Full text data of HSD17B12
HSD17B12
[Confidence: high (present in two of the MS resources)]
Estradiol 17-beta-dehydrogenase 12; 1.1.1.62 (17-beta-hydroxysteroid dehydrogenase 12; 17-beta-HSD 12; 3-ketoacyl-CoA reductase; KAR; 1.3.1.-)
Estradiol 17-beta-dehydrogenase 12; 1.1.1.62 (17-beta-hydroxysteroid dehydrogenase 12; 17-beta-HSD 12; 3-ketoacyl-CoA reductase; KAR; 1.3.1.-)
hRBCD
IPI00007676
IPI00007676 Steroid dehydrogenase homolog, Aldo-keto reductase family 1 member C3 Steroid dehydrogenase homolog, Aldo-keto reductase family 1 member C3 membrane n/a n/a n/a n/a 1 n/a n/a n/a n/a n/a 3 1 n/a 1 n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
IPI00007676 Steroid dehydrogenase homolog, Aldo-keto reductase family 1 member C3 Steroid dehydrogenase homolog, Aldo-keto reductase family 1 member C3 membrane n/a n/a n/a n/a 1 n/a n/a n/a n/a n/a 3 1 n/a 1 n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
UniProt
Q53GQ0
ID DHB12_HUMAN Reviewed; 312 AA.
AC Q53GQ0; A8K9B0; D3DR23; Q96JU2; Q9Y6G8;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
read moreDT 02-OCT-2007, sequence version 2.
DT 22-JAN-2014, entry version 90.
DE RecName: Full=Estradiol 17-beta-dehydrogenase 12;
DE EC=1.1.1.62;
DE AltName: Full=17-beta-hydroxysteroid dehydrogenase 12;
DE Short=17-beta-HSD 12;
DE AltName: Full=3-ketoacyl-CoA reductase;
DE Short=KAR;
DE EC=1.3.1.-;
GN Name=HSD17B12;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Liu T., Zhang J., Fu G., Zhang Q., Ye M., Zhou J., Wu J., Shen Y.,
RA Yu M., Chen S., Mao M., Chen Z.;
RT "Human steroid dehydrogenase homologue, complete cds.";
RL Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT LEU-280.
RC TISSUE=Liver, Placenta, Thymus, and Thyroid;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT LEU-280.
RC TISSUE=Liver;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT LEU-280.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pancreas;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PROTEIN SEQUENCE OF 26-35; 65-72; 104-117; 157-179 AND 207-221, AND
RP MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V.;
RL Submitted (JUN-2005) to UniProtKB.
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
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 [8]
RP TISSUE SPECIFICITY.
RX PubMed=16113833; DOI=10.1267/THRO05020412;
RA Gnatenko D.V., Cupit L.D., Huang E.C., Dhundale A., Perrotta P.L.,
RA Bahou W.F.;
RT "Platelets express steroidogenic 17beta-hydroxysteroid dehydrogenases.
RT Distinct profiles predict the essential thrombocythemic phenotype.";
RL Thromb. Haemost. 94:412-421(2005).
RN [9]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY, AND
RP MUTAGENESIS OF VAL-196 AND PHE-234.
RX PubMed=16166196; DOI=10.1210/me.2005-0058;
RA Luu-The V., Tremblay P., Labrie F.;
RT "Characterization of type 12 17beta-hydroxysteroid dehydrogenase, an
RT isoform of type 3 17beta-hydroxysteroid dehydrogenase responsible for
RT estradiol formation in women.";
RL Mol. Endocrinol. 20:437-443(2006).
RN [10]
RP INTERACTION WITH ELOVL1 AND LASS2.
RX PubMed=20937905; DOI=10.1073/pnas.1005572107;
RA Ohno Y., Suto S., Yamanaka M., Mizutani Y., Mitsutake S., Igarashi Y.,
RA Sassa T., Kihara A.;
RT "ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingolipid
RT synthesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:18439-18444(2010).
RN [11]
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.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Catalyzes the transformation of estrone (E1) into
CC estradiol (E2), suggesting a central role in estrogen formation.
CC Its strong expression in ovary and mammary gland suggest that it
CC may constitute the major enzyme responsible for the conversion of
CC E1 to E2 in women. Also has 3-ketoacyl-CoA reductase activity,
CC reducing both long chain 3-ketoacyl-CoAs and long chain fatty
CC acyl-CoAs, suggesting a role in long fatty acid elongation.
CC -!- CATALYTIC ACTIVITY: 17-beta-estradiol + NAD(P)(+) = estrone +
CC NAD(P)H.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=3.5 uM for estrone;
CC -!- PATHWAY: Steroid biosynthesis; estrogen biosynthesis.
CC -!- PATHWAY: Lipid metabolism; fatty acid biosynthesis.
CC -!- SUBUNIT: Interacts with ELOVL1 and LASS2.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass
CC membrane protein.
CC -!- TISSUE SPECIFICITY: Expressed in most tissues tested. Highly
CC expressed in the ovary and mammary. Expressed in platelets.
CC -!- DOMAIN: The di-lysine motif confers endoplasmic reticulum
CC localization for type I membrane proteins (By similarity).
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases
CC (SDR) family. 17-beta-HSD 3 subfamily.
CC -!- SEQUENCE CAUTION:
CC Sequence=AK027882; Type=Frameshift; Positions=92;
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DR EMBL; AF078850; AAD44482.1; -; mRNA.
DR EMBL; AK027882; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AK074952; BAG52039.1; -; mRNA.
DR EMBL; AK075216; BAG52086.1; -; mRNA.
DR EMBL; AK222881; BAD96601.1; -; mRNA.
DR EMBL; AK292625; BAF85314.1; -; mRNA.
DR EMBL; CH471064; EAW68082.1; -; Genomic_DNA.
DR EMBL; CH471064; EAW68088.1; -; Genomic_DNA.
DR EMBL; BC012043; AAH12043.1; -; mRNA.
DR RefSeq; NP_057226.1; NM_016142.2.
DR UniGene; Hs.132513; -.
DR ProteinModelPortal; Q53GQ0; -.
DR SMR; Q53GQ0; 50-280.
DR IntAct; Q53GQ0; 6.
DR STRING; 9606.ENSP00000278353; -.
DR ChEMBL; CHEMBL5998; -.
DR PhosphoSite; Q53GQ0; -.
DR DMDM; 158931120; -.
DR PaxDb; Q53GQ0; -.
DR PRIDE; Q53GQ0; -.
DR DNASU; 51144; -.
DR Ensembl; ENST00000278353; ENSP00000278353; ENSG00000149084.
DR GeneID; 51144; -.
DR KEGG; hsa:51144; -.
DR UCSC; uc001mxq.4; human.
DR CTD; 51144; -.
DR GeneCards; GC11P043577; -.
DR HGNC; HGNC:18646; HSD17B12.
DR HPA; HPA016427; -.
DR MIM; 609574; gene.
DR neXtProt; NX_Q53GQ0; -.
DR PharmGKB; PA38618; -.
DR eggNOG; COG0300; -.
DR HOGENOM; HOG000039237; -.
DR HOVERGEN; HBG005478; -.
DR InParanoid; Q53GQ0; -.
DR KO; K10251; -.
DR OMA; QWSTSLG; -.
DR PhylomeDB; Q53GQ0; -.
DR BRENDA; 1.1.1.62; 2681.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_15493; Steroid hormones.
DR SABIO-RK; Q53GQ0; -.
DR UniPathway; UPA00094; -.
DR UniPathway; UPA00769; -.
DR GeneWiki; HSD17B12; -.
DR GenomeRNAi; 51144; -.
DR NextBio; 54008; -.
DR PRO; PR:Q53GQ0; -.
DR ArrayExpress; Q53GQ0; -.
DR Bgee; Q53GQ0; -.
DR CleanEx; HS_HSD17B12; -.
DR Genevestigator; Q53GQ0; -.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0031012; C:extracellular matrix; IEA:Ensembl.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR GO; GO:0004303; F:estradiol 17-beta-dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0008201; F:heparin binding; IEA:Ensembl.
DR GO; GO:0006703; P:estrogen biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0030198; P:extracellular matrix organization; IEA:Ensembl.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0035338; P:long-chain fatty-acyl-CoA biosynthetic process; TAS:Reactome.
DR GO; GO:0010811; P:positive regulation of cell-substrate adhesion; IEA:Ensembl.
DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR GO; GO:0019432; P:triglyceride biosynthetic process; TAS:Reactome.
DR Gene3D; 3.40.50.720; -; 1.
DR InterPro; IPR002198; DH_sc/Rdtase_SDR.
DR InterPro; IPR002347; Glc/ribitol_DH.
DR InterPro; IPR016040; NAD(P)-bd_dom.
DR InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR Pfam; PF00106; adh_short; 1.
DR PIRSF; PIRSF000126; 11-beta-HSD1; 1.
DR PRINTS; PR00081; GDHRDH.
DR PRINTS; PR00080; SDRFAMILY.
DR PROSITE; PS00061; ADH_SHORT; 1.
PE 1: Evidence at protein level;
KW Complete proteome; Direct protein sequencing; Endoplasmic reticulum;
KW Lipid biosynthesis; Lipid metabolism; Membrane; NADP; Oxidoreductase;
KW Polymorphism; Reference proteome; Steroid biosynthesis; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1 312 Estradiol 17-beta-dehydrogenase 12.
FT /FTId=PRO_0000248368.
FT TRANSMEM 4 24 Helical; (Potential).
FT TRANSMEM 182 202 Helical; (Potential).
FT TRANSMEM 271 291 Helical; (Potential).
FT NP_BIND 50 79 NADP (By similarity).
FT MOTIF 308 312 Di-lysine motif.
FT ACT_SITE 202 202 Proton acceptor (By similarity).
FT BINDING 189 189 Substrate (By similarity).
FT VARIANT 280 280 S -> L (in dbSNP:rs11555762).
FT /FTId=VAR_027277.
FT MUTAGEN 196 196 V->W: No effect.
FT MUTAGEN 234 234 F->A: Allows the conversion of
FT androstenedione to testosterone.
SQ SEQUENCE 312 AA; 34324 MW; 8518336D7F514E50 CRC64;
MESALPAAGF LYWVGAGTVA YLALRISYSL FTALRVWGVG NEAGVGPGLG EWAVVTGSTD
GIGKSYAEEL AKHGMKVVLI SRSKDKLDQV SSEIKEKFKV ETRTIAVDFA SEDIYDKIKT
GLAGLEIGIL VNNVGMSYEY PEYFLDVPDL DNVIKKMINI NILSVCKMTQ LVLPGMVERS
KGAILNISSG SGMLPVPLLT IYSATKTFVD FFSQCLHEEY RSKGVFVQSV LPYFVATKLA
KIRKPTLDKP SPETFVKSAI KTVGLQSRTN GYLIHALMGS IISNLPSWIY LKIVMNMNKS
TRAHYLKKTK KN
//
ID DHB12_HUMAN Reviewed; 312 AA.
AC Q53GQ0; A8K9B0; D3DR23; Q96JU2; Q9Y6G8;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
read moreDT 02-OCT-2007, sequence version 2.
DT 22-JAN-2014, entry version 90.
DE RecName: Full=Estradiol 17-beta-dehydrogenase 12;
DE EC=1.1.1.62;
DE AltName: Full=17-beta-hydroxysteroid dehydrogenase 12;
DE Short=17-beta-HSD 12;
DE AltName: Full=3-ketoacyl-CoA reductase;
DE Short=KAR;
DE EC=1.3.1.-;
GN Name=HSD17B12;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Liu T., Zhang J., Fu G., Zhang Q., Ye M., Zhou J., Wu J., Shen Y.,
RA Yu M., Chen S., Mao M., Chen Z.;
RT "Human steroid dehydrogenase homologue, complete cds.";
RL Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT LEU-280.
RC TISSUE=Liver, Placenta, Thymus, and Thyroid;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT LEU-280.
RC TISSUE=Liver;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT LEU-280.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pancreas;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PROTEIN SEQUENCE OF 26-35; 65-72; 104-117; 157-179 AND 207-221, AND
RP MASS SPECTROMETRY.
RC TISSUE=B-cell lymphoma;
RA Bienvenut W.V.;
RL Submitted (JUN-2005) to UniProtKB.
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
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 [8]
RP TISSUE SPECIFICITY.
RX PubMed=16113833; DOI=10.1267/THRO05020412;
RA Gnatenko D.V., Cupit L.D., Huang E.C., Dhundale A., Perrotta P.L.,
RA Bahou W.F.;
RT "Platelets express steroidogenic 17beta-hydroxysteroid dehydrogenases.
RT Distinct profiles predict the essential thrombocythemic phenotype.";
RL Thromb. Haemost. 94:412-421(2005).
RN [9]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY, AND
RP MUTAGENESIS OF VAL-196 AND PHE-234.
RX PubMed=16166196; DOI=10.1210/me.2005-0058;
RA Luu-The V., Tremblay P., Labrie F.;
RT "Characterization of type 12 17beta-hydroxysteroid dehydrogenase, an
RT isoform of type 3 17beta-hydroxysteroid dehydrogenase responsible for
RT estradiol formation in women.";
RL Mol. Endocrinol. 20:437-443(2006).
RN [10]
RP INTERACTION WITH ELOVL1 AND LASS2.
RX PubMed=20937905; DOI=10.1073/pnas.1005572107;
RA Ohno Y., Suto S., Yamanaka M., Mizutani Y., Mitsutake S., Igarashi Y.,
RA Sassa T., Kihara A.;
RT "ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingolipid
RT synthesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:18439-18444(2010).
RN [11]
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.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Catalyzes the transformation of estrone (E1) into
CC estradiol (E2), suggesting a central role in estrogen formation.
CC Its strong expression in ovary and mammary gland suggest that it
CC may constitute the major enzyme responsible for the conversion of
CC E1 to E2 in women. Also has 3-ketoacyl-CoA reductase activity,
CC reducing both long chain 3-ketoacyl-CoAs and long chain fatty
CC acyl-CoAs, suggesting a role in long fatty acid elongation.
CC -!- CATALYTIC ACTIVITY: 17-beta-estradiol + NAD(P)(+) = estrone +
CC NAD(P)H.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=3.5 uM for estrone;
CC -!- PATHWAY: Steroid biosynthesis; estrogen biosynthesis.
CC -!- PATHWAY: Lipid metabolism; fatty acid biosynthesis.
CC -!- SUBUNIT: Interacts with ELOVL1 and LASS2.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass
CC membrane protein.
CC -!- TISSUE SPECIFICITY: Expressed in most tissues tested. Highly
CC expressed in the ovary and mammary. Expressed in platelets.
CC -!- DOMAIN: The di-lysine motif confers endoplasmic reticulum
CC localization for type I membrane proteins (By similarity).
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases
CC (SDR) family. 17-beta-HSD 3 subfamily.
CC -!- SEQUENCE CAUTION:
CC Sequence=AK027882; Type=Frameshift; Positions=92;
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DR EMBL; AF078850; AAD44482.1; -; mRNA.
DR EMBL; AK027882; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AK074952; BAG52039.1; -; mRNA.
DR EMBL; AK075216; BAG52086.1; -; mRNA.
DR EMBL; AK222881; BAD96601.1; -; mRNA.
DR EMBL; AK292625; BAF85314.1; -; mRNA.
DR EMBL; CH471064; EAW68082.1; -; Genomic_DNA.
DR EMBL; CH471064; EAW68088.1; -; Genomic_DNA.
DR EMBL; BC012043; AAH12043.1; -; mRNA.
DR RefSeq; NP_057226.1; NM_016142.2.
DR UniGene; Hs.132513; -.
DR ProteinModelPortal; Q53GQ0; -.
DR SMR; Q53GQ0; 50-280.
DR IntAct; Q53GQ0; 6.
DR STRING; 9606.ENSP00000278353; -.
DR ChEMBL; CHEMBL5998; -.
DR PhosphoSite; Q53GQ0; -.
DR DMDM; 158931120; -.
DR PaxDb; Q53GQ0; -.
DR PRIDE; Q53GQ0; -.
DR DNASU; 51144; -.
DR Ensembl; ENST00000278353; ENSP00000278353; ENSG00000149084.
DR GeneID; 51144; -.
DR KEGG; hsa:51144; -.
DR UCSC; uc001mxq.4; human.
DR CTD; 51144; -.
DR GeneCards; GC11P043577; -.
DR HGNC; HGNC:18646; HSD17B12.
DR HPA; HPA016427; -.
DR MIM; 609574; gene.
DR neXtProt; NX_Q53GQ0; -.
DR PharmGKB; PA38618; -.
DR eggNOG; COG0300; -.
DR HOGENOM; HOG000039237; -.
DR HOVERGEN; HBG005478; -.
DR InParanoid; Q53GQ0; -.
DR KO; K10251; -.
DR OMA; QWSTSLG; -.
DR PhylomeDB; Q53GQ0; -.
DR BRENDA; 1.1.1.62; 2681.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_15493; Steroid hormones.
DR SABIO-RK; Q53GQ0; -.
DR UniPathway; UPA00094; -.
DR UniPathway; UPA00769; -.
DR GeneWiki; HSD17B12; -.
DR GenomeRNAi; 51144; -.
DR NextBio; 54008; -.
DR PRO; PR:Q53GQ0; -.
DR ArrayExpress; Q53GQ0; -.
DR Bgee; Q53GQ0; -.
DR CleanEx; HS_HSD17B12; -.
DR Genevestigator; Q53GQ0; -.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0031012; C:extracellular matrix; IEA:Ensembl.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR GO; GO:0004303; F:estradiol 17-beta-dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0008201; F:heparin binding; IEA:Ensembl.
DR GO; GO:0006703; P:estrogen biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0030198; P:extracellular matrix organization; IEA:Ensembl.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0035338; P:long-chain fatty-acyl-CoA biosynthetic process; TAS:Reactome.
DR GO; GO:0010811; P:positive regulation of cell-substrate adhesion; IEA:Ensembl.
DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR GO; GO:0019432; P:triglyceride biosynthetic process; TAS:Reactome.
DR Gene3D; 3.40.50.720; -; 1.
DR InterPro; IPR002198; DH_sc/Rdtase_SDR.
DR InterPro; IPR002347; Glc/ribitol_DH.
DR InterPro; IPR016040; NAD(P)-bd_dom.
DR InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR Pfam; PF00106; adh_short; 1.
DR PIRSF; PIRSF000126; 11-beta-HSD1; 1.
DR PRINTS; PR00081; GDHRDH.
DR PRINTS; PR00080; SDRFAMILY.
DR PROSITE; PS00061; ADH_SHORT; 1.
PE 1: Evidence at protein level;
KW Complete proteome; Direct protein sequencing; Endoplasmic reticulum;
KW Lipid biosynthesis; Lipid metabolism; Membrane; NADP; Oxidoreductase;
KW Polymorphism; Reference proteome; Steroid biosynthesis; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1 312 Estradiol 17-beta-dehydrogenase 12.
FT /FTId=PRO_0000248368.
FT TRANSMEM 4 24 Helical; (Potential).
FT TRANSMEM 182 202 Helical; (Potential).
FT TRANSMEM 271 291 Helical; (Potential).
FT NP_BIND 50 79 NADP (By similarity).
FT MOTIF 308 312 Di-lysine motif.
FT ACT_SITE 202 202 Proton acceptor (By similarity).
FT BINDING 189 189 Substrate (By similarity).
FT VARIANT 280 280 S -> L (in dbSNP:rs11555762).
FT /FTId=VAR_027277.
FT MUTAGEN 196 196 V->W: No effect.
FT MUTAGEN 234 234 F->A: Allows the conversion of
FT androstenedione to testosterone.
SQ SEQUENCE 312 AA; 34324 MW; 8518336D7F514E50 CRC64;
MESALPAAGF LYWVGAGTVA YLALRISYSL FTALRVWGVG NEAGVGPGLG EWAVVTGSTD
GIGKSYAEEL AKHGMKVVLI SRSKDKLDQV SSEIKEKFKV ETRTIAVDFA SEDIYDKIKT
GLAGLEIGIL VNNVGMSYEY PEYFLDVPDL DNVIKKMINI NILSVCKMTQ LVLPGMVERS
KGAILNISSG SGMLPVPLLT IYSATKTFVD FFSQCLHEEY RSKGVFVQSV LPYFVATKLA
KIRKPTLDKP SPETFVKSAI KTVGLQSRTN GYLIHALMGS IISNLPSWIY LKIVMNMNKS
TRAHYLKKTK KN
//
MIM
609574
*RECORD*
*FIELD* NO
609574
*FIELD* TI
*609574 17-@BETA-HYDROXYSTEROID DEHYDROGENASE XII; HSD17B12
;;17-@BETA-HSD XII;;
3-@KETOACYL-CoA REDUCTASE; KAR
read more*FIELD* TX
DESCRIPTION
The enzyme 17-beta hydroxysteroid dehydrogenase-12 (HSD17B12) uses NADPH
to reduce 3-ketoacyl-CoA to 3-hydroxyacyl-CoA during the second step of
fatty acid elongation.
CLONING
Using BLAST analysis with the sequence of yeast genes encoding a
3-ketoacyl-CoA reductase as query, Moon and Horton (2003) identified
human and mouse cDNAs corresponding to HSD17B12. The human HSD17B12 gene
encodes a protein of 312 amino acids containing a dilysine endoplasmic
reticulum (ER)-retention motif at the C terminus and 4 predicted
transmembrane domains. Mouse and human HSD17B12 share 82% amino acid
identity. Northern blot analysis showed expression of a 2.9-kb HSD17B12
transcript in all human tissues tested, with highest levels seen in
liver, muscle, and kidney. Using immunofluorescence, Moon and Horton
(2003) showed that HSD17B12 localizes to the ER.
GENE FUNCTION
Moon and Horton (2003) showed that KAR functions as a 3-ketoacyl-CoA
reductase, reducing both long chain 3-ketoacyl-CoAs and long chain fatty
acyl-CoAs. Analysis of liver HSD17B12 mRNA in transgenic mice with
altered levels of sterol regulatory element-binding proteins (SREBPs;
see 184756) showed no change in HSD17B12 expression compared to wildtype
mice, suggesting that HSD17B12 is not regulated by SREBPs.
*FIELD* RF
1. Moon, Y.-A.; Horton, J. D.: Identification of two mammalian reductases
involved in the two-carbon fatty acyl elongation cascade. J. Biol.
Chem. 278: 7335-7343, 2003.
*FIELD* CD
Laura L. Baxter: 9/12/2005
*FIELD* ED
alopez: 09/12/2005
*RECORD*
*FIELD* NO
609574
*FIELD* TI
*609574 17-@BETA-HYDROXYSTEROID DEHYDROGENASE XII; HSD17B12
;;17-@BETA-HSD XII;;
3-@KETOACYL-CoA REDUCTASE; KAR
read more*FIELD* TX
DESCRIPTION
The enzyme 17-beta hydroxysteroid dehydrogenase-12 (HSD17B12) uses NADPH
to reduce 3-ketoacyl-CoA to 3-hydroxyacyl-CoA during the second step of
fatty acid elongation.
CLONING
Using BLAST analysis with the sequence of yeast genes encoding a
3-ketoacyl-CoA reductase as query, Moon and Horton (2003) identified
human and mouse cDNAs corresponding to HSD17B12. The human HSD17B12 gene
encodes a protein of 312 amino acids containing a dilysine endoplasmic
reticulum (ER)-retention motif at the C terminus and 4 predicted
transmembrane domains. Mouse and human HSD17B12 share 82% amino acid
identity. Northern blot analysis showed expression of a 2.9-kb HSD17B12
transcript in all human tissues tested, with highest levels seen in
liver, muscle, and kidney. Using immunofluorescence, Moon and Horton
(2003) showed that HSD17B12 localizes to the ER.
GENE FUNCTION
Moon and Horton (2003) showed that KAR functions as a 3-ketoacyl-CoA
reductase, reducing both long chain 3-ketoacyl-CoAs and long chain fatty
acyl-CoAs. Analysis of liver HSD17B12 mRNA in transgenic mice with
altered levels of sterol regulatory element-binding proteins (SREBPs;
see 184756) showed no change in HSD17B12 expression compared to wildtype
mice, suggesting that HSD17B12 is not regulated by SREBPs.
*FIELD* RF
1. Moon, Y.-A.; Horton, J. D.: Identification of two mammalian reductases
involved in the two-carbon fatty acyl elongation cascade. J. Biol.
Chem. 278: 7335-7343, 2003.
*FIELD* CD
Laura L. Baxter: 9/12/2005
*FIELD* ED
alopez: 09/12/2005