ID ORML1_MOUSE Reviewed; 153 AA.
AC Q921I0; Q8BK13;
DT 08-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 02-SEP-2026, entry version 146.
DE RecName: Full=ORM1-like protein 1;
GN Name=Ormdl1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Liver;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=31880535; DOI=10.7554/elife.51067;
RA Clarke B.A., Majumder S., Zhu H., Lee Y.T., Kono M., Li C., Khanna C.,
RA Blain H., Schwartz R., Huso V.L., Byrnes C., Tuymetova G., Dunn T.M.,
RA Allende M.L., Proia R.L.;
RT "The Ormdl genes regulate the sphingolipid synthesis pathway to ensure
RT proper myelination and neurologic function in mice.";
RL Elife 8:0-0(2019).
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
CC (PubMed:31880535). When complexed to SPT, the binding of ceramides to
CC its N-terminus stabilizes a conformation that block SPT substrate
CC entry, 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:0000269|PubMed:31880535}.
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 -!- DISRUPTION PHENOTYPE: No overt phenotype; due to the redundancy with
CC other ORMDL proteins (PubMed:31880535). Simultaneous knockdown of
CC ORMDL1 and ORMDL2 do not exhibit any visible phenotype; they remain
CC fertile and show no sign of neurodegeneration (PubMed:31880535). Double
CC knockdown of ORMDL1 and ORMDL3 show elevated brain levels of
CC sphingolipids, compared with single ORMDL3 knockout and wild-type
CC animals (PubMed:31880535). At 8 weeks of age, both male and female
CC ORMDL1/3 double knockout mice weigh significantly less than wild-type
CC mice and exhibit impaired myelination and motor-function abnormalities
CC (PubMed:31880535). The triple knockout ORMDL1, ORMDL2 and ORMDL3 is not
CC viable (PubMed:31880535). {ECO:0000269|PubMed:31880535}.
CC -!- SIMILARITY: Belongs to the ORM family. {ECO:0000305}.
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DR EMBL; AK050385; BAC34226.1; -; mRNA.
DR EMBL; AK077562; BAC36865.1; -; mRNA.
DR EMBL; BC012315; AAH12315.1; -; mRNA.
DR EMBL; BC023695; AAH23695.1; -; mRNA.
DR EMBL; BC025572; AAH25572.1; -; mRNA.
DR CCDS; CCDS14952.1; -.
DR RefSeq; NP_663492.3; NM_145517.4.
DR AlphaFoldDB; Q921I0; -.
DR SMR; Q921I0; -.
DR BioGRID; 230590; 8.
DR FunCoup; Q921I0; 2452.
DR IntAct; Q921I0; 1.
DR STRING; 10090.ENSMUSP00000027266; -.
DR PhosphoSitePlus; Q921I0; -.
DR jPOST; Q921I0; -.
DR PaxDb; 10090-ENSMUSP00000027266; -.
DR PeptideAtlas; Q921I0; -.
DR ProteomicsDB; 294346; -.
DR Pumba; Q921I0; -.
DR DNASU; 227102; -.
DR Ensembl; ENSMUST00000027266.4; ENSMUSP00000027266.4; ENSMUSG00000026097.10.
DR GeneID; 227102; -.
DR KEGG; mmu:227102; -.
DR UCSC; uc011wks.1; mouse.
DR AGR; MGI:2181669; -.
DR CTD; 94101; -.
DR MGI; MGI:2181669; Ormdl1.
DR VEuPathDB; HostDB:ENSMUSG00000026097; -.
DR eggNOG; KOG3319; Eukaryota.
DR GeneTree; ENSGT00950000183178; -.
DR HOGENOM; CLU_072117_3_0_1; -.
DR InParanoid; Q921I0; -.
DR OMA; IVSAFRC; -.
DR OrthoDB; 1932233at2759; -.
DR PhylomeDB; Q921I0; -.
DR Reactome; R-MMU-1660661; Sphingolipid de novo biosynthesis.
DR BioGRID-ORCS; 227102; 3 hits in 75 CRISPR screens.
DR PRO; PR:Q921I0; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q921I0; protein.
DR Bgee; ENSMUSG00000026097; Expressed in urinary bladder urothelium and 255 other cell types or tissues.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:GO_Central.
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 GO; GO:1900060; P:negative regulation of ceramide biosynthetic process; ISO:MGI.
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_0000215631"
FT TOPO_DOM 1..21
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 22..42
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 43..46
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 47..67
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 68..100
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 101..121
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 122..123
FT /note="Extracellular"
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"
FT CONFLICT 123
FT /note="H -> N (in Ref. 1; BAC36865)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 153 AA; 17355 MW; A592BCA2BEB1AC6B CRC64;
MNVGVAHSEV NPNTRVMNSR GMWLTYALGV GLLHIVLLSI PFCSVPVAWT LTNIIHNLGM
YVFLHAVKGT PFETPDQGRA RLLTHWEQLD YGVQFTSSRK FFTISPIILY FLASFYTKYD
PTHFILNTAS LLSVLIPKMP QLHGVRIFGI NKY
//
