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Protein

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

Gene

NSDHL

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

Cholesterol biosynthesis, Cholesterol metabolism, Lipid biosynthesis, Lipid metabolism, Steroid biosynthesis, Steroid metabolism, Sterol biosynthesis, Sterol metabolism

Keywords - Ligandi

NAD

Enzyme and pathway databases

BioCyciMetaCyc:HS07423-MONOMER.
ZFISH: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

HGNCiHGNC:13398. NSDHL.

Subcellular locationi

  • Endoplasmic reticulum membrane 1 Publication; Single-pass membrane protein 1 Publication
  • Lipid droplet 1 Publication

  • Note: Trafficking through the Golgi is necessary for ER membrane localization.

Topology

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

GO - Cellular componenti

Complete GO annotation...

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 rs104894909dbSNPEnsembl.1
Natural variantiVAR_065289182A → P in CHILD. 1 PublicationCorresponds to variant rs104894904dbSNPEnsembl.1
Natural variantiVAR_010208205G → S in CHILD. 1 PublicationCorresponds to variant rs104894901dbSNPEnsembl.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.
MalaCardsiNSDHL.
MIMi300831. phenotype.
308050. phenotype.
OpenTargetsiENSG00000147383.
Orphaneti139. CHILD syndrome.
251383. CK syndrome.
PharmGKBiPA134959020.

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-2DPAGEQ15738.

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

BioGridi119131. 20 interactors.
IntActiQ15738. 12 interactors.
MINTiMINT-5001307.
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.
OMAiEPMRDQV.
OrthoDBiEOG091G0BS8.
PhylomeDBiQ15738.
TreeFamiTF354279.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
InterProiIPR002225. 3Beta_OHSteriod_DH/Estase.
IPR016040. NAD(P)-bd_dom.
[Graphical view]
PfamiPF01073. 3Beta_HSD. 1 hit.
[Graphical view]
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 rs104894909dbSNPEnsembl.1
Natural variantiVAR_065289182A → P in CHILD. 1 PublicationCorresponds to variant rs104894904dbSNPEnsembl.1
Natural variantiVAR_010208205G → S in CHILD. 1 PublicationCorresponds to variant rs104894901dbSNPEnsembl.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.

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliQ15738.
SMRiQ15738.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119131. 20 interactors.
IntActiQ15738. 12 interactors.
MINTiMINT-5001307.
STRINGi9606.ENSP00000359297.

PTM databases

iPTMnetiQ15738.
PhosphoSitePlusiQ15738.
SwissPalmiQ15738.

Polymorphism and mutation databases

BioMutaiNSDHL.
DMDMi8488997.

2D gel databases

REPRODUCTION-2DPAGEQ15738.

Proteomic databases

EPDiQ15738.
MaxQBiQ15738.
PaxDbiQ15738.
PeptideAtlasiQ15738.
PRIDEiQ15738.

Protocols and materials databases

DNASUi50814.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi50814.
DisGeNETi50814.
GeneCardsiNSDHL.
GeneReviewsiNSDHL.
HGNCiHGNC:13398. NSDHL.
HPAiHPA000248.
HPA000571.
MalaCardsiNSDHL.
MIMi300275. gene.
300831. phenotype.
308050. phenotype.
neXtProtiNX_Q15738.
OpenTargetsiENSG00000147383.
Orphaneti139. CHILD syndrome.
251383. CK syndrome.
PharmGKBiPA134959020.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

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

Miscellaneous databases

GeneWikiiNSDHL.
GenomeRNAii50814.
PROiQ15738.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000147383.
CleanExiHS_NSDHL.
ExpressionAtlasiQ15738. baseline and differential.
GenevisibleiQ15738. HS.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
InterProiIPR002225. 3Beta_OHSteriod_DH/Estase.
IPR016040. NAD(P)-bd_dom.
[Graphical view]
PfamiPF01073. 3Beta_HSD. 1 hit.
[Graphical view]
SUPFAMiSSF51735. SSF51735. 2 hits.
ProtoNetiSearch...

Entry informationi

Entry nameiNSDHL_HUMAN
AccessioniPrimary (citable) accession number: Q15738
Secondary accession number(s): D3DWT6, O00344
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: May 30, 2000
Last modified: November 2, 2016
This is version 154 of the entry and version 2 of the sequence. [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

Documents

  1. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.