Reviewed, UniProtKB/Swiss-Prot P14060 (3BHS1_HUMAN)

Names and origin

Protein names

Recommended name:
    3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1
Alternative name(s):
    3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type I
      Short name=3-beta-HSD I
    Trophoblast antigen FDO161G
Including the following 2 domains:
    1- Recommended name:
            3-beta-hydroxy-Delta(5)-steroid dehydrogenase
              EC=1.1.1.145
        Alternative name(s):
            3-beta-hydroxy-5-ene steroid dehydrogenase
            Progesterone reductase
    2- Recommended name:
            Steroid Delta-isomerase
              EC=5.3.3.1
        Alternative name(s):
            Delta-5-3-ketosteroid isomerase

Gene names

Name:	HSD3B1
Synonyms:	3BH, HSDB3A

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	373 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	3-beta-HSD is a bifunctional enzyme, that catalyzes the oxidative conversion of Delta(5)-ene-3-beta-hydroxy steroid, and the oxidative conversion of ketosteroids. The 3-beta-HSD enzymatic system plays a crucial role in the biosynthesis of all classes of hormonal steroids. Efficiently catalyzes the transformation of pregnenolone to progesterone, 17-alpha-hydroxypregnenolone to 17-alpha-hydroxyprogesterone, DHEA to 4-androstenedione, dihydrotestosterone to 5-alpha-androstane-3 beta,17 beta-diol, dehydroepiandrosterone to androstenedione and 5-alpha-androstan-3 beta,17 beta-diol to 5-alpha-dihydrotestosterone. Ref.2 Ref.6
Catalytic activity	A 3-beta-hydroxy-Delta(5)-steroid + NAD+ = a 3-oxo-Delta(5)-steroid + NADH. A 3-oxo-Delta(5)-steroid = a 3-oxo-Delta(4)-steroid.
Pathway	Lipid metabolism; steroid biosynthesis.
Subcellular location	Endoplasmic reticulum membrane; Single-pass membrane protein. Mitochondrion membrane; Single-pass membrane protein.
Tissue specificity	Placenta and skin. Predominantly expressed in mammary gland tissue.
Sequence similarities	Belongs to the 3-beta-HSD family.
Sequence caution	The sequence AAA36001.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	Steroidogenesis
Cellular component	Endoplasmic reticulum Membrane Mitochondrion
Coding sequence diversity	Polymorphism
Domain	Transmembrane
Ligand	NAD
Molecular function	Isomerase Oxidoreductase
Technical term	Complete proteome Direct protein sequencing Multifunctional enzyme
Gene Ontology (GO)
Biological process	androgen biosynthetic process Traceable author statement. Source: UniProtKB estrogen biosynthetic process Traceable author statement. Source: UniProtKB oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell microsome Inferred from direct assay. Source: UniProtKB mitochondrial inner membrane Inferred from direct assay. Source: UniProtKB mitochondrial intermembrane space Inferred from direct assay. Source: UniProtKB smooth endoplasmic reticulum membrane Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	3-beta-hydroxy-delta5-steroid dehydrogenase activity Ref.6 Inferred from sequence or structural similarity. Source: UniProtKB binding Inferred from electronic annotation. Source: InterPro steroid delta-isomerase activity Ref.6 Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Ref.1
	Chain	2 – 373	372	3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1		PRO_0000087774
Regions
	Transmembrane	288 – 308	21	Potential
Sites
	Active site	155	1	Proton acceptor By similarity
	Binding site	159	1	NAD By similarity
Natural variations
	Natural variant	54	1	T → I: dbSNP rs3088283.		VAR_048096
	Natural variant	71	1	R → I: dbSNP rs4986952.		VAR_048097
	Natural variant	79	1	I → V: dbSNP rs6201. Ref.9		VAR_014174
	Natural variant	90	1	G → S: dbSNP rs6684974.		VAR_048098
	Natural variant	286	1	F → L: dbSNP rs6205. Ref.9		VAR_014175
	Natural variant	367	1	T → N: dbSNP rs1047303. Ref.4 Ref.8		VAR_000005

Sequences

	Sequence		Length	Mass (Da)
	P14060-1 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 2C76616E7EA7433A	FASTA	373	42,252
	10 20 30 40 50 60 MTGWSCLVTG AGGFLGQRII RLLVKEKELK EIRVLDKAFG PELREEFSKL QNKTKLTVLE 70 80 90 100 110 120 GDILDEPFLK RACQDVSVII HTACIIDVFG VTHRESIMNV NVKGTQLLLE ACVQASVPVF 130 140 150 160 170 180 IYTSSIEVAG PNSYKEIIQN GHEEEPLENT WPAPYPHSKK LAEKAVLAAN GWNLKNGGTL 190 200 210 220 230 240 YTCALRPMYI YGEGSRFLSA SINEALNNNG ILSSVGKFST VNPVYVGNVA WAHILALRAL 250 260 270 280 290 300 QDPKKAPSIR GQFYYISDDT PHQSYDNLNY TLSKEFGLRL DSRWSFPLSL MYWIGFLLEI 310 320 330 340 350 360 VSFLLRPIYT YRPPFNRHIV TLSNSVFTFS YKKAQRDLAY KPLYSWEEAK QKTVEWVGSL 370 VDRHKETLKS KTQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Full length cDNA structure and deduced amino acid sequence of human 3 beta-hydroxy-5-ene steroid dehydrogenase." Luu-The V., Lachance Y., Labrie F., Leblanc G., Thomas J.L., Strickler R.C., Labrie C. Mol. Endocrinol. 3:1310-1312(1989) [PubMed: 2779585] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 2-30.
[2]	"Human 3 beta-hydroxysteroid dehydrogenase/delta 5-->4-isomerase from placenta: expression in nonsteroidogenic cells of a protein that catalyzes the dehydrogenation/isomerization of C21 and C19 steroids." Lorence M.C., Murry B.A., Trant J.M., Mason J.I. Endocrinology 126:2493-2498(1990) [PubMed: 2139411] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION. Tissue: Placenta.
[3]	"Structural analysis of the gene encoding human 3 beta-hydroxysteroid dehydrogenase/delta 5-->4-isomerase." Lorence M.C., Corbin C.J., Kamimura N., Mahendroo M.S., Mason J.I. Mol. Endocrinol. 4:1850-1855(1990) [PubMed: 2082186] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Characterization of human 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase gene and its expression in mammalian cells." Lachance Y., Luu-The V., Labrie C., Simard J., Dumont M., Launoit Y.D., Guerin S., Leblanc G., Labrie F. J. Biol. Chem. 265:20469-20475(1990) [PubMed: 2243100] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ASN-367.
[5]	"Molecular cloning and expression of human trophoblast antigen FDO161G and its identification as 3 beta-hydroxy-5-ene steroid dehydrogenase." Nickson D.A., McBride M.W., Zeinali S., Hawes C.S., Petropoulos A., Mueller U.W., Sutcliffe R.G. J. Reprod. Fertil. 93:149-156(1991) [PubMed: 1920284] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Placenta.
[6]	"Characterization, expression, and immunohistochemical localization of 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase in human skin." Dumont M., Van L.T., Dupont E., Pelletier G., Labrie F. J. Invest. Dermatol. 99:415-421(1992) [PubMed: 1401999] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION.
[7]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Placenta.
[8]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ASN-367. Tissue: Skin.
[9]	"Characterization of single-nucleotide polymorphisms in coding regions of human genes." Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S. Nat. Genet. 22:231-238(1999) [PubMed: 10391209] [Abstract] Cited for: VARIANTS VAL-79 AND LEU-286.
[10]	Erratum Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S. Nat. Genet. 23:373-373(1999)
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M27137 mRNA. Translation: AAA36015.1. X53321 mRNA. Translation: CAA37408.1. M35493 mRNA. Translation: AAA51538.1. M63397, M63395, M63396 Genomic DNA. Translation: AAA51662.1. M28392, M28162, M28391 Genomic DNA. Translation: AAA36001.1. Sequence problems. M38180 Genomic DNA. Translation: AAA51831.1. X55997 mRNA. Translation: CAA39469.1. S45679 mRNA. Translation: AAB23543.1. AK291556 mRNA. Translation: BAF84245.1. BC031999 mRNA. Translation: AAH31999.1.
IPI	IPI00843838.
PIR	DEHUHS. A36551.
RefSeq	NP_000853.1.
UniGene	Hs.364941
3D structure databases
SMR	P14060. Positions 5-364.
ModBase	Search...
Protein-protein interaction databases
STRING	P14060.
Proteomic databases
PRIDE	P14060.
Genome annotation databases
Ensembl	ENST00000235547; ENSP00000235547; ENSG00000203857; Homo sapiens. [Genome view] ENST00000369413; ENSP00000358421; ENSG00000203857; Homo sapiens. [Genome view]
GeneID	3283.
KEGG	hsa:3283.
UCSC	uc001ehv.1. human.
Organism-specific databases
CTD	3283.
GeneCards	GC01P119852.
H-InvDB	HIX0000948. HIX0057008.
HGNC	HGNC:5217. HSD3B1.
MIM	109715. gene.
PharmGKB	PA29486.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG18589.
HOVERGEN	P14060.
InParanoid	P14060.
PhylomeDB	P14060.
Enzyme and pathway databases
BRENDA	1.1.1.145. 247. 5.3.3.1. 247.
Reactome	REACT_15314. Hormone biosynthesis. REACT_602. Metabolism of lipids and lipoproteins.
Gene expression databases
ArrayExpress	P14060.
Bgee	P14060.
CleanEx	HS_HSD3B1.
Genevestigator	P14060.
GermOnline	ENSG00000203857. Homo sapiens.
Family and domain databases
InterPro	IPR016040. NAD(P)-bd_dom. [Graphical view]
Gene3D	G3DSA:3.40.50.720. NAD(P)-bd. 1 hit.
ProtoNet	Search...
Other Resources
DrugBank	DB00157. NADH. DB01108. Trilostane.
NextBio	13031.
SOURCE	Search...

Entry information

Entry name

3BHS1_HUMAN

Accession

Primary (citable) accession number: P14060
Secondary accession number(s): A8K691, Q14545, Q8IV65

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1990
Last sequence update:	January 23, 2007
Last modified:	February 9, 2010
This is version 110 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.