1K2F,2A25,2AN6


Conserved Protein Domain Family
Sina
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cd03829: Sina 
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Seven in absentia (Sina) protein family, C-terminal substrate binding domain; composed of the Drosophila Sina protein, the mammalian Sina homolog (Siah), the plant protein SINAT5, and similar proteins. Sina, Siah and SINAT5 are RING-containing proteins that function as E3 ubiquitin ligases, acting either as single proteins or as a part of multiprotein complexes. Sina is expressed in many cells in the developing eye but is essential specifically for R7 photoreceptor cell development. Sina cooperates with Phyllopod (Phyl), Ebi and the E2 ubiquitin-conjugating enzyme Ubcd1 to catalyze the ubiquitination and subsequent degradation of Tramtrack (Ttk88); Ttk88 is a transcriptional repressor that blocks photoreceptor differentiation. Similarly, the mammalian homologue Siah1 cooperates with SIP (Siah-interacting protein), Ebi and the adaptor protein Skp1, to target beta-catenin for ubiquitination and degradation via a p53-dependent mechanism. SINAT5 targets NAC1 for ubiquitin-mediated degradation resulting in the downregulation of auxin, a hormone that controls many aspects of plant development. Other targets of Sina family proteins include c-Myb, synaptophysin, group 1 glutamate receptors, promyelocytic leukemia protein, alpha-synuclein, synphilin-1 and alpha-ketoglutarate dehydrogenase, among others. Sina proteins also bind proteins that are not targets for ubiquitination such as Phyl, adenomatous polyposis coli, VAV, BAG-1 and Dab-1. Siah binds to a consensus motif, PXAXVXP, which is present in Siah-binding proteins. Siah is a dimeric protein consisting of an N-terminal RING domain, two zinc finger motifs and a C-terminal substrate-binding domain (SBD); this SBD contains an eight-stranded antiparallel beta-sandwich fold similar to the MATH (meprin and TRAF-C homology) domain.
Links
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Statistics
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PSSM-Id: 239753
Aligned: 16 rows
Threshold Bit Score: 187.209
Created: 18-May-2006
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
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Conserved site includes 7 residues -Click on image for an interactive view with Cn3D
Feature 1:substrate binding site [chemical binding site]
Evidence:
  • Structure:2A25_A; Human Siah monomer binds the SIP peptide; contacts at 3.5A
    - View structure with Cn3D
  • Structure:2AN6_CD; Mus musculus Siah dimer binds two PHYL peptides; contacts at 3.5A
    - View structure with Cn3D
  • Comment:There are two substrate binding sites on the Siah dimer separated by a distance of 45A. Siah binds to a consensus PXAXVXP motif found in Siah-binding proteins.
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Sequence Alignment
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Format: Row Display: Color Bits: Type Selection: 
Feature 1            ### # #        ##                                                        
1K2F_A     63 ITTLQGeDIVFLATDINLpgaVDWVMMQSCFGFHFMLVLEKQEky---dGHQQFFAIVQLIGTRkqaENFAYRLELNGHR 139 house mouse
2A25_A     66 ITTLQGeDIVFLATDINLpgaVDWVMMQSCFGFHFMLVLEKQEky---dGHQQFFAIVQLIGTRkqaENFAYRLELNGHR 142 human
2AN6_D     64 ITTLQGeDIVFLATDINLpgaVDWVMMQSCFGFHFMLVLEKQEky---dGHQQFFAIVQLIGTRkqaENFAYRLELNGHR 140 house mouse
XP_414105 524 ITTLQGeDIVFLATDINLpgaVDWVMMQSCFGFHFMLVLEKQEky---dGHQQFFAIVQLIGTRkqaENFAYRLELNGHR 600 chicken
Q7ZVG6    155 ITTLQGeDIVFLATDINLpgaVDWVMMQSCFGFHFMLVLEKQEky---dGHQQFFAIVQLIGTRkqaENFAYRLELNGHR 231 zebrafish
XP_417044 106 INILQGaEIVFLATDMHLpapTDWIIMHSCLGHQFLLVLRKQEky---kGHPQFFATMMLIGTQtqaDNFTYRLELNRNQ 182 chicken
AAH41372  160 VDILQGaEIVFLATDMHLpapADWIIMHSCLGHHFLLVLRKQErh---eGHPQFFATMMLIGTPtqaDCFTYRLELNRNH 236 human
AAL90183  220 VITMEGnDIIFLATNVNLegaLDWTMVQSCHGRHFLLSLEKINlg---eDCQQYFTACRMIGSMkdaAEFVYNISLEAYN 296 fruit fly
AAO67521  240 ITTLQGeDIVFLATDISLpgaVDWVMMQSCFGHSFMLVLEKQEr----vPDQIFFALVQLIGTRkqaDQFVYRLELNGHR 315 Schistosoma mansoni
Q965X6    204 ITTLQGeDIVFLATDINLpgaVDWVMMQSCFDYNFMLVLEKQEkydpaqPTQMFYAVVQLIGSKkeaDNFVYRLELSASR 283 nematode

Feature 1                                                       
1K2F_A    140 RRLTWEATPRSIheGIATAIMNSDCLVFDTSIAQLFaenGNLGINVTISM 189 house mouse
2A25_A    143 RRLTWEATPRSIheGIATAIMNSDCLVFDTSIAQLFaenGNLGINVTISM 192 human
2AN6_D    141 RRLTWEATPRSIheGIATAIMNSDCLVFDTSIAQLFaenGNLGINVTISM 190 house mouse
XP_414105 601 RRLTWEATPRSIheGIATAIMNSDCLVFDTSIAQLFaenGNLGINVTISM 650 chicken
Q7ZVG6    232 RRLTWEATPRSIheGIATAIMNSDCLVFDTSIAQLFaenGNLGINVTISM 281 zebrafish
XP_417044 183 RRLKWEATPRSVleCIDSIISDGDCLVLNTSLAQLFadnGSLAIGIAITT 232 chicken
AAH41372  237 RRLKWEATPRSVleCVDSVITDGDCLVLNTSLAQLFsdnGSLAIGIAITA 286 human
AAL90183  297 RTLRWQSKPRSIr-ENFSSFTNADFLVLNKHTVELFsedGNLALNVVIRK 345 fruit fly
AAO67521  316 RRLTWEACPRSIhdGVQSAIAVSDCLVFDSNTAHSFaenGNLGINVTISQ 365 Schistosoma mansoni
Q965X6    284 RRMSWEATPRSIheGVVVAIQQSDCLAFDSNAAQLFaenGNLGINVTISR 333 nematode

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