P16232 (DHI1_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Corticosteroid 11-beta-dehydrogenase isozyme 1
EC=1.1.1.146

Alternative name(s):
11-beta-hydroxysteroid dehydrogenase 1
Short name=11-DH
Short name=11-beta-HSD1

Gene names

Name:	Hsd11b1
Synonyms:	Hsd11

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	288 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes reversibly the conversion of corticosterone to 11-dehydrocorticosterone.
Catalytic activity	An 11-beta-hydroxysteroid + NADP+ = an 11-oxosteroid + NADPH.
Subunit structure	Homodimer By similarity.
Subcellular location	Endoplasmic reticulum membrane; Single-pass type II membrane protein.
Tissue specificity	Liver, kidney, testis and placenta.
Developmental stage	Expression of both isoforms is found in 1 week-old rats. Expression increases exponentially up to 4 weeks but after this time there is no further increase up to 16 weeks.
Post-translational modification	Glycosylated.
Sequence similarities	Belongs to the short-chain dehydrogenases/reductases (SDR) family.

Ontologies

Keywords
Biological process	Lipid metabolism Steroid metabolism
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Alternative promoter usage
Domain	Signal-anchor Transmembrane Transmembrane helix
Ligand	NADP
Molecular function	Oxidoreductase
PTM	Glycoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to estradiol stimulus Inferred from expression pattern PubMed 19380458. Source: RGD glucocorticoid biosynthetic process Inferred from direct assay Ref.5. Source: RGD glucocorticoid catabolic process Inferred from direct assay Ref.5. Source: RGD phthalate metabolic process Inferred from expression pattern PubMed 19815848. Source: RGD regulation of pentose-phosphate shunt Inferred from direct assay PubMed 16234247. Source: RGD response to nutrient levels Inferred from expression pattern PubMed 16941667. Source: RGD
Cellular_component	apical part of cell Inferred from direct assay PubMed 12810566. Source: RGD endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW nuclear membrane Inferred from direct assay PubMed 11250946. Source: RGD rough endoplasmic reticulum Inferred from direct assay PubMed 11250946. Source: RGD
Molecular_function	11-beta-hydroxysteroid dehydrogenase (NADP+) activity Inferred from electronic annotation. Source: EC 11-beta-hydroxysteroid dehydrogenase [NAD(P)] activity Inferred from direct assay Ref.1. Source: RGD NADP binding Inferred from direct assay PubMed 15761036. Source: RGD steroid binding Inferred from physical interaction PubMed 15761036. Source: RGD
Complete GO annotation...

Alternative products

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

Isoform 11-HSD1A (identifier: P16232-1)

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 11-HSD1B (identifier: P16232-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-26: Missing.

Note: Kidney-specific.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 288	288	Corticosteroid 11-beta-dehydrogenase isozyme 1		PRO_0000054623
Regions
	Topological domain	1 – 4	4	Cytoplasmic Potential
	Transmembrane	5 – 20	16	Helical; Signal-anchor for type II membrane protein; Potential
	Topological domain	21 – 288	268	Lumenal Potential
	Nucleotide binding	37 – 63	27	NADP By similarity
	Nucleotide binding	88 – 89	2	NADP By similarity
	Nucleotide binding	115 – 117	3	NADP By similarity
	Nucleotide binding	179 – 183	5	NADP By similarity
	Nucleotide binding	212 – 218	7	NADP By similarity
Sites
	Active site	179	1	Proton acceptor By similarity
	Binding site	166	1	Substrate By similarity
Amino acid modifications
	Glycosylation	158	1	N-linked (GlcNAc...) Potential
	Glycosylation	203	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	1 – 26	26	Missing in isoform 11-HSD1B.		VSP_012616
Experimental info
	Mutagenesis	110	1	D → N: Slight loss of activity.
	Mutagenesis	179	1	Y → F or S: Complete loss of activity. Ref.8
	Mutagenesis	183	1	K → R: Complete loss of activity. Ref.8
	Sequence conflict	31	1	K → N in CAA71447. Ref.4
	Sequence conflict	235	1	E → Q in AAA40886. Ref.1
	Sequence conflict	241	1	Missing in AAA40886. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 11-HSD1A [UniParc]. Last modified October 10, 2002. Version 2. Checksum: AC445C0D92004808	FASTA	288	31,883
	10 20 30 40 50 60 MKKYLLPVLV LCLGYYYSTN EEFRPEMLQG KKVIVTGASK GIGREMAYHL SKMGAHVVLT 70 80 90 100 110 120 ARSEEGLQKV VSRCLELGAA SAHYIAGTME DMAFAERFVV EAGKLLGGLD MLILNHITQT 130 140 150 160 170 180 TMSLFHDDIH SVRRSMEVNF LSYVVLSTAA LPMLKQSNGS IAIISSMAGK MTQPLIASYS 190 200 210 220 230 240 ASKFALDGFF STIRKEHLMT KVNVSITLCV LGFIDTETAL KETSGIILSQ AAPKEECALE 250 260 270 280 IIKGTVLRKD EVYYDKSSWT PLLLGNPGRR IMEFLSLRSY NRDLFVSN
	Isoform 11-HSD1B [UniParc]. Checksum: 22616268BA4DF8C9	FASTA	262	28,732
	10 20 30 40 50 60 MLQGKKVIVT GASKGIGREM AYHLSKMGAH VVLTARSEEG LQKVVSRCLE LGAASAHYIA 70 80 90 100 110 120 GTMEDMAFAE RFVVEAGKLL GGLDMLILNH ITQTTMSLFH DDIHSVRRSM EVNFLSYVVL 130 140 150 160 170 180 STAALPMLKQ SNGSIAIISS MAGKMTQPLI ASYSASKFAL DGFFSTIRKE HLMTKVNVSI 190 200 210 220 230 240 TLCVLGFIDT ETALKETSGI ILSQAAPKEE CALEIIKGTV LRKDEVYYDK SSWTPLLLGN 250 260 PGRRIMEFLS LRSYNRDLFV SN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and expression of rat cDNA encoding corticosteroid 11 beta-dehydrogenase." Agarwal A.K., Monder C., Eckstein B., White P.C. J. Biol. Chem. 264:18939-18943(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 11-HSD1A). Tissue: Liver.
[2]	"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: Kidney.
[3]	"Differential promoter usage by the rat 11 beta-hydroxysteroid dehydrogenase gene." Moisan M.P., Edwards C.R., Seckl J.R. Mol. Endocrinol. 6:1082-1087(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE OF 1-69 (ISOFORMS 11-HSD1A AND 11-HSD1B), ALTERNATIVE PROMOTER USAGE.
[4]	"C/EBP regulates hepatic transcription of 11beta-hydroxysteroid dehydrogenase type 1. A novel mechanism for cross-talk between the C/EBP and glucocorticoid signaling pathways." Williams L.J.S., Lyons V., MacLeod I., Rajan V., Darlington G.J., Poli V., Seckl J.R., Chapman K.E. J. Biol. Chem. 275:30232-30239(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-69 (ISOFORM 11-HSD1A). Strain: Sprague-Dawley.
[5]	"Purification of full-length recombinant human and rat type 1 11beta-hydroxysteroid dehydrogenases with retained oxidoreductase activities." Nobel C.S.I., Dunas F., Abrahmsen L.B. Protein Expr. Purif. 26:349-356(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE OF 21-273.
[6]	"Tissue-specific expression of an 11 beta-hydroxysteroid dehydrogenase with a truncated N-terminal domain. A potential mechanism for differential intracellular localization within mineralocorticoid target cells." Krozowski Z., Obeyesekere V., Smith R., Mercer W. J. Biol. Chem. 267:2569-2574(1992) [PubMed] [Europe PMC] [Abstract] Cited for: PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 11-HSD1A AND 11-HSD1B), ALTERNATIVE PROMOTER USAGE. Strain: Sprague-Dawley. Tissue: Kidney.
[7]	"The syndrome of apparent mineralocorticoid excess: its association with 11 beta-dehydrogenase and 5 beta-reductase deficiency and some consequences for corticosteroid metabolism." Monder C., Shackleton C.H.L., Bradlow H.L., New M.I., Stoner E., Iohan F., Lakshmi V. J. Clin. Endocrinol. Metab. 63:550-557(1986) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 1-40.
[8]	"Tyr-179 and Lys-183 are essential for enzymatic activity of 11 beta-hydroxysteroid dehydrogenase." Obeid J., White P.C. Biochem. Biophys. Res. Commun. 188:222-227(1992) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF TYR-179 AND LYS-183.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	J05107 mRNA. Translation: AAA40886.1. BC078865 mRNA. Translation: AAH78865.1. S43333 Genomic DNA. Translation: AAB22993.1. Y10420 Genomic DNA. Translation: CAA71447.1. M77835 mRNA. Translation: AAA40600.1.
IPI	IPI00211096. IPI00760118.
PIR	DXRTBH. A34430.
RefSeq	NP_058776.2. NM_017080.2.
UniGene	Rn.231830. Rn.888.
3D structure databases
ProteinModelPortal	P16232.
SMR	P16232. Positions 21-285.
ModBase	Search...
Proteomic databases
PaxDb	P16232.
PRIDE	P16232.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000007870; ENSRNOP00000007870; ENSRNOG00000005861.
GeneID	25116.
KEGG	rno:25116.
Organism-specific databases
CTD	3290.
RGD	2834. Hsd11b1.
Phylogenomic databases
eggNOG	NOG268650.
GeneTree	ENSGT00700000104225.
HOGENOM	HOG000010276.
HOVERGEN	HBG005481.
KO	K15680.
Enzyme and pathway databases
SABIO-RK	P16232.
Gene expression databases
ArrayExpress	P16232.
Genevestigator	P16232.
GermOnline	ENSRNOG00000005861. Rattus norvegicus.
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]
PRINTS	PR00081. GDHRDH.
PROSITE	PS00061. ADH_SHORT. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P16232.
ChEMBL	CHEMBL2391.
NextBio	605481.

Entry information

Entry name

DHI1_RAT

Accession

Primary (citable) accession number: P16232
Secondary accession number(s): O09170, Q6LDH6

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	October 10, 2002
Last modified:	April 3, 2013
This is version 117 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program