2E3M,2E3Q,3H3R,2E3P,2Z9Z


Conserved Protein Domain Family
START_STARD11-like

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cd08872: START_STARD11-like 
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Ceramide-binding START domain of mammalian STARD11 and related domains
This subfamily includes the steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domains of mammalian STARD11 and related domains. The START domain family belongs to the SRPBCC (START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC) domain superfamily of proteins that bind hydrophobic ligands. SRPBCC domains have a deep hydrophobic ligand-binding pocket. STARD11 can mediate transfer of the natural ceramide isomers, dihydroceramide and phytoceramide, as well as ceramides having C14, C16, C18, and C20 chains. They can also transfer diacylglycerol, but with a lower efficiency. STARD11 is synthesized from two major transcripts: a larger one encoding Goodpasture antigen-binding protein (GPBP)/ceramide transporter long form (CERTL); and a smaller one encoding GPBPdelta26/CERT, which is deleted for 26 amino acids. Both splicing variants mediate ceramide transfer from the ER to the Golgi, in a non-vesicular manner. It is likely that these two carry out different functions in specific sub-cellular locations. These proteins have roles in brain homeostasis and disease processes. GPBP/CERTL exists in multiple isoforms originating from alternative translation initiation sites and post-translational modifications. Goodpasture syndrome is a human disorder caused by antibodies directed against the a3-chain of collagen type IV. GPBP/CERTL binds and phosphorylates this antigen. The human gene encoding STARD11 is referred to as COL4A3BP referring to its collagen binding function. It is unknown whether the ceramide-transfer function of GPBP/CERTL is related to this collagen interaction. The expression of GPBP/CERTL is elevated in these and other spontaneous autoimmune disorders including cutaneous lupus erythematosus, pemphigoid, and lichen planus. GPBL/CERTL contains an N-terminal pleckstrin homology domain (PH), which targets the protein to the Golgi, a middle region containing two serine-rich domains (SR1, SR2), a FFAT (two phenylalanine amino acids in an acidic tract) motif which is involved in endoplasmic reticulum targeting, and this C-terminal SMART domain. The shorter splicing variant, CERT, lacks the SR2 domain.
Statistics
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PSSM-Id: 176881
View PSSM: cd08872
Aligned: 19 rows
Threshold Bit Score: 376.681
Threshold Setting Gi: 167523365
Created: 30-Jul-2009
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
ceramide
Conserved site includes 29 residues -Click on image for an interactive view with Cn3D
Feature 1:ceramide binding site [chemical binding site]
Evidence:
  • Structure:2E3P_A ; human STARD11(GPBPdeletion26/CERT) START domain binds C16-cearmide (P1), contacts at 4A
    View structure with Cn3D
  • Structure:2E3Q_A; human STARD11(GPBPdeletion26/CERT) START domain binds C18- ceramide (P212121), contacts at 4A
    View structure with Cn3D
  • Structure:3H3R_A; human STARD11(GPBPdeletion26/CERT) START domain binds an inhibitor (Hpa-14), contacts at 4A.
    View structure with Cn3D
  • Comment:(1R,3R)-N-(3-Hydroxy-1-hydroxymethyl-3-phenylpropyl)alkanamide (HPA) is a synthesized analogue of ceramide. It inhibits ceramide transport by CERT.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                                                                 #     #
2E3M_A        21 THRFVQKVEEMVQNHMTYSLQDVGgd-anWQLVVEEGEMKVYRREVEENGIVLDPLKATHAVKGVTGHEVCNYFWnvDVR 99  human
2E3P_A        21 THRFVQKVEEMVQNHMTYSLQDVGgd-anWQLVVEEGEMKVYRREVEENGIVLDPLKATHAVKGVTGHEVCNYFWnvDVR 99  human
XP_002168208 337 KHRLSKEVDSKLKEFLTLLKENVEapnsgWDLVFEDGEMRVYRKDYEVDTIVCDPMKASHVIPGVTGREACHYFFdkDVR 416 green hydra
XP_002131261 301 THEHSEALNQRIKEHLALLDHSDPda-ngWEQITEDGEMKVYRKELVQDGLICDPLKAVHSVGLVTAKEMCHYFWfpDVR 379 Ciona intestinalis
XP_392830    355 KHRLWPEIEKITMEQLHYARLEVGag--gWQLFAEDGDMRMYRREEEADGLVVDPLKACHVVKGVTGHEVCEIFFspEYR 432 honey bee
XP_002428838 344 HSSLWPEIEKISAEQIKYALQEVGsg-snWHLFAEEGEMKLYKREEMVNGMVMDPLKACHVVQGVTGHEMCHYFFspDVR 422 human body louse
NP_648199    363 SHALWPEIDRVCKEQLHYAREGVGqdgngWQIFADEGEIKMYKREEEVNGLVMDPLKAYHTVQGVTAREMCHYFFmpEFR 442 fruit fly
XP_001947052 153 KHTYWPEIERVVAEQIRSARMGLGkg--aWQLFVEDGEMKMYRREVEEDGLVVDPLKATHQVKGITGRELCHYFFypEYR 230 pea aphid
XP_002406093 318 TKPFPACTSFGEPNSCSTEQWGWGeg--gWQLFAEDGEMKMYRREVEEAGVVCDPLKAVHVVRGVTGREVCHYFFspEVR 395 black-legged tick
XP_001201591 370 EHKLSQQCNEKVEENIKYAFSKIEs---tWDLIHVEGEMKVYKSEQEIDGVVCDPLKATHTIRNVTSQEMCFTFWdvNVR 446 purple urchin
Feature 1          ## ##                 # ## ## #  # # #                          #             
2E3M_A       100 NDWETTIENFHVVETLADNAIIIYQTHKRVWPASQRDVLYLSVIRKIPalte-----ndpETWIVCNFSVDHds-aPLNn 173 human
2E3P_A       100 NDWETTIENFHVVETLADNAIIIYQTHKRVWPASQRDVLYLSVIRKIPalte-----ndpETWIVCNFSVDHds-aPLNn 173 human
XP_002168208 417 LDWEISVEKVKVIEKLSENTLIFHQLMKRIWPSVQRDMCFVSHIRQLPkdevdhldkeigHPWTVVNIATEHde-aKDN- 494 green hydra
XP_002131261 380 RDWEETVDVFDVLETLDEATTINYQTHKQVWPAAQRDCLYLSSMVKVDnppsvg-dkiphDTWIVCNFSVDHpeanPVS- 457 Ciona intestinalis
XP_392830    433 TGWEATLEDMTVIEHISKDTLIFLQTHKRIWPASQRDALFWSHMRRVSddqd----pdahDLWIVCNHSTEHpd-fPPNt 507 honey bee
XP_002428838 423 MEWETTLDSSTVIEALDKNTLIFYQVHKRIWPASQRDAVFWSHKKSIPnqtd----aegqDIWTVTNHSVDLqe-fPANt 497 human body louse
NP_648199    443 NDWETTLEDCTILEKISADTLLFLQTHKRIWPASQRDAQFWSHMRKITdnle----pgarDMWVVCNNSTEYakqeSKNg 518 fruit fly
XP_001947052 231 YDWEGTLETMNVVDKIAEDTILFHQIHKRIWPAAQRDATFWSHLTHVPdeenk--sedspHMWATVNSSVELps-hPPNg 307 pea aphid
XP_002406093 396 FDWETTLENMEVLEVVEPLTVIVHQIHKRVWPATQRDALFWSHMARAPnved----pdahDVWIVCNHSCDTpp-vPLG- 469 black-legged tick
XP_001201591 447 MEWDTTLDITNTLEVLSQDTVISHQLMKRVWPATQRDTCFVSHLRKLDlsiqn---tqdvGSWLVINFSTEHp---KATs 520 purple urchin
Feature 1             # # #                            #   # #        #  ## ###  #               
2E3M_A       174 -RCVRAKINVAMICQTLVSPPEgn-qEISRDNILCKITYVANVNPGGWAPASVLRAVAKREYPKFLKRFTSYVQEKTAGK 251 human
2E3P_A       174 -RCVRAKINVAMICQTLVSPPEgn-qEISRDNILCKITYVANVNPGGWAPASVLRAVAKREYPKFLKRFTSYVQEKTAGK 251 human
XP_002168208 495 -KYIRAVANVIMVCQTFAIGEVkk-kKYTRENIACKITYMAQVNPGGWAPPTVVRQMSKREYPKFLRKFSSFVQNVTKDK 572 green hydra
XP_002131261 458 -GCVRALIEVALICQTFITLPKdg-gPITRDCLQCDIIYVANVNPGGWAPASVLRSIYKREYPKFLNRFTNYVQQKTKDL 535 Ciona intestinalis
XP_392830    508 gKCVRVYLTVCLVCQTFIDPPKde-eEIKRENLTCKITYCSVVNPGGWAPASVLRAVYKREYPKFLKRFTSFCIEQCKDK 586 honey bee
XP_002428838 498 gKTVRIYLTVCLLCQTFVDPPKtg-lNISRENLRCKITYCSVINPGGWAPAAALRQVYKREYPKFVKRFTAYVVDRCKSK 576 human body louse
NP_648199    519 -KCVRIFLTVILACQTHLPEGYvkgqPLNRNDLTCKITYCSVVNPGGWAPASALRAVYKREYPKFLKRFTGYVIDQCKDK 597 fruit fly
XP_001947052 308 gKQVRIYLTIILMGQTIISPAAkg-rEIKRDDITCKITYCAVVNPGGWAPSSVLRAVYKREYPKFLKRFTAYVLEKTKNL 386 pea aphid
XP_002406093 470 -KCVRVRLTVCLMCQTFVDPPQpn-sEITRDNLSCKITYCSTINPGGWAPASVLRAVYKREYPKFLKRFTQYVKDQTECK 547 black-legged tick
XP_001201591 521 -KCIRAKVNVSMLCQTFLDPPDipieKATRENLVCKIFYVAHANPGGWVPGSVLRTVYKREYPKFLRKFSTYVHEKCKDK 599 purple urchin
Feature 1            
2E3M_A       252 PILF 255 human
2E3P_A       252 PILF 255 human
XP_002168208 573 PLML 576 green hydra
XP_002131261 536 KLLF 539 Ciona intestinalis
XP_392830    587 PIIF 590 honey bee
XP_002428838 577 PIMF 580 human body louse
NP_648199    598 PIMF 601 fruit fly
XP_001947052 387 PIKL 390 pea aphid
XP_002406093 548 PILF 551 black-legged tick
XP_001201591 600 PIKW 603 purple urchin

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