Conserved Protein Domain Family
Delta4-sphingolipid-FADS-like
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cd03508: Delta4-sphingolipid-FADS-like 
The Delta4-sphingolipid Fatty Acid Desaturase (Delta4-sphingolipid-FADS)-like CD includes the integral-membrane enzymes, dihydroceramide Delta-4 desaturase, involved in the synthesis of sphingosine; and the human membrane fatty acid (lipid) desaturase (MLD), reported to modulate biosynthesis of the epidermal growth factor receptor; and other related proteins. These proteins are found in various eukaryotes including vertebrates, higher plants, and fungi. Studies show that MLD is localized to the endoplasmic reticulum. As with other members of this superfamily, this domain family has extensive hydrophobic regions that would be capable of spanning the membrane bilayer at least twice. Comparison of sequences also reveals the existence of three regions of conserved histidine cluster motifs that contain eight histidine residues: HXXXH, HXXHH, and HXXHH. These histidine residues are reported to be catalytically essential and proposed to be the ligands for the iron atoms contained within the homolog, stearoyl CoA desaturase.
Links
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Statistics
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PSSM-Id: 239585
Aligned: 18 rows
Threshold Bit Score: 395.474
Created: 17-Feb-2006
Updated: 2-Oct-2020
Structure
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Aligned Rows:
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putative
Feature 1:putative di-iron ligands [ion binding site]
Evidence:
  • Comment:Putative catalytically essential di-iron binding histidine residues; based on similarity to stearoyl-CoA desaturase.
  • Comment:Mutation of any one of these eight histidines in stearoyl-CoA desaturase resulted in complete inactivity.
  • Citation:PMID 7947684
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Sequence Alignment
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Format: Row Display: Color Bits: Type Selection: 
Feature 1                                                                         #   #       
30913054   45 ILKAHPEIASLNGyepltkwiVLGVVSLQFTCAYLLsqss---llswKFFLTAYFIGAFCnQNLFLAIHELSHNLGfk-- 119 fission yeast
CAD70987   65 IIKAHPEVTKLCGpepltkwvVLGVVSLQFLLAHLLrdts---ffswKFWLTAYVFGATCnQNLFLAIHEISHNLAfr-- 139 Neurospora crassa
CAG90549   46 ILAKYPEVRKLTGyepktkwyIFGILILQFSVAYYLrnts---lfsfKFIALAYLIGATCnQAIFLAIHELSHNLLfk-- 120 Debaryomyces hanse...
XP_758798 179 ILKAHPEVKRLMGyepltkyvSFGVLVLQLCVAIYLsqctllhpfswQFLLVAYAIGGTAnQNTFLAIHEITHNLAfr-- 256 Ustilago maydis 521
CAJ05378    2 LKAHGAEIKKLYGpdpwlrylMTPFVLLQIYLGYRAkdm-----gwpTLLLVGYFVGGTItHSCFLAIHEATHGLCff-- 74  Leishmania major
AAX81003   39 LEKYSSEIKKLYGpdpltwkiATAVVLFQIFLGSLAssm-----swpVFLLTAYAIGGTAtHNSFLAVHEITHNLAfr-- 111 Trypanosoma brucei
7297049    26 ILEKYPQIKKLFGhdpnfkwvAGAMVLTQILALFVVkdl-----swsWLIVAAYCFGGIInHSLMLAVHEISHNLAfghs 100 fruit fly
CAH65363   26 ILAKHPEIKALMKpdynliwvVMLMVAAQLTAFYLVrdl-----dwkWVVFWAYVFGSCIsHSMTLAIHEISHNSAfgng 100 chicken
XP_694195  26 ILAKYPEIKSLMGhdpqlkwvVSGMVLTQLLACYMVhel-----swkWVLFWAYAFGGCInHSLTLAIHDISHNVAfgtk 100 zebrafish
AAH54207   26 ILAKYPQIKNLMGpdphfkwiVTFMVMVQILSCFIVrdl-----pwkWLLFCSYAFGGVInHSLTLAIHDISHNVAfgnk 100 African clawed frog

Feature 1                                #  ##                                                
30913054  120 kTLYNRAYCLFANLPVGAPFAASFRPYHMEHHAYQGvDGMDTDLPTRAELILFdnvlgKAFFCTFQLLFYAFRPLVVRrl 199 fission yeast
CAD70987  140 sPTANRLFAIVANLPIAVPYSASFRPYHLTHHKSLGvDGLDTDLPTAFEALFLdsilgKAFFCTFQIFFYALRPMAIYrv 219 Neurospora crassa
CAG90549  121 kPLHNKLFAIFTNMPIGIPYSASFQPYHQLHHKFLGdEYLDADLPTKFEGIFLsnvlgKVFFAIFQILFYALRPMFVTqi 200 Debaryomyces hanse...
XP_758798 257 gLRANRLWAILVNAAIGVPYAMAFKPYHLEHHKYLGeDGTDTDLPTKFESVVLrnvlgKAFFATFQIFFYALRPGFVRaq 336 Ustilago maydis 521
CAJ05378   75 mPLYNDLYALFVNLVVPVPYAMMFKTYHAEHHRYLGwDGIDSDVPTRFEGRYLssyagKFFFLTFQVLFYALRPTVVRti 154 Leishmania major
AAX81003  112 kAVHNELFAIFLNIIVPLPYAMGFKSHHRDHHNYLGwERVDPDLPTALEGKLLssyigKFFFVTFQVFFYALRPTLVRkm 191 Trypanosoma brucei
7297049   101 rPMHNRILGFICNLPIGLPMSISFKKYHLEHHRYQGdEAIDTDIPTLLEARLFdttfgKFLWVCLQPFFYIFRPLIINpk 180 fruit fly
CAH65363  101 rAMWNRWFGIFANLPLGLPYSISFKRYHMDHHRYLGgDGIDVDIPTNFEGWFFctrfrKFIWIVLQPFFYAIRPLCINpk 180 chicken
XP_694195 101 rARWNRWFAMFANLPIGLPYSASFKKYHIDHHRYLGgDGLDVDIPTDLEGWFFctparKVLWLFLQPLFYALRPLIVNpk 180 zebrafish
AAH54207  101 sARWNRFFGMFANLPIGVPYSTSFKKYHIDHHRYLGgDGLDVDIPTDFEGRFFctpirKVLWIVIQPLLYVLRPLYVNpk 180 African clawed frog

Feature 1                                                                                     
30913054  200 pftLMHFWNIIVQFSFDYLVVRYVGw-----RALAYFFMSSFLAGSLHPTAGHFLSEHYNmtrtrlia---------sgp 265 fission yeast
CAD70987  220 pftWVHWLNLTIQLFFDYAIVFLLPdslftaNSLLYFLLSSFLAGSLHPTAGHFIAEHYVyekitpear--------npd 291 Neurospora crassa
CAG90549  201 kftYIHLLNIAYQVLVDYLMVHNWGg-----RSLGYFIMSSFLAGSLHPCAGHFIAEHYVlnenntprsgnsekatanis 275 Debaryomyces hanse...
XP_758798 337 rptIWHLLNITFILLFNTLLVRTFGw-----TPLIYLLESSFFAGSLHPCAAHFIAEHYMfgg----------------- 394 Ustilago maydis 521
CAJ05378  155 kfeKLHVMNYVVQLTFNLLVYYFWGw-----WPLLYFLLCTFLGTSWHPLAGHFISEHFVlag----------------- 212 Leishmania major
AAX81003  192 kitRMHVLNIVAQIIFDVIFYMLFGp-----WCIIYFFLSLVLGTGWHPLAGHFLTEHYIfqg----------------- 249 Trypanosoma brucei
7297049   181 pptRLEIINTVVQLTFNALIVYFLGw-----KPLAYLLIGSILAMGLHPVAGHFISEHYMfa------------------ 237 fruit fly
CAH65363  181 pitRLEIINLLAQLFFDIVIYYLWGa-----KSIFYMLAGSVLGLGLHPISGHFIAEHYMfl------------------ 237 chicken
XP_694195 181 pvtRLEMLNAAVQFVVDIIIYYFWGl-----KPIVYLISGSILCMGLHPISGHFIAEHYMft------------------ 237 zebrafish
AAH54207  181 pitHLEIINALVQFSFDLIIYYLWGl-----KPVAYLIAGSCLSMGFHPISGHFIAEHYMfl------------------ 237 African clawed frog

Feature 1                             #  ##                                                   
30913054  266 gketpLETFSYYGPLNFFVYNAGYHIEHHDFPYVAWTRIGKVRELAPEFYDNIPdckSWCGIIYQFITDsnVGMWCRVKR 345 fission yeast
CAD70987  292 nkipvPETFSYYGPLNWVTYNVGLHNEHHDFPAIPWTRLPKLYEIASEFYEGLPqhrSWTHVLWQFIFDeeIGMRCRVKR 371 Neurospora crassa
CAG90549  276 kellpEETYSYYGPLNRLTWNVGYHNEHHDFPYIAWTKLPELRRIAAEFYDPLPqveSWCGVIWWFCFSdiNTLWNRVKR 355 Debaryomyces hanse...
XP_758798 395 ---iqQETWSYYGALNILAYNVGYHNEHHDFPSVPWTRLPQLRKIAPEFYDCLPrhtSWPMVTVRFILGndSGLWARVKR 471 Ustilago maydis 521
CAJ05378  213 --nggQETFSYYGPLNWLMWNVGYHVEHHDFPNIPWTRIGKLNTIAPEFYVDLHrtkSWPGALFDFLLDpnVSLCSRVVR 290 Leishmania major
AAX81003  250 --dgsQETFSYYGPLNWLAWNVGHHVEHHDFPYVPWRHLHKLREIAPEFYENLEvtpSWPLALYDFVFKvnMNPFSRTVR 327 Trypanosoma brucei
7297049   238 ---kgFETYSYYGPLNWITFNVGYHNEHHDFPAVPGSRLPEVKRIAKEFYDTMPqhtSWTRVLYDFIMDpaVGPYARVKR 314 fruit fly
CAH65363  238 ---kgHETYSYYGPLNLLTFNVGYHNEHHDFPNIPGKSLPLVKKIAAEYYDNLPqynSWIKVLYDFVMDdtISPYSRMKR 314 chicken
XP_694195 238 ---kgHETYSYYGPLNLITFNVGYHMEHHDFPSIPGSKLPEVKRIAAEYYDSLPqhtSWMRVLWDFVFDdsIGPYARIKR 314 zebrafish
AAH54207  238 ---kgYETYSYYGPLNLLTFNVGYHMEHHDFPSIPGSKLSLVRKIAPEYYDTLPyhtSWGRVLWDFIFCkeLGPFSRVKR 314 African clawed frog

Feature 1      
30913054  346 K 346 fission yeast
CAD70987  372 K 372 Neurospora crassa
CAG90549  356 N 356 Debaryomyces hansenii CBS767
XP_758798 472 P 472 Ustilago maydis 521
CAJ05378  291 E 291 Leishmania major
AAX81003  328 R 328 Trypanosoma brucei
7297049   315 R 315 fruit fly
CAH65363  315 Q 315 chicken
XP_694195 315 Q 315 zebrafish
AAH54207  315 E 315 African clawed frog

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