT 454
Cdd:cd15812  160 FCLGAPKSGQMVISTVT 176

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 444726835 278 DVVPDPTSAYPYLLLYESRQRRYLSSPPEGsiLCSK-DRFMAYPCAVGQKTFSSGRHYWEVGMNLTGDalWALGVCRDNV 356
Cdd:cd15819    3 NVTLDPDTAHPALILSEDGRSVTWGETRQD--LPENpERFDSLPCVLGQEGFTSGRHYWEVEVGDRTS--WDLGVCRDNV 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444726835 357 SRKDRVPKSPENGFWVVQLSKGKkYSSTMSAPIPVTLTEPPSHMGIFLDFEAGEVSFYSVNDGSHLHTYSQGAFPGPLQP 436
Cdd:cd15819   79 MRKGRVTLSPENGFWAIRLYGNE-YWALTSPETPLTLKEPPRRVGIFLDYEAGDVSFYNMTDGSHIYTFPQTAFSGPLRP 157

                        170
                 ....*....|....
gi 444726835 437 FFCLGAPKSGQMVI 450
Cdd:cd15819  158 FFRLWSSDSGPLTI 171

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 444726835 275 FQ-EDVVPDPTSAYPYLLLYESRQRRYLSSPPEgSILCSKDRFMAYPCAVGQKTFSSGRHYWEVGMnltGD-ALWALGVC 352
Cdd:cd15820    1 FQpADVILDPDTANPILLISEDQRSLQWADEPQ-NLPDNPKRFDWHYCVLGCKSFTSGRHFWEVEV---GDrKEWYVGVC 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444726835 353 RDNVSRKDRVPKSPENGFWVVQLSKGKKYSSTMSAPIPVTLTEPPSHMGIFLDFEAGEVSFYSVNDGSHLHTYSQGAFPG 432
Cdd:cd15820   77 RENVERKLWVKMAPENGFWTIGLSDGNDYQALTDPRTKLTIANPPQRVGVFLDYETGEVSFYNAMDGSHIYTFPHTSFSG 156

                 ....*.
gi 444726835 433 PLQPFF 438
Cdd:cd15820  157 PLYPVF 162

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 444726835 270 EVLKGFQEDVVPDPTSAYPYLLLYESRQ-----RRYLSSPPegsilcSKDRFMAYPCAVGQKTFSSGRHYWEVGMnltGD 344
Cdd:cd15829   12 KIIKKFRVDVTLDPETAHPNLLVSEDKKcvtftKKKQRVPD------SPKRFTVNPVVLGFPGFHSGRHFWEVEV---GD 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444726835 345 -ALWALGVCRDNVSRKDRVPKSPENGFWVVQLSKGKkYSSTMSAPIPVTLTEPPSHMGIFLDFEAGEVSFYSVNDGSHLH 423
Cdd:cd15829   83 kPEWAVGVCKDSLSTKARRPPSGQQGCWRIQLQGGD-YDAPGAVPPPLLLEVKPRGIGVFLDYELGEISFYNMPEKSHIH 161

                        170
                 ....*....|....*...
gi 444726835 424 TYsQGAFPGPLQPFFCLG 441
Cdd:cd15829  162 TF-TDTFSGPLRPYFYVG 178

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 444726835 272 LKGFQEDVVPDPTSAYPYLLLYESRQRRYLSSPPEGsILCSKDRFMAYPCAVGQKTFSSGRHYWEVGM-NLTGdalWALG 350
Cdd:cd15815    8 LRRHQVSVTLDPDTAHPELTLSKDQRQVTYGRCQEN-LDASPKRFTVLPCVLGCEGFTSGRHYFEVDVgEGTG---WDVG 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444726835 351 VCRDNVSRKDRVPKSPENGFWVVQLSKGKKYSSTMSAPIPVTLTEPPSHMGIFLDFEAGEVSFYSVNDGSHLHTYSQGAF 430
Cdd:cd15815   84 VCLENVQRGFGMKQEPEFGFWTIRLCEEDGYVALTSPPTPLPLREKPLVVGVFLDYEAGLVSFYNMTTGSHIFTFPKASF 163

                 ....*....
gi 444726835 431 PGPLQPFFC 439
Cdd:cd15815  164 SDTLRPYFQ 172

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 444726835 282 DPTSAYPYLLLYESRQRRYLSSPPEgSILCSKDRFMAYPCAVGQKTFSSGRHYWEVgmNLTGDALWALGVCRDNVSRKDR 361
Cdd:cd12900    8 DPDTANPWLILSKDRRQVRLGDTHQ-NVPENEERFDNYPMVLGAQRFNSGKHYWEV--DVTGKEAWDLGVCRDSVRRKGQ 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444726835 362 VPKSPENGFWVVQLSKGKkYSSTMSAPIPVTLTEPPSHMGIFLDFEAGEVSFYSVND-GSHLHTYSQGAFPGPLQPFFCL 440
Cdd:cd12900   85 FLLSPENGFWTIWLWNKK-YEAGTSPQTTLHLQVPPCQVGIFLDYEAGVVSFYNITDhGSLIYTFSECAFTGPLRPFFNP 163

                 ....*.
gi 444726835 441 GAPKSG 446
Cdd:cd12900  164 GFNDSG 169

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 444726835 278 DVVPDPTSAYPYLLLYES-RQRRYlsSPPEGSILCSKDRFMAYPCAVGQKTFSSGRHYWEVGMnltGD-ALWALGVCRDN 355
Cdd:cd15814    3 DVTLDPDTAYPSLILSDNlRQVRY--SYLQQDLPDNPERFNLFPCVLGSPCFIAGRHYWEVEV---GDkAKWTIGVCEDS 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444726835 356 VSRKDRVPKSPENGFWVVQLSKGKKYSSTMSAPIPVTLTEPPSHMGIFLDFEAGEVSFYSVNDGSHLHTYSQGAFPGPLQ 435
Cdd:cd15814   78 VCRKGGVTSAPQNGFWAVSLWYGKEYWALTSPMTALPLRTPLQRVGIFLDYDAGEVSFYNVTERCHTFTFSHATFCGPVR 157

                        170
                 ....*....|....*...
gi 444726835 436 PFFCL---GAPKSGQMVI 450
Cdd:cd15814  158 PYFSLsysGGKSAAPLII 175

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 444726835 278 DVVPDPTSAYPYLLLYESRQ-------RRYLSSPPEgsilcskdRFMAYPCAVGQKTFSSGRHYWEVGMNLTGDalWALG 350
Cdd:cd12888    1 NVTLDPDTAHPRLVLSEDRKsvrwgdtRQDLPDNPE--------RFDTWPCVLGCEGFTSGRHYWEVEVGDGGG--WAVG 70

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444726835 351 VCRDNVSRKDRVPKSPENGFWVVQLSkGKKYSSTMSAPIPVTLTEPPSHMGIFLDFEAGEVSFYSVNDGSHLHTYSQGAF 430
Cdd:cd12888   71 VARESVRRKGEISFSPEEGIWAVGQW-GGQYWALTSPETPLPLSEVPRRIRVYLDYEGGQVAFFDADNEAPIFTFPPASF 149

                        170
                 ....*....|..
gi 444726835 431 PGP-LQPFFCLG 441
Cdd:cd12888  150 AGErIFPWFWVG 161

RING finger, HC subclass, found in tripartite motif-containing protein TRIM17 and similar proteins; TRIM17, also known as RING finger protein 16 (RNF16) or testis RING finger protein (Terf), is a crucial E3 ubiquitin ligase that is necessary and sufficient for neuronal apoptosis and contributes to Mcl-1 ubiquitination in cerebellar granule neurons (CGNs). It interacts in a SUMO-dependent manner with nuclear factor of activated T cell NFATc3 transcription factor, and thus inhibits the activity of NFATc3 by preventing its nuclear localization. In contrast, it binds to and inhibits NFATc4 transcription factor in a SUMO-independent manner. Moreover, TRIM17 stimulates degradation of kinetochore protein ZW10 interacting protein (ZWINT), a known component of the kinetochore complex required for the mitotic spindle checkpoint, and negatively regulates cell proliferation. TRIM17 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 444726835   9 KLQEEATCSICLDYFIDPVMTTCGHNFCRECIQLSWEKAKGKKGRRKRKSSFSCPECREMSPQRNLRPNR 78
Cdd:cd16595    1 RLQEEATCSICLDYFTDPVMTTCGHNFCRACIQLSWEKARGKKGRRKQKGSFPCPECREMSPQRNLRPNR 70

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444726835 279 VVPDPTSAYPYLLLYE-------SRQRRYLSSPPEgsilcskdRFMAYPCAVGQKTFSSGRHYWEVgmnLTGD-ALWALG 350
Cdd:cd12893    2 VTLDPNTAHPWLSLSEdltsvrySSEKQQLPDNPE--------RFDPYPCVLGSEGFTSGKHSWDV---EVGDnTSWMLG 70

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444726835 351 VCRDNVSRKDRVPKSPENGFWVVQLSKGKKYSSTMSAP-IPVTLTEPPSHMGIFLDFEAGEVSFYSVNDGSHLHTYSQgA 429
Cdd:cd12893   71 VAKESVQRKGKFTLSPESGFWTIGFSEGKYSARTSPEPrTPLRVKQKPQRIRVQLDWDRGKVSFSDPDTNTHIHTFTH-T 149

                        170
                 ....*....|....*.
gi 444726835 430 FPGPLQPFFCLGAPKS 445
Cdd:cd12893  150 FTERVFPYFYTGCKSE 165

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 444726835 282 DPTSAYPYLLLYESRQ-------RRYLSSPPEgsilcskdRFMAYPCAVGQKTFSSGRHYWEVgmNLTGDALWALGVCRD 354
Cdd:cd15818   18 DPKTAHPNLILSEDLTcvwhgdtKQMLPDNPE--------RFDSSVAVLGSEGFTSGKHYWEV--EVAKKTKWTLGVVRE 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444726835 355 NVSRKDRVPKSPENGFWVVQLSKGKKYSSTMSAPIPVTLTEPPSHMGIFLDFEAGEVSFYSVNDGSHLHTYSQgAFPGPL 434
Cdd:cd15818   88 SINRKGNCPLSPEDGFWLLRLRNQNELKALDVPSFSLTLTSNLNKVGIYLDYEGGQVSFYNANTMSHIYTFSD-TFTEKI 166

                 ....*
gi 444726835 435 QPFFC 439
Cdd:cd15818  167 YPYFC 171

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 444726835   330 SGRHYWEVGMNLTGDalWALGVCRDNVSRKDRVPKSPENGFWVVQLSKGKKYSSTMSAPIPVTLTEPPSHMGIFLDFEAG 409
Cdd:smart00449   1 SGRHYFEVEIGDGGH--WRVGVATKSVPRGYFALLGEDKGSWGYDGDGGKKYHNSTGPEYGLPLQEPGDVIGCFLDLEAG 78

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 444726835   410 EVSFYSVNDGSHLHTYSQGAFPGPLQPFFCLGAPKSGQMVI 450
Cdd:smart00449  79 TISFYKNGKYLHGLAFFDVKFSGPLYPAFSLGSGNSVRLNF 119

PRY/SPRY domain in tripartite motif-binding protein 4 (TRIM4), also known as RING finger protein 87 (RNF87); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM4 which is also known as RING finger protein 87 (RNF87). TRIM4 domain is composed of RING/B-box/coiled-coil core and also known as RBCC protein. It is a positive regulator of RIG-I-mediated interferon (IFN) induction. It regulates virus-induced IFN induction and cellular antiviral innate immunity by targeting RIG-I for K63-linked poly-ubiquitination. Over-expression of TRIM4 enhances virus-triggered activation of transcription factors IRF3 and NF-kappaB, as well as IFN-beta induction. Expression of TRIM4 differs significantly in Huntington's Disease (HD) neural cells when compared with wild-type controls, possibly impacting down-regulation of the Huntingtin (HTT) gene, which is involved in the regulation of diverse cellular activities that are impaired in Huntington's Disease (HD) cells.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444726835 314 DRFMAYPCAVGQKTFSSGRHYWEVGmnlTGDAL-WALGVCRDNV-SRKDRVPKSPENGFWVVQLSKGKkYSSTMSAPIPV 391
Cdd:cd15809   58 ERFQHLPCVLGKNVFTSGKHYWEVE---NRDSLeIAVGVCREDVmGITDGSEMSPHVGIWAICWSSAG-YRPLTSSPVSP 133

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 444726835 392 TLTEPPSH-MGIFLDFEAGEVSFYSVNDGSHLHTYSqGAFPGPLQPFFCL 440
Cdd:cd15809  134 TKQEPALHrVGVFLDHGAGEVSFYSAVDGVHLHTFS-CPLVSRLRPFFWL 182

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 444726835 282 DPTSAYPYLLLyesrqRRYLSSPPEGSILC----SKDRFMAYPCAVGQKTFSSGRHYWEVgmnLTGD-ALWALGVCRDNV 356
Cdd:cd13743   17 DPLTAHPMLEL-----SKGNTVVECGLLAQrlpsNPERFDYSNCVLASRGFSSGKHYWEV---VVGSkSKWRLGLIKGTT 88

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444726835 357 SRKDRVPKSPENGFWVVQLSKGKKYSSTMSAPIPVTLTEPPSHMGIFLDFEAGEVSFYSVNDGSHLHT-YS-QGAFPGPL 434
Cdd:cd13743   89 SRKGKLNKSPENGVWLIGLKEGRVYEAFANPRVPLPLSTRPQRIGVFLDYEKGELTFYNADSPDELVPiYTfQAEFQGKL 168

                 ....
gi 444726835 435 QPFF 438
Cdd:cd13743  169 YPLL 172

PRY/SPRY domain in tripartite motif-containing protein 34 (TRIM34), also known as RING finger protein 21 (RNF21) or interferon-responsive finger protein (IFP1); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM34, also known as RING finger protein 21 (RNF21) or interferon-responsive finger protein (IFP1). TRIM34 domain is composed of RING/B-box/coiled-coil core and also known as RBCC protein. The TRIM21 cDNA possesses at least three kinds of isoforms, due to alternative splicing, of which only the long and medium forms contain the SPRY domain. It is an interferon-induced protein, predominantly expressed in the testis, kidney, and ovary. The SPRY domain provides the capsid recognition motif that dictates specificity to retroviral restriction. While the PRY-SPRY domain provides specificity and the capsid recognition motif to retroviral restriction, TRIM34 binds HIV-1 capsid but does not restrict HIV-1 infection.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444726835 323 VGQKTFSSGRHYWEVgmNLTGDALWALGV-CRDNVSRKDRVPKS-----------PENGFWVVQLSKGKKYS----STMS 386
Cdd:cd15825   40 LGSQYFSSGKHYWEV--DVSKKTAWILGVyCRKRSRTFKYVRQGknhpnvysryrPQYGYWVIGLQNKSEYYafedSSTS 117

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 444726835 387 APIPVTL--TEPPSHMGIFLDFEAGEVSFYSV-NDGSHLHTYSQGAFPGPLQPFF 438
Cdd:cd15825  118 DPKVLTLsvATPPHRVGVFLDYEAGTVSFFNVtNHGSLIYKFSKCCFSQPVYPYF 172