Estradiol 17-beta-dehydrogenase 12 - Homo sapiens (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)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

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Protein attributes

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

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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: K_M=3.5 µM for estrone
Sequence caution	The sequence AK027882 differs from that shown. Reason: Frameshift at position 92.

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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	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 membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	estradiol 17-beta-dehydrogenase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

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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

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Sequences

Sequence

Length

Mass (Da)

Tools

Q53GQ0-1 [UniParc].

Last modified October 2, 2007. Version 2.
Checksum: 8518336D7F514E50
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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

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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. Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT LEU-280. Tissue: Liver 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.

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Cross-references

Sequence databases
	AF078850 mRNA. Translation: AAD44482.1. AK027882 mRNA. No translation available. AK222881 mRNA. Translation: BAD96601.1. BC012043 mRNA. Translation: AAH12043.1.
IPI	IPI00007676.
RefSeq	NP_057226.1.
UniGene	Hs.132513
3D structure databases
ModBase	Search...
PTM databases
PhosphoSite	Q53GQ0.
Proteomic databases
PRIDE	Q53GQ0.
Genome annotation databases
Ensembl	ENSG00000149084. Homo sapiens. [Contig view]
GeneID	51144.
KEGG	hsa:51144.
NMPDR	fig\|9606.3.peg.5483.
Organism-specific databases
GeneCards	GC11P043658.
HGNC	HGNC:18646. HSD17B12.
HPA	HPA016427.
MIM	609574. gene.
PharmGKB	PA38618.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q53GQ0.
HOVERGEN	Q53GQ0.
OMA	Q53GQ0. YPEYFLD.
Enzyme and pathway databases
BRENDA	1.1.1.62. 247.
Gene expression databases
ArrayExpress	Q53GQ0.
Bgee	Q53GQ0.
CleanEx	HS_HSD17B12.
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...

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Entry information

Entry name

DHB12_HUMAN

Accession

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

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 5, 2006
Last sequence update:	October 2, 2007
Last modified:	June 16, 2009
This is version 42 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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Relevant documents

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PATHWAY comments

Index of metabolic and biosynthesis pathways

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Natural variations

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

PTM databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents