DHI1_HUMAN
ID DHI1_HUMAN Reviewed; 292 AA.
AC P28845; B2R9Z1; D3DT89;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 212.
DE RecName: Full=11-beta-hydroxysteroid dehydrogenase 1 {ECO:0000303|PubMed:10497248, ECO:0000303|PubMed:14973125};
DE Short=11-DH;
DE Short=11-beta-HSD1 {ECO:0000303|PubMed:10497248, ECO:0000303|PubMed:14973125, ECO:0000303|PubMed:27927697};
DE EC=1.1.1.146 {ECO:0000269|PubMed:10497248, ECO:0000269|PubMed:12460758, ECO:0000269|PubMed:14973125, ECO:0000269|PubMed:15152005, ECO:0000269|PubMed:21453287, ECO:0000269|PubMed:30902677, ECO:0000269|PubMed:8319583};
DE AltName: Full=7-oxosteroid reductase;
DE EC=1.1.1.201 {ECO:0000269|PubMed:14973125, ECO:0000269|PubMed:15095019, ECO:0000269|PubMed:15152005, ECO:0000269|PubMed:17593962, ECO:0000269|PubMed:21453287};
DE AltName: Full=Corticosteroid 11-beta-dehydrogenase isozyme 1 {ECO:0000305};
DE AltName: Full=Short chain dehydrogenase/reductase family 26C member 1;
GN Name=HSD11B1 {ECO:0000312|HGNC:HGNC:5208}; Synonyms=HSD11, HSD11L, SDR26C1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY.
RC TISSUE=Testis;
RX PubMed=1885595; DOI=10.1016/s0021-9258(18)55351-5;
RA Tannin G.M., Agarwal A.K., Monder C., New M.I., White P.C.;
RT "The human gene for 11 beta-hydroxysteroid dehydrogenase. Structure, tissue
RT distribution, and chromosomal localization.";
RL J. Biol. Chem. 266:16653-16658(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RX PubMed=12414862; DOI=10.1210/jc.2001-011375;
RA Draper N., Echwald S.M., Lavery G.G., Walker E.A., Fraser R., Davies E.,
RA Soerensen T.I.A., Astrup A., Adamski J., Hewison M., Connell J.M.,
RA Pedersen O., Stewart P.M.;
RT "Association studies between microsatellite markers within the gene
RT encoding human 11beta-hydroxysteroid dehydrogenase type 1 and body mass
RT index, waist to hip ratio, and glucocorticoid metabolism.";
RL J. Clin. Endocrinol. Metab. 87:4984-4990(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=8319583; DOI=10.1210/endo.133.1.8319583;
RA Moore C.C., Mellon S.H., Murai J., Siiteri P.K., Miller W.L.;
RT "Structure and function of the hepatic form of 11 beta-hydroxysteroid
RT dehydrogenase in the squirrel monkey, an animal model of glucocorticoid
RT resistance.";
RL Endocrinology 133:368-375(1993).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR
RP LOCATION, TOPOLOGY, GLYCOSYLATION, AND MUTAGENESIS OF LYS-5; 5-LYS-LYS-6;
RP LYS-6; 18-TYR--TYR-21 AND 19-TYR--TYR-21.
RX PubMed=10497248; DOI=10.1074/jbc.274.40.28762;
RA Odermatt A., Arnold P., Stauffer A., Frey B.M., Frey F.J.;
RT "The N-terminal anchor sequences of 11beta-hydroxysteroid dehydrogenases
RT determine their orientation in the endoplasmic reticulum membrane.";
RL J. Biol. Chem. 274:28762-28770(1999).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, AND TISSUE SPECIFICITY.
RX PubMed=11481269;
RA Rauz S., Walker E.A., Shackleton C.H., Hewison M., Murray P.I.,
RA Stewart P.M.;
RT "Expression and putative role of 11 beta-hydroxysteroid dehydrogenase
RT isozymes within the human eye.";
RL Invest. Ophthalmol. Vis. Sci. 42:2037-2042(2001).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=12460758; DOI=10.1016/s1046-5928(02)00547-8;
RA Nobel C.S.I., Dunas F., Abrahmsen L.B.;
RT "Purification of full-length recombinant human and rat type 1 11beta-
RT hydroxysteroid dehydrogenases with retained oxidoreductase activities.";
RL Protein Expr. Purif. 26:349-356(2002).
RN [11]
RP INVOLVEMENT IN CORTRD2.
RX PubMed=12858176; DOI=10.1038/ng1214;
RA Draper N., Walker E.A., Bujalska I.J., Tomlinson J.W., Chalder S.M.,
RA Arlt W., Lavery G.G., Bedendo O., Ray D.W., Laing I., Malunowicz E.,
RA White P.C., Hewison M., Mason P.J., Connell J.M., Shackleton C.H.L.,
RA Stewart P.M.;
RT "Mutations in the genes encoding 11beta-hydroxysteroid dehydrogenase type 1
RT and hexose-6-phosphate dehydrogenase interact to cause cortisone reductase
RT deficiency.";
RL Nat. Genet. 34:434-439(2003).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=14973125; DOI=10.1074/jbc.m313615200;
RA Schweizer R.A.S., Zuercher M., Balazs Z., Dick B., Odermatt A.;
RT "Rapid hepatic metabolism of 7-ketocholesterol by 11beta-hydroxysteroid
RT dehydrogenase type 1: species-specific differences between the rat, human,
RT and hamster enzyme.";
RL J. Biol. Chem. 279:18415-18424(2004).
RN [13]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=15095019; DOI=10.1007/s00018-003-3476-y;
RA Hult M., Elleby B., Shafqat N., Svensson S., Rane A., Joernvall H.,
RA Abrahmsen L., Oppermann U.;
RT "Human and rodent type 1 11beta-hydroxysteroid dehydrogenases are 7beta-
RT hydroxycholesterol dehydrogenases involved in oxysterol metabolism.";
RL Cell. Mol. Life Sci. 61:992-999(2004).
RN [14]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, TOPOLOGY, AND
RP MUTAGENESIS OF 5-LYS-LYS-6; GLU-25; 25-GLU-GLU-26; GLU-26 AND
RP 35-LYS-LYS-36.
RX PubMed=15152005; DOI=10.1074/jbc.m313666200;
RA Frick C., Atanasov A.G., Arnold P., Ozols J., Odermatt A.;
RT "Appropriate function of 11beta-hydroxysteroid dehydrogenase type 1 in the
RT endoplasmic reticulum lumen is dependent on its N-terminal region sharing
RT similar topological determinants with 50-kDa esterase.";
RL J. Biol. Chem. 279:31131-31138(2004).
RN [15]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY
RP REGULATION, AND SUBCELLULAR LOCATION.
RX PubMed=15280030; DOI=10.1016/j.febslet.2004.06.065;
RA Atanasov A.G., Nashev L.G., Schweizer R.A., Frick C., Odermatt A.;
RT "Hexose-6-phosphate dehydrogenase determines the reaction direction of
RT 11beta-hydroxysteroid dehydrogenase type 1 as an oxoreductase.";
RL FEBS Lett. 571:129-133(2004).
RN [16]
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=17593962; DOI=10.1371/journal.pone.0000561;
RA Nashev L.G., Chandsawangbhuwana C., Balazs Z., Atanasov A.G., Dick B.,
RA Frey F.J., Baker M.E., Odermatt A.;
RT "Hexose-6-phosphate dehydrogenase modulates 11beta-hydroxysteroid
RT dehydrogenase type 1-dependent metabolism of 7-keto- and 7beta-hydroxy-
RT neurosteroids.";
RL PLoS ONE 2:e561-e561(2007).
RN [17]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-123 AND ASN-162.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [18]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE
RP SPECIFICITY.
RX PubMed=21453287; DOI=10.1042/bj20110022;
RA Odermatt A., Da Cunha T., Penno C.A., Chandsawangbhuwana C., Reichert C.,
RA Wolf A., Dong M., Baker M.E.;
RT "Hepatic reduction of the secondary bile acid 7-oxolithocholic acid is
RT mediated by 11beta-hydroxysteroid dehydrogenase 1.";
RL Biochem. J. 436:621-629(2011).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [20]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=27927697; DOI=10.1530/joe-16-0495;
RA Tsachaki M., Meyer A., Weger B., Kratschmar D.V., Tokarz J., Adamski J.,
RA Belting H.G., Affolter M., Dickmeis T., Odermatt A.;
RT "Absence of 11-keto reduction of cortisone and 11-ketotestosterone in the
RT model organism zebrafish.";
RL J. Endocrinol. 232:323-335(2017).
RN [21]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=30902677; DOI=10.1016/j.jsbmb.2019.03.011;
RA Beck K.R., Kanagaratnam S., Kratschmar D.V., Birk J., Yamaguchi H.,
RA Sailer A.W., Seuwen K., Odermatt A.;
RT "Enzymatic interconversion of the oxysterols 7beta,25-dihydroxycholesterol
RT and 7-keto,25-hydroxycholesterol by 11beta-hydroxysteroid dehydrogenase
RT type 1 and 2.";
RL J. Steroid Biochem. Mol. Biol. 190:19-28(2019).
RN [22] {ECO:0000312|PDB:1XU7, ECO:0000312|PDB:1XU9}
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 24-292 IN COMPLEX WITH NADP AND
RP SUBSTRATE ANALOG, AND SUBUNIT.
RX PubMed=15513927; DOI=10.1074/jbc.m411104200;
RA Hosfield D.J., Wu Y., Skene R.J., Hilgers M., Jennings A., Snell G.P.,
RA Aertgeerts K.;
RT "Conformational flexibility in crystal structures of human 11beta-
RT hydroxysteroid dehydrogenase type I provide insights into glucocorticoid
RT interconversion and enzyme regulation.";
RL J. Biol. Chem. 280:4639-4648(2005).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 24-284 IN COMPLEXES WITH
RP ADAMANTANE SULFONE AND SULFONAMIDE INHIBITORS, AND CATALYTIC ACTIVITY.
RX PubMed=17070044; DOI=10.1016/j.bmcl.2006.10.008;
RA Sorensen B., Winn M., Rohde J., Shuai Q., Wang J., Fung S., Monzon K.,
RA Chiou W., Stolarik D., Imade H., Pan L., Deng X., Chovan L.,
RA Longenecker K., Judge R., Qin W., Brune M., Camp H., Frevert E.U.,
RA Jacobson P., Link J.T.;
RT "Adamantane sulfone and sulfonamide 11-beta-HSD1 Inhibitors.";
RL Bioorg. Med. Chem. Lett. 17:527-532(2007).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 25-292 IN COMPLEX WITH NADP AND
RP INHIBITOR, SUBUNIT, AND CATALYTIC ACTIVITY.
RX PubMed=17919905; DOI=10.1016/j.bmcl.2007.09.070;
RA Yuan C., St Jean D.J. Jr., Liu Q., Cai L., Li A., Han N., Moniz G.,
RA Askew B., Hungate R.W., Johansson L., Tedenborg L., Pyring D., Williams M.,
RA Hale C., Chen M., Cupples R., Zhang J., Jordan S., Bartberger M.D., Sun Y.,
RA Emery M., Wang M., Fotsch C.;
RT "The discovery of 2-anilinothiazolones as 11beta-HSD1 inhibitors.";
RL Bioorg. Med. Chem. Lett. 17:6056-6061(2007).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 24-292 IN COMPLEX WITH NADP AND
RP INHIBITOR.
RX PubMed=18485702; DOI=10.1016/j.bmcl.2008.04.069;
RA Wang H., Ruan Z., Li J.J., Simpkins L.M., Smirk R.A., Wu S.C.,
RA Hutchins R.D., Nirschl D.S., Van Kirk K., Cooper C.B., Sutton J.C., Ma Z.,
RA Golla R., Seethala R., Salyan M.E.K., Nayeem A., Krystek S.R. Jr.,
RA Sheriff S., Camac D.M., Morin P.E., Carpenter B., Robl J.A., Zahler R.,
RA Gordon D.A., Hamann L.G.;
RT "Pyridine amides as potent and selective inhibitors of 11beta-
RT hydroxysteroid dehydrogenase type 1.";
RL Bioorg. Med. Chem. Lett. 18:3168-3172(2008).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 24-292 IN COMPLEX WITH NADP AND
RP INHIBITOR.
RX PubMed=18069989; DOI=10.1111/j.1747-0285.2007.00603.x;
RA Hale C., Veniant M., Wang Z., Chen M., McCormick J., Cupples R.,
RA Hickman D., Min X., Sudom A., Xu H., Matsumoto G., Fotsch C.,
RA St Jean D.J. Jr., Wang M.;
RT "Structural characterization and pharmacodynamic effects of an orally
RT active 11beta-hydroxysteroid dehydrogenase type 1 inhibitor.";
RL Chem. Biol. Drug Des. 71:36-44(2008).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 24-292 IN COMPLEX WITH NADP AND
RP INHIBITOR.
RX PubMed=18553955; DOI=10.1021/jm800310g;
RA Julian L.D., Wang Z., Bostick T., Caille S., Choi R., DeGraffenreid M.,
RA Di Y., He X., Hungate R.W., Jaen J.C., Liu J., Monshouwer M., McMinn D.,
RA Rew Y., Sudom A., Sun D., Tu H., Ursu S., Walker N., Yan X., Ye Q.,
RA Powers J.P.;
RT "Discovery of novel, potent benzamide inhibitors of 11beta-hydroxysteroid
RT dehydrogenase type 1 (11beta-HSD1) exhibiting oral activity in an enzyme
RT inhibition ex vivo model.";
RL J. Med. Chem. 51:3953-3960(2008).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 24-292 IN COMPLEX WITH NADP AND
RP INHIBITOR.
RX PubMed=19217779; DOI=10.1016/j.bmcl.2009.01.058;
RA Rew Y., McMinn D.L., Wang Z., He X., Hungate R.W., Jaen J.C., Sudom A.,
RA Sun D., Tu H., Ursu S., Villemure E., Walker N.P.C., Yan X., Ye Q.,
RA Powers J.P.;
RT "Discovery and optimization of piperidyl benzamide derivatives as a novel
RT class of 11beta-HSD1 inhibitors.";
RL Bioorg. Med. Chem. Lett. 19:1797-1801(2009).
RN [29]
RP VARIANT [LARGE SCALE ANALYSIS] GLU-148.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Controls the reversible conversion of biologically active
CC glucocorticoids such as cortisone to cortisol, and 11-
CC dehydrocorticosterone to corticosterone in the presence of NADP(H)
CC (PubMed:10497248, PubMed:12460758, PubMed:14973125, PubMed:15152005,
CC PubMed:15280030, PubMed:17593962, PubMed:21453287, PubMed:27927697,
CC PubMed:30902677). Participates in the corticosteroid receptor-mediated
CC anti-inflammatory response, as well as metabolic and homeostatic
CC processes (PubMed:12414862, PubMed:10497248, PubMed:15152005,
CC PubMed:21453287). Plays a role in the secretion of aqueous humor in the
CC eye, maintaining a normotensive, intraocular environment
CC (PubMed:11481269). Bidirectional in vitro, predominantly functions as a
CC reductase in vivo, thereby increasing the concentration of active
CC glucocorticoids (PubMed:12414862, PubMed:10497248, PubMed:11481269,
CC PubMed:12460758). It has broad substrate specificity, besides
CC glucocorticoids, it accepts other steroid and sterol substrates
CC (PubMed:15095019, PubMed:15152005, PubMed:17593962, PubMed:21453287).
CC Interconverts 7-oxo- and 7-hydroxy-neurosteroids such as 7-
CC oxopregnenolone and 7beta-hydroxypregnenolone, 7-
CC oxodehydroepiandrosterone (3beta-hydroxy-5-androstene-7,17-dione) and
CC 7beta-hydroxydehydroepiandrosterone (3beta,7beta-dihydroxyandrost-5-en-
CC 17-one), among others (PubMed:17593962). Catalyzes the stereo-specific
CC conversion of the major dietary oxysterol, 7-ketocholesterol (7-
CC oxocholesterol), into the more polar 7-beta-hydroxycholesterol
CC metabolite (PubMed:15095019, PubMed:15152005). 7-oxocholesterol is one
CC of the most important oxysterols, it participates in several events
CC such as induction of apoptosis, accumulation in atherosclerotic
CC lesions, lipid peroxidation, and induction of foam cell formation
CC (PubMed:15095019). Mediates the 7-oxo reduction of 7-oxolithocholate
CC mainly to chenodeoxycholate, and to a lesser extent to
CC ursodeoxycholate, both in its free form and when conjugated to glycine
CC or taurine, providing a link between glucocorticoid activation and bile
CC acid metabolism (PubMed:21453287). Catalyzes the synthesis of 7-beta-
CC 25-dihydroxycholesterol from 7-oxo-25-hydroxycholesterol in vitro,
CC which acts as ligand for the G-protein-coupled receptor (GPCR) Epstein-
CC Barr virus-induced gene 2 (EBI2) and may thereby regulate immune cell
CC migration (PubMed:30902677). {ECO:0000269|PubMed:10497248,
CC ECO:0000269|PubMed:12460758, ECO:0000269|PubMed:14973125,
CC ECO:0000269|PubMed:15095019, ECO:0000269|PubMed:15152005,
CC ECO:0000269|PubMed:17593962, ECO:0000269|PubMed:21453287,
CC ECO:0000269|PubMed:27927697, ECO:0000269|PubMed:30902677,
CC ECO:0000303|PubMed:10497248, ECO:0000303|PubMed:11481269,
CC ECO:0000303|PubMed:12414862, ECO:0000303|PubMed:12460758,
CC ECO:0000303|PubMed:15095019, ECO:0000303|PubMed:15152005,
CC ECO:0000303|PubMed:21453287}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an 11beta-hydroxysteroid + NADP(+) = an 11-oxosteroid + H(+) +
CC NADPH; Xref=Rhea:RHEA:11388, ChEBI:CHEBI:15378, ChEBI:CHEBI:35346,
CC ChEBI:CHEBI:47787, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC EC=1.1.1.146; Evidence={ECO:0000269|PubMed:10497248,
CC ECO:0000269|PubMed:11481269, ECO:0000269|PubMed:12460758,
CC ECO:0000269|PubMed:14973125, ECO:0000269|PubMed:15152005,
CC ECO:0000269|PubMed:15280030, ECO:0000269|PubMed:17070044,
CC ECO:0000269|PubMed:17593962, ECO:0000269|PubMed:17919905,
CC ECO:0000269|PubMed:21453287, ECO:0000269|PubMed:27927697,
CC ECO:0000269|PubMed:30902677, ECO:0000269|PubMed:8319583};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11389;
CC Evidence={ECO:0000269|PubMed:10497248, ECO:0000269|PubMed:12460758,
CC ECO:0000269|PubMed:14973125, ECO:0000269|PubMed:15152005,
CC ECO:0000269|PubMed:21453287, ECO:0000269|PubMed:30902677,
CC ECO:0000269|PubMed:8319583, ECO:0000305|PubMed:15280030,
CC ECO:0000305|PubMed:17593962, ECO:0000305|PubMed:27927697};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:11390;
CC Evidence={ECO:0000269|PubMed:10497248, ECO:0000269|PubMed:11481269,
CC ECO:0000269|PubMed:12460758, ECO:0000269|PubMed:14973125,
CC ECO:0000269|PubMed:15152005, ECO:0000269|PubMed:21453287,
CC ECO:0000269|PubMed:30902677, ECO:0000269|PubMed:8319583,
CC ECO:0000305|PubMed:15280030, ECO:0000305|PubMed:17593962,
CC ECO:0000305|PubMed:27927697};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cortisone + H(+) + NADPH = cortisol + NADP(+);
CC Xref=Rhea:RHEA:68616, ChEBI:CHEBI:15378, ChEBI:CHEBI:16962,
CC ChEBI:CHEBI:17650, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC Evidence={ECO:0000269|PubMed:11481269, ECO:0000269|PubMed:12460758,
CC ECO:0000269|PubMed:15152005, ECO:0000269|PubMed:15280030,
CC ECO:0000269|PubMed:17593962, ECO:0000269|PubMed:21453287,
CC ECO:0000269|PubMed:27927697, ECO:0000269|PubMed:30902677,
CC ECO:0000269|PubMed:8319583};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68617;
CC Evidence={ECO:0000269|PubMed:11481269, ECO:0000269|PubMed:12460758,
CC ECO:0000269|PubMed:15152005, ECO:0000269|PubMed:21453287,
CC ECO:0000269|PubMed:30902677, ECO:0000269|PubMed:8319583,
CC ECO:0000305|PubMed:15280030, ECO:0000305|PubMed:17593962,
CC ECO:0000305|PubMed:27927697};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:68618;
CC Evidence={ECO:0000269|PubMed:12460758, ECO:0000269|PubMed:15152005,
CC ECO:0000269|PubMed:21453287, ECO:0000269|PubMed:30902677,
CC ECO:0000269|PubMed:8319583, ECO:0000305|PubMed:15280030,
CC ECO:0000305|PubMed:17593962, ECO:0000305|PubMed:27927697};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=corticosterone + NADP(+) = 11-dehydrocorticosterone + H(+) +
CC NADPH; Xref=Rhea:RHEA:42200, ChEBI:CHEBI:15378, ChEBI:CHEBI:16827,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:78600;
CC Evidence={ECO:0000269|PubMed:10497248, ECO:0000269|PubMed:14973125};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42201;
CC Evidence={ECO:0000269|PubMed:10497248, ECO:0000269|PubMed:14973125};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:42202;
CC Evidence={ECO:0000269|PubMed:10497248, ECO:0000269|PubMed:14973125};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 7beta-hydroxysteroid + NADP(+) = a 7-oxosteroid + H(+) +
CC NADPH; Xref=Rhea:RHEA:20233, ChEBI:CHEBI:15378, ChEBI:CHEBI:35349,
CC ChEBI:CHEBI:47789, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC EC=1.1.1.201; Evidence={ECO:0000269|PubMed:14973125,
CC ECO:0000269|PubMed:15095019, ECO:0000269|PubMed:15152005,
CC ECO:0000269|PubMed:17593962, ECO:0000269|PubMed:21453287};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:20235;
CC Evidence={ECO:0000269|PubMed:14973125, ECO:0000269|PubMed:15095019,
CC ECO:0000269|PubMed:15152005, ECO:0000269|PubMed:21453287,
CC ECO:0000305|PubMed:17593962};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=7-oxocholesterol + H(+) + NADPH = 7beta-hydroxycholesterol +
CC NADP(+); Xref=Rhea:RHEA:68656, ChEBI:CHEBI:15378, ChEBI:CHEBI:42989,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:64294;
CC Evidence={ECO:0000269|PubMed:14973125, ECO:0000269|PubMed:15095019,
CC ECO:0000269|PubMed:15152005};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68657;
CC Evidence={ECO:0000269|PubMed:14973125, ECO:0000269|PubMed:15095019,
CC ECO:0000269|PubMed:15152005};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chenodeoxycholate + NADP(+) = 7-oxolithocholate + H(+) +
CC NADPH; Xref=Rhea:RHEA:53820, ChEBI:CHEBI:15378, ChEBI:CHEBI:36234,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:78605;
CC Evidence={ECO:0000269|PubMed:21453287};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:53822;
CC Evidence={ECO:0000269|PubMed:21453287};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=7-oxolithocholate + H(+) + NADPH = NADP(+) + ursodeoxycholate;
CC Xref=Rhea:RHEA:47540, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:78604, ChEBI:CHEBI:78605;
CC Evidence={ECO:0000269|PubMed:21453287};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47541;
CC Evidence={ECO:0000269|PubMed:21453287};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glycochenodeoxycholate + NADP(+) = 7-oxoglycolithocholate +
CC H(+) + NADPH; Xref=Rhea:RHEA:65056, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:36252, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:137818; Evidence={ECO:0000269|PubMed:21453287};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:65058;
CC Evidence={ECO:0000269|PubMed:21453287};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NADP(+) + taurochenodeoxycholate = 7-oxotaurolithocholate +
CC H(+) + NADPH; Xref=Rhea:RHEA:65060, ChEBI:CHEBI:9407,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:137724; Evidence={ECO:0000269|PubMed:21453287};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:65062;
CC Evidence={ECO:0000269|PubMed:21453287};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=NADP(+) + tauroursodeoxycholate = 7-oxotaurolithocholate +
CC H(+) + NADPH; Xref=Rhea:RHEA:68980, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:132028,
CC ChEBI:CHEBI:137724; Evidence={ECO:0000269|PubMed:21453287};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:68982;
CC Evidence={ECO:0000269|PubMed:21453287};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glycoursodeoxycholate + NADP(+) = 7-oxoglycolithocholate +
CC H(+) + NADPH; Xref=Rhea:RHEA:68976, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:132030,
CC ChEBI:CHEBI:137818; Evidence={ECO:0000269|PubMed:21453287};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:68978;
CC Evidence={ECO:0000269|PubMed:21453287};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=7-oxopregnenolone + H(+) + NADPH = 7beta-hydroxypregnenolone +
CC NADP(+); Xref=Rhea:RHEA:69436, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:183806, ChEBI:CHEBI:183807;
CC Evidence={ECO:0000269|PubMed:17593962};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69437;
CC Evidence={ECO:0000305|PubMed:17593962};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3beta,7alpha-dihydroxyandrost-5-en-17-one + NADP(+) = 3beta-
CC hydroxy-5-androstene-7,17-dione + H(+) + NADPH; Xref=Rhea:RHEA:69440,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:81471, ChEBI:CHEBI:183808;
CC Evidence={ECO:0000269|PubMed:17593962};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69441;
CC Evidence={ECO:0000305|PubMed:17593962};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3beta-hydroxy-5-androstene-7,17-dione + H(+) + NADPH =
CC 3beta,7beta-dihydroxyandrost-5-en-17-one + NADP(+);
CC Xref=Rhea:RHEA:69452, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:183368, ChEBI:CHEBI:183808;
CC Evidence={ECO:0000269|PubMed:17593962};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69453;
CC Evidence={ECO:0000305|PubMed:17593962};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3beta-hydroxy-5alpha-androstane-7,17-dione + H(+) + NADPH =
CC 3beta,7beta-dihydroxy-5alpha-androstan-17-one + NADP(+);
CC Xref=Rhea:RHEA:69456, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:79834, ChEBI:CHEBI:183809;
CC Evidence={ECO:0000269|PubMed:17593962};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69457;
CC Evidence={ECO:0000305|PubMed:17593962};
CC -!- ACTIVITY REGULATION: Hexose-6-phosphate dehydrogenase (H6PD) provides
CC cosubstrate NADPH, and the glucose-6-phosphate transporter in the ER-
CC membrane supplies the substrate for H6PDH, their activities stimulate
CC the reduction of cortisone and abolish the oxidation of cortisol.
CC {ECO:0000269|PubMed:15280030, ECO:0000269|PubMed:17593962}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=163 nM for corticosterone {ECO:0000269|PubMed:10497248};
CC KM=594 nM for 11-dehydrocorticosterone {ECO:0000269|PubMed:10497248,
CC ECO:0000269|PubMed:14973125};
CC KM=165 nM for corticosterone {ECO:0000269|PubMed:14973125};
CC KM=564 nM for 7-oxocholesterol {ECO:0000269|PubMed:14973125};
CC KM=0.140 uM for cortisone {ECO:0000269|PubMed:8319583};
CC KM=1.66 uM for cortisol {ECO:0000269|PubMed:8319583};
CC KM=0.6 uM for cortisone {ECO:0000269|PubMed:12460758};
CC KM=1.7 uM for cortisol {ECO:0000269|PubMed:12460758};
CC KM=803 nM for cortisone {ECO:0000269|PubMed:15152005};
CC KM=665 nM for cortisone {ECO:0000269|PubMed:15280030};
CC KM=1093 nM for cortisol {ECO:0000269|PubMed:15280030};
CC KM=826 nM for cortisol {ECO:0000269|PubMed:15152005};
CC KM=980 nM for 7-oxolithocholate {ECO:0000269|PubMed:21453287};
CC Vmax=0.42 nmol/min/mg enzyme with corticosterone as substrate
CC {ECO:0000269|PubMed:10497248};
CC Vmax=0.51 nmol/min/mg enzyme with 11-dehydrocorticosterone as
CC substrate {ECO:0000269|PubMed:10497248, ECO:0000269|PubMed:14973125};
CC Vmax=0.45 nmol/min/mg enzyme with corticosterone as substrate
CC {ECO:0000269|PubMed:14973125};
CC Vmax=0.21 nmol/min/mg enzyme with 7-oxocholesterol as substrate
CC {ECO:0000269|PubMed:14973125};
CC Vmax=540 nmol/h/ug enzyme with cortisol as substrate
CC {ECO:0000269|PubMed:8319583};
CC Vmax=0.216 nmol/min/mg enzyme with cortisone as substrate
CC {ECO:0000269|PubMed:8319583};
CC Vmax=0.76 nmol/h/mg enzyme with cortisone as substrate
CC {ECO:0000269|PubMed:15280030};
CC Vmax=3.8 nmol/min/mg enzyme with cortisone as substrate
CC {ECO:0000269|PubMed:12460758};
CC Vmax=1.74 nmol/h/mg enzyme with cortisol as substrate
CC {ECO:0000269|PubMed:15280030};
CC Vmax=69.8 nmol/min/mg enzyme with cortisol as substrate
CC {ECO:0000269|PubMed:12460758};
CC Vmax=0.72 nmol/h/mg enzyme with cortisone as substrate
CC {ECO:0000269|PubMed:15152005};
CC Vmax=1.59 nmol/h/mg enzyme with cortisone as substrate
CC {ECO:0000269|PubMed:30902677};
CC Vmax=0.64 nmol/h/mg enzyme with cortisol as substrate
CC {ECO:0000269|PubMed:15152005};
CC Vmax=2.8 nmol/h/mg enzyme with 7-oxolithocholate as substrate
CC {ECO:0000269|PubMed:21453287};
CC -!- PATHWAY: Steroid metabolism. {ECO:0000305}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:15513927,
CC ECO:0000269|PubMed:17919905, ECO:0000269|PubMed:18069989,
CC ECO:0000269|PubMed:18485702, ECO:0000269|PubMed:18553955,
CC ECO:0000269|PubMed:19217779}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:10497248, ECO:0000269|PubMed:15280030}; Single-pass
CC type II membrane protein {ECO:0000269|PubMed:10497248}.
CC -!- TISSUE SPECIFICITY: Widely expressed, highest expression in liver,
CC lower in testis, ovary, lung, foreskin fibroblasts, and much lower in
CC kidney (PubMed:1885595). Expressed in liver (at protein level)
CC (PubMed:21453287). Expressed in the basal cells of the corneal
CC epithelium and in the ciliary nonpigmented epithelium (both at mRNA and
CC at protein level) (PubMed:11481269). {ECO:0000269|PubMed:11481269,
CC ECO:0000269|PubMed:1885595, ECO:0000269|PubMed:21453287}.
CC -!- PTM: Glycosylated. {ECO:0000269|PubMed:10497248,
CC ECO:0000269|PubMed:19159218}.
CC -!- DISEASE: Cortisone reductase deficiency 2 (CORTRD2) [MIM:614662]: An
CC autosomal dominant error of cortisone metabolism characterized by a
CC failure to regenerate cortisol from cortisone, resulting in increased
CC cortisol clearance, activation of the hypothalamic- pituitary axis and
CC ACTH-mediated adrenal androgen excess. Clinical features include
CC hyperandrogenism resulting in hirsutism, oligo- amenorrhea, and
CC infertility in females and premature pseudopuberty in males.
CC {ECO:0000269|PubMed:12858176}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; M76665; AAC31757.1; -; Genomic_DNA.
DR EMBL; M76661; AAC31757.1; JOINED; Genomic_DNA.
DR EMBL; M76662; AAC31757.1; JOINED; Genomic_DNA.
DR EMBL; M76663; AAC31757.1; JOINED; Genomic_DNA.
DR EMBL; M76664; AAC31757.1; JOINED; Genomic_DNA.
DR EMBL; AY044084; AAK83653.1; -; Genomic_DNA.
DR EMBL; AY044083; AAK83653.1; JOINED; Genomic_DNA.
DR EMBL; AK313973; BAG36688.1; -; mRNA.
DR EMBL; AL022398; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL031316; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471100; EAW93445.1; -; Genomic_DNA.
DR EMBL; CH471100; EAW93446.1; -; Genomic_DNA.
DR EMBL; BC012593; AAH12593.1; -; mRNA.
DR CCDS; CCDS1489.1; -.
DR PIR; A41173; DXHUBH.
DR RefSeq; NP_001193670.1; NM_001206741.1.
DR RefSeq; NP_005516.1; NM_005525.3.
DR RefSeq; NP_861420.1; NM_181755.2.
DR PDB; 1XU7; X-ray; 1.80 A; A/B/C/D=24-292.
DR PDB; 1XU9; X-ray; 1.55 A; A/B/C/D=24-292.
DR PDB; 2BEL; X-ray; 2.11 A; A/B/C/D=26-284.
DR PDB; 2ILT; X-ray; 2.30 A; A=24-285.
DR PDB; 2IRW; X-ray; 3.10 A; A/B/C/D/E/F/G/H=26-289.
DR PDB; 2RBE; X-ray; 1.90 A; A/B/C/D=25-292.
DR PDB; 3BYZ; X-ray; 2.69 A; A/B/C/D=25-292.
DR PDB; 3BZU; X-ray; 2.25 A; A/B/C/D=24-292.
DR PDB; 3CH6; X-ray; 2.35 A; A/B/D/E=24-292.
DR PDB; 3CZR; X-ray; 2.35 A; A/B=24-292.
DR PDB; 3D3E; X-ray; 2.60 A; A/B/C/D=24-292.
DR PDB; 3D4N; X-ray; 2.50 A; A/B/C/D=24-292.
DR PDB; 3D5Q; X-ray; 2.55 A; A/B/C/D=24-292.
DR PDB; 3EY4; X-ray; 3.00 A; A/B/C/D=25-292.
DR PDB; 3FCO; X-ray; 2.65 A; A/B=24-291.
DR PDB; 3FRJ; X-ray; 2.30 A; A/B=24-292.
DR PDB; 3H6K; X-ray; 2.19 A; A/B/C/D=24-292.
DR PDB; 3HFG; X-ray; 2.30 A; A/B/C/D=24-292.
DR PDB; 3OQ1; X-ray; 2.60 A; A/B/C/D=24-292.
DR PDB; 3PDJ; X-ray; 2.30 A; A/B=24-292.
DR PDB; 3QQP; X-ray; 2.72 A; A/B/C/D=24-292.
DR PDB; 3TFQ; X-ray; 1.80 A; A/B/D/E=24-292.
DR PDB; 4BB5; X-ray; 2.20 A; A/B/C/D=1-292.
DR PDB; 4BB6; X-ray; 2.55 A; A/B=1-292.
DR PDB; 4C7J; X-ray; 2.16 A; A/B/C/D=24-292.
DR PDB; 4C7K; X-ray; 1.91 A; A/B/C/D=24-292.
DR PDB; 4HFR; X-ray; 2.73 A; A/B=24-292.
DR PDB; 4HX5; X-ray; 2.19 A; A/B/C/D=24-292.
DR PDB; 4IJU; X-ray; 2.35 A; A/B/D/E=24-292.
DR PDB; 4IJV; X-ray; 2.35 A; A/B/D/E=24-292.
DR PDB; 4IJW; X-ray; 2.35 A; A/B/D/E=24-292.
DR PDB; 4K1L; X-ray; 1.96 A; A/B/C/D=24-292.
DR PDB; 4P38; X-ray; 2.80 A; A/B=26-290.
DR PDB; 4YYZ; X-ray; 3.20 A; A/B=26-284.
DR PDB; 5PGU; X-ray; 2.35 A; A/B/D/E=24-292.
DR PDB; 5PGV; X-ray; 2.35 A; A/B/D/E=24-292.
DR PDB; 5PGW; X-ray; 2.37 A; A/B/D/E=24-292.
DR PDB; 5PGX; X-ray; 2.50 A; A/B/D/E=24-292.
DR PDB; 5PGY; X-ray; 2.07 A; A/B/D/E=24-292.
DR PDB; 5QII; X-ray; 2.45 A; A/B/D/E=24-292.
DR PDBsum; 1XU7; -.
DR PDBsum; 1XU9; -.
DR PDBsum; 2BEL; -.
DR PDBsum; 2ILT; -.
DR PDBsum; 2IRW; -.
DR PDBsum; 2RBE; -.
DR PDBsum; 3BYZ; -.
DR PDBsum; 3BZU; -.
DR PDBsum; 3CH6; -.
DR PDBsum; 3CZR; -.
DR PDBsum; 3D3E; -.
DR PDBsum; 3D4N; -.
DR PDBsum; 3D5Q; -.
DR PDBsum; 3EY4; -.
DR PDBsum; 3FCO; -.
DR PDBsum; 3FRJ; -.
DR PDBsum; 3H6K; -.
DR PDBsum; 3HFG; -.
DR PDBsum; 3OQ1; -.
DR PDBsum; 3PDJ; -.
DR PDBsum; 3QQP; -.
DR PDBsum; 3TFQ; -.
DR PDBsum; 4BB5; -.
DR PDBsum; 4BB6; -.
DR PDBsum; 4C7J; -.
DR PDBsum; 4C7K; -.
DR PDBsum; 4HFR; -.
DR PDBsum; 4HX5; -.
DR PDBsum; 4IJU; -.
DR PDBsum; 4IJV; -.
DR PDBsum; 4IJW; -.
DR PDBsum; 4K1L; -.
DR PDBsum; 4P38; -.
DR PDBsum; 4YYZ; -.
DR PDBsum; 5PGU; -.
DR PDBsum; 5PGV; -.
DR PDBsum; 5PGW; -.
DR PDBsum; 5PGX; -.
DR PDBsum; 5PGY; -.
DR PDBsum; 5QII; -.
DR AlphaFoldDB; P28845; -.
DR SMR; P28845; -.
DR BioGRID; 109523; 24.
DR DIP; DIP-59618N; -.
DR IntAct; P28845; 5.
DR STRING; 9606.ENSP00000355995; -.
DR BindingDB; P28845; -.
DR ChEMBL; CHEMBL4235; -.
DR DrugBank; DB08280; (1S,3R,4S,5S,7S)-4-{[2-(4-METHOXYPHENOXY)-2-METHYLPROPANOYL]AMINO}ADAMANTANE-1-CARBOXAMIDE.
DR DrugBank; DB07049; (2R)-1-[(4-tert-butylphenyl)sulfonyl]-2-methyl-4-(4-nitrophenyl)piperazine.
DR DrugBank; DB06992; (3,3-dimethylpiperidin-1-yl)(6-(3-fluoro-4-methylphenyl)pyridin-2-yl)methanone.
DR DrugBank; DB08771; (5R)-2-[(2-Fluorophenyl)amino]-5-isopropyl-1,3-thiazol-4(5H)-one.
DR DrugBank; DB07866; (5S)-2-(Cyclooctylamino)-5-methyl-5-propyl-1,3-thiazol-4(5H)-one.
DR DrugBank; DB07310; (5S)-2-{[(1S)-1-(2-fluorophenyl)ethyl]amino}-5-methyl-5-(trifluoromethyl)-1,3-thiazol-4(5H)-one.
DR DrugBank; DB07017; (5S)-2-{[(1S)-1-(4-Fluorophenyl)ethyl]amino}-5-(2-hydroxy-2-propanyl)-5-methyl-1,3-thiazol-4(5H)-one.
DR DrugBank; DB07624; 1-{[(3R)-3-methyl-4-({4-[(1S)-2,2,2-trifluoro-1-hydroxy-1-methylethyl]phenyl}sulfonyl)piperazin-1-yl]methyl}cyclopropanecarboxamide.
DR DrugBank; DB08277; 2-(2-CHLORO-4-FLUOROPHENOXY)-2-METHYL-N-[(1R,2S,3S,5S,7S)-5-(METHYLSULFONYL)-2-ADAMANTYL]PROPANAMIDE.
DR DrugBank; DB07056; 2-(6-{[(3-chloro-2-methylphenyl)sulfonyl]amino}pyridin-2-yl)-N,N-diethylacetamide.
DR DrugBank; DB03814; 2-(N-morpholino)ethanesulfonic acid.
DR DrugBank; DB02329; Carbenoxolone.
DR DrugBank; DB04652; Corticosterone.
DR DrugBank; DB01234; Dexamethasone.
DR DrugBank; DB14649; Dexamethasone acetate.
DR DrugBank; DB00687; Fludrocortisone.
DR DrugBank; DB13751; Glycyrrhizic acid.
DR DrugBank; DB00741; Hydrocortisone.
DR DrugBank; DB05064; INCB13739.
DR DrugBank; DB16220; Lonapegsomatropin.
DR DrugBank; DB00959; Methylprednisolone.
DR DrugBank; DB07619; N-cyclopropyl-N-(trans-4-pyridin-3-ylcyclohexyl)-4-[(1S)-2,2,2-trifluoro-1-hydroxy-1-methylethyl]benzamide.
DR DrugBank; DB07316; N-{1-[(1-carbamoylcyclopropyl)methyl]piperidin-4-yl}-N-cyclopropyl-4-[(1S)-2,2,2-trifluoro-1-hydroxy-1-methylethyl]benzamide.
DR DrugBank; DB00461; Nabumetone.
DR DrugBank; DB00157; NADH.
DR DrugBank; DB03461; Nicotinamide adenine dinucleotide phosphate.
DR DrugBank; DB14631; Prednisolone phosphate.
DR DrugBank; DB00635; Prednisone.
DR DrugBank; DB15093; Somapacitan.
DR DrugCentral; P28845; -.
DR GuidetoPHARMACOLOGY; 2763; -.
DR SwissLipids; SLP:000000809; -.
DR GlyConnect; 1158; 2 N-Linked glycans (2 sites).
DR GlyGen; P28845; 3 sites, 2 N-linked glycans (2 sites).
DR iPTMnet; P28845; -.
DR PhosphoSitePlus; P28845; -.
DR BioMuta; HSD11B1; -.
DR DMDM; 118569; -.
DR EPD; P28845; -.
DR jPOST; P28845; -.
DR MassIVE; P28845; -.
DR PaxDb; P28845; -.
DR PeptideAtlas; P28845; -.
DR PRIDE; P28845; -.
DR ProteomicsDB; 54504; -.
DR Antibodypedia; 34595; 427 antibodies from 41 providers.
DR DNASU; 3290; -.
DR Ensembl; ENST00000367027.5; ENSP00000355994.3; ENSG00000117594.10.
DR Ensembl; ENST00000367028.6; ENSP00000355995.1; ENSG00000117594.10.
DR GeneID; 3290; -.
DR KEGG; hsa:3290; -.
DR MANE-Select; ENST00000367027.5; ENSP00000355994.3; NM_005525.4; NP_005516.1.
DR CTD; 3290; -.
DR DisGeNET; 3290; -.
DR GeneCards; HSD11B1; -.
DR HGNC; HGNC:5208; HSD11B1.
DR HPA; ENSG00000117594; Tissue enriched (liver).
DR MalaCards; HSD11B1; -.
DR MIM; 600713; gene.
DR MIM; 614662; phenotype.
DR neXtProt; NX_P28845; -.
DR OpenTargets; ENSG00000117594; -.
DR Orphanet; 168588; Hyperandrogenism due to cortisone reductase deficiency.
DR PharmGKB; PA29476; -.
DR VEuPathDB; HostDB:ENSG00000117594; -.
DR eggNOG; KOG1205; Eukaryota.
DR GeneTree; ENSGT00940000160097; -.
DR InParanoid; P28845; -.
DR OMA; SMEDMTF; -.
DR OrthoDB; 906746at2759; -.
DR PhylomeDB; P28845; -.
DR TreeFam; TF329114; -.
DR BioCyc; MetaCyc:HS04154-MON; -.
DR BRENDA; 1.1.1.146; 2681.
DR BRENDA; 1.1.1.B40; 2681.
DR PathwayCommons; P28845; -.
DR Reactome; R-HSA-194002; Glucocorticoid biosynthesis.
DR SABIO-RK; P28845; -.
DR SignaLink; P28845; -.
DR BioGRID-ORCS; 3290; 12 hits in 1073 CRISPR screens.
DR ChiTaRS; HSD11B1; human.
DR EvolutionaryTrace; P28845; -.
DR GeneWiki; 11%CE%B2-hydroxysteroid_dehydrogenase_type_1; -.
DR GenomeRNAi; 3290; -.
DR Pharos; P28845; Tclin.
DR PRO; PR:P28845; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P28845; protein.
DR Bgee; ENSG00000117594; Expressed in decidua and 157 other tissues.
DR ExpressionAtlas; P28845; baseline and differential.
DR Genevisible; P28845; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0070524; F:11-beta-hydroxysteroid dehydrogenase (NADP+) activity; IDA:UniProtKB.
DR GO; GO:0047022; F:7-beta-hydroxysteroid dehydrogenase (NADP+) activity; IEA:RHEA.
DR GO; GO:0102196; F:cortisol dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0050661; F:NADP binding; IDA:UniProtKB.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0005496; F:steroid binding; IBA:GO_Central.
DR GO; GO:0030324; P:lung development; IEA:Ensembl.
DR GO; GO:0006706; P:steroid catabolic process; IBA:GO_Central.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR InterPro; IPR002347; SDR_fam.
DR Pfam; PF00106; adh_short; 1.
DR PRINTS; PR00081; GDHRDH.
DR SUPFAM; SSF51735; SSF51735; 1.
DR PROSITE; PS00061; ADH_SHORT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Disease variant; Endoplasmic reticulum; Glycoprotein;
KW Lipid metabolism; Membrane; NADP; Oxidoreductase; Reference proteome;
KW Signal-anchor; Steroid metabolism; Transmembrane; Transmembrane helix.
FT CHAIN 1..292
FT /note="11-beta-hydroxysteroid dehydrogenase 1"
FT /id="PRO_0000054619"
FT TOPO_DOM 1..7
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 8..24
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 25..292
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT ACT_SITE 183
FT /note="Proton acceptor"
FT BINDING 41..67
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:15513927,
FT ECO:0000269|PubMed:17919905, ECO:0000269|PubMed:18069989,
FT ECO:0000269|PubMed:18485702, ECO:0000269|PubMed:18553955,
FT ECO:0000269|PubMed:19217779"
FT BINDING 92..93
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:15513927,
FT ECO:0000269|PubMed:17919905, ECO:0000269|PubMed:18069989,
FT ECO:0000269|PubMed:18485702, ECO:0000269|PubMed:18553955,
FT ECO:0000269|PubMed:19217779"
FT BINDING 119..121
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:15513927,
FT ECO:0000269|PubMed:17919905, ECO:0000269|PubMed:18069989,
FT ECO:0000269|PubMed:18485702, ECO:0000269|PubMed:18553955,
FT ECO:0000269|PubMed:19217779"
FT BINDING 170
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:15513927,
FT ECO:0007744|PDB:1XU7, ECO:0007744|PDB:1XU9"
FT BINDING 183..187
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:15513927,
FT ECO:0000269|PubMed:17919905, ECO:0000269|PubMed:18069989,
FT ECO:0000269|PubMed:18485702, ECO:0000269|PubMed:18553955,
FT ECO:0000269|PubMed:19217779"
FT BINDING 218..222
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:15513927,
FT ECO:0000269|PubMed:17919905, ECO:0000269|PubMed:18069989,
FT ECO:0000269|PubMed:18485702, ECO:0000269|PubMed:18553955,
FT ECO:0000269|PubMed:19217779"
FT CARBOHYD 123
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 162
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 207
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 148
FT /note="V -> E (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035845"
FT MUTAGEN 5..6
FT /note="KK->RR: Predominantly inverted topology. No effect
FT on activity."
FT /evidence="ECO:0000269|PubMed:10497248,
FT ECO:0000269|PubMed:15152005"
FT MUTAGEN 5..6
FT /note="KK->SS: Inverted topology. Reduced Vmax."
FT /evidence="ECO:0000269|PubMed:10497248,
FT ECO:0000269|PubMed:15152005"
FT MUTAGEN 5
FT /note="K->R: Predominantly inverted topology. No effect on
FT activity."
FT /evidence="ECO:0000269|PubMed:10497248"
FT MUTAGEN 5
FT /note="K->S: Inverted topology. No effect on activity."
FT /evidence="ECO:0000269|PubMed:10497248"
FT MUTAGEN 6
FT /note="K->R: No effect on topology. Increased Km for
FT corticosterone."
FT /evidence="ECO:0000269|PubMed:10497248"
FT MUTAGEN 6
FT /note="K->S: No effect on topology or activity."
FT /evidence="ECO:0000269|PubMed:10497248"
FT MUTAGEN 18..21
FT /note="YYYY->AAAA: No effect on topology. Reduced Vmax."
FT /evidence="ECO:0000269|PubMed:10497248"
FT MUTAGEN 18..21
FT /note="YYYY->FFFF: No effect on topology or activity."
FT /evidence="ECO:0000269|PubMed:10497248"
FT MUTAGEN 19..21
FT /note="YYY->AYA: No effect on topology. Reduced Vmax."
FT /evidence="ECO:0000269|PubMed:10497248"
FT MUTAGEN 25..26
FT /note="EE->KK: Inverted topology. Reduced Vmax."
FT /evidence="ECO:0000269|PubMed:15152005"
FT MUTAGEN 25..26
FT /note="EE->KQ: No effect on topology. Reduced Vmax."
FT /evidence="ECO:0000269|PubMed:15152005"
FT MUTAGEN 25..26
FT /note="EE->QQ: Reduced Vmax."
FT /evidence="ECO:0000269|PubMed:15152005"
FT MUTAGEN 25
FT /note="E->K,Q: No effect on activity."
FT /evidence="ECO:0000269|PubMed:15152005"
FT MUTAGEN 26
FT /note="E->K: No effect on activity."
FT /evidence="ECO:0000269|PubMed:15152005"
FT MUTAGEN 35..36
FT /note="KK->SS: Complete loss of activity."
FT /evidence="ECO:0000269|PubMed:15152005"
FT HELIX 29..32
FT /evidence="ECO:0007829|PDB:1XU9"
FT STRAND 36..41
FT /evidence="ECO:0007829|PDB:1XU9"
FT HELIX 45..56
FT /evidence="ECO:0007829|PDB:1XU9"
FT STRAND 60..66
FT /evidence="ECO:0007829|PDB:1XU9"
FT HELIX 68..81
FT /evidence="ECO:0007829|PDB:1XU9"
FT STRAND 84..90
FT /evidence="ECO:0007829|PDB:1XU9"
FT STRAND 93..95
FT /evidence="ECO:0007829|PDB:4YYZ"
FT HELIX 96..110
FT /evidence="ECO:0007829|PDB:1XU9"
FT STRAND 114..118
FT /evidence="ECO:0007829|PDB:1XU9"
FT HELIX 133..143
FT /evidence="ECO:0007829|PDB:1XU9"
FT HELIX 145..161
FT /evidence="ECO:0007829|PDB:1XU9"
FT STRAND 164..170
FT /evidence="ECO:0007829|PDB:1XU9"
FT HELIX 171..173
FT /evidence="ECO:0007829|PDB:1XU9"
FT HELIX 181..204
FT /evidence="ECO:0007829|PDB:1XU9"
FT STRAND 209..215
FT /evidence="ECO:0007829|PDB:1XU9"
FT HELIX 221..226
FT /evidence="ECO:0007829|PDB:1XU9"
FT HELIX 229..234
FT /evidence="ECO:0007829|PDB:1XU9"
FT HELIX 238..250
FT /evidence="ECO:0007829|PDB:1XU9"
FT STRAND 254..258
FT /evidence="ECO:0007829|PDB:1XU9"
FT HELIX 262..267
FT /evidence="ECO:0007829|PDB:1XU9"
FT HELIX 271..280
FT /evidence="ECO:0007829|PDB:1XU9"
FT HELIX 281..283
FT /evidence="ECO:0007829|PDB:1XU9"
FT HELIX 287..290
FT /evidence="ECO:0007829|PDB:4C7J"
SQ SEQUENCE 292 AA; 32401 MW; 4632D0F3BBEFC474 CRC64;
MAFMKKYLLP ILGLFMAYYY YSANEEFRPE MLQGKKVIVT GASKGIGREM AYHLAKMGAH
VVVTARSKET LQKVVSHCLE LGAASAHYIA GTMEDMTFAE QFVAQAGKLM GGLDMLILNH
ITNTSLNLFH DDIHHVRKSM EVNFLSYVVL TVAALPMLKQ SNGSIVVVSS LAGKVAYPMV
AAYSASKFAL DGFFSSIRKE YSVSRVNVSI TLCVLGLIDT ETAMKAVSGI VHMQAAPKEE
CALEIIKGGA LRQEEVYYDS SLWTTLLIRN PCRKILEFLY STSYNMDRFI NK
