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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}.
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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
 
 
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