DHB12_MOUSE
ID DHB12_MOUSE Reviewed; 312 AA.
AC O70503; Q3TID1; Q3U7V9; Q542N3; Q8CI39;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Very-long-chain 3-oxoacyl-CoA reductase {ECO:0000305};
DE EC=1.1.1.330 {ECO:0000250|UniProtKB:Q53GQ0};
DE AltName: Full=17-beta-hydroxysteroid dehydrogenase 12 {ECO:0000250|UniProtKB:Q53GQ0};
DE Short=17-beta-HSD 12 {ECO:0000250|UniProtKB:Q53GQ0};
DE AltName: Full=3-ketoacyl-CoA reductase {ECO:0000250|UniProtKB:Q53GQ0};
DE Short=KAR {ECO:0000250|UniProtKB:Q53GQ0};
DE AltName: Full=Estradiol 17-beta-dehydrogenase 12 {ECO:0000250|UniProtKB:Q53GQ0};
DE EC=1.1.1.62 {ECO:0000250|UniProtKB:Q53GQ0};
DE AltName: Full=KIK-I;
GN Name=Hsd17b12 {ECO:0000312|MGI:MGI:1926967}; Synonyms=Kik1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=BALB/cJ; TISSUE=Liver;
RA Gambotto A., Pagliano O., Robbins P., Deleo A.;
RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=BALB/cJ, C57BL/6J, and NOD;
RC TISSUE=Bone marrow, Cerebellum, Colon, Head, Lung, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=FVB/N-3; TISSUE=Mammary tumor;
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 [4]
RP TISSUE SPECIFICITY, AND CATALYTIC ACTIVITY.
RX PubMed=12482854; DOI=10.1074/jbc.m211684200;
RA Moon Y.-A., Horton J.D.;
RT "Identification of two mammalian reductases involved in the two-carbon
RT fatty acyl elongation cascade.";
RL J. Biol. Chem. 278:7335-7343(2003).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Catalyzes the second of the four reactions of the long-chain
CC fatty acids elongation cycle. This endoplasmic reticulum-bound
CC enzymatic process, allows the addition of two carbons to the chain of
CC long- and very long-chain fatty acids/VLCFAs per cycle. This enzyme has
CC a 3-ketoacyl-CoA reductase activity, reducing 3-ketoacyl-CoA to 3-
CC hydroxyacyl-CoA, within each cycle of fatty acid elongation. Thereby,
CC it may participate in the production of VLCFAs of different chain
CC lengths that are involved in multiple biological processes as
CC precursors of membrane lipids and lipid mediators. May also catalyze
CC the transformation of estrone (E1) into estradiol (E2) and play a role
CC in estrogen formation. {ECO:0000250|UniProtKB:Q53GQ0}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a very-long-chain (3R)-3-hydroxyacyl-CoA + NADP(+) = a very-
CC long-chain 3-oxoacyl-CoA + H(+) + NADPH; Xref=Rhea:RHEA:48680,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:85440, ChEBI:CHEBI:90725; EC=1.1.1.330;
CC Evidence={ECO:0000250|UniProtKB:Q53GQ0};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17beta-estradiol + NAD(+) = estrone + H(+) + NADH;
CC Xref=Rhea:RHEA:24612, ChEBI:CHEBI:15378, ChEBI:CHEBI:16469,
CC ChEBI:CHEBI:17263, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.62;
CC Evidence={ECO:0000250|UniProtKB:Q53GQ0};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17beta-estradiol + NADP(+) = estrone + H(+) + NADPH;
CC Xref=Rhea:RHEA:24616, ChEBI:CHEBI:15378, ChEBI:CHEBI:16469,
CC ChEBI:CHEBI:17263, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.62;
CC Evidence={ECO:0000250|UniProtKB:Q53GQ0};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-oxooctadecanoyl-CoA + H(+) + NADPH = (3R)-
CC hydroxyoctadecanoyl-CoA + NADP(+); Xref=Rhea:RHEA:39151,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:71407, ChEBI:CHEBI:76374;
CC Evidence={ECO:0000269|PubMed:12482854};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(7Z,10Z,13Z,16Z)-3-oxodocosatetraenoyl-CoA + H(+) + NADPH =
CC (3R)-hydroxy-(7Z,10Z,13Z,16Z)-docosatetraenoyl-CoA + NADP(+);
CC Xref=Rhea:RHEA:39323, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:73852, ChEBI:CHEBI:76415;
CC Evidence={ECO:0000250|UniProtKB:Q53GQ0};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(7Z,10Z,13Z,16Z,19Z)-3-oxodocosapentaenoyl-CoA + H(+) + NADPH
CC = (3R)-hydroxy-(7Z,10Z,13Z,16Z,19Z)-docosapentaenoyl-CoA + NADP(+);
CC Xref=Rhea:RHEA:39459, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:73863, ChEBI:CHEBI:76460;
CC Evidence={ECO:0000250|UniProtKB:Q53GQ0};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(8Z,11Z,14Z)-3-oxoeicosatrienoyl-CoA + H(+) + NADPH = (3R)-
CC hydroxy-(8Z,11Z,14Z)-eicosatrienoyl-CoA + NADP(+);
CC Xref=Rhea:RHEA:39311, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:71481, ChEBI:CHEBI:76411;
CC Evidence={ECO:0000250|UniProtKB:Q53GQ0};
CC -!- PATHWAY: Lipid metabolism; fatty acid biosynthesis.
CC {ECO:0000250|UniProtKB:Q53GQ0}.
CC -!- PATHWAY: Steroid biosynthesis; estrogen biosynthesis.
CC {ECO:0000250|UniProtKB:Q53GQ0}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q53GQ0}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q53GQ0}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O70503-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O70503-2; Sequence=VSP_020255;
CC -!- TISSUE SPECIFICITY: Expressed in most tissues tested.
CC {ECO:0000269|PubMed:12482854}.
CC -!- DOMAIN: The di-lysine motif confers endoplasmic reticulum localization
CC for type I membrane proteins. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. 17-beta-HSD 3 subfamily. {ECO:0000305}.
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DR EMBL; AF064635; AAC16885.1; -; mRNA.
DR EMBL; AK078841; BAC37418.1; -; mRNA.
DR EMBL; AK081869; BAC38354.1; -; mRNA.
DR EMBL; AK082715; BAC38583.1; -; mRNA.
DR EMBL; AK088521; BAC40401.1; -; mRNA.
DR EMBL; AK150849; BAE29906.1; -; mRNA.
DR EMBL; AK152489; BAE31260.1; -; mRNA.
DR EMBL; AK166027; BAE38530.1; -; mRNA.
DR EMBL; AK167908; BAE39915.1; -; mRNA.
DR EMBL; BC037620; AAH37620.1; -; mRNA.
DR CCDS; CCDS16458.1; -. [O70503-1]
DR RefSeq; NP_062631.1; NM_019657.4. [O70503-1]
DR AlphaFoldDB; O70503; -.
DR SMR; O70503; -.
DR BioGRID; 207914; 7.
DR IntAct; O70503; 2.
DR MINT; O70503; -.
DR STRING; 10090.ENSMUSP00000028619; -.
DR SwissLipids; SLP:000000434; -.
DR iPTMnet; O70503; -.
DR PhosphoSitePlus; O70503; -.
DR SwissPalm; O70503; -.
DR EPD; O70503; -.
DR jPOST; O70503; -.
DR MaxQB; O70503; -.
DR PaxDb; O70503; -.
DR PeptideAtlas; O70503; -.
DR PRIDE; O70503; -.
DR ProteomicsDB; 279351; -. [O70503-1]
DR ProteomicsDB; 279352; -. [O70503-2]
DR Antibodypedia; 3090; 206 antibodies from 24 providers.
DR DNASU; 56348; -.
DR Ensembl; ENSMUST00000028619; ENSMUSP00000028619; ENSMUSG00000027195. [O70503-1]
DR GeneID; 56348; -.
DR KEGG; mmu:56348; -.
DR UCSC; uc008lgp.1; mouse. [O70503-1]
DR CTD; 51144; -.
DR MGI; MGI:1926967; Hsd17b12.
DR VEuPathDB; HostDB:ENSMUSG00000027195; -.
DR eggNOG; KOG1014; Eukaryota.
DR GeneTree; ENSGT00940000154860; -.
DR HOGENOM; CLU_010194_38_0_1; -.
DR InParanoid; O70503; -.
DR OMA; FLQHWSS; -.
DR PhylomeDB; O70503; -.
DR TreeFam; TF314591; -.
DR Reactome; R-MMU-193048; Androgen biosynthesis.
DR Reactome; R-MMU-75876; Synthesis of very long-chain fatty acyl-CoAs.
DR UniPathway; UPA00094; -.
DR UniPathway; UPA00769; -.
DR BioGRID-ORCS; 56348; 23 hits in 75 CRISPR screens.
DR ChiTaRS; Hsd17b12; mouse.
DR PRO; PR:O70503; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; O70503; protein.
DR Bgee; ENSMUSG00000027195; Expressed in tail skin and 265 other tissues.
DR ExpressionAtlas; O70503; baseline and differential.
DR Genevisible; O70503; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0031012; C:extracellular matrix; IDA:MGI.
DR GO; GO:0009923; C:fatty acid elongase complex; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0044594; F:17-beta-hydroxysteroid dehydrogenase (NAD+) activity; IEA:RHEA.
DR GO; GO:0102339; F:3-oxo-arachidoyl-CoA reductase activity; IEA:UniProtKB-EC.
DR GO; GO:0102340; F:3-oxo-behenoyl-CoA reductase activity; IEA:UniProtKB-EC.
DR GO; GO:0102342; F:3-oxo-cerotoyl-CoA reductase activity; IEA:UniProtKB-EC.
DR GO; GO:0102341; F:3-oxo-lignoceroyl-CoA reductase activity; IEA:UniProtKB-EC.
DR GO; GO:0005518; F:collagen binding; IDA:MGI.
DR GO; GO:0001968; F:fibronectin binding; IDA:MGI.
DR GO; GO:0008201; F:heparin binding; IDA:MGI.
DR GO; GO:0016509; F:long-chain-3-hydroxyacyl-CoA dehydrogenase activity; ISO:MGI.
DR GO; GO:0050062; F:long-chain-fatty-acyl-CoA reductase activity; ISO:MGI.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0006703; P:estrogen biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0030198; P:extracellular matrix organization; IDA:MGI.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0010811; P:positive regulation of cell-substrate adhesion; IDA:MGI.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR InterPro; IPR002347; SDR_fam.
DR Pfam; PF00106; adh_short; 1.
DR PRINTS; PR00081; GDHRDH.
DR PRINTS; PR00080; SDRFAMILY.
DR SUPFAM; SSF51735; SSF51735; 1.
DR PROSITE; PS00061; ADH_SHORT; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Endoplasmic reticulum; Lipid biosynthesis;
KW Lipid metabolism; Membrane; NADP; Oxidoreductase; Reference proteome;
KW Steroid biosynthesis; Transmembrane; Transmembrane helix.
FT CHAIN 1..312
FT /note="Very-long-chain 3-oxoacyl-CoA reductase"
FT /id="PRO_0000054576"
FT TRANSMEM 4..24
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 182..202
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 269..285
FT /note="Helical"
FT /evidence="ECO:0000255"
FT MOTIF 308..312
FT /note="Di-lysine motif"
FT /evidence="ECO:0000250"
FT ACT_SITE 202
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 50..79
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 189
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..135
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_020255"
FT CONFLICT 2
FT /note="E -> V (in Ref. 2; BAE39915)"
FT /evidence="ECO:0000305"
FT CONFLICT 256
FT /note="V -> M (in Ref. 2; BAE29906/BAE31260)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 312 AA; 34742 MW; 7D255188FA1F8DDB CRC64;
MECAPPAAGF LYWVGASTIA YLALRASYSL FRAFQVWCVG NEALVGPRLG EWAVVTGGTD
GIGKAYAEEL AKRGMKIVLI SRSQDKLNQV SNNIKEKFNV ETRTIAVDFS LDDIYDKIKT
GLSGLEIGVL VNNVGMSYEY PEYFLEIPDL DNTIKKLINI NVLSVCKVTR LVLPGMVERS
KGVILNISSA SGMLPVPLLT IYSATKAFVD FFSQCLHEEY KSKGIFVQSV MPYLVATKLA
KIQKPTLDKP SAETFVKSAI KTVGLQTRTT GYVIHSLMGS INSIMPRWMY FKIIMGFSKS
LRNRYLKKRK KN
