SCS3_YEAST
ID SCS3_YEAST Reviewed; 380 AA.
AC P53012; D6VU22; E9P8W2;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Acyl-coenzyme A diphosphatase SCS3 {ECO:0000255|HAMAP-Rule:MF_03231};
DE EC=3.6.1.- {ECO:0000255|HAMAP-Rule:MF_03231};
DE AltName: Full=FIT family protein SCS3 {ECO:0000255|HAMAP-Rule:MF_03231, ECO:0000303|PubMed:7706223};
GN Name=SCS3 {ECO:0000255|HAMAP-Rule:MF_03231, ECO:0000303|PubMed:7706223};
GN Synonyms=FIT2B; OrderedLocusNames=YGL126W {ECO:0000312|SGD:S000003094};
GN ORFNames=G2868;
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 [GENOMIC DNA], AND FUNCTION.
RC STRAIN=SP-1;
RX PubMed=7706223; DOI=10.1093/oxfordjournals.jbchem.a124681;
RA Hosaka K., Nikawa J., Kodaki T., Ishizu H., Yamashita S.;
RT "Cloning and sequence of the SCS3 gene which is required for inositol
RT prototrophy in Saccharomyces cerevisiae.";
RL J. Biochem. 116:1317-1321(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8896269;
RX DOI=10.1002/(sici)1097-0061(199609)12:10b<1047::aid-yea991>3.0.co;2-n;
RA Tizon B., Rodriguez-Torres A.M., Rodriguez-Belmonte E., Cadahia J.L.,
RA Cerdan E.;
RT "Identification of a putative methylenetetrahydrofolate reductase by
RT sequence analysis of a 6.8 kb DNA fragment of yeast chromosome VII.";
RL Yeast 12:1047-1051(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169869;
RA Tettelin H., Agostoni-Carbone M.L., Albermann K., Albers M., Arroyo J.,
RA Backes U., Barreiros T., Bertani I., Bjourson A.J., Brueckner M.,
RA Bruschi C.V., Carignani G., Castagnoli L., Cerdan E., Clemente M.L.,
RA Coblenz A., Coglievina M., Coissac E., Defoor E., Del Bino S., Delius H.,
RA Delneri D., de Wergifosse P., Dujon B., Durand P., Entian K.-D., Eraso P.,
RA Escribano V., Fabiani L., Fartmann B., Feroli F., Feuermann M.,
RA Frontali L., Garcia-Gonzalez M., Garcia-Saez M.I., Goffeau A.,
RA Guerreiro P., Hani J., Hansen M., Hebling U., Hernandez K., Heumann K.,
RA Hilger F., Hofmann B., Indge K.J., James C.M., Klima R., Koetter P.,
RA Kramer B., Kramer W., Lauquin G., Leuther H., Louis E.J., Maillier E.,
RA Marconi A., Martegani E., Mazon M.J., Mazzoni C., McReynolds A.D.K.,
RA Melchioretto P., Mewes H.-W., Minenkova O., Mueller-Auer S., Nawrocki A.,
RA Netter P., Neu R., Nombela C., Oliver S.G., Panzeri L., Paoluzi S.,
RA Plevani P., Portetelle D., Portillo F., Potier S., Purnelle B., Rieger M.,
RA Riles L., Rinaldi T., Robben J., Rodrigues-Pousada C.,
RA Rodriguez-Belmonte E., Rodriguez-Torres A.M., Rose M., Ruzzi M.,
RA Saliola M., Sanchez-Perez M., Schaefer B., Schaefer M., Scharfe M.,
RA Schmidheini T., Schreer A., Skala J., Souciet J.-L., Steensma H.Y.,
RA Talla E., Thierry A., Vandenbol M., van der Aart Q.J.M., Van Dyck L.,
RA Vanoni M., Verhasselt P., Voet M., Volckaert G., Wambutt R., Watson M.D.,
RA Weber N., Wedler E., Wedler H., Wipfli P., Wolf K., Wright L.F.,
RA Zaccaria P., Zimmermann M., Zollner A., Kleine K.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome VII.";
RL Nature 387:81-84(1997).
RN [4]
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 [5]
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 [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 FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=26504167; DOI=10.1083/jcb.201505067;
RA Choudhary V., Ojha N., Golden A., Prinz W.A.;
RT "A conserved family of proteins facilitates nascent lipid droplet budding
RT from the ER.";
RL J. Cell Biol. 211:261-271(2015).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF GLU-354.
RX PubMed=29417057; DOI=10.15698/mic2018.02.614;
RA Hayes M., Choudhary V., Ojha N., Shin J.J., Han G.S., Carman G.M.,
RA Loewen C.J., Prinz W.A., Levine T.;
RT "Fat storage-inducing transmembrane (FIT or FITM) proteins are related to
RT lipid phosphatase/phosphotransferase enzymes.";
RL Microb. Cell 5:88-103(2017).
RN [10]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=29526591; DOI=10.1016/j.cub.2018.02.020;
RA Choudhary V., Golani G., Joshi A.S., Cottier S., Schneiter R., Prinz W.A.,
RA Kozlov M.M.;
RT "Architecture of lipid droplets in endoplasmic reticulum is determined by
RT phospholipid intrinsic curvature.";
RL Curr. Biol. 28:915-926(2018).
RN [11]
RP FUNCTION, AND MUTAGENESIS OF HIS-235 AND HIS-350.
RX PubMed=32915949; DOI=10.1083/jcb.202006111;
RA Becuwe M., Bond L.M., Pinto A.F.M., Boland S., Mejhert N., Elliott S.D.,
RA Cicconet M., Graham M.M., Liu X.N., Ilkayeva O., Saghatelian A.,
RA Walther T.C., Farese R.V.;
RT "FIT2 is an acyl-coenzyme A diphosphatase crucial for endoplasmic reticulum
RT homeostasis.";
RL J. Cell Biol. 219:0-0(2020).
CC -!- FUNCTION: Fatty acyl-coenzyme A (CoA) diphosphatase that hydrolyzes
CC fatty acyl-CoA to yield acyl-4'-phosphopantetheine and adenosine 3',5'-
CC bisphosphate. Preferentially hydrolyzes unsaturated long-chain acyl-CoA
CC substrates in the endoplasmic reticulum (ER) lumen (By similarity).
CC This catalytic activity is required for maintaining ER structure and
CC for lipid droplets (LDs) biogenesis, which are lipid storage organelles
CC involved in maintaining lipid and energy homeostasis (PubMed:26504167,
CC PubMed:29526591, PubMed:32915949) (By similarity). May directly bind to
CC diacylglycerol (DAGs) and triacylglycerol, which is also important for
CC LD biogenesis (By similarity). May support directional budding of
CC nacent LDs from the ER into the cytosol by reducing DAG levels at sites
CC of LD formation (PubMed:29526591) (By similarity). May play a role in
CC the regulation of cell morphology and cytoskeletal organization (By
CC similarity). Involved in phospholipid biosynthesis (PubMed:7706223,
CC PubMed:29417057, PubMed:32915949) (By similarity).
CC {ECO:0000250|UniProtKB:P59266, ECO:0000250|UniProtKB:Q8N6M3,
CC ECO:0000255|HAMAP-Rule:MF_03231, ECO:0000269|PubMed:26504167,
CC ECO:0000269|PubMed:29417057, ECO:0000269|PubMed:29526591,
CC ECO:0000269|PubMed:32915949, ECO:0000269|PubMed:7706223}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an acyl-CoA + H2O = adenosine 3',5'-bisphosphate + an acyl-4'-
CC phosphopantetheine + 2 H(+); Xref=Rhea:RHEA:50044, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:58342, ChEBI:CHEBI:58343,
CC ChEBI:CHEBI:132023; Evidence={ECO:0000255|HAMAP-Rule:MF_03231};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50045;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03231};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z)-octadecenoyl-CoA + H2O = adenosine 3',5'-bisphosphate + 2
CC H(+) + S-(9Z-octadecenoyl)-4'-phosphopantetheine;
CC Xref=Rhea:RHEA:65564, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57387, ChEBI:CHEBI:58343, ChEBI:CHEBI:156553;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03231};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65565;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03231};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA + H2O = adenosine 3',5'-
CC bisphosphate + 2 H(+) + S-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-4'-
CC phosphopantetheine; Xref=Rhea:RHEA:65568, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57368, ChEBI:CHEBI:58343,
CC ChEBI:CHEBI:156554; Evidence={ECO:0000255|HAMAP-Rule:MF_03231};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65569;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03231};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + hexadecanoyl-CoA = adenosine 3',5'-bisphosphate + 2 H(+)
CC + S-hexadecanoyl-4'-phosphopantetheine; Xref=Rhea:RHEA:50032,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57379,
CC ChEBI:CHEBI:58343, ChEBI:CHEBI:132018; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_03231};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50033;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03231};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000255|HAMAP-Rule:MF_03231, ECO:0000269|PubMed:26504167,
CC ECO:0000269|PubMed:29417057, ECO:0000269|PubMed:29526591}; Multi-pass
CC membrane protein {ECO:0000255|HAMAP-Rule:MF_03231}. Note=Enriched at
CC sites of lipid droplet (LD) biogenesis. {ECO:0000269|PubMed:29526591}.
CC -!- MISCELLANEOUS: Present with 538 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the FIT family. Fungal FIT2B/SCS3 subfamily.
CC {ECO:0000255|HAMAP-Rule:MF_03231}.
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DR EMBL; D21200; BAA04742.1; -; Genomic_DNA.
DR EMBL; Z72648; CAA96835.1; -; Genomic_DNA.
DR EMBL; Z72647; CAA96834.1; -; Genomic_DNA.
DR EMBL; AY558499; AAS56825.1; -; Genomic_DNA.
DR EMBL; BK006941; DAA07983.1; -; Genomic_DNA.
DR PIR; S53293; S53293.
DR RefSeq; NP_011389.3; NM_001180991.3.
DR AlphaFoldDB; P53012; -.
DR SMR; P53012; -.
DR BioGRID; 33125; 207.
DR DIP; DIP-1209N; -.
DR IntAct; P53012; 7.
DR MINT; P53012; -.
DR STRING; 4932.YGL126W; -.
DR PaxDb; P53012; -.
DR PRIDE; P53012; -.
DR EnsemblFungi; YGL126W_mRNA; YGL126W; YGL126W.
DR GeneID; 852751; -.
DR KEGG; sce:YGL126W; -.
DR SGD; S000003094; SCS3.
DR VEuPathDB; FungiDB:YGL126W; -.
DR eggNOG; KOG3750; Eukaryota.
DR GeneTree; ENSGT00530000063693; -.
DR HOGENOM; CLU_048143_2_1_1; -.
DR InParanoid; P53012; -.
DR OMA; HDPSGHI; -.
DR BioCyc; YEAST:G3O-30622-MON; -.
DR Reactome; R-SCE-8964572; Lipid particle organization.
DR PRO; PR:P53012; -.
DR Proteomes; UP000002311; Chromosome VII.
DR RNAct; P53012; protein.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:SGD.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; IMP:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0016818; F:hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides; IDA:UniProtKB.
DR GO; GO:0140042; P:lipid droplet formation; IMP:UniProtKB.
DR GO; GO:0034389; P:lipid droplet organization; IBA:GO_Central.
DR GO; GO:0019915; P:lipid storage; IBA:GO_Central.
DR GO; GO:1900481; P:negative regulation of diacylglycerol biosynthetic process; IMP:UniProtKB.
DR GO; GO:0008654; P:phospholipid biosynthetic process; IMP:SGD.
DR GO; GO:0006644; P:phospholipid metabolic process; IMP:SGD.
DR GO; GO:1900480; P:regulation of diacylglycerol biosynthetic process; IMP:UniProtKB.
DR HAMAP; MF_03231; SCS3; 1.
DR InterPro; IPR019388; FIT.
DR InterPro; IPR046400; SCS3.
DR PANTHER; PTHR23129; PTHR23129; 1.
DR Pfam; PF10261; Scs3p; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Hydrolase; Lipid biosynthesis; Lipid metabolism;
KW Membrane; Phospholipid biosynthesis; Phospholipid metabolism;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..380
FT /note="Acyl-coenzyme A diphosphatase SCS3"
FT /id="PRO_0000097635"
FT TOPO_DOM 1..7
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 8..28
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 29..43
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 44..64
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 65..88
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 89..109
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 110..233
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 234..254
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 255..325
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 326..346
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 347..356
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 357..377
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 378..380
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT ACT_SITE 235
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03231"
FT ACT_SITE 350
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03231"
FT MUTAGEN 235
FT /note="H->A: Inositol auxotrophy. Impaired ER morphology
FT with the apparition of clumps of ER membrane."
FT /evidence="ECO:0000269|PubMed:32915949"
FT MUTAGEN 350
FT /note="H->A: Inositol auxotrophy. Impaired ER morphology
FT with the apparition of clumps of ER membrane."
FT /evidence="ECO:0000269|PubMed:32915949"
FT MUTAGEN 354
FT /note="E->A: Temperature sensitive. Inositol auxotroph at
FT 37 degrees Celsius, but partially supports growth on
FT inositol at 25 degrees Celsius. Impaired ER morphology and
FT aberrant lipid droplet (LD) budding."
FT /evidence="ECO:0000269|PubMed:29417057"
FT MUTAGEN 354
FT /note="E->K,V: Inositol auxotrophy. Impaired ER morphology
FT and aberrant lipid droplet (LD) budding."
FT /evidence="ECO:0000269|PubMed:29417057"
FT MUTAGEN 354
FT /note="E->Q,D: No defect in inositol biosynthesis. Aberrant
FT lipid droplet (LD) budding."
FT /evidence="ECO:0000269|PubMed:29417057"
FT CONFLICT 240
FT /note="T -> A (in Ref. 5; AAS56825)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 380 AA; 42735 MW; E0A7A890C780ACD3 CRC64;
MSSKWFNAIH LLVCPLTVLV GYLMNAYGYG AALQATLNKD GLVNAMLVKK GWFWTSLVGW
WCIIRYRAVP GATGRDRRHI VQSFKRYAIL TVWWYVFTQG IWFGVGPIMD LVFVYTGGHC
HYDVFDDAGH VNEDFQGSVT RTNRALALIH NVLTLHGHHQ EHRQQQLWDR SIGSIQGALQ
ATQPKTPKNV TASAAAAINT FIHDQMHRWQ GPLTTSAQCR RFGGHWAGGH DPSGHVFLAT
LMCMFLLGEL RVFGRRALAH LYAQKWQLVR LVTRLFDTGP LWTWRRCGGG SMTCGARLWR
AIVEPPVTCA AALLRLTRCI ACDHPVIILL TLLVTWLWQL LLTAVASRFH TVREHMSGLL
AAYIVTGLVY ARDAAALRPV
