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Protein

Sterol-4-alpha-carboxylate 3-dehydrogenase, decarboxylating

Gene

NSDHL

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

Functioni

Involved in the sequential removal of two C-4 methyl groups in post-squalene cholesterol biosynthesis.1 Publication

Catalytic activityi

A 3-beta-hydroxysteroid-4-alpha-carboxylate + NAD(P)+ = a 3-oxosteroid + CO2 + NAD(P)H.

Pathwayi: zymosterol biosynthesis

This protein is involved in step 4 of the subpathway that synthesizes zymosterol from lanosterol.
Proteins known to be involved in the 6 steps of the subpathway in this organism are:
  1. Lanosterol 14-alpha demethylase (CYP51A1)
  2. no protein annotated in this organism
  3. Methylsterol monooxygenase 1 (MSMO1)
  4. Sterol-4-alpha-carboxylate 3-dehydrogenase, decarboxylating (NSDHL)
  5. 3-keto-steroid reductase (HSD17B7)
  6. no protein annotated in this organism
This subpathway is part of the pathway zymosterol biosynthesis, which is itself part of Steroid biosynthesis.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes zymosterol from lanosterol, the pathway zymosterol biosynthesis and in Steroid biosynthesis.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei172Proton acceptorBy similarity1
Binding sitei176NADBy similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionOxidoreductase
Biological processCholesterol biosynthesis, Cholesterol metabolism, Lipid biosynthesis, Lipid metabolism, Steroid biosynthesis, Steroid metabolism, Sterol biosynthesis, Sterol metabolism
LigandNAD

Enzyme and pathway databases

BioCyciMetaCyc:HS07423-MONOMER
ReactomeiR-HSA-191273 Cholesterol biosynthesis
UniPathwayiUPA00770; UER00757

Names & Taxonomyi

Protein namesi
Recommended name:
Sterol-4-alpha-carboxylate 3-dehydrogenase, decarboxylating (EC:1.1.1.170)
Alternative name(s):
Protein H105e3
Gene namesi
Name:NSDHL
Synonyms:H105E3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

EuPathDBiHostDB:ENSG00000147383.10
HGNCiHGNC:13398 NSDHL
MIMi300275 gene
neXtProtiNX_Q15738

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei298 – 318HelicalSequence analysisAdd BLAST21

Keywords - Cellular componenti

Endoplasmic reticulum, Lipid droplet, Membrane

Pathology & Biotechi

Involvement in diseasei

Congenital hemidysplasia with ichthyosiform erythroderma and limb defects (CHILD)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn X-linked dominant disorder of lipid metabolism with disturbed cholesterol biosynthesis, which typically results in male lethality. Clinically, it is characterized by congenital, unilateral, ichthyosisform erythroderma with striking lateralization, sharp midline demarcation, and ipsilateral limb defects and hypoplasia of the body. Limbs defects range from hypoplasia of digits or ribs to complete amelia, often including scoliosis.
See also OMIM:308050
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_010207105A → V in CHILD. 1 PublicationCorresponds to variant dbSNP:rs104894909Ensembl.1
Natural variantiVAR_065289182A → P in CHILD. 1 PublicationCorresponds to variant dbSNP:rs104894904Ensembl.1
Natural variantiVAR_010208205G → S in CHILD. 1 PublicationCorresponds to variant dbSNP:rs104894901Ensembl.1
CK syndrome (CKS)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by mild to severe cognitive impairment, seizures, microcephaly, cerebral cortical malformations, dysmorphic facial features, and thin body habitus.
See also OMIM:300831
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_065290232Missing in CKS; temperature-sensitive hypomorphic mutation; able to correctly fold and function at 30 degrees Celsius; impaired function at 37 degrees Celsius due to abnormal folding and protein degradation. 1 Publication1

Keywords - Diseasei

Disease mutation, Ichthyosis, Mental retardation

Organism-specific databases

DisGeNETi50814
GeneReviewsiNSDHL
MalaCardsiNSDHL
MIMi300831 phenotype
308050 phenotype
OpenTargetsiENSG00000147383
Orphaneti139 CHILD syndrome
251383 CK syndrome
PharmGKBiPA134959020

Chemistry databases

DrugBankiDB00157 NADH

Polymorphism and mutation databases

BioMutaiNSDHL
DMDMi8488997

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000877991 – 373Sterol-4-alpha-carboxylate 3-dehydrogenase, decarboxylatingAdd BLAST373

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei22PhosphothreonineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ15738
MaxQBiQ15738
PaxDbiQ15738
PeptideAtlasiQ15738
PRIDEiQ15738

2D gel databases

REPRODUCTION-2DPAGEiQ15738

PTM databases

iPTMnetiQ15738
PhosphoSitePlusiQ15738
SwissPalmiQ15738

Expressioni

Tissue specificityi

Brain, heart, liver, lung, kidney, skin and placenta.

Gene expression databases

BgeeiENSG00000147383
CleanExiHS_NSDHL
ExpressionAtlasiQ15738 baseline and differential
GenevisibleiQ15738 HS

Organism-specific databases

HPAiHPA000248
HPA000571

Interactioni

Protein-protein interaction databases

BioGridi11913123 interactors.
IntActiQ15738 16 interactors.
MINTiQ15738
STRINGi9606.ENSP00000359297

Structurei

3D structure databases

ProteinModelPortaliQ15738
SMRiQ15738
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi359 – 362Prevents secretion from ER4

Sequence similaritiesi

Belongs to the 3-beta-HSD family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1430 Eukaryota
COG0451 LUCA
GeneTreeiENSGT00550000074557
HOGENOMiHOG000167989
HOVERGENiHBG054675
InParanoidiQ15738
KOiK07748
OMAiHYYSCER
OrthoDBiEOG091G0BS8
PhylomeDBiQ15738
TreeFamiTF354279

Family and domain databases

InterProiView protein in InterPro
IPR002225 3Beta_OHSteriod_DH/Estase
IPR036291 NAD(P)-bd_dom_sf
PfamiView protein in Pfam
PF01073 3Beta_HSD, 1 hit
SUPFAMiSSF51735 SSF51735, 2 hits

Sequencei

Sequence statusi: Complete.

Q15738-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEPAVSEPMR DQVARTHLTE DTPKVNADIE KVNQNQAKRC TVIGGSGFLG
60 70 80 90 100
QHMVEQLLAR GYAVNVFDIQ QGFDNPQVRF FLGDLCSRQD LYPALKGVNT
110 120 130 140 150
VFHCASPPPS SNNKELFYRV NYIGTKNVIE TCKEAGVQKL ILTSSASVIF
160 170 180 190 200
EGVDIKNGTE DLPYAMKPID YYTETKILQE RAVLGANDPE KNFLTTAIRP
210 220 230 240 250
HGIFGPRDPQ LVPILIEAAR NGKMKFVIGN GKNLVDFTFV ENVVHGHILA
260 270 280 290 300
AEQLSRDSTL GGKAFHITND EPIPFWTFLS RILTGLNYEA PKYHIPYWVA
310 320 330 340 350
YYLALLLSLL VMVISPVIQL QPTFTPMRVA LAGTFHYYSC ERAKKAMGYQ
360 370
PLVTMDDAME RTVQSFRHLR RVK
Length:373
Mass (Da):41,900
Last modified:May 30, 2000 - v2
Checksum:i30A6E5CE91ED1C77
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_010207105A → V in CHILD. 1 PublicationCorresponds to variant dbSNP:rs104894909Ensembl.1
Natural variantiVAR_065289182A → P in CHILD. 1 PublicationCorresponds to variant dbSNP:rs104894904Ensembl.1
Natural variantiVAR_010208205G → S in CHILD. 1 PublicationCorresponds to variant dbSNP:rs104894901Ensembl.1
Natural variantiVAR_065290232Missing in CKS; temperature-sensitive hypomorphic mutation; able to correctly fold and function at 30 degrees Celsius; impaired function at 37 degrees Celsius due to abnormal folding and protein degradation. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U47105 mRNA Translation: AAC50558.2
U82671 Genomic DNA No translation available.
CH471172 Genomic DNA Translation: EAW72898.1
CH471172 Genomic DNA Translation: EAW72899.1
BC000245 mRNA Translation: AAH00245.1
BC007816 mRNA Translation: AAH07816.1
CCDSiCCDS14717.1
RefSeqiNP_001123237.1, NM_001129765.1
NP_057006.1, NM_015922.2
XP_011529480.1, XM_011531178.2
UniGeneiHs.57698

Genome annotation databases

EnsembliENST00000370274; ENSP00000359297; ENSG00000147383
ENST00000440023; ENSP00000391854; ENSG00000147383
GeneIDi50814
KEGGihsa:50814
UCSCiuc004fgs.2 human

Similar proteinsi

Entry informationi

Entry nameiNSDHL_HUMAN
AccessioniPrimary (citable) accession number: Q15738
Secondary accession number(s): D3DWT6, O00344
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: May 30, 2000
Last modified: March 28, 2018
This is version 163 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome