ID   FAS2_CANPC              Reviewed;        1884 AA.
AC   G8BAW7;
DT   03-OCT-2012, integrated into UniProtKB/Swiss-Prot.
DT   25-JAN-2012, sequence version 1.
DT   03-AUG-2022, entry version 53.
DE   RecName: Full=Fatty acid synthase subunit alpha;
DE            EC=2.3.1.86;
DE   Includes:
DE     RecName: Full=Acyl carrier;
DE   Includes:
DE     RecName: Full=3-oxoacyl-[acyl-carrier-protein] reductase;
DE              EC=1.1.1.100;
DE     AltName: Full=Beta-ketoacyl reductase;
DE   Includes:
DE     RecName: Full=3-oxoacyl-[acyl-carrier-protein] synthase;
DE              EC=2.3.1.41;
DE     AltName: Full=Beta-ketoacyl synthase;
GN   Name=FAS2; OrderedLocusNames=CPAR2_807400;
OS   Candida parapsilosis (strain CDC 317 / ATCC MYA-4646) (Yeast) (Monilia
OS   parapsilosis).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC   Saccharomycetales; Debaryomycetaceae; Candida/Lodderomyces clade; Candida.
OX   NCBI_TaxID=578454;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=CDC 317 / ATCC MYA-4646;
RX   PubMed=19465905; DOI=10.1038/nature08064;
RA   Butler G., Rasmussen M.D., Lin M.F., Santos M.A.S., Sakthikumar S.,
RA   Munro C.A., Rheinbay E., Grabherr M., Forche A., Reedy J.L., Agrafioti I.,
RA   Arnaud M.B., Bates S., Brown A.J.P., Brunke S., Costanzo M.C.,
RA   Fitzpatrick D.A., de Groot P.W.J., Harris D., Hoyer L.L., Hube B.,
RA   Klis F.M., Kodira C., Lennard N., Logue M.E., Martin R., Neiman A.M.,
RA   Nikolaou E., Quail M.A., Quinn J., Santos M.C., Schmitzberger F.F.,
RA   Sherlock G., Shah P., Silverstein K.A.T., Skrzypek M.S., Soll D.,
RA   Staggs R., Stansfield I., Stumpf M.P.H., Sudbery P.E., Srikantha T.,
RA   Zeng Q., Berman J., Berriman M., Heitman J., Gow N.A.R., Lorenz M.C.,
RA   Birren B.W., Kellis M., Cuomo C.A.;
RT   "Evolution of pathogenicity and sexual reproduction in eight Candida
RT   genomes.";
RL   Nature 459:657-662(2009).
RN   [2]
RP   GENOME REANNOTATION.
RC   STRAIN=CDC 317 / ATCC MYA-4646;
RX   PubMed=22192698; DOI=10.1186/1471-2164-12-628;
RA   Guida A., Lindstaedt C., Maguire S.L., Ding C., Higgins D.G., Corton N.J.,
RA   Berriman M., Butler G.;
RT   "Using RNA-seq to determine the transcriptional landscape and the hypoxic
RT   response of the pathogenic yeast Candida parapsilosis.";
RL   BMC Genomics 12:628-628(2011).
RN   [3]
RP   INDUCTION BY HYPOXIA AND BIOFILM FORMATION.
RX   PubMed=19151323; DOI=10.1128/ec.00350-08;
RA   Rossignol T., Ding C., Guida A., d'Enfert C., Higgins D.G., Butler G.;
RT   "Correlation between biofilm formation and the hypoxic response in Candida
RT   parapsilosis.";
RL   Eukaryot. Cell 8:550-559(2009).
RN   [4]
RP   FUNCTION, INDUCTION BY CARBON SOURCES, AND DISRUPTION PHENOTYPE.
RX   PubMed=20027295; DOI=10.1371/journal.pone.0008421;
RA   Nguyen L.N., Trofa D., Nosanchuk J.D.;
RT   "Fatty acid synthase impacts the pathobiology of Candida parapsilosis in
RT   vitro and during mammalian infection.";
RL   PLoS ONE 4:E8421-E8421(2009).
CC   -!- FUNCTION: Fatty acid synthetase catalyzes the formation of long-chain
CC       fatty acids from acetyl-CoA, malonyl-CoA and NADPH. The alpha subunit
CC       contains domains for: acyl carrier protein, 3-oxoacyl-[acyl-carrier-
CC       protein] reductase, and 3-oxoacyl-[acyl-carrier-protein] synthase.
CC       {ECO:0000269|PubMed:20027295}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=acetyl-CoA + 2n H(+) + n malonyl-CoA + 2n NADPH = a long-chain
CC         fatty acyl-CoA + n CO2 + n CoA + H2O + 2n NADP(+);
CC         Xref=Rhea:RHEA:22896, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288,
CC         ChEBI:CHEBI:57384, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC         ChEBI:CHEBI:83139; EC=2.3.1.86;
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a fatty acyl-[ACP] + H(+) + malonyl-[ACP] = a 3-oxoacyl-[ACP]
CC         + CO2 + holo-[ACP]; Xref=Rhea:RHEA:22836, Rhea:RHEA-COMP:9623,
CC         Rhea:RHEA-COMP:9685, Rhea:RHEA-COMP:9916, Rhea:RHEA-COMP:14125,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:64479,
CC         ChEBI:CHEBI:78449, ChEBI:CHEBI:78776, ChEBI:CHEBI:138651;
CC         EC=2.3.1.41;
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a (3R)-hydroxyacyl-[ACP] + NADP(+) = a 3-oxoacyl-[ACP] + H(+)
CC         + NADPH; Xref=Rhea:RHEA:17397, Rhea:RHEA-COMP:9916, Rhea:RHEA-
CC         COMP:9945, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC         ChEBI:CHEBI:78776, ChEBI:CHEBI:78827; EC=1.1.1.100;
CC   -!- SUBUNIT: Fatty acid synthase is composed of alpha and beta subunits.
CC       {ECO:0000250}.
CC   -!- INDUCTION: Expression significantly elevated by the presence of
CC       glucose. Down-regulated by unsaturated fatty acids oleic acid and Tween
CC       80. Up-regulated during in vitro biofilm formation and hypoxic
CC       conditions. {ECO:0000269|PubMed:19151323, ECO:0000269|PubMed:20027295}.
CC   -!- DISRUPTION PHENOTYPE: Essential for growth in fatty acid-free medium,
CC       but dispensable in medium with fatty acids. The growth in the presence
CC       of fatty acid depends on the type. Able to grow in a concentration-
CC       dependent manner in the presence of myristic acid, palmitic acid, or
CC       Tween 80 as the fatty acid sources, but unable to grow in the presence
CC       of unsaturated fatty like acids stearic acid or oleic acid.
CC       Intracellular survival in the murine macrophage line J774.16 is
CC       significantly reduced compared to wild type or heterozygous fungal
CC       cells. Required for systemic infection in mice. Impaired in its
CC       capacity to form biofilms on polysterene and silicone surfaces.
CC       {ECO:0000269|PubMed:20027295}.
CC   -!- MISCELLANEOUS: It can potentially be a fungicidal target. Inhibition of
CC       FAS2 by cerulenin impeds the growth of wild-type and heterozygous
CC       strains (PubMed:20027295). {ECO:0000305|PubMed:20027295}.
CC   -!- SIMILARITY: Belongs to the thiolase-like superfamily. Fungal fatty acid
CC       synthetase subunit alpha family. {ECO:0000305}.
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DR   EMBL; HE605205; CCE42191.1; -; Genomic_DNA.
DR   AlphaFoldDB; G8BAW7; -.
DR   SMR; G8BAW7; -.
DR   STRING; 578454.G8BAW7; -.
DR   PRIDE; G8BAW7; -.
DR   EnsemblFungi; CCE42191; CCE42191; CPAR2_807400.
DR   CGD; CAL0000152877; FAS2.
DR   VEuPathDB; FungiDB:CPAR2_807400; -.
DR   eggNOG; ENOG502QQJX; Eukaryota.
DR   Proteomes; UP000005221; Chromosome 8.
DR   GO; GO:0005835; C:fatty acid synthase complex; IEA:EnsemblFungi.
DR   GO; GO:0004316; F:3-oxoacyl-[acyl-carrier-protein] reductase (NADPH) activity; IEA:UniProtKB-EC.
DR   GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:UniProtKB-EC.
DR   GO; GO:0004321; F:fatty-acyl-CoA synthase activity; IEA:UniProtKB-EC.
DR   GO; GO:0008897; F:holo-[acyl-carrier-protein] synthase activity; IEA:EnsemblFungi.
DR   GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR   GO; GO:0006633; P:fatty acid biosynthetic process; IMP:CGD.
DR   GO; GO:0042759; P:long-chain fatty acid biosynthetic process; IEA:EnsemblFungi.
DR   GO; GO:0044011; P:single-species biofilm formation on inanimate substrate; IMP:CGD.
DR   Gene3D; 3.40.47.10; -; 1.
DR   Gene3D; 3.90.470.20; -; 1.
DR   HAMAP; MF_00101; AcpS; 1.
DR   InterPro; IPR008278; 4-PPantetheinyl_Trfase_dom.
DR   InterPro; IPR037143; 4-PPantetheinyl_Trfase_dom_sf.
DR   InterPro; IPR002582; ACPS.
DR   InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR   InterPro; IPR040899; Fas_alpha_ACP.
DR   InterPro; IPR026025; FAS_alpha_yeast.
DR   InterPro; IPR041550; FASI_helical.
DR   InterPro; IPR018201; Ketoacyl_synth_AS.
DR   InterPro; IPR014031; Ketoacyl_synth_C.
DR   InterPro; IPR014030; Ketoacyl_synth_N.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   InterPro; IPR009081; PP-bd_ACP.
DR   InterPro; IPR004568; Ppantetheine-prot_Trfase_dom.
DR   InterPro; IPR002347; SDR_fam.
DR   InterPro; IPR016039; Thiolase-like.
DR   Pfam; PF01648; ACPS; 1.
DR   Pfam; PF00106; adh_short; 1.
DR   Pfam; PF18325; Fas_alpha_ACP; 1.
DR   Pfam; PF18314; FAS_I_H; 1.
DR   Pfam; PF00109; ketoacyl-synt; 1.
DR   Pfam; PF02801; Ketoacyl-synt_C; 1.
DR   PIRSF; PIRSF000454; FAS_yeast_alpha; 1.
DR   SUPFAM; SSF51735; SSF51735; 1.
DR   SUPFAM; SSF52151; SSF52151; 1.
DR   SUPFAM; SSF53901; SSF53901; 2.
DR   SUPFAM; SSF56214; SSF56214; 1.
DR   TIGRFAMs; TIGR00556; pantethn_trn; 1.
DR   PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR   PROSITE; PS50075; CARRIER; 1.
DR   PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE   2: Evidence at transcript level;
KW   Fatty acid biosynthesis; Fatty acid metabolism; Lipid biosynthesis;
KW   Lipid metabolism; Magnesium; Metal-binding; Multifunctional enzyme; NAD;
KW   NADP; Oxidoreductase; Phosphopantetheine; Phosphoprotein;
KW   Reference proteome; Transferase.
FT   CHAIN           1..1884
FT                   /note="Fatty acid synthase subunit alpha"
FT                   /id="PRO_0000419251"
FT   DOMAIN          147..222
FT                   /note="Carrier"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   REGION          91..141
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          583..613
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          677..873
FT                   /note="Beta-ketoacyl reductase"
FT                   /evidence="ECO:0000250"
FT   REGION          1147..1361
FT                   /note="Beta-ketoacyl synthase"
FT                   /evidence="ECO:0000250"
FT   COMPBIAS        583..604
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        1303
FT                   /note="For beta-ketoacyl synthase activity"
FT                   /evidence="ECO:0000250"
FT   BINDING         1770..1772
FT                   /ligand="acetyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57288"
FT                   /evidence="ECO:0000250"
FT   BINDING         1770
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250"
FT   BINDING         1771
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250"
FT   BINDING         1772
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250"
FT   BINDING         1796
FT                   /ligand="acetyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57288"
FT                   /evidence="ECO:0000250"
FT   BINDING         1806
FT                   /ligand="acetyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57288"
FT                   /evidence="ECO:0000250"
FT   BINDING         1815..1825
FT                   /ligand="acetyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57288"
FT                   /evidence="ECO:0000250"
FT   BINDING         1839..1842
FT                   /ligand="acetyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57288"
FT                   /evidence="ECO:0000250"
FT   BINDING         1869..1871
FT                   /ligand="acetyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57288"
FT                   /evidence="ECO:0000250"
FT   BINDING         1870
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250"
FT   BINDING         1871
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         182
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ   SEQUENCE   1884 AA;  206941 MW;  33DCED9F65C58282 CRC64;
     MKPEIEQELS HTLLTELLAY QFASPVRWIE TQDVFLKQHN TERVIEIGPS PTLAGMASRT
     IKAKYQSYDA ALSLQRQVLC YSKDAKEIYY TPDPAEPPAA EEPKAETGKE SAPAASAAAA
     AATQPAAAVA PPPQSAGPVE SIPDEPVKAS LLIHVLVAQK LKKPLDAVPM SKAIKDLVNG
     KSTVQNEILG DLGKEFGSTP EKPEETPLEE LAEQFQDTFS GSLGKTSTSL IGRLMSSKMP
     GGFSITNARK YLESRFGLGP GRQDSVLLTA LCNEPASRLG SEGDAKSFLD TMAQKYASHA
     GISLSSPSAG GASSGAGAAV VDSAALDALI AENKKLARQQ LETLARYLQV DLTKGEKAFI
     KEKEATTVLQ QELDLWEAEH GEFYAKGIKP VFSPLKSRTY DSYWNWARQD LLSMWFDILF
     GKLTSVDRET INQCIQIMNR ANPTLIKFMQ YHVELCPTYR GETYKLGKRL GEQLIENCKQ
     ILGQSPVYKD VSRITGPKTT VSAKGDIVYE EANKESVRKF EQYVFEMAQG GSMTKMKQSS
     IQEDLARVYK AISKQASRDS KLELQKVYDQ LLKVVEGSTE IETEQTTQDA LAIPTGSNTP
     TEEDELSTAS DDDEIASLPD KTSIAQPVSS TIPNKTIPFL HIQSKSESGN WEYDRKLSSI
     YLDGLESAAI NGLTFKDKYV LVTGAGAGSI GAEILQGLIS GGAKVIVTTS RYSKKVTEYY
     QNMYARYGAA GSTLIVVPFN QGSKQDVDAL VEYIYNDQKK GGLGWDLDVI IPFAAIPENG
     NGIDNIDSKS EFAHRIMLTN LLRLLGAVKA RKTTDTRPAQ CILPLSPNHG TFGFDGLYSE
     SKISLETLFN RWYSEDWGTK LTICGAIIGW TRGTGLMSAN NIIAEGIEKL GVRTFSQKEM
     AFNILGLLTP EIVNLCQEEP VMADLNGGLQ FIDNLKEFTS KLRNDLTETA DIRRAVSIES
     AIEQKVVNGD NVDSNYNKVT VRPRANMKFD FPTLKSYDEI KQIAPDLEGM LDLENVVVVT
     GFAEVGPWGN ARTRWEMESK GEFSLEGAIE MAWIMGMIKY HNGNLKGKPY SGWIDAKTQT
     PVDDKDIKAK YEEEILEHSG IRLIEPELFN GYDPKKKQMI QEVVIQHDLE PFECSKETAE
     QYKHEHGDKC EISEIEESGE YSVRILKGAT LFIPKALRFD RLVAGQIPTG WDARTYGIPE
     DTINQVDPIT LYVLVATVEA LLSAGITDPY EFYKYVHVSE VGNCSGSGMG GVSALRGMFK
     DRYADKPVQN DILQESFINT MSAWVNMLLL SASGPIKTPV GACATAVESV DIGIETILSG
     KAKVVMVGGY DDFQEEGSYE FANMNATSSA IDEFKHGRTP KEMSRPTTTT RNGFMEAQGS
     GIQVIMSADL ALKMGVPIHA VLAMSATATD KIGRSVPAPG KGILTTAREH HGNLKYPSPL
     LNVKYRKRQL SKRLDQIKSW ESSELNYLQE EAHLAKEEFG EEFSEAEFLR ERTEEIYRES
     KRQVADAKKQ WGNAFYKSDP RIAPLRGALA TFNLTIDDIG VASFHGTSTV ANDKNESATI
     DSMMKHLGRS EGNPVFGVFQ KYLTGHPKGA AGAWMLNGAI QILESGIVPG NRNADNVDKV
     LEQYEYVLYP SRSIQTDGIK AVSVTSFGFG QKGAQAVVVH PDYLYAVLDR STYEDYAKRV
     TARNKKTYRY MHNAITRNTM FVAKDKAPYS DELTMDVYLD PLARVSKTKN EFVFTKKSVQ
     SDKSYVSNIA NSTAKALSSL NKSSKGVGVD VELLSELNID NETFLERNFT PEEIKYCQNS
     ANPQASFTGT WSAKEATFKA LGVSSQGGGA SLKEIEIVRD GNGAPQVVLN DNAKAAAKAA
     GVKNVNVSIS HDDFQATAVA LSEF