ID NSDHL_HUMAN Reviewed; 373 AA.
AC Q15738; D3DWT6; O00344;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2000, sequence version 2.
DT 27-MAR-2024, entry version 197.
DE RecName: Full=Sterol-4-alpha-carboxylate 3-dehydrogenase, decarboxylating;
DE EC=1.1.1.170 {ECO:0000250|UniProtKB:Q9R1J0};
DE AltName: Full=Protein H105e3;
GN Name=NSDHL; Synonyms=H105E3;
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 [MRNA].
RC TISSUE=Heart;
RA Levin M.L., Herman G.E.;
RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10854409; DOI=10.1101/gr.10.6.758;
RA Mallon A.-M., Platzer M., Bate R., Gloeckner G., Botcherby M.R.M.,
RA Nordsiek G., Strivens M.A., Kioschis P., Dangel A., Cunningham D.,
RA Straw R.N.A., Weston P., Gilbert M., Fernando S., Goodall K., Hunter G.,
RA Greystrong J.S., Clarke D., Kimberley C., Goerdes M., Blechschmidt K.,
RA Rump A., Hinzmann B., Mundy C.R., Miller W., Poustka A., Herman G.E.,
RA Rhodes M., Denny P., Rosenthal A., Brown S.D.M.;
RT "Comparative genome sequence analysis of the Bpa/Str region in mouse and
RT man.";
RL Genome Res. 10:758-775(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
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=Eye;
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 PRELIMINARY NUCLEOTIDE SEQUENCE [MRNA] OF 224-373.
RC TISSUE=Heart;
RX PubMed=8828036; DOI=10.1101/gr.6.6.465;
RA Levin M.L., Chatterjee A., Pragliola A., Worley K.C., Wehnert M.,
RA Zhuchenko O., Smith R.F., Lee C.C., Herman G.E.;
RT "A comparative transcription map of the murine bare patches (Bpa) and
RT striated (Str) critical regions and human Xq28.";
RL Genome Res. 6:465-477(1996).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-22, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [12]
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 [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [14]
RP VARIANTS CHILD VAL-105 AND SER-205.
RX PubMed=10710235;
RX DOI=10.1002/(sici)1096-8628(20000214)90:4<339::aid-ajmg15>3.3.co;2-x;
RA Konig A., Happle R., Bornholdt D., Engel H., Grzeschik K.H.;
RT "Mutations in the NSDHL gene, encoding a 3beta-hydroxysteroid
RT dehydrogenase, cause CHILD syndrome.";
RL Am. J. Med. Genet. 90:339-346(2000).
RN [15]
RP VARIANT CHILD PRO-182.
RX PubMed=11907515; DOI=10.1067/mjd.2002.113680;
RA Konig A., Happle R., Fink-Puches R., Soyer H.P., Bornholdt D., Engel H.,
RA Grzeschik K.H.;
RT "A novel missense mutation of NSDHL in an unusual case of CHILD syndrome
RT showing bilateral, almost symmetric involvement.";
RL J. Am. Acad. Dermatol. 46:594-596(2002).
RN [16]
RP VARIANT CKS LYS-232 DEL, CHARACTERIZATION OF VARIANT CKS LYS-232 DEL, AND
RP SUBCELLULAR LOCATION.
RX PubMed=21129721; DOI=10.1016/j.ajhg.2010.11.004;
RA McLarren K.W., Severson T.M., du Souich C., Stockton D.W., Kratz L.E.,
RA Cunningham D., Hendson G., Morin R.D., Wu D., Paul J.E., An J.,
RA Nelson T.N., Chou A., DeBarber A.E., Merkens L.S., Michaud J.L.,
RA Waters P.J., Yin J., McGillivray B., Demos M., Rouleau G.A.,
RA Grzeschik K.H., Smith R., Tarpey P.S., Shears D., Schwartz C.E., Gecz J.,
RA Stratton M.R., Arbour L., Hurlburt J., Van Allen M.I., Herman G.E.,
RA Zhao Y., Moore R., Kelley R.I., Jones S.J., Steiner R.D., Raymond F.L.,
RA Marra M.A., Boerkoel C.F.;
RT "Hypomorphic temperature-sensitive alleles of NSDHL cause CK syndrome.";
RL Am. J. Hum. Genet. 87:905-914(2010).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) IN COMPLEX WITH NAD, AND SUBUNIT.
RX PubMed=32140747; DOI=10.1007/s00018-020-03490-2;
RA Kim D.G., Cho S., Lee K.Y., Cheon S.H., Yoon H.J., Lee J.Y., Kim D.,
RA Shin K.S., Koh C.H., Koo J.S., Choi Y., Lee H.H., Oh Y.K., Jeong Y.S.,
RA Chung S.J., Baek M., Jung K.Y., Lim H.J., Kim H.S., Park S.J., Lee J.Y.,
RA Lee S.J., Lee B.J.;
RT "Crystal structures of human NSDHL and development of its novel inhibitor
RT with the potential to suppress EGFR activity.";
RL Cell. Mol. Life Sci. 78:207-225(2021).
CC -!- FUNCTION: Catalyzes the NAD(P)(+)-dependent oxidative decarboxylation
CC of the C4 methyl groups of 4-alpha-carboxysterols in post-squalene
CC cholesterol biosynthesis (By similarity). Also plays a role in the
CC regulation of the endocytic trafficking of EGFR (By similarity).
CC {ECO:0000250|UniProtKB:Q9R1J0}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 3beta-hydroxysteroid-4alpha-carboxylate + NADP(+) = a 3-
CC oxosteroid + CO2 + NADPH; Xref=Rhea:RHEA:34771, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:47788, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:136966; EC=1.1.1.170;
CC Evidence={ECO:0000250|UniProtKB:Q9R1J0};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 3beta-hydroxysteroid-4alpha-carboxylate + NAD(+) = a 3-
CC oxosteroid + CO2 + NADH; Xref=Rhea:RHEA:34775, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:47788, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:136966; EC=1.1.1.170;
CC Evidence={ECO:0000250|UniProtKB:Q9R1J0};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4alpha-carboxyzymosterol + NADP(+) = CO2 + NADPH +
CC zymosterone; Xref=Rhea:RHEA:33455, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:52386, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:143575; Evidence={ECO:0000250|UniProtKB:Q9R1J0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33456;
CC Evidence={ECO:0000250|UniProtKB:Q9R1J0};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4alpha-carboxy-4beta-methyl-5alpha-cholest-8-en-3beta-ol +
CC NADP(+) = 4alpha-methyl-5alpha-cholest-8-en-3-one + CO2 + NADPH;
CC Xref=Rhea:RHEA:46828, ChEBI:CHEBI:16526, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:87047, ChEBI:CHEBI:87050;
CC Evidence={ECO:0000250|UniProtKB:Q9R1J0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46829;
CC Evidence={ECO:0000250|UniProtKB:Q9R1J0};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4alpha-carboxy-5alpha-cholest-8-ene-3beta-ol + NADP(+) =
CC 5alpha-cholest-8-en-3-one + CO2 + NADPH; Xref=Rhea:RHEA:46848,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:87055, ChEBI:CHEBI:87056;
CC Evidence={ECO:0000250|UniProtKB:Q9R1J0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46849;
CC Evidence={ECO:0000250|UniProtKB:Q9R1J0};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4beta-methylzymosterol-4alpha-carboxylate + NADP(+) = 3-
CC dehydro-4-methylzymosterol + CO2 + NADPH; Xref=Rhea:RHEA:33447,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:50593, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:64925; EC=1.1.1.170;
CC Evidence={ECO:0000250|UniProtKB:Q9R1J0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33448;
CC Evidence={ECO:0000250|UniProtKB:Q9R1J0};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4beta-methylzymosterol-4alpha-carboxylate + NAD(+) = 3-
CC dehydro-4-methylzymosterol + CO2 + NADH; Xref=Rhea:RHEA:47160,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:50593, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:64925;
CC Evidence={ECO:0000250|UniProtKB:Q9R1J0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47161;
CC Evidence={ECO:0000250|UniProtKB:Q9R1J0};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4alpha-carboxy-5alpha-cholest-8-ene-3beta-ol + NAD(+) =
CC 5alpha-cholest-8-en-3-one + CO2 + NADH; Xref=Rhea:RHEA:47172,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945,
CC ChEBI:CHEBI:87055, ChEBI:CHEBI:87056;
CC Evidence={ECO:0000250|UniProtKB:Q9R1J0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47173;
CC Evidence={ECO:0000250|UniProtKB:Q9R1J0};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4alpha-carboxy-4beta-methyl-5alpha-cholest-8-en-3beta-ol +
CC NAD(+) = 4alpha-methyl-5alpha-cholest-8-en-3-one + CO2 + NADH;
CC Xref=Rhea:RHEA:47168, ChEBI:CHEBI:16526, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:87047, ChEBI:CHEBI:87050;
CC Evidence={ECO:0000250|UniProtKB:Q9R1J0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47169;
CC Evidence={ECO:0000250|UniProtKB:Q9R1J0};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4alpha-carboxyzymosterol + NAD(+) = CO2 + NADH + zymosterone;
CC Xref=Rhea:RHEA:47164, ChEBI:CHEBI:16526, ChEBI:CHEBI:52386,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:143575;
CC Evidence={ECO:0000250|UniProtKB:Q9R1J0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47165;
CC Evidence={ECO:0000250|UniProtKB:Q9R1J0};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=21.4 uM for NADH {ECO:0000269|PubMed:32140747};
CC KM=151.5 uM for NADP(+) {ECO:0000269|PubMed:32140747};
CC -!- PATHWAY: Steroid biosynthesis; zymosterol biosynthesis; zymosterol from
CC lanosterol: step 4/6.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:32140747}.
CC -!- INTERACTION:
CC Q15738; P54253: ATXN1; NbExp=3; IntAct=EBI-4280135, EBI-930964;
CC Q15738; Q8TEB9: RHBDD1; NbExp=3; IntAct=EBI-4280135, EBI-9916444;
CC Q15738; Q9Y320: TMX2; NbExp=3; IntAct=EBI-4280135, EBI-6447886;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:21129721}; Single-pass membrane protein
CC {ECO:0000255}. Lipid droplet {ECO:0000250|UniProtKB:Q9R1J0}.
CC Note=Trafficking through the Golgi is necessary for ER membrane
CC localization. {ECO:0000250|UniProtKB:Q9R1J0}.
CC -!- TISSUE SPECIFICITY: Brain, heart, liver, lung, kidney, skin and
CC placenta.
CC -!- DISEASE: Congenital hemidysplasia with ichthyosiform erythroderma and
CC limb defects (CHILD) [MIM:308050]: An X-linked dominant disorder of
CC lipid metabolism with disturbed cholesterol biosynthesis, which
CC typically results in male lethality. Clinically, it is characterized by
CC congenital, unilateral, ichthyosisform erythroderma with striking
CC lateralization, sharp midline demarcation, and ipsilateral limb defects
CC and hypoplasia of the body. Limbs defects range from hypoplasia of
CC digits or ribs to complete amelia, often including scoliosis.
CC {ECO:0000269|PubMed:10710235, ECO:0000269|PubMed:11907515}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: CK syndrome (CKS) [MIM:300831]: An X-linked recessive disorder
CC characterized by mild to severe cognitive impairment, seizures,
CC microcephaly, cerebral cortical malformations, dysmorphic facial
CC features, and thin body habitus. {ECO:0000269|PubMed:21129721}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the 3-beta-HSD family. {ECO:0000305}.
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DR EMBL; U47105; AAC50558.2; -; mRNA.
DR EMBL; U82671; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471172; EAW72898.1; -; Genomic_DNA.
DR EMBL; CH471172; EAW72899.1; -; Genomic_DNA.
DR EMBL; BC000245; AAH00245.1; -; mRNA.
DR EMBL; BC007816; AAH07816.1; -; mRNA.
DR CCDS; CCDS14717.1; -.
DR RefSeq; NP_001123237.1; NM_001129765.1.
DR RefSeq; NP_057006.1; NM_015922.2.
DR RefSeq; XP_011529480.1; XM_011531178.2.
DR PDB; 6JKG; X-ray; 2.90 A; A/B=31-267.
DR PDB; 6JKH; X-ray; 3.00 A; A/B=31-267.
DR PDBsum; 6JKG; -.
DR PDBsum; 6JKH; -.
DR AlphaFoldDB; Q15738; -.
DR SMR; Q15738; -.
DR BioGRID; 119131; 169.
DR IntAct; Q15738; 31.
DR MINT; Q15738; -.
DR STRING; 9606.ENSP00000359297; -.
DR DrugBank; DB00157; NADH.
DR GlyGen; Q15738; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q15738; -.
DR PhosphoSitePlus; Q15738; -.
DR SwissPalm; Q15738; -.
DR BioMuta; NSDHL; -.
DR DMDM; 8488997; -.
DR REPRODUCTION-2DPAGE; Q15738; -.
DR EPD; Q15738; -.
DR jPOST; Q15738; -.
DR MassIVE; Q15738; -.
DR MaxQB; Q15738; -.
DR PaxDb; 9606-ENSP00000359297; -.
DR PeptideAtlas; Q15738; -.
DR ProteomicsDB; 60727; -.
DR Pumba; Q15738; -.
DR Antibodypedia; 349; 172 antibodies from 25 providers.
DR DNASU; 50814; -.
DR Ensembl; ENST00000370274.8; ENSP00000359297.3; ENSG00000147383.11.
DR Ensembl; ENST00000440023.5; ENSP00000391854.1; ENSG00000147383.11.
DR Ensembl; ENST00000709998.1; ENSP00000517980.1; ENSG00000292192.1.
DR Ensembl; ENST00000710000.1; ENSP00000517982.1; ENSG00000292192.1.
DR GeneID; 50814; -.
DR KEGG; hsa:50814; -.
DR MANE-Select; ENST00000370274.8; ENSP00000359297.3; NM_015922.3; NP_057006.1.
DR UCSC; uc004fgs.2; human.
DR AGR; HGNC:13398; -.
DR CTD; 50814; -.
DR DisGeNET; 50814; -.
DR GeneCards; NSDHL; -.
DR GeneReviews; NSDHL; -.
DR HGNC; HGNC:13398; NSDHL.
DR HPA; ENSG00000147383; Low tissue specificity.
DR MalaCards; NSDHL; -.
DR MIM; 300275; gene.
DR MIM; 300831; phenotype.
DR MIM; 308050; phenotype.
DR neXtProt; NX_Q15738; -.
DR OpenTargets; ENSG00000147383; -.
DR Orphanet; 139; CHILD syndrome.
DR Orphanet; 251383; CK syndrome.
DR PharmGKB; PA134959020; -.
DR VEuPathDB; HostDB:ENSG00000147383; -.
DR eggNOG; KOG1430; Eukaryota.
DR GeneTree; ENSGT00940000158229; -.
DR InParanoid; Q15738; -.
DR OMA; STAHWFD; -.
DR OrthoDB; 1133at2759; -.
DR PhylomeDB; Q15738; -.
DR TreeFam; TF354279; -.
DR BioCyc; MetaCyc:HS07423-MONOMER; -.
DR BRENDA; 1.1.1.170; 2681.
DR PathwayCommons; Q15738; -.
DR Reactome; R-HSA-191273; Cholesterol biosynthesis.
DR SignaLink; Q15738; -.
DR UniPathway; UPA00770; UER00757.
DR BioGRID-ORCS; 50814; 18 hits in 782 CRISPR screens.
DR GeneWiki; NSDHL; -.
DR GenomeRNAi; 50814; -.
DR Pharos; Q15738; Tbio.
DR PRO; PR:Q15738; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; Q15738; Protein.
DR Bgee; ENSG00000147383; Expressed in cervix squamous epithelium and 185 other cell types or tissues.
DR ExpressionAtlas; Q15738; baseline and differential.
DR Genevisible; Q15738; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:LIFEdb.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0005811; C:lipid droplet; IDA:UniProtKB.
DR GO; GO:0003854; F:3-beta-hydroxy-delta5-steroid dehydrogenase activity; TAS:ProtInc.
DR GO; GO:0102175; F:3-beta-hydroxysteroid dehydrogenase/C4-decarboxylase activity; IEA:RHEA.
DR GO; GO:0103066; F:4alpha-carboxy-4beta-methyl-5alpha-cholesta-8-en-3beta-ol:NAD(P)+ 3-oxidoreductase (decarboxylating) activity; IEA:UniProtKB-EC.
DR GO; GO:0103067; F:4alpha-carboxy-5alpha-cholesta-8-en-3beta-ol:NAD(P)+ 3-dehydrogenase (decarboxylating) activity; IEA:UniProtKB-EC.
DR GO; GO:0000252; F:C-3 sterol dehydrogenase (C-4 sterol decarboxylase) activity; TAS:Reactome.
DR GO; GO:0016616; F:oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor; IBA:GO_Central.
DR GO; GO:0047012; F:sterol-4-alpha-carboxylate 3-dehydrogenase (decarboxylating) activity; IEA:UniProtKB-EC.
DR GO; GO:0006695; P:cholesterol biosynthetic process; TAS:Reactome.
DR GO; GO:0008203; P:cholesterol metabolic process; IBA:GO_Central.
DR GO; GO:0001942; P:hair follicle development; IEA:Ensembl.
DR GO; GO:0060716; P:labyrinthine layer blood vessel development; IEA:Ensembl.
DR GO; GO:0007224; P:smoothened signaling pathway; IEA:Ensembl.
DR CDD; cd09813; 3b-HSD-NSDHL-like_SDR_e; 1.
DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1.
DR InterPro; IPR002225; 3Beta_OHSteriod_DH/Estase.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR PANTHER; PTHR43245; BIFUNCTIONAL POLYMYXIN RESISTANCE PROTEIN ARNA; 1.
DR PANTHER; PTHR43245:SF51; SHORT CHAIN DEHYDROGENASE_REDUCTASE FAMILY 42E, MEMBER 2; 1.
DR Pfam; PF01073; 3Beta_HSD; 1.
DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cholesterol biosynthesis;
KW Cholesterol metabolism; Disease variant; Endoplasmic reticulum; Ichthyosis;
KW Intellectual disability; Lipid biosynthesis; Lipid droplet;
KW Lipid metabolism; Membrane; NAD; Oxidoreductase; Phosphoprotein;
KW Reference proteome; Steroid biosynthesis; Steroid metabolism;
KW Sterol biosynthesis; Sterol metabolism; Transmembrane; Transmembrane helix.
FT CHAIN 1..373
FT /note="Sterol-4-alpha-carboxylate 3-dehydrogenase,
FT decarboxylating"
FT /id="PRO_0000087799"
FT TRANSMEM 298..318
FT /note="Helical"
FT /evidence="ECO:0000255"
FT MOTIF 370..373
FT /note="Prevents secretion from ER"
FT /evidence="ECO:0000250|UniProtKB:Q9R1J0"
FT ACT_SITE 172
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q12068"
FT BINDING 176
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q12068"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22223895,
FT ECO:0007744|PubMed:22814378"
FT MOD_RES 22
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VARIANT 105
FT /note="A -> V (in CHILD; dbSNP:rs104894909)"
FT /evidence="ECO:0000269|PubMed:10710235"
FT /id="VAR_010207"
FT VARIANT 182
FT /note="A -> P (in CHILD; dbSNP:rs104894904)"
FT /evidence="ECO:0000269|PubMed:11907515"
FT /id="VAR_065289"
FT VARIANT 205
FT /note="G -> S (in CHILD; dbSNP:rs104894901)"
FT /evidence="ECO:0000269|PubMed:10710235"
FT /id="VAR_010208"
FT VARIANT 232
FT /note="Missing (in CKS; temperature-sensitive hypomorphic
FT mutation; able to correctly fold and complement Erg26
FT mutant yeast at 30 degrees Celsius; Abolishes ability to
FT complement Erg26 mutant yeast at 37 degrees Celsius due to
FT abnormal folding and protein degradation)"
FT /evidence="ECO:0000269|PubMed:21129721"
FT /id="VAR_065290"
FT STRAND 38..43
FT /evidence="ECO:0007829|PDB:6JKG"
FT TURN 44..46
FT /evidence="ECO:0007829|PDB:6JKG"
FT HELIX 48..59
FT /evidence="ECO:0007829|PDB:6JKG"
FT STRAND 63..67
FT /evidence="ECO:0007829|PDB:6JKG"
FT STRAND 78..82
FT /evidence="ECO:0007829|PDB:6JKH"
FT HELIX 88..95
FT /evidence="ECO:0007829|PDB:6JKG"
FT STRAND 99..103
FT /evidence="ECO:0007829|PDB:6JKG"
FT HELIX 109..111
FT /evidence="ECO:0007829|PDB:6JKH"
FT HELIX 114..121
FT /evidence="ECO:0007829|PDB:6JKG"
FT HELIX 123..134
FT /evidence="ECO:0007829|PDB:6JKG"
FT STRAND 139..143
FT /evidence="ECO:0007829|PDB:6JKG"
FT HELIX 146..149
FT /evidence="ECO:0007829|PDB:6JKG"
FT HELIX 171..185
FT /evidence="ECO:0007829|PDB:6JKG"
FT TURN 189..192
FT /evidence="ECO:0007829|PDB:6JKG"
FT STRAND 193..199
FT /evidence="ECO:0007829|PDB:6JKG"
FT STRAND 212..217
FT /evidence="ECO:0007829|PDB:6JKG"
FT STRAND 220..223
FT /evidence="ECO:0007829|PDB:6JKG"
FT STRAND 226..229
FT /evidence="ECO:0007829|PDB:6JKG"
FT TURN 231..234
FT /evidence="ECO:0007829|PDB:6JKG"
FT STRAND 235..237
FT /evidence="ECO:0007829|PDB:6JKG"
FT HELIX 239..256
FT /evidence="ECO:0007829|PDB:6JKG"
FT HELIX 258..260
FT /evidence="ECO:0007829|PDB:6JKG"
FT STRAND 263..267
FT /evidence="ECO:0007829|PDB:6JKG"
SQ SEQUENCE 373 AA; 41900 MW; 30A6E5CE91ED1C77 CRC64;
MEPAVSEPMR DQVARTHLTE DTPKVNADIE KVNQNQAKRC TVIGGSGFLG QHMVEQLLAR
GYAVNVFDIQ QGFDNPQVRF FLGDLCSRQD LYPALKGVNT VFHCASPPPS SNNKELFYRV
NYIGTKNVIE TCKEAGVQKL ILTSSASVIF EGVDIKNGTE DLPYAMKPID YYTETKILQE
RAVLGANDPE KNFLTTAIRP HGIFGPRDPQ LVPILIEAAR NGKMKFVIGN GKNLVDFTFV
ENVVHGHILA AEQLSRDSTL GGKAFHITND EPIPFWTFLS RILTGLNYEA PKYHIPYWVA
YYLALLLSLL VMVISPVIQL QPTFTPMRVA LAGTFHYYSC ERAKKAMGYQ PLVTMDDAME
RTVQSFRHLR RVK
//
