SCS2_YEAST
ID SCS2_YEAST Reviewed; 244 AA.
AC P40075; D3DM26;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Vesicle-associated membrane protein-associated protein SCS2;
DE Short=VAMP-associated protein SCS2;
DE AltName: Full=Choline sensitivity suppressor protein 2;
DE AltName: Full=VAP homolog 1;
GN Name=SCS2; OrderedLocusNames=YER120W;
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].
RX PubMed=8537323; DOI=10.1093/oxfordjournals.jbchem.a124889;
RA Nikawa J., Murakami A., Esumi E., Hosaka K.;
RT "Cloning and sequence of the SCS2 gene, which can suppress the defect of
RT INO1 expression in an inositol auxotrophic mutant of Saccharomyces
RT cerevisiae.";
RL J. Biochem. 118:39-45(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169868;
RA Dietrich F.S., Mulligan J.T., Hennessy K.M., Yelton M.A., Allen E.,
RA Araujo R., Aviles E., Berno A., Brennan T., Carpenter J., Chen E.,
RA Cherry J.M., Chung E., Duncan M., Guzman E., Hartzell G., Hunicke-Smith S.,
RA Hyman R.W., Kayser A., Komp C., Lashkari D., Lew H., Lin D., Mosedale D.,
RA Nakahara K., Namath A., Norgren R., Oefner P., Oh C., Petel F.X.,
RA Roberts D., Sehl P., Schramm S., Shogren T., Smith V., Taylor P., Wei Y.,
RA Botstein D., Davis R.W.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome V.";
RL Nature 387:78-81(1997).
RN [3]
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 [4]
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 [5]
RP PROTEIN SEQUENCE OF 2-14; 85-113; 144-156 AND 166-180, CLEAVAGE OF
RP INITIATOR METHIONINE, ACETYLATION AT SER-2, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RA Bienvenut W.V., Peters C.;
RL Submitted (JUN-2005) to UniProtKB.
RN [6]
RP TOPOLOGY, AND SUBCELLULAR LOCATION.
RX PubMed=9537365; DOI=10.1128/jb.180.7.1700-1708.1998;
RA Kagiwada S., Hosaka K., Murata M., Nikawa J., Takatsuki A.;
RT "The Saccharomyces cerevisiae SCS2 gene product, a homolog of a
RT synaptobrevin-associated protein, is an integral membrane protein of the
RT endoplasmic reticulum and is required for inositol metabolism.";
RL J. Bacteriol. 180:1700-1708(1998).
RN [7]
RP FUNCTION, INTERACTION WITH OPI1, AND SUBCELLULAR LOCATION.
RX PubMed=12727870; DOI=10.1093/emboj/cdg201;
RA Loewen C.J.R., Roy A., Levine T.P.;
RT "A conserved ER targeting motif in three families of lipid binding proteins
RT and in Opi1p binds VAP.";
RL EMBO J. 22:2025-2035(2003).
RN [8]
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 [9]
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 [10]
RP INTERACTION WITH OPI1, AND SUBCELLULAR LOCATION.
RX PubMed=15455074; DOI=10.1371/journal.pbio.0020342;
RA Brickner J.H., Walter P.;
RT "Gene recruitment of the activated INO1 locus to the nuclear membrane.";
RL PLoS Biol. 2:1843-1852(2004).
RN [11]
RP FUNCTION, AND MUTAGENESIS OF LYS-40; 41-THR-THR-42 AND LYS-120.
RX PubMed=15668246; DOI=10.1074/jbc.m500147200;
RA Loewen C.J.R., Levine T.P.;
RT "A highly conserved binding site in vesicle-associated membrane protein-
RT associated protein (VAP) for the FFAT motif of lipid-binding proteins.";
RL J. Biol. Chem. 280:14097-14104(2005).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-106, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=YAL6B;
RX PubMed=15665377; DOI=10.1074/mcp.m400219-mcp200;
RA Gruhler A., Olsen J.V., Mohammed S., Mortensen P., Faergeman N.J., Mann M.,
RA Jensen O.N.;
RT "Quantitative phosphoproteomics applied to the yeast pheromone signaling
RT pathway.";
RL Mol. Cell. Proteomics 4:310-327(2005).
RN [13]
RP FFAT MOTIF-BINDING, AND MUTAGENESIS OF LYS-84 AND LEU-86.
RX PubMed=16004875; DOI=10.1016/j.str.2005.04.010;
RA Kaiser S.E., Brickner J.H., Reilein A.R., Fenn T.D., Walter P.,
RA Brunger A.T.;
RT "Structural basis of FFAT motif-mediated ER targeting.";
RL Structure 13:1035-1045(2005).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-106, AND IDENTIFICATION BY
RP 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).
CC -!- FUNCTION: Targets proteins containing a FFAT motif to endoplasmic
CC reticulum membranes. Regulates phospholipid biosynthesis by modulating
CC the subcellular localization of the transcriptional repressor OPI1.
CC {ECO:0000269|PubMed:12727870, ECO:0000269|PubMed:15668246}.
CC -!- SUBUNIT: Interacts with OPI1. {ECO:0000269|PubMed:12727870,
CC ECO:0000269|PubMed:15455074}.
CC -!- INTERACTION:
CC P40075; Q00402: NUM1; NbExp=4; IntAct=EBI-16735, EBI-12386;
CC P40075; P21957: OPI1; NbExp=3; IntAct=EBI-16735, EBI-12555;
CC P40075; P38713: OSH3; NbExp=2; IntAct=EBI-16735, EBI-12630;
CC P40075; Q07657: SHS1; NbExp=4; IntAct=EBI-16735, EBI-22083;
CC P40075; P39523: YMR124W; NbExp=4; IntAct=EBI-16735, EBI-27256;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass type
CC IV membrane protein. Nucleus membrane; Single-pass type IV membrane
CC protein.
CC -!- DOMAIN: The MSP domain is required for binding to the FFAT motif of
CC target proteins.
CC -!- MISCELLANEOUS: Present with 3497 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the VAMP-associated protein (VAP) (TC 9.B.17)
CC family. {ECO:0000305}.
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DR EMBL; D44493; BAA07936.1; -; Genomic_DNA.
DR EMBL; U18916; AAC03218.1; -; Genomic_DNA.
DR EMBL; AY693125; AAT93144.1; -; Genomic_DNA.
DR EMBL; BK006939; DAA07780.1; -; Genomic_DNA.
DR PIR; S50623; S50623.
DR RefSeq; NP_011046.3; NM_001179010.3.
DR PDB; 6LP4; X-ray; 2.05 A; A=1-128.
DR PDBsum; 6LP4; -.
DR AlphaFoldDB; P40075; -.
DR SMR; P40075; -.
DR BioGRID; 36865; 364.
DR DIP; DIP-2272N; -.
DR IntAct; P40075; 57.
DR MINT; P40075; -.
DR STRING; 4932.YER120W; -.
DR iPTMnet; P40075; -.
DR MaxQB; P40075; -.
DR PaxDb; P40075; -.
DR PRIDE; P40075; -.
DR EnsemblFungi; YER120W_mRNA; YER120W; YER120W.
DR GeneID; 856856; -.
DR KEGG; sce:YER120W; -.
DR SGD; S000000922; SCS2.
DR VEuPathDB; FungiDB:YER120W; -.
DR eggNOG; KOG0439; Eukaryota.
DR GeneTree; ENSGT00940000172509; -.
DR HOGENOM; CLU_072622_1_0_1; -.
DR InParanoid; P40075; -.
DR OMA; HEAIHEN; -.
DR BioCyc; YEAST:G3O-30284-MON; -.
DR Reactome; R-SCE-6798695; Neutrophil degranulation.
DR Reactome; R-SCE-9013106; RHOC GTPase cycle.
DR Reactome; R-SCE-9609523; Insertion of tail-anchored proteins into the endoplasmic reticulum membrane.
DR PRO; PR:P40075; -.
DR Proteomes; UP000002311; Chromosome V.
DR RNAct; P40075; protein.
DR GO; GO:0005935; C:cellular bud neck; IPI:SGD.
DR GO; GO:0005934; C:cellular bud tip; IDA:SGD.
DR GO; GO:0000781; C:chromosome, telomeric region; IEA:GOC.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:SGD.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IDA:SGD.
DR GO; GO:0005635; C:nuclear envelope; IDA:SGD.
DR GO; GO:0031965; C:nuclear membrane; IDA:SGD.
DR GO; GO:0071561; C:nucleus-vacuole junction; IDA:SGD.
DR GO; GO:0005886; C:plasma membrane; IDA:SGD.
DR GO; GO:0033149; F:FFAT motif binding; IMP:SGD.
DR GO; GO:0035091; F:phosphatidylinositol binding; IDA:SGD.
DR GO; GO:0048309; P:endoplasmic reticulum inheritance; IMP:SGD.
DR GO; GO:0090158; P:endoplasmic reticulum membrane organization; IGI:SGD.
DR GO; GO:0061163; P:endoplasmic reticulum polarization; IDA:SGD.
DR GO; GO:0061817; P:endoplasmic reticulum-plasma membrane tethering; IBA:GO_Central.
DR GO; GO:0042308; P:negative regulation of protein import into nucleus; IMP:SGD.
DR GO; GO:0008654; P:phospholipid biosynthetic process; IMP:SGD.
DR GO; GO:0032377; P:regulation of intracellular lipid transport; IMP:SGD.
DR GO; GO:0060304; P:regulation of phosphatidylinositol dephosphorylation; IGI:SGD.
DR GO; GO:0031509; P:subtelomeric heterochromatin assembly; IMP:SGD.
DR Gene3D; 2.60.40.10; -; 1.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR000535; MSP_dom.
DR InterPro; IPR008962; PapD-like_sf.
DR InterPro; IPR016763; VAP.
DR PANTHER; PTHR10809; PTHR10809; 1.
DR Pfam; PF00635; Motile_Sperm; 1.
DR PIRSF; PIRSF019693; VAMP-associated; 1.
DR SUPFAM; SSF49354; SSF49354; 1.
DR PROSITE; PS50202; MSP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Direct protein sequencing;
KW Endoplasmic reticulum; Membrane; Nucleus; Phosphoprotein;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.5"
FT CHAIN 2..244
FT /note="Vesicle-associated membrane protein-associated
FT protein SCS2"
FT /id="PRO_0000213467"
FT TOPO_DOM 2..222
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 223..243
FT /note="Helical; Anchor for type IV membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 244
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT DOMAIN 3..126
FT /note="MSP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00132"
FT REGION 135..219
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 193..219
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000269|Ref.5"
FT MOD_RES 106
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:15665377,
FT ECO:0007744|PubMed:19779198"
FT MUTAGEN 40
FT /note="K->N: Disrupts binding to FFAT motif and causes OPI1
FT mislocalization."
FT /evidence="ECO:0000269|PubMed:15668246"
FT MUTAGEN 41..42
FT /note="TT->AA: Disrupts binding to FFAT motif and causes
FT OPI1 mislocalization."
FT /evidence="ECO:0000269|PubMed:15668246"
FT MUTAGEN 84
FT /note="K->D: Disrupts binding to FFAT motif; when
FT associated with D-86."
FT /evidence="ECO:0000269|PubMed:16004875"
FT MUTAGEN 86
FT /note="L->D: Disrupts binding to FFAT motif; when
FT associated with D-84."
FT /evidence="ECO:0000269|PubMed:16004875"
FT MUTAGEN 120
FT /note="K->N: Reduces binding to FFAT motif and impairs OPI1
FT function."
FT /evidence="ECO:0000269|PubMed:15668246"
FT STRAND 4..7
FT /evidence="ECO:0007829|PDB:6LP4"
FT STRAND 9..15
FT /evidence="ECO:0007829|PDB:6LP4"
FT STRAND 21..29
FT /evidence="ECO:0007829|PDB:6LP4"
FT STRAND 31..33
FT /evidence="ECO:0007829|PDB:6LP4"
FT STRAND 35..42
FT /evidence="ECO:0007829|PDB:6LP4"
FT TURN 44..46
FT /evidence="ECO:0007829|PDB:6LP4"
FT STRAND 47..56
FT /evidence="ECO:0007829|PDB:6LP4"
FT STRAND 61..68
FT /evidence="ECO:0007829|PDB:6LP4"
FT STRAND 84..91
FT /evidence="ECO:0007829|PDB:6LP4"
FT HELIX 101..112
FT /evidence="ECO:0007829|PDB:6LP4"
FT HELIX 113..115
FT /evidence="ECO:0007829|PDB:6LP4"
FT STRAND 117..126
FT /evidence="ECO:0007829|PDB:6LP4"
SQ SEQUENCE 244 AA; 26926 MW; 45390E24E31D392E CRC64;
MSAVEISPDV LVYKSPLTEQ STEYASISNN SDQTIAFKVK TTAPKFYCVR PNAAVVAPGE
TIQVQVIFLG LTEEPAADFK CRDKFLVITL PSPYDLNGKA VADVWSDLEA EFKQQAISKK
IKVKYLISPD VHPAQNQNIQ ENKETVEPVV QDSEPKEVPA VVNEKEVPAE PETQPPVQVK
KEEVPPVVQK TVPHENEKQT SNSTPAPQNQ IKEAATVPAE NESSSMGIFI LVALLILVLG
WFYR
