SPRY domain in the suppressor of cytokine signaling 3 (SOCS3) family; The SPRY domain-containing SOCS box protein family (SPSB1-4, also known as SSB-1 to -4) is composed of a central SPRY protein interaction domain and a C-terminal SOCS box. All four SPSB proteins interact with c-Met, the hepatocyte growth factor receptor, but SOCS3 regulates cellular response to a variety of cytokines such as leukemia inhibitory factor (LIF) and interleukin 6. SOCS3, along with SOCS1, are expressed by immune cells and cells of the central nervous system (CNS) and have the potential to impact immune processes within the CNS. In non-small cell lung cancer (NSCLC), SOCS3 is silenced and proline-rich tyrosine kinase 2 (Pyk2) is over-expressed; it has been suggested that SOCS3 could be an effective way to prevent the progression of NSCLC due to its role in regulating Pyk2 expression.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2181405802   1 MEYSCGTAAIRGTKELGDGQHFWEIKMTSPVYGTDMMVGIGTSDVDLDKYHHTFCSLLGRDEDSWGLSYTGLLHHKGDKT 80
Cdd:cd12876    26 PDYSCGTAAVRGTKPLTNGQHYWEIKMSSPVYGTDMMVGVGTKKADLHAYRYEFCSLLGEDEESWGLSYKGLLWHDGQSR 105

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2181405802  81 SFSSRFG-QGSIIGVHLDTWHGTLTFFKNRKCIGVAATRLQNRR-FYPMVCSTAAKSSMKVIRSCASSTSLQYLCCYRLR 158
Cdd:cd12876   106 PYTSPFGnQGTIIGVHLDMWRGTLTFYKNGKPLGVAFTGLNGVKpLYPMVSSTAAKSEMKLINSRSFPVSLQDRCCAALR 185

SPRY domain in the suppressor of cytokine signaling 3 (SOCS3) family; The SPRY domain-containing SOCS box protein family (SPSB1-4, also known as SSB-1 to -4) is composed of a central SPRY protein interaction domain and a C-terminal SOCS box. All four SPSB proteins interact with c-Met, the hepatocyte growth factor receptor, but SOCS3 regulates cellular response to a variety of cytokines such as leukemia inhibitory factor (LIF) and interleukin 6. SOCS3, along with SOCS1, are expressed by immune cells and cells of the central nervous system (CNS) and have the potential to impact immune processes within the CNS. In non-small cell lung cancer (NSCLC), SOCS3 is silenced and proline-rich tyrosine kinase 2 (Pyk2) is over-expressed; it has been suggested that SOCS3 could be an effective way to prevent the progression of NSCLC due to its role in regulating Pyk2 expression.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2181405802   1 MEYSCGTAAIRGTKELGDGQHFWEIKMTSPVYGTDMMVGIGTSDVDLDKYHHTFCSLLGRDEDSWGLSYTGLLHHKGDKT 80
Cdd:cd12876    26 PDYSCGTAAVRGTKPLTNGQHYWEIKMSSPVYGTDMMVGVGTKKADLHAYRYEFCSLLGEDEESWGLSYKGLLWHDGQSR 105

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2181405802  81 SFSSRFG-QGSIIGVHLDTWHGTLTFFKNRKCIGVAATRLQNRR-FYPMVCSTAAKSSMKVIRSCASSTSLQYLCCYRLR 158
Cdd:cd12876   106 PYTSPFGnQGTIIGVHLDMWRGTLTFYKNGKPLGVAFTGLNGVKpLYPMVSSTAAKSEMKLINSRSFPVSLQDRCCAALR 185

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 2181405802  21 HFWEIKMTSPvYGTDMMVGIGTSDVDLDKYHHtfcslLGRDEDSWGLS-YTGLLHH--KGDKTSfSSRFGQGSIIGVHLD 97
Cdd:pfam00622   2 HYFEVEIFGQ-DGGGWRVGWATKSVPRKGERF-----LGDESGSWGYDgWTGKKYWasTSPLTG-LPLFEPGDVIGCFLD 74

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 2181405802  98 TWHGTLTFFKNRKCIGVAATRLQNRR-FYPMVCSTAAKSSM 137
Cdd:pfam00622  75 YEAGTISFTKNGKSLGYAFRDVPFAGpLFPAVSLGAGEGLK 115

The SOCS box acts as a bridge between specific substrate- binding domains and more generic proteins that comprise a large family of E3 ubiquitin protein ligases;

                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 2181405802  148 SLQYLCCYRLRQLRpnsgDTLEGLPLPPGLKQVLHNK 184
Cdd:smart00969   2 SLQHLCRLAIRRSL----GGIDKLPLPPRLKDYLLYY 34

SPRY domain in the suppressor of cytokine signaling 3 (SOCS3) family; The SPRY domain-containing SOCS box protein family (SPSB1-4, also known as SSB-1 to -4) is composed of a central SPRY protein interaction domain and a C-terminal SOCS box. All four SPSB proteins interact with c-Met, the hepatocyte growth factor receptor, but SOCS3 regulates cellular response to a variety of cytokines such as leukemia inhibitory factor (LIF) and interleukin 6. SOCS3, along with SOCS1, are expressed by immune cells and cells of the central nervous system (CNS) and have the potential to impact immune processes within the CNS. In non-small cell lung cancer (NSCLC), SOCS3 is silenced and proline-rich tyrosine kinase 2 (Pyk2) is over-expressed; it has been suggested that SOCS3 could be an effective way to prevent the progression of NSCLC due to its role in regulating Pyk2 expression.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2181405802   1 MEYSCGTAAIRGTKELGDGQHFWEIKMTSPVYGTDMMVGIGTSDVDLDKYHHTFCSLLGRDEDSWGLSYTGLLHHKGDKT 80
Cdd:cd12876    26 PDYSCGTAAVRGTKPLTNGQHYWEIKMSSPVYGTDMMVGVGTKKADLHAYRYEFCSLLGEDEESWGLSYKGLLWHDGQSR 105

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2181405802  81 SFSSRFG-QGSIIGVHLDTWHGTLTFFKNRKCIGVAATRLQNRR-FYPMVCSTAAKSSMKVIRSCASSTSLQYLCCYRLR 158
Cdd:cd12876   106 PYTSPFGnQGTIIGVHLDMWRGTLTFYKNGKPLGVAFTGLNGVKpLYPMVSSTAAKSEMKLINSRSFPVSLQDRCCAALR 185

SPRY domain in Fbxo45 and suppressors of cytokine signaling (SOCS) proteins; This family consists of the SPRY domain-containing SOCS box protein family (SPSB1-4, also known as SSB-1 to -4) as well as F-box protein 45 (Fbxo45), a novel synaptic E3 and ubiquitin ligase. The SPSB protein is composed of a central SPRY protein interaction domain and a C-terminal SOCS box. SPSB1, SPSB2, and SPSB4 interact with prostate apoptosis response protein 4 (Par-4) and are negative regulators that recruit the ECS E3 ubiquitin ligase complex to polyubiquitinate inducible nitric-oxide synthase (iNOS), resulting in its proteasomal degradation. Fbxo45 is related to this family; it is located N-terminal to the SPRY domain, and known to induce the degradation of a synaptic vesicle-priming factor, Munc13-1, via the SPRY domain, thus playing an important role in the regulation of neurotransmission by modulating Munc13-1 at the synapse. Suppressor of cytokine signaling (SOCS) proteins negatively regulate signaling from JAK-associated cytokine receptor complexes, and play key roles in the regulation of immune homeostasis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2181405802   7 TAAIRGTKELGDGQHFWEIKMTSPVYGTDMMVGIGTSDVDLDKYHHTfcSLLGRDEDSWGLSYT-GLLHHKGDKT----- 80
Cdd:cd12875    30 TDAIRGKKGYTRGLHAWEVKWISRPRGSHAVVGVATKDAPLQCDGYV--TLLGSNSESWGWDLGdNKLYHNGKKVigsyp 107

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2181405802  81 SFSSRFGQGSIIGVHLDTWHGTLTFFKNRKCIGVAATRLQNRRFYPMVCSTAAKSSMKVI 140
Cdd:cd12875   108 AKSENYQVPDRILVILDMEDGTLAFEANGEYLGVAFRGLPGKLLYPAVSAVYGNCEIRLI 167

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 2181405802  21 HFWEIKMTSPvYGTDMMVGIGTSDVDLDKYHHtfcslLGRDEDSWGLS-YTGLLHH--KGDKTSfSSRFGQGSIIGVHLD 97
Cdd:pfam00622   2 HYFEVEIFGQ-DGGGWRVGWATKSVPRKGERF-----LGDESGSWGYDgWTGKKYWasTSPLTG-LPLFEPGDVIGCFLD 74

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 2181405802  98 TWHGTLTFFKNRKCIGVAATRLQNRR-FYPMVCSTAAKSSM 137
Cdd:pfam00622  75 YEAGTISFTKNGKSLGYAFRDVPFAGpLFPAVSLGAGEGLK 115

SPRY domain in the suppressor of cytokine signaling 1, 2, 4 families (SOCS1, SOCS2, SOCS4); The SPRY domain-containing SOCS box protein family (SPSB1-4, also known as SSB-1 to -4) is composed of a central SPRY protein interaction domain and a C-terminal SOCS box. All four SPSB proteins interact with c-Met, the hepatocyte growth factor receptor, but only SPSB1, SPSB2, and SPSB4 interact with prostate apoptosis response protein 4 (Par-4). They are negative regulators that recruit the ECS E3 ubiquitin ligase complex to polyubiquitinate inducible nitric-oxide synthase (iNOS), resulting in its proteasomal degradation, thus contributing to protection against the cytotoxic effect of iNOS in activated macrophages. It has been shown that SPSB1 and SPSB4 induce the degradation of iNOS more strongly than SPSB2. The Drosophila melanogaster SPSB1 homolog, GUSTAVUS, interacts with the DEAD box RNA helicase Vasa. Suppressor of cytokine signaling (SOCS) proteins negatively regulate signaling from JAK-associated cytokine receptor complexes, and play key roles in the regulation of immune homeostasis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2181405802   7 TAAIRGTKELGDGQHFWEIKMTSPVYGTDMMVGIGTSDVDLDKYHhtFCSLLGRDEDSWGLSYT-GLLHHKGDKTS---F 82
Cdd:cd12906    31 TDCIRGKVGYSRGLHVWEITWPTRQRGTHAVVGVATKDAPLHCVG--YTSLVGSNEESWGWDIGrNKLYHDSKNQPgwtY 108

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2181405802  83 SSRFGQGSI------IGVHLDTWHGTLTFFKNRKCIGVAATRLQNRRFYPMV 128
Cdd:cd12906   109 PAFLEPDENfvvpdkFLVVLDMDEGTLSFVVDGQYLGVAFRGLKGKKLYPIV 160

SPRY domain-like in bacteria; This family contains SPRY-like domains that are found only in bacterial and are mostly uncharacterized. 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 eukaryotic 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).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2181405802  19 GQHFWEIKMTSPVYGTDMMVGIGTSDVdldkyhhTFCSLLGRDED-SWGLS---YTGLLH-HKGDKTSFSSRFGQGSIIG 93
Cdd:cd12886     1 GKWYWEVTVVSSAASTYAGIGVANAAA-------TGNNGLNGIELsSIGYSlgvYSGNKLsNGSSVATYGAGFTAGDVIG 73

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 2181405802  94 VHLDTWHGTLTFFKNRKCIGVAA------TRLQNRRFYPMVC 129
Cdd:cd12886    74 VALDLDAGKIWFYKNGVWQGGGDpapgtnPAFAGTAMYPAVT 115

SPRY domain in Ran binding proteins 9 and 10; This family includes SPRY domain in Ran binding protein (RBP or RanBPM) 9 and 10, and similar proteins. RanBP9 (also known as RanBPM), a binding partner of Ran, is a small Ras-like GTPase that exerts multiple functions via interactions with various proteins. RanBP9 and RanBP10 also act as androgen receptor (AR) coactivators. Both consist of the N-terminal proline- and glutamine-rich regions, the SPRY domain, and LisH-CTLH and CRA motifs. SPRY domain of RanBPM forms a complex with CD39, a prototypic member of the NTPDase family, thus down-regulating activity substantially. RanBP10 enhances the transcriptional activity of AR in a ligand-dependent manner and exhibits a protein expression pattern different from RanBPM in various cell lines. RanBP10 is highly expressed in AR-positive prostate cancer LNCaP cells, while RanBPM is abundant in WI-38 and MCF-7 cells.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2181405802  19 GQHFWEIKMTSPvyGTDMMVGIG--TSDVDLDKyhhtfcsLLGRDEDSWGlsytgllHHKGDKTSFSSR---------FG 87
Cdd:cd12909    25 GIYYFEVKIISK--GRDGYIGIGfsTKDVNLNR-------LPGWEPHSWG-------YHGDDGHSFCSSgtgkpygptFT 88

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 2181405802  88 QGSIIGVHLDTWHGTLTFFKNRKCIGVAATRLQNRRFYPMV 128
Cdd:cd12909    89 TGDVIGCGINFRDNTAFYTKNGVNLGIAFRDIKKGNLYPTV 129

SOCS (suppressors of cytokine signaling) box of SOCS-like proteins. The CIS/SOCS family of proteins is characterized by the presence of a C-terminal SOCS box and a central SH2 domain. These intracellular proteins regulate the responses of immune cells to cytokines. Identified as negative regulators of the cytokine-JAK-STAT pathway, they seem to play a role in many immunological and pathological processes. The function of the SOCS box is the recruitment of the ubiquitin-transferase system. Related SOCS boxes are also present in Rab40-like proteins and insect proteins of unknown function that also contain a NEUZ (domain in neuralized proteins) domain.

                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 2181405802 148 SLQYLCCYRLRQLRpnSGDTLEGLPLPPGLKQVLHNK 184
Cdd:cd03717     5 SLQHLCRFVIRQCT--RRDLIDQLPLPRRLKDYLKEY 39

PRY/SPRY domain in tripartite motif-containing proteins 1, 9, 18, 36, 46, 67,76 (TRIM1, TRIM9, TRIM18, TRIM36, TRIM46, TRIM67, TRIM76); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of several Class I TRIM proteins, including TRIM1, TRIM9, TRIM18, TRIM36, TRIM46, TRIM67 and TRIM76. TRIM1 (also known as MID2) and its close homolog, TRIM18 (also known as MID1), both contain a B30.2-like domain at their C-terminus and a single fibronectin type III (FN3) motif between it and their N-terminal RBCC domain. Their coiled-coil motifs mediate both homo- and heterodimerization, a prerequisite for association of the rapamycin-sensitive PP2A regulatory subunit Alpha 4 with microtubules. Mutations in TRIM18 have shown to cause Opitz syndrome, a disorder causing congenital anomalies such as cleft lip and palate as well as heart defects. TRIM9 is expressed mainly in the cerebral cortex, and functions as an E3 ubiquitin ligase. Its immunoreactivity is severely decreased in affected brain areas in Parkinson's disease and dementia with Lewy bodies, possibly playing an important role in the regulation of neuronal function and participating in pathological process of Lewy body disease through its ligase. TRIM36 interacts with centromere protein-H, one of the kinetochore proteins and possibly associates with chromosome segregation; an excess of TRIM36 may cause chromosomal instability. TRIM46 has not yet been characterized. TRIM67 negatively regulates Ras activity via degradation of 80K-H, leading to neural differentiation, including neuritogenesis. TRIM76 (also known as cardiomyopathy-associated protein 5 or CMYA5) is a muscle-specific member of the TRIM superfamily, but lacks the RING domain. It is possibly involved in protein kinase A signaling as well as vesicular trafficking. It has also been implicated in Duchenne muscular dystrophy and cardiac disease. The PRY-SPRY domain in these TRIM families is suggested to serve as the target binding site.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2181405802  16 LGD-----GQHFWEIKMTSpvyGTDMMVGIGTSDVDLDKYhhtfcslLGRDEDSWGLSYTG----LLHHKGDKTSFSSrf 86
Cdd:cd13734    46 LGDvaissGRHYWEVSVSR---STSYRVGVAYKSAPRDED-------LGKNSTSWCLSRDNnrytARHDGKVVDLRVT-- 113

                          90       100
                  ....*....|....*....|
gi 2181405802  87 GQGSIIGVHLDTWHGTLTFF 106
Cdd:cd13734   114 GHPARIGVLLDYDNGTLSFY 133

SPRY domain in heterogeneous nuclear ribonucleoprotein U-like (hnRNP) protein 1; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of heterogeneous nuclear ribonucleoprotein U-like (hnRNP) protein 1 (also known as HNRPUL1 ) which is a major constituent of nuclear matrix or scaffold and binds directly to DNA sequences through the N-terminal acidic region named serum amyloid P (SAP). Its function is specifically modulated by E1B-55kDa in adenovirus-infected cells. HNRPUL1 also participates in ATR protein kinase signaling pathways during adenovirus infection. Two transcript variants encoding different isoforms have been found for this gene. When associated with bromodomain-containing protein 7 (BRD7), it activates transcription of glucocorticoid-responsive promoter in the absence of ligand-stimulation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2181405802  54 FCSL-LGRDEDSWGLSYTGLLHHKGDKTSFSSRFGQGSIIGVHLD--TWHGTLTFFKNRKCIGVA----ATRLQNRRFYP 126
Cdd:cd12884    80 SSSLqLGEEEFSYGYGSTGKKSTNCKFEDYGEPFGENDVIGCYLDfeSEPVEISFSKNGKDLGVAfkisKEELGGKALFP 159

                  ....
gi 2181405802 127 MVCS 130
Cdd:cd12884   160 HVLT 163

PRY/SPRY domain in tripartite motif-containing (TRIM) proteins, including TRIM14-like, TRIM16-like, TRIM25-like, TRIM47-like, TRIM65 and RNF135, and stonustoxin; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of several Class I TRIM proteins, including TRIM14, TRIM16 and TRIM25, TRIM47 as well as RING finger protein RNF135 and stonustoxin, a secreted poisonous protein of the stonefish Synanceja horrida. TRIM16 (also known as estrogen-responsive B box protein or EBBP) has E3 ubiquitin ligase activity. It is a regulator of keratinocyte differentiation and a tumor suppressor in retinoid-sensitive neuroblastoma. TRIM25 (also called Efp) ubiquitinates the N terminus of the viral RNA receptor retinoic acid-inducible gene-I (RIG-I) in response to viral infection, leading to activation of the RIG-I signaling pathway, thus resulting in type I interferon production to limit viral replication. It has been shown that the influenza A virus targets TRIM25 and disables its antiviral function. TRIM47, also known as GOA (Gene overexpressed in astrocytoma protein) or RNF100 (RING finger protein 100), is highly expressed in kidney tubular cells, but low expressed in most tissue. It is overexpressed in astrocytoma tumor cells and plays an important role in the process of dedifferentiation that is associated with astrocytoma tumorigenesis. RNF135 ubiquitinates RIG-I (retinoic acid-inducible gene-I) to promote interferon-beta induction during the early phase of viral infection. Stonustoxin (STNX) is a hypotensive and lethal protein factor that also possesses other biological activities such as species-specific hemolysis (due to its ability to form pores in the cell membrane) and platelet aggregation, edema-induction, and endothelium-dependent vasorelaxation (mediated by the nitric oxide pathway and activation of potassium channels). The PRY-SPRY domain in these TRIM families is suggested to serve as the target binding site.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2181405802  12 GTKELGDGQHFWEIKMTSpvygtDMMVGIGTSDVDLDKYHHtfCSLLGRDEDSWGLSYTGLLH---HKGDKTSFSSRFGQ 88
Cdd:cd12891    44 STQSFSSGRHYWEVEVSE-----SGGWSVGVAYPSIERKGD--ESRIGRNDKSWCLEWQDKSFsawHNNEETPLPSVSSR 116

                          90
                  ....*....|....*...
gi 2181405802  89 gsIIGVHLDTWHGTLTFF 106
Cdd:cd12891   117 --RLGVYLDYEAGRLSFY 132

PRY/SPRY domain in RING finger protein RNF135; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of the RING finger protein RNF135 (also known as Riplet/RNF135), which ubiquitinates RIG-I (retinoic acid-inducible gene-I) to promote interferon-beta induction during the early phase of viral infection. Normally, RIG-I is activated by TRIM25 in response to viral infection, leading to activation of the RIG-I signaling pathway, thus resulting in type I interferon production to limit viral replication. However, RNF135, consisting of an N-terminal RING finger domain, C-terminal SPRY and PRY motifs and showing sequence similarity to TRIM25, acts as an alternative factor that promotes RIG-I activation independent of TRIM25.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2181405802  13 TKELGDGQHFWEIKMTspvYGTDMMVGIGTSDVDLDKYhhtfcslLGRDEDSWGLSYTGLLH----HKGDKTSFSSrfGQ 88
Cdd:cd12902    45 SQAFSSGQHYWEVDTR---QCSHWAVGVASWEMSRDQM-------LGRTMDSWCIEWKGTGQlsawHMNKETVLGS--DK 112

                          90
                  ....*....|....*...
gi 2181405802  89 GSIIGVHLDTWHGTLTFF 106
Cdd:cd12902   113 PRVVGIWLDLEEGKLAFY 130

The SOCS box acts as a bridge between specific substrate- binding domains and more generic proteins that comprise a large family of E3 ubiquitin protein ligases;

                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 2181405802  148 SLQYLCCYRLRQLRpnsgDTLEGLPLPPGLKQVLHNK 184
Cdd:smart00969   2 SLQHLCRLAIRRSL----GGIDKLPLPPRLKDYLLYY 34

suppressors of cytokine signalling; suppressors of cytokine signalling

                           10        20        30
                   ....*....|....*....|....*....|....
gi 2181405802  148 SLQYLCCYRLRQLRPNsgDTLEGLPLPPGLKQVL 181
Cdd:smart00253   9 SLQHLCRFTIRRCTRT--DQIKTLPLPPKLKDYL 40