FOX2_CANTR
ID FOX2_CANTR Reviewed; 906 AA.
AC P22414;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 2.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=Peroxisomal hydratase-dehydrogenase-epimerase;
DE Short=HDE;
DE AltName: Full=Multifunctional beta-oxidation protein;
DE Short=MFP;
DE Includes:
DE RecName: Full=2-enoyl-CoA hydratase;
DE EC=4.2.1.119;
DE Includes:
DE RecName: Full=(3R)-3-hydroxyacyl-CoA dehydrogenase;
DE EC=1.1.1.n12;
OS Candida tropicalis (Yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Debaryomycetaceae; Candida/Lodderomyces clade; Candida.
OX NCBI_TaxID=5482;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=ATCC 20336 / pK233 / NCYC 997;
RX PubMed=3267241; DOI=10.1016/0378-1119(88)90428-3;
RA Nuttley W.M., Aitchison J.D., Rachubinski R.A.;
RT "cDNA cloning and primary structure determination of the peroxisomal
RT trifunctional enzyme hydratase-dehydrogenase-epimerase from the yeast
RT Candida tropicalis pK233.";
RL Gene 69:171-180(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 20336 / pK233 / NCYC 997;
RX PubMed=1937002; DOI=10.1016/0378-1119(91)90524-f;
RA Aitchison J.D., Sloots J.A., Nuttley W.M., Rachubinski R.A.;
RT "Glucose-responsive and oleic acid-responsive elements in the gene encoding
RT the peroxisomal trifunctional enzyme of Candida tropicalis.";
RL Gene 105:129-134(1991).
RN [3]
RP SIMILARITY TO SHORT CHAIN DEHYDROGENASES OF N-TERMINAL DOMAIN.
RX PubMed=2394320; DOI=10.1096/fasebj.4.12.2394320;
RA Baker M.E.;
RT "A common ancestor for Candida tropicalis and dehydrogenases that
RT synthesize antibiotics and steroids.";
RL FASEB J. 4:3028-3032(1990).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 628-906 OF APOENZYME AND IN
RP COMPLEX WITH SUBSTRATE, AND REACTION MECHANISM.
RX PubMed=15051722; DOI=10.1074/jbc.m400293200;
RA Koski M.K., Haapalainen A.M., Hiltunen J.K., Glumoff T.;
RT "A two-domain structure of one subunit explains unique features of
RT eukaryotic hydratase 2.";
RL J. Biol. Chem. 279:24666-24672(2004).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.22 ANGSTROMS) OF 1-604.
RX PubMed=16574148; DOI=10.1016/j.jmb.2006.03.001;
RA Ylianttila M.S., Pursiainen N.V., Haapalainen A.M., Juffer A.H.,
RA Poirier Y., Hiltunen J.K., Glumoff T.;
RT "Crystal structure of yeast peroxisomal multifunctional enzyme: structural
RT basis for substrate specificity of (3R)-hydroxyacyl-CoA dehydrogenase
RT units.";
RL J. Mol. Biol. 358:1286-1295(2006).
CC -!- FUNCTION: Second trifunctional enzyme acting on the beta-oxidation
CC pathway for fatty acids, possessing hydratase-dehydrogenase-epimerase
CC activities. Converts trans-2-enoyl-CoA via D-3-hydroxyacyl-CoA to 3-
CC ketoacyl-CoA.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a (3R)-3-hydroxyacyl-CoA = a (2E)-enoyl-CoA + H2O;
CC Xref=Rhea:RHEA:26526, ChEBI:CHEBI:15377, ChEBI:CHEBI:57319,
CC ChEBI:CHEBI:58856; EC=4.2.1.119;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a (3R)-3-hydroxyacyl-CoA + NAD(+) = a 3-oxoacyl-CoA + H(+) +
CC NADH; Xref=Rhea:RHEA:32711, ChEBI:CHEBI:15378, ChEBI:CHEBI:57319,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:90726;
CC EC=1.1.1.n12;
CC -!- PATHWAY: Lipid metabolism; fatty acid beta-oxidation.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:15051722}.
CC -!- SUBCELLULAR LOCATION: Peroxisome.
CC -!- INDUCTION: By growth on N-alkanes or fatty acids.
CC -!- DOMAIN: Contains two SDR domains.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; M22765; AAA62847.1; -; mRNA.
DR EMBL; X57854; CAA40989.1; -; Genomic_DNA.
DR PIR; S32607; S32607.
DR PDB; 1PN2; X-ray; 1.95 A; A/B/C/D=627-906.
DR PDB; 1PN4; X-ray; 2.35 A; A/B/C/D=627-906.
DR PDB; 2ET6; X-ray; 2.22 A; A=1-604.
DR PDBsum; 1PN2; -.
DR PDBsum; 1PN4; -.
DR PDBsum; 2ET6; -.
DR AlphaFoldDB; P22414; -.
DR SMR; P22414; -.
DR VEuPathDB; FungiDB:CTMYA2_054890; -.
DR VEuPathDB; FungiDB:CTRG_05506; -.
DR BRENDA; 4.2.1.119; 1146.
DR UniPathway; UPA00659; -.
DR EvolutionaryTrace; P22414; -.
DR GO; GO:0005777; C:peroxisome; IEA:UniProtKB-SubCell.
DR GO; GO:0106386; F:(3R)-hydroxyacyl-CoA dehydrogenase (NAD) activity; IEA:RHEA.
DR GO; GO:0003857; F:3-hydroxyacyl-CoA dehydrogenase activity; IEA:EnsemblFungi.
DR GO; GO:0004300; F:enoyl-CoA hydratase activity; IEA:EnsemblFungi.
DR GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
DR GO; GO:0006635; P:fatty acid beta-oxidation; IEA:UniProtKB-UniPathway.
DR InterPro; IPR029069; HotDog_dom_sf.
DR InterPro; IPR002539; MaoC-like_dom.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR InterPro; IPR002347; SDR_fam.
DR Pfam; PF00106; adh_short; 2.
DR Pfam; PF01575; MaoC_dehydratas; 1.
DR PRINTS; PR00081; GDHRDH.
DR PRINTS; PR00080; SDRFAMILY.
DR SUPFAM; SSF51735; SSF51735; 2.
DR SUPFAM; SSF54637; SSF54637; 2.
DR PROSITE; PS00061; ADH_SHORT; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Fatty acid metabolism; Isomerase; Lipid metabolism; Lyase;
KW Multifunctional enzyme; NAD; Oxidoreductase; Peroxisome; Repeat.
FT CHAIN 1..906
FT /note="Peroxisomal hydratase-dehydrogenase-epimerase"
FT /id="PRO_0000054698"
FT DOMAIN 782..893
FT /note="MaoC-like"
FT REGION 5..228
FT /note="Short-chain dehydrogenase like 1"
FT REGION 319..532
FT /note="Short-chain dehydrogenase like 2"
FT REGION 600..633
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 904..906
FT /note="Microbody targeting signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 602..633
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 163
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT ACT_SITE 467
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 12..36
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 20
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 39
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 74..75
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 98
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 150
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 163..167
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 195..198
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 326..350
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT BINDING 454
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:15051722"
FT BINDING 699..700
FT /ligand="(3R)-3-hydroxydecanoyl-CoA"
FT /ligand_id="ChEBI:CHEBI:74272"
FT BINDING 729
FT /ligand="(3R)-3-hydroxydecanoyl-CoA"
FT /ligand_id="ChEBI:CHEBI:74272"
FT BINDING 808..813
FT /ligand="(3R)-3-hydroxydecanoyl-CoA"
FT /ligand_id="ChEBI:CHEBI:74272"
FT BINDING 831
FT /ligand="(3R)-3-hydroxydecanoyl-CoA"
FT /ligand_id="ChEBI:CHEBI:74272"
FT BINDING 856
FT /ligand="(3R)-3-hydroxydecanoyl-CoA"
FT /ligand_id="ChEBI:CHEBI:74272"
FT CONFLICT 540
FT /note="F -> S (in Ref. 1; AAA62847)"
FT /evidence="ECO:0000305"
FT STRAND 10..13
FT /evidence="ECO:0007829|PDB:2ET6"
FT TURN 14..17
FT /evidence="ECO:0007829|PDB:2ET6"
FT HELIX 19..30
FT /evidence="ECO:0007829|PDB:2ET6"
FT STRAND 34..38
FT /evidence="ECO:0007829|PDB:2ET6"
FT HELIX 53..63
FT /evidence="ECO:0007829|PDB:2ET6"
FT STRAND 67..71
FT /evidence="ECO:0007829|PDB:2ET6"
FT HELIX 78..89
FT /evidence="ECO:0007829|PDB:2ET6"
FT STRAND 94..97
FT /evidence="ECO:0007829|PDB:2ET6"
FT TURN 107..109
FT /evidence="ECO:0007829|PDB:2ET6"
FT HELIX 112..122
FT /evidence="ECO:0007829|PDB:2ET6"
FT HELIX 124..140
FT /evidence="ECO:0007829|PDB:2ET6"
FT STRAND 143..148
FT /evidence="ECO:0007829|PDB:2ET6"
FT HELIX 151..155
FT /evidence="ECO:0007829|PDB:2ET6"
FT HELIX 161..181
FT /evidence="ECO:0007829|PDB:2ET6"
FT HELIX 182..184
FT /evidence="ECO:0007829|PDB:2ET6"
FT STRAND 186..193
FT /evidence="ECO:0007829|PDB:2ET6"
FT HELIX 198..201
FT /evidence="ECO:0007829|PDB:2ET6"
FT HELIX 206..209
FT /evidence="ECO:0007829|PDB:2ET6"
FT HELIX 214..224
FT /evidence="ECO:0007829|PDB:2ET6"
FT STRAND 226..228
FT /evidence="ECO:0007829|PDB:2ET6"
FT STRAND 235..239
FT /evidence="ECO:0007829|PDB:2ET6"
FT STRAND 242..250
FT /evidence="ECO:0007829|PDB:2ET6"
FT HELIX 264..274
FT /evidence="ECO:0007829|PDB:2ET6"
FT HELIX 284..286
FT /evidence="ECO:0007829|PDB:2ET6"
FT STRAND 292..294
FT /evidence="ECO:0007829|PDB:2ET6"
FT HELIX 297..304
FT /evidence="ECO:0007829|PDB:2ET6"
FT STRAND 324..329
FT /evidence="ECO:0007829|PDB:2ET6"
FT HELIX 333..344
FT /evidence="ECO:0007829|PDB:2ET6"
FT STRAND 348..352
FT /evidence="ECO:0007829|PDB:2ET6"
FT HELIX 358..366
FT /evidence="ECO:0007829|PDB:2ET6"
FT STRAND 370..374
FT /evidence="ECO:0007829|PDB:2ET6"
FT HELIX 378..393
FT /evidence="ECO:0007829|PDB:2ET6"
FT STRAND 398..401
FT /evidence="ECO:0007829|PDB:2ET6"
FT TURN 411..413
FT /evidence="ECO:0007829|PDB:2ET6"
FT HELIX 416..426
FT /evidence="ECO:0007829|PDB:2ET6"
FT HELIX 428..443
FT /evidence="ECO:0007829|PDB:2ET6"
FT STRAND 447..452
FT /evidence="ECO:0007829|PDB:2ET6"
FT HELIX 455..458
FT /evidence="ECO:0007829|PDB:2ET6"
FT HELIX 465..485
FT /evidence="ECO:0007829|PDB:2ET6"
FT HELIX 486..488
FT /evidence="ECO:0007829|PDB:2ET6"
FT STRAND 490..497
FT /evidence="ECO:0007829|PDB:2ET6"
FT HELIX 518..520
FT /evidence="ECO:0007829|PDB:2ET6"
FT HELIX 522..527
FT /evidence="ECO:0007829|PDB:2ET6"
FT STRAND 539..543
FT /evidence="ECO:0007829|PDB:2ET6"
FT STRAND 546..554
FT /evidence="ECO:0007829|PDB:2ET6"
FT STRAND 562..564
FT /evidence="ECO:0007829|PDB:2ET6"
FT HELIX 567..577
FT /evidence="ECO:0007829|PDB:2ET6"
FT STRAND 581..583
FT /evidence="ECO:0007829|PDB:2ET6"
FT HELIX 590..602
FT /evidence="ECO:0007829|PDB:2ET6"
FT STRAND 632..635
FT /evidence="ECO:0007829|PDB:1PN2"
FT HELIX 637..646
FT /evidence="ECO:0007829|PDB:1PN2"
FT HELIX 651..653
FT /evidence="ECO:0007829|PDB:1PN4"
FT HELIX 654..657
FT /evidence="ECO:0007829|PDB:1PN2"
FT HELIX 668..675
FT /evidence="ECO:0007829|PDB:1PN2"
FT HELIX 679..682
FT /evidence="ECO:0007829|PDB:1PN2"
FT TURN 683..687
FT /evidence="ECO:0007829|PDB:1PN2"
FT STRAND 688..691
FT /evidence="ECO:0007829|PDB:1PN2"
FT HELIX 694..696
FT /evidence="ECO:0007829|PDB:1PN2"
FT STRAND 697..706
FT /evidence="ECO:0007829|PDB:1PN2"
FT STRAND 708..710
FT /evidence="ECO:0007829|PDB:1PN2"
FT STRAND 713..729
FT /evidence="ECO:0007829|PDB:1PN2"
FT STRAND 732..743
FT /evidence="ECO:0007829|PDB:1PN2"
FT TURN 744..746
FT /evidence="ECO:0007829|PDB:1PN2"
FT STRAND 749..759
FT /evidence="ECO:0007829|PDB:1PN2"
FT HELIX 774..777
FT /evidence="ECO:0007829|PDB:1PN2"
FT STRAND 788..794
FT /evidence="ECO:0007829|PDB:1PN2"
FT HELIX 799..803
FT /evidence="ECO:0007829|PDB:1PN2"
FT HELIX 804..806
FT /evidence="ECO:0007829|PDB:1PN2"
FT HELIX 811..813
FT /evidence="ECO:0007829|PDB:1PN2"
FT HELIX 816..821
FT /evidence="ECO:0007829|PDB:1PN2"
FT HELIX 831..846
FT /evidence="ECO:0007829|PDB:1PN2"
FT STRAND 849..856
FT /evidence="ECO:0007829|PDB:1PN2"
FT STRAND 865..872
FT /evidence="ECO:0007829|PDB:1PN2"
FT STRAND 874..884
FT /evidence="ECO:0007829|PDB:1PN2"
FT TURN 885..888
FT /evidence="ECO:0007829|PDB:1PN2"
FT STRAND 889..899
FT /evidence="ECO:0007829|PDB:1PN2"
SQ SEQUENCE 906 AA; 99469 MW; 65AB88C8671C967B CRC64;
MSPVDFKDKV VIITGAGGGL GKYYSLEFAK LGAKVVVNDL GGALNGQGGN SKAADVVVDE
IVKNGGVAVA DYNNVLDGDK IVETAVKNFG TVHVIINNAG ILRDASMKKM TEKDYKLVID
VHLNGAFAVT KAAWPYFQKQ KYGRIVNTSS PAGLYGNFGQ ANYASAKSAL LGFAETLAKE
GAKYNIKANA IAPLARSRMT ESILPPPMLE KLGPEKVAPL VLYLSSAENE LTGQFFEVAA
GFYAQIRWER SGGVLFKPDQ SFTAEVVAKR FSEILDYDDS RKPEYLKNQY PFMLNDYATL
TNEARKLPAN DASGAPTVSL KDKVVLITGA GAGLGKEYAK WFAKYGAKVV VNDFKDATKT
VDEIKAAGGE AWPDQHDVAK DSEAIIKNVI DKYGTIDILV NNAGILRDRS FAKMSKQEWD
SVQQVHLIGT FNLSRLAWPY FVEKQFGRII NITSTSGIYG NFGQANYSSS KAGILGLSKT
MAIEGAKNNI KVNIVAPHAE TAMTLTIFRE QDKNLYHADQ VAPLLVYLGT DDVPVTGETF
EIGGGWIGNT RWQRAKGAVS HDEHTTVEFI KEHLNEITDF TTDTENPKST TESSMAILSA
VGGDDDDDDE DEEEDEGDEE EDEEDEEEDD PVWRFDDRDV ILYNIALGAT TKQLKYVYEN
DSDFQVIPTF GHLITFNSGK SQNSFAKLLR NFNPMLLLHG EHYLKVHSWP PPTEGEIKTT
FEPIATTPKG TNVVIVHGSK SVDNKSGELI YSNEATYFIR NCQADNKVYA DRPAFATNQF
LAPKRAPDYQ VDVPVSEDLA ALYRLSGDRN PLHIDPNFAK GAKFPKPILH GMCTYGLSAK
ALIDKFGMFN EIKARFTGIV FPGETLRVLA WKESDDTIVF QTHVVDRGTI AINNAAIKLV
GDKAKI
