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 70887547  54 HSWNNDDRSLNIFVKEDNKLIFHRHPVAQSTDAIRGRVGYTRGLHVWEISWAMRQRGTHAVVGVATGEAPLHSVGYTALV 133
Cdd:cd12906   1 HAWNPDDRSLNIFVKEDDPLTFHRHPVAQSTDCIRGKVGYSRGLHVWEITWPTRQRGTHAVVGVATKDAPLHCVGYTSLV 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 70887547 134 GNNSESWGWDLGRNKLYHDGKNQPSRTYPAFLEPDETFIVPDSFLVVLDMDEGTLSFIVDGQYLGVAFRGLKGKKLYPVV 213
Cdd:cd12906  81 GSNEESWGWDIGRNKLYHDSKNQPGWTYPAFLEPDENFVVPDKFLVVLDMDEGTLSFVVDGQYLGVAFRGLKGKKLYPIV 160

                       170
                ....*....|....
gi 70887547 214 SAVWGHCEIRIRYI 227
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 70887547  54 HSWNNDDRSLNIFVKEDNKLIFHRHPVAQSTDAIRGRVGYTRGLHVWEISWAMRQRGTHAVVGVATGEAPLHSVGYTALV 133
Cdd:cd12906   1 HAWNPDDRSLNIFVKEDDPLTFHRHPVAQSTDCIRGKVGYSRGLHVWEITWPTRQRGTHAVVGVATKDAPLHCVGYTSLV 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 70887547 134 GNNSESWGWDLGRNKLYHDGKNQPSRTYPAFLEPDETFIVPDSFLVVLDMDEGTLSFIVDGQYLGVAFRGLKGKKLYPVV 213
Cdd:cd12906  81 GSNEESWGWDIGRNKLYHDSKNQPGWTYPAFLEPDENFVVPDKFLVVLDMDEGTLSFVVDGQYLGVAFRGLKGKKLYPIV 160

                       170
                ....*....|....
gi 70887547 214 SAVWGHCEIRIRYI 227
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 70887547    98 HVWEISWaMRQRGTHAVVGVATGEAPLHSVGYtalVGNNSESWGWDLGRNKLYHDGknQPSRTYPAFLEPdetfivPDSF 177
Cdd:pfam00622   2 HYFEVEI-FGQDGGGWRVGWATKSVPRKGERF---LGDESGSWGYDGWTGKKYWAS--TSPLTGLPLFEP------GDVI 69

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 70887547   178 LVVLDMDEGTLSFIVDGQYLGVAFRGLKG-KKLYPVVSAVWGHCEIRI 224
Cdd:pfam00622  70 GCFLDYEAGTISFTKNGKSLGYAFRDVPFaGPLFPAVSLGAGEGLKFN 117

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 70887547   233 EPLPLMDLCRRSVRVALGRERLSEIHGLPLPASLKNYLL 271
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 70887547  54 HSWNNDDRSLNIFVKEDNKLIFHRHPVAQSTDAIRGRVGYTRGLHVWEISWAMRQRGTHAVVGVATGEAPLHSVGYTALV 133
Cdd:cd12906   1 HAWNPDDRSLNIFVKEDDPLTFHRHPVAQSTDCIRGKVGYSRGLHVWEITWPTRQRGTHAVVGVATKDAPLHCVGYTSLV 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 70887547 134 GNNSESWGWDLGRNKLYHDGKNQPSRTYPAFLEPDETFIVPDSFLVVLDMDEGTLSFIVDGQYLGVAFRGLKGKKLYPVV 213
Cdd:cd12906  81 GSNEESWGWDIGRNKLYHDSKNQPGWTYPAFLEPDENFVVPDKFLVVLDMDEGTLSFVVDGQYLGVAFRGLKGKKLYPIV 160

                       170
                ....*....|....
gi 70887547 214 SAVWGHCEIRIRYI 227
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 70887547  54 HSWNNDDRSLNIFVKEdNKLIFHRHPVAQSTDAIRGRVGYTRGLHVWEISWAmRQRGTHAVVGVATGEAPLHSVGYTALV 133
Cdd:cd12907   1 HAWNPNDCSRNIYIKP-NGFTLHRNPVAQSTDGARGKIGFSSGRHAWEVWWE-GPLGTVAVVGIATKHAPLQCQGYVALL 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 70887547 134 GNNSESWGWDLGRNKLYHDGKNQPsrTYPAFLEPdETFIVPDSFLVVLDMDEGTLSFIVDGQYLGVAFRGLKGKKLYPVV 213
Cdd:cd12907  79 GSDDQSWGWNLVDNHLLHNGDSQG--NYPQCNNA-PKYQVGERIRVILDCEDNTLAFERGYEFLGVAFRGLPPTKLYPAV 155

                       170
                ....*....|....
gi 70887547 214 SAVWGHCEIRIRYI 227
Cdd:cd12907 156 SAVYGNTEVSMVYL 169

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 70887547 232 PEPLPLMDLCRRSVRVALGRERLSEIHGLPLPASLKNYLLYQ 273
Cdd:cd03718   1 PEPLPLMDLCRRRVRVALGRDRLEEIEQLPLPPSLKNYLLYQ 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 70887547    98 HVWEISWaMRQRGTHAVVGVATGEAPLHSVGYtalVGNNSESWGWDLGRNKLYHDGknQPSRTYPAFLEPdetfivPDSF 177
Cdd:pfam00622   2 HYFEVEI-FGQDGGGWRVGWATKSVPRKGERF---LGDESGSWGYDGWTGKKYWAS--TSPLTGLPLFEP------GDVI 69

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 70887547   178 LVVLDMDEGTLSFIVDGQYLGVAFRGLKG-KKLYPVVSAVWGHCEIRI 224
Cdd:pfam00622  70 GCFLDYEAGTISFTKNGKSLGYAFRDVPFaGPLFPAVSLGAGEGLKFN 117

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 70887547 232 PEPLPLMDLCRRSVRVALGRERLSEIHGLPLPASLKNYLLYQ 273
Cdd:cd03743   1 PEPLPLMDLCRRSARQALGRHRLHHIQSLPLPQTLKNYLQYQ 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 70887547 232 PEPLPLMDLCRRSVRVALGRERLSEIHGLPLPASLKNYLLYQ 273
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 70887547   233 EPLPLMDLCRRSVRVALGRERLSEIHGLPLPASLKNYLL 271
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 70887547 234 PLPLMDLCRRSVRVALGRERLSEIHGLPLPASLKNYLLYQ 273
Cdd:cd03721   3 PRPLAHLCRLKVRTLIGINRIKLIDTLPLPPRLIRYLNHQ 42

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 70887547 234 PLPLMDLCRRSVRVALGRERLSEIHGLPLPASLKNYLLYQ 273
Cdd:cd03720   3 PRSLLSLCRIAVRRALGKQRLSLICSLPLPDPIKKFLLHE 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 70887547    235 LPLMDLCRRSVRVALGRerlseIHGLPLPASLKNYLLYQ 273
Cdd:smart00969   1 RSLQHLCRLAIRRSLGG-----IDKLPLPPRLKDYLLYY 34

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 70887547 234 PLPLMDLCRRSVRVALGRERLSEIHGLPLPASLKNYLLYQ 273
Cdd:cd03728   3 PPSLMQLCRLCIRKCFGRKQHHKIHKLHLPEPLKHFLLYR 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 70887547  40 LLDMPSASQDIQVqhswNNDDRSLNIFVKEDNKLIFHRHPVAQSTDAIRGRVGYTRGLHVWEISwamRQRGTHAVVGVAT 119
Cdd:cd13734   2 KLDPKTAHRKLRL----SNDNLTVEYDPEGSKDQAAVLPRRFTGSPAVLGDVAISSGRHYWEVS---VSRSTSYRVGVAY 74

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 70887547 120 GEAPLHSvgytaLVGNNSESWGWDLGRNKLY--HDGKNQPSRTYPaflepdetfiVPDSFLVVLDMDEGTLSFIVDGQYL 197
Cdd:cd13734  75 KSAPRDE-----DLGKNSTSWCLSRDNNRYTarHDGKVVDLRVTG----------HPARIGVLLDYDNGTLSFYDAESKQ 139

                       170       180
                ....*....|....*....|..
gi 70887547 198 G-VAFRGLKGKKLYPVVsAVWG 218
Cdd:cd13734 140 HlYTFHVDFEGPVCPAF-AVWN 160

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        40
                ....*....|....*....|....*....|....*....|.
gi 70887547 233 EPLPLMDLCRRSVRVALGRERlseIHGLPLPASLKNYLLYQ 273
Cdd:cd03717   2 SVRSLQHLCRFVIRQCTRRDL---IDQLPLPRRLKDYLKEY 39

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 70887547 234 PLPLMDLCRRSVRVALGRERLSEIHGLPLPASLKNYLL 271
Cdd:cd03723   3 PRSLQHLCRCAIRKLLGSRCHKLVPQLSLPTSLKNYLL 40

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 70887547 234 PLPLMDLCRRSVRVALGRERL---SEIHGLPLPASLKNYLLYQ 273
Cdd:cd03731   3 PRPLKHLCRLKIRKLMGLQKLqqpSSMKKLPLPPALKRYILYK 45

SOCS (suppressors of cytokine signaling) box of ASB14-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 70887547 234 PLPLMDLCRRSVRVALGRERLSE---IHGLPLPASLKNYLLYQ 273
Cdd:cd03730   3 PRSLKHLCRLKIRACMGRLRLRCpvfMSFLPLPNRLKAYILYK 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 70887547 234 PLPLMDLCRRSVRVALGRERLSEIHGLPLPASLKNYLLY 272
Cdd:cd03729   3 PLSLQQLCRINLRKALGTRALEKIAKLNIPNRIIDYLSY 41

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 70887547 115 VGVATGEAPLHSVgytaLVGNNSESWG--WDlgrNKLYHDG--KNQPSRTypaflePDETFIVPDSFlvvldmDEGTLSF 190
Cdd:cd12880  45 VGLATRKTDLNRV----PLGNDAESWVlrSD---GTIWHNGevIHKLKQL------VEEGDVIGVTY------DHVELNF 105

                        90       100
                ....*....|....*....|...
gi 70887547 191 IVDGQYLGVAFRGLKGkKLYPVV 213
Cdd:cd12880 106 YLNGKPLDCPITGIKG-TVYPVV 127

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 70887547  87 IRGRVGYTRGLHVWEIsWAMRQRGT---HAVVGVATGEAPLHsvgytALVGNNSESWGW-DLGRNKlYHDGKNQPsRTYP 162
Cdd:cd12872  19 ARANHGVREGKWYFEV-KILEGGGTetgHVRVGWSRREASLQ-----APVGYDKYSYAIrDKDGSK-FHQSRGKP-YGEP 90

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|...
gi 70887547 163 AFLEPDetfIVpdSFLVVLdmdeGTLSFIVDGQYLGVAFRGLKGKKLY-PVVS 214
Cdd:cd12872  91 GFKEGD---VI--GFLITL----PKIEFFKNGKSQGVAFEDIYGTGGYyPAVS 134

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 70887547  87 IRGRVGYTRGLHVWEI------SWamrqrgthaVVGVATgeaplHSVGYTALVGNNSESWGWDLGrnklYHDGKNQpSRT 160
Cdd:cd12893  44 VLGSEGFTSGKHSWDVevgdntSW---------MLGVAK-----ESVQRKGKFTLSPESGFWTIG----FSEGKYS-ART 104

                        90       100       110
                ....*....|....*....|....*....|.
gi 70887547 161 YPAFLEPDETFIVPDSFLVVLDMDEGTLSFI 191
Cdd:cd12893 105 SPEPRTPLRVKQKPQRIRVQLDWDRGKVSFS 135

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 70887547 233 EPLPLMDLCRRSVRVALGRERLSEIHGLPLPASLKNYLLYQ 273
Cdd:cd03726   2 QPRTLQDLCRIKIRHCIGLQNLKLLDELPIAKVMKDYLKHK 42