NSDHL_BOVIN
ID NSDHL_BOVIN Reviewed; 356 AA.
AC Q3ZBE9;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 27-SEP-2005, sequence version 1.
DT 03-AUG-2022, entry version 108.
DE RecName: Full=Sterol-4-alpha-carboxylate 3-dehydrogenase, decarboxylating;
DE EC=1.1.1.170 {ECO:0000250|UniProtKB:Q9R1J0};
GN Name=NSDHL;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Crossbred X Angus; TISSUE=Ileum;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
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. Also plays a role in the regulation of the
CC endocytic trafficking of EGFR. {ECO:0000250|UniProtKB:Q15738}.
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 -!- PATHWAY: Steroid biosynthesis; zymosterol biosynthesis; zymosterol from
CC lanosterol: step 4/6.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q15738}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q9R1J0}; 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 -!- SIMILARITY: Belongs to the 3-beta-HSD family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; BC103389; AAI03390.1; -; mRNA.
DR RefSeq; NP_001030559.1; NM_001035482.2.
DR RefSeq; XP_015316952.1; XM_015461466.1.
DR AlphaFoldDB; Q3ZBE9; -.
DR SMR; Q3ZBE9; -.
DR STRING; 9913.ENSBTAP00000012167; -.
DR PaxDb; Q3ZBE9; -.
DR PeptideAtlas; Q3ZBE9; -.
DR PRIDE; Q3ZBE9; -.
DR Ensembl; ENSBTAT00000012167; ENSBTAP00000012167; ENSBTAG00000009231.
DR GeneID; 616694; -.
DR KEGG; bta:616694; -.
DR CTD; 50814; -.
DR VEuPathDB; HostDB:ENSBTAG00000009231; -.
DR VGNC; VGNC:56932; NSDHL.
DR eggNOG; KOG1430; Eukaryota.
DR GeneTree; ENSGT00940000158229; -.
DR HOGENOM; CLU_007383_6_8_1; -.
DR InParanoid; Q3ZBE9; -.
DR OMA; WGPGDTQ; -.
DR OrthoDB; 930591at2759; -.
DR TreeFam; TF354279; -.
DR Reactome; R-BTA-191273; Cholesterol biosynthesis.
DR UniPathway; UPA00770; UER00757.
DR Proteomes; UP000009136; Chromosome X.
DR Bgee; ENSBTAG00000009231; Expressed in diaphragm and 104 other tissues.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005811; C:lipid droplet; ISS:UniProtKB.
DR GO; GO:0003854; F:3-beta-hydroxy-delta5-steroid dehydrogenase activity; IEA:InterPro.
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; IEA:UniProtKB-EC.
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; IEA:UniProtKB-KW.
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 InterPro; IPR002225; 3Beta_OHSteriod_DH/Estase.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR Pfam; PF01073; 3Beta_HSD; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Cholesterol biosynthesis; Cholesterol metabolism;
KW Endoplasmic reticulum; Lipid biosynthesis; Lipid droplet; Lipid metabolism;
KW Membrane; NAD; Oxidoreductase; Reference proteome; Steroid biosynthesis;
KW Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..356
FT /note="Sterol-4-alpha-carboxylate 3-dehydrogenase,
FT decarboxylating"
FT /id="PRO_0000327830"
FT TRANSMEM 281..301
FT /note="Helical"
FT /evidence="ECO:0000255"
FT MOTIF 353..356
FT /note="Prevents secretion from ER"
FT /evidence="ECO:0000250|UniProtKB:Q9R1J0"
FT ACT_SITE 155
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q12068"
FT BINDING 159
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:0000250|UniProtKB:Q15738"
SQ SEQUENCE 356 AA; 39902 MW; 9C9D1DB6C1250006 CRC64;
MEQAAGEPTR TCLTEDIPKA KRCTVIGGCG FLGQHMVEQL LARGYAVNVF DIRQGFDNPR
VQFFLGDLCS QQDLYPALKG VSTVFHCASP PPFNNNKELF YRVNYIGTKN VIETCKEAGV
QKLILTSSAS VIFEGVDIKN GTEDLPYATK PIDYYTETKI LQERAVLGAH DPEKNFLTTA
IRPHGIFGPR DPQLVPILIE AAKKGKMKFM IGNGKNLVDF TFVENVVHGH ILAAEHLSQD
TALGGKAFHI TNDEPIPFWT FLSRILTGLN YEAPKYHIPY WLAYYLALLV SLLVMVISPV
IQLQPTFTPM RVALAGTFHY YSCEKAKKLM GYRPLVTMDD AVDKTVRSFH HLRKVM
