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Q15738 (NSDHL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 131. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Sterol-4-alpha-carboxylate 3-dehydrogenase, decarboxylating

EC=1.1.1.170
Alternative name(s):
Protein H105e3
Gene names
Name:NSDHL
Synonyms:H105E3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length373 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Catalytic activity

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

Pathway

Steroid biosynthesis; zymosterol biosynthesis; zymosterol from lanosterol: step 4/6.

Subcellular location

Membrane; Single-pass membrane protein Potential.

Tissue specificity

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

Involvement in disease

Congenital hemidysplasia with ichthyosiform erythroderma and limb defects (CHILD) [MIM:308050]: An 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11 Ref.12

CK syndrome (CKS) [MIM:300831]: A disorder characterized by mild to severe cognitive impairment, seizures, microcephaly, cerebral cortical malformations, dysmorphic facial features, and thin body habitus.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.13

Sequence similarities

Belongs to the 3-beta-HSD family.

Ontologies

Keywords
   Biological processCholesterol biosynthesis
Cholesterol metabolism
Lipid biosynthesis
Lipid metabolism
Steroid biosynthesis
Steroid metabolism
Sterol biosynthesis
Sterol metabolism
   Cellular componentMembrane
   DiseaseDisease mutation
Ichthyosis
Mental retardation
   DomainTransmembrane
Transmembrane helix
   LigandNAD
   Molecular functionOxidoreductase
   PTMAcetylation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcholesterol biosynthetic process

Traceable author statement. Source: Reactome

hair follicle development

Inferred from electronic annotation. Source: Ensembl

labyrinthine layer blood vessel development

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

smoothened signaling pathway

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentendoplasmic reticulum

Inferred from direct assay. Source: LIFEdb

endoplasmic reticulum membrane

Traceable author statement. Source: Reactome

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

intracellular membrane-bounded organelle

Inferred from direct assay. Source: HPA

lipid particle

Inferred from direct assay PubMed 14741744PubMed 21498505. Source: UniProtKB

   Molecular_function3-beta-hydroxy-delta5-steroid dehydrogenase activity

Traceable author statement Ref.11. Source: ProtInc

sterol-4-alpha-carboxylate 3-dehydrogenase (decarboxylating) activity

Inferred from electronic annotation. Source: UniProtKB-EC

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 373373Sterol-4-alpha-carboxylate 3-dehydrogenase, decarboxylating
PRO_0000087799

Regions

Transmembrane298 – 31821Helical; Potential

Sites

Active site1721Proton acceptor By similarity
Binding site1761NAD By similarity

Amino acid modifications

Modified residue11N-acetylmethionine Ref.9 Ref.10

Natural variations

Natural variant1051A → V in CHILD. Ref.11
VAR_010207
Natural variant1821A → P in CHILD. Ref.12
VAR_065289
Natural variant2051G → S in CHILD. Ref.11
VAR_010208
Natural variant2321Missing 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. Ref.13
VAR_065290

Sequences

Sequence LengthMass (Da)Tools
Q15738 [UniParc].

Last modified May 30, 2000. Version 2.
Checksum: 30A6E5CE91ED1C77

FASTA37341,900
        10         20         30         40         50         60 
MEPAVSEPMR DQVARTHLTE DTPKVNADIE KVNQNQAKRC TVIGGSGFLG QHMVEQLLAR 

        70         80         90        100        110        120 
GYAVNVFDIQ QGFDNPQVRF FLGDLCSRQD LYPALKGVNT VFHCASPPPS SNNKELFYRV 

       130        140        150        160        170        180 
NYIGTKNVIE TCKEAGVQKL ILTSSASVIF EGVDIKNGTE DLPYAMKPID YYTETKILQE 

       190        200        210        220        230        240 
RAVLGANDPE KNFLTTAIRP HGIFGPRDPQ LVPILIEAAR NGKMKFVIGN GKNLVDFTFV 

       250        260        270        280        290        300 
ENVVHGHILA AEQLSRDSTL GGKAFHITND EPIPFWTFLS RILTGLNYEA PKYHIPYWVA 

       310        320        330        340        350        360 
YYLALLLSLL VMVISPVIQL QPTFTPMRVA LAGTFHYYSC ERAKKAMGYQ PLVTMDDAME 

       370 
RTVQSFRHLR RVK 

« Hide

References

« Hide 'large scale' references
[1]Levin M.L., Herman G.E.
Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Heart.
[2]"Comparative genome sequence analysis of the Bpa/Str region in mouse and man."
Mallon A.-M., Platzer M., Bate R., Gloeckner G., Botcherby M.R.M., Nordsiek G., Strivens M.A., Kioschis P., Dangel A., Cunningham D., Straw R.N.A., Weston P., Gilbert M., Fernando S., Goodall K., Hunter G., Greystrong J.S., Clarke D. expand/collapse author list , Kimberley C., Goerdes M., Blechschmidt K., Rump A., Hinzmann B., Mundy C.R., Miller W., Poustka A., Herman G.E., Rhodes M., Denny P., Rosenthal A., Brown S.D.M.
Genome Res. 10:758-775(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"The DNA sequence and comparative analysis of human chromosome 10."
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. expand/collapse author list , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The DNA sequence of the human X chromosome."
Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. expand/collapse author list , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R.
Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Eye.
[7]"A comparative transcription map of the murine bare patches (Bpa) and striated (Str) critical regions and human Xq28."
Levin M.L., Chatterjee A., Pragliola A., Worley K.C., Wehnert M., Zhuchenko O., Smith R.F., Lee C.C., Herman G.E.
Genome Res. 6:465-477(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: PRELIMINARY NUCLEOTIDE SEQUENCE [MRNA] OF 224-373.
Tissue: Heart.
[8]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]"Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"Mutations in the NSDHL gene, encoding a 3beta-hydroxysteroid dehydrogenase, cause CHILD syndrome."
Konig A., Happle R., Bornholdt D., Engel H., Grzeschik K.H.
Am. J. Med. Genet. 90:339-346(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CHILD VAL-105 AND SER-205.
[12]"A novel missense mutation of NSDHL in an unusual case of CHILD syndrome showing bilateral, almost symmetric involvement."
Konig A., Happle R., Fink-Puches R., Soyer H.P., Bornholdt D., Engel H., Grzeschik K.H.
J. Am. Acad. Dermatol. 46:594-596(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CHILD PRO-182.
[13]"Hypomorphic temperature-sensitive alleles of NSDHL cause CK syndrome."
McLarren K.W., Severson T.M., du Souich C., Stockton D.W., Kratz L.E., Cunningham D., Hendson G., Morin R.D., Wu D., Paul J.E., An J., Nelson T.N., Chou A., DeBarber A.E., Merkens L.S., Michaud J.L., Waters P.J., Yin J. expand/collapse author list , McGillivray B., Demos M., Rouleau G.A., Grzeschik K.H., Smith R., Tarpey P.S., Shears D., Schwartz C.E., Gecz J., Stratton M.R., Arbour L., Hurlburt J., Van Allen M.I., Herman G.E., Zhao Y., Moore R., Kelley R.I., Jones S.J., Steiner R.D., Raymond F.L., Marra M.A., Boerkoel C.F.
Am. J. Hum. Genet. 87:905-914(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CKS LYS-232 DEL, CHARACTERIZATION OF VARIANT CKS LYS-232 DEL.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_001123237.1. NM_001129765.1.
NP_057006.1. NM_015922.2.
UniGeneHs.57698.

3D structure databases

ProteinModelPortalQ15738.
SMRQ15738. Positions 39-366.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid119131. 1 interaction.
IntActQ15738. 1 interaction.
MINTMINT-5001307.
STRING9606.ENSP00000359297.

Chemistry

DrugBankDB00157. NADH.

PTM databases

PhosphoSiteQ15738.

Polymorphism databases

DMDM8488997.

2D gel databases

REPRODUCTION-2DPAGEQ15738.

Proteomic databases

PaxDbQ15738.
PeptideAtlasQ15738.
PRIDEQ15738.

Protocols and materials databases

DNASU50814.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000370274; ENSP00000359297; ENSG00000147383.
ENST00000440023; ENSP00000391854; ENSG00000147383.
ENST00000597693; ENSP00000468920; ENSG00000269336.
ENST00000601774; ENSP00000471515; ENSG00000269336.
GeneID50814.
KEGGhsa:50814.
UCSCuc004fgs.1. human.

Organism-specific databases

CTD50814.
GeneCardsGC0XP151999.
HGNCHGNC:13398. NSDHL.
HPAHPA000248.
HPA000571.
MIM300275. gene.
300831. phenotype.
308050. phenotype.
neXtProtNX_Q15738.
Orphanet139. CHILD syndrome.
251383. CK syndrome.
PharmGKBPA134959020.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0451.
HOGENOMHOG000167989.
HOVERGENHBG054675.
InParanoidQ15738.
KOK07748.
OMAEPMRDQV.
PhylomeDBQ15738.
TreeFamTF354279.

Enzyme and pathway databases

BioCycMetaCyc:HS07423-MONOMER.
ReactomeREACT_111217. Metabolism.
UniPathwayUPA00770; UER00757.

Gene expression databases

ArrayExpressQ15738.
BgeeQ15738.
CleanExHS_NSDHL.
GenevestigatorQ15738.

Family and domain databases

Gene3D3.40.50.720. 1 hit.
InterProIPR002225. 3Beta_OHSteriod_DH/Estase.
IPR016040. NAD(P)-bd_dom.
[Graphical view]
PfamPF01073. 3Beta_HSD. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiNSDHL.
GenomeRNAi50814.
NextBio53261.
PROQ15738.
SOURCESearch...

Entry information

Entry nameNSDHL_HUMAN
AccessionPrimary (citable) accession number: Q15738
Secondary accession number(s): D3DWT6, O00344
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: May 30, 2000
Last modified: April 16, 2014
This is version 131 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome X

Human chromosome X: entries, gene names and cross-references to MIM