ID   HACD_YEAST              Reviewed;         217 AA.
AC   P40857; D6VW87;
DT   01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1995, sequence version 1.
DT   27-MAR-2024, entry version 167.
DE   RecName: Full=Very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase PHS1 {ECO:0000305};
DE            EC=4.2.1.134 {ECO:0000269|PubMed:17719544, ECO:0000269|PubMed:18272525};
DE   AltName: Full=3-hydroxyacyl-CoA dehydratase PHS1;
DE            Short=HACD;
DE   AltName: Full=PTPLA homolog involved in sphingolipid biosynthesis protein 1;
GN   Name=PHS1; OrderedLocusNames=YJL097W; ORFNames=J0902;
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].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=7871887; DOI=10.1002/yea.320101112;
RA   Miosga T., Boles E., Schaaff-Gerstenschlaeger I., Schmitt S.,
RA   Zimmermann F.K.;
RT   "Sequence and function analysis of a 9.74 kb fragment of Saccharomyces
RT   cerevisiae chromosome X including the BCK1 gene.";
RL   Yeast 10:1481-1488(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=8641269; DOI=10.1002/j.1460-2075.1996.tb00557.x;
RA   Galibert F., Alexandraki D., Baur A., Boles E., Chalwatzis N., Chuat J.-C.,
RA   Coster F., Cziepluch C., de Haan M., Domdey H., Durand P., Entian K.-D.,
RA   Gatius M., Goffeau A., Grivell L.A., Hennemann A., Herbert C.J.,
RA   Heumann K., Hilger F., Hollenberg C.P., Huang M.-E., Jacq C.,
RA   Jauniaux J.-C., Katsoulou C., Kirchrath L., Kleine K., Kordes E.,
RA   Koetter P., Liebl S., Louis E.J., Manus V., Mewes H.-W., Miosga T.,
RA   Obermaier B., Perea J., Pohl T.M., Portetelle D., Pujol A., Purnelle B.,
RA   Ramezani Rad M., Rasmussen S.W., Rose M., Rossau R.,
RA   Schaaff-Gerstenschlaeger I., Smits P.H.M., Scarcez T., Soriano N.,
RA   To Van D., Tzermia M., Van Broekhoven A., Vandenbol M., Wedler H.,
RA   von Wettstein D., Wambutt R., Zagulski M., Zollner A., Karpfinger-Hartl L.;
RT   "Complete nucleotide sequence of Saccharomyces cerevisiae chromosome X.";
RL   EMBO J. 15:2031-2049(1996).
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   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   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   [7]
RP   FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX   PubMed=17719544; DOI=10.1016/j.cell.2007.06.031;
RA   Denic V., Weissman J.S.;
RT   "A molecular caliper mechanism for determining very long-chain fatty acid
RT   length.";
RL   Cell 130:663-677(2007).
RN   [8]
RP   FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, MUTAGENESIS OF TYR-149 AND
RP   GLU-156, ACTIVE SITE, CATALYTIC ACTIVITY, AND PATHWAY.
RX   PubMed=18272525; DOI=10.1074/jbc.m708993200;
RA   Kihara A., Sakuraba H., Ikeda M., Denpoh A., Igarashi Y.;
RT   "Membrane topology and essential amino acid residues of Phs1, a 3-
RT   hydroxyacyl-CoA dehydratase involved in very long-chain fatty acid
RT   elongation.";
RL   J. Biol. Chem. 283:11199-11209(2008).
RN   [9]
RP   FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP   MUTAGENESIS OF GLU-60; GLN-79; ARG-83; GLU-116; ARG-119; ARG-141 AND
RP   GLY-152.
RX   PubMed=23416297; DOI=10.1016/j.febslet.2013.02.006;
RA   Yazawa T., Naganuma T., Yamagata M., Kihara A.;
RT   "Identification of residues important for the catalysis, structure
RT   maintenance, and substrate specificity of yeast 3-hydroxyacyl-CoA
RT   dehydratase Phs1.";
RL   FEBS Lett. 587:804-809(2013).
CC   -!- FUNCTION: Catalyzes the third of the four reactions of the long-chain
CC       fatty acids elongation cycle. This endoplasmic reticulum-bound
CC       enzymatic process, allows the addition of two carbons to the chain of
CC       long- and very long-chain fatty acids/VLCFAs per cycle. This enzyme
CC       catalyzes the dehydration of the 3-hydroxyacyl-CoA intermediate into
CC       trans-2,3-enoyl-CoA, within each cycle of fatty acid elongation.
CC       Thereby, it participates in the production of VLCFAs of different chain
CC       lengths that are involved in multiple biological processes as
CC       precursors of membrane lipids and lipid mediators.
CC       {ECO:0000269|PubMed:17719544, ECO:0000269|PubMed:18272525,
CC       ECO:0000269|PubMed:23416297}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a very-long-chain (3R)-3-hydroxyacyl-CoA = a very-long-chain
CC         (2E)-enoyl-CoA + H2O; Xref=Rhea:RHEA:45812, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:83728, ChEBI:CHEBI:85440; EC=4.2.1.134;
CC         Evidence={ECO:0000269|PubMed:17719544, ECO:0000269|PubMed:18272525};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(3R)-hydroxyeicosanoyl-CoA = (2E)-eicosenoyl-CoA + H2O;
CC         Xref=Rhea:RHEA:39175, ChEBI:CHEBI:15377, ChEBI:CHEBI:74691,
CC         ChEBI:CHEBI:76373; Evidence={ECO:0000269|PubMed:17719544};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39176;
CC         Evidence={ECO:0000269|PubMed:17719544};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(3R)-hydroxydocosanoyl-CoA = (2E)-docosenoyl-CoA + H2O;
CC         Xref=Rhea:RHEA:39187, ChEBI:CHEBI:15377, ChEBI:CHEBI:74692,
CC         ChEBI:CHEBI:76375; Evidence={ECO:0000269|PubMed:17719544};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39188;
CC         Evidence={ECO:0000269|PubMed:17719544};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(3R)-hydroxyoctadecanoyl-CoA = (2E)-octadecenoyl-CoA + H2O;
CC         Xref=Rhea:RHEA:39155, ChEBI:CHEBI:15377, ChEBI:CHEBI:71412,
CC         ChEBI:CHEBI:76374; Evidence={ECO:0000269|PubMed:17719544};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39156;
CC         Evidence={ECO:0000269|PubMed:17719544};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(3R)-hydroxytetracosanoyl-CoA = (2E)-tetracosenoyl-CoA + H2O;
CC         Xref=Rhea:RHEA:39199, ChEBI:CHEBI:15377, ChEBI:CHEBI:74693,
CC         ChEBI:CHEBI:76377; Evidence={ECO:0000269|PubMed:17719544};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39200;
CC         Evidence={ECO:0000269|PubMed:17719544};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(3R)-hydroxyhexacosanoyl-CoA = (2E)-hexacosenoyl-CoA + H2O;
CC         Xref=Rhea:RHEA:39211, ChEBI:CHEBI:15377, ChEBI:CHEBI:74281,
CC         ChEBI:CHEBI:76378; Evidence={ECO:0000269|PubMed:17719544};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39212;
CC         Evidence={ECO:0000269|PubMed:17719544};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(3R)-hydroxyhexadecanoyl-CoA = (2E)-hexadecenoyl-CoA + H2O;
CC         Xref=Rhea:RHEA:39159, ChEBI:CHEBI:15377, ChEBI:CHEBI:61526,
CC         ChEBI:CHEBI:74278; Evidence={ECO:0000269|PubMed:23416297};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39160;
CC         Evidence={ECO:0000269|PubMed:23416297};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=5.5 uM for 3-hydroxypalmitoyl-CoA {ECO:0000269|PubMed:23416297};
CC         Vmax=84 pmol/min/ng enzyme {ECO:0000269|PubMed:23416297};
CC   -!- PATHWAY: Lipid metabolism; fatty acid biosynthesis.
CC       {ECO:0000269|PubMed:17719544, ECO:0000269|PubMed:18272525}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC       {ECO:0000269|PubMed:18272525}; Multi-pass membrane protein
CC       {ECO:0000255}. Vacuole membrane {ECO:0000269|PubMed:14562095}; Multi-
CC       pass membrane protein {ECO:0000255}.
CC   -!- SIMILARITY: Belongs to the very long-chain fatty acids dehydratase HACD
CC       family. {ECO:0000305}.
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DR   EMBL; X77923; CAA54893.1; -; Genomic_DNA.
DR   EMBL; Z49372; CAA89391.1; -; Genomic_DNA.
DR   EMBL; AY557855; AAS56181.1; -; Genomic_DNA.
DR   EMBL; BK006943; DAA08703.1; -; Genomic_DNA.
DR   PIR; S50296; S50296.
DR   RefSeq; NP_012438.1; NM_001181530.1.
DR   AlphaFoldDB; P40857; -.
DR   BioGRID; 33660; 284.
DR   DIP; DIP-2104N; -.
DR   IntAct; P40857; 32.
DR   STRING; 4932.YJL097W; -.
DR   SwissLipids; SLP:000000492; -.
DR   CarbonylDB; P40857; -.
DR   PaxDb; 4932-YJL097W; -.
DR   PeptideAtlas; P40857; -.
DR   TopDownProteomics; P40857; -.
DR   EnsemblFungi; YJL097W_mRNA; YJL097W; YJL097W.
DR   GeneID; 853348; -.
DR   KEGG; sce:YJL097W; -.
DR   AGR; SGD:S000003633; -.
DR   SGD; S000003633; PHS1.
DR   VEuPathDB; FungiDB:YJL097W; -.
DR   eggNOG; KOG3187; Eukaryota.
DR   GeneTree; ENSGT00530000062962; -.
DR   HOGENOM; CLU_034302_6_1_1; -.
DR   InParanoid; P40857; -.
DR   OMA; WSYILWQ; -.
DR   OrthoDB; 276005at2759; -.
DR   BioCyc; MetaCyc:MONOMER3O-85; -.
DR   BioCyc; YEAST:MONOMER3O-85; -.
DR   BRENDA; 4.2.1.134; 984.
DR   Reactome; R-SCE-75876; Synthesis of very long-chain fatty acyl-CoAs.
DR   UniPathway; UPA00094; -.
DR   BioGRID-ORCS; 853348; 4 hits in 10 CRISPR screens.
DR   PRO; PR:P40857; -.
DR   Proteomes; UP000002311; Chromosome X.
DR   RNAct; P40857; Protein.
DR   GO; GO:0005783; C:endoplasmic reticulum; HDA:SGD.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:SGD.
DR   GO; GO:0000324; C:fungal-type vacuole; IDA:SGD.
DR   GO; GO:0000329; C:fungal-type vacuole membrane; HDA:SGD.
DR   GO; GO:0042175; C:nuclear outer membrane-endoplasmic reticulum membrane network; HDA:SGD.
DR   GO; GO:0018812; F:3-hydroxyacyl-CoA dehydratase activity; IMP:SGD.
DR   GO; GO:0004300; F:enoyl-CoA hydratase activity; IDA:SGD.
DR   GO; GO:0102158; F:very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase activity; IEA:UniProtKB-EC.
DR   GO; GO:0030497; P:fatty acid elongation; IMP:SGD.
DR   GO; GO:0030148; P:sphingolipid biosynthetic process; IMP:SGD.
DR   GO; GO:0007034; P:vacuolar transport; IMP:SGD.
DR   GO; GO:0042761; P:very long-chain fatty acid biosynthetic process; IBA:GO_Central.
DR   InterPro; IPR007482; Tyr_Pase-like_PTPLA.
DR   PANTHER; PTHR11035; VERY-LONG-CHAIN (3R)-3-HYDROXYACYL-COA DEHYDRATASE; 1.
DR   PANTHER; PTHR11035:SF3; VERY-LONG-CHAIN (3R)-3-HYDROXYACYL-COA DEHYDRATASE; 1.
DR   Pfam; PF04387; PTPLA; 1.
PE   1: Evidence at protein level;
KW   Endoplasmic reticulum; Fatty acid biosynthesis; Fatty acid metabolism;
KW   Lipid biosynthesis; Lipid metabolism; Lyase; Membrane; Reference proteome;
KW   Transmembrane; Transmembrane helix; Vacuole.
FT   CHAIN           1..217
FT                   /note="Very-long-chain (3R)-3-hydroxyacyl-CoA dehydratase
FT                   PHS1"
FT                   /id="PRO_0000203047"
FT   TOPO_DOM        1..11
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        12..29
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        30..47
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        48..66
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        67..76
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        77..94
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        95..99
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        100..117
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        118..142
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        143..160
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        161..178
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        179..196
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        197..217
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   MOTIF           214..217
FT                   /note="Endoplasmic reticulum retention signal"
FT   ACT_SITE        149
FT                   /evidence="ECO:0000305|PubMed:18272525"
FT   ACT_SITE        156
FT                   /evidence="ECO:0000305|PubMed:18272525"
FT   MUTAGEN         60
FT                   /note="E->A: Digitonin sensitive, reduces structural
FT                   integrity of the protein. Affects the substrate
FT                   specificity."
FT                   /evidence="ECO:0000269|PubMed:23416297"
FT   MUTAGEN         79
FT                   /note="Q->A: Digitonin sensitive, reduces structural
FT                   integrity of the protein."
FT                   /evidence="ECO:0000269|PubMed:23416297"
FT   MUTAGEN         83
FT                   /note="R->A: Greatly inhibits the fatty acid elongation
FT                   cycle. Displays normal KM but reduced Vmax values."
FT                   /evidence="ECO:0000269|PubMed:23416297"
FT   MUTAGEN         116
FT                   /note="E->A: Exhibits a moderate fatty acid elongation
FT                   defect."
FT                   /evidence="ECO:0000269|PubMed:23416297"
FT   MUTAGEN         119
FT                   /note="R->A: Exhibits a moderate fatty acid elongation
FT                   defect."
FT                   /evidence="ECO:0000269|PubMed:23416297"
FT   MUTAGEN         141
FT                   /note="R->A: Digitonin sensitive, reduces structural
FT                   integrity of the protein. Greatly inhibits the fatty acid
FT                   elongation cycle. Displays a higher KM and lower Vmax
FT                   values."
FT                   /evidence="ECO:0000269|PubMed:23416297"
FT   MUTAGEN         149
FT                   /note="Y->A: No catalytic activity."
FT                   /evidence="ECO:0000269|PubMed:18272525"
FT   MUTAGEN         152
FT                   /note="G->A: Greatly inhibits the fatty acid elongation
FT                   cycle. Displays normal KM but reduced Vmax values."
FT                   /evidence="ECO:0000269|PubMed:23416297"
FT   MUTAGEN         156
FT                   /note="E->A: No catalytic activity."
FT                   /evidence="ECO:0000269|PubMed:18272525"
SQ   SEQUENCE   217 AA;  24511 MW;  5C87BC9563FB83AA CRC64;
     MSKKLASPLS FLPLYNLLSA VGWSYLLYLV ISLYPKVGQP AFFYQTKNVA TLVQCGAIIE
     IINSFLGVVR SPLLTTVAQV SSRLLVVLGI FQLLPNTSGV QSVVYISLLL AWSITEIVRY
     LYYFFMLVFK NGAPKILILL RYNLFWILYP TGVASELRII YCALNAAESQ YSLLYKRILI
     AAMLAYIPGF PMLFLHMVAQ RKKVMKSLRS SFGKKLI
//