SEC14_YEAST
ID SEC14_YEAST Reviewed; 304 AA.
AC P24280; D6VZQ3;
DT 01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=SEC14 cytosolic factor;
DE AltName: Full=Phosphatidylinositol/phosphatidylcholine transfer protein;
DE Short=PI/PC TP;
GN Name=SEC14; Synonyms=PIT1; OrderedLocusNames=YMR079W; ORFNames=YM9582.04;
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], FUNCTION, AND SUBCELLULAR LOCATION.
RC STRAIN=CTY1-1A;
RX PubMed=2466847; DOI=10.1083/jcb.108.4.1271;
RA Bankaitis V.A., Malehorn D.E., Emr S.D., Greene R.;
RT "The Saccharomyces cerevisiae SEC14 gene encodes a cytosolic factor that is
RT required for transport of secretory proteins from the yeast Golgi
RT complex.";
RL J. Cell Biol. 108:1271-1281(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169872;
RA Bowman S., Churcher C.M., Badcock K., Brown D., Chillingworth T.,
RA Connor R., Dedman K., Devlin K., Gentles S., Hamlin N., Hunt S., Jagels K.,
RA Lye G., Moule S., Odell C., Pearson D., Rajandream M.A., Rice P.,
RA Skelton J., Walsh S.V., Whitehead S., Barrell B.G.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XIII.";
RL Nature 387:90-93(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 PROTEIN SEQUENCE OF 2-31.
RX PubMed=2407740; DOI=10.1016/s0021-9258(19)39620-6;
RA Aitken J.F., van Heusden G.P.H., Temkin M., Dowhan W.;
RT "The gene encoding the phosphatidylinositol transfer protein is essential
RT for cell growth.";
RL J. Biol. Chem. 265:4711-4717(1990).
RN [5]
RP FUNCTION.
RX PubMed=2215682; DOI=10.1038/347561a0;
RA Bankaitis V.A., Aitken J.R., Cleves A.E., Dowhan W.;
RT "An essential role for a phospholipid transfer protein in yeast Golgi
RT function.";
RL Nature 347:561-562(1990).
RN [6]
RP SUBCELLULAR LOCATION.
RX PubMed=1997207; DOI=10.1016/0092-8674(91)90508-v;
RA Cleves A.E., McGee T.P., Whitters E.A., Champion K.M., Aitken J.R.,
RA Dowhan W., Goebl M., Bankaitis V.A.;
RT "Mutations in the CDP-choline pathway for phospholipid biosynthesis bypass
RT the requirement for an essential phospholipid transfer protein.";
RL Cell 64:789-800(1991).
RN [7]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=7816798; DOI=10.1073/pnas.92.1.112;
RA Skinner H.B., McGee T.P., McMaster C.R., Fry M.R., Bell R.M.,
RA Bankaitis V.A.;
RT "The Saccharomyces cerevisiae phosphatidylinositol-transfer protein effects
RT a ligand-dependent inhibition of choline-phosphate cytidylyltransferase
RT activity.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:112-116(1995).
RN [8]
RP FUNCTION, AND MUTAGENESIS OF LYS-66 AND LYS-239.
RX PubMed=10488334; DOI=10.1016/s1097-2765(00)80366-4;
RA Phillips S.E., Sha B., Topalof L., Xie Z., Alb J.G., Klenchin V.A.,
RA Swigart P., Cockcroft S., Martin T.F., Luo M., Bankaitis V.A.;
RT "Yeast Sec14p deficient in phosphatidylinositol transfer activity is
RT functional in vivo.";
RL Mol. Cell 4:187-197(1999).
RN [9]
RP CATALYTIC ACTIVITY.
RX PubMed=10848624; DOI=10.1091/mbc.11.6.1989;
RA Li X., Routt S.M., Xie Z., Cui X., Fang M., Kearns M.A., Bard M.,
RA Kirsch D.R., Bankaitis V.A.;
RT "Identification of a novel family of nonclassic yeast phosphatidylinositol
RT transfer proteins whose function modulates phospholipase D activity and
RT Sec14p-independent cell growth.";
RL Mol. Biol. Cell 11:1989-2005(2000).
RN [10]
RP SUBCELLULAR LOCATION.
RX PubMed=12869188; DOI=10.1046/j.1432-1033.2003.03688.x;
RA Schnabl M., Oskolkova O.V., Holic R., Brezna B., Pichler H., Zagorsek M.,
RA Kohlwein S.D., Paltauf F., Daum G., Griac P.;
RT "Subcellular localization of yeast Sec14 homologues and their involvement
RT in regulation of phospholipid turnover.";
RL Eur. J. Biochem. 270:3133-3145(2003).
RN [11]
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 [12]
RP FUNCTION.
RX PubMed=16997918; DOI=10.1074/jbc.m603054200;
RA Smirnova T.I., Chadwick T.G., MacArthur R., Poluektov O., Song L.,
RA Ryan M.M., Schaaf G., Bankaitis V.A.;
RT "The chemistry of phospholipid binding by the Saccharomyces cerevisiae
RT phosphatidylinositol transfer protein Sec14p as determined by EPR
RT spectroscopy.";
RL J. Biol. Chem. 281:34897-34908(2006).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-302, AND IDENTIFICATION BY
RP 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 [14]
RP FUNCTION.
RX PubMed=19129178; DOI=10.1074/jbc.m808732200;
RA Curwin A.J., Fairn G.D., McMaster C.R.;
RT "Phospholipid transfer protein Sec14 is required for trafficking from
RT endosomes and regulates distinct trans-Golgi export pathways.";
RL J. Biol. Chem. 284:7364-7375(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-302, 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).
RN [16]
RP UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-42 AND LYS-84, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22106047; DOI=10.1002/pmic.201100166;
RA Starita L.M., Lo R.S., Eng J.K., von Haller P.D., Fields S.;
RT "Sites of ubiquitin attachment in Saccharomyces cerevisiae.";
RL Proteomics 12:236-240(2012).
RN [17]
RP FUNCTION, AND MUTAGENESIS OF GLY-266.
RX PubMed=23383173; DOI=10.1371/journal.pone.0055388;
RA Curwin A.J., Leblanc M.A., Fairn G.D., McMaster C.R.;
RT "Localization of lipid raft proteins to the plasma membrane is a major
RT function of the phospholipid transfer protein Sec14.";
RL PLoS ONE 8:e55388-e55388(2013).
RN [18]
RP FUNCTION.
RX PubMed=32828847; DOI=10.1016/j.bbamem.2020.183450;
RA Sugiura T., Nakao H., Ikeda K., Khan D., Nile A.H., Bankaitis V.A.,
RA Nakano M.;
RT "Biophysical parameters of the Sec14 phospholipid exchange cycle - Effect
RT of lipid packing in membranes.";
RL Biochim. Biophys. Acta 1863:183450-183450(2021).
RN [19] {ECO:0007744|PDB:1AUA}
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 4-299.
RX PubMed=9461221; DOI=10.1038/35179;
RA Sha B., Phillips S.E., Bankaitis V.A., Luo M.;
RT "Crystal structure of the Saccharomyces cerevisiae phosphatidylinositol-
RT transfer protein.";
RL Nature 391:506-510(1998).
RN [20] {ECO:0007744|PDB:6F0E}
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS).
RX PubMed=29307839; DOI=10.1016/j.chembiol.2017.12.007;
RA Pries V., Nocker C., Khan D., Johnen P., Hong Z., Tripathi A., Keller A.L.,
RA Fitz M., Perruccio F., Filipuzzi I., Thavam S., Aust T., Riedl R.,
RA Ziegler S., Bono F., Schaaf G., Bankaitis V.A., Waldmann H., Hoepfner D.;
RT "Target identification and mechanism of action of picolinamide and
RT benzamide chemotypes with antifungal properties.";
RL Cell Chem. Biol. 25:279-290.e7(2018).
CC -!- FUNCTION: Required for transport of secretory proteins from the Golgi
CC complex. Catalyzes the transfer of phosphatidylinositol (PI) and
CC phosphatidylcholine (PC) between membranes in vitro. Essential for
CC viability and secretion (PubMed:2466847, PubMed:2215682). Exchanges its
CC bound phospholipid with phospholipid monomers that reside in membrane
CC bilayers (PubMed:16997918). Regulates specific trans-Golgi export
CC pathways, like transport from endosomes to the trans-Golgi or transport
CC from the plasma membrane to the vacuole at the level of the endosome
CC (PubMed:19129178). Increased membrane curvature and lipid unsaturation
CC levels at the trans-Golgi membrane promotes membrane binding and
CC phospholipid transfer of SEC14. Thus, SEC14 may act at the trans-Golgi
CC membrane to exchange lipids and promote vesicle formation
CC (PubMed:32828847). The phosphatidylcholine-bound form of SEC14
CC represses the CDP-choline pathway activity by inhibiting CCTase, the
CC rate-determining enzyme of the CDP-choline pathway (PubMed:7816798). PI
CC binding/transfer is dispensable for function in vivo (PubMed:10488334).
CC Required for trafficking and localization of lipid raft proteins to the
CC plasma membrane (PubMed:23383173). {ECO:0000269|PubMed:10488334,
CC ECO:0000269|PubMed:16997918, ECO:0000269|PubMed:19129178,
CC ECO:0000269|PubMed:2215682, ECO:0000269|PubMed:23383173,
CC ECO:0000269|PubMed:2466847, ECO:0000269|PubMed:32828847,
CC ECO:0000269|PubMed:7816798}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol)(in) = a
CC 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol)(out);
CC Xref=Rhea:RHEA:38691, ChEBI:CHEBI:57880;
CC Evidence={ECO:0000269|PubMed:10848624};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38692;
CC Evidence={ECO:0000269|PubMed:10848624};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine(in) = a 1,2-diacyl-
CC sn-glycero-3-phosphocholine(out); Xref=Rhea:RHEA:38571,
CC ChEBI:CHEBI:57643; Evidence={ECO:0000269|PubMed:10848624};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38572;
CC Evidence={ECO:0000269|PubMed:10848624};
CC -!- ACTIVITY REGULATION: The inhibitor activity of SEC14 is controlled by
CC whether PI or PC is bound to SEC14. The pPC-bound form of SEC14 is an
CC inhibitor, while the PI-bound form is not. The phospholipid
CC binding/exchange activity of SEC14 represents a mechanism by which the
CC regulatory activity of SEC14 is itself controlled.
CC {ECO:0000269|PubMed:7816798}.
CC -!- INTERACTION:
CC P24280; P38797: PTC7; NbExp=4; IntAct=EBI-16535, EBI-24588;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000269|PubMed:1997207}; Peripheral membrane protein. Cytoplasm
CC {ECO:0000269|PubMed:12869188, ECO:0000269|PubMed:1997207,
CC ECO:0000269|PubMed:2466847}.
CC -!- MISCELLANEOUS: Present with 84300 molecules/cell in log phase SD
CC medium. {ECO:0000269|PubMed:14562106}.
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DR EMBL; X15483; CAA33511.1; -; Genomic_DNA.
DR EMBL; Z49259; CAA89225.1; -; Genomic_DNA.
DR EMBL; BK006946; DAA09977.1; -; Genomic_DNA.
DR PIR; A30106; A30106.
DR RefSeq; NP_013796.1; NM_001182578.1.
DR PDB; 1AUA; X-ray; 2.50 A; A=4-299.
DR PDB; 6F0E; X-ray; 2.60 A; A=1-304.
DR PDBsum; 1AUA; -.
DR PDBsum; 6F0E; -.
DR AlphaFoldDB; P24280; -.
DR SMR; P24280; -.
DR BioGRID; 35255; 269.
DR DIP; DIP-1610N; -.
DR IntAct; P24280; 8.
DR MINT; P24280; -.
DR STRING; 4932.YMR079W; -.
DR SwissLipids; SLP:000000359; -.
DR iPTMnet; P24280; -.
DR MaxQB; P24280; -.
DR PaxDb; P24280; -.
DR PRIDE; P24280; -.
DR EnsemblFungi; YMR079W_mRNA; YMR079W; YMR079W.
DR GeneID; 855103; -.
DR KEGG; sce:YMR079W; -.
DR SGD; S000004684; SEC14.
DR VEuPathDB; FungiDB:YMR079W; -.
DR eggNOG; KOG1471; Eukaryota.
DR GeneTree; ENSGT00530000066638; -.
DR HOGENOM; CLU_014001_0_1_1; -.
DR InParanoid; P24280; -.
DR OMA; CECAGGC; -.
DR BioCyc; YEAST:G3O-32781-MON; -.
DR EvolutionaryTrace; P24280; -.
DR PRO; PR:P24280; -.
DR Proteomes; UP000002311; Chromosome XIII.
DR RNAct; P24280; protein.
DR GO; GO:0005737; C:cytoplasm; IDA:SGD.
DR GO; GO:0005829; C:cytosol; IDA:SGD.
DR GO; GO:0005794; C:Golgi apparatus; IDA:SGD.
DR GO; GO:0000139; C:Golgi membrane; IDA:SGD.
DR GO; GO:0008525; F:phosphatidylcholine transporter activity; IDA:SGD.
DR GO; GO:0008526; F:phosphatidylinositol transfer activity; IDA:SGD.
DR GO; GO:0030437; P:ascospore formation; IMP:SGD.
DR GO; GO:0043001; P:Golgi to plasma membrane protein transport; IMP:SGD.
DR GO; GO:0006896; P:Golgi to vacuole transport; IMP:SGD.
DR GO; GO:0048194; P:Golgi vesicle budding; IDA:SGD.
DR GO; GO:2001246; P:negative regulation of phosphatidylcholine biosynthetic process; IDA:SGD.
DR GO; GO:1901352; P:negative regulation of phosphatidylglycerol biosynthetic process; IMP:SGD.
DR GO; GO:0046488; P:phosphatidylinositol metabolic process; IMP:SGD.
DR GO; GO:0015914; P:phospholipid transport; IDA:SGD.
DR CDD; cd00170; SEC14; 1.
DR Gene3D; 3.40.525.10; -; 1.
DR InterPro; IPR001251; CRAL-TRIO_dom.
DR InterPro; IPR036865; CRAL-TRIO_dom_sf.
DR InterPro; IPR011074; CRAL/TRIO_N_dom.
DR InterPro; IPR036273; CRAL/TRIO_N_dom_sf.
DR Pfam; PF00650; CRAL_TRIO; 1.
DR Pfam; PF03765; CRAL_TRIO_N; 1.
DR SMART; SM01100; CRAL_TRIO_N; 1.
DR SMART; SM00516; SEC14; 1.
DR SUPFAM; SSF46938; SSF46938; 1.
DR SUPFAM; SSF52087; SSF52087; 1.
DR PROSITE; PS50191; CRAL_TRIO; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Direct protein sequencing; Golgi apparatus;
KW Isopeptide bond; Membrane; Phosphoprotein; Protein transport;
KW Reference proteome; Transport; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:2407740"
FT CHAIN 2..304
FT /note="SEC14 cytosolic factor"
FT /id="PRO_0000210744"
FT DOMAIN 99..272
FT /note="CRAL-TRIO"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00056"
FT MOD_RES 302
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18407956,
FT ECO:0007744|PubMed:19779198"
FT CROSSLNK 42
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0007744|PubMed:22106047"
FT CROSSLNK 84
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0007744|PubMed:22106047"
FT MUTAGEN 66
FT /note="K->A: Inactivates phosphatidylinositol, but not
FT phosphatidylcholine, transfer activity, but rescues the
FT lethality and Golgi secretory defects associated with sec14
FT null mutations; when associated with A-239."
FT /evidence="ECO:0000269|PubMed:10488334"
FT MUTAGEN 239
FT /note="K->A: Inactivates phosphatidylinositol, but not
FT phosphatidylcholine, transfer activity, but rescues the
FT lethality and Golgi secretory defects associated with sec14
FT null mutations; when associated with A-66."
FT /evidence="ECO:0000269|PubMed:10488334"
FT MUTAGEN 266
FT /note="G->D: In SEC14(ts); temperature-sesnitive allele
FT that is targeted to the proteasome at the restrictive
FT temperature."
FT /evidence="ECO:0000269|PubMed:23383173"
FT HELIX 6..10
FT /evidence="ECO:0007829|PDB:1AUA"
FT TURN 26..28
FT /evidence="ECO:0007829|PDB:1AUA"
FT HELIX 33..46
FT /evidence="ECO:0007829|PDB:1AUA"
FT HELIX 55..64
FT /evidence="ECO:0007829|PDB:1AUA"
FT TURN 65..67
FT /evidence="ECO:0007829|PDB:1AUA"
FT HELIX 69..86
FT /evidence="ECO:0007829|PDB:1AUA"
FT HELIX 88..90
FT /evidence="ECO:0007829|PDB:1AUA"
FT HELIX 91..94
FT /evidence="ECO:0007829|PDB:1AUA"
FT HELIX 100..103
FT /evidence="ECO:0007829|PDB:1AUA"
FT HELIX 104..106
FT /evidence="ECO:0007829|PDB:1AUA"
FT STRAND 110..114
FT /evidence="ECO:0007829|PDB:1AUA"
FT STRAND 120..124
FT /evidence="ECO:0007829|PDB:1AUA"
FT HELIX 126..128
FT /evidence="ECO:0007829|PDB:1AUA"
FT HELIX 131..134
FT /evidence="ECO:0007829|PDB:1AUA"
FT TURN 135..137
FT /evidence="ECO:0007829|PDB:1AUA"
FT HELIX 140..156
FT /evidence="ECO:0007829|PDB:1AUA"
FT HELIX 158..166
FT /evidence="ECO:0007829|PDB:1AUA"
FT STRAND 173..178
FT /evidence="ECO:0007829|PDB:1AUA"
FT HELIX 184..204
FT /evidence="ECO:0007829|PDB:1AUA"
FT STRAND 209..216
FT /evidence="ECO:0007829|PDB:1AUA"
FT HELIX 219..228
FT /evidence="ECO:0007829|PDB:1AUA"
FT HELIX 229..231
FT /evidence="ECO:0007829|PDB:1AUA"
FT HELIX 234..237
FT /evidence="ECO:0007829|PDB:1AUA"
FT STRAND 240..242
FT /evidence="ECO:0007829|PDB:1AUA"
FT HELIX 248..251
FT /evidence="ECO:0007829|PDB:1AUA"
FT TURN 252..254
FT /evidence="ECO:0007829|PDB:1AUA"
FT STRAND 257..261
FT /evidence="ECO:0007829|PDB:1AUA"
FT HELIX 262..264
FT /evidence="ECO:0007829|PDB:1AUA"
FT HELIX 272..274
FT /evidence="ECO:0007829|PDB:1AUA"
FT HELIX 277..279
FT /evidence="ECO:0007829|PDB:6F0E"
FT HELIX 284..286
FT /evidence="ECO:0007829|PDB:1AUA"
FT HELIX 288..290
FT /evidence="ECO:0007829|PDB:1AUA"
SQ SEQUENCE 304 AA; 34901 MW; CCB69404A8A0963B CRC64;
MVTQQEKEFL ESYPQNCPPD ALPGTPGNLD SAQEKALAEL RKLLEDAGFI ERLDDSTLLR
FLRARKFDVQ LAKEMFENCE KWRKDYGTDT ILQDFHYDEK PLIAKFYPQY YHKTDKDGRP
VYFEELGAVN LHEMNKVTSE ERMLKNLVWE YESVVQYRLP ACSRAAGHLV ETSCTIMDLK
GISISSAYSV MSYVREASYI SQNYYPERMG KFYIINAPFG FSTAFRLFKP FLDPVTVSKI
FILGSSYQKE LLKQIPAENL PVKFGGKSEV DESKGGLYLS DIGPWRDPKY IGPEGEAPEA
FSMK
