Q53GQ0 (DHB12_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	312 AA.
Sequence status	Complete.
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.7 Ref.9
Catalytic activity	17-beta-estradiol + NAD(P)+ = estrone + NAD(P)H.
Pathway	Steroid biosynthesis; estrogen biosynthesis. Lipid metabolism; fatty acid biosynthesis.
Subunit structure	Interacts with ELOVL1 and LASS2. Ref.10
Subcellular location	Endoplasmic reticulum membrane; Multi-pass membrane protein Ref.7.
Tissue specificity	Expressed in most tissues tested. Highly expressed in the ovary and mammary. Expressed in platelets. Ref.7 Ref.8 Ref.9
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 Ref.9
Sequence caution	The sequence AK027882 differs from that shown. Reason: Frameshift at position 92.

Ontologies

Keywords
Biological process	Lipid biosynthesis Lipid metabolism Steroid biosynthesis
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane Transmembrane helix
Ligand	NADP
Molecular function	Oxidoreductase
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	estrogen biosynthetic process Inferred from electronic annotation. Source: UniProtKB-UniPathway extracellular matrix organization Inferred from electronic annotation. Source: Compara fatty acid biosynthetic process Inferred from electronic annotation. Source: UniProtKB-UniPathway long-chain fatty-acyl-CoA biosynthetic process Traceable author statement. Source: Reactome positive regulation of cell-substrate adhesion Inferred from electronic annotation. Source: Compara small molecule metabolic process Traceable author statement. Source: Reactome triglyceride biosynthetic process Traceable author statement. Source: Reactome
Cellular_component	endoplasmic reticulum membrane Traceable author statement. Source: Reactome extracellular matrix Inferred from electronic annotation. Source: Compara integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	estradiol 17-beta-dehydrogenase activity Inferred from electronic annotation. Source: EC heparin binding Inferred from electronic annotation. Source: Compara nucleotide binding Inferred from electronic annotation. Source: InterPro
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	Helical; Potential
	Transmembrane	182 – 202	21	Helical; Potential
	Transmembrane	271 – 291	21	Helical; 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. Ref.2 Ref.3 Ref.4 Corresponds to variant rs11555762 [ dbSNP | Ensembl ].		VAR_027277
Experimental info
	Mutagenesis	196	1	V → W: No effect. Ref.9
	Mutagenesis	234	1	F → A: Allows the conversion of androstenedione to testosterone. Ref.9

Sequences

	Sequence		Length	Mass (Da)
	Q53GQ0 [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] [Europe PMC] [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]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT LEU-280.
[5]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Pancreas.
[6]	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.
[7]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[8]	"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] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[9]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY, MUTAGENESIS OF VAL-196 AND PHE-234.
[10]	"ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingolipid synthesis." Ohno Y., Suto S., Yamanaka M., Mizutani Y., Mitsutake S., Igarashi Y., Sassa T., Kihara A. Proc. Natl. Acad. Sci. U.S.A. 107:18439-18444(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ELOVL1 AND LASS2.
[11]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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. CH471064 Genomic DNA. Translation: EAW68082.1. CH471064 Genomic DNA. Translation: EAW68088.1. BC012043 mRNA. Translation: AAH12043.1.
IPI	IPI00007676.
RefSeq	NP_057226.1. NM_016142.2.
UniGene	Hs.132513.
3D structure databases
HSSP	HSSP built from PDB template 1YB1 based on UniProtKB Q8NBQ5.
ProteinModelPortal	Q53GQ0.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q53GQ0. 5 interactions.
STRING	9606.ENSP00000278353.
PTM databases
PhosphoSite	Q53GQ0.
Polymorphism databases
DMDM	158931120.
Proteomic databases
PaxDb	Q53GQ0.
PRIDE	Q53GQ0.
Protocols and materials databases
DNASU	51144.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000278353; ENSP00000278353; ENSG00000149084.
GeneID	51144.
KEGG	hsa:51144.
UCSC	uc001mxq.4. human.
Organism-specific databases
CTD	51144.
GeneCards	GC11P043577.
HGNC	HGNC:18646. HSD17B12.
HPA	HPA016427.
MIM	609574. gene.
neXtProt	NX_Q53GQ0.
PharmGKB	PA38618.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0300.
HOGENOM	HOG000039237.
HOVERGEN	HBG005478.
InParanoid	Q53GQ0.
KO	K10251.
OMA	MNKSTRA.
OrthoDB	EOG4HMJB0.
PhylomeDB	Q53GQ0.
Enzyme and pathway databases
BRENDA	1.1.1.62. 2681.
Reactome	REACT_111217. Metabolism.
SABIO-RK	Q53GQ0.
UniPathway	UPA00094. UPA00769.
Gene expression databases
ArrayExpress	Q53GQ0.
Bgee	Q53GQ0.
CleanEx	HS_HSD17B12.
Genevestigator	Q53GQ0.
GermOnline	ENSG00000149084. Homo sapiens.
Family and domain databases
Gene3D	3.40.50.720. 1 hit.
InterPro	IPR002198. DH_sc/Rdtase_SDR. IPR002347. Glc/ribitol_DH. IPR016040. NAD(P)-bd_dom. IPR020904. Sc_DH/Rdtase_CS. [Graphical view]
Pfam	PF00106. adh_short. 1 hit. [Graphical view]
PIRSF	PIRSF000126. 11-beta-HSD1. 1 hit.
PRINTS	PR00081. GDHRDH. PR00080. SDRFAMILY.
PROSITE	PS00061. ADH_SHORT. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL5998.
GenomeRNAi	51144.
NextBio	54008.
SOURCE	Search...

Entry information

Entry name

DHB12_HUMAN

Accession

Primary (citable) accession number: Q53GQ0
Secondary accession number(s): A8K9B0 , D3DR23, Q96JU2, Q9Y6G8

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 5, 2006
Last sequence update:	October 2, 2007
Last modified:	May 1, 2013
This is version 83 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.