[1]	NUCLEOTIDE SEQUENCE [MRNA]. TISSUE=Kidney; DOI=10.1016/0303-7207(94)90176-7; PubMed=7859916 [NCBI, ExPASy, EBI, Israel, Japan] Albiston A.L., Obeyesekere V.R., Smith R.E., Krozowski Z.S.; "Cloning and tissue distribution of the human 11 beta-hydroxysteroid dehydrogenase type 2 enzyme."; Mol. Cell. Endocrinol. 105:R11-R17(1994).
[2]	NUCLEOTIDE SEQUENCE [GENOMIC DNA]. TISSUE=Kidney; DOI=10.1006/geno.1995.1231; PubMed=8530071 [NCBI, ExPASy, EBI, Israel, Japan] Agarwal A.K., Rogerson F.M., Mune T., White P.C.; "Gene structure and chromosomal localization of the human HSD11K gene encoding the kidney (type 2) isozyme of 11 beta-hydroxysteroid dehydrogenase."; Genomics 29:195-199(1995).
[3]	NUCLEOTIDE SEQUENCE [MRNA]. TISSUE=Placenta; PubMed=8611140 [NCBI, ExPASy, EBI, Israel, Japan] Brown R.W., Chapman K.E., Kotelevtsev Y., Yau J.L., Lindsay R.S., Brett L., Leckie C., Murad P., Lyons V., Mullins J.J., Edwards C.R.W., Seckl J.R.; "Cloning and production of antisera to human placental 11 beta-hydroxysteroid dehydrogenase type 2."; Biochem. J. 313:1007-1017(1996).
[4]	NUCLEOTIDE SEQUENCE [GENOMIC DNA]. SeattleSNPs variation discovery resource; Submitted (JUN-2007) to the EMBL/GenBank/DDBJ databases.
[5]	NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
[6]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. TISSUE=Ovary; DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan] The MGC Project Team; "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."; Genome Res. 14:2121-2127(2004).
[7]	PROTEIN SEQUENCE OF 19-24; 77-84; 102-112; 134-154; 191-198; 214-227; 229-235; 256-266; 272-278 AND 375-401. TISSUE=Placenta; PubMed=8611186 [NCBI, ExPASy, EBI, Israel, Japan] Brown R.W., Chapman K.E., Murad P., Edwards C.R., Seckl J.R.; "Purification of 11 beta-hydroxysteroid dehydrogenase type 2 from human placenta utilizing a novel affinity labelling technique."; Biochem. J. 313:997-1005(1996).
[8]	NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 90-221. Amin H.K., Hoeppner W.; "Human hydroxysteroid dehydrogenase type 2 HSD11B2."; Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases.
[9]	NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 182-211; 235-264 AND 325-354, AND VARIANTS AME CYS-186; CYS-208; 250-PRO-SER-251 AND 337-ARG-TYR-338 DELINS HIS. DOI=10.1210/jc.80.11.3145; PubMed=7593417 [NCBI, ExPASy, EBI, Israel, Japan] Wilson R.C., Harbison M.D., Krozowski Z.S., Funder J.W., Shackleton C.H.L., Hanauske-Abel H.M., Wei J.-Q., Hertecant J., Moran A., Neiberger R.E., Balfe J.W., Fattah A., Daneman D., Licholai T., New M.I.; "Several homozygous mutations in the gene for 11 beta-hydroxysteroid dehydrogenase type 2 in patients with apparent mineralocorticoid excess."; J. Clin. Endocrinol. Metab. 80:3145-3150(1995).
[10]	CHARACTERIZATION. DOI=10.1016/S0140-6736(87)91014-2; PubMed=2889032 [NCBI, ExPASy, EBI, Israel, Japan] Stewart P.M., Wallace A.M., Valentino R., Burt D., Shackleton C.H.L., Edwards C.R.W.; "Mineralocorticoid activity of liquorice: 11-beta-hydroxysteroid dehydrogenase deficiency comes of age."; Lancet 2:821-824(1987).
[11]	INTERACTION WITH NR3C2. DOI=10.1074/jbc.M100374200; PubMed=11350956 [NCBI, ExPASy, EBI, Israel, Japan] Odermatt A., Arnold P., Frey F.J.; "The intracellular localization of the mineralocorticoid receptor is regulated by 11beta-hydroxysteroid dehydrogenase type 2."; J. Biol. Chem. 276:28484-28492(2001).
[12]	VARIANT AME CYS-337. DOI=10.1210/jc.80.7.2263; PubMed=7608290 [NCBI, ExPASy, EBI, Israel, Japan] Wilson R.C., Krozowski Z.S., Li K., Obeyesekere V.R., Razzaghy-Azar M., Harbison M.D., Wei J.-Q., Shackleton C.H.L., Funder J.W., New M.I.; "A mutation in the HSD11B2 gene in a family with apparent mineralocorticoid excess."; J. Clin. Endocrinol. Metab. 80:2263-2266(1995).
[13]	CHARACTERIZATION OF VARIANTS AME CYS-208; CYS-213; 250-PRO-SER-251 AND 337-ARG-TYR-338 DELINS HIS. DOI=10.1038/ng0895-394; PubMed=7670488 [NCBI, ExPASy, EBI, Israel, Japan] Mune T., Rogerson F.M., Nikkilae H., Agarwal A.K., White P.C.; "Human hypertension caused by mutations in the kidney isozyme of 11 beta-hydroxysteroid dehydrogenase."; Nat. Genet. 10:394-399(1995).
[14]	CHARACTERIZATION OF VARIANTS AME HIS-208 AND 337-ARG-TYR-338 DELINS HIS. DOI=10.1210/jc.82.12.4054; PubMed=9398712 [NCBI, ExPASy, EBI, Israel, Japan] Kitanaka S., Katsumata N., Tanae A., Hibi I., Takeyama K., Fuse H., Kato S., Tanaka T.; "A new compound heterozygous mutation in the 11 beta-hydroxysteroid dehydrogenase type 2 gene in a case of apparent mineralocorticoid excess."; J. Clin. Endocrinol. Metab. 82:4054-4058(1997).
[15]	CHARACTERIZATION OF VARIANT AME CYS-279. DOI=10.1086/301955; PubMed=9683587 [NCBI, ExPASy, EBI, Israel, Japan] Li A., Tedde R., Krozowski Z.S., Pala A., Li K.X.Z., Shackleton C.H.L., Mantero F., Palermo M., Stewart P.M.; "Molecular basis for hypertension in the 'type II variant' of apparent mineralocorticoid excess."; Am. J. Hum. Genet. 63:370-379(1998).
[16]	VARIANTS AME CYS-186; CYS-208; ASN-244; ARG-250; 250-PRO-SER-251; CYS-337 AND 337-ARG-TYR-338 DELINS HIS. DOI=10.1210/jc.83.7.2244; PubMed=9661590 [NCBI, ExPASy, EBI, Israel, Japan] Dave-Sharma S., Wilson R.C., Harbison M.D., Newfield R., Azar M.R., Krozowski Z.S., Funder J.W., Shackleton C.H.L., Bradlow H.L., Wei J.-Q., Hertecant J., Moran A., Neiberger R.E., Balfe J.W., Fattah A., Daneman D., Akkurt H.I., De Santis C., New M.I.; "Examination of genotype and phenotype relationships in 14 patients with apparent mineralocorticoid excess."; J. Clin. Endocrinol. Metab. 83:2244-2254(1998).
[17]	CHARACTERIZATION OF VARIANT AME CYS-213. DOI=10.1210/jc.83.12.4391; PubMed=9851783 [NCBI, ExPASy, EBI, Israel, Japan] Rogoff D., Smolenicka Z., Bergada I., Vallejo G., Barontini M., Heinrich J.J., Ferrari P.; "The codon 213 of the 11beta-hydroxysteroid dehydrogenase type 2 gene is a hot spot for mutations in apparent mineralocorticoid excess."; J. Clin. Endocrinol. Metab. 83:4391-4393(1998).
[18]	CHARACTERIZATION OF VARIANT HYPERTENSION LEU-227. DOI=10.1073/pnas.95.17.10200; PubMed=9707624 [NCBI, ExPASy, EBI, Israel, Japan] Wilson R.C., Dave-Sharma S., Wei J.-Q., Obeyesekere V.R., Li K., Ferrari P., Krozowski Z.S., Shackleton C.H.L., Bradlow L., Wiens T., New M.I.; "A genetic defect resulting in mild low-renin hypertension."; Proc. Natl. Acad. Sci. U.S.A. 95:10200-10205(1998).
[19]	CHARACTERIZATION OF VARIANTS AME CYS-213 AND VAL-328. PubMed=10489390 [NCBI, ExPASy, EBI, Israel, Japan] Morineau G., Marc J.-M., Boudi A., Galons H., Gourmelen M., Corvol P., Pascoe L., Fiet J.; "Genetic, biochemical, and clinical studies of patients with A328V or R213C mutations in 11betaHSD2 causing apparent mineralocorticoid excess."; Hypertension 34:435-441(1999).
[20]	CHARACTERIZATION OF VARIANTS AME ARG-179; PHE-180; HIS-208; VAL-237 AND VAL-328. PubMed=10523339 [NCBI, ExPASy, EBI, Israel, Japan] Nunez B.S., Rogerson F.M., Mune T., Igarashi Y., Nakagawa Y., Phillipov G., Moudgil A., Travis L.B., Palermo M., Shackleton C.H.L., White P.C.; "Mutants of 11beta-hydroxysteroid dehydrogenase (11-HSD2) with partial activity: improved correlations between genotype and biochemical phenotype in apparent mineralocorticoid excess."; Hypertension 34:638-642(1999).
[21]	CHARACTERIZATION OF AME VARIANT 114-LEU-GLU-115 DEL, AND MUTAGENESIS OF GLU-115. DOI=10.1210/jc.86.3.1247; PubMed=11238516 [NCBI, ExPASy, EBI, Israel, Japan] Odermatt A., Dick B., Arnold P., Zaehner T., Plueschke V., Deregibus M.N., Repetto H., Frey B.M., Frey F.J., Ferrari P.; "A mutation in the cofactor-binding domain of 11beta-hydroxysteroid dehydrogenase type 2 associated with mineralocorticoid hypertension."; J. Clin. Endocrinol. Metab. 86:1247-1252(2001).

Comments

FUNCTION: Catalyzes the conversion of cortisol to the inactive metabolite cortisone. Modulates intracellular glucocorticoid levels, thus protecting the nonselective mineralocorticoid receptor from occupation by glucocorticoids.
CATALYTIC ACTIVITY: An 11-beta-hydroxysteroid + NAD⁺ = an 11-oxosteroid + NADH.
ENZYME REGULATION: Inhibited by glycyrrhetinic acid (derived from liquorice), carbenoloxone and 11-alpha-OH-progesterone (By similarity).
SUBUNIT: Interacts with ligand-free cytoplasmic NR3C2.
SUBCELLULAR LOCATION: Microsome. Endoplasmic reticulum (Potential).
TISSUE SPECIFICITY: Found in placenta, kidney, pancreas, prostate, ovary, small intestine and colon.
DISEASE: Defects in HSD11B2 are the cause of apparent mineralocorticoid excess (AME) [MIM:218030]. AME is a potentially fatal disease characterized by severe juvenile low-renin hypertension, sodium retention, hypokalemia and low levels of aldosterone. It often leads to nephrocalcinosis.
MISCELLANEOUS: Consumption of large amounts of liquorice can lead to apparent mineralocorticoid excess and hypertension.
SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR) family.
WEB RESOURCE: Name=GeneReviews; URL="http://www.genetests.org/query?gene=HSD11B2";.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

U14631; AAA91969.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
U27317; AAB48544.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
U26726; AAC50356.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
EF694683; ABS29267.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
CH471092; EAW83134.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC036780; AAH36780.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC064536; AAH64536.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AY046280; AAK91586.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

IPI00300050; -.

S62789; S62789.

NP_000187.3; -.

3D structure databases

HSSP

P14061; 1FDU. [HSSP ENTRY / PDB]

ModBase

P80365.

Enzyme and pathway databases

BRENDA

1.1.1.146; 247.

Organism-specific databases

GC16P066022; -.

HIX0026979; -.

HGNC:5209; HSD11B2.

218030; gene+phenotype. [NCBI / EBI]

Orphanet

320; Apparent mineralocorticoid excess.

PharmGKB

PA29477; -.

Gene expression databases

Bgee

P80365; -.

CleanEx

HS_HSD11B2; -.

GermOnline

ENSG00000176387; Homo sapiens.

Ontologies

GO:0005783;	Cellular component: endoplasmic reticulum (inferred from electronic annotation from UniProtKB-SubCell).
GO:0005792;	Cellular component: microsome (inferred from electronic annotation from UniProtKB-SubCell).
GO:0006704;	Biological process: glucocorticoid biosynthetic process (traceable author statement from ProtInc).
GO:0055114;	Biological process: oxidation reduction (inferred from electronic annotation from UniProtKB-KW).
QuickGo view.

Family and domain databases

InterPro

IPR002198; DH_sc/Rdtase_SDR.
IPR002347; Glc/ribitol_DH.
IPR016040; NAD(P)-bd_dom.
Graphical view of domain structure.

Gene3D

G3DSA:3.40.50.720; NAD(P)-bd; 1.

PANTHER

PTHR19410; ADH_short_C2; 1.

Pfam

PF00106; adh_short; 1.
Pfam graphical view of domain structure.

PRINTS

PR00081; GDHRDH.

PROSITE

PS00061; ADH_SHORT; 1.

Proteomic databases

PRIDE

P80365; -.

Genome annotation databases

Ensembl

ENSG00000176387; Homo sapiens. [Contig view]

GeneID

3291; -.

KEGG

hsa:3291; -.

Phylogenomic databases

HOGENOM

P80365; -.

HOVERGEN

P80365; -.

OMA

P80365; NAGHNEV.

Other

DrugBank

DB00157; NADH.

NextBio

13055; -.

SOURCE

HSD11B2; Homo sapiens.

ProtoNet

P80365.

UniRef

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

Direct protein sequencing; Disease mutation; Endoplasmic reticulum; Microsome; NAD; Oxidoreductase; Polymorphism.

Features

Feature table viewer

`Key`	`From To`	`Length`	`Description`	`FTId`
`CHAIN`	`1 405`	`405`	`Corticosteroid 11-beta-dehydrogenase isozyme 2.`	`PRO_0000054627`
`NP_BIND`	`82 111`	`30`	`NAD (By similarity).`
`ACT_SITE`	`232 232`		`Proton acceptor (By similarity).`
`BINDING`	`219 219`		`Substrate (By similarity).`
`VARIANT`	`114 115`	`2`	`Missing (in AME; reduces enzyme activity by at least 95%).`	`VAR_015634`
`VARIANT`	`147 147`	`1`	`R -> H (in dbSNP:rs13306425 [NCBI]).`	`VAR_052317`
`VARIANT`	`179 179`	`1`	`L -> R (in AME; abolishes enzyme activity).`	`VAR_015635`
`VARIANT`	`180 180`	`1`	`S -> F (in AME; reduces enzyme activity).`	`VAR_015636`
`VARIANT`	`186 186`	`1`	`R -> C (in AME).`	`VAR_015637`
`VARIANT`	`208 208`	`1`	`R -> C (in AME; reduces enzyme activity by at least 95%).`	`VAR_006958`
`VARIANT`	`208 208`	`1`	`R -> H (in AME; abolishes enzyme activity).`	`VAR_015638`
`VARIANT`	`213 213`	`1`	`R -> C (in AME; reduces enzyme activity by ca. 90%).`	`VAR_006959`
`VARIANT`	`227 227`	`1`	`P -> L (in hypertension; decreases affinity for cortisol).`	`VAR_015639`
`VARIANT`	`237 237`	`1`	`A -> V (in AME; reduces enzyme activity).`	`VAR_015640`
`VARIANT`	`244 244`	`1`	`D -> N (in AME; associated with R-250).`	`VAR_015641`
`VARIANT`	`250 251`	`2`	`LL -> PS (in AME; abolishes enzyme activity).`	`VAR_015643`
`VARIANT`	`250 250`	`1`	`L -> R (in AME; associated with N-244).`	`VAR_015642`
`VARIANT`	`279 279`	`1`	`R -> C (in AME; decreases enzyme activity by ca. 33%).`	`VAR_015644`
`VARIANT`	`328 328`	`1`	`A -> V (in AME; abolishes enzyme activity).`	`VAR_015645`
`VARIANT`	`337 338`	`2`	`RY -> H (in AME; abolishes enzyme activity).`	`VAR_015647`
`VARIANT`	`337 337`	`1`	`R -> C (in AME).`	`VAR_015646`
`MUTAGEN`	`115 115`		`E->K,Q: Abolishes cofactor specificity.`
`CONFLICT`	`148 148`		`V -> F (in Ref. 2; AAB48544).`
`CONFLICT`	`148 148`		`V -> L (in Ref. 1; AAA91969).`
`CONFLICT`	`350 350`		`I -> T (in Ref. 6; AAH64536).`
`CONFLICT`	`392 392`		`D -> G (in Ref. 6; AAH36780).`

Sequence information

Length: 405 AA [This is the length of the unprocessed precursor]

Molecular weight: 44127 Da [This is the MW of the unprocessed precursor]

CRC64: 4AB269E269982D24 [This is a checksum on the sequence]

        10         20         30         40         50         60 
MERWPWPSGG AWLLVAARAL LQLLRSDLRL GRPLLAALAL LAALDWLCQR LLPPPAALAV 

        70         80         90        100        110        120 
LAAAGWIALS RLARPQRLPV ATRAVLITGC DSGFGKETAK KLDSMGFTVL ATVLELNSPG 

       130        140        150        160        170        180 
AIELRTCCSP RLRLLQMDLT KPGDISRVLE FTKAHTTSTG LWGLVNNAGH NEVVADAELS 

       190        200        210        220        230        240 
PVATFRSCME VNFFGALELT KGLLPLLRSS RGRIVTVGSP AGDMPYPCLG AYGTSKAAVA 

       250        260        270        280        290        300 
LLMDTFSCEL LPWGVKVSII QPGCFKTESV RNVGQWEKRK QLLLANLPQE LLQAYGKDYI 

       310        320        330        340        350        360 
EHLHGQFLHS LRLAMSDLTP VVDAITDALL AARPRRRYYP GQGLGLMYFI HYYLPEGLRR 

       370        380        390        400 
RFLQAFFISH CLPRALQPGQ PGTTPPQDAA QDPNLSPGPS PAVAR

P80365 in FASTA format

View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools