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 226423903 222 AEPHSLLHLSRLCVRHNLGDTRLGQVSALPLPPAMKRYLLYQ 263
Cdd:cd03719    1 AEPHSLLHLSRLCVRHALGDTRLGQVSALPLPPAMKRYLLYQ 42

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 226423903   89 HAWEISWpLEQRGTHAVVGVATALAPLQTDHYaalLGSNSESWGWDIGRGKLYHQSKGPGAPQYPAGTqgeqlevPERLL 168
Cdd:pfam00622   2 HYFEVEI-FGQDGGGWRVGWATKSVPRKGERF---LGDESGSWGYDGWTGKKYWASTSPLTGLPLFEP-------GDVIG 70

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 226423903  169 VVLDMEEGTLGYAIGGTYLGPAFRGLKGR-TLYPAVSAVWGQCQVRIRYLG 218
Cdd:pfam00622  71 CFLDYEAGTISFTKNGKSLGYAFRDVPFAgPLFPAVSLGAGEGLKFNFGLR 121

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 226423903    86 RGLHAWEISWpleQRGTHAVVGVATALAPLqtdHYAALLGSNSESWGWDIGRGKLYHQSKGpgaPQYPAGTQgeqlEVPE 165
Cdd:smart00449   1 SGRHYFEVEI---GDGGHWRVGVATKSVPR---GYFALLGEDKGSWGYDGDGGKKYHNSTG---PEYGLPLQ----EPGD 67

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 226423903   166 RLLVVLDMEEGTLGYAIGGTYL-GPAFRGLK-GRTLYPAVSaVWGQCQVRIRY 216
Cdd:smart00449  68 VIGCFLDLEAGTISFYKNGKYLhGLAFFDVKfSGPLYPAFS-LGSGNSVRLNF 119

suppressors of cytokine signalling; suppressors of cytokine signalling

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 226423903   219 ERRAEPHSLLHLsrlCVRHNLGDTRLGQVSALPLPPAMKRYLLY 262
Cdd:smart00253   2 PRPSNVPSLQHL---CRFTIRRCTRTDQIKTLPLPPKLKDYLSY 42

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 226423903  46 HGWNPKDCSENIEVKEGGLYFERRPVAQSTDGARGKRGYSRGLHAWEISWPLEQRGTHAVVGVATALAPLQTDHYAALLG 125
Cdd:cd12875    1 HGWNPADCSKNIYIKEDGLTFHRRPVAQSTDAIRGKKGYTRGLHAWEVKWISRPRGSHAVVGVATKDAPLQCDGYVTLLG 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226423903 126 SNSESWGWDIGRGKLYHQSKgPGAPQYPAGTqgEQLEVPERLLVVLDMEEGTLGYAIGGTYLGPAFRGLKGRTLYPAVSA 205
Cdd:cd12875   81 SNSESWGWDLGDNKLYHNGK-KVIGSYPAKS--ENYQVPDRILVILDMEDGTLAFEANGEYLGVAFRGLPGKLLYPAVSA 157

                        170
                 ....*....|..
gi 226423903 206 VWGQCQVRIRYL 217
Cdd:cd12875  158 VYGNCEIRLIYL 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 226423903   89 HAWEISWpLEQRGTHAVVGVATALAPLQTDHYaalLGSNSESWGWDIGRGKLYHQSKGPGAPQYPAGTqgeqlevPERLL 168
Cdd:pfam00622   2 HYFEVEI-FGQDGGGWRVGWATKSVPRKGERF---LGDESGSWGYDGWTGKKYWASTSPLTGLPLFEP-------GDVIG 70

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 226423903  169 VVLDMEEGTLGYAIGGTYLGPAFRGLKGR-TLYPAVSAVWGQCQVRIRYLG 218
Cdd:pfam00622  71 CFLDYEAGTISFTKNGKSLGYAFRDVPFAgPLFPAVSLGAGEGLKFNFGLR 121

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 226423903    86 RGLHAWEISWpleQRGTHAVVGVATALAPLqtdHYAALLGSNSESWGWDIGRGKLYHQSKGpgaPQYPAGTQgeqlEVPE 165
Cdd:smart00449   1 SGRHYFEVEI---GDGGHWRVGVATKSVPR---GYFALLGEDKGSWGYDGDGGKKYHNSTG---PEYGLPLQ----EPGD 67

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 226423903   166 RLLVVLDMEEGTLGYAIGGTYL-GPAFRGLK-GRTLYPAVSaVWGQCQVRIRY 216
Cdd:smart00449  68 VIGCFLDLEAGTISFYKNGKYLhGLAFFDVKfSGPLYPAFS-LGSGNSVRLNF 119

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 226423903  87 GLHAWEISWPLEQRGtHAVVGVATALAPLQTDHYaalLGSNSESWGWDIGR-GKLYHQSKGPGAPQYPAGtqgeqlevpE 165
Cdd:cd11709    1 GKWYWEVRVDSGNGG-LIQVGWATKSFSLDGEGG---VGDDEESWGYDGSRlRKGHGGSSGPGGRPWKSG---------D 67

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 226423903 166 RLLVVLDMEEGTLGYAIGGTYLGPAFRGL--KGRTLYPAVSAVWGQcQVRIR 215
Cdd:cd11709   68 VVGCLLDLDEGTLSFSLNGKDLGVAFTNLflKGGGLYPAVSLGSGQ-GVTIN 118

SOCS (suppressors of cytokine signaling) box. The SOCS box is found in the C-terminal region of CIS/SOCS family proteins (in combination with a SH2 domain), ASBs (ankyrin repeat-containing proteins with a SOCS box), SSBs (SPRY domain-containing proteins with a SOCS box), and WSBs (WD40 repeat-containing proteins with a SOCS box), as well as, other miscellaneous proteins. The 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 226423903 223 EPHSLLHLSRLCVRHNLGDTRLGQVSALPLPPAMKRYLLYQ 263
Cdd:cd03587    1 NPRSLQHLCRLAIRRCLGKRRLDLIDKLPLPPRLKDYLLYK 41

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 226423903 223 EPHSLLHLSRLCVRHNLGDTRLGQVSALPLPPAMKRYLLYQ 263
Cdd:cd03718    2 EPLPLMDLCRRRVRVALGRDRLEEIEQLPLPPSLKNYLLYQ 42

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 226423903   226 SLLHLSRLCVRHnlgdtRLGQVSALPLPPAMKRYLLYQ 263
Cdd:smart00969   2 SLQHLCRLAIRR-----SLGGIDKLPLPPRLKDYLLYY 34

SPRY domain in HERC1; This SPRY domain is found in the HERC1, a large protein related to chromosome condensation regulator RCC1. It is widely expressed in many tissues, playing an important role in intracellular membrane trafficking in the cytoplasm as well as Golgi apparatus. HERC1 also interacts with tuberous sclerosis 2 (TSC2, tuberin), which suppresses cell growth, and results in the destabilization of TSC2. However, the biological function of HERC1 has yet to be defined.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226423903  83 GYSRGLHAWEISWPLEQRGTHA-VVGVATAlaPLQTDHYAallgSNSESWGWDIGRGKLYHQskgpgapqypagtqGEQL 161
Cdd:cd12881   38 GISSGCYQWKFYLVKENRGNEGtCVGVSRK--PVTDFNYR----TSSDMWLYRAYNGNLYHN--------------GEQL 97

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 226423903 162 EVPER-------LLVVLDMEEGTLGYAIGGTYLGPAFRGLKGRTLYPAVS 204
Cdd:cd12881   98 LRLSSkfhqgdyITVVLDMEEGTLSFGKNGEEPGVAFEDVDATELYPCVM 147

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 226423903  76 DGARGKRGYSRGLHAWEISwplEQRGTHAVVGVATALAPlqtdhYAALLGSNSESWGWDIGRGKLY--HQSKgpgapQYP 153
Cdd:cd13734   43 PAVLGDVAISSGRHYWEVS---VSRSTSYRVGVAYKSAP-----RDEDLGKNSTSWCLSRDNNRYTarHDGK-----VVD 109

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 226423903 154 AGTQGEqlevPERLLVVLDMEEGTLGYAIGGTYLGP-AFRGLKGRTLYPAVsAVW-GQCQVR 213
Cdd:cd13734  110 LRVTGH----PARIGVLLDYDNGTLSFYDAESKQHLyTFHVDFEGPVCPAF-AVWnGSLTLH 166

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 226423903 224 PHSLLHLSRLCVRHNLGDTRLGQVSA---LPLPPAMKRYLLYQ 263
Cdd:cd03731    3 PRPLKHLCRLKIRKLMGLQKLQQPSSmkkLPLPPALKRYILYK 45

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 226423903 224 PHSLLHLSRLCVRHNLGDTRLGQVSALPLPPAMKRYLLYQ 263
Cdd:cd03721    3 PRPLAHLCRLKVRTLIGINRIKLIDTLPLPPRLIRYLNHQ 42

SPRY domain in Ash2; This SPRY domain is found at the C-terminus of Ash2 (absent, small, or homeotic discs 2) -like proteins, core components of all mixed-lineage leukemia (MLL) family histone methyltransferases. Ash2 is a member of the trithorax group of transcriptional regulators of the Hox genes. Recent studies show that the SPRY domain of Ash2 mediates the interaction with RbBP5 and has an important role in regulating the methyltransferase activity of MLL complexes. In yeast, Ash2 is involved in histone methylation and is required for the earliest stages of embryogenesis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226423903  78 ARGKRGYSRGLHAWEISW--PLEQRGTHAVVGVATALAPLQtdhyaALLGSNSESWGW-DIGrGKLYHQSKG--PGAPQY 152
Cdd:cd12872   19 ARANHGVREGKWYFEVKIleGGGTETGHVRVGWSRREASLQ-----APVGYDKYSYAIrDKD-GSKFHQSRGkpYGEPGF 92

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 226423903 153 PAG-TQGEQLEVPErllvvldmeegtLGYAIGGTYLGPAFRGLKGR-TLYPAVSaVWGQCQVRIR 215
Cdd:cd12872   93 KEGdVIGFLITLPK------------IEFFKNGKSQGVAFEDIYGTgGYYPAVS-LYKGATVTIN 144

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 226423903  48 WNPKDCSENIEVKEGGLyferrpVAQSTD-----GARGKRG-YSRGLHAWEISwPLEQ---RgthavVGVATALAPLqtd 118
Cdd:cd12873    1 MNPYDRDAALAISPDGL------LCQSREekgwqGCRATKGvKGKGKYYYEVT-VTDEglcR-----VGWSTEDASL--- 65

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 226423903 119 hyaaLLGSNSESWGWDiGRGKLYH--QSKGPGAPQypagTQGEqlevperllVV---LDMEEGTLGYAIGGTYLGPAFR- 192
Cdd:cd12873   66 ----DLGTDKFGFGYG-GTGKKSHgrQFDDYGEPF----GLGD---------VIgcyLDLDNGTISFSKNGKDLGKAFDi 127

                        170       180       190
                 ....*....|....*....|....*....|
gi 226423903 193 --GLKGRTLYPAVsaVWGQCQVRIRYLGER 220
Cdd:cd12873  128 ppHLRNSALFPAV--CLKNAEVEFNFGDKP 155

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 226423903 224 PHSLLHLSRLCVRHNLGDTRLGQVSALPLPPAMKRYLLYQ 263
Cdd:cd03728    3 PPSLMQLCRLCIRKCFGRKQHHKIHKLHLPEPLKHFLLYR 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 226423903 226 SLLHLSRLCVRHNLGDTrlgQVSALPLPPAMKRYLLYQ 263
Cdd:cd03733    5 SLQHLCRMALRRVMTTQ---QVLALPIPKKMKEFLTYR 39

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        40
                 ....*....|....*....|....*....|....*....|
gi 226423903 226 SLLHLSRLCVRHNLGDTRLGQ---VSALPLPPAMKRYLLY 262
Cdd:cd03722    5 SLTHLCRLEIRSSLKSERLRSdsfICQLPLPRSLQDYLLY 44

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
                 ....*....|....*....|....*....|....*...
gi 226423903 224 PHSLLHLSRLCVRHNLGDTRLGQVSALPLPPAMKRYLL 261
Cdd:cd03723    3 PRSLQHLCRCAIRKLLGSRCHKLVPQLSLPTSLKNYLL 40