Q15738 (NSDHL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Sterol-4-alpha-carboxylate 3-dehydrogenase, decarboxylating
EC=1.1.1.170

Alternative name(s):
Protein H105e3

Gene names

Name:	NSDHL
Synonyms:	H105E3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	373 AA.
Sequence status	Complete.
Protein existence	Evidence 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.9 Ref.10 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.11
Sequence similarities	Belongs to the 3-beta-HSD family.

Ontologies

Keywords
Biological process	Cholesterol biosynthesis Cholesterol metabolism Lipid biosynthesis Lipid metabolism Steroid biosynthesis Steroid metabolism Sterol biosynthesis Sterol metabolism
Cellular component	Membrane
Disease	Disease mutation Ichthyosis Mental retardation
Domain	Transmembrane Transmembrane helix
Ligand	NAD
Molecular function	Oxidoreductase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cholesterol biosynthetic process Traceable author statement. Source: Reactome hair follicle development Inferred from electronic annotation. Source: Compara labyrinthine layer blood vessel development Inferred from electronic annotation. Source: Compara smoothened signaling pathway Inferred from electronic annotation. Source: Compara
Cellular_component	endoplasmic reticulum membrane Traceable author statement. Source: Reactome integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW lipid particle Inferred from direct assay PubMed 14741744. Source: UniProtKB
Molecular_function	3-beta-hydroxy-delta5-steroid dehydrogenase activity Traceable author statement Ref.9. Source: ProtInc nucleotide binding Inferred from electronic annotation. Source: InterPro sterol-4-alpha-carboxylate 3-dehydrogenase (decarboxylating) activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 373	373	Sterol-4-alpha-carboxylate 3-dehydrogenase, decarboxylating		PRO_0000087799
Regions
	Transmembrane	298 – 318	21	Helical; Potential
Sites
	Active site	172	1	Proton acceptor By similarity
	Binding site	176	1	NAD By similarity
Natural variations
	Natural variant	105	1	A → V in CHILD. Ref.9		VAR_010207
	Natural variant	182	1	A → P in CHILD. Ref.10		VAR_065289
	Natural variant	205	1	G → S in CHILD. Ref.9		VAR_010208
	Natural variant	232	1	Missing 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.11		VAR_065290

Sequences

	Sequence		Length	Mass (Da)
	Q15738 [UniParc]. Last modified May 30, 2000. Version 2. Checksum: 30A6E5CE91ED1C77	FASTA	373	41,900
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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. , 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]	"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.
[10]	"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.
[11]	"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. , 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.
IPI	IPI00019407.
RefSeq	NP_001123237.1. NM_001129765.1. NP_057006.1. NM_015922.2.
UniGene	Hs.57698.
3D structure databases
ProteinModelPortal	Q15738.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q15738. 1 interaction.
STRING	9606.ENSP00000359297.
PTM databases
PhosphoSite	Q15738.
Polymorphism databases
DMDM	8488997.
2D gel databases
REPRODUCTION-2DPAGE	Q15738.
Proteomic databases
PaxDb	Q15738.
PeptideAtlas	Q15738.
PRIDE	Q15738.
Protocols and materials databases
DNASU	50814.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000370274; ENSP00000359297; ENSG00000147383. ENST00000440023; ENSP00000391854; ENSG00000147383. ENST00000597693; ENSP00000468920; ENSG00000269336. ENST00000601774; ENSP00000471515; ENSG00000269336.
GeneID	50814.
KEGG	hsa:50814.
UCSC	uc004fgs.1. human.
Organism-specific databases
CTD	50814.
GeneCards	GC0XP151999.
HGNC	HGNC:13398. NSDHL.
HPA	HPA000248. HPA000571.
MIM	300275. gene. 300831. phenotype. 308050. phenotype.
neXtProt	NX_Q15738.
Orphanet	139. CHILD syndrome. 251383. CK syndrome.
PharmGKB	PA134959020.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0451.
HOGENOM	HOG000167989.
HOVERGEN	HBG054675.
InParanoid	Q15738.
KO	K07748.
OMA	IQLQPTF.
OrthoDB	EOG4NKBVW.
PhylomeDB	Q15738.
Enzyme and pathway databases
BioCyc	MetaCyc:HS07423-MONOMER.
Reactome	REACT_111217. Metabolism.
UniPathway	UPA00770; UER00757.
Gene expression databases
ArrayExpress	Q15738.
Bgee	Q15738.
CleanEx	HS_NSDHL.
Genevestigator	Q15738.
GermOnline	ENSG00000147383. Homo sapiens.
Family and domain databases
Gene3D	3.40.50.720. 1 hit.
InterPro	IPR002225. 3Beta_OHSteriod_DH/Estase. IPR016040. NAD(P)-bd_dom. [Graphical view]
Pfam	PF01073. 3Beta_HSD. 1 hit. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB00157. NADH.
GenomeRNAi	50814.
NextBio	53261.
SOURCE	Search...

Entry information

Entry name

NSDHL_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 122 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.