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P80365 (DHI2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 134. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Corticosteroid 11-beta-dehydrogenase isozyme 2

EC=1.1.1.-
Alternative name(s):
11-beta-hydroxysteroid dehydrogenase type 2
Short name=11-DH2
Short name=11-beta-HSD2
11-beta-hydroxysteroid dehydrogenase type II
Short name=-HSD11 type II
NAD-dependent 11-beta-hydroxysteroid dehydrogenase
Short name=11-beta-HSD
Gene names
Name:HSD11B2
Synonyms:HSD11K
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length405 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (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 structure

Interacts with ligand-free cytoplasmic NR3C2. Ref.12

Subcellular location

Microsome. Endoplasmic reticulum Ref.24.

Tissue specificity

Found in placenta, kidney, pancreas, prostate, ovary, small intestine and colon.

Involvement in disease

Apparent mineralocorticoid excess (AME) [MIM:218030]: An autosomal recessive form of low-renin hypertension. It is usually diagnosed within the first years of life and is characterized by polyuria and polydipsia, failure to thrive, hypernatremia, severe hypertension with low renin and aldosterone levels, profound hypokalemia with metabolic alkalosis, and most often nephrocalcinosis.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24

Miscellaneous

Consumption of large amounts of liquorice can lead to apparent mineralocorticoid excess and hypertension.

Sequence similarities

Belongs to the short-chain dehydrogenases/reductases (SDR) family.

Biophysicochemical properties

Kinetic parameters:

X.

KM=26.1 nM for cortisol (Ref.23) Ref.23 Ref.24

KM=785 nM for cortisol (Ref.24)

KM=77 nM for cortisterone

Vmax=64.1 nmol/h/mg enzyme toward cortisterone

Vmax=66 nmol/h/mg enzyme toward cortisol

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 405405Corticosteroid 11-beta-dehydrogenase isozyme 2
PRO_0000054627

Regions

Nucleotide binding82 – 11130NAD By similarity
Region335 – 3395Essential for protein stability

Sites

Active site2321Proton acceptor By similarity
Binding site2191Substrate By similarity

Natural variations

Natural variant114 – 1152Missing in AME; reduces enzyme activity by at least 95%.
VAR_015634
Natural variant1471R → H.
Corresponds to variant rs13306425 [ dbSNP | Ensembl ].
VAR_052317
Natural variant1791L → R in AME; abolishes enzyme activity. Ref.21
VAR_015635
Natural variant1801S → F in AME; reduces enzyme activity. Ref.21
VAR_015636
Natural variant1861R → C in AME. Ref.10 Ref.17
VAR_015637
Natural variant2081R → C in AME; reduces enzyme activity by at least 95%. Ref.10 Ref.14 Ref.17
VAR_006958
Natural variant2081R → H in AME; abolishes enzyme activity. Ref.15 Ref.21
VAR_015638
Natural variant2131R → C in AME; reduces enzyme activity by ca. 90%. Ref.14 Ref.18 Ref.20
VAR_006959
Natural variant2231D → N in AME; reduces enzyme activity to about 6% of wild type. Ref.23
VAR_066514
Natural variant2271P → L in hypertension; decreases affinity for cortisol. Ref.19
VAR_015639
Natural variant2371A → V in AME; reduces enzyme activity. Ref.21
VAR_015640
Natural variant2441D → N in AME; associated with R-250. Ref.17
VAR_015641
Natural variant250 – 2512LL → PS in AME; abolishes enzyme activity.
VAR_015643
Natural variant2501L → R in AME; associated with N-244. Ref.17
VAR_015642
Natural variant2791R → C in AME; decreases enzyme activity by ca. 33%. Ref.16
VAR_015644
Natural variant3281A → V in AME; abolishes enzyme activity. Ref.20 Ref.21
VAR_015645
Natural variant337 – 3382RY → H in AME; abolishes enzyme activity.
VAR_015647
Natural variant3371R → C in AME; decreased half-life from 21 to 4 hours compared to wild-type, probably due to degradation via the proteasomal pathway. Ref.13 Ref.17 Ref.24
VAR_066515
Natural variant3381Y → H in AME; abolishes enzyme activity; decreased half-life from 21 to 3 hours compared to wild-type, probably due to degradation via the proteasomal pathway. Ref.24
VAR_015646

Experimental info

Mutagenesis1151E → K or Q: Abolishes cofactor specificity. Ref.22
Mutagenesis3351R → A or Q: Reduced enzyme activity. Ref.24
Mutagenesis3351R → K: No effect on enzyme activity. Ref.24
Mutagenesis3361R → A or Q: Almost complete loss of enzyme activity. Ref.24
Mutagenesis3361R → K: Reduced enzyme activity. Ref.24
Mutagenesis3371R → A or Q: Almost complete loss of enzyme activity. Ref.24
Mutagenesis3371R → K: Reduced enzyme activity. Ref.24
Mutagenesis3381Y → F or A: Complete loss of enzyme activity. Ref.24
Mutagenesis3391Y → A, F or H: Reduced enzyme activity. Ref.24
Sequence conflict1481V → F in AAB48544. Ref.2
Sequence conflict1481V → L in AAA91969. Ref.1
Sequence conflict3501I → T in AAH64536. Ref.7
Sequence conflict3921D → G in AAH36780. Ref.7

Sequences

Sequence LengthMass (Da)Tools
P80365 [UniParc].

Last modified April 30, 2003. Version 2.
Checksum: 4AB269E269982D24

FASTA40544,127
        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 

« Hide

References

« Hide 'large scale' references
[1]"Cloning and tissue distribution of the human 11 beta-hydroxysteroid dehydrogenase type 2 enzyme."
Albiston A.L., Obeyesekere V.R., Smith R.E., Krozowski Z.S.
Mol. Cell. Endocrinol. 105:R11-R17(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Kidney.
[2]"Gene structure and chromosomal localization of the human HSD11K gene encoding the kidney (type 2) isozyme of 11 beta-hydroxysteroid dehydrogenase."
Agarwal A.K., Rogerson F.M., Mune T., White P.C.
Genomics 29:195-199(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Kidney.
[3]"Cloning and production of antisera to human placental 11 beta-hydroxysteroid dehydrogenase type 2."
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.
Biochem. J. 313:1007-1017(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Placenta.
[4]SeattleSNPs variation discovery resource
Submitted (JUN-2007) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]NHLBI resequencing and genotyping service (RS&G)
Submitted (DEC-2008) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]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 (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"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: Ovary.
[8]"Purification of 11 beta-hydroxysteroid dehydrogenase type 2 from human placenta utilizing a novel affinity labelling technique."
Brown R.W., Chapman K.E., Murad P., Edwards C.R., Seckl J.R.
Biochem. J. 313:997-1005(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: 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.
[9]"Human hydroxysteroid dehydrogenase type 2 HSD11B2."
Amin H.K., Hoeppner W.
Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 90-221.
[10]"Several homozygous mutations in the gene for 11 beta-hydroxysteroid dehydrogenase type 2 in patients with apparent mineralocorticoid excess."
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.
J. Clin. Endocrinol. Metab. 80:3145-3150(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 182-211; 235-264 AND 325-354, VARIANTS AME CYS-186; CYS-208; 250-PRO-SER-251 AND 337-ARG-TYR-338 DELINS HIS.
[11]"Mineralocorticoid activity of liquorice: 11-beta-hydroxysteroid dehydrogenase deficiency comes of age."
Stewart P.M., Wallace A.M., Valentino R., Burt D., Shackleton C.H.L., Edwards C.R.W.
Lancet 2:821-824(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION.
[12]"The intracellular localization of the mineralocorticoid receptor is regulated by 11beta-hydroxysteroid dehydrogenase type 2."
Odermatt A., Arnold P., Frey F.J.
J. Biol. Chem. 276:28484-28492(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NR3C2.
[13]"A mutation in the HSD11B2 gene in a family with apparent mineralocorticoid excess."
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.
J. Clin. Endocrinol. Metab. 80:2263-2266(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AME CYS-337.
[14]"Human hypertension caused by mutations in the kidney isozyme of 11 beta-hydroxysteroid dehydrogenase."
Mune T., Rogerson F.M., Nikkilae H., Agarwal A.K., White P.C.
Nat. Genet. 10:394-399(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS AME CYS-208; CYS-213; 250-PRO-SER-251 AND 337-ARG-TYR-338 DELINS HIS.
[15]"A new compound heterozygous mutation in the 11 beta-hydroxysteroid dehydrogenase type 2 gene in a case of apparent mineralocorticoid excess."
Kitanaka S., Katsumata N., Tanae A., Hibi I., Takeyama K., Fuse H., Kato S., Tanaka T.
J. Clin. Endocrinol. Metab. 82:4054-4058(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS AME HIS-208 AND 337-ARG-TYR-338 DELINS HIS.
[16]"Molecular basis for hypertension in the 'type II variant' of apparent mineralocorticoid excess."
Li A., Tedde R., Krozowski Z.S., Pala A., Li K.X.Z., Shackleton C.H.L., Mantero F., Palermo M., Stewart P.M.
Am. J. Hum. Genet. 63:370-379(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT AME CYS-279.
[17]"Examination of genotype and phenotype relationships in 14 patients with apparent mineralocorticoid excess."
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.
J. Clin. Endocrinol. Metab. 83:2244-2254(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS AME CYS-186; CYS-208; ASN-244; ARG-250; 250-PRO-SER-251; CYS-337 AND 337-ARG-TYR-338 DELINS HIS.
[18]"The codon 213 of the 11beta-hydroxysteroid dehydrogenase type 2 gene is a hot spot for mutations in apparent mineralocorticoid excess."
Rogoff D., Smolenicka Z., Bergada I., Vallejo G., Barontini M., Heinrich J.J., Ferrari P.
J. Clin. Endocrinol. Metab. 83:4391-4393(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT AME CYS-213.
[19]"A genetic defect resulting in mild low-renin hypertension."
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.
Proc. Natl. Acad. Sci. U.S.A. 95:10200-10205(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT HYPERTENSION LEU-227.
[20]"Genetic, biochemical, and clinical studies of patients with A328V or R213C mutations in 11betaHSD2 causing apparent mineralocorticoid excess."
Morineau G., Marc J.-M., Boudi A., Galons H., Gourmelen M., Corvol P., Pascoe L., Fiet J.
Hypertension 34:435-441(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS AME CYS-213 AND VAL-328.
[21]"Mutants of 11beta-hydroxysteroid dehydrogenase (11-HSD2) with partial activity: improved correlations between genotype and biochemical phenotype in apparent mineralocorticoid excess."
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.
Hypertension 34:638-642(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS AME ARG-179; PHE-180; HIS-208; VAL-237 AND VAL-328.
[22]"A mutation in the cofactor-binding domain of 11beta-hydroxysteroid dehydrogenase type 2 associated with mineralocorticoid hypertension."
Odermatt A., Dick B., Arnold P., Zaehner T., Plueschke V., Deregibus M.N., Repetto H., Frey B.M., Frey F.J., Ferrari P.
J. Clin. Endocrinol. Metab. 86:1247-1252(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT AME 114-LEU-GLU-115 DEL, MUTAGENESIS OF GLU-115.
[23]"Two homozygous mutations in the 11 beta-hydroxysteroid dehydrogenase type 2 gene in a case of apparent mineralocorticoid excess."
Carvajal C.A., Gonzalez A.A., Romero D.G., Gonzalez A., Mosso L.M., Lagos E.T., Hevia Mdel P., Rosati M.P., Perez-Acle T.O., Gomez-Sanchez C.E., Montero J.A., Fardella C.E.
J. Clin. Endocrinol. Metab. 88:2501-2507(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AME ASN-223, BIOPHYSICOCHEMICAL PROPERTIES.
[24]"Impaired protein stability of 11beta-hydroxysteroid dehydrogenase type 2: a novel mechanism of apparent mineralocorticoid excess."
Atanasov A.G., Ignatova I.D., Nashev L.G., Dick B., Ferrari P., Frey F.J., Odermatt A.
J. Am. Soc. Nephrol. 18:1262-1270(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS AME CYS-337 AND HIS-338, SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF ARG-335; ARG-336; ARG-337; TYR-338 AND TYR-339.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U14631 mRNA. Translation: AAA91969.1.
U27317 Genomic DNA. Translation: AAB48544.1.
U26726 mRNA. Translation: AAC50356.1.
EF694683 Genomic DNA. Translation: ABS29267.1.
FJ515828 Genomic DNA. Translation: ACS13714.1.
CH471092 Genomic DNA. Translation: EAW83134.1.
BC036780 mRNA. Translation: AAH36780.1.
BC064536 mRNA. Translation: AAH64536.1.
AY046280 Genomic DNA. Translation: AAK91586.1.
PIRS62789.
RefSeqNP_000187.3. NM_000196.3.
UniGeneHs.1376.

3D structure databases

ProteinModelPortalP80365.
SMRP80365. Positions 2-339.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109524. 4 interactions.

Chemistry

BindingDBP80365.
ChEMBLCHEMBL3746.
DrugBankDB00157. NADH.

PTM databases

PhosphoSiteP80365.

Polymorphism databases

DMDM30316367.

Proteomic databases

PaxDbP80365.
PRIDEP80365.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000326152; ENSP00000316786; ENSG00000176387.
GeneID3291.
KEGGhsa:3291.
UCSCuc002etd.3. human.

Organism-specific databases

CTD3291.
GeneCardsGC16P067465.
HGNCHGNC:5209. HSD11B2.
HPACAB032443.
MIM218030. phenotype.
614232. gene.
neXtProtNX_P80365.
Orphanet320. Apparent mineralocorticoid excess.
PharmGKBPA29477.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1028.
HOVERGENHBG005482.
InParanoidP80365.
KOK00071.
OMARSCMEVN.
OrthoDBEOG7FXZZX.
PhylomeDBP80365.
TreeFamTF325617.

Enzyme and pathway databases

BRENDA1.1.1.146. 2681.

Gene expression databases

ArrayExpressP80365.
BgeeP80365.
CleanExHS_HSD11B2.
GenevestigatorP80365.

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]
PRINTSPR00081. GDHRDH.
PROSITEPS00061. ADH_SHORT. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSHSD11B2. human.
GeneWikiCorticosteroid_11-beta-dehydrogenase_isozyme_2.
GenomeRNAi3291.
NextBio13055.
PROP80365.
SOURCESearch...

Entry information

Entry nameDHI2_HUMAN
AccessionPrimary (citable) accession number: P80365
Secondary accession number(s): A7LB28 expand/collapse secondary AC list , C5HTY7, Q13194, Q6P2G9, Q8N439, Q96QN8, Q9UC50, Q9UC51, Q9UCW5, Q9UCW6, Q9UCW7, Q9UCW8
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: April 30, 2003
Last modified: March 19, 2014
This is version 134 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

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 16

Human chromosome 16: entries, gene names and cross-references to MIM