ID ORM2_YEAST Reviewed; 216 AA.
AC Q06144; D6VYY8;
DT 08-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 02-SEP-2026, entry version 178.
DE RecName: Full=Protein ORM2;
GN Name=ORM2; OrderedLocusNames=YLR350W;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169871; DOI=10.1038/387s087;
RA Johnston M., Hillier L.W., Riles L., Albermann K., Andre B., Ansorge W.,
RA Benes V., Brueckner M., Delius H., Dubois E., Duesterhoeft A.,
RA Entian K.-D., Floeth M., Goffeau A., Hebling U., Heumann K.,
RA Heuss-Neitzel D., Hilbert H., Hilger F., Kleine K., Koetter P., Louis E.J.,
RA Messenguy F., Mewes H.-W., Miosga T., Moestl D., Mueller-Auer S.,
RA Nentwich U., Obermaier B., Piravandi E., Pohl T.M., Portetelle D.,
RA Purnelle B., Rechmann S., Rieger M., Rinke M., Rose M., Scharfe M.,
RA Scherens B., Scholler P., Schwager C., Schwarz S., Underwood A.P.,
RA Urrestarazu L.A., Vandenbol M., Verhasselt P., Vierendeels F., Voet M.,
RA Volckaert G., Voss H., Wambutt R., Wedler E., Wedler H., Zimmermann F.K.,
RA Zollner A., Hani J., Hoheisel J.D.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XII.";
RL Nature 387:87-90(1997).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=17322287; DOI=10.1101/gr.6037607;
RA Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F.,
RA Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J.,
RA Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J.,
RA Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D.,
RA LaBaer J.;
RT "Approaching a complete repository of sequence-verified protein-encoding
RT clones for Saccharomyces cerevisiae.";
RL Genome Res. 17:536-543(2007).
RN [4]
RP NOMENCLATURE.
RX PubMed=12093374; DOI=10.1186/gb-2002-3-6-research0027;
RA Hjelmqvist L., Tuson M., Marfany G., Herrero E., Balcells S.,
RA Gonzalez-Duarte R.;
RT "ORMDL proteins are a conserved new family of endoplasmic reticulum
RT membrane proteins.";
RL Genome Biol. 3:RESEARCH0027.1-RESEARCH0027.13(2002).
RN [5]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=14562095; DOI=10.1038/nature02026;
RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA Weissman J.S., O'Shea E.K.;
RT "Global analysis of protein localization in budding yeast.";
RL Nature 425:686-691(2003).
RN [6]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [7]
RP TOPOLOGY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 208353 / W303-1A;
RX PubMed=16847258; DOI=10.1073/pnas.0604075103;
RA Kim H., Melen K., Oesterberg M., von Heijne G.;
RT "A global topology map of the Saccharomyces cerevisiae membrane proteome.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:11142-11147(2006).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-18, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ADR376;
RX PubMed=17330950; DOI=10.1021/pr060559j;
RA Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J.,
RA Elias J.E., Gygi S.P.;
RT "Large-scale phosphorylation analysis of alpha-factor-arrested
RT Saccharomyces cerevisiae.";
RL J. Proteome Res. 6:1190-1197(2007).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT "A multidimensional chromatography technology for in-depth phosphoproteome
RT analysis.";
RL Mol. Cell. Proteomics 7:1389-1396(2008).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-9; SER-15 AND SER-22, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19779198; DOI=10.1126/science.1172867;
RA Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.;
RT "Global analysis of Cdk1 substrate phosphorylation sites provides insights
RT into evolution.";
RL Science 325:1682-1686(2009).
RN [11]
RP FUNCTION, PHOSPHORYLATION, SUBCELLULAR LOCATION, IDENTIFICATION IN THE
RP SPOTS COMPLEX, AND MUTAGENESIS OF SER-9; SER-15; THR-18; THR-36 AND
RP 46-SER--SER-48.
RX PubMed=20182505; DOI=10.1038/nature08787;
RA Breslow D.K., Collins S.R., Bodenmiller B., Aebersold R., Simons K.,
RA Shevchenko A., Ejsing C.S., Weissman J.S.;
RT "Orm family proteins mediate sphingolipid homeostasis.";
RL Nature 463:1048-1053(2010).
RN [12] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=39490931; DOI=10.1016/j.jlr.2024.100683;
RA Ren J., Rieger R., Pereira de Sa N., Kelapire D., Del Poeta M.,
RA Hannun Y.A.;
RT "Orm proteins control ceramide synthesis and endocytosis via LCB-mediated
RT Ypk1 regulation.";
RL J. Lipid Res. 65:100683-100683(2024).
CC -!- FUNCTION: Component of the SPOTS complex that acts as a negative
CC regulator of sphingolipid synthesis (PubMed:39490931). Acts by
CC inhibiting serine palmitoyltransferases (LCB1 and LCB2) activity
CC (PubMed:20182505). Along with ORM1, plays a role in the phosphorylation
CC of LAC1 and YPK1, the distribution of actin patches between mother and
CC daughter cells, and in endocytosis (PubMed:39490931).
CC {ECO:0000269|PubMed:20182505, ECO:0000269|PubMed:39490931}.
CC -!- SUBUNIT: Component of the SPOTS complex, at least composed of LCB1/2
CC (LCB1 and/or LCB2), ORM1/2 (ORM1 and/or ORM2), SAC1 and TSC3.
CC {ECO:0000269|PubMed:20182505}.
CC -!- INTERACTION:
CC Q06144; Q05031: DFG5; NbExp=3; IntAct=EBI-34916, EBI-27512;
CC Q06144; P25045: LCB1; NbExp=7; IntAct=EBI-34916, EBI-10059;
CC Q06144; P53224: ORM1; NbExp=6; IntAct=EBI-34916, EBI-12592;
CC Q06144; Q06144: ORM2; NbExp=4; IntAct=EBI-34916, EBI-34916;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:14562095, ECO:0000269|PubMed:20182505}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:14562095,
CC ECO:0000269|PubMed:20182505}.
CC -!- PTM: Phosphorylated in case of disruption of sphingolipid synthesis
CC (PubMed:20182505). Phosphorylation regulates the inhibitory activity of
CC serine palmitoyltransferases (LCB1 and LCB2) (PubMed:20182505).
CC {ECO:0000269|PubMed:20182505}.
CC -!- DISRUPTION PHENOTYPE: Double knockout of ORM1 and ORM2 exhibits defect
CC in ceramide synthesis, increasing the level of total sphingolipids and
CC causing phytosphingosine and dihydrosphingosine to accumulate; the
CC accumulation of phytosphingosine reduces the phosphorylation of both
CC YPK1 and LAC1 (PubMed:39490931). The mutant also exhibits random
CC distribution of actin patches between mother and daughter cells, and
CC shows a defect in endocytosis (PubMed:39490931). Defects are rescued by
CC YPK2 A-239 mutation or TSC3 deletion in ORM1 and ORM2 double knockout
CC mutant background (PubMed:39490931). {ECO:0000269|PubMed:39490931}.
CC -!- MISCELLANEOUS: Present with 5240 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the ORM family. {ECO:0000305}.
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DR EMBL; U19028; AAB67252.1; -; Genomic_DNA.
DR EMBL; AY692908; AAT92927.1; -; Genomic_DNA.
DR EMBL; BK006945; DAA09654.1; -; Genomic_DNA.
DR PIR; S51352; S51352.
DR RefSeq; NP_013454.1; NM_001182239.1.
DR PDB; 8IAJ; EM; 3.10 A; D/H=1-216.
DR PDB; 8IAK; EM; 3.10 A; D/H=1-216.
DR PDB; 8IAM; EM; 3.10 A; D/H=1-216.
DR PDBsum; 8IAJ; -.
DR PDBsum; 8IAK; -.
DR PDBsum; 8IAM; -.
DR AlphaFoldDB; Q06144; -.
DR EMDB; EMD-35304; -.
DR EMDB; EMD-35306; -.
DR EMDB; EMD-35310; -.
DR SMR; Q06144; -.
DR BioGRID; 31612; 561.
DR ComplexPortal; CPX-3158; SPOTS complex.
DR DIP; DIP-5579N; -.
DR FunCoup; Q06144; 481.
DR IntAct; Q06144; 45.
DR MINT; Q06144; -.
DR STRING; 4932.YLR350W; -.
DR iPTMnet; Q06144; -.
DR PaxDb; 4932-YLR350W; -.
DR PeptideAtlas; Q06144; -.
DR TopDownProteomics; Q06144; -.
DR EnsemblFungi; YLR350W_mRNA; YLR350W; YLR350W.
DR GeneID; 851064; -.
DR KEGG; sce:YLR350W; -.
DR AGR; SGD:S000004342; -.
DR SGD; S000004342; ORM2.
DR VEuPathDB; FungiDB:YLR350W; -.
DR eggNOG; KOG3319; Eukaryota.
DR HOGENOM; CLU_072117_2_1_1; -.
DR InParanoid; Q06144; -.
DR OMA; WTAYILI; -.
DR OrthoDB; 1932233at2759; -.
DR BioCyc; YEAST:G3O-32425-MONOMER; -.
DR Reactome; R-SCE-6798695; Neutrophil degranulation.
DR BioGRID-ORCS; 851064; 7 hits in 10 CRISPR screens.
DR PRO; PR:Q06144; -.
DR Proteomes; UP000002311; Chromosome XII.
DR RNAct; Q06144; protein.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0017059; C:serine palmitoyltransferase complex; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0006672; P:ceramide metabolic process; IBA:GO_Central.
DR GO; GO:0090156; P:intracellular sphingolipid homeostasis; IMP:UniProtKB.
DR GO; GO:0090155; P:negative regulation of sphingolipid biosynthetic process; IMP:UniProtKB.
DR GO; GO:0006986; P:response to unfolded protein; IMP:SGD.
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 3D-structure; Endocytosis; Endoplasmic reticulum; Lipid metabolism;
KW Membrane; Phosphoprotein; Reference proteome; Sphingolipid metabolism;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..216
FT /note="Protein ORM2"
FT /id="PRO_0000215646"
FT TOPO_DOM 1..78
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 79..99
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 100..103
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 104..124
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 125..148
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 149..169
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 170..177
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 178..198
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 199..216
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..50
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 17..38
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 9
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19779198"
FT MOD_RES 15
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19779198"
FT MOD_RES 18
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:17330950"
FT MOD_RES 22
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19779198"
FT MOD_RES 29
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P53224"
FT MOD_RES 51
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P53224"
FT MUTAGEN 9
FT /note="S->A: Induces dysregulation of sphingolipid
FT synthesis; when associated with A-15, A-18, A-36 and 46-A--
FT A-48."
FT /evidence="ECO:0000269|PubMed:20182505"
FT MUTAGEN 15
FT /note="S->A: Induces dysregulation of sphingolipid
FT synthesis; when associated with A-9, A-18, A-36 and 46-A--
FT A-48."
FT /evidence="ECO:0000269|PubMed:20182505"
FT MUTAGEN 18
FT /note="T->A: Induces dysregulation of sphingolipid
FT synthesis; when associated with A-9, A-15, A-36 and 46-A--
FT A-48."
FT /evidence="ECO:0000269|PubMed:20182505"
FT MUTAGEN 36
FT /note="T->A: Induces dysregulation of sphingolipid
FT synthesis; when associated with A-9, A-15, A-18 and 46-A--
FT A-48."
FT /evidence="ECO:0000269|PubMed:20182505"
FT MUTAGEN 46..48
FT /note="SSS->AAA: Induces dysregulation of sphingolipid
FT synthesis; when associated with A-9, A-15, A-18, and A-36."
FT /evidence="ECO:0000269|PubMed:20182505"
FT STRAND 48..52
FT /evidence="ECO:0007829|PDB:8IAJ"
FT HELIX 53..56
FT /evidence="ECO:0007829|PDB:8IAJ"
FT HELIX 58..65
FT /evidence="ECO:0007829|PDB:8IAJ"
FT HELIX 74..76
FT /evidence="ECO:0007829|PDB:8IAJ"
FT HELIX 80..97
FT /evidence="ECO:0007829|PDB:8IAJ"
FT HELIX 102..118
FT /evidence="ECO:0007829|PDB:8IAJ"
FT HELIX 119..123
FT /evidence="ECO:0007829|PDB:8IAJ"
FT STRAND 132..138
FT /evidence="ECO:0007829|PDB:8IAM"
FT HELIX 141..144
FT /evidence="ECO:0007829|PDB:8IAJ"
FT HELIX 145..147
FT /evidence="ECO:0007829|PDB:8IAJ"
FT HELIX 153..169
FT /evidence="ECO:0007829|PDB:8IAJ"
FT TURN 170..172
FT /evidence="ECO:0007829|PDB:8IAJ"
FT HELIX 177..186
FT /evidence="ECO:0007829|PDB:8IAJ"
FT HELIX 187..191
FT /evidence="ECO:0007829|PDB:8IAJ"
FT HELIX 193..195
FT /evidence="ECO:0007829|PDB:8IAK"
FT STRAND 196..199
FT /evidence="ECO:0007829|PDB:8IAK"
FT STRAND 202..204
FT /evidence="ECO:0007829|PDB:8IAJ"
FT TURN 207..210
FT /evidence="ECO:0007829|PDB:8IAJ"
SQ SEQUENCE 216 AA; 24855 MW; 2F474503CAB7C195 CRC64;
MIDRTKNESP AFEESPLTPN VSNLKPFPSQ SNKISTPVTD HRRRRSSSVI SHVEQETFED
ENDQQMLPNM NATWVDQRGA WLIHIVVIVL LRLFYSLFGS TPKWTWTLTN MTYIIGFYIM
FHLVKGTPFD FNGGAYDNLT MWEQINDETL YTPTRKFLLI VPIVLFLISN QYYRNDMTLF
LSNLAVTVLI GVVPKLGITH RLRISIPGIT GRAQIS
//
