HFD1_YEAST
ID HFD1_YEAST Reviewed; 532 AA.
AC Q04458; D6VZT3;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Fatty aldehyde dehydrogenase HFD1;
DE EC=1.2.1.3 {ECO:0000269|PubMed:22633490};
DE EC=1.2.1.64 {ECO:0000269|PubMed:27669165, ECO:0000269|PubMed:27693056};
DE AltName: Full=Hexadecenal dehydrogenase {ECO:0000305|PubMed:22633490};
GN Name=HFD1; OrderedLocusNames=YMR110C; ORFNames=YM9718.09C;
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 [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 [2]
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 [3]
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 [4]
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 [5]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 76625 / YPH499;
RX PubMed=14576278; DOI=10.1073/pnas.2135385100;
RA Sickmann A., Reinders J., Wagner Y., Joppich C., Zahedi R.P., Meyer H.E.,
RA Schoenfisch B., Perschil I., Chacinska A., Guiard B., Rehling P.,
RA Pfanner N., Meisinger C.;
RT "The proteome of Saccharomyces cerevisiae mitochondria.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:13207-13212(2003).
RN [6]
RP SUBCELLULAR LOCATION, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=16689936; DOI=10.1111/j.1742-4658.2006.05171.x;
RA Burri L., Vascotto K., Gentle I.E., Chan N.C., Beilharz T., Stapleton D.I.,
RA Ramage L., Lithgow T.;
RT "Integral membrane proteins in the mitochondrial outer membrane of
RT Saccharomyces cerevisiae.";
RL FEBS J. 273:1507-1515(2006).
RN [7]
RP SUBCELLULAR LOCATION, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=16407407; DOI=10.1091/mbc.e05-08-0740;
RA Zahedi R.P., Sickmann A., Boehm A.M., Winkler C., Zufall N.,
RA Schoenfisch B., Guiard B., Pfanner N., Meisinger C.;
RT "Proteomic analysis of the yeast mitochondrial outer membrane reveals
RT accumulation of a subclass of preproteins.";
RL Mol. Biol. Cell 17:1436-1450(2006).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-111, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ADR376;
RX PubMed=17330950; DOI=10.1021/pr060559j;
RA Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J.,
RA Elias J.E., Gygi S.P.;
RT "Large-scale phosphorylation analysis of alpha-factor-arrested
RT Saccharomyces cerevisiae.";
RL J. Proteome Res. 6:1190-1197(2007).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-111, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=17287358; DOI=10.1073/pnas.0607084104;
RA Chi A., Huttenhower C., Geer L.Y., Coon J.J., Syka J.E.P., Bai D.L.,
RA Shabanowitz J., Burke D.J., Troyanskaya O.G., Hunt D.F.;
RT "Analysis of phosphorylation sites on proteins from Saccharomyces
RT cerevisiae by electron transfer dissociation (ETD) mass spectrometry.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:2193-2198(2007).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-111, 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 [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-111, 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 [12]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=22633490; DOI=10.1016/j.molcel.2012.04.033;
RA Nakahara K., Ohkuni A., Kitamura T., Abe K., Naganuma T., Ohno Y.,
RA Zoeller R.A., Kihara A.;
RT "The Sjogren-Larsson syndrome gene encodes a hexadecenal dehydrogenase of
RT the sphingosine 1-phosphate degradation pathway.";
RL Mol. Cell 46:461-471(2012).
RN [13]
RP SUBCELLULAR LOCATION.
RX PubMed=24868093; DOI=10.1194/jlr.m050229;
RA Currie E., Guo X., Christiano R., Chitraju C., Kory N., Harrison K.,
RA Haas J., Walther T.C., Farese R.V. Jr.;
RT "High-confidence proteomic analysis of yeast lipid droplets identifies
RT additional droplet proteins and reveals connections to dolichol synthesis
RT and sterol acetylation.";
RL J. Lipid Res. 55:1465-1477(2014).
RN [14]
RP FUNCTION, CATALYTIC ACTIVITY, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP SER-241.
RX PubMed=27693056; DOI=10.1016/j.chembiol.2016.08.008;
RA Payet L.A., Leroux M., Willison J.C., Kihara A., Pelosi L., Pierrel F.;
RT "Mechanistic details of early steps in coenzyme Q biosynthesis pathway in
RT yeast.";
RL Cell Chem. Biol. 23:1241-1250(2016).
RN [15]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF CYS-273.
RX PubMed=27669165; DOI=10.1038/nbt.3683;
RA Stefely J.A., Kwiecien N.W., Freiberger E.C., Richards A.L., Jochem A.,
RA Rush M.J.P., Ulbrich A., Robinson K.P., Hutchins P.D., Veling M.T., Guo X.,
RA Kemmerer Z.A., Connors K.J., Trujillo E.A., Sokol J., Marx H.,
RA Westphall M.S., Hebert A.S., Pagliarini D.J., Coon J.J.;
RT "Mitochondrial protein functions elucidated by multi-omic mass spectrometry
RT profiling.";
RL Nat. Biotechnol. 34:1191-1197(2016).
CC -!- FUNCTION: Catalyzes the oxidation of long-chain aliphatic aldehydes to
CC fatty acids. Responsible for conversion of the sphingosine 1-phosphate
CC (S1P) degradation product hexadecenal to hexadecenoic acid
CC (PubMed:22633490). Involved in coenzyme Q (CoQ) biosynthesis,
CC catalyzing the last step in the tyrosine to 4-hydroxybenzoate (4-HB)
CC pathway. Oxidizes 4-hydroxybenzaldehyde (4-Hbz) to 4-HB, the aromatic
CC precursor for coenzyme Q (PubMed:27693056, PubMed:27669165).
CC {ECO:0000269|PubMed:22633490, ECO:0000269|PubMed:27669165,
CC ECO:0000269|PubMed:27693056}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an aldehyde + H2O + NAD(+) = a carboxylate + 2 H(+) + NADH;
CC Xref=Rhea:RHEA:16185, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17478, ChEBI:CHEBI:29067, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945; EC=1.2.1.3;
CC Evidence={ECO:0000269|PubMed:22633490};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 H(+) + hexadecanoate + NADH = H2O + hexadecanal + NAD(+);
CC Xref=Rhea:RHEA:33739, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17600, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945; Evidence={ECO:0000269|PubMed:22633490};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:33741;
CC Evidence={ECO:0000305|PubMed:22633490};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4-hydroxybenzaldehyde + H2O + NAD(+) = 4-hydroxybenzoate + 2
CC H(+) + NADH; Xref=Rhea:RHEA:20305, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17597, ChEBI:CHEBI:17879,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.2.1.64;
CC Evidence={ECO:0000269|PubMed:27669165, ECO:0000269|PubMed:27693056};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20306;
CC Evidence={ECO:0000305|PubMed:27669165, ECO:0000305|PubMed:27693056};
CC -!- SUBCELLULAR LOCATION: Lipid droplet {ECO:0000269|PubMed:24868093}.
CC Mitochondrion outer membrane {ECO:0000269|PubMed:14576278,
CC ECO:0000269|PubMed:16407407, ECO:0000269|PubMed:16689936}; Single-pass
CC membrane protein {ECO:0000255}. Endosome membrane
CC {ECO:0000269|PubMed:14562095}; Single-pass membrane protein
CC {ECO:0000255}. Cytoplasmic granule membrane {ECO:0000305}; Single-pass
CC membrane protein {ECO:0000255}.
CC -!- DISRUPTION PHENOTYPE: Results in coenzyme Q deficiency.
CC {ECO:0000269|PubMed:27693056}.
CC -!- MISCELLANEOUS: Present with 2930 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the aldehyde dehydrogenase family.
CC {ECO:0000305}.
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DR EMBL; Z49702; CAA89746.1; -; Genomic_DNA.
DR EMBL; BK006946; DAA10007.1; -; Genomic_DNA.
DR PIR; S54571; S54571.
DR RefSeq; NP_013828.1; NM_001182610.1.
DR AlphaFoldDB; Q04458; -.
DR SMR; Q04458; -.
DR BioGRID; 35286; 77.
DR DIP; DIP-4437N; -.
DR IntAct; Q04458; 8.
DR MINT; Q04458; -.
DR STRING; 4932.YMR110C; -.
DR SwissLipids; SLP:000000197; -.
DR SwissLipids; SLP:000000241; -.
DR iPTMnet; Q04458; -.
DR MaxQB; Q04458; -.
DR PaxDb; Q04458; -.
DR PRIDE; Q04458; -.
DR EnsemblFungi; YMR110C_mRNA; YMR110C; YMR110C.
DR GeneID; 855137; -.
DR KEGG; sce:YMR110C; -.
DR SGD; S000004716; HFD1.
DR VEuPathDB; FungiDB:YMR110C; -.
DR eggNOG; KOG2456; Eukaryota.
DR GeneTree; ENSGT00940000167857; -.
DR HOGENOM; CLU_005391_3_1_1; -.
DR InParanoid; Q04458; -.
DR OMA; RHGKRWM; -.
DR BioCyc; MetaCyc:G3O-32806-MON; -.
DR BioCyc; YEAST:G3O-32806-MON; -.
DR Reactome; R-SCE-1660661; Sphingolipid de novo biosynthesis.
DR Reactome; R-SCE-211945; Phase I - Functionalization of compounds.
DR Reactome; R-SCE-389599; Alpha-oxidation of phytanate.
DR Reactome; R-SCE-6798695; Neutrophil degranulation.
DR Reactome; R-SCE-9603798; Class I peroxisomal membrane protein import.
DR Reactome; R-SCE-9609523; Insertion of tail-anchored proteins into the endoplasmic reticulum membrane.
DR Reactome; R-SCE-9696273; RND1 GTPase cycle.
DR PRO; PR:Q04458; -.
DR Proteomes; UP000002311; Chromosome XIII.
DR RNAct; Q04458; protein.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; HDA:SGD.
DR GO; GO:0005768; C:endosome; HDA:SGD.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0031307; C:integral component of mitochondrial outer membrane; IDA:SGD.
DR GO; GO:0005811; C:lipid droplet; IDA:SGD.
DR GO; GO:0005741; C:mitochondrial outer membrane; HDA:SGD.
DR GO; GO:0005739; C:mitochondrion; HDA:SGD.
DR GO; GO:0018484; F:4-hydroxybenzaldehyde dehydrogenase activity; IMP:SGD.
DR GO; GO:0004029; F:aldehyde dehydrogenase (NAD+) activity; IBA:GO_Central.
DR GO; GO:0047770; F:carboxylate reductase activity; IMP:SGD.
DR GO; GO:0043878; F:glyceraldehyde-3-phosphate dehydrogenase (NAD+) (non-phosphorylating) activity; IEA:UniProtKB-EC.
DR GO; GO:0046185; P:aldehyde catabolic process; IMP:SGD.
DR GO; GO:0006081; P:cellular aldehyde metabolic process; IMP:SGD.
DR GO; GO:0006665; P:sphingolipid metabolic process; IMP:SGD.
DR GO; GO:0006744; P:ubiquinone biosynthetic process; IMP:SGD.
DR GO; GO:0032180; P:ubiquinone biosynthetic process from tyrosine; IMP:SGD.
DR Gene3D; 3.40.309.10; -; 1.
DR Gene3D; 3.40.605.10; -; 1.
DR InterPro; IPR016161; Ald_DH/histidinol_DH.
DR InterPro; IPR016163; Ald_DH_C.
DR InterPro; IPR029510; Ald_DH_CS_GLU.
DR InterPro; IPR016162; Ald_DH_N.
DR InterPro; IPR015590; Aldehyde_DH_dom.
DR InterPro; IPR012394; Aldehyde_DH_NAD(P).
DR PANTHER; PTHR43570; PTHR43570; 1.
DR Pfam; PF00171; Aldedh; 1.
DR PIRSF; PIRSF036492; ALDH; 1.
DR SUPFAM; SSF53720; SSF53720; 1.
DR PROSITE; PS00687; ALDEHYDE_DEHYDR_GLU; 1.
PE 1: Evidence at protein level;
KW Endosome; Lipid droplet; Membrane; Mitochondrion;
KW Mitochondrion outer membrane; NAD; Oxidoreductase; Phosphoprotein;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..532
FT /note="Fatty aldehyde dehydrogenase HFD1"
FT /id="PRO_0000056597"
FT TRANSMEM 134..152
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ACT_SITE 236
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10007"
FT ACT_SITE 273
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10007"
FT BINDING 214..219
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255"
FT MOD_RES 111
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17287358,
FT ECO:0007744|PubMed:17330950, ECO:0007744|PubMed:18407956,
FT ECO:0007744|PubMed:19779198"
FT MUTAGEN 241
FT /note="S->L: Causes Q deficiency."
FT /evidence="ECO:0000269|PubMed:27693056"
FT MUTAGEN 273
FT /note="C->S: Abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:27669165"
SQ SEQUENCE 532 AA; 59979 MW; 6CAF4BFCF963AF88 CRC64;
MSNDGSKILN YTPVSKIDEI VEISRNFFFE KQLKLSHENN PRKKDLEFRQ LQLKKLYYAV
KDHEEELIDA MYKDFHRNKI ESVLNETTKL MNDILHLIEI LPKLIKPRRV SDSSPPFMFG
KTIVEKISRG SVLIIAPFNF PLLLAFAPLA AALAAGNTIV LKPSELTPHT AVVMENLLTT
AGFPDGLIQV VQGAIDETTR LLDCGKFDLI FYTGSPRVGS IVAEKAAKSL TPCVLELGGK
SPTFITENFK ASNIKIALKR IFFGAFGNSG QICVSPDYLL VHKSIYPKVI KECESVLNEF
YPSFDEQTDF TRMIHEPAYK KAVASINSTN GSKIVPSKIS INSDTEDLCL VPPTIVYNIG
WDDPLMKQEN FAPVLPIIEY EDLDETINKI IEEHDTPLVQ YIFSDSQTEI NRILTRLRSG
DCVVGDTVIH VGITDAPFGG IGTSGYGNYG GYYGFNTFSH ERTIFKQPYW NDFTLFMRYP
PNSAQKEKLV RFAMERKPWF DRNGNNKWGL RQYFSLSAAV ILISTIYAHC SS
