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Literature summary for 1.1.1.105 extracted from

  • Wu, L.; Belyaeva, O.V.; Adams, M.K.; Klyuyeva, A.V.; Lee, S.A.; Goggans, K.R.; Kesterson, R.A.; Popov, K.M.; Kedishvili, N.Y.
    Mice lacking the epidermal retinol dehydrogenases SDR16C5 and SDR16C6 display accelerated hair growth and enlarged meibomian glands (2019), J. Biol. Chem., 294, 17060-17074 .
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
recombinant expression of C-terminally His6-tagged enzyme in Spodoptera frugiperda Sf9 cell microsomes, mitochondria from RDHE2S-expressing Sf9 cells exhibit a much lower activity than RDHE2S microsomes under the same assay conditions. Transient recombinant expression of C-terminally FLAG-tagged enzyme in HEK-293 cells. Quantitative RT-PCR enzyme expression analysis Mus musculus
recombinant expression of C-terminally His6-tagged enzyme in Spodoptera frugiperda Sf9 cell microsomes, no activity toward all-trans-retinol is detected using the microsomal and mitochondrial preparations of recombinant murine RDHE2 protein expressed in Spodoptera frugiperda Sf9 cells. Funtional transient recombinant expression of C-terminally FLAG-tagged enzyme in HEK-293 cells, the activity of RDHE2 resulted in a 3fold increase in RA biosynthesis relative to mock-transfected cells. Quantitative RT-PCR enzyme expression analysis Mus musculus

Protein Variants

Protein Variants Comment Organism
additional information generation of single knockout Rdhe2-/- and Rdhe2-/-,Rdhe2s-/- double-knockout mice (DKO) lacking both RDHE2 and RDHE2S using CRISPR-mediated gene editing. Phenotypes of femal DKO mice compared to male wild-type mice, overview. Elevated expression of hair-follicle growth and differentiation marker genes in DKO skin relative to littermate wild-type skin. The lack of expression of RDHE2 and RDHE2S results in enlargement of meibomian glands of DKO animals Mus musculus
additional information generation of single knockout Rdhe2s-/- and Rdhe2-/-,Rdhe2s-/- double-knockout mice (DKO) lacking both RDHE2 and RDHE2S using CRISPR-mediated gene editing. Phenotypes of femal DKO mice compared to male wild-type mice, overview. Elevated expression of hair-follicle growth and differentiation marker genes in DKO skin relative to littermate wild-type skin. The lack of expression of RDHE2 and RDHE2S results in enlargement of meibomian glands of DKO animals Mus musculus

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.00087
-
all-trans-retinol recombinant enzyme, pH and temperature not specified in the publication Mus musculus
0.0039
-
all-trans-retinal recombinant enzyme, pH and temperature not specified in the publication Mus musculus
0.011
-
NADH recombinant enzyme, pH and temperature not specified in the publication Mus musculus
0.086
-
11-cis-retinol recombinant enzyme, pH and temperature not specified in the publication Mus musculus
0.46
-
NAD+ recombinant enzyme, pH and temperature not specified in the publication Mus musculus

Localization

Localization Comment Organism GeneOntology No. Textmining
microsome enzyme RDHE2S is localized primarily in the microsomal membranes Mus musculus
-
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
all-trans-retinal + NADH + H+ Mus musculus
-
all-trans-retinol + NAD+
-
r
all-trans-retinal + NADH + H+ Mus musculus C57BL/6J
-
all-trans-retinol + NAD+
-
r
all-trans-retinol + NAD+ Mus musculus
-
all-trans-retinal + NADH + H+
-
r
all-trans-retinol + NAD+ Mus musculus C57BL/6J
-
all-trans-retinal + NADH + H+
-
r

Organism

Organism UniProt Comment Textmining
Mus musculus Q05A13
-
-
Mus musculus Q7TQA3
-
-
Mus musculus C57BL/6J Q05A13
-
-
Mus musculus C57BL/6J Q7TQA3
-
-

Source Tissue

Source Tissue Comment Organism Textmining
adipose tissue
-
Mus musculus
-
colon
-
Mus musculus
-
embryo Rdhe2 is observed starting at E12.5, increasing in abundance through E14.5. Both Rdhe2 and Rdhe2s are expressed from middle to late gestation Mus musculus
-
embryo Rdhe2s is detected earlier in development at E10.5 and persisted through E14.5. Both Rdhe2 and Rdhe2s are expressed from middle to late gestation Mus musculus
-
epidermis
-
Mus musculus
-
esophagus
-
Mus musculus
-
intestine
-
Mus musculus
-
additional information analysis of the expression patterns of RDHE2, quantitative RT-PCR enzyme expression analysis. The two transcripts of Rdhe2 and Rdhe2s exhibit a largely overlapping expression pattern with the highest expression levels in skin, followed by tongue, intestine, and esophagus, trace amounts of transcripts are detected in adipose tissue, colon, and possibly testis. Rdhe2 transcripts are detected in sebaceous glands and epidermis of adult wild-type C57BL/J6 mice by in situ hybridization Mus musculus
-
additional information analysis of the expression patterns of RDHE2S, quantitative RT-PCR enzyme expression analysis. The two transcripts of Rdhe2 and Rdhe2s exhibit a largely overlapping expression pattern with the highest expression levels in skin, followed by tongue, intestine, and esophagus, trace amounts of transcripts are detected in adipose tissue, colon, and possibly testis Mus musculus
-
sebaceous gland
-
Mus musculus
-
skin
-
Mus musculus
-
testis
-
Mus musculus
-
tongue
-
Mus musculus
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
11-cis-retinol + NAD+
-
Mus musculus 11-cis-retinal + NADH + H+
-
r
11-cis-retinol + NAD+
-
Mus musculus C57BL/6J 11-cis-retinal + NADH + H+
-
r
all-trans-retinal + NAD+ catalytic efficiency in the reductive direction is lower than in the oxidative direction Mus musculus all-trans-retinol + NADH + H+
-
r
all-trans-retinal + NAD+ catalytic efficiency in the reductive direction is lower than in the oxidative direction Mus musculus C57BL/6J all-trans-retinol + NADH + H+
-
r
all-trans-retinal + NADH + H+
-
Mus musculus all-trans-retinol + NAD+
-
r
all-trans-retinal + NADH + H+ catalytic efficiency in the reductive direction is lower than in the oxidative direction Mus musculus all-trans-retinol + NAD+
-
r
all-trans-retinal + NADH + H+
-
Mus musculus C57BL/6J all-trans-retinol + NAD+
-
r
all-trans-retinal + NADH + H+ catalytic efficiency in the reductive direction is lower than in the oxidative direction Mus musculus C57BL/6J all-trans-retinol + NAD+
-
r
all-trans-retinol + NAD+
-
Mus musculus all-trans-retinal + NADH + H+
-
r
all-trans-retinol + NAD+
-
Mus musculus C57BL/6J all-trans-retinal + NADH + H+
-
r
additional information in addition to all-trans-retinol, RDHE2S recognizes 11-cis-retinol as substrate Mus musculus ?
-
-
additional information no activity toward all-trans-retinol is detected using the microsomal and mitochondrial preparations of recombinant murine RDHE2 protein expressed in Spodoptera frugiperda Sf9 cells. But although inactive toward retinol in isolated microsomes, RDHE2 is able to function as a retinol dehydrogenase in intact cells Mus musculus ?
-
-
additional information in addition to all-trans-retinol, RDHE2S recognizes 11-cis-retinol as substrate Mus musculus C57BL/6J ?
-
-
additional information no activity toward all-trans-retinol is detected using the microsomal and mitochondrial preparations of recombinant murine RDHE2 protein expressed in Spodoptera frugiperda Sf9 cells. But although inactive toward retinol in isolated microsomes, RDHE2 is able to function as a retinol dehydrogenase in intact cells Mus musculus C57BL/6J ?
-
-

Synonyms

Synonyms Comment Organism
RDHE2
-
Mus musculus
RDHE2S
-
Mus musculus
retinol dehydrogenase epidermal 2
-
Mus musculus
SDR16C5
-
Mus musculus
SDR16C6
-
Mus musculus

Cofactor

Cofactor Comment Organism Structure
additional information poor activity with NADP+/NADPH Mus musculus
NAD+ preferred cofactor Mus musculus
NADH
-
Mus musculus

General Information

General Information Comment Organism
malfunction mice lacking both the epidermal retinol dehydrogenases SDR16C5 and SDR16C6 display accelerated hair growth and enlarged meibomian glands. The upregulation of hair-follicle stem cell genes is consistent with reduced retinoic acid signaling in the skin of the double-knockout mice Mus musculus
malfunction mice with targeted knockout of the more catalytically active SDR16C6 enzyme have no obvious phenotype, possibly due to functional redundancy, because Sdr16c5 and Sdr16c6 exhibit an overlapping expression pattern during later developmental stages and in adulthood. Mice lacking both epidermal retinol dehydrogenases SDR16C5 and SDR16C6 display accelerated hair growth and enlarged meibomian glands Mus musculus
metabolism two murine epidermal retinol dehydrogenases, short-chain dehydrogenase/reductase family 16C member 5 (SDR16C5 or RDHE2) and SDR16C6 (RDHE2S), contribute to retinoic acid biosynthesis in living cells and are also essential for the oxidation of retinol to retinaldehyde in vivo Mus musculus
metabolism two murine epidermal retinol dehydrogenases, short-chain dehydrogenase/reductase family 16C member 5 (SDR16C5 or RDHE2) and SDR16C6 (RDHE2S), contribute to retinoic acid biosynthesis in living cells and are also essential for the oxidation of retinol to retinaldehyde in vivo. RDHE2S is a more active enzyme than RDHE2 Mus musculus
physiological function the epidermal retinol dehydrogenase short-chain dehydrogenase/reductase family 16C member 5 (SDR16C5 or RDHE2) contributes to retinoic acid biosynthesis in living cells and is also essential for the oxidation of retinol to retinaldehyde in vivo. The retinol dehydrogenase activities of murine SDR16C5 and SDR16C6 enzymes are not critical for survival but are responsible for most of the retinol dehydrogenase activity in skin, essential for the regulation of the hair-follicle cycle, and required for the maintenance of both sebaceous and meibomian glands Mus musculus
physiological function the epidermal retinol dehydrogenase short-chain dehydrogenase/reductase family 16C member 6 (SDR16C6 or RDHE2S) contributes to retinoic acid biosynthesis in living cells and is also essential for the oxidation of retinol to retinaldehyde in vivo. RDHE2S is a more active enzyme than RDHE2. The upregulation of hair-follicle stem cell genes is consistent with reduced retinoic acid signaling in the skin of the double-knockout mice. The retinol dehydrogenase activities of murine SDR16C5 and SDR16C6 enzymes are not critical for survival but are responsible for most of the retinol dehydrogenase activity in skin, essential for the regulation of the hair-follicle cycle, and required for the maintenance of both sebaceous and meibomian glands Mus musculus