Q9H8P0 (PORED_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Polyprenol reductase
EC=1.3.1.94

Alternative name(s):
3-oxo-5-alpha-steroid 4-dehydrogenase 3
EC=1.3.1.22
Steroid 5-alpha-reductase 2-like
Steroid 5-alpha-reductase 3
Short name=S5AR 3
Short name=SR type 3

Gene names

Name:	SRD5A3
Synonyms:	SRD5A2L

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	318 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Plays a key role in early steps of protein N-linked glycosylation by being required for the conversion of polyprenol into dolichol. Dolichols are required for the synthesis of dolichol-linked monosaccharides and the oligosaccharide precursor used for N-glycosylation. Acts as a polyprenol reductase that promotes the reduction of the alpha-isoprene unit of polyprenols into dolichols in a NADP-dependent mechanism. Also able to convert testosterone (T) into 5-alpha-dihydrotestosterone (DHT). Ref.6 Ref.7
Catalytic activity	Ditrans,polycis-dolichol + NADP+ = ditrans,polycis-polyprenol + NADPH. Ref.6 Ref.7 A 3-oxo-5-alpha-steroid + NADP+ = a 3-oxo-Delta(4)-steroid + NADPH. Ref.6 Ref.7
Pathway	Protein modification; protein glycosylation. Ref.7
Subcellular location	Endoplasmic reticulum membrane; Multi-pass membrane protein Probable Ref.7.
Tissue specificity	Overexpressed in hormone-refractory prostate cancers (HRPC). Almost no or little expression in normal adult organs. Ref.6
Involvement in disease	Congenital disorder of glycosylation 1Q (CDG1Q) [MIM:612379]: A multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7 Ref.9 Kahrizi syndrome (KHRZ) [MIM:612713]: An autosomal recessive neurodevelopmental disorder characterized by mental retardation, cataracts, coloboma, kyphosis, and coarse facial features. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8
Sequence similarities	Belongs to the steroid 5-alpha reductase family. Polyprenol reductase subfamily.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Membrane
Disease	Cataract Congenital disorder of glycosylation Mental retardation
Domain	Transmembrane Transmembrane helix
Ligand	NADP
Molecular function	Oxidoreductase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	androgen biosynthetic process Traceable author statement. Source: Reactome dolichol metabolic process Inferred from direct assay Ref.7. Source: UniProtKB dolichol-linked oligosaccharide biosynthetic process Inferred from mutant phenotype Ref.7. Source: UniProtKB polyprenol catabolic process Inferred from direct assay Ref.7. Source: UniProtKB protein glycosylation Inferred from electronic annotation. Source: UniProtKB-UniPathway
Cellular_component	endoplasmic reticulum membrane Traceable author statement. Source: Reactome integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	3-oxo-5-alpha-steroid 4-dehydrogenase activity Inferred from direct assay Ref.6. Source: UniProtKB cholestenone 5-alpha-reductase activity Inferred from electronic annotation. Source: EC oxidoreductase activity, acting on the CH-CH group of donors, NAD or NADP as acceptor Inferred from direct assay Ref.7. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 318	318	Polyprenol reductase		PRO_0000317703
Regions
	Topological domain	1 – 11	11	Cytoplasmic Potential
	Transmembrane	12 – 34	23	Helical; Potential
	Topological domain	35 – 80	46	Lumenal Potential
	Transmembrane	81 – 101	21	Helical; Potential
	Topological domain	102 – 117	16	Cytoplasmic Potential
	Transmembrane	118 – 138	21	Helical; Potential
	Topological domain	139 – 157	19	Lumenal Potential
	Transmembrane	158 – 178	21	Helical; Potential
	Topological domain	179 – 194	16	Cytoplasmic Potential
	Transmembrane	195 – 215	21	Helical; Potential
	Topological domain	216 – 260	45	Lumenal Potential
	Transmembrane	261 – 281	21	Helical; Potential
	Topological domain	282 – 318	37	Cytoplasmic Potential
Experimental info
	Mutagenesis	296	1	H → A: Loss of function. Ref.6 Ref.7

Sequences

	Sequence		Length	Mass (Da)
	Q9H8P0 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: 404C7ECBB4A29E6B	FASTA	318	36,521
	10 20 30 40 50 60 MAPWAEAEHS ALNPLRAVWL TLTAAFLLTL LLQLLPPGLL PGCAIFQDLI RYGKTKCGEP 70 80 90 100 110 120 SRPAACRAFD VPKRYFSHFY IISVLWNGFL LWCLTQSLFL GAPFPSWLHG LLRILGAAQF 130 140 150 160 170 180 QGGELALSAF LVLVFLWLHS LRRLFECLYV SVFSNVMIHV VQYCFGLVYY VLVGLTVLSQ 190 200 210 220 230 240 VPMDGRNAYI TGKNLLMQAR WFHILGMMMF IWSSAHQYKC HVILGNLRKN KAGVVIHCNH 250 260 270 280 290 300 RIPFGDWFEY VSSPNYLAEL MIYVSMAVTF GFHNLTWWLV VTNVFFNQAL SAFLSHQFYK 310 SKFVSYPKHR KAFLPFLF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Ovary.
[2]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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.
[6]	"Novel 5 alpha-steroid reductase (SRD5A3, type-3) is overexpressed in hormone-refractory prostate cancer." Uemura M., Tamura K., Chung S., Honma S., Okuyama A., Nakamura Y., Nakagawa H. Cancer Sci. 99:81-86(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, MUTAGENESIS OF HIS-296.
[7]	"SRD5A3 is required for converting polyprenol to dolichol and is mutated in a congenital glycosylation disorder." Cantagrel V., Lefeber D.J., Ng B.G., Guan Z., Silhavy J.L., Bielas S.L., Lehle L., Hombauer H., Adamowicz M., Swiezewska E., De Brouwer A.P., Blumel P., Sykut-Cegielska J., Houliston S., Swistun D., Ali B.R., Dobyns W.B., Babovic-Vuksanovic D. , van Bokhoven H., Wevers R.A., Raetz C.R., Freeze H.H., Morava E., Al-Gazali L., Gleeson J.G. Cell 142:203-217(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, PATHWAY, SUBCELLULAR LOCATION, INVOLVEMENT IN CDG1Q, MUTAGENESIS OF HIS-296.
[8]	"Next generation sequencing in a family with autosomal recessive Kahrizi syndrome (OMIM 612713) reveals a homozygous frameshift mutation in SRD5A3." Kahrizi K., Hu C.H., Garshasbi M., Abedini S.S., Ghadami S., Kariminejad R., Ullmann R., Chen W., Ropers H.H., Kuss A.W., Najmabadi H., Tzschach A. Eur. J. Hum. Genet. 19:115-117(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN KHRZ.
[9]	"SRD5A3-CDG: A patient with a novel mutation." Kasapkara C.S., Tumer L., Ezgu F.S., Hasanoglu A., Race V., Matthijs G., Jaeken J. Eur. J. Paediatr. Neurol. 16:554-556(2012) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN CDG1Q.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK023414 mRNA. Translation: BAB14568.1. CR457312 mRNA. Translation: CAG33593.1. AC064824 Genomic DNA. Translation: AAY40904.1. CH471057 Genomic DNA. Translation: EAX05465.1. BC002480 mRNA. Translation: AAH02480.1.
IPI	IPI00002344.
RefSeq	NP_078868.1. NM_024592.4.
UniGene	Hs.39311.
3D structure databases
ProteinModelPortal	Q9H8P0.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9H8P0. 2 interactions.
STRING	9606.ENSP00000264228.
PTM databases
PhosphoSite	Q9H8P0.
Polymorphism databases
DMDM	74733864.
Proteomic databases
PaxDb	Q9H8P0.
PeptideAtlas	Q4W5Q6.
PRIDE	Q9H8P0.
Protocols and materials databases
DNASU	79644.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000264228; ENSP00000264228; ENSG00000128039.
GeneID	79644.
KEGG	hsa:79644.
UCSC	uc003hau.3. human.
Organism-specific databases
CTD	79644.
GeneCards	GC04P056212.
HGNC	HGNC:25812. SRD5A3.
HPA	HPA027006.
MIM	611715. gene. 612379. phenotype. 612713. phenotype.
neXtProt	NX_Q9H8P0.
Orphanet	139477. Al-Gazali-Dattani syndrome. 168972. Intellectual deficit, Kahrizi type.
PharmGKB	PA162404779.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG330066.
HOVERGEN	HBG057797.
InParanoid	Q9H8P0.
KO	K12345.
OMA	SSPHMFF.
OrthoDB	EOG47D9H9.
PhylomeDB	Q9H8P0.
Enzyme and pathway databases
BioCyc	MetaCyc:HS13249-MONOMER.
Reactome	REACT_111217. Metabolism. REACT_15493. Steroid hormones.
UniPathway	UPA00378.
Gene expression databases
ArrayExpress	Q9H8P0.
Bgee	Q9H8P0.
CleanEx	HS_SRD5A3.
Genevestigator	Q9H8P0.
Family and domain databases
InterPro	IPR001104. 3-oxo-5_a-steroid_4-DH_C. [Graphical view]
Pfam	PF02544. Steroid_dh. 1 hit. [Graphical view]
PROSITE	PS50244. S5A_REDUCTASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	79644.
NextBio	68779.
SOURCE	Search...

Entry information

Entry name

PORED_HUMAN

Accession

Primary (citable) accession number: Q9H8P0
Secondary accession number(s): Q4W5Q6

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 5, 2008
Last sequence update:	March 1, 2001
Last modified:	May 1, 2013
This is version 99 of the entry and version 1 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.