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 375331874  55 HAWNSDDRSLNIFIKDDDKLTFHRHPVAQSTDGIRGRVGYTRGLHVWRIHWPARQRGTHAVVGVATGDAPLHSVGYTSLV 134
Cdd:cd12906    1 HAWNPDDRSLNIFVKEDDPLTFHRHPVAQSTDCIRGKVGYSRGLHVWEITWPTRQRGTHAVVGVATKDAPLHCVGYTSLV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 375331874 135 GSDSESWGWDLGRNKLYHNSKNRPassAPTYPSFLEPEEAFVLPDTLMVVLDMDEGTLSFMVDGQYLGVAFRGLKGKKLY 214
Cdd:cd12906   81 GSNEESWGWDIGRNKLYHDSKNQP---GWTYPAFLEPDENFVVPDKFLVVLDMDEGTLSFVVDGQYLGVAFRGLKGKKLY 157

                        170
                 ....*....|....*..
gi 375331874 215 PIVSAVWGHCEITMRYI 231
Cdd:cd12906  158 PIVSAVWGHCEVTMKYI 174

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 375331874  55 HAWNSDDRSLNIFIKDDDKLTFHRHPVAQSTDGIRGRVGYTRGLHVWRIHWPARQRGTHAVVGVATGDAPLHSVGYTSLV 134
Cdd:cd12906    1 HAWNPDDRSLNIFVKEDDPLTFHRHPVAQSTDCIRGKVGYSRGLHVWEITWPTRQRGTHAVVGVATKDAPLHCVGYTSLV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 375331874 135 GSDSESWGWDLGRNKLYHNSKNRPassAPTYPSFLEPEEAFVLPDTLMVVLDMDEGTLSFMVDGQYLGVAFRGLKGKKLY 214
Cdd:cd12906   81 GSNEESWGWDIGRNKLYHDSKNQP---GWTYPAFLEPDENFVVPDKFLVVLDMDEGTLSFVVDGQYLGVAFRGLKGKKLY 157

                        170
                 ....*....|....*..
gi 375331874 215 PIVSAVWGHCEITMRYI 231
Cdd:cd12906  158 PIVSAVWGHCEVTMKYI 174

SOCS (suppressors of cytokine signaling) box of SSB1 and SSB4 (SPRY domain-containing SOCS box proteins)-like proteins. SSB proteins contain a central SPRY domain and a C-terminal SOCS. SSB1 and SSB4 has been shown to bind to MET, the receptor protein-tyrosine kinase for hepatocyte growth factor (HGF) and also interacts with prostate apoptosis response protein-4. Both types of interactions are mediated through the SPRY domain. The general function of the SOCS box is the recruitment of the ubiquitin-transferase system. The SOCS box interacts with Elongins B and C, Cullin-5 or Cullin-2, Rbx-1, and E2. Therefore, SOCS-box-containing proteins probably function as E3 ubiquitin ligases and mediate the degradation of proteins associated through their N-terminal regions.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 375331874 236 PEPLPLMDLCRRAARLALGRERLQEIETLPLPQSLKNYLQYQ 277
Cdd:cd03718    1 PEPLPLMDLCRRRVRVALGRDRLEEIEQLPLPPSLKNYLLYQ 42

SOCS box; 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 375331874  237 EPLPLMDLCRRAARLALGRERLQEIETLPLPQSLKNYLQ 275
Cdd:pfam07525   1 TPRSLQHLCRLAIRRALGKRRLGAIDKLPLPPLLKDYLL 39

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 375331874  55 HAWNSDDRSLNIFIKDDDKLTFHRHPVAQSTDGIRGRVGYTRGLHVWRIHWPARQRGTHAVVGVATGDAPLHSVGYTSLV 134
Cdd:cd12906    1 HAWNPDDRSLNIFVKEDDPLTFHRHPVAQSTDCIRGKVGYSRGLHVWEITWPTRQRGTHAVVGVATKDAPLHCVGYTSLV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 375331874 135 GSDSESWGWDLGRNKLYHNSKNRPassAPTYPSFLEPEEAFVLPDTLMVVLDMDEGTLSFMVDGQYLGVAFRGLKGKKLY 214
Cdd:cd12906   81 GSNEESWGWDIGRNKLYHDSKNQP---GWTYPAFLEPDENFVVPDKFLVVLDMDEGTLSFVVDGQYLGVAFRGLKGKKLY 157

                        170
                 ....*....|....*..
gi 375331874 215 PIVSAVWGHCEITMRYI 231
Cdd:cd12906  158 PIVSAVWGHCEVTMKYI 174

SPRY domain in the F-box family Fbxo45; Fbxo45 is a novel synaptic E3 and ubiquitin ligase, related to the suppressor of cytokine signaling (SOCS) proteins and located N-terminal to a SPRY (SPla and the ryanodine receptor) domain. Fbxo45 induces 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. F-box motifs are found in proteins that function as the substrate recognition component of SCF E3 complexes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 375331874  55 HAWNSDDRSLNIFIKDDDkLTFHRHPVAQSTDGIRGRVGYTRGLHVWRIHW--PArqrGTHAVVGVATGDAPLHSVGYTS 132
Cdd:cd12907    1 HAWNPNDCSRNIYIKPNG-FTLHRNPVAQSTDGARGKIGFSSGRHAWEVWWegPL---GTVAVVGIATKHAPLQCQGYVA 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 375331874 133 LVGSDSESWGWDLGRNKLYHNSKNRPassapTYPSFLEPEEaFVLPDTLMVVLDMDEGTLSFMVDGQYLGVAFRGLKGKK 212
Cdd:cd12907   77 LLGSDDQSWGWNLVDNHLLHNGDSQG-----NYPQCNNAPK-YQVGERIRVILDCEDNTLAFERGYEFLGVAFRGLPPTK 150

                        170
                 ....*....|....*....
gi 375331874 213 LYPIVSAVWGHCEITMRYI 231
Cdd:cd12907  151 LYPAVSAVYGNTEVSMVYL 169

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 375331874   99 HVWRIHWPaRQRGTHAVVGVATGDAPLHSVGYtslVGSDSESWGWDLGRNKLYHNSKnrpasSAPTYPSFLEPeeafvlP 178
Cdd:pfam00622   2 HYFEVEIF-GQDGGGWRVGWATKSVPRKGERF---LGDESGSWGYDGWTGKKYWAST-----SPLTGLPLFEP------G 66

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 375331874  179 DTLMVVLDMDEGTLSFMVDGQYLGVAFRGLKG-KKLYPIVSAVWG 222
Cdd:pfam00622  67 DVIGCFLDYEAGTISFTKNGKSLGYAFRDVPFaGPLFPAVSLGAG 111

SOCS (suppressors of cytokine signaling) box of SSB4 (SPRY domain-containing SOCS box proteins)-like proteins. SSB proteins contain a central SPRY domain and a C-terminal SOCS. SSB4 has been shown to bind to MET, the receptor protein-tyrosine kinase for hepatocyte growth factor (HGF). SSB4, like SSB2 and SSB1, also interacts with prostate apoptosis response protein-4. Both types of interactions are mediated through the SPRY domain. The general function of the SOCS box is the recruitment of the ubiquitin-transferase system. The SOCS box interacts with Elongins B and C, Cullin-5 or Cullin-2, Rbx-1, and E2. Therefore, SOCS-box-containing proteins probably function as E3 ubiquitin ligases and mediate the degradation of proteins associated through their N-terminal regions.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 375331874 236 PEPLPLMDLCRRAARLALGRERLQEIETLPLPQSLKNYLQYQ 277
Cdd:cd03743    1 PEPLPLMDLCRRSARQALGRHRLHHIQSLPLPQTLKNYLQYQ 42

SOCS (suppressors of cytokine signaling) box of SSB1 (SPRY domain-containing SOCS box proteins)-like proteins. SSB proteins contain a central SPRY domain and a C-terminal SOCS. SSB1 has been shown to bind to MET, the receptor protein-tyrosine kinase for hepatocyte growth factor (HGF), both the absence and the presence of HGF and enhances the HGF-MET-induced mitogen-activated protein kinases Erk-transcription factor Elk-1-serum response elements (SRE) pathway. SSB1, like SSB2 and SSB4, also interacts with prostate apoptosis response protein-4. Both types of interactions are mediated through the SPRY domain. The general function of the SOCS box is the recruitment of the ubiquitin-transferase system. The SOCS box interacts with Elongins B and C, Cullin-5 or Cullin-2, Rbx-1, and E2. Therefore, SOCS-box-containing proteins probably function as E3 ubiquitin ligases and mediate the degradation of proteins associated through their N-terminal regions.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 375331874 236 PEPLPLMDLCRRAARLALGRERLQEIETLPLPQSLKNYLQYQ 277
Cdd:cd03744    1 PEPLPLMDLCRRSVRLALGRERLSEIHTLPLPASLKNYLLYQ 42

SOCS (suppressors of cytokine signaling) box of ASB (ankyrin repeat and SOCS box) and SSB (SPRY domain-containing SOCS box proteins) protein families. ASB family members have a C-terminal SOCS box and an N-terminal ankyrin-related sequence of a variable number of repeats. SSB proteins contain a central SPRY domain and a C-terminal SOCS. Recently, it has been shown that all four SSB proteins interact with the MET, the receptor protein-tyrosine kinase for hepatocyte growth factor (HGF), and that SSB-1, SSB-2, and SSB-4 interact with prostate apoptosis response protein-4. Both types of interactions are mediated through the SPRY domain.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 375331874 236 PEPLPLMDLCRRAARLALGRERLQEIETLPLPQSLKNYLQYQ 277
Cdd:cd03716    1 STPRSLQHLCRLAIRRCLGRRRLELIKKLPLPPRLKDYLLYE 42

SOCS box; 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 375331874  237 EPLPLMDLCRRAARLALGRERLQEIETLPLPQSLKNYLQ 275
Cdd:pfam07525   1 TPRSLQHLCRLAIRRALGKRRLGAIDKLPLPPLLKDYLL 39

SOCS (suppressors of cytokine signaling) box of ASB2-like proteins. ASB family members have a C-terminal SOCS box and an N-terminal ankyrin-related sequence. ASB2 targets specific proteins to destruction by the proteasome in leukemia cells that have been induced to differentiate. The general function of the SOCS box is the recruitment of the ubiquitin-transferase system. The SOCS box interacts with Elongins B and C, Cullin-5 or Cullin-2, Rbx-1, and E2. Therefore, SOCS-box-containing proteins probably function as E3 ubiquitin ligases and mediate the degradation of proteins associated through their N-terminal regions.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 375331874 238 PLPLMDLCRRAARLALGRERLQEIETLPLPQSLKNYLQYQ 277
Cdd:cd03721    3 PRPLAHLCRLKVRTLIGINRIKLIDTLPLPPRLIRYLNHQ 42

SPRY domain associated with DEAD box gene DDX1; This SPRY domain is associated with the DEAD box gene, DDX1, an RNA-dependent ATPase involved in HIV-1 Rev function and virus replication. It is suggested that DDX1 acts as a cellular cofactor by promoting oligomerization of Rev on the Rev response element (RRE). DDX1 RNA is overexpressed in breast cancer, data showing a strong and independent association between poor prognosis and deregulation of the DEAD box protein DDX1, thus potentially serving as an effective prognostic biomarker for early recurrence in primary breast cancer. DDX1 also interacts with RelA and enhances nuclear factor kappaB-mediated transcription. DEAD-box proteins are associated with all levels of RNA metabolism and function, and have been implicated in translation initiation, transcription, RNA splicing, ribosome assembly, RNA transport, and RNA decay.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 375331874 116 VGVATGDAPLhsvgytsLVGSDSESWGWDlGRNKLYHNSKnrpassaptypsFLEPEEAFVLPDTLMVVLDMDEGTLSFM 195
Cdd:cd12873   56 VGWSTEDASL-------DLGTDKFGFGYG-GTGKKSHGRQ------------FDDYGEPFGLGDVIGCYLDLDNGTISFS 115

                         90       100
                 ....*....|....*....|....*.
gi 375331874 196 VDGQYLGVAFR---GLKGKKLYPIVS 218
Cdd:cd12873  116 KNGKDLGKAFDippHLRNSALFPAVC 141

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 375331874 127 SVGYTSL-VGSDSESWGWDlGRNKLYHNSKnrpassaptypsFLEPEEAFVLPDTLMVVLDMD--EGTLSFMVDGQYLGV 203
Cdd:cd12884   77 SVDSSSLqLGEEEFSYGYG-STGKKSTNCK------------FEDYGEPFGENDVIGCYLDFEsePVEISFSKNGKDLGV 143

                         90
                 ....*....|....*.
gi 375331874 204 AFR----GLKGKKLYP 215
Cdd:cd12884  144 AFKiskeELGGKALFP 159

SOCS (suppressors of cytokine signaling) box of SSB2 (SPRY domain-containing SOCS box proteins)-like proteins. SSB proteins contain a central SPRY domain and a C-terminal SOCS. SSB2 has been shown to bind to MET, the receptor protein-tyrosine kinase for hepatocyte growth factor (HGF). SSB2, like SSB4 and SSB1, also interacts with prostate apoptosis response protein-4. Both types of interactions are mediated through the SPRY domain. The general function of the SOCS box is the recruitment of the ubiquitin-transferase system. The SOCS box interacts with Elongins B and C, Cullin-5 or Cullin-2, Rbx-1, and E2. Therefore, SOCS-box-containing proteins probably function as E3 ubiquitin ligases and mediate the degradation of proteins associated through their N-terminal regions.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 375331874 237 EPLPLMDLCRRAARLALGRERLQEIETLPLPQSLKNYLQYQ 277
Cdd:cd03719    2 EPHSLLHLSRLCVRHALGDTRLGQVSALPLPPAMKRYLLYQ 42

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 375331874  86 DGIRGRVGYTRGLHVWRIHwpaRQRGTHAVVGVATGDAPLHSvgytsLVGSDSESWGWDLGRNKLY--HNSKNRPASSAP 163
Cdd:cd13734   43 PAVLGDVAISSGRHYWEVS---VSRSTSYRVGVAYKSAPRDE-----DLGKNSTSWCLSRDNNRYTarHDGKVVDLRVTG 114

                         90       100       110
                 ....*....|....*....|....*....|.
gi 375331874 164 typsflepeeafvLPDTLMVVLDMDEGTLSF 194
Cdd:cd13734  115 -------------HPARIGVLLDYDNGTLSF 132

SOCS (suppressors of cytokine signaling) box of ASB1-like proteins. ASB family members have a C-terminal SOCS box and an N-terminal ankyrin-related sequence. The general function of the SOCS box is the recruitment of the ubiquitin-transferase system. The SOCS box interacts with Elongins B and C, Cullin-5 or Cullin-2, Rbx-1, and E2. Therefore, SOCS-box-containing proteins probably function as E3 ubiquitin ligases and mediate the degradation of proteins associated through their N-terminal regions.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 375331874 238 PLPLMDLCRRAARLALGRERLQEIETLPLPQSLKNYLQYQ 277
Cdd:cd03720    3 PRSLLSLCRIAVRRALGKQRLSLICSLPLPDPIKKFLLHE 42

SOCS (suppressors of cytokine signaling) box of ASB3-like proteins. ASB family members have a C-terminal SOCS box and an N-terminal ankyrin-related sequence. ABS3 has been shown to be negative regulator of TNF-R2-mediated cellular responses to TNF-alpha by direct targeting of tumor necrosis factor receptor II (TNF-R2) for ubiquitination and proteasome-mediated degradation. The general function of the SOCS box is the recruitment of the ubiquitin-transferase system. The SOCS box interacts with Elongins B and C, Cullin-5 or Cullin-2, Rbx-1, and E2. Therefore, SOCS-box-containing proteins probably function as E3 ubiquitin ligases and mediate the degradation of proteins associated through their N-terminal regions.

                         10        20        30
                 ....*....|....*....|....*....|....*....
gi 375331874 241 LMDLCRRAARLALGRERLQE---IETLPLPQSLKNYLQY 276
Cdd:cd03722    6 LTHLCRLEIRSSLKSERLRSdsfICQLPLPRSLQDYLLY 44

SPRY domain at N-terminus of ring finger protein 123; This SPRY domain is found at the N-terminus of RING finger protein 123 domain (also known as E3 ubiquitin-protein ligase RNF123). The ring finger domain motif is present in a variety of functionally distinct proteins and known to be involved in protein-protein and protein-DNA interactions. RNF123 displays E3 ubiquitin ligase activity toward the cyclin-dependent kinase inhibitor p27 (Kip1).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 375331874 118 VATGDAPLHSVGYTSL---------VGSDSESWGWDLGRNKLYHnsknrpaSSAPTYPsflepeEAFVLPDTLMVVLDMD 188
Cdd:cd12882   17 VTLGTKGIMQIGWATIscrftqeegVGDTRDSYAYDGNRVRKWN-------VSTQKYG------EPWVAGDVIGCCIDLD 83

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 375331874 189 EGTLSFMVDGQYLGVAF---RGLKGKKLYPIVS-AVWGHCE 225
Cdd:cd12882   84 KGTISFYRNGRSLGVAFdnvRRGPGLAYFPAVSlSFGERLE 124

SPRY domain-containing protein 7; This family contains SPRY domain-containing protein 7 (also known as SPRY domain-containing protein 7 or CLL deletion region gene 6 protein homolog or CLLD6 or chronic lymphocytic leukemia deletion region gene 6 protein homolog). In humans, CLLD6 is highly expressed in heart, skeletal muscle, and testis as well as cancer cell lines. It also has cross-species conservation, suggesting that it is likely to carry out important cellular processes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 375331874 116 VGVATGDAPLHSVgytsLVGSDSESWG--WDlgrNKLYHNS--KNRPASSaptypsflePEEAfvlpDTLMVVLDMDEgt 191
Cdd:cd12880   45 VGLATRKTDLNRV----PLGNDAESWVlrSD---GTIWHNGevIHKLKQL---------VEEG----DVIGVTYDHVE-- 102

                         90       100
                 ....*....|....*....|....*.
gi 375331874 192 LSFMVDGQYLGVAFRGLKGkKLYPIV 217
Cdd:cd12880  103 LNFYLNGKPLDCPITGIKG-TVYPVV 127

SOCS (suppressors of cytokine signaling) box of ASB15-like proteins. ASB family members have a C-terminal SOCS box and an N-terminal ankyrin-related sequence. Human ASB15 is expressed predominantly in skeletal muscle and participates in the regulation of protein turnover and muscle cell development by stimulating protein synthesis and regulating differentiation of muscle cells. The general function of the SOCS box is the recruitment of the ubiquitin-transferase system. The SOCS box interacts with Elongins B and C, Cullin-5 or Cullin-2, Rbx-1, and E2. Therefore, SOCS-box-containing proteins probably function as E3 ubiquitin ligases and mediate the degradation of proteins associated through their N-terminal regions.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 375331874 238 PLPLMDLCRRAARLALGRERLQE---IETLPLPQSLKNYLQYQ 277
Cdd:cd03731    3 PRPLKHLCRLKIRKLMGLQKLQQpssMKKLPLPPALKRYILYK 45

SOCS (suppressors of cytokine signaling) box of ASB13-like proteins. ASB family members have a C-terminal SOCS box and an N-terminal ankyrin-related sequence. The general function of the SOCS box is the recruitment of the ubiquitin-transferase system. The SOCS box interacts with Elongins B and C, Cullin-5 or Cullin-2, Rbx-1, and E2. Therefore, SOCS-box-containing proteins probably function as E3 ubiquitin ligases and mediate the degradation of proteins associated through their N-terminal regions.

                         10        20        30
                 ....*....|....*....|....*....|....*....
gi 375331874 238 PLPLMDLCRRAARLALGRERLQEIETLPLPQSLKNYLQY 276
Cdd:cd03729    3 PLSLQQLCRINLRKALGTRALEKIAKLNIPNRIIDYLSY 41

suppressors of cytokine signalling; suppressors of cytokine signalling

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 375331874   237 EPLPLMDLCRRAARlalGRERLQEIETLPLPQSLKNYLQY 276
Cdd:smart00253   6 NVPSLQHLCRFTIR---RCTRTDQIKTLPLPPKLKDYLSY 42

SOCS (suppressors of cytokine signaling) box of WSB/SWiP-like proteins. This subfamily contains WSB-1 (SOCS-box-containing WD-40 protein), part of an E3 ubiquitin ligase for the thyroid-hormone-activating type 2 iodothyronine deiodinase (D2), and SWiP-1 (SOCS box and WD-repeats in Protein), a WD40-containing protein that is expressed in embryonic structures of chickens and regulated by Sonic Hedgehog (Shh), as well as, their isoforms WSB-2 and SWiP-2. The general function of the SOCS box is the recruitment of the ubiquitin-transferase system. The SOCS box interacts with Elongins B and C, Cullin-5 or Cullin-2, Rbx-1, and E2. Therefore, SOCS-box-containing proteins probably function as E3 ubiquitin ligases and mediate the degradation of proteins associated through their N-terminal regions.

                         10        20        30
                 ....*....|....*....|....*....|....*..
gi 375331874 241 LMDLCRRAARLALGRerlQEIETLPLPQSLKNYLQYQ 277
Cdd:cd03733    6 LQHLCRMALRRVMTT---QQVLALPIPKKMKEFLTYR 39