Polyprenol reductase

Details

Name
Polyprenol reductase
Synonyms
  • 1.3.1.94
  • 3-oxo-5-alpha-steroid 4-dehydrogenase 3
  • S5AR 3
  • SR type 3
  • SRD5A2L
  • Steroid 5-alpha-reductase 2-like
  • Steroid 5-alpha-reductase 3
Gene Name
SRD5A3
Organism
Humans
Amino acid sequence
>lcl|BSEQ0013344|Polyprenol reductase
MAPWAEAEHSALNPLRAVWLTLTAAFLLTLLLQLLPPGLLPGCAIFQDLIRYGKTKCGEP
SRPAACRAFDVPKRYFSHFYIISVLWNGFLLWCLTQSLFLGAPFPSWLHGLLRILGAAQF
QGGELALSAFLVLVFLWLHSLRRLFECLYVSVFSNVMIHVVQYCFGLVYYVLVGLTVLSQ
VPMDGRNAYITGKNLLMQARWFHILGMMMFIWSSAHQYKCHVILGNLRKNKAGVVIHCNH
RIPFGDWFEYVSSPNYLAELMIYVSMAVTFGFHNLTWWLVVTNVFFNQALSAFLSHQFYK
SKFVSYPKHRKAFLPFLF
Number of residues
318
Molecular Weight
36521.005
Theoretical pI
Not Available
GO Classification
Functions
3-oxo-5-alpha-steroid 4-dehydrogenase activity / cholestenone 5-alpha-reductase activity / oxidoreductase activity, acting on the CH-CH group of donors, NAD or NADP as acceptor / polyprenol reductase activity
Processes
androgen biosynthetic process / dolichol metabolic process / dolichol-linked oligosaccharide biosynthetic process / dolichyl diphosphate biosynthetic process / polyprenol catabolic process / protein glycosylation
Components
endoplasmic reticulum / endoplasmic reticulum membrane / integral component of membrane
General 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).
Specific Function
3-oxo-5-alpha-steroid 4-dehydrogenase activity
Pfam Domain Function
Transmembrane Regions
12-34 81-101 118-138 158-178 195-215 261-281
Cellular Location
Endoplasmic reticulum membrane
Gene sequence
>lcl|BSEQ0013345|Polyprenol reductase (SRD5A3)
ATGGCTCCCTGGGCGGAGGCCGAGCACTCGGCGCTGAACCCGCTGCGCGCGGTGTGGCTC
ACGCTGACCGCCGCCTTCCTGCTGACCCTACTGCTGCAGCTCCTGCCGCCCGGCCTGCTC
CCGGGCTGCGCGATCTTCCAGGACCTGATCCGCTATGGGAAAACCAAGTGTGGGGAGCCG
TCGCGCCCCGCCGCCTGCCGAGCCTTTGATGTCCCCAAGAGATATTTTTCCCACTTTTAT
ATCATCTCAGTGCTGTGGAATGGCTTCCTGCTTTGGTGCCTTACTCAATCTCTGTTCCTG
GGAGCACCTTTTCCAAGCTGGCTTCATGGTTTGCTCAGAATTCTCGGGGCGGCACAGTTC
CAGGGAGGGGAGCTGGCACTGTCTGCATTCTTAGTGCTAGTATTTCTGTGGCTGCACAGC
TTACGAAGACTCTTCGAGTGCCTCTACGTCAGTGTCTTCTCCAATGTCATGATTCACGTC
GTGCAGTACTGTTTTGGACTTGTCTATTATGTCCTTGTTGGCCTAACTGTGCTGAGCCAA
GTGCCAATGGATGGCAGGAATGCCTACATAACAGGGAAAAATCTATTGATGCAAGCACGG
TGGTTCCATATTCTTGGGATGATGATGTTCATCTGGTCATCTGCCCATCAGTATAAGTGC
CATGTTATTCTCGGCAATCTCAGGAAAAATAAAGCAGGAGTGGTCATTCACTGTAACCAC
AGGATCCCATTTGGAGACTGGTTTGAATATGTTTCTTCCCCTAACTACTTAGCAGAGCTG
ATGATCTACGTTTCCATGGCCGTCACCTTTGGGTTCCACAACTTAACTTGGTGGCTAGTG
GTGACAAATGTCTTCTTTAATCAGGCCCTGTCTGCCTTTCTCAGCCACCAATTCTACAAA
AGCAAATTTGTCTCTTACCCGAAGCATAGGAAAGCTTTCCTACCATTTTTGTTTTAA
Chromosome Location
4
Locus
4q12
External Identifiers
ResourceLink
UniProtKB IDQ9H8P0
UniProtKB Entry NamePORED_HUMAN
HGNC IDHGNC:25812
General References
  1. 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 TO, 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: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
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  3. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  4. Uemura M, Tamura K, Chung S, Honma S, Okuyama A, Nakamura Y, Nakagawa H: Novel 5 alpha-steroid reductase (SRD5A3, type-3) is overexpressed in hormone-refractory prostate cancer. Cancer Sci. 2008 Jan;99(1):81-6. Epub 2007 Nov 6. [Article]
  5. Cantagrel V, Lefeber DJ, Ng BG, Guan Z, Silhavy JL, Bielas SL, Lehle L, Hombauer H, Adamowicz M, Swiezewska E, De Brouwer AP, Blumel P, Sykut-Cegielska J, Houliston S, Swistun D, Ali BR, Dobyns WB, Babovic-Vuksanovic D, van Bokhoven H, Wevers RA, Raetz CR, Freeze HH, Morava E, Al-Gazali L, Gleeson JG: SRD5A3 is required for converting polyprenol to dolichol and is mutated in a congenital glycosylation disorder. Cell. 2010 Jul 23;142(2):203-17. doi: 10.1016/j.cell.2010.06.001. Epub 2010 Jul 15. [Article]
  6. Kahrizi K, Hu CH, Garshasbi M, Abedini SS, Ghadami S, Kariminejad R, Ullmann R, Chen W, Ropers HH, Kuss AW, Najmabadi H, Tzschach A: Next generation sequencing in a family with autosomal recessive Kahrizi syndrome (OMIM 612713) reveals a homozygous frameshift mutation in SRD5A3. Eur J Hum Genet. 2011 Jan;19(1):115-7. doi: 10.1038/ejhg.2010.132. Epub 2010 Aug 11. [Article]
  7. Kasapkara CS, Tumer L, Ezgu FS, Hasanoglu A, Race V, Matthijs G, Jaeken J: SRD5A3-CDG: a patient with a novel mutation. Eur J Paediatr Neurol. 2012 Sep;16(5):554-6. doi: 10.1016/j.ejpn.2011.12.011. Epub 2012 Jan 10. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00421SpironolactoneapprovedunknownantagonistDetails
DB13943Testosterone cypionateapprovednosubstrateDetails
DB13944Testosterone enanthateapprovednosubstrateDetails
DB01420Testosterone propionateapproved, investigational, vet_approved, withdrawnnosubstrateDetails
DB13946Testosterone undecanoateapproved, investigationalnosubstrateDetails
DB00717NorethisteroneapprovedunknownsubstrateDetails