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 807066371 223 EEPQSLLHLSRLCVRHALGDTRLGQISTLPLPPAMKRYLLYK 264
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 807066371   89 HAWEISWpLEQRGTHAVVGVATALAPLQADHYaalLGSNSESWGWDIGRGKLYHQSKGLEAPQYPAGPqgeqlvvPERLL 168
Cdd:pfam00622   2 HYFEVEI-FGQDGGGWRVGWATKSVPRKGERF---LGDESGSWGYDGWTGKKYWASTSPLTGLPLFEP-------GDVIG 70

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 807066371  169 VVLDMEEGTLGYSIGGTYLGPAFRGLKGR-TLYPSVSAVWGQCQVRI 214
Cdd:pfam00622  71 CFLDYEAGTISFTKNGKSLGYAFRDVPFAgPLFPAVSLGAGEGLKFN 117

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 807066371 223 EEPQSLLHLSRLCVRHALGDTRLGQISTLPLPPAMKRYLLYK 264
Cdd:cd03719    1 AEPHSLLHLSRLCVRHALGDTRLGQVSALPLPPAMKRYLLYQ 42

suppressors of cytokine signalling; suppressors of cytokine signalling

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 807066371   219 ERRVEEPQSLLHLsrlCVRHALGDTRLGQISTLPLPPAMKRYLLYK 264
Cdd:smart00253   1 LPRPSNVPSLQHL---CRFTIRRCTRTDQIKTLPLPPKLKDYLSYY 43

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 807066371  46 HGWNPKDCSENIDVKEGGLCFERRPVAQSTDGVRGKRGYSRGLHAWEISWPLEQRGTHAVVGVATALAPLQADHYAALLG 125
Cdd:cd12875    1 HGWNPADCSKNIYIKEDGLTFHRRPVAQSTDAIRGKKGYTRGLHAWEVKWISRPRGSHAVVGVATKDAPLQCDGYVTLLG 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 807066371 126 SNSESWGWDIGRGKLYHQSKGLEaPQYPAGpqGEQLVVPERLLVVLDMEEGTLGYSIGGTYLGPAFRGLKGRTLYPSVSA 205
Cdd:cd12875   81 SNSESWGWDLGDNKLYHNGKKVI-GSYPAK--SENYQVPDRILVILDMEDGTLAFEANGEYLGVAFRGLPGKLLYPAVSA 157

                        170
                 ....*....|..
gi 807066371 206 VWGQCQVRIRYM 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 807066371   89 HAWEISWpLEQRGTHAVVGVATALAPLQADHYaalLGSNSESWGWDIGRGKLYHQSKGLEAPQYPAGPqgeqlvvPERLL 168
Cdd:pfam00622   2 HYFEVEI-FGQDGGGWRVGWATKSVPRKGERF---LGDESGSWGYDGWTGKKYWASTSPLTGLPLFEP-------GDVIG 70

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 807066371  169 VVLDMEEGTLGYSIGGTYLGPAFRGLKGR-TLYPSVSAVWGQCQVRI 214
Cdd:pfam00622  71 CFLDYEAGTISFTKNGKSLGYAFRDVPFAgPLFPAVSLGAGEGLKFN 117

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 807066371 223 EEPQSLLHLSRLCVRHALGDTRLGQISTLPLPPAMKRYLLYK 264
Cdd:cd03719    1 AEPHSLLHLSRLCVRHALGDTRLGQVSALPLPPAMKRYLLYQ 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 807066371  87 GLHAWEISWPLEQRGtHAVVGVATALAPLQADHYaalLGSNSESWGWDIGRGKLYHQSKGleapqypaGPQGEQLVVPER 166
Cdd:cd11709    1 GKWYWEVRVDSGNGG-LIQVGWATKSFSLDGEGG---VGDDEESWGYDGSRLRKGHGGSS--------GPGGRPWKSGDV 68

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 807066371 167 LLVVLDMEEGTLGYSIGGTYLGPAFRGL--KGRTLYPSVSAVWGQcQVRIR 215
Cdd:cd11709   69 VGCLLDLDEGTLSFSLNGKDLGVAFTNLflKGGGLYPAVSLGSGQ-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 807066371 224 EPQSLLHLSRLCVRHALGDTRLGQISTLPLPPAMKRYLLYK 264
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 807066371 224 EPQSLLHLSRLCVRHALGDTRLGQISTLPLPPAMKRYLLYK 264
Cdd:cd03718    2 EPLPLMDLCRRRVRVALGRDRLEEIEQLPLPPSLKNYLLYQ 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 807066371 224 EPQSLLHLSRLCVRHALGDTRLGQISTLPLPPAMKRYLLYK 264
Cdd:cd03744    2 EPLPLMDLCRRSVRLALGRERLSEIHTLPLPASLKNYLLYQ 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
                 ....*....|....*....|....*....|....*....
gi 807066371 225 PQSLLHLSRLCVRHALGDTRLGQISTLPLPPAMKRYLLY 263
Cdd:cd03720    3 PRSLLSLCRIAVRRALGKQRLSLICSLPLPDPIKKFLLH 41

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 807066371 223 EEPQSLLHLSRLCVRHALGDTRLGQISTLPLPPAMKRYLLYK 264
Cdd:cd03721    1 EPPRPLAHLCRLKVRTLIGINRIKLIDTLPLPPRLIRYLNHQ 42

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 807066371  83 GYSRGLHAWEISWPLEQRGTHA-VVGVATAlaPLQADHYAallgSNSESWGWDIGRGKLYHQSKGLEA--PQYPAGpqge 159
Cdd:cd12881   38 GISSGCYQWKFYLVKENRGNEGtCVGVSRK--PVTDFNYR----TSSDMWLYRAYNGNLYHNGEQLLRlsSKFHQG---- 107

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 807066371 160 qlvvpERLLVVLDMEEGTLGYSIGGTYLGPAFRGLKGRTLYPSVS 204
Cdd:cd12881  108 -----DYITVVLDMEEGTLSFGKNGEEPGVAFEDVDATELYPCVM 147

SOCS (suppressors of cytokine signaling) box of ASB5-like proteins. ASB family members have a C-terminal SOCS box and an N-terminal ankyrin-related sequence. ASB5 has been implicated in the initiation of arteriogenesis. 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 807066371 225 PQSLLHLSRLCVRHALGDTRLGQISTLPLPPAMKRYLLYK 264
Cdd:cd03724    3 PSSLCQLCRLCIRNYIGRSRLHLIPQLQLPTLLKNFLQYR 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 807066371  48 WNPKDCSENIDVKEGGLCferrpvAQSTD-----GVRGKRG-YSRGLHAWEISwPLEQ---RgthavVGVATALAPLqad 118
Cdd:cd12873    1 MNPYDRDAALAISPDGLL------CQSREekgwqGCRATKGvKGKGKYYYEVT-VTDEglcR-----VGWSTEDASL--- 65

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 807066371 119 hyaaLLGSNSESWGWDiGRGKLYHQSKGLeapQYpagpqGEQLVVPERLLVVLDMEEGTLGYSIGGTYLGPAFR---GLK 195
Cdd:cd12873   66 ----DLGTDKFGFGYG-GTGKKSHGRQFD---DY-----GEPFGLGDVIGCYLDLDNGTISFSKNGKDLGKAFDippHLR 132

                 ....*....
gi 807066371 196 GRTLYPSVS 204
Cdd:cd12873  133 NSALFPAVC 141

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 807066371  78 VRGKRGYSRGLHAWEISW--PLEQRGTHAVVGVATALAPLQADhyaalLGSNSESWGW-DIGrGKLYHQSKGleaPQYPA 154
Cdd:cd12872   19 ARANHGVREGKWYFEVKIleGGGTETGHVRVGWSRREASLQAP-----VGYDKYSYAIrDKD-GSKFHQSRG---KPYGE 89

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 807066371 155 GPQGEQLVVPerLLVVLdmeeGTLGYSIGGTYLGPAFRGLKGR-TLYPSVSaVWGQCQVRIR 215
Cdd:cd12872   90 PGFKEGDVIG--FLITL----PKIEFFKNGKSQGVAFEDIYGTgGYYPAVS-LYKGATVTIN 144

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 807066371 223 EEPQSLLHLSRLCVRHALGDTRLGQISTLPLPPAMKRYLLYK 264
Cdd:cd03728    1 EGPPSLMQLCRLCIRKCFGRKQHHKIHKLHLPEPLKHFLLYR 42

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 807066371 226 QSLLHLSRLCVRHALgdtRLGQISTLPLPPAMKRYLLYK 264
Cdd:cd03741    4 QSLQHLCRFVIRKLV---RRDHIPALPLPRRLIDYLREK 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 807066371 227 SLLHLSRLCVRHALGDTRLGQ---ISTLPLPPAMKRYLLY 263
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 807066371 225 PQSLLHLSRLCVRHALGDTRLGQISTLPLPPAMKRYLL 262
Cdd:cd03723    3 PRSLQHLCRCAIRKLLGSRCHKLVPQLSLPTSLKNYLL 40

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

                         10        20
                 ....*....|....*....|....*....
gi 807066371 175 EGTLGYSIGGTYLGPAFRGLKGRTLYPSV 203
Cdd:cd12909  101 DNTAFYTKNGVNLGIAFRDIKKGNLYPTV 129