CLD1_YEAST
ID CLD1_YEAST Reviewed; 445 AA.
AC P53264; D6VUP3;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Cardiolipin-specific deacylase 1, mitochondrial {ECO:0000305};
DE EC=3.5.1.- {ECO:0000269|PubMed:19244244, ECO:0000269|PubMed:24318983, ECO:0000269|PubMed:27982579};
DE Flags: Precursor;
GN Name=CLD1; OrderedLocusNames=YGR110W; ORFNames=G6140;
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=8905931;
RX DOI=10.1002/(sici)1097-0061(19960930)12:12<1273::aid-yea21>3.0.co;2-j;
RA Hansen M., Albers M., Backes U., Coblenz A., Leuther H., Neu R.,
RA Schreer A., Schaefer B., Zimmermann M., Wolf K.;
RT "The sequence of a 23.4 kb segment on the right arm of chromosome VII from
RT Saccharomyces cerevisiae reveals CLB6, SPT6, RP28A and NUP57 genes, a Ty3
RT element and 11 new open reading frames.";
RL Yeast 12:1273-1277(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169869;
RA Tettelin H., Agostoni-Carbone M.L., Albermann K., Albers M., Arroyo J.,
RA Backes U., Barreiros T., Bertani I., Bjourson A.J., Brueckner M.,
RA Bruschi C.V., Carignani G., Castagnoli L., Cerdan E., Clemente M.L.,
RA Coblenz A., Coglievina M., Coissac E., Defoor E., Del Bino S., Delius H.,
RA Delneri D., de Wergifosse P., Dujon B., Durand P., Entian K.-D., Eraso P.,
RA Escribano V., Fabiani L., Fartmann B., Feroli F., Feuermann M.,
RA Frontali L., Garcia-Gonzalez M., Garcia-Saez M.I., Goffeau A.,
RA Guerreiro P., Hani J., Hansen M., Hebling U., Hernandez K., Heumann K.,
RA Hilger F., Hofmann B., Indge K.J., James C.M., Klima R., Koetter P.,
RA Kramer B., Kramer W., Lauquin G., Leuther H., Louis E.J., Maillier E.,
RA Marconi A., Martegani E., Mazon M.J., Mazzoni C., McReynolds A.D.K.,
RA Melchioretto P., Mewes H.-W., Minenkova O., Mueller-Auer S., Nawrocki A.,
RA Netter P., Neu R., Nombela C., Oliver S.G., Panzeri L., Paoluzi S.,
RA Plevani P., Portetelle D., Portillo F., Potier S., Purnelle B., Rieger M.,
RA Riles L., Rinaldi T., Robben J., Rodrigues-Pousada C.,
RA Rodriguez-Belmonte E., Rodriguez-Torres A.M., Rose M., Ruzzi M.,
RA Saliola M., Sanchez-Perez M., Schaefer B., Schaefer M., Scharfe M.,
RA Schmidheini T., Schreer A., Skala J., Souciet J.-L., Steensma H.Y.,
RA Talla E., Thierry A., Vandenbol M., van der Aart Q.J.M., Van Dyck L.,
RA Vanoni M., Verhasselt P., Voet M., Volckaert G., Wambutt R., Watson M.D.,
RA Weber N., Wedler E., Wedler H., Wipfli P., Wolf K., Wright L.F.,
RA Zaccaria P., Zimmermann M., Zollner A., Kleine K.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome VII.";
RL Nature 387:81-84(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 INDUCTION.
RX PubMed=10601195; DOI=10.1128/jb.181.24.7409-7413.1999;
RA ter Linde J.J.M., Liang H., Davis R.W., Steensma H.Y., van Dijken J.P.,
RA Pronk J.T.;
RT "Genome-wide transcriptional analysis of aerobic and anaerobic chemostat
RT cultures of Saccharomyces cerevisiae.";
RL J. Bacteriol. 181:7409-7413(1999).
RN [6]
RP INDUCTION.
RX PubMed=15878181; DOI=10.1016/j.mrfmmm.2005.02.005;
RA Caba E., Dickinson D.A., Warnes G.R., Aubrecht J.;
RT "Differentiating mechanisms of toxicity using global gene expression
RT analysis in Saccharomyces cerevisiae.";
RL Mutat. Res. 575:34-46(2005).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND DOMAIN.
RX PubMed=19244244; DOI=10.1074/jbc.m805511200;
RA Beranek A., Rechberger G., Knauer H., Wolinski H., Kohlwein S.D., Leber R.;
RT "Identification of a cardiolipin-specific phospholipase encoded by the gene
RT CLD1 (YGR110W) in yeast.";
RL J. Biol. Chem. 284:11572-11578(2009).
RN [8]
RP FUNCTION, ACTIVE SITE, SUBUNIT, SUBCELLULAR LOCATION, TOPOLOGY, AND
RP MUTAGENESIS OF SER-230; ASP-392; HIS-424 AND ASP-429.
RX PubMed=23637464; DOI=10.1091/mbc.e13-03-0121;
RA Baile M.G., Whited K., Claypool S.M.;
RT "Deacylation on the matrix side of the mitochondrial inner membrane
RT regulates cardiolipin remodeling.";
RL Mol. Biol. Cell 24:2008-2020(2013).
RN [9]
RP INDUCTION.
RX PubMed=24318983; DOI=10.1074/jbc.m113.529487;
RA Ye C., Lou W., Li Y., Chatzispyrou I.A., Huettemann M., Lee I.,
RA Houtkooper R.H., Vaz F.M., Chen S., Greenberg M.L.;
RT "Deletion of the cardiolipin-specific phospholipase Cld1 rescues growth and
RT life span defects in the tafazzin mutant: implications for Barth
RT syndrome.";
RL J. Biol. Chem. 289:3114-3125(2014).
RN [10]
RP CATALYTIC ACTIVITY, AND MUTAGENESIS OF TRP-170.
RX PubMed=27603010; DOI=10.1371/journal.pone.0162165;
RA Kar A., Beam H., Borror M.B., Luckow M., Gao X., Rea S.L.;
RT "CLD1 reverses the ubiquinone insufficiency of mutant cat5/coq7 in a
RT Saccharomyces cerevisiae model system.";
RL PLoS ONE 11:e0162165-e0162165(2016).
RN [11]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=27982579; DOI=10.1021/acschembio.6b00995;
RA Tyurina Y.Y., Lou W., Qu F., Tyurin V.A., Mohammadyani D., Liu J.,
RA Huettemann M., Frasso M.A., Wipf P., Bayir H., Greenberg M.L., Kagan V.E.;
RT "Lipidomics characterization of biosynthetic and remodeling pathways of
RT cardiolipins in genetically and nutritionally manipulated yeast cells.";
RL ACS Chem. Biol. 12:265-281(2017).
RN [12]
RP FUNCTION.
RX PubMed=29935382; DOI=10.1016/j.bbalip.2018.06.016;
RA Lou W., Ting H.C., Reynolds C.A., Tyurina Y.Y., Tyurin V.A., Li Y., Ji J.,
RA Yu W., Liang Z., Stoyanovsky D.A., Anthonymuthu T.S., Frasso M.A., Wipf P.,
RA Greenberger J.S., Bayir H., Kagan V.E., Greenberg M.L.;
RT "Genetic re-engineering of polyunsaturated phospholipid profile of
RT Saccharomyces cerevisiae identifies a novel role for Cld1 in mitigating the
RT effects of cardiolipin peroxidation.";
RL Biochim. Biophys. Acta 1863:1354-1368(2018).
CC -!- FUNCTION: Mitochondrial cardiolipin-specific phospholipase which
CC deacylates de novo synthesized cardiolipin (CL). Part of the remodeling
CC process of cardiolipin, which involves deacylation-reacylation of
CC premature cardiolipin. Has a strong substrate preference for palmitic
CC acid residues and generates monolysocardiolipin (MLCL) for TAZ1-
CC dependent reacylation with unsaturated fatty acids (PubMed:19244244,
CC PubMed:23637464). The hydrolytic selectivity of the enzyme toward C16-
CC CL substrates contributes to the preservation of C18:1-containing CL
CC species (PubMed:27982579). Has high specificity towards peroxidized
CC cardiolipids CL(OX). Required to mitigate oxidative stress by removing
CC CL(OX) (PubMed:29935382). {ECO:0000269|PubMed:19244244,
CC ECO:0000269|PubMed:23637464, ECO:0000269|PubMed:27982579,
CC ECO:0000269|PubMed:29935382}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a cardiolipin + H2O = 1'-[1,2-diacyl-sn-glycero-3-phospho],3'-
CC [1-acyl-sn-glycero-3-phospho]-glycerol + a fatty acid + H(+);
CC Xref=Rhea:RHEA:32935, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:28868, ChEBI:CHEBI:62237, ChEBI:CHEBI:64743;
CC Evidence={ECO:0000269|PubMed:19244244, ECO:0000269|PubMed:24318983,
CC ECO:0000269|PubMed:27982579};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:32936;
CC Evidence={ECO:0000305|PubMed:19244244, ECO:0000305|PubMed:24318983,
CC ECO:0000305|PubMed:27982579};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:23637464}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:19244244}.
CC Mitochondrion inner membrane {ECO:0000269|PubMed:23637464}; Peripheral
CC membrane protein {ECO:0000269|PubMed:23637464}; Matrix side
CC {ECO:0000269|PubMed:23637464}.
CC -!- INDUCTION: Expressed in aerobic conditions and under genotoxic stress
CC (PubMed:10601195, PubMed:15878181). Expression is increased during
CC respiratory growth and regulated by the heme activator protein
CC transcriptional activation complex (PubMed:24318983).
CC {ECO:0000269|PubMed:10601195, ECO:0000269|PubMed:15878181,
CC ECO:0000269|PubMed:24318983}.
CC -!- DOMAIN: The HXXXXD motif is essential for acyltransferase activity.
CC {ECO:0000305|PubMed:19244244}.
CC -!- SIMILARITY: Belongs to the peptidase S33 family. ABHD4/ABHD5 subfamily.
CC {ECO:0000305}.
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DR EMBL; Z72895; CAA97118.1; -; Genomic_DNA.
DR EMBL; AY692593; AAT92612.1; -; Genomic_DNA.
DR EMBL; BK006941; DAA08204.1; -; Genomic_DNA.
DR PIR; S64418; S64418.
DR RefSeq; NP_011625.3; NM_001181239.3.
DR AlphaFoldDB; P53264; -.
DR BioGRID; 33357; 23.
DR DIP; DIP-5605N; -.
DR IntAct; P53264; 1.
DR STRING; 4932.YGR110W; -.
DR SwissLipids; SLP:000000063; -.
DR ESTHER; yeast-cld1; CGI-58_ABHD5_ABHD4.
DR MaxQB; P53264; -.
DR PaxDb; P53264; -.
DR PRIDE; P53264; -.
DR EnsemblFungi; YGR110W_mRNA; YGR110W; YGR110W.
DR GeneID; 853007; -.
DR KEGG; sce:YGR110W; -.
DR SGD; S000003342; CLD1.
DR VEuPathDB; FungiDB:YGR110W; -.
DR eggNOG; KOG4409; Eukaryota.
DR GeneTree; ENSGT00940000176535; -.
DR HOGENOM; CLU_017361_3_1_1; -.
DR InParanoid; P53264; -.
DR OMA; DWMDPEG; -.
DR BioCyc; YEAST:G3O-30819-MON; -.
DR Reactome; R-SCE-1482839; Acyl chain remodelling of PE.
DR PRO; PR:P53264; -.
DR Proteomes; UP000002311; Chromosome VII.
DR RNAct; P53264; protein.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:SGD.
DR GO; GO:0005739; C:mitochondrion; IDA:SGD.
DR GO; GO:0052689; F:carboxylic ester hydrolase activity; IBA:GO_Central.
DR GO; GO:0042171; F:lysophosphatidic acid acyltransferase activity; IBA:GO_Central.
DR GO; GO:0004623; F:phospholipase A2 activity; IDA:SGD.
DR GO; GO:0035965; P:cardiolipin acyl-chain remodeling; IMP:SGD.
DR GO; GO:0032048; P:cardiolipin metabolic process; IDA:SGD.
DR GO; GO:0055088; P:lipid homeostasis; IBA:GO_Central.
DR GO; GO:0006654; P:phosphatidic acid biosynthetic process; IBA:GO_Central.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR000073; AB_hydrolase_1.
DR Pfam; PF00561; Abhydrolase_1; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
PE 1: Evidence at protein level;
KW Hydrolase; Membrane; Mitochondrion; Mitochondrion inner membrane;
KW Reference proteome; Transferase; Transit peptide.
FT TRANSIT 1..39
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 40..445
FT /note="Cardiolipin-specific deacylase 1, mitochondrial"
FT /id="PRO_0000202813"
FT DOMAIN 142..430
FT /note="AB hydrolase-1"
FT /evidence="ECO:0000255"
FT REGION 20..41
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 228..232
FT /note="GXSXG lipase motif"
FT /evidence="ECO:0000305|PubMed:19244244"
FT MOTIF 424..429
FT /note="HXXXXD acyl transferase motif"
FT /evidence="ECO:0000305|PubMed:19244244"
FT COMPBIAS 21..38
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 230
FT /note="Nucleophile"
FT /evidence="ECO:0000269|PubMed:23637464"
FT ACT_SITE 392
FT /note="Charge relay system"
FT /evidence="ECO:0000269|PubMed:23637464"
FT ACT_SITE 424
FT /note="Charge relay system"
FT /evidence="ECO:0000269|PubMed:23637464"
FT MUTAGEN 170
FT /note="W->R: Loss of function."
FT /evidence="ECO:0000269|PubMed:24318983"
FT MUTAGEN 230
FT /note="S->A: Abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:23637464"
FT MUTAGEN 392
FT /note="D->A: Abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:23637464"
FT MUTAGEN 424
FT /note="H->A: Abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:23637464"
FT MUTAGEN 429
FT /note="D->A: No effect."
FT /evidence="ECO:0000269|PubMed:23637464"
SQ SEQUENCE 445 AA; 52045 MW; 000A5A7A42A188C9 CRC64;
MFKSTLNSII RRPLKGFQLL RGADSSNTRP QSPRASARDV TEKQILRTPS APTAIPLREI
IYRVPSLFPR PLEDSVKDFR DFIKNEDAFQ TELLKTLPFY PTPSESKTAR LIRTVVDDEG
NYINEFCIRP RKTSVPEADL KHLVFIHGYG AGLGFFIKNF EDIPLLDNEW CIHAIDLPGY
GFSSRPKFPF EYPRDNIHSV QDWFHERIHT WFSKRNLLNR PEKNIVMAHS LGSYLMALYL
QKYKESPSFK KLILCSPAGV SYRDFNNTAS EVEKWKPPPW WYVKLWDRNI SPFTLVRNFR
QLGSKITSGW SYRRFKHILN GDPEQSKRFE ALHRYAYAIF NKRGSGEYLL SFALKCGGEP
RLSLEQQLFD GKKSDILKNS NCDWLWLYGD DDWMDVNGGL RVSRFLKEKL KQKSNVIIVP
HSGHHLYLDN YKFFNNILTK EMQKI
