DHB4_HUMAN
ID DHB4_HUMAN Reviewed; 736 AA.
AC P51659; B4DNV1; B4DVS5; E9PB82; F5HE57;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 219.
DE RecName: Full=Peroxisomal multifunctional enzyme type 2 {ECO:0000305};
DE Short=MFE-2 {ECO:0000303|PubMed:10671535};
DE AltName: Full=17-beta-hydroxysteroid dehydrogenase 4;
DE Short=17-beta-HSD 4;
DE AltName: Full=D-bifunctional protein {ECO:0000303|PubMed:15060085};
DE Short=DBP {ECO:0000303|PubMed:15060085};
DE AltName: Full=Multifunctional protein 2;
DE Short=MFP-2;
DE AltName: Full=Short chain dehydrogenase/reductase family 8C member 1;
DE Contains:
DE RecName: Full=(3R)-hydroxyacyl-CoA dehydrogenase;
DE EC=1.1.1.n12 {ECO:0000269|PubMed:9089413};
DE Contains:
DE RecName: Full=Enoyl-CoA hydratase 2;
DE EC=4.2.1.107 {ECO:0000269|PubMed:9482850};
DE EC=4.2.1.119 {ECO:0000269|PubMed:9089413};
DE AltName: Full=3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholest-24-enoyl-CoA hydratase;
GN Name=HSD17B4 {ECO:0000312|HGNC:HGNC:5213}; Synonyms=EDH17B4, SDR8C1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Liver;
RX PubMed=7487879; DOI=10.1042/bj3110437;
RA Adamski J., Normand T., Leenders F., Monte D., Begue A., Stehelin D.,
RA Jungblut P.W., de Launoit Y.;
RT "Molecular cloning of a novel widely expressed human 80 kDa 17 beta-
RT hydroxysteroid dehydrogenase IV.";
RL Biochem. J. 311:437-443(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 69-77; 81-90;
RP 261-270; 291-310; 312-339; 413-426; 451-459; 478-488 AND 590-631, FUNCTION,
RP CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=9089413; DOI=10.1093/oxfordjournals.jbchem.a021596;
RA Jiang L.L., Miyazawa S., Souri M., Hashimoto T.;
RT "Structure of D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA
RT dehydrogenase bifunctional protein.";
RL J. Biochem. 121:364-369(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9880674; DOI=10.1007/s003359900921;
RA Leenders F., Dolez V., Begue A., Moller G., Gloeckner J.C., de Launoit Y.,
RA Adamski J.;
RT "Structure of the gene for the human 17beta-hydroxysteroid dehydrogenase
RT type IV.";
RL Mamm. Genome 9:1036-1041(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3), AND VARIANTS
RP HIS-106 AND VAL-559.
RC TISSUE=Lung, and Spleen;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP FUNCTION, AND SUBUNIT.
RX PubMed=8902629; DOI=10.1093/oxfordjournals.jbchem.a021458;
RA Jiang L.L., Kobayashi A., Matsuura H., Fukushima H., Hashimoto T.;
RT "Purification and properties of human D-3-hydroxyacyl-CoA dehydratase:
RT medium-chain enoyl-CoA hydratase is D-3-hydroxyacyl-CoA dehydratase.";
RL J. Biochem. 120:624-632(1996).
RN [8]
RP MUTAGENESIS OF TYR-347; GLU-366; ASP-370; HIS-406; GLU-408; TYR-410;
RP ASP-490; TYR-505; ASP-510; HIS-515; ASP-517 AND HIS-532, CHARACTERIZATION
RP OF VARIANT DBPD SER-16, AND CATALYTIC ACTIVITY.
RX PubMed=10671535; DOI=10.1074/jbc.275.7.4965;
RA Qin Y.M., Haapalainen A.M., Kilpelainen S.H., Marttila M.S., Koski M.K.,
RA Glumoff T., Novikov D.K., Hiltunen J.K.;
RT "Human peroxisomal multifunctional enzyme type 2. Site-directed mutagenesis
RT studies show the importance of two protic residues for 2-enoyl-CoA
RT hydratase 2 activity.";
RL J. Biol. Chem. 275:4965-4972(2000).
RN [9]
RP CATALYTIC ACTIVITY.
RX PubMed=10706581;
RA Ferdinandusse S., Denis S., van Berkel E., Dacremont G., Wanders R.J.;
RT "Peroxisomal fatty acid oxidation disorders and 58 kDa sterol carrier
RT protein X (SCPx). Activity measurements in liver and fibroblasts using a
RT newly developed method.";
RL J. Lipid Res. 41:336-342(2000).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=15060085; DOI=10.1194/jlr.m300512-jlr200;
RA Ferdinandusse S., Denis S., Van Roermund C.W., Wanders R.J., Dacremont G.;
RT "Identification of the peroxisomal beta-oxidation enzymes involved in the
RT degradation of long-chain dicarboxylic acids.";
RL J. Lipid Res. 45:1104-1111(2004).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-304 AND SER-309, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [13]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-565; LYS-669 AND LYS-707, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-265, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-52, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 618-736 IN COMPLEX WITH LIGAND.
RX PubMed=11700068; DOI=10.1006/jmbi.2001.5084;
RA Haapalainen A.M., van Aalten D.M., Merilaeinen G., Jalonen J.E.,
RA Pirilae P., Wierenga R.K., Hiltunen J.K., Glumoff T.;
RT "Crystal structure of the liganded SCP-2-like domain of human peroxisomal
RT multifunctional enzyme type 2 at 1.75 A resolution.";
RL J. Mol. Biol. 313:1127-1138(2001).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 320-614.
RX PubMed=15644212; DOI=10.1016/j.jmb.2004.11.009;
RA Koski K.M., Haapalainen A.M., Hiltunen J.K., Glumoff T.;
RT "Crystal structure of 2-enoyl-CoA hydratase 2 from human peroxisomal
RT multifunctional enzyme type 2.";
RL J. Mol. Biol. 345:1157-1169(2005).
RN [20]
RP VARIANT DBPD SER-16, CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=9482850; DOI=10.1073/pnas.95.5.2128;
RA van Grunsven E.G., van Berkel E., Ijlst L., Vreken P., de Klerk J.B.C.,
RA Adamski J., Lemonde H., Clayton P.T., Cuebas D.A., Wanders R.J.A.;
RT "Peroxisomal D-hydroxyacyl-CoA dehydrogenase deficiency: resolution of the
RT enzyme defect and its molecular basis in bifunctional protein deficiency.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:2128-2133(1998).
RN [21]
RP VARIANT DBPD TYR-457, AND VARIANT ARG-511.
RX PubMed=10400999; DOI=10.1093/hmg/8.8.1509;
RA van Grunsven E.G., Mooijer P.A., Aubourg P., Wanders R.J.;
RT "Enoyl-CoA hydratase deficiency: identification of a new type of D-
RT bifunctional protein deficiency.";
RL Hum. Mol. Genet. 8:1509-1516(1999).
RN [22]
RP VARIANT DBPD PRO-106.
RX PubMed=11743515; DOI=10.1067/mpd.2001.119170;
RA Nakano K., Zhang Z., Shimozawa N., Kondo N., Ishii N., Funatsuka M.,
RA Shirakawa S., Itoh M., Takashima S., Une M., Kana-aki R.R., Mukai K.,
RA Osawa M., Suzuki Y.;
RT "D-bifunctional protein deficiency with fetal ascites, polyhydramnios, and
RT contractures of hands and toes.";
RL J. Pediatr. 139:865-867(2001).
RN [23]
RP VARIANT PRLTS1 CYS-217.
RX PubMed=20673864; DOI=10.1016/j.ajhg.2010.07.007;
RA Pierce S.B., Walsh T., Chisholm K.M., Lee M.K., Thornton A.M., Fiumara A.,
RA Opitz J.M., Levy-Lahad E., Klevit R.E., King M.C.;
RT "Mutations in the DBP-deficiency protein HSD17B4 cause ovarian dysgenesis,
RT hearing loss, and ataxia of Perrault Syndrome.";
RL Am. J. Hum. Genet. 87:282-288(2010).
RN [24]
RP VARIANTS HIS-106 AND VAL-559.
RX PubMed=25956234; DOI=10.1016/j.jns.2015.04.038;
RA Ahmed S., Jelani M., Alrayes N., Mohamoud H.S., Almramhi M.M., Anshasi W.,
RA Ahmed N.A., Wang J., Nasir J., Al-Aama J.Y.;
RT "Exome analysis identified a novel missense mutation in the CLPP gene in a
RT consanguineous Saudi family expanding the clinical spectrum of Perrault
RT Syndrome type-3.";
RL J. Neurol. Sci. 353:149-154(2015).
CC -!- FUNCTION: Bifunctional enzyme acting on the peroxisomal beta-oxidation
CC pathway for fatty acids. Catalyzes the formation of 3-ketoacyl-CoA
CC intermediates from straight-chain, 2-methyl-branched-chain fatty acids
CC bile acid intermediates. With EHHADH, catalyzes the hydration of trans-
CC 2-enoyl-CoA and the dehydrogenation of 3-hydroxyacyl-CoA, but with
CC opposite chiral specificity (PubMed:10671535).
CC {ECO:0000269|PubMed:10671535, ECO:0000269|PubMed:15060085,
CC ECO:0000269|PubMed:8902629, ECO:0000269|PubMed:9089413}.
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; Evidence={ECO:0000269|PubMed:9089413};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:32712;
CC Evidence={ECO:0000305|PubMed:15060085};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(24R,25R)-3alpha,7alpha,12alpha,24-tetrahydroxy-5beta-
CC cholestan-26-oyl-CoA = (24E)-3alpha,7alpha,12alpha-trihydroxy-5beta-
CC cholest-24-en-26-oyl-CoA + H2O; Xref=Rhea:RHEA:18933,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:59807, ChEBI:CHEBI:59879;
CC EC=4.2.1.107; Evidence={ECO:0000269|PubMed:10706581,
CC ECO:0000269|PubMed:9482850};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:18935;
CC Evidence={ECO:0000269|PubMed:10706581, ECO:0000269|PubMed:9482850};
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 Evidence={ECO:0000269|PubMed:9089413};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:26527;
CC Evidence={ECO:0000305|PubMed:15060085};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E)-octenoyl-CoA + H2O = (3R)-hydroxyoctanoyl-CoA;
CC Xref=Rhea:RHEA:40187, ChEBI:CHEBI:15377, ChEBI:CHEBI:62242,
CC ChEBI:CHEBI:74279; Evidence={ECO:0000269|PubMed:9089413};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40188;
CC Evidence={ECO:0000269|PubMed:9089413};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3R)-hydroxyoctanoyl-CoA + NAD(+) = 3-oxooctanoyl-CoA + H(+) +
CC NADH; Xref=Rhea:RHEA:40191, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:62619, ChEBI:CHEBI:74279;
CC Evidence={ECO:0000269|PubMed:9089413};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40192;
CC Evidence={ECO:0000269|PubMed:9089413};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3R)-hydroxyhexadecanoyl-CoA + NAD(+) = 3-oxohexadecanoyl-CoA
CC + H(+) + NADH; Xref=Rhea:RHEA:40243, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57349, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:74278; Evidence={ECO:0000269|PubMed:15060085};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40244;
CC Evidence={ECO:0000269|PubMed:15060085};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E)-hexadecenedioyl-CoA + H2O = (3R)-hydroxyhexadecanedioyl-
CC CoA; Xref=Rhea:RHEA:40255, ChEBI:CHEBI:15377, ChEBI:CHEBI:77075,
CC ChEBI:CHEBI:77079; Evidence={ECO:0000269|PubMed:15060085};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40256;
CC Evidence={ECO:0000269|PubMed:15060085};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3R)-hydroxyhexadecanedioyl-CoA + NAD(+) = 3-
CC oxohexadecanedioyl-CoA + H(+) + NADH; Xref=Rhea:RHEA:40263,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:77079, ChEBI:CHEBI:77081;
CC Evidence={ECO:0000269|PubMed:15060085};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40264;
CC Evidence={ECO:0000269|PubMed:15060085};
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:15060085};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:39161;
CC Evidence={ECO:0000269|PubMed:15060085};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3R)-3-hydroxydecanoyl-CoA = (2E)-decenoyl-CoA + H2O;
CC Xref=Rhea:RHEA:45992, ChEBI:CHEBI:15377, ChEBI:CHEBI:61406,
CC ChEBI:CHEBI:74272; Evidence={ECO:0000269|PubMed:10671535};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:45994;
CC Evidence={ECO:0000269|PubMed:10671535};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3R)-3-hydroxydecanoyl-CoA + NAD(+) = 3-oxodecanoyl-CoA + H(+)
CC + NADH; Xref=Rhea:RHEA:45832, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:62548, ChEBI:CHEBI:74272;
CC Evidence={ECO:0000269|PubMed:10671535};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45833;
CC Evidence={ECO:0000269|PubMed:10671535};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(24R,25R)-3alpha,7alpha,12alpha,24-tetrahydroxy-5beta-
CC cholestan-26-oyl-CoA + NAD(+) = 3alpha,7alpha,12alpha-trihydroxy-24-
CC oxo-5beta-cholestan-26-oyl-CoA + H(+) + NADH; Xref=Rhea:RHEA:47088,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:58507, ChEBI:CHEBI:59807;
CC Evidence={ECO:0000269|PubMed:10706581, ECO:0000269|PubMed:9482850};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47089;
CC Evidence={ECO:0000269|PubMed:10706581, ECO:0000269|PubMed:9482850};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=10 uM for D-3-hydroxy-octanoyl-CoA {ECO:0000269|PubMed:9089413};
CC KM=13 uM for NAD {ECO:0000269|PubMed:9089413};
CC KM=2.7 uM for 3-ketooctanoyl-CoA {ECO:0000269|PubMed:9089413};
CC KM=5.4 uM for NADH {ECO:0000269|PubMed:9089413};
CC KM=0.9 uM for (3S)-hydroxyhexadecanedioyl-CoA
CC {ECO:0000269|PubMed:15060085};
CC KM=12.8 uM for (3S)-hydroxyhexadecanoyl-CoA
CC {ECO:0000269|PubMed:15060085};
CC Vmax=8.8 umol/min/mg enzyme {ECO:0000269|PubMed:9089413};
CC -!- PATHWAY: Lipid metabolism; fatty acid beta-oxidation.
CC {ECO:0000269|PubMed:10706581, ECO:0000269|PubMed:15060085,
CC ECO:0000269|PubMed:9089413, ECO:0000269|PubMed:9482850}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:11700068,
CC ECO:0000269|PubMed:8902629}.
CC -!- SUBCELLULAR LOCATION: Peroxisome {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P51659-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P51659-2; Sequence=VSP_046152;
CC Name=3;
CC IsoId=P51659-3; Sequence=VSP_046153;
CC -!- TISSUE SPECIFICITY: Present in many tissues with highest concentrations
CC in liver, heart, prostate and testis.
CC -!- DISEASE: D-bifunctional protein deficiency (DBPD) [MIM:261515]:
CC Disorder of peroxisomal fatty acid beta-oxidation.
CC {ECO:0000269|PubMed:10400999, ECO:0000269|PubMed:10671535,
CC ECO:0000269|PubMed:11743515, ECO:0000269|PubMed:9482850}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Perrault syndrome 1 (PRLTS1) [MIM:233400]: A sex-influenced
CC disorder characterized by sensorineural deafness in both males and
CC females and ovarian dysgenesis in females. Some patients also have
CC neurologic manifestations, including mild intellectual disability and
CC cerebellar and peripheral nervous system involvement.
CC {ECO:0000269|PubMed:20673864}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: The protein is found both as a full-length peptide and
CC in a cleaved version.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
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DR EMBL; X87176; CAA60643.1; -; mRNA.
DR EMBL; AF057740; AAD08652.1; -; Genomic_DNA.
DR EMBL; AF057720; AAD08652.1; JOINED; Genomic_DNA.
DR EMBL; AF057721; AAD08652.1; JOINED; Genomic_DNA.
DR EMBL; AF057722; AAD08652.1; JOINED; Genomic_DNA.
DR EMBL; AF057723; AAD08652.1; JOINED; Genomic_DNA.
DR EMBL; AF057724; AAD08652.1; JOINED; Genomic_DNA.
DR EMBL; AF057725; AAD08652.1; JOINED; Genomic_DNA.
DR EMBL; AF057726; AAD08652.1; JOINED; Genomic_DNA.
DR EMBL; AF057727; AAD08652.1; JOINED; Genomic_DNA.
DR EMBL; AF057728; AAD08652.1; JOINED; Genomic_DNA.
DR EMBL; AF057729; AAD08652.1; JOINED; Genomic_DNA.
DR EMBL; AF057730; AAD08652.1; JOINED; Genomic_DNA.
DR EMBL; AF057731; AAD08652.1; JOINED; Genomic_DNA.
DR EMBL; AF057732; AAD08652.1; JOINED; Genomic_DNA.
DR EMBL; AF057733; AAD08652.1; JOINED; Genomic_DNA.
DR EMBL; AF057734; AAD08652.1; JOINED; Genomic_DNA.
DR EMBL; AF057735; AAD08652.1; JOINED; Genomic_DNA.
DR EMBL; AF057736; AAD08652.1; JOINED; Genomic_DNA.
DR EMBL; AF057737; AAD08652.1; JOINED; Genomic_DNA.
DR EMBL; AF057738; AAD08652.1; JOINED; Genomic_DNA.
DR EMBL; AF057739; AAD08652.1; JOINED; Genomic_DNA.
DR EMBL; AK298075; BAG60363.1; -; mRNA.
DR EMBL; AK301212; BAG62787.1; -; mRNA.
DR EMBL; AC024564; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC003098; AAH03098.1; -; mRNA.
DR CCDS; CCDS4126.1; -. [P51659-1]
DR CCDS; CCDS56378.1; -. [P51659-3]
DR CCDS; CCDS56379.1; -. [P51659-2]
DR PIR; S59136; S59136.
DR RefSeq; NP_000405.1; NM_000414.3. [P51659-1]
DR RefSeq; NP_001186220.1; NM_001199291.2. [P51659-2]
DR RefSeq; NP_001186221.1; NM_001199292.1. [P51659-3]
DR RefSeq; NP_001278956.1; NM_001292027.1.
DR RefSeq; NP_001278957.1; NM_001292028.1.
DR PDB; 1IKT; X-ray; 1.75 A; A=618-736.
DR PDB; 1S9C; X-ray; 3.00 A; A/B/C/D/E/F/G/H/I/J/K/L=318-615.
DR PDB; 1ZBQ; X-ray; 2.71 A; A/B/C/D/E/F=1-304.
DR PDB; 6Z1W; X-ray; 2.48 A; A=618-736.
DR PDB; 6Z1X; X-ray; 2.09 A; A=618-736.
DR PDBsum; 1IKT; -.
DR PDBsum; 1S9C; -.
DR PDBsum; 1ZBQ; -.
DR PDBsum; 6Z1W; -.
DR PDBsum; 6Z1X; -.
DR AlphaFoldDB; P51659; -.
DR SASBDB; P51659; -.
DR SMR; P51659; -.
DR BioGRID; 109528; 144.
DR IntAct; P51659; 54.
DR MINT; P51659; -.
DR STRING; 9606.ENSP00000420914; -.
DR ChEMBL; CHEMBL5814; -.
DR DrugBank; DB03192; (R)-3-hydroxydecanoyl-CoA.
DR DrugBank; DB00157; NADH.
DR SwissLipids; SLP:000000540; -.
DR GlyGen; P51659; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P51659; -.
DR PhosphoSitePlus; P51659; -.
DR SwissPalm; P51659; -.
DR BioMuta; HSD17B4; -.
DR DMDM; 1706396; -.
DR CPTAC; CPTAC-389; -.
DR CPTAC; CPTAC-390; -.
DR EPD; P51659; -.
DR jPOST; P51659; -.
DR MassIVE; P51659; -.
DR MaxQB; P51659; -.
DR PaxDb; P51659; -.
DR PeptideAtlas; P51659; -.
DR PRIDE; P51659; -.
DR ProteomicsDB; 19165; -.
DR ProteomicsDB; 27834; -.
DR ProteomicsDB; 56360; -. [P51659-1]
DR TopDownProteomics; P51659-1; -. [P51659-1]
DR Antibodypedia; 13742; 422 antibodies from 34 providers.
DR DNASU; 3295; -.
DR Ensembl; ENST00000414835.7; ENSP00000411960.3; ENSG00000133835.18. [P51659-2]
DR Ensembl; ENST00000510025.7; ENSP00000424940.3; ENSG00000133835.18. [P51659-1]
DR Ensembl; ENST00000515320.5; ENSP00000424613.1; ENSG00000133835.18. [P51659-3]
DR GeneID; 3295; -.
DR KEGG; hsa:3295; -.
DR MANE-Select; ENST00000510025.7; ENSP00000424940.3; NM_000414.4; NP_000405.1.
DR UCSC; uc003ksj.4; human. [P51659-1]
DR CTD; 3295; -.
DR DisGeNET; 3295; -.
DR GeneCards; HSD17B4; -.
DR GeneReviews; HSD17B4; -.
DR HGNC; HGNC:5213; HSD17B4.
DR HPA; ENSG00000133835; Tissue enhanced (liver).
DR MalaCards; HSD17B4; -.
DR MIM; 233400; phenotype.
DR MIM; 261515; phenotype.
DR MIM; 601860; gene.
DR neXtProt; NX_P51659; -.
DR OpenTargets; ENSG00000133835; -.
DR Orphanet; 300; Bifunctional enzyme deficiency.
DR Orphanet; 2855; Perrault syndrome.
DR PharmGKB; PA29481; -.
DR VEuPathDB; HostDB:ENSG00000133835; -.
DR eggNOG; KOG1206; Eukaryota.
DR GeneTree; ENSGT00940000158343; -.
DR HOGENOM; CLU_010194_18_4_1; -.
DR InParanoid; P51659; -.
DR OMA; LITEMWK; -.
DR PhylomeDB; P51659; -.
DR TreeFam; TF105656; -.
DR BioCyc; MetaCyc:HS05792-MON; -.
DR BRENDA; 4.2.1.119; 2681.
DR PathwayCommons; P51659; -.
DR Reactome; R-HSA-193368; Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol.
DR Reactome; R-HSA-2046106; alpha-linolenic acid (ALA) metabolism.
DR Reactome; R-HSA-389887; Beta-oxidation of pristanoyl-CoA.
DR Reactome; R-HSA-390247; Beta-oxidation of very long chain fatty acids.
DR Reactome; R-HSA-9033241; Peroxisomal protein import.
DR Reactome; R-HSA-9033500; TYSND1 cleaves peroxisomal proteins.
DR SABIO-RK; P51659; -.
DR SignaLink; P51659; -.
DR UniPathway; UPA00659; -.
DR BioGRID-ORCS; 3295; 47 hits in 1087 CRISPR screens.
DR ChiTaRS; HSD17B4; human.
DR EvolutionaryTrace; P51659; -.
DR GeneWiki; HSD17B4; -.
DR GenomeRNAi; 3295; -.
DR Pharos; P51659; Tbio.
DR PRO; PR:P51659; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; P51659; protein.
DR Bgee; ENSG00000133835; Expressed in right lobe of thyroid gland and 201 other tissues.
DR ExpressionAtlas; P51659; baseline and differential.
DR Genevisible; P51659; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005782; C:peroxisomal matrix; TAS:Reactome.
DR GO; GO:0005778; C:peroxisomal membrane; HDA:UniProtKB.
DR GO; GO:0005777; C:peroxisome; IDA:UniProtKB.
DR GO; GO:0106386; F:(3R)-hydroxyacyl-CoA dehydrogenase (NAD) activity; IEA:RHEA.
DR GO; GO:0044594; F:17-beta-hydroxysteroid dehydrogenase (NAD+) activity; IDA:UniProtKB.
DR GO; GO:0003857; F:3-hydroxyacyl-CoA dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0033989; F:3alpha,7alpha,12alpha-trihydroxy-5beta-cholest-24-enoyl-CoA hydratase activity; IEA:UniProtKB-EC.
DR GO; GO:0004300; F:enoyl-CoA hydratase activity; IDA:UniProtKB.
DR GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
DR GO; GO:0016508; F:long-chain-enoyl-CoA hydratase activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0008209; P:androgen metabolic process; IDA:UniProtKB.
DR GO; GO:0008210; P:estrogen metabolic process; IDA:UniProtKB.
DR GO; GO:0006635; P:fatty acid beta-oxidation; IDA:UniProtKB.
DR GO; GO:0036112; P:medium-chain fatty-acyl-CoA metabolic process; IDA:UniProtKB.
DR GO; GO:0001649; P:osteoblast differentiation; HDA:UniProtKB.
DR GO; GO:0060009; P:Sertoli cell development; IEA:Ensembl.
DR GO; GO:0000038; P:very long-chain fatty acid metabolic process; IEA:Ensembl.
DR GO; GO:0036111; P:very long-chain fatty-acyl-CoA metabolic process; IDA:UniProtKB.
DR Gene3D; 3.30.1050.10; -; 1.
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; IPR003033; SCP2_sterol-bd_dom.
DR InterPro; IPR036527; SCP2_sterol-bd_dom_sf.
DR InterPro; IPR002347; SDR_fam.
DR Pfam; PF00106; adh_short; 1.
DR Pfam; PF01575; MaoC_dehydratas; 1.
DR Pfam; PF02036; SCP2; 1.
DR PRINTS; PR00081; GDHRDH.
DR PRINTS; PR00080; SDRFAMILY.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF54637; SSF54637; 2.
DR SUPFAM; SSF55718; SSF55718; 1.
DR PROSITE; PS00061; ADH_SHORT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Deafness;
KW Direct protein sequencing; Disease variant; Fatty acid metabolism;
KW Isomerase; Lipid metabolism; Lyase; NAD; Oxidoreductase; Peroxisome;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..736
FT /note="Peroxisomal multifunctional enzyme type 2"
FT /id="PRO_0000054583"
FT CHAIN 1..311
FT /note="(3R)-hydroxyacyl-CoA dehydrogenase"
FT /id="PRO_0000400082"
FT CHAIN 312..736
FT /note="Enoyl-CoA hydratase 2"
FT /id="PRO_0000400083"
FT DOMAIN 484..600
FT /note="MaoC-like"
FT DOMAIN 624..736
FT /note="SCP2"
FT REGION 1..305
FT /note="(3R)-hydroxyacyl-CoA dehydrogenase"
FT REGION 322..622
FT /note="Enoyl-CoA hydratase 2"
FT MOTIF 734..736
FT /note="Microbody targeting signal"
FT /evidence="ECO:0000255"
FT ACT_SITE 164
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 13..37
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 21
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT BINDING 40
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT BINDING 75..76
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT BINDING 99
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT BINDING 151
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 164..168
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT BINDING 196..199
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT BINDING 406..407
FT /ligand="(3R)-3-hydroxydecanoyl-CoA"
FT /ligand_id="ChEBI:CHEBI:74272"
FT /evidence="ECO:0000250"
FT BINDING 435
FT /ligand="(3R)-3-hydroxydecanoyl-CoA"
FT /ligand_id="ChEBI:CHEBI:74272"
FT /evidence="ECO:0000250"
FT BINDING 510..515
FT /ligand="(3R)-3-hydroxydecanoyl-CoA"
FT /ligand_id="ChEBI:CHEBI:74272"
FT /evidence="ECO:0000250"
FT BINDING 533
FT /ligand="(3R)-3-hydroxydecanoyl-CoA"
FT /ligand_id="ChEBI:CHEBI:74272"
FT /evidence="ECO:0000250"
FT BINDING 563
FT /ligand="(3R)-3-hydroxydecanoyl-CoA"
FT /ligand_id="ChEBI:CHEBI:74272"
FT /evidence="ECO:0000250"
FT BINDING 706
FT /ligand="substrate"
FT BINDING 724
FT /ligand="substrate"
FT MOD_RES 46
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P51660"
FT MOD_RES 46
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P51660"
FT MOD_RES 52
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 57
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P51660"
FT MOD_RES 68
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P51660"
FT MOD_RES 84
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P51660"
FT MOD_RES 265
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 275
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P51660"
FT MOD_RES 304
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 309
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 356
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P51660"
FT MOD_RES 424
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P51660"
FT MOD_RES 565
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 579
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P51660"
FT MOD_RES 663
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P51660"
FT MOD_RES 669
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 707
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 725
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P51660"
FT VAR_SEQ 1..38
FT /note="MGSPLRFDGRVVLVTGAGAGLGRAYALAFAERGALVVV -> MVILEAPHLL
FT RRKEPETPGLSSRIGPSLCPGFCRKRSVSCCFQNLCNNPMEKIISQCRFFVSM (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_046152"
FT VAR_SEQ 20..37
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_046153"
FT VARIANT 16
FT /note="G -> S (in DBPD; no dehydrogenase activity;
FT dbSNP:rs137853096)"
FT /evidence="ECO:0000269|PubMed:10671535,
FT ECO:0000269|PubMed:9482850"
FT /id="VAR_037576"
FT VARIANT 90
FT /note="F -> L (in dbSNP:rs28943588)"
FT /id="VAR_052309"
FT VARIANT 106
FT /note="R -> H (in dbSNP:rs25640)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:25956234"
FT /id="VAR_014872"
FT VARIANT 106
FT /note="R -> P (in DBPD; dbSNP:rs25640)"
FT /evidence="ECO:0000269|PubMed:11743515"
FT /id="VAR_065906"
FT VARIANT 140
FT /note="K -> N (in dbSNP:rs28943589)"
FT /id="VAR_052310"
FT VARIANT 217
FT /note="Y -> C (in PRLTS1; dbSNP:rs387906825)"
FT /evidence="ECO:0000269|PubMed:20673864"
FT /id="VAR_065907"
FT VARIANT 292
FT /note="T -> S (in dbSNP:rs1143650)"
FT /id="VAR_024625"
FT VARIANT 427
FT /note="A -> V (in dbSNP:rs28943590)"
FT /id="VAR_052311"
FT VARIANT 457
FT /note="N -> Y (in DBPD; the mutation leads to an unstable
FT protein; dbSNP:rs137853097)"
FT /evidence="ECO:0000269|PubMed:10400999"
FT /id="VAR_065908"
FT VARIANT 491
FT /note="A -> T (in dbSNP:rs28943591)"
FT /id="VAR_052312"
FT VARIANT 511
FT /note="W -> R (in dbSNP:rs11539471)"
FT /evidence="ECO:0000269|PubMed:10400999"
FT /id="VAR_014873"
FT VARIANT 559
FT /note="I -> V (in dbSNP:rs11205)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:25956234"
FT /id="VAR_014874"
FT VARIANT 606
FT /note="A -> S (in dbSNP:rs15228)"
FT /id="VAR_052313"
FT VARIANT 687
FT /note="T -> I (in dbSNP:rs28943592)"
FT /id="VAR_052314"
FT VARIANT 728
FT /note="M -> V (in dbSNP:rs28943594)"
FT /id="VAR_052315"
FT MUTAGEN 347
FT /note="Y->A: No hydratase activity."
FT /evidence="ECO:0000269|PubMed:10671535"
FT MUTAGEN 366
FT /note="E->A: No hydratase activity."
FT /evidence="ECO:0000269|PubMed:10671535"
FT MUTAGEN 370
FT /note="D->A: No effect."
FT /evidence="ECO:0000269|PubMed:10671535"
FT MUTAGEN 406
FT /note="H->A: No effect."
FT /evidence="ECO:0000269|PubMed:10671535"
FT MUTAGEN 408
FT /note="E->A: No effect."
FT /evidence="ECO:0000269|PubMed:10671535"
FT MUTAGEN 410
FT /note="Y->A: No effect."
FT /evidence="ECO:0000269|PubMed:10671535"
FT MUTAGEN 490
FT /note="D->A: No effect."
FT /evidence="ECO:0000269|PubMed:10671535"
FT MUTAGEN 505
FT /note="Y->A: Completely inactive."
FT /evidence="ECO:0000269|PubMed:10671535"
FT MUTAGEN 510
FT /note="D->A: No hydratase activity."
FT /evidence="ECO:0000269|PubMed:10671535"
FT MUTAGEN 515
FT /note="H->A: Completely inactive."
FT /evidence="ECO:0000269|PubMed:10671535"
FT MUTAGEN 517
FT /note="D->A: No effect."
FT /evidence="ECO:0000269|PubMed:10671535"
FT MUTAGEN 532
FT /note="H->A: No effect."
FT /evidence="ECO:0000269|PubMed:10671535"
FT CONFLICT 587
FT /note="Q -> R (in Ref. 4; BAG60363)"
FT /evidence="ECO:0000305"
FT STRAND 11..14
FT /evidence="ECO:0007829|PDB:1ZBQ"
FT TURN 15..18
FT /evidence="ECO:0007829|PDB:1ZBQ"
FT HELIX 20..31
FT /evidence="ECO:0007829|PDB:1ZBQ"
FT STRAND 35..39
FT /evidence="ECO:0007829|PDB:1ZBQ"
FT HELIX 53..64
FT /evidence="ECO:0007829|PDB:1ZBQ"
FT STRAND 68..72
FT /evidence="ECO:0007829|PDB:1ZBQ"
FT HELIX 76..78
FT /evidence="ECO:0007829|PDB:1ZBQ"
FT HELIX 79..90
FT /evidence="ECO:0007829|PDB:1ZBQ"
FT STRAND 95..98
FT /evidence="ECO:0007829|PDB:1ZBQ"
FT HELIX 108..110
FT /evidence="ECO:0007829|PDB:1ZBQ"
FT HELIX 113..141
FT /evidence="ECO:0007829|PDB:1ZBQ"
FT STRAND 144..149
FT /evidence="ECO:0007829|PDB:1ZBQ"
FT HELIX 152..156
FT /evidence="ECO:0007829|PDB:1ZBQ"
FT HELIX 162..182
FT /evidence="ECO:0007829|PDB:1ZBQ"
FT HELIX 183..185
FT /evidence="ECO:0007829|PDB:1ZBQ"
FT STRAND 187..194
FT /evidence="ECO:0007829|PDB:1ZBQ"
FT TURN 199..204
FT /evidence="ECO:0007829|PDB:1ZBQ"
FT HELIX 207..212
FT /evidence="ECO:0007829|PDB:1ZBQ"
FT HELIX 215..217
FT /evidence="ECO:0007829|PDB:1ZBQ"
FT HELIX 219..225
FT /evidence="ECO:0007829|PDB:1ZBQ"
FT STRAND 236..240
FT /evidence="ECO:0007829|PDB:1ZBQ"
FT STRAND 243..251
FT /evidence="ECO:0007829|PDB:1ZBQ"
FT HELIX 266..271
FT /evidence="ECO:0007829|PDB:1ZBQ"
FT HELIX 273..277
FT /evidence="ECO:0007829|PDB:1ZBQ"
FT HELIX 288..303
FT /evidence="ECO:0007829|PDB:1ZBQ"
FT STRAND 335..339
FT /evidence="ECO:0007829|PDB:1S9C"
FT HELIX 341..350
FT /evidence="ECO:0007829|PDB:1S9C"
FT HELIX 358..360
FT /evidence="ECO:0007829|PDB:1S9C"
FT HELIX 361..364
FT /evidence="ECO:0007829|PDB:1S9C"
FT HELIX 375..377
FT /evidence="ECO:0007829|PDB:1S9C"
FT HELIX 378..381
FT /evidence="ECO:0007829|PDB:1S9C"
FT HELIX 383..385
FT /evidence="ECO:0007829|PDB:1S9C"
FT HELIX 401..403
FT /evidence="ECO:0007829|PDB:1S9C"
FT STRAND 405..415
FT /evidence="ECO:0007829|PDB:1S9C"
FT STRAND 419..432
FT /evidence="ECO:0007829|PDB:1S9C"
FT STRAND 440..462
FT /evidence="ECO:0007829|PDB:1S9C"
FT STRAND 490..496
FT /evidence="ECO:0007829|PDB:1S9C"
FT HELIX 501..505
FT /evidence="ECO:0007829|PDB:1S9C"
FT HELIX 506..508
FT /evidence="ECO:0007829|PDB:1S9C"
FT HELIX 513..515
FT /evidence="ECO:0007829|PDB:1S9C"
FT HELIX 518..522
FT /evidence="ECO:0007829|PDB:1S9C"
FT TURN 523..525
FT /evidence="ECO:0007829|PDB:1S9C"
FT HELIX 533..548
FT /evidence="ECO:0007829|PDB:1S9C"
FT HELIX 553..555
FT /evidence="ECO:0007829|PDB:1S9C"
FT STRAND 556..563
FT /evidence="ECO:0007829|PDB:1S9C"
FT STRAND 572..580
FT /evidence="ECO:0007829|PDB:1S9C"
FT STRAND 583..590
FT /evidence="ECO:0007829|PDB:1S9C"
FT TURN 591..593
FT /evidence="ECO:0007829|PDB:1S9C"
FT STRAND 596..605
FT /evidence="ECO:0007829|PDB:1S9C"
FT HELIX 624..646
FT /evidence="ECO:0007829|PDB:1IKT"
FT STRAND 648..670
FT /evidence="ECO:0007829|PDB:1IKT"
FT STRAND 674..679
FT /evidence="ECO:0007829|PDB:1IKT"
FT STRAND 685..691
FT /evidence="ECO:0007829|PDB:1IKT"
FT HELIX 692..699
FT /evidence="ECO:0007829|PDB:1IKT"
FT HELIX 705..710
FT /evidence="ECO:0007829|PDB:1IKT"
FT STRAND 713..719
FT /evidence="ECO:0007829|PDB:1IKT"
FT HELIX 720..733
FT /evidence="ECO:0007829|PDB:1IKT"
SQ SEQUENCE 736 AA; 79686 MW; 7B11E02483328BCE CRC64;
MGSPLRFDGR VVLVTGAGAG LGRAYALAFA ERGALVVVND LGGDFKGVGK GSLAADKVVE
EIRRRGGKAV ANYDSVEEGE KVVKTALDAF GRIDVVVNNA GILRDRSFAR ISDEDWDIIH
RVHLRGSFQV TRAAWEHMKK QKYGRIIMTS SASGIYGNFG QANYSAAKLG LLGLANSLAI
EGRKSNIHCN TIAPNAGSRM TQTVMPEDLV EALKPEYVAP LVLWLCHESC EENGGLFEVG
AGWIGKLRWE RTLGAIVRQK NHPMTPEAVK ANWKKICDFE NASKPQSIQE STGSIIEVLS
KIDSEGGVSA NHTSRATSTA TSGFAGAIGQ KLPPFSYAYT ELEAIMYALG VGASIKDPKD
LKFIYEGSSD FSCLPTFGVI IGQKSMMGGG LAEIPGLSIN FAKVLHGEQY LELYKPLPRA
GKLKCEAVVA DVLDKGSGVV IIMDVYSYSE KELICHNQFS LFLVGSGGFG GKRTSDKVKV
AVAIPNRPPD AVLTDTTSLN QAALYRLSGD WNPLHIDPNF ASLAGFDKPI LHGLCTFGFS
ARRVLQQFAD NDVSRFKAIK ARFAKPVYPG QTLQTEMWKE GNRIHFQTKV QETGDIVISN
AYVDLAPTSG TSAKTPSEGG KLQSTFVFEE IGRRLKDIGP EVVKKVNAVF EWHITKGGNI
GAKWTIDLKS GSGKVYQGPA KGAADTTIIL SDEDFMEVVL GKLDPQKAFF SGRLKARGNI
MLSQKLQMIL KDYAKL
