ID ORML3_BOVIN Reviewed; 153 AA.
AC Q0VD15;
DT 18-MAY-2010, integrated into UniProtKB/Swiss-Prot.
DT 05-SEP-2006, sequence version 1.
DT 02-SEP-2026, entry version 95.
DE RecName: Full=ORM1-like protein 3;
GN Name=ORMDL3;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Thalamus;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Plays an essential role in the homeostatic regulation of
CC sphingolipid de novo biosynthesis by modulating the activity of the
CC serine palmitoyltransferase (SPT) in response to ceramide levels. When
CC complexed to SPT, the binding of ceramides to its N-terminus stabilizes
CC a conformation that block SPT substrate entry, hence preventing SPT
CC catalytic activity. Through this mechanism, maintains ceramide levels
CC at sufficient concentrations for the production of complex
CC sphingolipids, but which prevents the accumulation of ceramides to
CC levels that trigger apoptosis. {ECO:0000250|UniProtKB:Q8N138}.
CC -!- SUBUNIT: Ceramide-sensitive subunit of the serine palmitoyltransferase
CC (SPT) complex, which is also composed of SPTLC1, SPTLC2/3 and SPTSSA/B.
CC {ECO:0000250|UniProtKB:Q8N138}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q8N138}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q8N138}.
CC -!- DOMAIN: Ceramides bind to ORMDL3 N-terminus and stabilize it in a
CC conformation that physically restricts the accessibility of the
CC substrates to their binding sites in the serine palmitoyltransferase
CC (SPT) complex, hence inhibiting SPT catalytic activity. In the absence
CC of ceramides, the N-terminus is flexible and permits substrate binding,
CC thus liberating SPT from inhibition. {ECO:0000250|UniProtKB:Q8N138}.
CC -!- PTM: When hydroxylated at Pro-137, ubiquitinated via 'Lys-48'-linkage,
CC leading to proteasomal degradation. In endothelial cells, ORMDL3
CC proteasomal degradation is controlled by the sphingosine 1-phosphate
CC receptor signaling pathway. {ECO:0000250|UniProtKB:Q8N138}.
CC -!- SIMILARITY: Belongs to the ORM family. {ECO:0000305}.
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DR EMBL; BC119888; AAI19889.1; -; mRNA.
DR RefSeq; NP_001069835.1; NM_001076367.1.
DR RefSeq; XP_005220811.1; XM_005220754.5.
DR RefSeq; XP_005220812.1; XM_005220755.5.
DR RefSeq; XP_024836193.1; XM_024980425.2.
DR AlphaFoldDB; Q0VD15; -.
DR SMR; Q0VD15; -.
DR FunCoup; Q0VD15; 1567.
DR STRING; 9913.ENSBTAP00000018402; -.
DR PaxDb; 9913-ENSBTAP00000018402; -.
DR GeneID; 615368; -.
DR KEGG; bta:615368; -.
DR CTD; 94103; -.
DR VEuPathDB; HostDB:ENSBTAG00000013855; -.
DR VGNC; VGNC:32454; ORMDL3.
DR eggNOG; KOG3319; Eukaryota.
DR HOGENOM; CLU_072117_3_0_1; -.
DR InParanoid; Q0VD15; -.
DR OMA; WTAYILI; -.
DR OrthoDB; 1932233at2759; -.
DR Reactome; R-BTA-1660661; Sphingolipid de novo biosynthesis.
DR Reactome; R-BTA-6798695; Neutrophil degranulation.
DR Proteomes; UP000009136; Chromosome 19.
DR Bgee; ENSBTAG00000013855; Expressed in subcutaneous adipose tissue and 107 other cell types or tissues.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0017059; C:serine palmitoyltransferase complex; ISS:UniProtKB.
DR GO; GO:0006672; P:ceramide metabolic process; ISS:UniProtKB.
DR InterPro; IPR007203; ORMDL.
DR PANTHER; PTHR12665; ORMDL PROTEINS; 1.
DR Pfam; PF04061; ORMDL; 1.
DR PIRSF; PIRSF018147; ORMDL; 1.
PE 2: Evidence at transcript level;
KW Endoplasmic reticulum; Hydroxylation; Membrane; Reference proteome;
KW Transmembrane; Transmembrane helix; Ubl conjugation.
FT CHAIN 1..153
FT /note="ORM1-like protein 3"
FT /id="PRO_0000394252"
FT TOPO_DOM 1..21
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q8N138, ECO:0000255"
FT TRANSMEM 22..42
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q8N138, ECO:0000255"
FT TRANSMEM 43..63
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q8N138, ECO:0000255"
FT TOPO_DOM 64..94
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q8N138, ECO:0000255"
FT TRANSMEM 95..117
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q8N138, ECO:0000255"
FT TOPO_DOM 118..121
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q8N138, ECO:0000255"
FT TRANSMEM 122..142
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q8N138, ECO:0000255"
FT TOPO_DOM 143..153
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q8N138, ECO:0000255"
FT REGION 1..17
FT /note="Important for ceramide level-sensing"
FT /evidence="ECO:0000250|UniProtKB:Q8N138"
FT MOD_RES 137
FT /note="Hydroxyproline"
FT /evidence="ECO:0000250|UniProtKB:Q8N138"
SQ SEQUENCE 153 AA; 17495 MW; 61F483CA5DF20B32 CRC64;
MNVGTAHSEV NPNTRVMNSR GIWLSYVLAI GLLHVVLLSI PFVSVPVVWT LTNLIHNMGM
YIFLHTVKGT PFETPDQGKA RLLTHWEQMD YGVQFTASRK FLTITPIVLY FLTSFYTKYD
QIHFILNTVS LMSVLIPKLP QLHGVRIFGI NKY
//
