SOCS (suppressors of cytokine signaling) box of WSB1/SWiP1-like proteins. This subfamily contains WSB-1 (SOCS-box-containing WD-40 protein), part of an E3 ubiquitin ligase for the thyroid-hormone-activating type 2 iodothyronine deiodinase (D2) and SWiP-1 (SOCS box and WD-repeats in Protein), a WD40-containing protein that is expressed in embryonic structures of chickens and regulated by Sonic Hedgehog (Shh). 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 1046849453 159 RQVSSLQHLCRMSIRRVMPTQEVQKLPVPSKMLEFLSYRV 198
Cdd:cd03746     1 RQVASLQHLCRMAIRRVMPTQQVKELPIPSKLLEFLTYRT 40

WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from its N-terminus and the WD dipeptide at its C-terminus and is 40 residues long, hence the name WD40; between GH and WD lies a conserved core; serves as a stable propeller-like platform to which proteins can bind either stably or reversibly; forms a propeller-like structure with several blades where each blade is composed of a four-stranded anti-parallel b-sheet; instances with few detectable copies are hypothesized to form larger structures by dimerization; each WD40 sequence repeat forms the first three strands of one blade and the last strand in the next blade; the last C-terminal WD40 repeat completes the blade structure of the first WD40 repeat to create the closed ring propeller-structure; residues on the top and bottom surface of the propeller are proposed to coordinate interactions with other proteins and/or small ligands; 7 copies of the repeat are present in this alignment.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046849453  15 VFLWNMDKYTMIRRLEGHHHDVVACDFSPDGALLATASYDTRVYVWDPHIGDTLMEF-GHlfppptpifagganDRWVRA 93
Cdd:cd00200   117 IKVWDVETGKCLTTLRGHTDWVNSVAFSPDGTFVASSSQDGTIKLWDLRTGKCVATLtGH--------------TGEVNS 182

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1046849453  94 VSFSHDGLHVASLADDKMVRFWSIGDDCPVQVAPLSNG--LCCAFSTDGSVLAAGTHDGSVYFW--ATPRQVSSLQ 165
Cdd:cd00200   183 VAFSPDGEKLLSSSSDGTIKLWDLSTGKCLGTLRGHENgvNSVAFSPDGYLLASGSEDGTIRVWdlRTGECVQTLS 258

suppressors of cytokine signalling; suppressors of cytokine signalling

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1046849453  155 WATPRQVSSLQHLCRMSIRRVMPTQEVQKLPVPSKMLEFLSYR 197
Cdd:smart00253   1 LPRPSNVPSLQHLCRFTIRRCTRTDQIKTLPLPPKLKDYLSYY 43

WD40 repeats; Note that these repeats are permuted with respect to the structural repeats (blades) of the beta propeller domain.

                           10        20        30
                   ....*....|....*....|....*....|....*.
gi 1046849453   26 IRRLEGHHHDVVACDFSPDGALLATASYDTRVYVWD 61
Cdd:smart00320   5 LKTLKGHTGPVTSVAFSPDGKYLASGSDDGTIKLWD 40

WD40 repeat [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046849453  17 LWNMDKYTMIRRLEGHHHDVVACDFSPDGALLATASYDTRVYVWDPHIGDTLMEF-GHlfppptpifagganDRWVRAVS 95
Cdd:COG2319   104 LWDLATGLLLRTLTGHTGAVRSVAFSPDGKTLASGSADGTVRLWDLATGKLLRTLtGH--------------SGAVTSVA 169

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1046849453  96 FSHDGLHVASLADDKMVRFWSIGDDCPVQVAPLSNG--LCCAFSTDGSVLAAGTHDGSVYFW--ATPRQVSSLQH 166
Cdd:COG2319   170 FSPDGKLLASGSDDGTVRLWDLATGKLLRTLTGHTGavRSVAFSPDGKLLASGSADGTVRLWdlATGKLLRTLTG 244

WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from its N-terminus and the WD dipeptide at its C-terminus and is 40 residues long, hence the name WD40; between GH and WD lies a conserved core; serves as a stable propeller-like platform to which proteins can bind either stably or reversibly; forms a propeller-like structure with several blades where each blade is composed of a four-stranded anti-parallel b-sheet; instances with few detectable copies are hypothesized to form larger structures by dimerization; each WD40 sequence repeat forms the first three strands of one blade and the last strand in the next blade; the last C-terminal WD40 repeat completes the blade structure of the first WD40 repeat to create the closed ring propeller-structure; residues on the top and bottom surface of the propeller are proposed to coordinate interactions with other proteins and/or small ligands; 7 copies of the repeat are present in this alignment.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046849453  15 VFLWNMDKYTMIRRLEGHHHDVVACDFSPDGALLATASYDTRVYVWDPHIGDTLMEF-GHlfppptpifagganDRWVRA 93
Cdd:cd00200   117 IKVWDVETGKCLTTLRGHTDWVNSVAFSPDGTFVASSSQDGTIKLWDLRTGKCVATLtGH--------------TGEVNS 182

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1046849453  94 VSFSHDGLHVASLADDKMVRFWSIGDDCPVQVAPLSNG--LCCAFSTDGSVLAAGTHDGSVYFW--ATPRQVSSLQ 165
Cdd:cd00200   183 VAFSPDGEKLLSSSSDGTIKLWDLSTGKCLGTLRGHENgvNSVAFSPDGYLLASGSEDGTIRVWdlRTGECVQTLS 258

WD40 domain, found in a number of eukaryotic proteins that cover a wide variety of functions including adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly; typically contains a GH dipeptide 11-24 residues from its N-terminus and the WD dipeptide at its C-terminus and is 40 residues long, hence the name WD40; between GH and WD lies a conserved core; serves as a stable propeller-like platform to which proteins can bind either stably or reversibly; forms a propeller-like structure with several blades where each blade is composed of a four-stranded anti-parallel b-sheet; instances with few detectable copies are hypothesized to form larger structures by dimerization; each WD40 sequence repeat forms the first three strands of one blade and the last strand in the next blade; the last C-terminal WD40 repeat completes the blade structure of the first WD40 repeat to create the closed ring propeller-structure; residues on the top and bottom surface of the propeller are proposed to coordinate interactions with other proteins and/or small ligands; 7 copies of the repeat are present in this alignment.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046849453  15 VFLWNMDKYTMIRRLEGHHHDVVACDFSPDGALLATASYDTRVYVWDPHIGDTLMEF-GHlfppptpifagganDRWVRA 93
Cdd:cd00200   159 IKLWDLRTGKCVATLTGHTGEVNSVAFSPDGEKLLSSSSDGTIKLWDLSTGKCLGTLrGH--------------ENGVNS 224

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1046849453  94 VSFSHDGLHVASLADDKMVRFWSIGDDCPVQVAPLSNG--LCCAFSTDGSVLAAGTHDGSVYFWA 156
Cdd:cd00200   225 VAFSPDGYLLASGSEDGTIRVWDLRTGECVQTLSGHTNsvTSLAWSPDGKRLASGSADGTIRIWD 289

SOCS (suppressors of cytokine signaling) box of WSB/SWiP-like proteins. This subfamily contains WSB-1 (SOCS-box-containing WD-40 protein), part of an E3 ubiquitin ligase for the thyroid-hormone-activating type 2 iodothyronine deiodinase (D2), and SWiP-1 (SOCS box and WD-repeats in Protein), a WD40-containing protein that is expressed in embryonic structures of chickens and regulated by Sonic Hedgehog (Shh), as well as, their isoforms WSB-2 and SWiP-2. The general function of the SOCS box is the recruitment of the ubiquitin-transferase system. The SOCS box interacts with Elongins B and C, Cullin-5 or Cullin-2, Rbx-1, and E2. Therefore, SOCS-box-containing proteins probably function as E3 ubiquitin ligases and mediate the degradation of proteins associated through their N-terminal regions.

                          10        20        30
                  ....*....|....*....|....*....|....*....
gi 1046849453 159 RQVSSLQHLCRMSIRRVMPTQEVQKLPVPSKMLEFLSYR 197
Cdd:cd03733     1 RVVSSLQHLCRMALRRVMTTQQVLALPIPKKMKEFLTYR 39

WD40 repeat [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046849453  13 KGVFLWNMDKYTMIRRLEGHHHDVVACDFSPDGALLATASYDTRVYVWDPHIGDTLMEF-GHlfppptpifagganDRWV 91
Cdd:COG2319   310 GTVRLWDLATGKLLRTLTGHTGAVRSVAFSPDGKTLASGSDDGTVRLWDLATGELLRTLtGH--------------TGAV 375

                          90       100
                  ....*....|....*....|....*...
gi 1046849453  92 RAVSFSHDGLHVASLADDKMVRFWSIGD 119
Cdd:COG2319   376 TSVAFSPDGRTLASGSADGTVRLWDLAT 403

suppressors of cytokine signalling; suppressors of cytokine signalling

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1046849453  155 WATPRQVSSLQHLCRMSIRRVMPTQEVQKLPVPSKMLEFLSYR 197
Cdd:smart00253   1 LPRPSNVPSLQHLCRFTIRRCTRTDQIKTLPLPPKLKDYLSYY 43

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
                  ....*....|....*....|....*....|....*...
gi 1046849453 160 QVSSLQHLCRMSIRRVMPTQEVQKLPVPSKMLEFLSYR 197
Cdd:cd03717     2 SVRSLQHLCRFVIRQCTRRDLIDQLPLPRRLKDYLKEY 39

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 1046849453 156 ATPRqvsSLQHLCRMSIRRVMPTQ---EVQKLPVPSKMLEFLSYR 197
Cdd:cd03716     1 STPR---SLQHLCRLAIRRCLGRRrleLIKKLPLPPRLKDYLLYE 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 1046849453 160 QVSSLQHLCRMSIRRVMPT---QEVQKLPVPSKMLEFL 194
Cdd:pfam07525   1 TPRSLQHLCRLAIRRALGKrrlGAIDKLPLPPLLKDYL 38

WD domain, G-beta repeat;

                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 1046849453  26 IRRLEGHHHDVVACDFSPDGALLATASYDTRVYVWD 61
Cdd:pfam00400   4 LKTLEGHTGSVTSLAFSPDGKLLASGSDDGTVKVWD 39

SOCS (suppressors of cytokine signaling) box of SOCS6-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. 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 1046849453 160 QVSSLQHLCRMSIRRVMPTQEVQKLPVPSKMLEFL 194
Cdd:cd03740     2 QVRSLQYLCRFVIRQYTRIDLIQKLPLPNKMKGYL 36

SOCS (suppressors of cytokine signaling) box of SOCS2-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. SOCS2 has recently been shown to regulate neuronal differentiation by controlling expression of a neurogenic transcription factor, Neurogenin-1. SOCS2 binds to GH receptors and inhibits the activation of STAT5b induced by GH. 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 1046849453 156 ATPrqvsSLQHLCRMSIRRVmpTQEVQKLPVPSKMLEFLS-YR 197
Cdd:cd03736     2 STP----SLQHLCRITINKC--TRQIQELPLPTRLKDYLTeYT 38

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
                  ....*....|....*....|....*....|....*...
gi 1046849453 163 SLQHLCRMSIRRVM---PTQEVQKLPVPSKMLEFLSYR 197
Cdd:cd03718     5 PLMDLCRRRVRVALgrdRLEEIEQLPLPPSLKNYLLYQ 42

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        40
                  ....*....|....*....|....*....|....*....|.
gi 1046849453 157 TPRqvsSLQHLCRMSIRRVMPTQ---EVQKLPVPSKMLEFL 194
Cdd:cd03723     2 TPR---SLQHLCRCAIRKLLGSRchkLVPQLSLPTSLKNYL 39

SOCS (suppressors of cytokine signaling) box of SOCS5-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. SOCS5 inhibits Th2 differentiation by inhibiting IL-4 signaling. 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 1046849453 163 SLQHLCRMSIRRVMPTQEVQKLPVPSKMLEFL 194
Cdd:cd03739     5 SLQYICRAVICRCTTYDGIDALPLPSMLQDFL 36

WD40 region of Ge1, enhancer of mRNA-decapping protein; Ge1_WD40 is the N-terminal region of Ge-1 or enhancer of mRNA-decapping proteins. WD40-repeat regions are involved in protein-protein interactions.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1046849453 122 PVQVAPLSNGL----------CCAFSTDGSVLAAGTHDGSVYFW 155
Cdd:pfam16529 170 PLQPAALESGYieieehsllvDAAFSPDGTALATASLDGEVKFF 213