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 1953073378 232 PEPLPLMDLCRRSVRLALGKERLGDIHTLPLPASLKAYLLYQ 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 1953073378 232 PEPLPLMDLCRRSVRLALGKERLGDIHTLPLPASLKAYLLYQ 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 1953073378   95 RGLHVWQITWamrQRGTHAVVGVATADAPLHsvgYTTLVGNNHESWGWDLGRNRLYHDGKnqpSKTYPAFLEPDetfivP 174
Cdd:smart00449   1 SGRHYFEVEI---GDGGHWRVGVATKSVPRG---YFALLGEDKGSWGYDGDGGKKYHNST---GPEYGLPLQEP-----G 66

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1953073378  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 1953073378  235 LPLMDLCRRSVRlalgkERLGDIHTLPLPASLKAYLLYQ 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 1953073378  54 HSWNNNDRSLNVFVKEDdKLIFHRHPVAQSTDAIRGKVGYTRGLHVWQITWAMRQRGTHAVVGVATADAPLHSVGYTTLV 133
Cdd:cd12875     1 HGWNPADCSKNIYIKED-GLTFHRRPVAQSTDAIRGKKGYTRGLHAWEVKWISRPRGSHAVVGVATKDAPLQCDGYVTLL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1953073378 134 GNNHESWGWDLGRNRLYHDGKnQPSKTYPAFLepdETFIVPDSFLVALDMDDGTLSFIVDGQYMGVAFRGLKGKKLYPVV 213
Cdd:cd12875    80 GSNSESWGWDLGDNKLYHNGK-KVIGSYPAKS---ENYQVPDRILVILDMEDGTLAFEANGEYLGVAFRGLPGKLLYPAV 155

                         170
                  ....*....|....
gi 1953073378 214 SAVWGHCEIRMRYL 227
Cdd:cd12875   156 SAVYGNCEIRLIYL 169

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 1953073378  55 SWNNNDRSLNV-FVKEDDKLIFHRHpVAQSTDAIRGKVGYTRGLHVWQITWAMRQRGTHAVVGVATADAPLHSVGY--TT 131
Cdd:cd12876     3 TWDERDKSPAVqLSDNNREVYFHPD-YSCGTAAVRGTKPLTNGQHYWEIKMSSPVYGTDMMVGVGTKKADLHAYRYefCS 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1953073378 132 LVGNNHESWGwdLG-RNRLYHDGKNQPsktypaFLEP--DETFIVPdsflVALDMDDGTLSFIVDGQYMGVAFRGLKG-K 207
Cdd:cd12876    82 LLGEDEESWG--LSyKGLLWHDGQSRP------YTSPfgNQGTIIG----VHLDMWRGTLTFYKNGKPLGVAFTGLNGvK 149

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 1953073378 208 KLYPVVSAVWGHCEIRM----RYLNGLDpeplplmDLCRRSVR 246
Cdd:cd12876   150 PLYPMVSSTAAKSEMKLinsrSFPVSLQ-------DRCCAALR 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 1953073378 232 PEPLPLMDLCRRSVRLALGKERLGDIHTLPLPASLKAYLLYQ 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 1953073378  96 GLHVWQITWaMRQRGTHAVVGVATADAPLHSvgyTTLVGNNHESWGWDLGRNRLYHDGKNQPSktypaflepDETFIVPD 175
Cdd:cd11709     1 GKWYWEVRV-DSGNGGLIQVGWATKSFSLDG---EGGVGDDEESWGYDGSRLRKGHGGSSGPG---------GRPWKSGD 67

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1953073378 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 1953073378 232 PEPLPLMDLCRRSVRLALGKERLGDIHTLPLPASLKAYLLYQ 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 1953073378 233 EPLPLMDLCRRSVRLALGKERLGDIHTLPLPASLKAYLLYQ 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 1953073378 233 EPLPLMDLCRRSVRLALGKERLGDIHTLPLPASLKAYLLYQ 273
Cdd:cd03719     2 EPHSLLHLSRLCVRHALGDTRLGQVSALPLPPAMKRYLLYQ 42

SOCS (suppressors of cytokine signaling) box of ASB2-like proteins. ASB family members have a C-terminal SOCS box and an N-terminal ankyrin-related sequence. ASB2 targets specific proteins to destruction by the proteasome in leukemia cells that have been induced to differentiate. The general function of the SOCS box is the recruitment of the ubiquitin-transferase system. The SOCS box interacts with Elongins B and C, Cullin-5 or Cullin-2, Rbx-1, and E2. Therefore, SOCS-box-containing proteins probably function as E3 ubiquitin ligases and mediate the degradation of proteins associated through their N-terminal regions.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1953073378 234 PLPLMDLCRRSVRLALGKERLGDIHTLPLPASLKAYLLYQ 273
Cdd:cd03721     3 PRPLAHLCRLKVRTLIGINRIKLIDTLPLPPRLIRYLNHQ 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 1953073378  235 LPLMDLCRRSVRlalgkERLGDIHTLPLPASLKAYLLYQ 273
Cdd:smart00969   1 RSLQHLCRLAIR-----RSLGGIDKLPLPPRLKDYLLYY 34

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 1953073378 133 VGNNHESWGWDLGRNRLYHDGknqpSKTYpaflepDETFIVPDSFLVALDMDDGTLSFIVDGQYMGVAF---RGLKGKKL 209
Cdd:cd12882    42 VGDTRDSYAYDGNRVRKWNVS----TQKY------GEPWVAGDVIGCCIDLDKGTISFYRNGRSLGVAFdnvRRGPGLAY 111

                          90
                  ....*....|...
gi 1953073378 210 YPVVS-AVWGHCE 221
Cdd:cd12882   112 FPAVSlSFGERLE 124

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 1953073378 237 LMDLCRRSVRLALGKERLGD---IHTLPLPASLKAYLLY 272
Cdd:cd03722     6 LTHLCRLEIRSSLKSERLRSdsfICQLPLPRSLQDYLLY 44

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 1953073378 234 PLPLMDLCRRSVRLALGKERLGDIHTLPLPASLKAYLLY 272
Cdd:cd03729     3 PLSLQQLCRINLRKALGTRALEKIAKLNIPNRIIDYLSY 41

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 1953073378  85 DAIRGKVGYTRGLHVWQITwamRQRGTHAVVGVATADAPLHSvgyttLVGNNHESWGWDLGRNRLY--HDGknqpsKTYP 162
Cdd:cd13734    43 PAVLGDVAISSGRHYWEVS---VSRSTSYRVGVAYKSAPRDE-----DLGKNSTSWCLSRDNNRYTarHDG-----KVVD 109

                          90       100
                  ....*....|....*....|....*....
gi 1953073378 163 AFLEPDetfivPDSFLVALDMDDGTLSFI 191
Cdd:cd13734   110 LRVTGH-----PARIGVLLDYDNGTLSFY 133

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 1953073378 233 EPLPLMDLCRRSVRLALGKErlgDIHTLPLPASLKAYLLYQ 273
Cdd:cd03717     2 SVRSLQHLCRFVIRQCTRRD---LIDQLPLPRRLKDYLKEY 39

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 1953073378 185 DGTLSFIVDGQYMGVAFRGLKGKKLYPVV 213
Cdd:cd12909   101 DNTAFYTKNGVNLGIAFRDIKKGNLYPTV 129

SOCS (suppressors of cytokine signaling) box of ASB8-like proteins. ASB family members have a C-terminal SOCS box and an N-terminal ankyrin-related sequence. Human ASB8 is highly transcribed in skeletal muscle and in lung carcinoma cell lines. 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 1953073378 234 PLPLMDLCRRSVRLALGKERLGD-IHTLPLPASLKAYLL 271
Cdd:cd03727     3 PGTLKALARYAVRRSLGVQYLPEaVKQLPLPRSVKEYLL 41

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 1953073378 234 PLPLMDLCRRSVRLALGKERL---GDIHTLPLPASLKAYLLYQ 273
Cdd:cd03731     3 PRPLKHLCRLKIRKLMGLQKLqqpSSMKKLPLPPALKRYILYK 45

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 1953073378 115 VGVATADAPLHSVgyttLVGNNHESWG--WDlgrNRLYHDG--KNQPSKTypaflePDETFIVPDSFlvaldmDDGTLSF 190
Cdd:cd12880    45 VGLATRKTDLNRV----PLGNDAESWVlrSD---GTIWHNGevIHKLKQL------VEEGDVIGVTY------DHVELNF 105

                          90       100
                  ....*....|....*....|...
gi 1953073378 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 1953073378 181 LDMDDGTLSFIVDGQYMGVAFR---GLKGKKLYPVVS 214
Cdd:cd12873   105 LDLDNGTISFSKNGKDLGKAFDippHLRNSALFPAVC 141