##gff-version 3 O15269 UniProtKB Chain 1 473 . . . ID=PRO_0000163853;Note=Serine palmitoyltransferase 1 O15269 UniProtKB Topological domain 1 15 . . . Note=Lumenal;Ontology_term=ECO:0000255;evidence=ECO:0000255 O15269 UniProtKB Transmembrane 16 36 . . . Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255 O15269 UniProtKB Topological domain 37 473 . . . Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255 O15269 UniProtKB Region 1 66 . . . Note=Interaction with SPTLC2;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:33558762;Dbxref=PMID:33558762 O15269 UniProtKB Modified residue 164 164 . . . Note=Phosphotyrosine%3B by ABL;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:23629659;Dbxref=PMID:23629659 O15269 UniProtKB Alternative sequence 143 143 . . . ID=VSP_043127;Note=In isoform 2. D->E;Ontology_term=ECO:0000303;evidence=ECO:0000303|PubMed:15489334;Dbxref=PMID:15489334 O15269 UniProtKB Alternative sequence 144 473 . . . ID=VSP_043128;Note=In isoform 2. Missing;Ontology_term=ECO:0000303;evidence=ECO:0000303|PubMed:15489334;Dbxref=PMID:15489334 O15269 UniProtKB Natural variant 20 20 . . . ID=VAR_088446;Note=In ALS27%3B this variant can be caused by 2 genetic variations%2C one of which has been shown to affect splicing%2C leading to exon 2 skipping%3B in patient's whole blood sample%2C only exon 2 deletion was observed%2C but not the missense variant per se%3B when exon 2 deletion variant is expressed in induced pluripotent stem cells (iPSC) differentiated into motor neuron-like cells%2C increased production of sphinganine and ceramides is observed%3B when exon 2 deletion variant is transfected into HEK293 cells%2C decreased response to inhibition mediated by ORMDL3 or ceramide is observed. A->S;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:34059824,ECO:0000269|PubMed:34459874;Dbxref=dbSNP:rs879254294,PMID:34059824,PMID:34459874 O15269 UniProtKB Natural variant 23 23 . . . ID=VAR_088447;Note=In ALS27%3B increased production of sphinganine and ceramides%2C when expressed in induced pluripotent stem cells (iPSC) differentiated into motor neuron-like cells%3B decreased response to inhibition mediated by ORMDL3 and ceramide%3B no effect on the interaction with ORMDL3. Y->F;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:34059824,ECO:0000269|PubMed:37308477;Dbxref=dbSNP:rs1554716504,PMID:34059824,PMID:37308477 O15269 UniProtKB Natural variant 38 38 . . . ID=VAR_088448;Note=In ALS27%3B uncertain significance. L->R;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:36204986;Dbxref=PMID:36204986 O15269 UniProtKB Natural variant 39 39 . . . ID=VAR_088449;Note=In ALS27%3B increased production of sphinganine and ceramides%2C when expressed in induced pluripotent stem cells (iPSC) differentiated into motor neuron-like cells%3B decreased response to inhibition mediated by ORMDL3 and ceramide%3B no effect on the interaction with ORMDL3. Missing;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:34059824,ECO:0000269|PubMed:34459874;Dbxref=dbSNP:rs1197928094,PMID:34059824,PMID:34459874 O15269 UniProtKB Natural variant 40 41 . . . ID=VAR_088450;Note=In ALS27%3B increased production of sphinganine and ceramides%2C when expressed in induced pluripotent stem cells (iPSC) differentiated into motor neuron-like cells%3B decreased response to inhibition mediated by ORMDL3 and ceramide%3B no effect on the interaction with ORMDL3. Missing;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:34059824;Dbxref=PMID:34059824 O15269 UniProtKB Natural variant 133 133 . . . ID=VAR_011392;Note=In HSAN1A%3B inactive in the heterodimeric SPT complex%3B largely reduced canonical activity towards serine%3B contrary to wild-type%2C uses alanine as substrate leading to the formation of 1-deoxysphinganine (1-deoxySa)%3B does not affect the interaction with SPTLC2. C->W;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:11242114,ECO:0000269|PubMed:19132419,ECO:0000269|PubMed:20504773,ECO:0000269|PubMed:21618344,ECO:0000269|PubMed:22302274;Dbxref=dbSNP:rs119482082,PMID:11242114,PMID:19132419,PMID:20504773,PMID:21618344,PMID:22302274 O15269 UniProtKB Natural variant 133 133 . . . ID=VAR_011393;Note=In HSAN1A%3B reduced canonical activity towards serine%3B does not affect the interaction with SPTLC2. C->Y;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:11242114,ECO:0000269|PubMed:19132419;Dbxref=dbSNP:rs119482081,PMID:11242114,PMID:19132419 O15269 UniProtKB Natural variant 144 144 . . . ID=VAR_011394;Note=In HSAN1A%3B reduced canonical activity towards serine%3B does not affect the interaction with SPTLC2. V->D;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:11242114,ECO:0000269|PubMed:19132419,ECO:0000269|PubMed:30420926;Dbxref=dbSNP:rs119482083,PMID:11242114,PMID:19132419,PMID:30420926 O15269 UniProtKB Natural variant 151 151 . . . ID=VAR_037889;Note=R->L;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:17060578;Dbxref=dbSNP:rs45461899,PMID:17060578 O15269 UniProtKB Natural variant 239 239 . . . ID=VAR_036610;Note=In a breast cancer sample%3B somatic mutation. R->W;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:16959974;Dbxref=dbSNP:rs542876370,PMID:16959974 O15269 UniProtKB Natural variant 310 310 . . . ID=VAR_068476;Note=Found in a patient with HSAN1A%3B uncertain significance. A->G;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:22302274;Dbxref=dbSNP:rs768841574,PMID:22302274 O15269 UniProtKB Natural variant 331 331 . . . ID=VAR_066245;Note=In HSAN1A%3B severe form with early onset%3B reduced canonical activity towards serine and increased production of deoxysphingolipids%3B no effect on subcellular location at the endoplasmic reticulum. S->F;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:19651702,ECO:0000269|PubMed:21618344,ECO:0000269|PubMed:24247255;Dbxref=dbSNP:rs267607087,PMID:19651702,PMID:21618344,PMID:24247255 O15269 UniProtKB Natural variant 331 331 . . . ID=VAR_073294;Note=In ALS27 and HSAN1A%3B reduced canonical activity towards serine and increased production of deoxysphingolipids. S->Y;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:23454272,ECO:0000269|PubMed:34459874;Dbxref=dbSNP:rs267607087,PMID:23454272,PMID:34459874 O15269 UniProtKB Natural variant 352 352 . . . ID=VAR_066246;Note=In HSAN1A%3B reduced canonical activity towards serine and increased production of deoxysphingolipids%3B no effect on subcellular location at the endoplasmic reticulum. A->V;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:19651702,ECO:0000269|PubMed:21618344;Dbxref=dbSNP:rs267607088,PMID:19651702,PMID:21618344 O15269 UniProtKB Natural variant 387 387 . . . ID=VAR_037890;Note=Does not affect catalytic activity towards serine%3B does not affect the interaction with SPTLC2. G->A;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:15037712,ECO:0000269|PubMed:19132419,ECO:0000269|PubMed:19651702;Dbxref=dbSNP:rs119482084,PMID:15037712,PMID:19132419,PMID:19651702 O15269 UniProtKB Mutagenesis 138 138 . . . Note=Decreased catalytic activity with L-serine and palmitoyl-CoA as substrates. F->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:33558762;Dbxref=PMID:33558762 O15269 UniProtKB Mutagenesis 164 164 . . . Note=Increased serine palmitoyltransferase activity and sphingolipid content. Y->F;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:23629659;Dbxref=PMID:23629659 O15269 UniProtKB Mutagenesis 337 337 . . . Note=Strongly decreased catalytic activity with L-serine and palmitoyl-CoA as substrates. F->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:33558762;Dbxref=PMID:33558762 O15269 UniProtKB Mutagenesis 338 338 . . . Note=Decreased catalytic activity with L-serine and palmitoyl-CoA as substrates. S->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:33558762;Dbxref=PMID:33558762 O15269 UniProtKB Helix 11 18 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7K0M O15269 UniProtKB Helix 22 39 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7K0M O15269 UniProtKB Helix 54 63 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7K0K O15269 UniProtKB Helix 78 80 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7K0K O15269 UniProtKB Beta strand 85 87 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7K0M O15269 UniProtKB Beta strand 91 95 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7K0K O15269 UniProtKB Beta strand 98 102 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7K0K O15269 UniProtKB Beta strand 108 110 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7K0J O15269 UniProtKB Helix 115 128 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7K0K O15269 UniProtKB Turn 136 139 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7K0K O15269 UniProtKB Helix 143 155 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7K0K O15269 UniProtKB Beta strand 159 166 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7K0K O15269 UniProtKB Helix 167 178 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7K0K O15269 UniProtKB Beta strand 184 188 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7K0K O15269 UniProtKB Helix 193 201 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7K0K O15269 UniProtKB Beta strand 205 209 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7K0K O15269 UniProtKB Helix 214 230 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7K0K O15269 UniProtKB Helix 232 237 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7K0K O15269 UniProtKB Beta strand 240 247 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7K0K O15269 UniProtKB Turn 249 251 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7K0K O15269 UniProtKB Helix 257 267 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7K0K O15269 UniProtKB Beta strand 270 274 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7K0K O15269 UniProtKB Turn 276 281 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7K0K O15269 UniProtKB Beta strand 282 286 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7K0M O15269 UniProtKB Helix 289 293 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7K0K O15269 UniProtKB Helix 297 299 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7K0K O15269 UniProtKB Beta strand 301 306 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7K0K O15269 UniProtKB Beta strand 309 311 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7K0K O15269 UniProtKB Beta strand 316 320 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7K0K O15269 UniProtKB Helix 322 331 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7K0K O15269 UniProtKB Helix 333 336 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7K0K O15269 UniProtKB Helix 343 358 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7K0K O15269 UniProtKB Helix 362 377 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7K0K O15269 UniProtKB Beta strand 381 387 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7K0K O15269 UniProtKB Beta strand 392 400 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7K0K O15269 UniProtKB Helix 405 420 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7K0K O15269 UniProtKB Turn 421 423 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7K0K O15269 UniProtKB Turn 433 435 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7K0K O15269 UniProtKB Beta strand 436 438 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:6M4O O15269 UniProtKB Beta strand 443 447 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7K0K O15269 UniProtKB Beta strand 450 452 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7K0N O15269 UniProtKB Helix 454 471 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:7K0K