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Identification
HMDB Protein ID HMDBP08861
Secondary Accession Numbers
  • 14588
Name Estradiol 17-beta-dehydrogenase 12
Synonyms
  1. 17-beta-HSD 12
  2. 17-beta-hydroxysteroid dehydrogenase 12
  3. 3-ketoacyl-CoA reductase
  4. KAR
Gene Name HSD17B12
Protein Type Unknown
Biological Properties
General Function Involved in oxidoreductase activity
Specific Function Catalyzes the transformation of estrone (E1) into estradiol (E2), suggesting a central role in estrogen formation. Its strong expression in ovary and mammary gland suggest that it may constitute the major enzyme responsible for the conversion of E1 to E2 in women. Also has 3-ketoacyl-CoA reductase activity, reducing both long chain 3-ketoacyl-CoAs and long chain fatty acyl-CoAs, suggesting a role in long fatty acid elongation.
Pathways
  • Biosynthesis of unsaturated fatty acids
  • estrogen biosynthesis
  • Fatty acid biosynthesis
  • Fatty acid elongation
  • Steroid hormone biosynthesis
Reactions
Estradiol + NAD(P)(+) → Estrone + NAD(P)H details
(3R)-3-Hydroxyacyl-CoA + NADP → 3-Oxoacyl-CoA + NADPH + Hydrogen Ion details
Estradiol + NAD → Estrone + NADH + Hydrogen Ion details
Estradiol + NADP → Estrone + NADPH + Hydrogen Ion details
Estriol + NAD → 16b-Hydroxyestrone + NADH + Hydrogen Ion details
Estriol + NADP → 16b-Hydroxyestrone + NADPH + Hydrogen Ion details
3-Oxooctadecanoyl-CoA + NADPH + Hydrogen Ion → 3-hydroxyoctadecanoyl-CoA + NADP details
11beta,17beta-Dihydroxy-4-androsten-3-one + NAD → 11b-Hydroxyandrost-4-ene-3,17-dione + NADH + Hydrogen Ion details
11beta,17beta-Dihydroxy-4-androsten-3-one + NADP → 11b-Hydroxyandrost-4-ene-3,17-dione + NADPH + Hydrogen Ion details
GO Classification
Biological Process
small molecule metabolic process
extracellular matrix organization
positive regulation of cell-substrate adhesion
fatty acid biosynthetic process
long-chain fatty-acyl-CoA biosynthetic process
triglyceride biosynthetic process
estrogen biosynthetic process
Cellular Component
endoplasmic reticulum membrane
extracellular matrix
integral to membrane
Function
binding
catalytic activity
oxidoreductase activity
Molecular Function
heparin binding
estradiol 17-beta-dehydrogenase activity
nucleotide binding
Process
metabolic process
oxidation reduction
Cellular Location
  1. Endoplasmic reticulum membrane
  2. Multi-pass membrane protein
Gene Properties
Chromosome Location 11
Locus 11p11.2
SNPs HSD17B12
Gene Sequence
>939 bp
ATGGAGAGCGCTCTCCCCGCCGCCGGCTTCCTGTACTGGGTCGGCGCGGGCACCGTGGCC
TACCTAGCCCTGCGTATTTCGTACTCGCTCTTCACGGCCCTCCGGGTCTGGGGAGTGGGG
AATGAGGCGGGGGTCGGCCCGGGGCTCGGAGAGTGGGCAGTTGTCACAGGTAGTACTGAT
GGAATTGGAAAATCATATGCAGAAGAGTTAGCAAAGCATGGAATGAAGGTTGTCCTTATC
AGCAGATCAAAGGATAAACTTGACCAGGTTTCCAGTGAAATAAAAGAAAAATTCAAAGTG
GAGACAAGAACCATTGCTGTTGACTTTGCATCAGAAGATATTTATGATAAAATTAAAACA
GGCTTGGCTGGTCTTGAAATCGGCATCTTAGTGAACAACGTGGGAATGTCGTATGAGTAT
CCTGAATACTTTTTGGATGTTCCTGACTTGGACAATGTGATCAAGAAAATGATAAATATT
AATATTCTTTCTGTTTGTAAGATGACACAATTGGTACTGCCTGGCATGGTGGAAAGATCC
AAAGGGGCTATTCTGAACATTTCATCTGGCAGTGGCATGCTCCCTGTCCCACTCTTGACC
ATCTATTCTGCAACCAAGACTTTTGTAGATTTCTTCTCTCAGTGCCTCCATGAGGAGTAT
AGGAGCAAGGGCGTCTTTGTGCAGAGTGTCCTGCCATACTTCGTAGCTACAAAACTGGCT
AAAATCCGGAAGCCAACTTTGGATAAGCCCTCTCCGGAGACGTTTGTGAAGTCTGCAATT
AAAACAGTCGGCCTGCAATCCCGAACCAATGGATACCTGATCCATGCTCTTATGGGCTCG
ATAATCTCAAACCTGCCTTCTTGGATTTATTTGAAAATAGTCATGAATATGAACAAGTCT
ACACGGGCTCACTATCTGAAGAAAACCAAGAAGAACTAA
Protein Properties
Number of Residues 312
Molecular Weight 34323.875
Theoretical pI 9.323
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Estradiol 17-beta-dehydrogenase 12
MESALPAAGFLYWVGAGTVAYLALRISYSLFTALRVWGVGNEAGVGPGLGEWAVVTGSTD
GIGKSYAEELAKHGMKVVLISRSKDKLDQVSSEIKEKFKVETRTIAVDFASEDIYDKIKT
GLAGLEIGILVNNVGMSYEYPEYFLDVPDLDNVIKKMININILSVCKMTQLVLPGMVERS
KGAILNISSGSGMLPVPLLTIYSATKTFVDFFSQCLHEEYRSKGVFVQSVLPYFVATKLA
KIRKPTLDKPSPETFVKSAIKTVGLQSRTNGYLIHALMGSIISNLPSWIYLKIVMNMNKS
TRAHYLKKTKKN
GenBank ID Protein 5531815
UniProtKB/Swiss-Prot ID Q53GQ0
UniProtKB/Swiss-Prot Entry Name DHB12_HUMAN
PDB IDs Not Available
GenBank Gene ID AF078850
GeneCard ID HSD17B12
GenAtlas ID HSD17B12
HGNC ID HGNC:18646
References
General References
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  3. Moon YA, Horton JD: Identification of two mammalian reductases involved in the two-carbon fatty acyl elongation cascade. J Biol Chem. 2003 Feb 28;278(9):7335-43. Epub 2002 Dec 13. [PubMed:12482854 ]
  4. Gnatenko DV, Cupit LD, Huang EC, Dhundale A, Perrotta PL, Bahou WF: Platelets express steroidogenic 17beta-hydroxysteroid dehydrogenases. Distinct profiles predict the essential thrombocythemic phenotype. Thromb Haemost. 2005 Aug;94(2):412-21. [PubMed:16113833 ]
  5. Luu-The V, Tremblay P, Labrie F: Characterization of type 12 17beta-hydroxysteroid dehydrogenase, an isoform of type 3 17beta-hydroxysteroid dehydrogenase responsible for estradiol formation in women. Mol Endocrinol. 2006 Feb;20(2):437-43. Epub 2005 Sep 15. [PubMed:16166196 ]