ORMDL3
entrez
94103
canonical
uniprot
Q8N138
canonical
ensembl
ENSG00000172057
resolver
ensp
ENSP00000304858
resolver
ensp
ENSP00000377724
resolver
ensp
ENSP00000464693
resolver
ensp
ENSP00000559306
resolver
ensp
ENSP00000559310
resolver
ensp
ENSP00000559313
resolver
ensp
ENSP00000559316
resolver
genesymbol
ORMDL3
resolver
hgnc
HGNC:16038
resolver
uniprot
B3KS83
resolver
uniprot
Q6UY83
resolver
uniprot_entry
ORML3_HUMAN
resolver
uniprot_sec
B3KS83
resolver
uniprot_sec
Q6UY83
resolver
amino_acid_sequence
MNVGTAHSEVNPNTRVMNSRGIWLSYVLAIGLLHIVLLSIPFVSVPVVWTLTNLIHNMGMYIFLHTVKGTPFETPDQGKARLLTHWEQMDYGVQFTASRKFLTITPIVLYFLTSFYTKYDQIHFVLNTVSLMSVLIPKLPQLHGVRIFGINKY
uniprot
proteins
disease_involvement
DISEASE: Asthma (ASTHMA) [MIM:600807]: The most common chronic disease affecting children and young adults. It is a complex genetic disorder with a heterogeneous phenotype, largely attributed to the interactions among many genes and between these genes and the environment. It is characterized by recurrent attacks of paroxysmal dyspnea, with wheezing due to spasmodic contraction of the bronchi. {ECO:0000269|PubMed:18395550, ECO:0000269|PubMed:18760456, ECO:0000269|PubMed:19133921}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry. SNPs on 17q21 locus that are associated with childhood asthma also show a consistent and strong association with transcript levels of ORMDL3, indicating that genetic variants regulating ORMDL3 expression are determinants of susceptibility to childhood asthma. {ECO:0000269|PubMed:17611496}.
uniprot
proteins
function
FUNCTION: Plays an essential role in the homeostatic regulation of sphingolipid de novo biosynthesis by modulating the activity of the serine palmitoyltransferase (SPT) in response to ceramide levels (PubMed:20182505, PubMed:30700557, PubMed:37308477). When complexed to SPT, the binding of ceramides to its N-terminus stabilizes a conformation that block SPT substrate entry, hence preventing SPT catalytic activity. Through this mechanism, maintains ceramide levels at sufficient concentrations for the production of complex sphingolipids, but which prevents the accumulation of ceramides to levels that trigger apoptosis (PubMed:37308477). {ECO:0000269|PubMed:20182505, ECO:0000269|PubMed:30700557, ECO:0000269|PubMed:37308477}.
uniprot
proteins
mass_dalton
17495
uniprot
proteins
mutagenesis
MUTAGEN 2..17; /note="Missing: Impaired negative regulation of SPT complex activity in the presence of ceramides."; /evidence="ECO:0000269|PubMed:37308477"; MUTAGEN 2..8; /note="Missing: Impaired negative regulation of SPT complex activity in the presence of ceramides."; /evidence="ECO:0000269|PubMed:37308477"; MUTAGEN 2; /note="Missing: Impaired negative regulation of SPT complex activity in the presence of ceramides."; /evidence="ECO:0000269|PubMed:37308477"; MUTAGEN 13; /note="N->A: Disrupted ceramide binding; impaired negative regulation of SPT complex activity in the presence of ceramides; in the absence of ceramides, reduced affinity of SPT complex towards palmitoyl-CoA."; /evidence="ECO:0000269|PubMed:37308477"; MUTAGEN 16; /note="V->R: Impaired negative regulation of SPT complex activity in the presence of ceramides."; /evidence="ECO:0000269|PubMed:37308477"; MUTAGEN 22; /note="I->R: Impaired negative regulation of SPT complex activity in the presence of ceramides."; /evidence="ECO:0000269|PubMed:37308477"; MUTAGEN 63; /note="F->P: Impaired negative regulation of SPT complex activity in the presence of ceramides."; /evidence="ECO:0000269|PubMed:37308477"; MUTAGEN 63; /note="F->R: Impaired negative regulation of SPT complex activity in the presence of ceramides."; /evidence="ECO:0000269|PubMed:37308477"; MUTAGEN 85; /note="H->A: No effect on the negative regulation of SPT complex activity in the presence of ceramides."; /evidence="ECO:0000269|PubMed:37308477"; MUTAGEN 137; /note="P->A: Increased protein levels; decreased ubiquitination; increased negative regulation of SPT complex activity."; /evidence="ECO:0000269|PubMed:36408842
uniprot
proteins
post_translational_modification
PTM: When hydroxylated at Pro-137, ubiquitinated via 'Lys-48'-linkage, leading to proteasomal degradation. In endothelial cells, ORMDL3 proteasomal degradation is controlled by the sphingosine 1-phosphate receptor signaling pathway. {ECO:0000269|PubMed:36408842}.
uniprot
proteins
protein_family
ORM family
uniprot
proteins
pubmed
12093374
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
17611496
uniprot
proteins
pubmed
18395550
uniprot
proteins
pubmed
18760456
uniprot
proteins
pubmed
19133921
uniprot
proteins
pubmed
19819884
uniprot
proteins
pubmed
20182505
uniprot
proteins
pubmed
30700557
uniprot
proteins
pubmed
33558761
uniprot
proteins
pubmed
33558762
uniprot
proteins
pubmed
36408842
uniprot
proteins
pubmed
37308477
uniprot
proteins
sequence_length
153
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000269|PubMed:12093374, ECO:0000269|PubMed:19819884}; Multi-pass membrane protein {ECO:0000269|PubMed:12093374, ECO:0000269|PubMed:19819884, ECO:0000269|PubMed:33558762}.
uniprot
proteins
transmembrane_region
TRANSMEM 22..44; /note="Helical"; /evidence="ECO:0000269|PubMed:33558762, ECO:0007744|PDB:6M4N, ECO:0007744|PDB:6M4O, ECO:0007744|PDB:7CQI, ECO:0007744|PDB:7CQK"; TRANSMEM 45..63; /note="Helical"; /evidence="ECO:0000269|PubMed:33558762, ECO:0007744|PDB:6M4N, ECO:0007744|PDB:6M4O, ECO:0007744|PDB:7CQI, ECO:0007744|PDB:7CQK"; TRANSMEM 101..117; /note="Helical"; /evidence="ECO:0000269|PubMed:33558762, ECO:0007744|PDB:6M4N, ECO:0007744|PDB:6M4O, ECO:0007744|PDB:7CQI, ECO:0007744|PDB:7CQK"; TRANSMEM 122..139; /note="Helical"; /evidence="ECO:0000269|PubMed:33558762, ECO:0007744|PDB:6M4N, ECO:0007744|PDB:6M4O, ECO:0007744|PDB:7CQI, ECO:0007744|PDB:7CQK
uniprot
proteins