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Protein

Corticosteroid 11-beta-dehydrogenase isozyme 2

Gene

HSD11B2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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.

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

Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Ligandi

NAD

Enzyme and pathway databases

BioCyciZFISH:ENSG00000176387-MONOMER.
BRENDAi1.1.1.B40. 2681.
ReactomeiR-HSA-194002. Glucocorticoid biosynthesis.

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

HGNCiHGNC:5209. HSD11B2.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Microsome

Pathology & Biotechi

Involvement in diseasei

Apparent mineralocorticoid excess (AME)5 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 rs768507002dbSNPEnsembl.1
Natural variantiVAR_006958208R → C in AME; reduces enzyme activity by at least 95%. 3 PublicationsCorresponds to variant rs121917780dbSNPEnsembl.1
Natural variantiVAR_015638208R → H in AME; abolishes enzyme activity. 2 PublicationsCorresponds to variant rs28934592dbSNPEnsembl.1
Natural variantiVAR_006959213R → C in AME; reduces enzyme activity by 90%. 3 PublicationsCorresponds to variant rs28934591dbSNPEnsembl.1
Natural variantiVAR_066514223D → N in AME; reduces enzyme activity to about 6% of wild type. 1 PublicationCorresponds to variant rs121917833dbSNPEnsembl.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 rs28934594dbSNPEnsembl.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 rs121917781dbSNPEnsembl.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 rs387907117dbSNPEnsembl.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.

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.

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.
GeneTreeiENSGT00860000133667.
HOVERGENiHBG005482.
InParanoidiP80365.
KOiK00071.
OMAiNAGHNEV.
OrthoDBiEOG091G0LMI.
PhylomeDBiP80365.
TreeFamiTF325617.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
InterProiIPR016040. NAD(P)-bd_dom.
IPR020904. Sc_DH/Rdtase_CS.
IPR002347. SDR_fam.
[Graphical view]
PANTHERiPTHR24322. PTHR24322. 2 hits.
PfamiPF00106. adh_short. 1 hit.
[Graphical view]
PRINTSiPR00081. GDHRDH.
SUPFAMiSSF51735. SSF51735. 1 hit.
PROSITEiPS00061. ADH_SHORT. 1 hit.
[Graphical view]

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 rs13306425dbSNPEnsembl.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 rs768507002dbSNPEnsembl.1
Natural variantiVAR_006958208R → C in AME; reduces enzyme activity by at least 95%. 3 PublicationsCorresponds to variant rs121917780dbSNPEnsembl.1
Natural variantiVAR_015638208R → H in AME; abolishes enzyme activity. 2 PublicationsCorresponds to variant rs28934592dbSNPEnsembl.1
Natural variantiVAR_006959213R → C in AME; reduces enzyme activity by 90%. 3 PublicationsCorresponds to variant rs28934591dbSNPEnsembl.1
Natural variantiVAR_066514223D → N in AME; reduces enzyme activity to about 6% of wild type. 1 PublicationCorresponds to variant rs121917833dbSNPEnsembl.1
Natural variantiVAR_015639227P → L in hypertension; decreases affinity for cortisol. 1 PublicationCorresponds to variant rs121917782dbSNPEnsembl.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 rs28934594dbSNPEnsembl.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 rs121917781dbSNPEnsembl.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 rs387907117dbSNPEnsembl.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

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliP80365.
SMRiP80365.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109524. 4 interactors.
STRINGi9606.ENSP00000316786.

Chemistry databases

BindingDBiP80365.
ChEMBLiCHEMBL3746.
SwissLipidsiSLP:000000810.

PTM databases

iPTMnetiP80365.
PhosphoSitePlusiP80365.

Polymorphism and mutation databases

BioMutaiHSD11B2.
DMDMi30316367.

Proteomic databases

EPDiP80365.
MaxQBiP80365.
PaxDbiP80365.
PeptideAtlasiP80365.
PRIDEiP80365.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi3291.
DisGeNETi3291.
GeneCardsiHSD11B2.
HGNCiHGNC:5209. HSD11B2.
HPAiCAB032443.
HPA042186.
HPA056385.
MalaCardsiHSD11B2.
MIMi218030. phenotype.
614232. gene.
neXtProtiNX_P80365.
OpenTargetsiENSG00000176387.
Orphaneti320. Apparent mineralocorticoid excess.
PharmGKBiPA29477.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1610. Eukaryota.
ENOG410Y7FK. LUCA.
GeneTreeiENSGT00860000133667.
HOVERGENiHBG005482.
InParanoidiP80365.
KOiK00071.
OMAiNAGHNEV.
OrthoDBiEOG091G0LMI.
PhylomeDBiP80365.
TreeFamiTF325617.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000176387-MONOMER.
BRENDAi1.1.1.B40. 2681.
ReactomeiR-HSA-194002. Glucocorticoid biosynthesis.

Miscellaneous databases

ChiTaRSiHSD11B2. human.
GeneWikiiCorticosteroid_11-beta-dehydrogenase_isozyme_2.
GenomeRNAii3291.
PROiP80365.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000176387.
CleanExiHS_HSD11B2.
ExpressionAtlasiP80365. baseline and differential.
GenevisibleiP80365. HS.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
InterProiIPR016040. NAD(P)-bd_dom.
IPR020904. Sc_DH/Rdtase_CS.
IPR002347. SDR_fam.
[Graphical view]
PANTHERiPTHR24322. PTHR24322. 2 hits.
PfamiPF00106. adh_short. 1 hit.
[Graphical view]
PRINTSiPR00081. GDHRDH.
SUPFAMiSSF51735. SSF51735. 1 hit.
PROSITEiPS00061. ADH_SHORT. 1 hit.
[Graphical view]
ProtoNetiSearch...

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 historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: April 30, 2003
Last modified: November 30, 2016
This is version 161 of the entry and version 2 of the sequence. [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

Miscellaneous

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

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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.