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 27-MAR-2024, entry version 228. 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:10706581, 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 fatty acid CC beta-oxidation pathway. Catalyzes two of the four reactions in fatty CC acid degradation: hydration of 2-enoyl-CoA (trans-2-enoyl-CoA) to CC produce (3R)-3-hydroxyacyl-CoA, and dehydrogenation of (3R)-3- CC hydroxyacyl-CoA to produce 3-ketoacyl-CoA (3-oxoacyl-CoA), which is CC further metabolized by SCPx. Can use straight-chain and branched-chain CC fatty acids, as well as bile acid intermediates as substrates. 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=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=right-to-left; Xref=Rhea:RHEA:26528; 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=(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 --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 PDB; 8AF2; X-ray; 2.51 A; A/B=618-736. DR PDB; 8AF3; X-ray; 1.52 A; A=618-736. DR PDBsum; 1IKT; -. DR PDBsum; 1S9C; -. DR PDBsum; 1ZBQ; -. DR PDBsum; 6Z1W; -. DR PDBsum; 6Z1X; -. DR PDBsum; 8AF2; -. DR PDBsum; 8AF3; -. DR AlphaFoldDB; P51659; -. DR SASBDB; P51659; -. DR SMR; P51659; -. DR BioGRID; 109528; 171. DR IntAct; P51659; 67. DR MINT; P51659; -. DR STRING; 9606.ENSP00000411960; -. DR ChEMBL; CHEMBL5814; -. DR DrugBank; DB03192; (R)-3-hydroxydecanoyl-CoA. DR DrugBank; DB00157; NADH. DR SwissLipids; SLP:000000540; -. DR GlyGen; P51659; 3 sites, 1 O-linked glycan (3 sites). 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; 9606-ENSP00000420914; -. DR PeptideAtlas; P51659; -. DR ProteomicsDB; 19165; -. DR ProteomicsDB; 27834; -. DR ProteomicsDB; 56360; -. [P51659-1] DR Pumba; P51659; -. DR TopDownProteomics; P51659-1; -. [P51659-1] DR Antibodypedia; 13742; 478 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 AGR; HGNC:5213; -. 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; 642945; Perrault syndrome type 1. DR Orphanet; 642976; Perrault syndrome type 2. 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; WATKVHT; -. DR OrthoDB; 2140828at2759; -. DR PhylomeDB; P51659; -. DR TreeFam; TF105656; -. DR BioCyc; MetaCyc:HS05792-MONOMER; -. 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 1171 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 203 other cell types or tissues. DR ExpressionAtlas; P51659; baseline and differential. 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:HPA. DR GO; GO:0106386; F:(3R)-hydroxyacyl-CoA dehydrogenase (NAD) activity; IEA:RHEA. DR GO; GO:0044594; F:17-beta-hydroxysteroid dehydrogenase (NAD+) activity; IBA:GO_Central. DR GO; GO:0018812; F:3-hydroxyacyl-CoA dehydratase 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:0004303; F:estradiol 17-beta-dehydrogenase [NAD(P)] activity; IDA:UniProtKB. DR GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW. 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 CDD; cd03448; HDE_HSD; 1. DR CDD; cd05353; hydroxyacyl-CoA-like_DH_SDR_c-like; 1. DR Gene3D; 1.10.287.4290; -; 1. DR Gene3D; 3.10.129.10; Hotdog Thioesterase; 2. DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1. DR Gene3D; 3.30.1050.10; SCP2 sterol-binding domain; 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 PANTHER; PTHR45024; DEHYDROGENASES, SHORT CHAIN; 1. DR PANTHER; PTHR45024:SF2; SCP2 DOMAIN-CONTAINING PROTEIN; 1. 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 SMART; SM00822; PKS_KR; 1. DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1. DR SUPFAM; SSF55718; SCP-like; 1. DR SUPFAM; SSF54637; Thioesterase/thiol ester dehydrase-isomerase; 2. DR PROSITE; PS00061; ADH_SHORT; 1. DR Genevisible; P51659; HS. 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:8AF3" FT STRAND 648..670 FT /evidence="ECO:0007829|PDB:8AF3" FT STRAND 674..679 FT /evidence="ECO:0007829|PDB:8AF3" FT STRAND 685..691 FT /evidence="ECO:0007829|PDB:8AF3" FT HELIX 692..699 FT /evidence="ECO:0007829|PDB:8AF3" FT HELIX 705..710 FT /evidence="ECO:0007829|PDB:8AF3" FT STRAND 713..718 FT /evidence="ECO:0007829|PDB:8AF3" FT HELIX 720..723 FT /evidence="ECO:0007829|PDB:8AF3" FT HELIX 729..732 FT /evidence="ECO:0007829|PDB:8AF3" FT HELIX 733..735 FT /evidence="ECO:0007829|PDB:8AF3" 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 //