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 386767096  56 HSWNSEDRSLNIFVKEDDKLTFHRHPVAQSTDCIRGKVGLTKGLHIWEIYWPTRQRGTHAVVGVCTADAPLHSVGYQSLV 135
Cdd:cd12906    1 HAWNPDDRSLNIFVKEDDPLTFHRHPVAQSTDCIRGKVGYSRGLHVWEITWPTRQRGTHAVVGVATKDAPLHCVGYTSLV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767096 136 GSTEQSWGWDLGRNKLYHDSKNCAGVTYPAILKNDEAFLVPDKFLVALDMDEGTLSFIVDQQYLGIAFRGLRGKKLYPIV 215
Cdd:cd12906   81 GSNEESWGWDIGRNKLYHDSKNQPGWTYPAFLEPDENFVVPDKFLVVLDMDEGTLSFVVDGQYLGVAFRGLKGKKLYPIV 160

                        170
                 ....*....|....
gi 386767096 216 SAVWGHCEITMRYI 229
Cdd:cd12906  161 SAVWGHCEVTMKYI 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 386767096  56 HSWNSEDRSLNIFVKEDDKLTFHRHPVAQSTDCIRGKVGLTKGLHIWEIYWPTRQRGTHAVVGVCTADAPLHSVGYQSLV 135
Cdd:cd12906    1 HAWNPDDRSLNIFVKEDDPLTFHRHPVAQSTDCIRGKVGYSRGLHVWEITWPTRQRGTHAVVGVATKDAPLHCVGYTSLV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767096 136 GSTEQSWGWDLGRNKLYHDSKNCAGVTYPAILKNDEAFLVPDKFLVALDMDEGTLSFIVDQQYLGIAFRGLRGKKLYPIV 215
Cdd:cd12906   81 GSNEESWGWDIGRNKLYHDSKNQPGWTYPAFLEPDENFVVPDKFLVVLDMDEGTLSFVVDGQYLGVAFRGLKGKKLYPIV 160

                        170
                 ....*....|....
gi 386767096 216 SAVWGHCEITMRYI 229
Cdd:cd12906  161 SAVWGHCEVTMKYI 174

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 386767096  100 HIWEIYWpTRQRGTHAVVGVCTADAPLHSVGYqslVGSTEQSWGWDLGRNKLYHDSkncagvTYPAIlkNDEAFLVPDKF 179
Cdd:pfam00622   2 HYFEVEI-FGQDGGGWRVGWATKSVPRKGERF---LGDESGSWGYDGWTGKKYWAS------TSPLT--GLPLFEPGDVI 69

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 386767096  180 LVALDMDEGTLSFIVDQQYLGIAFRGLRG-KKLYPIVSAVWG 220
Cdd:pfam00622  70 GCFLDYEAGTISFTKNGKSLGYAFRDVPFaGPLFPAVSLGAG 111

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        40
                  ....*....|....*....|....*....|....*....|
gi 386767096  235 EPLPLMDLCRRTIRQKIGRtNLEEHIQQLQLPLSMKTYLL 274
Cdd:pfam07525   1 TPRSLQHLCRLAIRRALGK-RRLGAIDKLPLPPLLKDYLL 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 386767096  56 HSWNSEDRSLNIFVKEDDKLTFHRHPVAQSTDCIRGKVGLTKGLHIWEIYWPTRQRGTHAVVGVCTADAPLHSVGYQSLV 135
Cdd:cd12906    1 HAWNPDDRSLNIFVKEDDPLTFHRHPVAQSTDCIRGKVGYSRGLHVWEITWPTRQRGTHAVVGVATKDAPLHCVGYTSLV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767096 136 GSTEQSWGWDLGRNKLYHDSKNCAGVTYPAILKNDEAFLVPDKFLVALDMDEGTLSFIVDQQYLGIAFRGLRGKKLYPIV 215
Cdd:cd12906   81 GSNEESWGWDIGRNKLYHDSKNQPGWTYPAFLEPDENFVVPDKFLVVLDMDEGTLSFVVDGQYLGVAFRGLKGKKLYPIV 160

                        170
                 ....*....|....
gi 386767096 216 SAVWGHCEITMRYI 229
Cdd:cd12906  161 SAVWGHCEVTMKYI 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 386767096  56 HSWNSEDRSLNIFVKEDDkLTFHRHPVAQSTDCIRGKVGLTKGLHIWEIYW--PTrqrGTHAVVGVCTADAPLHSVGYQS 133
Cdd:cd12907    1 HAWNPNDCSRNIYIKPNG-FTLHRNPVAQSTDGARGKIGFSSGRHAWEVWWegPL---GTVAVVGIATKHAPLQCQGYVA 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767096 134 LVGSTEQSWGWDLGRNKLYHDSKNCAgvTYPaILKNDEAFLVPDKFLVALDMDEGTLSFIVDQQYLGIAFRGLRGKKLYP 213
Cdd:cd12907   77 LLGSDDQSWGWNLVDNHLLHNGDSQG--NYP-QCNNAPKYQVGERIRVILDCEDNTLAFERGYEFLGVAFRGLPPTKLYP 153

                        170
                 ....*....|....*..
gi 386767096 214 IVSAVWGHCEITMRYIG 230
Cdd:cd12907  154 AVSAVYGNTEVSMVYLG 170

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 386767096 234 PEPLPLMDLCRRTIRQKIGRTNLeEHIQQLQLPLSMKTYLLYK 276
Cdd:cd03718    1 PEPLPLMDLCRRRVRVALGRDRL-EEIEQLPLPPSLKNYLLYQ 42

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767096  98 GLHIWEIYWPTRQRGtHAVVGVCTADAPLHSvgyQSLVGSTEQSWGWDLGRNKLYHDSKNcagvtypaiLKNDEAFLVPD 177
Cdd:cd11709    1 GKWYWEVRVDSGNGG-LIQVGWATKSFSLDG---EGGVGDDEESWGYDGSRLRKGHGGSS---------GPGGRPWKSGD 67

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 386767096 178 KFLVALDMDEGTLSFIVDQQYLGIAFRGLRGKK--LYPIVSAVWGH 221
Cdd:cd11709   68 VVGCLLDLDEGTLSFSLNGKDLGVAFTNLFLKGggLYPAVSLGSGQ 113

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 386767096 234 PEPLPLMDLCRRTIRQKIGRTNLeEHIQQLQLPLSMKTYLLYK 276
Cdd:cd03743    1 PEPLPLMDLCRRSARQALGRHRL-HHIQSLPLPQTLKNYLQYQ 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 386767096 234 PEPLPLMDLCRRTIRQKIGRTNLeEHIQQLQLPLSMKTYLLYK 276
Cdd:cd03716    1 STPRSLQHLCRLAIRRCLGRRRL-ELIKKLPLPPRLKDYLLYE 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        40
                  ....*....|....*....|....*....|....*....|
gi 386767096  235 EPLPLMDLCRRTIRQKIGRtNLEEHIQQLQLPLSMKTYLL 274
Cdd:pfam07525   1 TPRSLQHLCRLAIRRALGK-RRLGAIDKLPLPPLLKDYLL 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 386767096  41 ILLDMPPASRDLQLkhswnSEDRsLNIFVKEDDKLTFHRHPVAQSTDC--IRGKVGLTKGLHIWEIywpTRQRGTHAVVG 118
Cdd:cd13734    1 FKLDPKTAHRKLRL-----SNDN-LTVEYDPEGSKDQAAVLPRRFTGSpaVLGDVAISSGRHYWEV---SVSRSTSYRVG 71

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767096 119 VCTADAPlhsvGYQSLvGSTEQSWGWDLGRNKLY--HDSKNCagvtypaILKNDEaflVPDKFLVALDMDEGTLSFIVDQ 196
Cdd:cd13734   72 VAYKSAP----RDEDL-GKNSTSWCLSRDNNRYTarHDGKVV-------DLRVTG---HPARIGVLLDYDNGTLSFYDAE 136

                        170       180
                 ....*....|....*....|....*
gi 386767096 197 QYLGI-AFRGLRGKKLYPIVsAVWG 220
Cdd:cd13734  137 SKQHLyTFHVDFEGPVCPAF-AVWN 160

PRY/SPRY domain in tripartite motif-containing proteins, TRIM9 and TRIM67; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM9 proteins. TRIM9 protein is expressed mainly in the cerebral cortex, and functions as an E3 ubiquitin ligase. It has been shown that TRIM9 is localized to the neurons in the normal human brain and its immunoreactivity in affected brain areas in Parkinson's disease and dementia with Lewy bodies is severely decreased, possibly playing an important role in the regulation of neuronal function and participating in pathological process of Lewy body disease through its ligase. TRIM67 negatively regulates Ras activity via degradation of 80K-H, leading to neural differentiation, including neuritogenesis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386767096  91 GKVGLTKGLHIWEIYWPTRQRGTHAVVGVCTADaplhsVGYQSLVGSTEQSWG--------WDLGRNKlyHDSKNCAGVT 162
Cdd:cd12889   42 GSVGFSRGVHYWEVTIDRYDGHPDPAFGVARID-----VNKDKMLGKDDKGWSmyidnnrsWFLHNNE--HSNRTEGGIT 114

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 386767096 163 YPAILKndeaflvpdkflVALDMDEGTLSFIV-DQQYLGIAFRGLRGkKLYPIVS 216
Cdd:cd12889  115 VGSVVG------------VLLDLDRHTLSFYVnDEPQGPIAFRNLPG-VFYPAVS 156

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 386767096 117 VGVCTADAPLHSvgyQSLVGSTEQSWGWDLGRNKLYHDSKNCAGvtypailkndEAFLVPDKFLVALDMDEGTLSFIVDQ 196
Cdd:cd12882   27 IGWATISCRFTQ---EEGVGDTRDSYAYDGNRVRKWNVSTQKYG----------EPWVAGDVIGCCIDLDKGTISFYRNG 93

                         90       100       110
                 ....*....|....*....|....*....|.
gi 386767096 197 QYLGIAFRGLR---GKKLYPIVS-AVWGHCE 223
Cdd:cd12882   94 RSLGVAFDNVRrgpGLAYFPAVSlSFGERLE 124

SOCS (suppressors of cytokine signaling) box of ASB4 and ASB18 proteins. ASB family members have a C-terminal SOCS box and an N-terminal ankyrin-related sequence. Asb4 was identified as imprinted gene in mice. 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 386767096 236 PLPLMDLCRRTIRQKIGRtNLEEHIQQLQLPLSMKTYLLYKNR 278
Cdd:cd03723    3 PRSLQHLCRCAIRKLLGS-RCHKLVPQLSLPTSLKNYLLLEPE 44

SOCS (suppressors of cytokine signaling) box of ASB7-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 386767096 235 EPLPLMDLCRRTIRQKIGRTNLeEHIQQLQLPLSMKTYLLYK 276
Cdd:cd03726    2 QPRTLQDLCRIKIRHCIGLQNL-KLLDELPIAKVMKDYLKHK 42

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 386767096 235 EPLPLMDLCRRTIRQKIGRTNLEEhIQQLQLPLSMKTYLLYK 276
Cdd:cd03719    2 EPHSLLHLSRLCVRHALGDTRLGQ-VSALPLPPAMKRYLLYQ 42

SOCS (suppressors of cytokine signaling) box of ASB9 and 11 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 386767096 236 PLPLMDLCRRTIRQKIGRTNLEEhIQQLQLPLSMKTYLLYK 276
Cdd:cd03728    3 PPSLMQLCRLCIRKCFGRKQHHK-IHKLHLPEPLKHFLLYR 42

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 386767096 236 PLPLMDLCRRTIRQKIGRTNLEEhIQQLQLPLSMKTYLLYKNRR 279
Cdd:cd03721    3 PRPLAHLCRLKVRTLIGINRIKL-IDTLPLPPRLIRYLNHQETQ 45

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 386767096 239 LMDLCRRTIRQKIGRTNL--EEHIQQLQLPLSMKTYLLY 275
Cdd:cd03722    6 LTHLCRLEIRSSLKSERLrsDSFICQLPLPRSLQDYLLY 44

SOCS (suppressors of cytokine signaling) box of SOCS7-like proteins. Together with CIS1, the CIS/SOCS family of proteins is characterized by the presence of a C-terminal SOCS box and a central SH2 domain. SOCS7 is important in the functioning of neuronal 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
                 ....*....|....*....|....*....|....*....
gi 386767096 239 LMDLCRRTIRQKIGRtnleEHIQQLQLPLSMKTYLLYKN 277
Cdd:cd03741    6 LQHLCRFVIRKLVRR----DHIPALPLPRRLIDYLREKH 40