ID ORML1_DANRE Reviewed; 153 AA.
AC Q8JFB7;
DT 08-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 02-SEP-2026, entry version 113.
DE RecName: Full=ORM1-like protein 1;
GN Name=ormdl1; ORFNames=si:busm1-72b14.3, si:dz72b14.3;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney, and Retina;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (OCT-2003) 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 (By
CC similarity). When complexed to SPT, the binding of ceramides to its N-
CC terminus stabilizes a conformation that block SPT substrate entry,
CC hence preventing SPT catalytic activity. Through this mechanism,
CC maintains ceramide levels at sufficient concentrations for the
CC production of complex sphingolipids, but which prevents the
CC accumulation of ceramides to levels that trigger apoptosis (By
CC similarity). {ECO:0000250|UniProtKB:Q8N138,
CC ECO:0000250|UniProtKB:Q921I0}.
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:Q9P0S3}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q9P0S3}.
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 -!- SIMILARITY: Belongs to the ORM family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AL591593; CAD43469.1; -; Genomic_DNA.
DR EMBL; AL672217; CAD43441.1; -; Genomic_DNA.
DR EMBL; BC059514; AAH59514.1; -; mRNA.
DR EMBL; BC065474; AAH65474.1; -; mRNA.
DR EMBL; BC068376; AAH68376.1; -; mRNA.
DR RefSeq; NP_956387.1; NM_200093.1.
DR AlphaFoldDB; Q8JFB7; -.
DR SMR; Q8JFB7; -.
DR FunCoup; Q8JFB7; 1307.
DR STRING; 7955.ENSDARP00000021751; -.
DR PaxDb; 7955-ENSDARP00000021751; -.
DR Ensembl; ENSDART00000014660; ENSDARP00000021751; ENSDARG00000014333.
DR GeneID; 368632; -.
DR KEGG; dre:368632; -.
DR AGR; ZFIN:ZDB-GENE-030616-529; -.
DR CTD; 94101; -.
DR ZFIN; ZDB-GENE-030616-529; ormdl1.
DR eggNOG; KOG3319; Eukaryota.
DR GeneTree; ENSGT00950000183178; -.
DR HOGENOM; CLU_072117_3_0_1; -.
DR InParanoid; Q8JFB7; -.
DR OMA; IVSAFRC; -.
DR OrthoDB; 1932233at2759; -.
DR PhylomeDB; Q8JFB7; -.
DR Reactome; R-DRE-1660661; Sphingolipid de novo biosynthesis.
DR PRO; PR:Q8JFB7; -.
DR Proteomes; UP000000437; Chromosome 9.
DR Bgee; ENSDARG00000014333; Expressed in liver and 21 other cell types or tissues.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0017059; C:serine palmitoyltransferase complex; IBA:GO_Central.
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; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..153
FT /note="ORM1-like protein 1"
FT /id="PRO_0000215633"
FT TOPO_DOM 1..27
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 28..46
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 47..64
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 65..105
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 106..123
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 124..140
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 141..153
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
SQ SEQUENCE 153 AA; 17379 MW; A610964685796587 CRC64;
MNVGVAHSEV NPNTRVMNSR GIWLTYALGV GMLHIVLLSI PFFSVPVVWT LTNVIHNFGM
YVFMHAVKGT PFETPDQGKA RLLTHWEQLD YGVQFTSSRK FFTISPIILY FLASFYTKYD
TAHFVINTAS LLSVLIPKLP QLHGVRIFGI NKY
//
