HACD_YEAST
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 03-AUG-2022, entry version 159.
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
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; 282.
DR DIP; DIP-2104N; -.
DR IntAct; P40857; 32.
DR STRING; 4932.YJL097W; -.
DR SwissLipids; SLP:000000492; -.
DR CarbonylDB; P40857; -.
DR PaxDb; P40857; -.
DR PRIDE; P40857; -.
DR TopDownProteomics; P40857; -.
DR EnsemblFungi; YJL097W_mRNA; YJL097W; YJL097W.
DR GeneID; 853348; -.
DR KEGG; sce:YJL097W; -.
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; TKLYLFA; -.
DR BioCyc; MetaCyc:MON3O-85; -.
DR BioCyc; YEAST:MON3O-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 PRO; PR:P40857; -.
DR Proteomes; UP000002311; Chromosome X.
DR RNAct; P40857; protein.
DR GO; GO:0005783; C:endoplasmic reticulum; HDA: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:0030176; C:integral component of endoplasmic reticulum membrane; IDA:SGD.
DR GO; GO:0042175; C:nuclear outer membrane-endoplasmic reticulum membrane network; HDA:SGD.
DR GO; GO:0102343; F:3-hydroxy-arachidoyl-CoA dehydratase activity; IEA:UniProtKB-EC.
DR GO; GO:0102344; F:3-hydroxy-behenoyl-CoA dehydratase activity; IEA:UniProtKB-EC.
DR GO; GO:0102345; F:3-hydroxy-lignoceroyl-CoA dehydratase activity; IEA:UniProtKB-EC.
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 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; PTHR11035; 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
