Reviewed, UniProtKB/Swiss-Prot Q53GQ0 (DHB12_HUMAN)

Names and origin

Protein names

Recommended name:
    Estradiol 17-beta-dehydrogenase 12
    EC=1.1.1.62
Alternative name(s):
    17-beta-hydroxysteroid dehydrogenase 12
      Short name=17-beta-HSD 12
    3-ketoacyl-CoA reductase
      Short name=KAR
    EC=1.3.1.-

Gene names

Name:

HSD17B12

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	312 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

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. Ref.6 Ref.8
Catalytic activity	Estradiol-17-beta + NAD(P)+ = estrone + NAD(P)H.
Pathway	Steroid biosynthesis; estrogen biosynthesis. Lipid metabolism; fatty acid biosynthesis.
Subcellular location	Endoplasmic reticulum membrane; Multi-pass membrane protein. Ref.6
Tissue specificity	Expressed in most tissues tested. Highly expressed in the ovary and mammary. Expressed in platelets. Ref.6 Ref.8 Ref.7
Domain	The di-lysine motif confers endoplasmic reticulum localization for type I membrane proteins By similarity.
Sequence similarities	Belongs to the short-chain dehydrogenases/reductases (SDR) family. 17-beta-HSD 3 subfamily.
Biophysicochemical properties	Kinetic parameters: KM=3.5 µM for estrone
Sequence caution	The sequence AK027882 differs from that shown. Reason: Frameshift at position 92.

Ontologies

Keywords
Biological process	Lipid synthesis Steroid biosynthesis
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane
Ligand	NADP
Molecular function	Oxidoreductase
Technical term	Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW steroid biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	endoplasmic reticulum Inferred from electronic annotation. Source: UniProtKB-KW integral to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	estradiol 17-beta-dehydrogenase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 312	312	Estradiol 17-beta-dehydrogenase 12		PRO_0000248368
Regions
	Transmembrane	4 – 24	21	Potential
	Transmembrane	182 – 202	21	Potential
	Transmembrane	271 – 291	21	Potential
	Nucleotide binding	50 – 79	30	NADP By similarity
	Motif	308 – 312	5	Di-lysine motif
Sites
	Active site	202	1	Proton acceptor By similarity
	Binding site	189	1	Substrate By similarity
Natural variations
	Natural variant	280	1	S → L: dbSNP rs11555762. Ref.2 Ref.3		VAR_027277
Experimental info
	Mutagenesis	196	1	V → W: No effect. Ref.8
	Mutagenesis	234	1	F → A: Allows the conversion of androstenedione to testosterone. Ref.8

Sequences

	Sequence		Length	Mass (Da)
	Q53GQ0-1 [UniParc]. Last modified October 2, 2007. Version 2. Checksum: 8518336D7F514E50	FASTA	312	34,324
	10 20 30 40 50 60 MESALPAAGF LYWVGAGTVA YLALRISYSL FTALRVWGVG NEAGVGPGLG EWAVVTGSTD 70 80 90 100 110 120 GIGKSYAEEL AKHGMKVVLI SRSKDKLDQV SSEIKEKFKV ETRTIAVDFA SEDIYDKIKT 130 140 150 160 170 180 GLAGLEIGIL VNNVGMSYEY PEYFLDVPDL DNVIKKMINI NILSVCKMTQ LVLPGMVERS 190 200 210 220 230 240 KGAILNISSG SGMLPVPLLT IYSATKTFVD FFSQCLHEEY RSKGVFVQSV LPYFVATKLA 250 260 270 280 290 300 KIRKPTLDKP SPETFVKSAI KTVGLQSRTN GYLIHALMGS IISNLPSWIY LKIVMNMNKS 310 TRAHYLKKTK KN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human steroid dehydrogenase homologue, complete cds." Liu T., Zhang J., Fu G., Zhang Q., Ye M., Zhou J., Wu J., Shen Y., Yu M., Chen S., Mao M., Chen Z. Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT LEU-280. Tissue: Liver, Placenta, Thymus and Thyroid.
[3]	Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT LEU-280. Tissue: Liver.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Pancreas.
[5]	Bienvenut W.V. Submitted (JUN-2005) to UniProtKB Cited for: PROTEIN SEQUENCE OF 26-35; 65-72; 104-117; 157-179 AND 207-221, MASS SPECTROMETRY. Tissue: B-cell lymphoma.
[6]	"Identification of two mammalian reductases involved in the two-carbon fatty acyl elongation cascade." Moon Y.-A., Horton J.D. J. Biol. Chem. 278:7335-7343(2003) [PubMed: 12482854] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[7]	"Platelets express steroidogenic 17beta-hydroxysteroid dehydrogenases. Distinct profiles predict the essential thrombocythemic phenotype." Gnatenko D.V., Cupit L.D., Huang E.C., Dhundale A., Perrotta P.L., Bahou W.F. Thromb. Haemost. 94:412-421(2005) [PubMed: 16113833] [Abstract] Cited for: TISSUE SPECIFICITY.
[8]	"Characterization of type 12 17beta-hydroxysteroid dehydrogenase, an isoform of type 3 17beta-hydroxysteroid dehydrogenase responsible for estradiol formation in women." Luu-The V., Tremblay P., Labrie F. Mol. Endocrinol. 20:437-443(2006) [PubMed: 16166196] [Abstract] Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY, MUTAGENESIS OF VAL-196 AND PHE-234.
[9]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF078850 mRNA. Translation: AAD44482.1. AK027882 mRNA. No translation available. AK074952 mRNA. Translation: BAG52039.1. AK075216 mRNA. Translation: BAG52086.1. AK222881 mRNA. Translation: BAD96601.1. AK292625 mRNA. Translation: BAF85314.1. BC012043 mRNA. Translation: AAH12043.1.
IPI	IPI00007676.
RefSeq	NP_057226.1.
UniGene	Hs.132513
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	Q53GQ0.
PTM databases
PhosphoSite	Q53GQ0.
Proteomic databases
PRIDE	Q53GQ0.
Genome annotation databases
Ensembl	ENST00000278353; ENSP00000278353; ENSG00000149084; Homo sapiens. [Genome view] ENST00000395700; ENSP00000379052; ENSG00000149084; Homo sapiens. [Genome view]
GeneID	51144.
KEGG	hsa:51144.
NMPDR	fig|9606.3.peg.5483.
UCSC	uc001mxq.2. human.
Organism-specific databases
CTD	51144.
GeneCards	GC11P043658.
HGNC	HGNC:18646. HSD17B12.
HPA	HPA016427.
MIM	609574. gene.
PharmGKB	PA38618.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q53GQ0.
HOVERGEN	Q53GQ0.
OMA	YPEYFLD.
Enzyme and pathway databases
BRENDA	1.1.1.62. 247.
Gene expression databases
ArrayExpress	Q53GQ0.
Bgee	Q53GQ0.
CleanEx	HS_HSD17B12.
Genevestigator	Q53GQ0.
GermOnline	ENSG00000149084. Homo sapiens.
Family and domain databases
InterPro	IPR002198. DH_sc/Rdtase_SDR. IPR002347. Glc/ribitol_DH. IPR016040. NAD(P)-bd_dom. [Graphical view]
Gene3D	G3DSA:3.40.50.720. NAD(P)-bd. 1 hit.
PANTHER	PTHR19410. ADH_short_C2. 1 hit.
Pfam	PF00106. adh_short. 1 hit. [Graphical view]
PRINTS	PR00081. GDHRDH. PR00080. SDRFAMILY.
PROSITE	PS00061. ADH_SHORT. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	54008.
SOURCE	Search...

Entry information

Entry name

DHB12_HUMAN

Accession

Primary (citable) accession number: Q53GQ0
Secondary accession number(s): A8K9B0, Q96JU2, Q9Y6G8

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 5, 2006
Last sequence update:	October 2, 2007
Last modified:	November 3, 2009
This is version 48 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.