NSDHL_RAT
ID NSDHL_RAT Reviewed; 362 AA.
AC Q5PPL3;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 04-JAN-2005, sequence version 1.
DT 03-AUG-2022, entry version 116.
DE RecName: Full=Sterol-4-alpha-carboxylate 3-dehydrogenase, decarboxylating;
DE EC=1.1.1.170 {ECO:0000250|UniProtKB:Q9R1J0};
GN Name=Nsdhl;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
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).
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}.
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DR EMBL; BC087626; AAH87626.1; -; mRNA.
DR RefSeq; NP_001009399.1; NM_001009399.1.
DR AlphaFoldDB; Q5PPL3; -.
DR SMR; Q5PPL3; -.
DR IntAct; Q5PPL3; 2.
DR STRING; 10116.ENSRNOP00000022985; -.
DR jPOST; Q5PPL3; -.
DR PaxDb; Q5PPL3; -.
DR PRIDE; Q5PPL3; -.
DR Ensembl; ENSRNOT00000091154; ENSRNOP00000069662; ENSRNOG00000057814.
DR GeneID; 309262; -.
DR KEGG; rno:309262; -.
DR CTD; 50814; -.
DR RGD; 1359337; Nsdhl.
DR eggNOG; KOG1430; Eukaryota.
DR GeneTree; ENSGT00940000158229; -.
DR HOGENOM; CLU_007383_6_8_1; -.
DR InParanoid; Q5PPL3; -.
DR OMA; WGPGDTQ; -.
DR OrthoDB; 930591at2759; -.
DR PhylomeDB; Q5PPL3; -.
DR TreeFam; TF354279; -.
DR Reactome; R-RNO-191273; Cholesterol biosynthesis.
DR SABIO-RK; Q5PPL3; -.
DR UniPathway; UPA00770; UER00757.
DR PRO; PR:Q5PPL3; -.
DR Proteomes; UP000002494; Chromosome X.
DR Bgee; ENSRNOG00000057814; Expressed in liver and 20 other tissues.
DR Genevisible; Q5PPL3; RN.
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; ISO:RGD.
DR GO; GO:0001942; P:hair follicle development; ISO:RGD.
DR GO; GO:0060716; P:labyrinthine layer blood vessel development; ISO:RGD.
DR GO; GO:0007224; P:smoothened signaling pathway; ISO:RGD.
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..362
FT /note="Sterol-4-alpha-carboxylate 3-dehydrogenase,
FT decarboxylating"
FT /id="PRO_0000327831"
FT TRANSMEM 289..309
FT /note="Helical"
FT /evidence="ECO:0000255"
FT MOTIF 359..362
FT /note="Prevents secretion from ER"
FT /evidence="ECO:0000250|UniProtKB:Q9R1J0"
FT ACT_SITE 161
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q12068"
FT BINDING 165
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 362 AA; 40412 MW; 35B224A8CA20C114 CRC64;
MEQAVRSESK KGQVTGTDLI NEVSKAKKCT VIGGSGFLGQ HMVEQLLSRG YAVNVFDVRQ
GFDNPRVQFF IGDLCNQQDL YPALKGVSTV FHCASPPSNS NNKELFYRVN STGTKTVIET
CKEAGVQKLI LTSSASVVFE GVDIKNGTED LPYAMKPIDY YTETKILQER AVLDANDPKK
NFLTAAIRPH GIFGPRDPQL VPVLIDAARK GKMKFMIGNG KNLVDFTFVE NVVHGHILAA
EHLSRDAGLG GKAFHITNDE PIPFWTFLSR ILTGLNYEAP KYHIPYRVAY YLAFLLSLLV
MVLSPLIQIQ TTFTPFRVAL AGTFHYYSCE KAKKLIGYRP LVTMDDAVER TVQSFHHLRK
DK