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Protein

Corticosteroid 11-beta-dehydrogenase isozyme 1

Gene

HSD11B1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes reversibly the conversion of cortisol to the inactive metabolite cortisone. Catalyzes reversibly the conversion of 7-ketocholesterol to 7-beta-hydroxycholesterol. In intact cells, the reaction runs only in one direction, from 7-ketocholesterol to 7-beta-hydroxycholesterol (By similarity).By similarity

Catalytic activityi

An 11-beta-hydroxysteroid + NADP+ = an 11-oxosteroid + NADPH.4 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei170Substrate1
Active sitei183Proton acceptor1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi41 – 67NADP6 PublicationsAdd BLAST27
Nucleotide bindingi92 – 93NADP6 Publications2
Nucleotide bindingi119 – 121NADP6 Publications3
Nucleotide bindingi183 – 187NADP6 Publications5
Nucleotide bindingi218 – 222NADP6 Publications5

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionOxidoreductase
Biological processLipid metabolism, Steroid metabolism
LigandNADP

Enzyme and pathway databases

BioCyciMetaCyc:HS04154-MONOMER.
BRENDAi1.1.1.146. 2681.
1.1.1.B40. 2681.
ReactomeiR-HSA-194002. Glucocorticoid biosynthesis.
SABIO-RKiP28845.

Chemistry databases

SwissLipidsiSLP:000000809.

Names & Taxonomyi

Protein namesi
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
Short chain dehydrogenase/reductase family 26C member 1
Gene namesi
Name:HSD11B1
Synonyms:HSD11, HSD11L, SDR26C1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:5208. HSD11B1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 7CytoplasmicSequence analysis7
Transmembranei8 – 24Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST17
Topological domaini25 – 292LumenalSequence analysisAdd BLAST268

GO - Cellular componenti

  • endoplasmic reticulum membrane Source: Reactome
  • integral component of membrane Source: UniProtKB-KW
  • membrane Source: UniProtKB

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Involvement in diseasei

Cortisone reductase deficiency (CRD)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionIn CRD, activation of cortisone to cortisol does not occur, resulting in adrenocorticotropin-mediated androgen excess and a phenotype resembling polycystic ovary syndrome (PCOS).
See also OMIM:604931

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi5 – 6KK → RR: Predominantly inverted topology. No effect on activity. 2 Publications2
Mutagenesisi5 – 6KK → SS: Inverted topology. Reduced Vmax. 2 Publications2
Mutagenesisi5K → R: Predominantly inverted topology. No effect on activity. 1 Publication1
Mutagenesisi5K → S: Inverted topology. No effect on activity. 1 Publication1
Mutagenesisi6K → R: No effect on topology. Increased Km for corticosterone. 1 Publication1
Mutagenesisi6K → S: No effect on topology or activity. 1 Publication1
Mutagenesisi18 – 21YYYY → AAAA: No effect on topology. Reduced Vmax. 1 Publication4
Mutagenesisi18 – 21YYYY → FFFF: No effect on topology or activity. 1 Publication4
Mutagenesisi19 – 21YYY → AYA: No effect on topology. Reduced Vmax. 1 Publication3
Mutagenesisi25 – 26EE → KK: Inverted topology. Reduced Vmax. 1 Publication2
Mutagenesisi25 – 26EE → KQ: No effect on topology. Reduced Vmax. 1 Publication2
Mutagenesisi25 – 26EE → QQ: Reduced Vmax. 1 Publication2
Mutagenesisi25E → K or Q: No effect on activity. 1 Publication1
Mutagenesisi26E → K: No effect on activity. 1 Publication1
Mutagenesisi35 – 36KK → SS: Complete loss of activity. 1 Publication2

Organism-specific databases

DisGeNETi3290.
MalaCardsiHSD11B1.
MIMi604931. phenotype.
OpenTargetsiENSG00000117594.
Orphaneti168588. Hyperandrogenism due to cortisone reductase deficiency.
PharmGKBiPA29476.

Chemistry databases

ChEMBLiCHEMBL4235.
DrugBankiDB07049. (2R)-1-[(4-tert-butylphenyl)sulfonyl]-2-methyl-4-(4-nitrophenyl)piperazine.
DB03461. 2'-Monophosphoadenosine 5'-Diphosphoribose.
DB03814. 2-(N-Morpholino)-Ethanesulfonic Acid.
DB02329. Carbenoxolone.
DB05064. INCB13739.
DB00157. NADH.
DB00635. Prednisone.
GuidetoPHARMACOLOGYi2763.

Polymorphism and mutation databases

BioMutaiHSD11B1.
DMDMi118569.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000546191 – 292Corticosteroid 11-beta-dehydrogenase isozyme 1Add BLAST292

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi123N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi162N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi207N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

Glycosylated.2 Publications

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiP28845.
PeptideAtlasiP28845.
PRIDEiP28845.

PTM databases

iPTMnetiP28845.
PhosphoSitePlusiP28845.

Expressioni

Tissue specificityi

Widely expressed. Highest expression in liver.

Gene expression databases

BgeeiENSG00000117594.
CleanExiHS_HSD11B1.
ExpressionAtlasiP28845. baseline and differential.
GenevisibleiP28845. HS.

Organism-specific databases

HPAiHPA047729.

Interactioni

Subunit structurei

Homodimer.6 Publications

Protein-protein interaction databases

BioGridi109523. 15 interactors.
DIPiDIP-59618N.
IntActiP28845. 1 interactor.
STRINGi9606.ENSP00000261465.

Chemistry databases

BindingDBiP28845.

Structurei

Secondary structure

1292
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi29 – 32Combined sources4
Beta strandi36 – 41Combined sources6
Helixi45 – 56Combined sources12
Beta strandi60 – 66Combined sources7
Helixi68 – 81Combined sources14
Beta strandi84 – 90Combined sources7
Beta strandi93 – 95Combined sources3
Helixi96 – 110Combined sources15
Beta strandi114 – 118Combined sources5
Helixi133 – 143Combined sources11
Helixi145 – 161Combined sources17
Beta strandi164 – 170Combined sources7
Helixi171 – 173Combined sources3
Helixi181 – 204Combined sources24
Beta strandi209 – 215Combined sources7
Helixi221 – 226Combined sources6
Helixi229 – 234Combined sources6
Helixi238 – 250Combined sources13
Beta strandi254 – 258Combined sources5
Helixi262 – 267Combined sources6
Helixi271 – 280Combined sources10
Helixi281 – 283Combined sources3
Helixi287 – 290Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1XU7X-ray1.80A/B/C/D24-292[»]
1XU9X-ray1.55A/B/C/D24-292[»]
2BELX-ray2.11A/B/C/D26-284[»]
2ILTX-ray2.30A24-285[»]
2IRWX-ray3.10A/B/C/D/E/F/G/H26-289[»]
2RBEX-ray1.90A/B/C/D25-292[»]
3BYZX-ray2.69A/B/C/D25-292[»]
3BZUX-ray2.25A/B/C/D24-292[»]
3CH6X-ray2.35A/B/D/E24-292[»]
3CZRX-ray2.35A/B24-292[»]
3D3EX-ray2.60A/B/C/D24-292[»]
3D4NX-ray2.50A/B/C/D24-292[»]
3D5QX-ray2.55A/B/C/D24-292[»]
3EY4X-ray3.00A/B/C/D25-292[»]
3FCOX-ray2.65A/B24-291[»]
3FRJX-ray2.30A/B24-292[»]
3H6KX-ray2.19A/B/C/D24-292[»]
3HFGX-ray2.30A/B/C/D24-292[»]
3OQ1X-ray2.60A/B/C/D24-292[»]
3PDJX-ray2.30A/B24-292[»]
3QQPX-ray2.72A/B/C/D24-292[»]
3TFQX-ray1.80A/B/D/E24-292[»]
4BB5X-ray2.20A/B/C/D1-292[»]
4BB6X-ray2.55A/B1-292[»]
4C7JX-ray2.16A/B/C/D24-292[»]
4C7KX-ray1.91A/B/C/D24-292[»]
4HFRX-ray2.73A/B24-292[»]
4HX5X-ray2.19A/B/C/D24-292[»]
4IJUX-ray2.35A/B/D/E24-292[»]
4IJVX-ray2.35A/B/D/E24-292[»]
4IJWX-ray2.35A/B/D/E24-292[»]
4K1LX-ray1.96A/B/C/D24-292[»]
4P38X-ray2.80A/B26-290[»]
4YYZX-ray3.20A/B26-284[»]
ProteinModelPortaliP28845.
SMRiP28845.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP28845.

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1205. Eukaryota.
COG1028. LUCA.
GeneTreeiENSGT00880000138008.
HOGENOMiHOG000010276.
HOVERGENiHBG005481.
InParanoidiP28845.
KOiK15680.
OMAiIGREMAY.
OrthoDBiEOG091G0H0R.
PhylomeDBiP28845.
TreeFamiTF329114.

Family and domain databases

InterProiView protein in InterPro
IPR016040. NAD(P)-bd_dom.
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.

P28845-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAFMKKYLLP ILGLFMAYYY YSANEEFRPE MLQGKKVIVT GASKGIGREM
60 70 80 90 100
AYHLAKMGAH VVVTARSKET LQKVVSHCLE LGAASAHYIA GTMEDMTFAE
110 120 130 140 150
QFVAQAGKLM GGLDMLILNH ITNTSLNLFH DDIHHVRKSM EVNFLSYVVL
160 170 180 190 200
TVAALPMLKQ SNGSIVVVSS LAGKVAYPMV AAYSASKFAL DGFFSSIRKE
210 220 230 240 250
YSVSRVNVSI TLCVLGLIDT ETAMKAVSGI VHMQAAPKEE CALEIIKGGA
260 270 280 290
LRQEEVYYDS SLWTTLLIRN PCRKILEFLY STSYNMDRFI NK
Length:292
Mass (Da):32,401
Last modified:January 23, 2007 - v3
Checksum:i4632D0F3BBEFC474
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_035845148V → E in a breast cancer sample; somatic mutation. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M76665
, M76661, M76662, M76663, M76664 Genomic DNA. Translation: AAC31757.1.
AY044084, AY044083 Genomic DNA. Translation: AAK83653.1.
AK313973 mRNA. Translation: BAG36688.1.
AL022398, AL031316 Genomic DNA. Translation: CAA18541.2.
AL031316, AL022398 Genomic DNA. Translation: CAI20063.1.
CH471100 Genomic DNA. Translation: EAW93445.1.
CH471100 Genomic DNA. Translation: EAW93446.1.
BC012593 mRNA. Translation: AAH12593.1.
CCDSiCCDS1489.1.
PIRiA41173. DXHUBH.
RefSeqiNP_001193670.1. NM_001206741.1.
NP_005516.1. NM_005525.3.
NP_861420.1. NM_181755.2.
UniGeneiHs.195040.

Genome annotation databases

EnsembliENST00000367027; ENSP00000355994; ENSG00000117594.
ENST00000367028; ENSP00000355995; ENSG00000117594.
GeneIDi3290.
KEGGihsa:3290.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiDHI1_HUMAN
AccessioniPrimary (citable) accession number: P28845
Secondary accession number(s): B2R9Z1, D3DT89
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: January 23, 2007
Last modified: August 30, 2017
This is version 182 of the entry and version 3 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families