Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Corticosteroid 11-beta-dehydrogenase isozyme 2

Gene

HSD11B2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Catalyzes the conversion of cortisol to the inactive metabolite cortisone. Modulates intracellular glucocorticoid levels, thus protecting the nonselective mineralocorticoid receptor from occupation by glucocorticoids.

Miscellaneous

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

Catalytic activityi

An 11-beta-hydroxysteroid + NAD+ = an 11-oxosteroid + NADH.

Enzyme regulationi

Inhibited by glycyrrhetinic acid (derived from liquorice), carbenoloxone and 11-alpha-OH-progesterone.By similarity

Kineticsi

  1. KM=26.1 nM for cortisol2 Publications
  2. KM=785 nM for cortisol2 Publications
  3. KM=77 nM for cortisterone2 Publications
  1. Vmax=64.1 nmol/h/mg enzyme toward cortisterone2 Publications
  2. Vmax=66 nmol/h/mg enzyme toward cortisol2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei219SubstrateBy similarity1
Active sitei232Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi82 – 111NADBy similarityAdd BLAST30

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionOxidoreductase
LigandNAD

Enzyme and pathway databases

BRENDAi1.1.1.B40 2681
ReactomeiR-HSA-194002 Glucocorticoid biosynthesis
SABIO-RKiP80365
SIGNORiP80365

Chemistry databases

SwissLipidsiSLP:000000810

Names & Taxonomyi

Protein namesi
Recommended 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:
11-HSD type II
Short name:
11-beta-HSD type II
NAD-dependent 11-beta-hydroxysteroid dehydrogenase
Short name:
11-beta-HSD
Short chain dehydrogenase/reductase family 9C member 3
Gene namesi
Name:HSD11B2
Synonyms:HSD11K1 Publication, SDR9C3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

EuPathDBiHostDB:ENSG00000176387.6
HGNCiHGNC:5209 HSD11B2
MIMi614232 gene
neXtProtiNX_P80365

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Endoplasmic reticulum, Microsome

Pathology & Biotechi

Involvement in diseasei

Apparent mineralocorticoid excess (AME)12 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn 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.
See also OMIM:218030
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_015634114 – 115Missing in AME; reduces enzyme activity by at least 95%. 1 Publication2
Natural variantiVAR_015635179L → R in AME; abolishes enzyme activity. 1 Publication1
Natural variantiVAR_015636180S → F in AME; reduces enzyme activity. 1 Publication1
Natural variantiVAR_015637186R → C in AME. 2 PublicationsCorresponds to variant dbSNP:rs768507002Ensembl.1
Natural variantiVAR_006958208R → C in AME; reduces enzyme activity by at least 95%. 3 PublicationsCorresponds to variant dbSNP:rs121917780EnsemblClinVar.1
Natural variantiVAR_015638208R → H in AME; abolishes enzyme activity. 2 PublicationsCorresponds to variant dbSNP:rs28934592EnsemblClinVar.1
Natural variantiVAR_006959213R → C in AME; reduces enzyme activity by 90%. 3 PublicationsCorresponds to variant dbSNP:rs28934591EnsemblClinVar.1
Natural variantiVAR_066514223D → N in AME; reduces enzyme activity to about 6% of wild type. 1 PublicationCorresponds to variant dbSNP:rs121917833EnsemblClinVar.1
Natural variantiVAR_015640237A → V in AME; reduces enzyme activity. 1 Publication1
Natural variantiVAR_015641244D → N in AME; associated with R-250. 1 Publication1
Natural variantiVAR_015643250 – 251LL → PS in AME; abolishes enzyme activity. 2
Natural variantiVAR_015642250L → R in AME; associated with N-244. 1 Publication1
Natural variantiVAR_015644279R → C in AME; decreases enzyme activity by 33%. 1 PublicationCorresponds to variant dbSNP:rs28934594EnsemblClinVar.1
Natural variantiVAR_015645328A → V in AME; abolishes enzyme activity. 2 Publications1
Natural variantiVAR_015647337 – 338RY → H in AME; abolishes enzyme activity. 4 Publications2
Natural variantiVAR_066515337R → C in AME; decreased half-life from 21 to 4 hours compared to wild-type, probably due to degradation via the proteasomal pathway. 3 PublicationsCorresponds to variant dbSNP:rs121917781EnsemblClinVar.1
Natural variantiVAR_015646338Y → 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. 1 PublicationCorresponds to variant dbSNP:rs387907117EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi115E → K or Q: Abolishes cofactor specificity. 1 Publication1
Mutagenesisi335R → A or Q: Reduced enzyme activity. 1 Publication1
Mutagenesisi335R → K: No effect on enzyme activity. 1 Publication1
Mutagenesisi336R → A or Q: Almost complete loss of enzyme activity. 1 Publication1
Mutagenesisi336R → K: Reduced enzyme activity. 1 Publication1
Mutagenesisi337R → A or Q: Almost complete loss of enzyme activity. 1 Publication1
Mutagenesisi337R → K: Reduced enzyme activity. 1 Publication1
Mutagenesisi338Y → F or A: Complete loss of enzyme activity. 1 Publication1
Mutagenesisi339Y → A, F or H: Reduced enzyme activity. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi3291
MalaCardsiHSD11B2
MIMi218030 phenotype
OpenTargetsiENSG00000176387
Orphaneti320 Apparent mineralocorticoid excess
PharmGKBiPA29477

Chemistry databases

ChEMBLiCHEMBL3746
DrugBankiDB01569 Formebolone
DB00157 NADH

Polymorphism and mutation databases

BioMutaiHSD11B2
DMDMi30316367

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000546271 – 405Corticosteroid 11-beta-dehydrogenase isozyme 2Add BLAST405

Proteomic databases

EPDiP80365
MaxQBiP80365
PaxDbiP80365
PeptideAtlasiP80365
PRIDEiP80365
ProteomicsDBi57680

PTM databases

iPTMnetiP80365
PhosphoSitePlusiP80365

Expressioni

Tissue specificityi

Expressed in kidney, pancreas, prostate, ovary, small intestine and colon. At midgestation, expressed at high levels in placenta and in fetal kidney and, at much lower levels, in fetal lung and testis (PubMed:8530071).1 Publication

Gene expression databases

BgeeiENSG00000176387
CleanExiHS_HSD11B2
ExpressionAtlasiP80365 baseline and differential
GenevisibleiP80365 HS

Organism-specific databases

HPAiCAB032443
HPA042186
HPA056385

Interactioni

Subunit structurei

Interacts with ligand-free cytoplasmic NR3C2.1 Publication

Protein-protein interaction databases

BioGridi109524, 4 interactors
STRINGi9606.ENSP00000316786

Chemistry databases

BindingDBiP80365

Structurei

3D structure databases

ProteinModelPortaliP80365
SMRiP80365
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni335 – 339Essential for protein stability5

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG1610 Eukaryota
ENOG410Y7FK LUCA
GeneTreeiENSGT00920000148940
HOVERGENiHBG005482
InParanoidiP80365
KOiK00071
OMAiGEDYIEH
OrthoDBiEOG091G0LMI
PhylomeDBiP80365
TreeFamiTF325617

Family and domain databases

InterProiView protein in InterPro
IPR036291 NAD(P)-bd_dom_sf
IPR020904 Sc_DH/Rdtase_CS
IPR002347 SDR_fam
PfamiView protein in Pfam
PF00106 adh_short, 1 hit
PRINTSiPR00081 GDHRDH
SUPFAMiSSF51735 SSF51735, 1 hit
PROSITEiView protein in PROSITE
PS00061 ADH_SHORT, 1 hit

Sequencei

Sequence statusi: Complete.

P80365-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MERWPWPSGG AWLLVAARAL LQLLRSDLRL GRPLLAALAL LAALDWLCQR
60 70 80 90 100
LLPPPAALAV LAAAGWIALS RLARPQRLPV ATRAVLITGC DSGFGKETAK
110 120 130 140 150
KLDSMGFTVL ATVLELNSPG AIELRTCCSP RLRLLQMDLT KPGDISRVLE
160 170 180 190 200
FTKAHTTSTG LWGLVNNAGH NEVVADAELS PVATFRSCME VNFFGALELT
210 220 230 240 250
KGLLPLLRSS RGRIVTVGSP AGDMPYPCLG AYGTSKAAVA LLMDTFSCEL
260 270 280 290 300
LPWGVKVSII QPGCFKTESV RNVGQWEKRK QLLLANLPQE LLQAYGKDYI
310 320 330 340 350
EHLHGQFLHS LRLAMSDLTP VVDAITDALL AARPRRRYYP GQGLGLMYFI
360 370 380 390 400
HYYLPEGLRR RFLQAFFISH CLPRALQPGQ PGTTPPQDAA QDPNLSPGPS

PAVAR
Length:405
Mass (Da):44,127
Last modified:April 30, 2003 - v2
Checksum:i4AB269E269982D24
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti148V → F in AAB48544 (PubMed:8530071).Curated1
Sequence conflicti148V → L in AAA91969 (PubMed:7859916).Curated1
Sequence conflicti350I → T in AAH64536 (PubMed:15489334).Curated1
Sequence conflicti392D → G in AAH36780 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_015634114 – 115Missing in AME; reduces enzyme activity by at least 95%. 1 Publication2
Natural variantiVAR_052317147R → H. Corresponds to variant dbSNP:rs13306425EnsemblClinVar.1
Natural variantiVAR_015635179L → R in AME; abolishes enzyme activity. 1 Publication1
Natural variantiVAR_015636180S → F in AME; reduces enzyme activity. 1 Publication1
Natural variantiVAR_015637186R → C in AME. 2 PublicationsCorresponds to variant dbSNP:rs768507002Ensembl.1
Natural variantiVAR_006958208R → C in AME; reduces enzyme activity by at least 95%. 3 PublicationsCorresponds to variant dbSNP:rs121917780EnsemblClinVar.1
Natural variantiVAR_015638208R → H in AME; abolishes enzyme activity. 2 PublicationsCorresponds to variant dbSNP:rs28934592EnsemblClinVar.1
Natural variantiVAR_006959213R → C in AME; reduces enzyme activity by 90%. 3 PublicationsCorresponds to variant dbSNP:rs28934591EnsemblClinVar.1
Natural variantiVAR_066514223D → N in AME; reduces enzyme activity to about 6% of wild type. 1 PublicationCorresponds to variant dbSNP:rs121917833EnsemblClinVar.1
Natural variantiVAR_015639227P → L in hypertension; decreases affinity for cortisol. 1 PublicationCorresponds to variant dbSNP:rs121917782EnsemblClinVar.1
Natural variantiVAR_015640237A → V in AME; reduces enzyme activity. 1 Publication1
Natural variantiVAR_015641244D → N in AME; associated with R-250. 1 Publication1
Natural variantiVAR_015643250 – 251LL → PS in AME; abolishes enzyme activity. 2
Natural variantiVAR_015642250L → R in AME; associated with N-244. 1 Publication1
Natural variantiVAR_015644279R → C in AME; decreases enzyme activity by 33%. 1 PublicationCorresponds to variant dbSNP:rs28934594EnsemblClinVar.1
Natural variantiVAR_015645328A → V in AME; abolishes enzyme activity. 2 Publications1
Natural variantiVAR_015647337 – 338RY → H in AME; abolishes enzyme activity. 4 Publications2
Natural variantiVAR_066515337R → C in AME; decreased half-life from 21 to 4 hours compared to wild-type, probably due to degradation via the proteasomal pathway. 3 PublicationsCorresponds to variant dbSNP:rs121917781EnsemblClinVar.1
Natural variantiVAR_015646338Y → 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. 1 PublicationCorresponds to variant dbSNP:rs387907117EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS10837.1
PIRiS62789
RefSeqiNP_000187.3, NM_000196.3
UniGeneiHs.1376

Genome annotation databases

EnsembliENST00000326152; ENSP00000316786; ENSG00000176387
GeneIDi3291
KEGGihsa:3291
UCSCiuc002etd.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiDHI2_HUMAN
AccessioniPrimary (citable) accession number: P80365
Secondary accession number(s): A7LB28
, C5HTY7, Q13194, Q6P2G9, Q8N439, Q96QN8, Q9UC50, Q9UC51, Q9UCW5, Q9UCW6, Q9UCW7, Q9UCW8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: April 30, 2003
Last modified: June 20, 2018
This is version 175 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health