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Q9H8P0 (PORED_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 108. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | 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:
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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length318 AA.
Sequence statusComplete.
Protein existenceEvidence 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 componentEndoplasmic reticulum
Membrane
   DiseaseCataract
Congenital disorder of glycosylation
Mental retardation
   DomainTransmembrane
Transmembrane helix
   LigandNADP
   Molecular functionOxidoreductase
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processandrogen biosynthetic process

Traceable author statement. Source: Reactome

cellular protein metabolic 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

dolichyl diphosphate biosynthetic process

Traceable author statement. Source: Reactome

polyprenol catabolic process

Inferred from direct assay Ref.7. Source: UniProtKB

post-translational protein modification

Traceable author statement. Source: Reactome

protein N-linked glycosylation via asparagine

Traceable author statement. Source: Reactome

small molecule metabolic process

Traceable author statement. Source: Reactome

steroid metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentendoplasmic reticulum

Inferred from direct assay Ref.7. Source: UniProtKB

endoplasmic reticulum membrane

Traceable author statement. Source: Reactome

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular_function3-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: UniProtKB-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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 318318Polyprenol reductase
PRO_0000317703

Regions

Topological domain1 – 1111Cytoplasmic Potential
Transmembrane12 – 3423Helical; Potential
Topological domain35 – 8046Lumenal Potential
Transmembrane81 – 10121Helical; Potential
Topological domain102 – 11716Cytoplasmic Potential
Transmembrane118 – 13821Helical; Potential
Topological domain139 – 15719Lumenal Potential
Transmembrane158 – 17821Helical; Potential
Topological domain179 – 19416Cytoplasmic Potential
Transmembrane195 – 21521Helical; Potential
Topological domain216 – 26045Lumenal Potential
Transmembrane261 – 28121Helical; Potential
Topological domain282 – 31837Cytoplasmic Potential

Experimental info

Mutagenesis2961H → A: Loss of function. Ref.6 Ref.7

Sequences

Sequence LengthMass (Da)Tools
Q9H8P0 [UniParc].

Last modified March 1, 2001. Version 1.
Checksum: 404C7ECBB4A29E6B

FASTA31836,521
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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. 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 (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. expand/collapse author list , 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.
RefSeqNP_078868.1. NM_024592.4.
UniGeneHs.39311.

3D structure databases

ProteinModelPortalQ9H8P0.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid122772. 3 interactions.
IntActQ9H8P0. 2 interactions.
STRING9606.ENSP00000264228.

Chemistry

ChEMBLCHEMBL2363075.

PTM databases

PhosphoSiteQ9H8P0.

Polymorphism databases

DMDM74733864.

Proteomic databases

PaxDbQ9H8P0.
PeptideAtlasQ4W5Q6.
PRIDEQ9H8P0.

Protocols and materials databases

DNASU79644.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000264228; ENSP00000264228; ENSG00000128039.
GeneID79644.
KEGGhsa:79644.
UCSCuc003hau.3. human.

Organism-specific databases

CTD79644.
GeneCardsGC04P056212.
HGNCHGNC:25812. SRD5A3.
HPAHPA027006.
MIM611715. gene.
612379. phenotype.
612713. phenotype.
neXtProtNX_Q9H8P0.
Orphanet324737. SRD5A3-CDG.
PharmGKBPA162404779.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG330066.
HOVERGENHBG057797.
InParanoidQ9H8P0.
KOK12345.
OMASSPHMFF.
OrthoDBEOG72ZCFT.
PhylomeDBQ9H8P0.
TreeFamTF315011.

Enzyme and pathway databases

BioCycMetaCyc:HS13249-MONOMER.
ReactomeREACT_111217. Metabolism.
REACT_15493. Steroid hormones.
REACT_17015. Metabolism of proteins.
UniPathwayUPA00378.

Gene expression databases

ArrayExpressQ9H8P0.
BgeeQ9H8P0.
CleanExHS_SRD5A3.
GenevestigatorQ9H8P0.

Family and domain databases

InterProIPR001104. 3-oxo-5_a-steroid_4-DH_C.
[Graphical view]
PfamPF02544. Steroid_dh. 1 hit.
[Graphical view]
PROSITEPS50244. S5A_REDUCTASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiSRD5A3.
GenomeRNAi79644.
NextBio68779.
PROQ9H8P0.
SOURCESearch...

Entry information

Entry namePORED_HUMAN
AccessionPrimary (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: April 16, 2014
This is version 108 of the entry and version 1 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 chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM