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Q53GQ0 (DHB12_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 96. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length312 AA.
Sequence statusComplete.
Protein existenceEvidence 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 processLipid biosynthesis
Lipid metabolism
Steroid biosynthesis
   Cellular componentEndoplasmic reticulum
Membrane
   Coding sequence diversityPolymorphism
   DomainTransmembrane
Transmembrane helix
   LigandNADP
   Molecular functionOxidoreductase
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processcellular lipid metabolic process

Traceable author statement. Source: Reactome

estrogen biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-UniPathway

extracellular matrix organization

Inferred from electronic annotation. Source: Ensembl

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: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

triglyceride biosynthetic process

Traceable author statement. Source: Reactome

   Cellular_componentendoplasmic reticulum membrane

Traceable author statement. Source: Reactome

extracellular matrix

Inferred from electronic annotation. Source: Ensembl

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular_functionestradiol 17-beta-dehydrogenase activity

Inferred from electronic annotation. Source: UniProtKB-EC

heparin binding

Inferred from electronic annotation. Source: Ensembl

protein binding

Inferred from physical interaction Ref.10. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 312312Estradiol 17-beta-dehydrogenase 12
PRO_0000248368

Regions

Transmembrane4 – 2421Helical; Potential
Transmembrane182 – 20221Helical; Potential
Transmembrane271 – 29121Helical; Potential
Nucleotide binding50 – 7930NADP By similarity
Motif308 – 3125Di-lysine motif

Sites

Active site2021Proton acceptor By similarity
Binding site1891Substrate By similarity

Natural variations

Natural variant2801S → L. Ref.2 Ref.3 Ref.4
Corresponds to variant rs11555762 [ dbSNP | Ensembl ].
VAR_027277

Experimental info

Mutagenesis1961V → W: No effect. Ref.9
Mutagenesis2341F → A: Allows the conversion of androstenedione to testosterone. Ref.9

Sequences

Sequence LengthMass (Da)Tools
Q53GQ0 [UniParc].

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

FASTA31234,324
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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, IDENTIFICATION BY 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.
CCDSCCDS7905.1.
RefSeqNP_057226.1. NM_016142.2.
UniGeneHs.132513.

3D structure databases

ProteinModelPortalQ53GQ0.
SMRQ53GQ0. Positions 51-294.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid119328. 14 interactions.
IntActQ53GQ0. 6 interactions.
STRING9606.ENSP00000278353.

Chemistry

ChEMBLCHEMBL5998.

PTM databases

PhosphoSiteQ53GQ0.

Polymorphism databases

DMDM158931120.

Proteomic databases

MaxQBQ53GQ0.
PaxDbQ53GQ0.
PRIDEQ53GQ0.

Protocols and materials databases

DNASU51144.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000278353; ENSP00000278353; ENSG00000149084.
GeneID51144.
KEGGhsa:51144.
UCSCuc001mxq.4. human.

Organism-specific databases

CTD51144.
GeneCardsGC11P043577.
HGNCHGNC:18646. HSD17B12.
HPAHPA016427.
MIM609574. gene.
neXtProtNX_Q53GQ0.
PharmGKBPA38618.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0300.
HOGENOMHOG000039237.
HOVERGENHBG005478.
InParanoidQ53GQ0.
KOK10251.
OMAKHGMKVV.
PhylomeDBQ53GQ0.
TreeFamTF314591.

Enzyme and pathway databases

BRENDA1.1.1.62. 2681.
ReactomeREACT_111217. Metabolism.
REACT_15493. Steroid hormones.
SABIO-RKQ53GQ0.
UniPathwayUPA00094.
UPA00769.

Gene expression databases

ArrayExpressQ53GQ0.
BgeeQ53GQ0.
CleanExHS_HSD17B12.
GenevestigatorQ53GQ0.

Family and domain databases

Gene3D3.40.50.720. 1 hit.
InterProIPR002198. DH_sc/Rdtase_SDR.
IPR002347. Glc/ribitol_DH.
IPR016040. NAD(P)-bd_dom.
IPR020904. Sc_DH/Rdtase_CS.
[Graphical view]
PfamPF00106. adh_short. 1 hit.
[Graphical view]
PIRSFPIRSF000126. 11-beta-HSD1. 1 hit.
PRINTSPR00081. GDHRDH.
PR00080. SDRFAMILY.
PROSITEPS00061. ADH_SHORT. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiHSD17B12.
GenomeRNAi51144.
NextBio54008.
PROQ53GQ0.
SOURCESearch...

Entry information

Entry nameDHB12_HUMAN
AccessionPrimary (citable) accession number: Q53GQ0
Secondary accession number(s): A8K9B0 expand/collapse secondary AC list , D3DR23, Q96JU2, Q9Y6G8
Entry history
Integrated into UniProtKB/Swiss-Prot: September 5, 2006
Last sequence update: October 2, 2007
Last modified: July 9, 2014
This is version 96 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

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