ID ORML2_MOUSE Reviewed; 153 AA.
AC Q9CQZ0; Q8CF72; Q9CSJ7; Q9CVL6;
DT 08-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 02-SEP-2026, entry version 151.
DE RecName: Full=ORM1-like protein 2;
GN Name=Ormdl2;
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] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Kidney, and Pancreas;
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] (ISOFORM 1).
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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
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:Q53FV1}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q53FV1}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q53FV1}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9CQZ0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9CQZ0-2; Sequence=VSP_016051;
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 (PubMed:31880535).
CC Simultaneous knockdown of ORMDL1 and ORMDL2 do not exhibit any visible
CC phenotype (PubMed:31880535). Simultaneous knockdown of ORMDL2 and
CC ORMDL3 show elevated brain levels of sphingolipids, compared with wild-
CC type animals, but remain fertile and show no sign of neurodegeneration
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; AK002583; BAB22207.1; -; mRNA.
DR EMBL; AK002824; BAC25010.1; -; mRNA.
DR EMBL; AK007548; BAB25101.1; -; mRNA.
DR EMBL; AK012681; BAB28407.1; -; mRNA.
DR EMBL; AK013455; BAB28864.1; -; mRNA.
DR EMBL; BC002146; AAH02146.1; -; mRNA.
DR CCDS; CCDS24295.1; -. [Q9CQZ0-1]
DR RefSeq; NP_001346098.1; NM_001359169.1. [Q9CQZ0-1]
DR RefSeq; NP_001346099.1; NM_001359170.1. [Q9CQZ0-1]
DR RefSeq; NP_001346100.1; NM_001359171.1. [Q9CQZ0-1]
DR RefSeq; NP_077142.1; NM_024180.6. [Q9CQZ0-1]
DR AlphaFoldDB; Q9CQZ0; -.
DR SMR; Q9CQZ0; -.
DR BioGRID; 211758; 1.
DR FunCoup; Q9CQZ0; 1506.
DR IntAct; Q9CQZ0; 7.
DR STRING; 10090.ENSMUSP00000026409; -.
DR iPTMnet; Q9CQZ0; -.
DR PhosphoSitePlus; Q9CQZ0; -.
DR jPOST; Q9CQZ0; -.
DR PaxDb; 10090-ENSMUSP00000026409; -.
DR PeptideAtlas; Q9CQZ0; -.
DR ProteomicsDB; 294347; -. [Q9CQZ0-1]
DR ProteomicsDB; 294348; -. [Q9CQZ0-2]
DR Pumba; Q9CQZ0; -.
DR TopDownProteomics; Q9CQZ0-1; -. [Q9CQZ0-1]
DR Antibodypedia; 53765; 78 antibodies from 16 providers.
DR DNASU; 66844; -.
DR Ensembl; ENSMUST00000026409.5; ENSMUSP00000026409.4; ENSMUSG00000025353.6. [Q9CQZ0-1]
DR Ensembl; ENSMUST00000217685.2; ENSMUSP00000151644.2; ENSMUSG00000025353.6. [Q9CQZ0-2]
DR Ensembl; ENSMUST00000219215.2; ENSMUSP00000151335.2; ENSMUSG00000025353.6. [Q9CQZ0-1]
DR Ensembl; ENSMUST00000219524.2; ENSMUSP00000151697.2; ENSMUSG00000025353.6. [Q9CQZ0-1]
DR GeneID; 66844; -.
DR KEGG; mmu:66844; -.
DR UCSC; uc007hoo.2; mouse. [Q9CQZ0-1]
DR AGR; MGI:1914094; -.
DR CTD; 29095; -.
DR MGI; MGI:1914094; Ormdl2.
DR VEuPathDB; HostDB:ENSMUSG00000025353; -.
DR eggNOG; KOG3319; Eukaryota.
DR GeneTree; ENSGT00950000183178; -.
DR HOGENOM; CLU_072117_3_0_1; -.
DR InParanoid; Q9CQZ0; -.
DR OMA; STHYTHF; -.
DR OrthoDB; 1932233at2759; -.
DR PhylomeDB; Q9CQZ0; -.
DR Reactome; R-MMU-1660661; Sphingolipid de novo biosynthesis.
DR BioGRID-ORCS; 66844; 2 hits in 78 CRISPR screens.
DR PRO; PR:Q9CQZ0; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q9CQZ0; protein.
DR Bgee; ENSMUSG00000025353; Expressed in right kidney and 235 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; 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 1: Evidence at protein level;
KW Alternative splicing; Endoplasmic reticulum; Membrane; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..153
FT /note="ORM1-like protein 2"
FT /id="PRO_0000215637"
FT TOPO_DOM 1..21
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 22..42
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 43..63
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 64..105
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 106..126
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 127..153
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..59
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_016051"
FT CONFLICT 37
FT /note="L -> P (in Ref. 1; BAB28407)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 153 AA; 17390 MW; 3ECCA8B2DB88ED66 CRC64;
MNVGVAHSEV NPNTRVMNSR GIWLAYIILV GLLHVVLLSI PFFSIPVVWT LTNVIHNLAM
YIFLHTVKGT PFETPDQGKA RLLTHWEQMD YGLQFTSSRK FLSISPIVLY LLASFYTKYD
AAHFLINTAS LLSVLLPKLP QFHGVRLFGI NKY
//
