Reviewed, UniProtKB/Swiss-Prot O70503 (DHB12_MOUSE)

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.-
    KIK-I

Gene names

Name:	Hsd17b12
Synonyms:	Kik1

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	312 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at transcript 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 females. 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 By similarity.
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 By similarity.
Tissue specificity	Expressed in most tissues tested. Ref.4
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.

Ontologies

Keywords
Biological process	Lipid synthesis Steroid biosynthesis
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Alternative splicing
Domain	Transmembrane
Ligand	NADP
Molecular function	Oxidoreductase
Gene Ontology (GO)
Biological process	extracellular matrix organization Inferred from direct assay. Source: MGI oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of cell-substrate adhesion Inferred from direct assay. Source: MGI steroid biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell extracellular matrix Inferred from direct assay. Source: MGI integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	collagen binding Inferred from direct assay. Source: MGI estradiol 17-beta-dehydrogenase activity Inferred from electronic annotation. Source: EC fibronectin binding Inferred from direct assay. Source: MGI heparin binding Inferred from direct assay. Source: MGI
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O70503-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: O70503-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-135: Missing.

Note: No experimental confirmation available.

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_0000054576
Regions
	Transmembrane	4 – 24	21	Potential
	Transmembrane	182 – 202	21	Potential
	Transmembrane	269 – 285	17	Potential
	Nucleotide binding	50 – 79	30	NADP By similarity
	Motif	308 – 312	5	Di-lysine motif By similarity
Sites
	Active site	202	1	Proton acceptor By similarity
	Binding site	189	1	Substrate By similarity
Natural variations
	Alternative sequence	1 – 135	135	Missing in isoform 2.		VSP_020255
Experimental info
	Sequence conflict	2	1	E → V in BAE39915. Ref.2
	Sequence conflict	256	1	V → M in BAE29906. Ref.2
	Sequence conflict	256	1	V → M in BAE31260. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified August 1, 1998. Version 1. Checksum: 7D255188FA1F8DDB	FASTA	312	34,742
	10 20 30 40 50 60 MECAPPAAGF LYWVGASTIA YLALRASYSL FRAFQVWCVG NEALVGPRLG EWAVVTGGTD 70 80 90 100 110 120 GIGKAYAEEL AKRGMKIVLI SRSQDKLNQV SNNIKEKFNV ETRTIAVDFS LDDIYDKIKT 130 140 150 160 170 180 GLSGLEIGVL VNNVGMSYEY PEYFLEIPDL DNTIKKLINI NVLSVCKVTR LVLPGMVERS 190 200 210 220 230 240 KGVILNISSA SGMLPVPLLT IYSATKAFVD FFSQCLHEEY KSKGIFVQSV MPYLVATKLA 250 260 270 280 290 300 KIQKPTLDKP SAETFVKSAI KTVGLQTRTT GYVIHSLMGS INSIMPRWMY FKIIMGFSKS 310 LRNRYLKKRK KN
	Isoform 2. Checksum: CAC34046DDAE3A0D	FASTA	177	20,127
	10 20 30 40 50 60 MSYEYPEYFL EIPDLDNTIK KLININVLSV CKVTRLVLPG MVERSKGVIL NISSASGMLP 70 80 90 100 110 120 VPLLTIYSAT KAFVDFFSQC LHEEYKSKGI FVQSVMPYLV ATKLAKIQKP TLDKPSAETF 130 140 150 160 170 VKSAIKTVGL QTRTTGYVIH SLMGSINSIM PRWMYFKIIM GFSKSLRNRY LKKRKKN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	Gambotto A., Pagliano O., Robbins P., Deleo A. Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Strain: BALB/c. Tissue: Liver.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Strain: BALB/c, C57BL/6J and NOD. Tissue: Bone marrow, Cerebellum, Colon, Head, Lung and Thymus.
[3]	"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] (ISOFORM 2). Strain: FVB/N-3. Tissue: Mammary tumor.
[4]	"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: TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF064635 mRNA. Translation: AAC16885.1. AK078841 mRNA. Translation: BAC37418.1. AK081869 mRNA. Translation: BAC38354.1. AK082715 mRNA. Translation: BAC38583.1. AK088521 mRNA. Translation: BAC40401.1. AK150849 mRNA. Translation: BAE29906.1. AK152489 mRNA. Translation: BAE31260.1. AK166027 mRNA. Translation: BAE38530.1. AK167908 mRNA. Translation: BAE39915.1. BC037620 mRNA. Translation: AAH37620.1.
IPI	IPI00119219. IPI00785470.
RefSeq	NP_062631.1.
UniGene	Mm.22505
3D structure databases
HSSP	HSSP built from PDB template 2AE1 based on UniProtKB P50163.
ModBase	Search...
PTM databases
PhosphoSite	O70503.
Proteomic databases
PRIDE	O70503.
Genome annotation databases
Ensembl	ENSMUSG00000027195. Mus musculus. [Contig view]
GeneID	56348.
KEGG	mmu:56348.
Organism-specific databases
MGI	MGI:1926967. Hsd17b12.
Phylogenomic databases
HOVERGEN	O70503.
OMA	O70503. YPEYFLD.
Enzyme and pathway databases
BRENDA	1.1.1.62. 244.
Gene expression databases
ArrayExpress	O70503.
Bgee	O70503.
CleanEx	MM_HSD17B12.
GermOnline	ENSMUSG00000027195. Mus musculus.
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	312340.
SOURCE	Search...

Entry information

Entry name

DHB12_MOUSE

Accession

Primary (citable) accession number: O70503
Secondary accession number(s): Q3TID1 , Q3U7V9, Q542N3, Q8CI39

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 15, 1998
Last sequence update:	August 1, 1998
Last modified:	June 16, 2009
This is version 74 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)