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 165971613 232 PEPLPLMDLCRRSVRLALGKERLGAIPALPLPASLKAYLLYQ 273
Cdd:cd03744    1 PEPLPLMDLCRRSVRLALGRERLSEIHTLPLPASLKNYLLYQ 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 165971613 232 PEPLPLMDLCRRSVRLALGKERLGAIPALPLPASLKAYLLYQ 273
Cdd:cd03744    1 PEPLPLMDLCRRSVRLALGRERLSEIHTLPLPASLKNYLLYQ 42

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 165971613    95 RGLHVWQITWamrQRGTHAVVGVATADAPLHsvgYTTLVGNNHESWGWDLGRNRLYHDGKnqpSKTYPAFLEPDetfivP 174
Cdd:smart00449   1 SGRHYFEVEI---GDGGHWRVGVATKSVPRG---YFALLGEDKGSWGYDGDGGKKYHNST---GPEYGLPLQEP-----G 66

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 165971613   175 DSFLVALDMDDGTLSFIVDGQY-MGVAFRGLK-GKKLYPVVSaVWGHCEIRMRY 226
Cdd:smart00449  67 DVIGCFLDLEAGTISFYKNGKYlHGLAFFDVKfSGPLYPAFS-LGSGNSVRLNF 119

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 165971613   235 LPLMDLCRRSVRlalgkERLGAIPALPLPASLKAYLLYQ 273
Cdd:smart00969   1 RSLQHLCRLAIR-----RSLGGIDKLPLPPRLKDYLLYY 34

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 165971613  54 HSWNNNDRSLNVFVKEDdKLIFHRHPVAQSTDAIRGKVGYTRGLHVWQITWAMRQRGTHAVVGVATADAPLHSVGYTTLV 133
Cdd:cd12875    1 HGWNPADCSKNIYIKED-GLTFHRRPVAQSTDAIRGKKGYTRGLHAWEVKWISRPRGSHAVVGVATKDAPLQCDGYVTLL 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 165971613 134 GNNHESWGWDLGRNRLYHDGKnQPSKTYPAFLepdETFIVPDSFLVALDMDDGTLSFIVDGQYMGVAFRGLKGKKLYPVV 213
Cdd:cd12875   80 GSNSESWGWDLGDNKLYHNGK-KVIGSYPAKS---ENYQVPDRILVILDMEDGTLAFEANGEYLGVAFRGLPGKLLYPAV 155

                        170
                 ....*....|...
gi 165971613 214 SAVWGHCEIRMRY 226
Cdd:cd12875  156 SAVYGNCEIRLIY 168

SPRY domain in the suppressor of cytokine signaling 3 (SOCS3) family; 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 SOCS3 regulates cellular response to a variety of cytokines such as leukemia inhibitory factor (LIF) and interleukin 6. SOCS3, along with SOCS1, are expressed by immune cells and cells of the central nervous system (CNS) and have the potential to impact immune processes within the CNS. In non-small cell lung cancer (NSCLC), SOCS3 is silenced and proline-rich tyrosine kinase 2 (Pyk2) is over-expressed; it has been suggested that SOCS3 could be an effective way to prevent the progression of NSCLC due to its role in regulating Pyk2 expression.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 165971613  55 SWNNNDRSLNV-FVKEDDKLIFHRHpVAQSTDAIRGKVGYTRGLHVWQITWAMRQRGTHAVVGVATADAPLHSVGY--TT 131
Cdd:cd12876    3 TWDERDKSPAVqLSDNNREVYFHPD-YSCGTAAVRGTKPLTNGQHYWEIKMSSPVYGTDMMVGVGTKKADLHAYRYefCS 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 165971613 132 LVGNNHESWGwdLG-RNRLYHDGKNQPsktypaFLEP--DETFIVPdsflVALDMDDGTLSFIVDGQYMGVAFRGLKG-K 207
Cdd:cd12876   82 LLGEDEESWG--LSyKGLLWHDGQSRP------YTSPfgNQGTIIG----VHLDMWRGTLTFYKNGKPLGVAFTGLNGvK 149

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....
gi 165971613 208 KLYPVVSAVWGHCEIRM-----RYVNgldpeplpLMDLCRRSVR 246
Cdd:cd12876  150 PLYPMVSSTAAKSEMKLinsrsFPVS--------LQDRCCAALR 185

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 165971613 232 PEPLPLMDLCRRSVRLALGKERLGAIPALPLPASLKAYLLYQ 273
Cdd:cd03718    1 PEPLPLMDLCRRRVRVALGRDRLEEIEQLPLPPSLKNYLLYQ 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 165971613  96 GLHVWQITWaMRQRGTHAVVGVATADAPLHSvgyTTLVGNNHESWGWDLGRNRLYHDGKNQPSktypaflepDETFIVPD 175
Cdd:cd11709    1 GKWYWEVRV-DSGNGGLIQVGWATKSFSLDG---EGGVGDDEESWGYDGSRLRKGHGGSSGPG---------GRPWKSGD 67

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 165971613 176 SFLVALDMDDGTLSFIVDGQYMGVAFRGLKGKK--LYPVVSAVWGH-CEIR 223
Cdd:cd11709   68 VVGCLLDLDEGTLSFSLNGKDLGVAFTNLFLKGggLYPAVSLGSGQgVTIN 118

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 165971613 232 PEPLPLMDLCRRSVRLALGKERLGAIPALPLPASLKAYLLYQ 273
Cdd:cd03743    1 PEPLPLMDLCRRSARQALGRHRLHHIQSLPLPQTLKNYLQYQ 42

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 165971613 233 EPLPLMDLCRRSVRLALGKERLGAIPALPLPASLKAYLLYQ 273
Cdd:cd03587    1 NPRSLQHLCRLAIRRCLGKRRLDLIDKLPLPPRLKDYLLYK 41

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 165971613 233 EPLPLMDLCRRSVRLALGKERLGAIPALPLPASLKAYLLYQ 273
Cdd:cd03719    2 EPHSLLHLSRLCVRHALGDTRLGQVSALPLPPAMKRYLLYQ 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 165971613 234 PLPLMDLCRRSVRLALGKERLGAIPALPLPASLKAYLLYQ 273
Cdd:cd03720    3 PRSLLSLCRIAVRRALGKQRLSLICSLPLPDPIKKFLLHE 42

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 165971613  89 GKVGYTRGLHVWQITWAMRQRGTHAVVGVATADaplhsVGYTTLVGNNHESWGWDLGRNR--LYHDGKNQpSKTypafle 166
Cdd:cd12889   42 GSVGFSRGVHYWEVTIDRYDGHPDPAFGVARID-----VNKDKMLGKDDKGWSMYIDNNRswFLHNNEHS-NRT------ 109

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 165971613 167 pdETFIVPDSFL-VALDMDDGTLSFIVDGQYMG-VAFRGLKGkKLYPVVS 214
Cdd:cd12889  110 --EGGITVGSVVgVLLDLDRHTLSFYVNDEPQGpIAFRNLPG-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 165971613 133 VGNNHESWGWDLGRNRLYHDGknqpSKTYpaflepDETFIVPDSFLVALDMDDGTLSFIVDGQYMGVAF---RGLKGKKL 209
Cdd:cd12882   42 VGDTRDSYAYDGNRVRKWNVS----TQKY------GEPWVAGDVIGCCIDLDKGTISFYRNGRSLGVAFdnvRRGPGLAY 111

                         90
                 ....*....|...
gi 165971613 210 YPVVS-AVWGHCE 221
Cdd:cd12882  112 FPAVSlSFGERLE 124

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 165971613 234 PLPLMDLCRRSVRLALGKERLGAIPALPLPASLKAYLLY 272
Cdd:cd03729    3 PLSLQQLCRINLRKALGTRALEKIAKLNIPNRIIDYLSY 41

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 165971613 234 PLPLMDLCRRSVRLALGKERLGAIPALPLPASLKAYLLYQ 273
Cdd:cd03724    3 PSSLCQLCRLCIRNYIGRSRLHLIPQLQLPTLLKNFLQYR 42

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

                         10        20        30
                 ....*....|....*....|....*....|....*....
gi 165971613 237 LMDLCRRSVRLALGKERLGA---IPALPLPASLKAYLLY 272
Cdd:cd03722    6 LTHLCRLEIRSSLKSERLRSdsfICQLPLPRSLQDYLLY 44

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 165971613  85 DAIRGKVGYTRGLHVWQITwamRQRGTHAVVGVATADAPLHSvgyttLVGNNHESWGWDLGRNRLY--HDGknqpsKTYP 162
Cdd:cd13734   43 PAVLGDVAISSGRHYWEVS---VSRSTSYRVGVAYKSAPRDE-----DLGKNSTSWCLSRDNNRYTarHDG-----KVVD 109

                         90       100
                 ....*....|....*....|....*....
gi 165971613 163 AFLEPDetfivPDSFLVALDMDDGTLSFI 191
Cdd:cd13734  110 LRVTGH-----PARIGVLLDYDNGTLSFY 133

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 165971613 234 PLPLMDLCRRSVRLALGKERLGAIPALPLPASLKAYLLYQ 273
Cdd:cd03728    3 PPSLMQLCRLCIRKCFGRKQHHKIHKLHLPEPLKHFLLYR 42

suppressors of cytokine signalling; suppressors of cytokine signalling

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 165971613   233 EPLPLMDLCRRSVRlalGKERLGAIPALPLPASLKAYLLY 272
Cdd:smart00253   6 NVPSLQHLCRFTIR---RCTRTDQIKTLPLPPKLKDYLSY 42

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 165971613 185 DGTLSFIVDGQYMGVAFRGLKGKKLYPVV 213
Cdd:cd12909  101 DNTAFYTKNGVNLGIAFRDIKKGNLYPTV 129

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 165971613 115 VGVATADAPLHSVgyttLVGNNHESWG--WDlgrNRLYHDG--KNQPSKTypaflePDETFIVPDSFlvaldmDDGTLSF 190
Cdd:cd12880   45 VGLATRKTDLNRV----PLGNDAESWVlrSD---GTIWHNGevIHKLKQL------VEEGDVIGVTY------DHVELNF 105

                         90       100
                 ....*....|....*....|...
gi 165971613 191 IVDGQYMGVAFRGLKGkKLYPVV 213
Cdd:cd12880  106 YLNGKPLDCPITGIKG-TVYPVV 127

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
                 ....*....|....*....|....*....|....*..
gi 165971613 181 LDMDDGTLSFIVDGQYMGVAFR---GLKGKKLYPVVS 214
Cdd:cd12873  105 LDLDNGTISFSKNGKDLGKAFDippHLRNSALFPAVC 141